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Dunn C, Shapiro J, Lee M, Wong R, Lee B, Wong HL, Loft M, Jalali A, Gibbs P. Measuring quality in the care of metastatic colorectal cancer utilising available registry data: A modified Delphi study. Eur J Cancer 2025; 214:115142. [PMID: 39615331 DOI: 10.1016/j.ejca.2024.115142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Revised: 11/06/2024] [Accepted: 11/10/2024] [Indexed: 12/20/2024]
Abstract
BACKGROUND AND AIMS The current lack of quality indicators for patients with metastatic colorectal cancer compromises our ability to examine the quality of care delivered, and to ensure optimal patient outcomes. We sought to define a novel set of quality indicators that could be assessed using available data from a prospective comprehensive clinical colorectal cancer registry, ultimately enabling us to explore local practice and benchmark performance between institutions. METHODS We performed a systematic review of the literature to review existing quality indicators for metastatic colorectal cancer. We engaged an expert panel of medical oncologists in a two-step modified Delphi analysis, using online questionnaires to rate and refine our initial list of candidate indicators, and to generate potential new ones. RESULTS Thirty-five unique quality indicators for metastatic colorectal cancer were identified from the literature. Nine of these 35 were able to be captured in TRACC, and an additional 3 novel indicators, also captured in TRACC, were added to the list to reflect current practice. After 2 online surveys of eight medical oncologists, a final list of 14 quality indicators were recommended for inclusion. CONCLUSION A modified Delphi method was used to propose a set of 14 novel quality indicators to be extracted from an existing comprehensive metastatic colorectal cancer clinical registry. The quality indicators intentionally encompassed critical components of modern, multi-disciplinary care, spanning the treatment continuum across diagnosis to end of life. These will be used in work underway utilising TRACC data to identify potential gaps in care and avenues for quality improvement.
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Affiliation(s)
- Catherine Dunn
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
| | | | - Margaret Lee
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; Western Health, Melbourne, Australia; Eastern Health Clinical School, Monash University, Melbourne, Australia
| | - Rachel Wong
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; Eastern Health Clinical School, Monash University, Melbourne, Australia; Epworth Healthcare, Melbourne, Australia
| | - Belinda Lee
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; Northern Health, Melbourne, Australia; Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Hui-Li Wong
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Matthew Loft
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; Western Health, Melbourne, Australia
| | - Azim Jalali
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; Western Health, Melbourne, Australia; Northern Health, Melbourne, Australia; LaTrobe Regional Hospital, Melbourne, Australia
| | - Peter Gibbs
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; Western Health, Melbourne, Australia; Melbourne Private, Melbourne, Australia; Western Private, Melbourne, Australia
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Milanzi E, Pelly RM, Hayes IP, Gibbs P, Faragher I, Reece JC. Accuracy of Baseline Magnetic Resonance Imaging for Staging Rectal Cancer Patients Proceeding Directly to Surgery. J Surg Oncol 2024; 130:1674-1682. [PMID: 39233560 PMCID: PMC11849709 DOI: 10.1002/jso.27852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 08/08/2024] [Accepted: 08/19/2024] [Indexed: 09/06/2024]
Abstract
BACKGROUND AND OBJECTIVES High-resolution magnetic resonance imaging (MRI) accuracy for staging preoperative rectal cancer varies across studies. We examined MRI accuracy for T- and N-staging of rectal cancer compared with final histopathology of the resected specimen in a large Australian cohort who did not receive neoadjuvant therapy or radiation. METHODS Retrospective analysis of prospectively-collected clinical data from 153 rectal adenocarcinomas locally staged by high-resolution MRI between January 2012 and December 2019 that did not undergo chemoradiotherapy or radiation before surgery. T- and N-stage agreement between MRI and final histopathology was assessed using Kappa statistic. Agreement at each T-stage was evaluated using log-linear modeling. N-staging accuracy was examined using positive and negative predictive values. RESULTS Overall agreement between MRI and final histopathology for T-stage and N-stage was 55% and 65%, respectively. Kappa statistic found higher agreement between MRI and final histopathology for T-staging (κ = 0.33) versus N-staging (κ = 0.18). MRI correctly assessed 91% of T1 tumors, 43% of T2 tumors, 65% of T3 tumors, and 80% of T4 tumors. MRI accuracy was higher for N-negative tumors (74.1%) than for N-positive tumors (44.4%). CONCLUSION MRI is moderately accurate at staging T1, T3, and T4 rectal tumors but caution when staging tumors as T2 is advised. Greater accuracy for staging N-negative versus N-positive tumors is indicated.
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Affiliation(s)
- Elasma Milanzi
- Neuroepidemiology Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global HealthThe University of MelbourneCarltonVictoriaAustralia
| | - Rachel M. Pelly
- Neuroepidemiology Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global HealthThe University of MelbourneCarltonVictoriaAustralia
| | - Ian P. Hayes
- Colorectal Surgery UnitRoyal Melbourne HospitalParkvilleVictoriaAustralia
- Department of SurgeryThe University of MelbourneParkvilleVictoriaAustralia
| | - Peter Gibbs
- Personalised Oncology DivisionWalter and Eliza Hall InstituteParkvilleVictoriaAustralia
| | - Ian Faragher
- Colorectal Surgery UnitWestern HealthMelbourneVictoriaAustralia
| | - Jeanette C. Reece
- Neuroepidemiology Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global HealthThe University of MelbourneCarltonVictoriaAustralia
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Degeling K, To YH, Trapani K, Athan S, Gibbs P, IJzerman MJ, Franchini F. Predicting the Population Health Economic Impact of Current and New Cancer Treatments for Colorectal Cancer: A Data-Driven Whole Disease Simulation Model for Predicting the Number of Patients with Colorectal Cancer by Stage and Treatment Line in Australia. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2024; 27:1382-1392. [PMID: 38977190 DOI: 10.1016/j.jval.2024.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 05/03/2024] [Accepted: 06/13/2024] [Indexed: 07/10/2024]
Abstract
OBJECTIVES Effective healthcare planning, resource allocation, and budgeting require accurate predictions of the number of patients needing treatment at specific cancer stages and treatment lines. The Predicting the Population Health Economic Impact of Current and New Cancer Treatments (PRIMCAT) for Colorectal Cancer (CRC) simulation model (PRIMCAT-CRC) was developed to meet this requirement for all CRC stages and relevant molecular profiles in Australia. METHODS Real-world data were used to estimate treatment utilization and time-to-event distributions. This populated a discrete-event simulation, projecting the number of patients receiving treatment across all disease stages and treatment lines for CRC and forecasting the number of patients likely to utilize future treatments. Illustrative analyses were undertaken, estimating treatments across disease stages and treatment lines over a 5-year period (2022-2026). We demonstrated the model's applicability through a case study introducing pembrolizumab as a first-line treatment for mismatch-repair-deficient stage IV. RESULTS Clinical registry data from 7163 patients informed the model. The model forecasts 15 738 incident and 2821 prevalent cases requiring treatment in 2022, rising to 15 921 and 2871, respectively, by 2026. Projections show that over 2022 to 2026, there will be a total of 116 752 treatments initiated, with 43% intended for stage IV disease. The introduction of pembrolizumab is projected for 706 patients annually, totaling 3530 individuals starting treatment with pembrolizumab over the forecasted period, without significantly altering downstream utilization of subsequent treatments. CONCLUSIONS PRIMCAT-CRC is a versatile tool that can be used to estimate the eligible patient populations for novel cancer therapies, thereby reducing uncertainty for policymakers in decisions to publicly reimburse new treatments.
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Affiliation(s)
- Koen Degeling
- Cancer Health Services Research, Centre for Health Policy, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia; Cancer Health Services Research, Centre for Cancer Research, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia
| | - Yat Hang To
- Personalized Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Karen Trapani
- Cancer Health Services Research, Centre for Health Policy, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia; Cancer Health Services Research, Centre for Cancer Research, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia
| | - Sophy Athan
- Cancer Health Services Research, Centre for Health Policy, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia
| | - Peter Gibbs
- Personalized Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; Department of Medical Oncology, Western Health, Melbourne, Victoria, Australia
| | - Maarten J IJzerman
- Cancer Health Services Research, Centre for Health Policy, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia; Cancer Health Services Research, Centre for Cancer Research, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia; Department of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Erasmus School of Health Policy and Management, Rotterdam, The Netherlands
| | - Fanny Franchini
- Cancer Health Services Research, Centre for Health Policy, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia; Cancer Health Services Research, Centre for Cancer Research, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia; Department of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
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Jalali A, Smith S, Kim G, Wong H, Lee M, Yeung J, Loft M, Wong R, Shapiro JD, Kosmider S, Tie J, Ananda S, Ma B, Burge M, Jennens R, Lee B, Johns J, Lim L, Dean A, Nott L, Gibbs P. Early onset metastatic colorectal cancer in Australia. Cancer Treat Res Commun 2024; 40:100827. [PMID: 38885543 DOI: 10.1016/j.ctarc.2024.100827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 04/29/2024] [Accepted: 06/11/2024] [Indexed: 06/20/2024]
Abstract
BACKGROUND Colorectal cancer (CRC) incidence and mortality rates have been increasing among young patients (YP), for uncertain reasons. It is unclear whether YP have a distinct tumor biology or merit a different treatment approach to older patients (OP). METHODS We reviewed prospectively collected data from consecutive patients with metastatic CRC (MCRC) enrolled in the multi-site Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Australian registry. Clinicopathological features, treatment and survival outcomes were compared between YP (<50 years) and OP (≥50 years). RESULTS Of 3692 patients diagnosed August 2009 - March 2023, 14 % (513) were YP. YP were more likely than OP to be female (52% vs. 40 %, P < 0.0001), have ECOG performance status 0-1 (94% vs. 81 %, P < 0.0001), to have a left-sided primary (72% vs. 63 %, P = 0.0008) and to have fewer comorbidities (90% vs. 60 % Charleston score 0, P < 0.0001). There were no differences in the available molecular status, which was more complete in YP. YP were more likely to have de novo metastatic disease (71% vs. 57 %, P < 0.0001). YP were more likely to undergo curative hepatic resection (27% vs. 17 %, P < 0.0001), to receive any chemotherapy (93% vs. 78 % (P < 0.0001), and to receive 3+ lines of chemotherapy (30% vs. 24 % (P < 0.0034)). Median first-line progression free survival (10.2 versus 10.6 months) was similar for YP vs OP, but overall survival (32.1 versus 25.4 months, HR = 0.745, P < 0.0001) was longer in YP. CONCLUSION Known prognostic variables mostly favored YP versus OP with newly diagnosed mCRC, who were also more heavily treated. Consistent with this, overall survival outcomes were improved. This data does not support that CRC in YP represent a distinct subset of mCRC patients, or that a modified treatment approach is warranted.
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Affiliation(s)
- A Jalali
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, Western Health, VIC, Australia; Department of Medical Oncology, Northern Health, VIC, Australia; Department of Medical Oncology, Latrobe Regional Hospital, VIC, Australia.
| | - S Smith
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, St Vincent's Hospital Melbourne, VIC, Australia
| | - G Kim
- Department of Medical Oncology, Western Health, VIC, Australia
| | - H Wong
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, VIC, Australia
| | - M Lee
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, Western Health, VIC, Australia; Department of Medical Oncology, Eastern Health, VIC, Australia; Eastern Health Clinical School, Monash University, VIC, Australia
| | - J Yeung
- Department of Colorectal Surgery, Western Health, University of Melbourne, VIC, Australia; Department of Surgery, Western Precinct, University of Melbourne, VIC, Australia
| | - M Loft
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, VIC, Australia
| | - R Wong
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Eastern Health Clinical School, Monash University, VIC, Australia; Department of Surgery, Western Precinct, University of Melbourne, VIC, Australia
| | - J D Shapiro
- Department of Medical Oncology, Cabrini Hospital, VIC, Australia
| | - S Kosmider
- Department of Medical Oncology, Western Health, VIC, Australia
| | - J Tie
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, VIC, Australia
| | - S Ananda
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, Western Health, VIC, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, VIC, Australia
| | - B Ma
- The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong
| | - M Burge
- Department of Medical Oncology, Royal Brisbane Hospital, QLD, Australia
| | - R Jennens
- Department of Medical Oncology, Epworth Health, VIC, Australia
| | - B Lee
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, Northern Health, VIC, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, VIC, Australia
| | - J Johns
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, VIC, Australia
| | - L Lim
- Department of Medical Oncology, Eastern Health, VIC, Australia
| | - A Dean
- Department of Medical Oncology, St John of God Hospital, WA, Australia
| | - L Nott
- Department of Medical Oncology, Royal Hobart Hospital, TAS, Australia
| | - P Gibbs
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, Western Health, VIC, Australia
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Smith S, Drummond K, Dowling A, Bennett I, Campbell D, Freilich R, Phillips C, Ahern E, Reeves S, Campbell R, Collins IM, Johns J, Dumas M, Hong W, Gibbs P, Gately L. Improving Clinical Registry Data Quality via Linkage With Survival Data From State-Based Population Registries. JCO Clin Cancer Inform 2024; 8:e2400025. [PMID: 38924710 DOI: 10.1200/cci.24.00025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 03/26/2024] [Accepted: 05/03/2024] [Indexed: 06/28/2024] Open
Abstract
PURPOSE Real-world data (RWD) collected on patients treated as part of routine clinical care form the basis of cancer clinical registries. Capturing accurate death data can be challenging, with inaccurate survival data potentially compromising the integrity of registry-based research. Here, we explore the utility of data linkage (DL) to state-based registries to enhance the capture of survival outcomes. METHODS We identified consecutive adult patients with brain tumors treated in the state of Victoria from the Brain Tumour Registry Australia: Innovation and Translation (BRAIN) database, who had no recorded date of death and no follow-up within the last 6 months. Full name and date of birth were used to match patients in the BRAIN registry with those in the Victorian Births, Deaths and Marriages (BDM) registry. Overall survival (OS) outcomes were compared pre- and post-DL. RESULTS Of the 7,346 clinical registry patients, 5,462 (74%) had no date of death and no follow-up recorded within the last 6 months. Of the 5,462 patients, 1,588 (29%) were matched with a date of death in BDM. Factors associated with an increased number of matches were poor prognosis tumors, older age, and social disadvantage. OS was significantly overestimated pre-DL compared with post-DL for the entire cohort (pre- v post-DL: hazard ratio, 1.43; P < .001; median, 29.9 months v 16.7 months) and for most individual tumor types. This finding was present independent of the tumor prognosis. CONCLUSION As revealed by linkage with BDM, a high proportion of patients in a brain cancer clinical registry had missing death data, contributed to by informative censoring, inflating OS calculations. DL to pertinent registries on an ongoing basis should be considered to ensure accurate reporting of survival data and interpretation of RWD outcomes.
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Affiliation(s)
- Samuel Smith
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
- Department of Medical Oncology, St Vincent's Hospital Melbourne, Fitzroy, VIC, Australia
| | - Kate Drummond
- University of Melbourne, Parkville, VIC, Australia
- Department of Neurosurgery, Royal Melbourne Hospital, Parkville, VIC, Australia
| | - Anthony Dowling
- Department of Medical Oncology, St Vincent's Hospital Melbourne, Fitzroy, VIC, Australia
- University of Melbourne, Parkville, VIC, Australia
| | - Iwan Bennett
- Department of Neurosurgery, Alfred Health, Prahran, VIC, Australia
| | - David Campbell
- Department of Medical Oncology, Barwon Health, Geelong, VIC, Australia
| | - Ronnie Freilich
- Department of Neurology, Cabrini Hospital, Malvern, VIC, Australia
| | - Claire Phillips
- Department of Radiation Oncology, Peter MacCallum Cancer Centre, Parkville, VIC, Australia
| | - Elizabeth Ahern
- Department of Medical Oncology, Monash Health, Clayton, VIC, Australia
| | - Simone Reeves
- Department of Radiation Oncology, Ballarat Austin Radiation Oncology Centre, Ballarat, VIC, Australia
| | - Robert Campbell
- Department of Medical Oncology, Bendigo Health, Bendigo, VIC, Australia
| | - Ian M Collins
- Department of Medical Oncology, South West Oncology, Warnambool, VIC, Australia
| | - Julie Johns
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
| | - Megan Dumas
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
| | - Wei Hong
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
| | - Peter Gibbs
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
| | - Lucy Gately
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
- Department of Neurosurgery, Alfred Health, Prahran, VIC, Australia
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Tan T, Mouradov D, Lee M, Gard G, Hirokawa Y, Li S, Lin C, Li F, Luo H, Wu K, Palmieri M, Leong E, Clarke J, Sakthianandeswaren A, Brasier H, Tie J, Tebbutt NC, Jalali A, Wong R, Burgess AW, Gibbs P, Sieber OM. Unified framework for patient-derived, tumor-organoid-based predictive testing of standard-of-care therapies in metastatic colorectal cancer. Cell Rep Med 2023; 4:101335. [PMID: 38118423 PMCID: PMC10783557 DOI: 10.1016/j.xcrm.2023.101335] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 09/11/2023] [Accepted: 11/18/2023] [Indexed: 12/22/2023]
Abstract
Predictive drug testing of patient-derived tumor organoids (PDTOs) holds promise for personalizing treatment of metastatic colorectal cancer (mCRC), but prospective data are limited to chemotherapy regimens with conflicting results. We describe a unified framework for PDTO-based predictive testing across standard-of-care chemotherapy and biologic and targeted therapy options. In an Australian community cohort, PDTO predictions based on treatment-naive patients (n = 56) and response rates from first-line mCRC clinical trials achieve 83% accuracy for forecasting responses in patients receiving palliative treatments (18 patients, 29 treatments). Similar assay accuracy is achieved in a prospective study of third-line or later mCRC treatment, AGITG FORECAST-1 (n = 30 patients). "Resistant" predictions are associated with inferior progression-free survival; misclassification rates are similar by regimen. Liver metastases are the optimal site for sampling, with testing achievable within 7 weeks for 68.8% cases. Our findings indicate that PDTO drug panel testing can provide predictive information for multifarious standard-of-care therapies for mCRC.
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Affiliation(s)
- Tao Tan
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia
| | - Dmitri Mouradov
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia
| | - Margaret Lee
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Oncology, Western Health, Footscray, VIC 3011, Australia; Department of Medical Oncology, Eastern Health, Box Hill, VIC 3128, Australia; Eastern Health Clinical School, Faculty of Medicine, Nursing, and Health Sciences, Monash University, Box Hill, VIC 3128, Australia
| | - Grace Gard
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Oncology, Western Health, Footscray, VIC 3011, Australia
| | - Yumiko Hirokawa
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
| | - Shan Li
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
| | - Cong Lin
- HIM-BGI Omics Center, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, BGI Research, Hangzhou 310000, China; Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, BGI Research, Shenzhen 518083, China
| | - Fuqiang Li
- HIM-BGI Omics Center, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, BGI Research, Hangzhou 310000, China; Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, BGI Research, Shenzhen 518083, China
| | - Huijuan Luo
- HIM-BGI Omics Center, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, BGI Research, Hangzhou 310000, China; Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, BGI Research, Shenzhen 518083, China
| | - Kui Wu
- HIM-BGI Omics Center, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, BGI Research, Hangzhou 310000, China; Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, BGI Research, Shenzhen 518083, China
| | - Michelle Palmieri
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia
| | - Evelyn Leong
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
| | - Jordan Clarke
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
| | - Anuratha Sakthianandeswaren
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia
| | - Helen Brasier
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
| | - Jeanne Tie
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia; Department of Medical Oncology, Western Health, Footscray, VIC 3011, Australia
| | - Niall C Tebbutt
- Department of Medical Oncology, Olivia Newton-John Cancer Wellness & Research Centre, Austin Health, Heidelberg, VIC 3084, Australia
| | - Azim Jalali
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Oncology, Western Health, Footscray, VIC 3011, Australia; Department of Cancer Services, Latrobe Regional Hospital, Traralogon, VIC 3844, Australia; Department of Medical Oncology, The Northern Hospital, Epping, VIC 3076, Australia
| | - Rachel Wong
- Department of Medical Oncology, Eastern Health, Box Hill, VIC 3128, Australia; Eastern Health Clinical School, Faculty of Medicine, Nursing, and Health Sciences, Monash University, Box Hill, VIC 3128, Australia
| | - Antony W Burgess
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia; Department of Surgery, The University of Melbourne, Parkville, VIC 3050, Australia
| | - Peter Gibbs
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia; Department of Medical Oncology, Western Health, Footscray, VIC 3011, Australia
| | - Oliver M Sieber
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia; Department of Surgery, The University of Melbourne, Parkville, VIC 3050, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
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Causa Andrieu P, Golia Pernicka JS, Yaeger R, Lupton K, Batch K, Zulkernine F, Simpson AL, Taya M, Gazit L, Nguyen H, Nicholas K, Gangai N, Sevilimedu V, Dickinson S, Paroder V, Bates DD, Do R. Natural Language Processing of Computed Tomography Reports to Label Metastatic Phenotypes With Prognostic Significance in Patients With Colorectal Cancer. JCO Clin Cancer Inform 2022; 6:e2200014. [PMID: 36103642 PMCID: PMC9848599 DOI: 10.1200/cci.22.00014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 06/04/2022] [Accepted: 08/04/2022] [Indexed: 01/21/2023] Open
Abstract
PURPOSE Natural language processing (NLP) applied to radiology reports can help identify clinically relevant M1 subcategories of patients with colorectal cancer (CRC). The primary purpose was to compare the overall survival (OS) of CRC according to American Joint Committee on Cancer TNM staging and explore an alternative classification. The secondary objective was to estimate the frequency of metastasis for each organ. METHODS Retrospective study of CRC who underwent computed tomography (CT) chest, abdomen, and pelvis between July 1, 2009, and March 26, 2019, at a tertiary cancer center, previously labeled for the presence or absence of metastasis by an NLP prediction model. Patients were classified in M0, M1a, M1b, and M1c (American Joint Committee on Cancer), or an alternative classification on the basis of the metastasis organ number: M1, single; M2, two; M3, three or more organs. Cox regression models were used to estimate hazard ratios; Kaplan-Meier curves were used to visualize survival curves using the two M1 subclassifications. RESULTS Nine thousand nine hundred twenty-eight patients with a total of 48,408 CT chest, abdomen, and pelvis reports were included. On the basis of NLP prediction, the median OS of M1a, M1b, and M1c was 4.47, 1.72, and 1.52 years, respectively. The median OS of M1, M2, and M3 was 4.24, 2.05, and 1.04 years, respectively. Metastases occurred most often in liver (35.8%), abdominopelvic lymph nodes (32.9%), lungs (29.3%), peritoneum (22.0%), thoracic nodes (19.9%), bones (9.2%), and pelvic organs (7.5%). Spleen and adrenal metastases occurred in < 5%. CONCLUSION NLP applied to a large radiology report database can identify clinically relevant metastatic phenotypes and be used to investigate new M1 substaging for CRC. Patients with three or more metastatic disease organs have the worst prognosis, with an OS of 1 year.
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Affiliation(s)
| | | | - Rona Yaeger
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Kaelan Lupton
- School of Computing, Queens University, Kingston, Canada
| | - Karen Batch
- School of Computing, Queens University, Kingston, Canada
| | | | | | - Michio Taya
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Lior Gazit
- Department of Strategy and Innovation, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Huy Nguyen
- Department of Strategy and Innovation, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Kevin Nicholas
- Department of Strategy and Innovation, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Natalie Gangai
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Varadan Sevilimedu
- Biostatistics Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Shannan Dickinson
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Viktoriya Paroder
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - David D.B. Bates
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Richard Do
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
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8
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Lee B, Gately L, Lok SW, Tran B, Lee M, Wong R, Markman B, Dunn K, Wong V, Loft M, Jalili A, Anton A, To R, Andrews M, Gibbs P. Leveraging Comprehensive Cancer Registry Data to Enable a Broad Range of Research, Audit and Patient Support Activities. Cancers (Basel) 2022; 14:cancers14174131. [PMID: 36077668 PMCID: PMC9454529 DOI: 10.3390/cancers14174131] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 08/21/2022] [Accepted: 08/24/2022] [Indexed: 12/03/2022] Open
Abstract
Simple Summary Registry data has the potential to support a broad range of research, audit and education initiatives. Here, we describe the experience and learnings of a series of large multi-institutional cancer registries that leverage real-world clinical data for a range of purposes, that informs the conduct and output of each registry in a virtuous cycle. Lessons learnt include the need for careful and continuous curation of information being collected, regular database updates, and the need for a continued focus on data quality. As a standalone resource, each registry has supported numerous projects, but linkage with external datasets with patients in common has enhanced the research potential. Multiple projects have linked registry data with matched tissue specimens to support the discovery and valiation of prognostic and predictive markers in the tumour and blood specimens. Registry-based biomarker trials have been successfully supported, generating novel and practice-changing data. Registry-based clinical trials, particularly studies exploring the best use of drug options are now complementing the research conducted in traditional clinical trials. More recent projects supported by the registries include health economic studies, personalised patient education material, and increased consumer engagement, including consumer entered data. Abstract Traditional cancer registries have often been siloed efforts, established by single groups with limited objectives. There is the potential for registry data to support a broad range of research, audit and education initiatives. Here, we describe the establishment of a series of comprehensive cancer registries across the spectrum of common solid cancers. The experience and learnings of each registry team as they develop, implement and then use collected data for a range of purposes, that informs the conduct and output of other registries in a virtuous cycle. Each registry is multi-site, multi-disciplinary and aims to collect data of maximal interest and value to a broad range of enquiry, which would be accessible to any researcher with a high-quality proposal. Lessons learnt include the need for careful and continuous curation of data fields, with regular database updates, and the need for a continued focus on data quality. The registry data as a standalone resource has supported numerous projects, but linkage with external datasets with patients in common has enhanced the audit and research potential. Multiple projects have linked registry data with matched tissue specimens to support prognostic and predictive biomarker studies, both validation and discovery. Registry-based biomarker trials have been successfully supported, generating novel and practice-changing data. Registry-based clinical trials, particularly randomised studies exploring the optimal use of available therapy options are now complementing the research conducted in traditional clinical trials. More recent projects supported by the registries include health economic studies, personalised patient education material, and increased consumer engagement, including consumer entered data.
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Affiliation(s)
- Belinda Lee
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Oncology, Northern Health, Epping, VIC 3076, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia
- School of Medicine and Dentistry, University of Melbourne, Parkville, VIC 3010, Australia
- Correspondence:
| | - Lucy Gately
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Cabrini Haematology and Oncology Centre, Malvern, VIC 3144, Australia
| | - Sheau Wen Lok
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia
| | - Ben Tran
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia
| | - Margaret Lee
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Oncology, Eastern Health, Melbourne, VIC 3151, Australia
- Department of Medical Oncology, Western Hospital, Melbourne, VIC 3021, Australia
| | - Rachel Wong
- Department of Medical Oncology, Eastern Health, Melbourne, VIC 3151, Australia
- Eastern Health Clinical School, Monash University, Clayton, VIC 3800, Australia
| | - Ben Markman
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Oncology, Alfred Health, Melbourne, VIC 3004, Australia
| | - Kate Dunn
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia
| | - Vanessa Wong
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Oncology, Ballarat Health Service, Ballarat Central, VIC 3350, Australia
| | - Matthew Loft
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
| | - Azim Jalili
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Oncology, Northern Health, Epping, VIC 3076, Australia
- Department of Medical Oncology, Western Hospital, Melbourne, VIC 3021, Australia
| | - Angelyn Anton
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Oncology, Eastern Health, Melbourne, VIC 3151, Australia
| | - Richard To
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia
- School of Medicine and Dentistry, University of Melbourne, Parkville, VIC 3010, Australia
| | - Miles Andrews
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Oncology, Alfred Health, Melbourne, VIC 3004, Australia
| | - Peter Gibbs
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- School of Medicine and Dentistry, University of Melbourne, Parkville, VIC 3010, Australia
- Department of Medical Oncology, Western Hospital, Melbourne, VIC 3021, Australia
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9
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Gately L, Drummond K, Rosenthal M, Harrup R, Dowling A, Gogos A, Lwin Z, Collins I, Campbell D, Ahern E, Phillips C, Gan HK, Bennett I, Sieber OM, Gibbs P. Beyond standard data collection – the promise and potential of BRAIN (Brain tumour Registry Australia INnovation and translation registry). BMC Cancer 2022; 22:604. [PMID: 35655179 PMCID: PMC9161524 DOI: 10.1186/s12885-022-09700-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 05/25/2022] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Real-world data (RWD) is increasingly being embraced as an invaluable source of information to address clinical and policy-relevant questions that are unlikely to ever be answered by clinical trials. However, the largely unrealised potential of RWD is the value to be gained by supporting prospective studies and translational research. Here we describe the design and implementation of an Australian brain cancer registry, BRAIN, which is pursuing these opportunities.
Methods
BRAIN was designed by a panel of clinicians in conjunction with BIOGRID to capture comprehensive clinical data on patients diagnosed with brain tumours from diagnosis through treatment to recurrence or death. Extensive internal and external testing was undertaken, followed by implementation at multiple sites across Victoria and Tasmania.
Results
Between February 2021 and December 2021, a total of 350 new patients from 10 sites, including one private and two regional, were entered into BRAIN. Additionally, BRAIN supports the world’s first registry trial in neuro-oncology, EX-TEM, addressing the optimal duration of post-radiation temozolomide; and BioBRAIN, a dedicated brain tumour translational program providing a pipeline for biospecimen collection matched with linked clinical data.
Conclusions
Here we report on the first data collection effort in brain tumours for Australia, which we believe to be unique worldwide given the number of sites and patients involved and the extent to which the registry resource is being leveraged to support clinical and translational research. Further directions such as passive data flow and data linkages, use of artificial intelligence and inclusion of patient-entered data are being explored.
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10
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Hunger M, Bardenheuer K, Passey A, Schade R, Sharma R, Hague C. The Value of Federated Data Networks in Oncology: What Research Questions Do They Answer? Outcomes From a Systematic Literature Review. VALUE IN HEALTH : THE JOURNAL OF THE INTERNATIONAL SOCIETY FOR PHARMACOECONOMICS AND OUTCOMES RESEARCH 2022; 25:855-868. [PMID: 35249830 DOI: 10.1016/j.jval.2021.11.1357] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 10/22/2021] [Accepted: 11/14/2021] [Indexed: 06/14/2023]
Abstract
OBJECTIVES Real-world evidence (RWE) plays an important role in addressing key research questions of interest to healthcare decision makers. Federated data networks (FDNs) apply novel technology to enable the conduct of RWE studies with multiple partners, without the need to share the individual partner's data set. A systematic review of the published literature was performed to determine which types of research questions can best be addressed through FDNs, specifically in the field of oncology. METHODS Systematic searches of MEDLINE and Embase were undertaken to identify the types of research questions that had been addressed in studies using FDNs. Additional information was retrieved about study characteristics, statistical methods, and the FDN itself. RESULTS In total, 40 publications were included where research questions on the following had been addressed (multiple categories possible): disease natural history (58%), safety surveillance (18%), treatment pathways (15%), comparative effectiveness (10%), and cost/resource use studies (3%)-13% of studies had to be left uncategorized. A total of 50% of the studies were run with data partners in networks of ≤5. The size of the networks ranged from 227 patients to >5 million patients. Statistical methods used included distributed learning and distributed regression methods. CONCLUSIONS Further work is needed to raise awareness of the important role that FDNs can play in leveraging readily available RWE to address key research questions of interest in cancer and the benefits to the research community in engaging in federated data initiatives with a long-term perspective.
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Affiliation(s)
- Matthias Hunger
- ICON plc, Global Health Economics, Outcomes Research and Epidemiology, Dublin
| | | | | | - René Schade
- ICON plc, Global Health Economics, Outcomes Research and Epidemiology, Dublin
| | - Ruchika Sharma
- ICON plc, Global Health Economics, Outcomes Research and Epidemiology, Dublin
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11
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Tham N, Skandarajah A, Hayes IP. Colorectal cancer databases and registries in Australia: what data is available? ANZ J Surg 2021; 92:27-33. [PMID: 34569698 DOI: 10.1111/ans.17221] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 08/29/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND There are multiple data sources relating to colorectal cancer (CRC) nationwide. Prospective clinical cancer databases, population-based registries and linked administrative data are powerful tools in clinical outcomes research and provide real-world perspective on cancer treatments. This study aims to review the different Australian data sources for CRC from the perspective of conducting comparative research studies using a PICO (patient, intervention, comparison, outcome) framework. METHODS Data dictionaries from the different data sources were evaluated for the types of exposure and outcome variables contained to highlight their differing research utility. RESULTS State or territory-based cancer registries contain limited histology, cancer staging and treatment detail. They enable investigation of population-level patterns in overall survival (OS) of cancer patients with different demographics. Prospective clinical cancer databases contain more detail, especially surgical. Their strength is in auditing short-term surgical outcomes. They vary in the amount of data collected for other cancer treatments and completion of follow up data. Linked administrative databases have broad population coverage but less surgical detail. They provide population-level data on treatment patterns, short-term outcome measures and OS, as well as long-term surgical outcomes such as identifying patients who did not undergo stoma reversal. These databases cannot assess disease-free survival. CONCLUSION Of the various CRC data sources within Australia, linked administrative databases have the potential to provide the widest population coverage combined with the broadest range of exposures and outcomes, and arguably the most research utility.
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Affiliation(s)
- Nicole Tham
- Colorectal Surgical Unit, The Royal Melbourne Hospital, Parkville, Victoria, Australia.,Department of General Surgical Specialties, The Royal Melbourne Hospital, Parkville, Victoria, Australia.,Department of Surgery, The University of Melbourne, Melbourne, Victoria, Australia
| | - Anita Skandarajah
- Department of General Surgical Specialties, The Royal Melbourne Hospital, Parkville, Victoria, Australia.,Department of Surgery, The University of Melbourne, Melbourne, Victoria, Australia
| | - Ian P Hayes
- Colorectal Surgical Unit, The Royal Melbourne Hospital, Parkville, Victoria, Australia.,Department of General Surgical Specialties, The Royal Melbourne Hospital, Parkville, Victoria, Australia.,Department of Surgery, The University of Melbourne, Melbourne, Victoria, Australia
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12
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Jalali A, Gard G, Banks S, Dunn C, Wong HL, Wong R, Lee M, Gately L, Loft M, Shapiro JD, Kosmider S, Tie J, Ananda S, Yeung JM, Jennens R, Lee B, McKendrick J, Lim L, Khattak A, Gibbs P. Initial experience of TAS-102 chemotherapy in Australian patients with Chemo-refractory metastatic colorectal cancer. Curr Probl Cancer 2021; 46:100793. [PMID: 34565601 DOI: 10.1016/j.currproblcancer.2021.100793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 08/09/2021] [Accepted: 08/20/2021] [Indexed: 11/24/2022]
Abstract
For patients with refractory metastatic colorectal cancer (mCRC) treatment with Trifluridine/Tipiracil, also known as TAS-102, improves overall survival. This study aims to investigate the efficacy and safety of TAS-102 in a real-world population from Victoria, Australia. A retrospective analysis of prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry was undertaken. The characteristics and outcomes of patients receiving TAS-102 were assessed and compared to those enrolled in the registration study (RECOURSE). Across 13 sites, 107 patients were treated with TAS-102. The median age was 60 years (range: 31-83), compared to 63 for RECOURSE. Comparing registry TAS-102-treated and RECOURSE patients, 75% vs 100% were ECOG performance status 0-1, 74% vs 79% had initiated treatment more than 18 months from diagnosis of metastatic disease and 36% vs 49% were RAS wild-type. Median time on treatment was 10.4 weeks (range: 1.7-32). Median progression-free survival (PFS) was 3.3 months compared to 2 months in RECOURSE, while median overall survival was the same at 7.1 months. Two patients (2.3%) had febrile neutropenia and there were no treatment-related deaths, where TAS-102 dose at treatment initiation was at clinician discretion.TRACC registry patients treated with TAS-102 were younger than those from the RECOURSE trial, with similar overall survival observed. Less strict application of RECIST criteria and less frequent imaging may have contributed to an apparently longer PFS.
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Affiliation(s)
- A Jalali
- Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, Western Health, VIC, Australia; Department of Medical Oncology, Latrobe Regional Hospital, VIC, Australia.
| | - G Gard
- Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, VIC, Australia
| | - S Banks
- Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, VIC, Australia
| | - C Dunn
- Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, VIC, Australia
| | - H L Wong
- Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, VIC, Australia
| | - R Wong
- Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, Eastern Health, VIC, Australia; Eastern Health Clinical School, Monash University, VIC, Australia
| | - M Lee
- Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, Western Health, VIC, Australia; Department of Medical Oncology, Eastern Health, VIC, Australia; Eastern Health Clinical School, Monash University, VIC, Australia
| | - L Gately
- Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, VIC, Australia
| | - M Loft
- Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, VIC, Australia
| | - J D Shapiro
- Department of Medical Oncology, Cabrini Hospital, VIC, Australia
| | - S Kosmider
- Department of Medical Oncology, Western Health, VIC, Australia
| | - J Tie
- Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, Western Health, VIC, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, VIC, Australia
| | - S Ananda
- Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, Western Health, VIC, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, VIC, Australia; Department of Medical Oncology, Epworth Health, VIC, Australia
| | - J M Yeung
- Department of Surgery, Western Health, University of Melbourne, VIC, Australia; Western Health Chronic Disease Alliance, Western Health, VIC, Australia
| | - R Jennens
- Department of Medical Oncology, Epworth Health, VIC, Australia
| | - B Lee
- Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, VIC, Australia; Department of Medical Oncology, Northern Health, VIC, Australia
| | - J McKendrick
- Department of Medical Oncology, Eastern Health, VIC, Australia; Department of Medical Oncology, Epworth Health, VIC, Australia
| | - L Lim
- Department of Medical Oncology, Eastern Health, VIC, Australia
| | - A Khattak
- Department of Medical Oncology, Fiona Stanley Hospital, WA, Australia
| | - P Gibbs
- Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, VIC, Australia; Department of Medical Oncology, Western Health, VIC, Australia
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13
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To YH, Degeling K, Kosmider S, Wong R, Lee M, Dunn C, Gard G, Jalali A, Wong V, IJzerman M, Gibbs P, Tie J. Circulating Tumour DNA as a Potential Cost-Effective Biomarker to Reduce Adjuvant Chemotherapy Overtreatment in Stage II Colorectal Cancer. PHARMACOECONOMICS 2021; 39:953-964. [PMID: 34089503 DOI: 10.1007/s40273-021-01047-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 05/18/2021] [Indexed: 06/12/2023]
Abstract
BACKGROUND AND OBJECTIVE Substantial adjuvant chemotherapy (AC) overtreatment for stage II colorectal cancer results in a health and financial burden. Circulating tumour DNA (ctDNA) can improve patient selection for AC by detecting micro-metastatic disease. We estimated the health economic potential of ctDNA-guided AC for stage II colorectal cancer. METHODS A cost-utility analysis was performed to compare ctDNA-guided AC to standard of care, where 22.6% of standard of care patients and all ctDNA-positive patients (8.7% of tested patients) received AC and all ctDNA-negative patients (91.3%) did not. A third preference-sensitive ctDNA strategy was included where 6.8% of ctDNA-negative patients would receive AC. A state-transition model was populated using data from a prospective cohort study and clinical registries. Health and economic outcomes were discounted at 5% over a lifetime horizon from a 2019 Australian payer perspective. Extensive scenario and probabilistic analyses quantified model uncertainty. RESULTS Compared to standard of care, the ctDNA and preference-sensitive ctDNA strategies increased quality-adjusted life-years by 0.20 (95% confidence interval - 0.40 to 0.81) and 0.19 (- 0.40 to 0.78), and resulted in incremental costs of AUD - 4055 (- 16,853 to 8472) and AUD - 2284 (- 14,685 to 10,116), respectively. Circulating tumour DNA remained cost effective at a willingness to pay of AUD 20,000 per quality-adjusted life-year gained throughout most scenario analyses in which the proportion of ctDNA-positive patients cured by AC and compliance to a ctDNA-negative test results were decreased. CONCLUSIONS Circulating tumour-guided AC is a potentially cost-effective strategy towards reducing overtreatment in stage II colorectal cancer. Results from ongoing randomised clinical studies will be important to reduce uncertainty in the estimates.
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Affiliation(s)
- Yat Hang To
- Personalised Oncology Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Melbourne, VIC, 3052, Australia.
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
| | - Koen Degeling
- Cancer Health Services Research, Centre for Cancer, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia
- Cancer Health Services Research, Centre for Health Policy, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia
| | - Suzanne Kosmider
- Department of Medical Oncology, Western Health, Melbourne, VIC, Australia
| | - Rachel Wong
- Personalised Oncology Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Melbourne, VIC, 3052, Australia
- Department of Medical Oncology, Eastern Health, Melbourne, VIC, Australia
- Eastern Health Clinical School, Faculty of Medicine, Nursing and Health Science, Monash University, Melbourne, VIC, Australia
| | - Margaret Lee
- Personalised Oncology Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Melbourne, VIC, 3052, Australia
- Department of Medical Oncology, Western Health, Melbourne, VIC, Australia
- Department of Medical Oncology, Eastern Health, Melbourne, VIC, Australia
- Eastern Health Clinical School, Faculty of Medicine, Nursing and Health Science, Monash University, Melbourne, VIC, Australia
| | - Catherine Dunn
- Personalised Oncology Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Melbourne, VIC, 3052, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
| | - Grace Gard
- Personalised Oncology Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Melbourne, VIC, 3052, Australia
- Department of Medical Oncology, Western Health, Melbourne, VIC, Australia
| | - Azim Jalali
- Personalised Oncology Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Melbourne, VIC, 3052, Australia
- Department of Medical Oncology, Western Health, Melbourne, VIC, Australia
- Department of Medical Oncology, LaTrobe Regional Hospital, Traralgon, VIC, Australia
| | - Vanessa Wong
- Personalised Oncology Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Melbourne, VIC, 3052, Australia
- Department of Medical Oncology, Ballarat Health, Ballarat, VIC, Australia
| | - Maarten IJzerman
- Cancer Health Services Research, Centre for Cancer, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia
- Cancer Health Services Research, Centre for Health Policy, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia
- Department of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
| | - Peter Gibbs
- Personalised Oncology Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Melbourne, VIC, 3052, Australia
- Department of Medical Oncology, Western Health, Melbourne, VIC, Australia
- Faculty of Medicine and Health Sciences, University of Melbourne, Melbourne, VIC, Australia
| | - Jeanne Tie
- Personalised Oncology Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Melbourne, VIC, 3052, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
- Department of Medical Oncology, Western Health, Melbourne, VIC, Australia
- Faculty of Medicine and Health Sciences, University of Melbourne, Melbourne, VIC, Australia
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14
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Treatment and Outcomes of Oligometastatic Colorectal Cancer Limited to Lymph Node Metastases. Clin Colorectal Cancer 2021; 20:e233-e239. [PMID: 34289941 DOI: 10.1016/j.clcc.2021.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 06/19/2021] [Accepted: 06/20/2021] [Indexed: 11/20/2022]
Abstract
INTRODUCTION The optimal management of isolated distant lymph node metastases (IDLNM) from a colorectal primary, is not clearly established. We aimed to analyze the outcomes of patients with IDLNM treated with systemic therapies plus locoregional therapy with curative intent versus systemic therapies with palliative intent. MATERIALS & METHODS Clinical data were collected and reviewed from the Treatment of Recurrent and Advanced Colorectal Cancer registry, a prospective, comprehensive registry for metastatic colorectal cancer (mCRC) treated at multiple tertiary hospitals across Australia. Clinicopathological characteristics, treatment modalities and survival outcomes were analyzed in patients with IDLNM and compared to patients with disease at other sites. RESULTS Of 3408 mCRC patients diagnosed 2009 to 2020, with median follow-up of 38.0 months, 93 (2.7%) were found to have IDLNM. Compared to mCRC at other sites, patients with IDLNM were younger (mean age: 62.1 vs. 65.6 years, P = .02), more likely to have metachronous disease (57.0% vs. 38.9%, P < .01), be KRAS wild-type (74.6% vs. 53.9%, P< .01) and BRAF mutant (12.9% vs. 6.2%, P = .01). Amongst mCRC patients with IDLNM, 24 (25.8%) received treatment with curative intent and had a significantly better overall median survival than those treated with palliative intent (73.5 months vs. 23.2 months, P = .01). These 24 patients had an overall median survival similar (62.7 months, P = .82) to patients with isolated liver or lung metastases also treated with curative intent. CONCLUSION Curative treatment strategies (radiotherapy or surgery), with or without systemic therapy, should be considered for mCRC patients with IDLNM where appropriate as assessed by the multidisciplinary team.
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15
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Dunn C, Hong W, Gibbs P, Ackland S, Sjoquist K, Tebbutt NC, Price T, Burge M. Personalizing First-Line Systemic Therapy in Metastatic Colorectal Cancer: Is There a Role for Initial Low-Intensity Therapy in 2021 and Beyond? A Perspective From Members of the Australasian Gastrointestinal Trials Group. Clin Colorectal Cancer 2021; 20:245-255. [PMID: 34103264 DOI: 10.1016/j.clcc.2021.05.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 04/16/2021] [Accepted: 05/02/2021] [Indexed: 01/18/2023]
Abstract
Palliative chemotherapy is the cornerstone of treatment for the majority of patients with metastatic colorectal cancer, with the aim of increasing length and quality of life. Although guidelines outline the available treatment options in the first line, they provide limited guidance on choice and intensity of the chemotherapy backbone. Data from the TRIBE and TRIBE2 studies confirm a survival benefit with triplet FOLFOXIRI and bevacizumab, and this is a preferred option for younger patients with good performance status able to tolerate it. However, the relative benefit of a fluoropyrimidine doublet with oxaliplatin or irinotecan over single-agent fluoropyrimidine with or without a biologic is less certain; the available data demonstrate that single-agent fluoropyrimidine plus a biologic with planned sequencing of subsequent agents can produce similar overall survival outcomes with reduced toxicity. Our analysis of local real-world registry data suggests that this is an underutilized approach, particularly in younger and fitter patients. Established prognostic factors, including patient age, performance status, tumor sidedness, and biomarkers such as RAS/BRAF, are key in treatment selection; patients with left-sided RAS/BRAF wild-type disease or patients with low tumor bulk may be ideal for a less intensive regimen. Further studies are required to confirm the value of less-intensive regimens in the modern era, where the incorporation of biologic therapies has become routine and where non-chemotherapy options are emerging as viable options for molecularly defined patient subsets.
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Affiliation(s)
- Catherine Dunn
- Gibbs Lab, Personalised Medicine Division, Walter and Eliza Hall Institute, Melbourne, Victoria, Australia.
| | - Wei Hong
- Gibbs Lab, Personalised Medicine Division, Walter and Eliza Hall Institute, Melbourne, Victoria, Australia
| | - Peter Gibbs
- Gibbs Lab, Personalised Medicine Division, Walter and Eliza Hall Institute, Melbourne, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia; Department of Medical Oncology, Western Health, Melbourne, Victoria, Australia
| | - Stephen Ackland
- Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, New South Wales, Australia
| | - Katrin Sjoquist
- NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia; Cancer Care Centre, St. George Hospital, Kogarah, New South Wales, Australia
| | - Niall C Tebbutt
- Department of Medical Oncology, Austin Health, Melbourne, Victoria, Australia; Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia
| | - Timothy Price
- Department of Medical Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia
| | - Matthew Burge
- Department of Medical Oncology, Royal Brisbane Hospital, Herston, Queensland, Australia
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16
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Min ST, Roohullah A, Tognela A, Jalali A, Lee M, Wong R, Shapiro J, Burge M, Yip D, Nott L, Zimet A, Lee B, Dean A, Steel S, Wong HL, Gibbs P, Lim SHS. Patient demographics and management landscape of metastatic colorectal cancer in the third-line setting: Real-world data in an australian population. Asia Pac J Clin Oncol 2021; 18:e56-e63. [PMID: 33870631 DOI: 10.1111/ajco.13553] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 12/02/2020] [Indexed: 11/28/2022]
Abstract
BACKGROUND Colorectal cancer is the third most common cancer and second leading cause of cancer mortality in Australia, thus carrying a significant disease burden. AIMS This analysis aims to explore real-world treatment landscape of metastatic colorectal cancer in the third-line setting. METHODS We retrospectively analysed treatment of recurrent and advanced colorectal cancer (TRACC) registry database from 2009 onwards. Patients treated with palliative intent who progressed after two lines of therapies were included. One treatment line was defined as any combination of systemic therapy given until progression. RESULTS Out of 1820 patients treated palliatively, 32% (590 patients) met study criteria. Of these, 43% (254 patients) proceeded to third-line therapy, equating to 14% of all metastatic patients. In KRAS mutant or unknown tumours (97 patients), fluoropyrimidine (FP)-oxaliplatin combination was the most common choice (51%), followed by FP-irinotecan (15%), trifluridine/tipiracil (11%), mono-chemotherapy (10%), regorafenib (5%) and others (7%). Majority of FP-doublet (83%) was given as rechallenge. In 157 patients with KRAS wildtype disease, monotherapy with EGFR inhibitor was most commonly used (41%), followed by EGFR inhibitor with chemotherapy (20%), FP-doublet (18%), mono-chemotherapy (6%), trifluridine/tipiracil (6%), regorafenib (1%) and others (8%). Median overall survival was 7.1 months (range 0.4-41.2), and median time on third-line treatment was 3 months (range 0.1-40). CONCLUSIONS In real-world Australian population, treatment choices differed based on KRAS status and will likely change with the availability of newer drugs on the pharmaceutical benefits scheme. Survival outcomes are comparable to newer agents in clinical trials for select patients.
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Affiliation(s)
- Sandy Tun Min
- Macarthur Cancer Therapy Centre, Campbelltown, New South Wales, Australia
| | - Aflah Roohullah
- Macarthur Cancer Therapy Centre, Campbelltown, New South Wales, Australia.,School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia
| | - Annette Tognela
- Macarthur Cancer Therapy Centre, Campbelltown, New South Wales, Australia.,School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia
| | - Azim Jalali
- Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.,Department of Medical Oncology, Western Health, St Albans, Victoria, Australia
| | - Margaret Lee
- Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.,Department of Medical Oncology, Western Health, St Albans, Victoria, Australia.,Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia
| | - Rachel Wong
- Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.,Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia.,Department of Medicine, Monash University, Clayton, Victoria, Australia.,Epworth Health Care, Box Hill, Victoria, Australia
| | - Jeremy Shapiro
- Department of Medicine, Monash University, Clayton, Victoria, Australia.,Cabrini Haematology and Oncology Centre, Malvern, Victoria, Australia
| | - Matthew Burge
- Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.,Faculty of Medicine, University of Queensland, St Lucia, Queensland, Australia
| | - Desmond Yip
- Department of Medical Oncology, Canberra and Calvary Hospitals, Garran, Australia Capital Territory, Australia
| | - Louise Nott
- Royal Hobart Hospital, Hobart, Tasmania, Australia
| | - Allan Zimet
- Epworth HealthCare, Richmond, Victoria, Australia
| | - Belinda Lee
- Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.,Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,The Northern Hospital, Epping, Victoria, Australia
| | - Andrew Dean
- Department of Medical Oncology, St John of God Hospital, Subiaco, Western Australia, Australia
| | - Simone Steel
- Peninsula Private Hospital, Frankston, Victoria, Australia
| | - Hui-Li Wong
- Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.,Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Peter Gibbs
- Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.,Department of Medical Oncology, Western Health, St Albans, Victoria, Australia.,Department of Medical Oncology, Royal Melbourne Hospital, Parkville, Victoria, Australia.,Faculty of Medicine, University of Melbourne, Parkville, Victoria, Australia
| | - Stephanie Hui-Su Lim
- Macarthur Cancer Therapy Centre, Campbelltown, New South Wales, Australia.,School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia.,Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia
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17
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Kostos L, Hong W, Lee B, Tran B, Lok SW, Anton A, Gard G, To YH, Wong V, Shapiro J, Wong R, Wong S, de Boer R, Gibbs P. Cancer clinical trial vs real-world outcomes for standard of care first-line treatment in the advanced disease setting. Int J Cancer 2021; 149:409-419. [PMID: 33729581 DOI: 10.1002/ijc.33568] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 02/25/2021] [Accepted: 03/02/2021] [Indexed: 01/05/2023]
Abstract
Clinical trials have strict eligibility criteria, potentially limiting external validity. However, while often discussed this has seldom been explored, particularly across cancer types and at variable time frames posttrial completion. We examined comprehensive registry data (January 2014 to June 2019) for standard first-line treatments for metastatic colorectal cancer (CRC), advanced pancreatic cancer (PC), metastatic HER2-amplified breast cancer (BC) and castrate-resistant prostate cancer (CaP). Registry patient characteristics and outcomes were compared to the practice-changing trial. Registry patients were older than the matched trial cohort by a median of 2-6 years (all P = <.01) for the CRC, BC and PC cohorts. The proportion of Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 patients was lower for CRC (94.1% vs 99.2%, P = .001) and BC (94.9% vs 99.3%, P = .001). Progression-free survival (PFS) for registry patients was similar to the trial patients or significantly longer (CaP, Hazard Ratio [HR] = 0.65, P = <.001). Overall survival (OS) was also similar or significantly longer (CaP, HR 0.49, P = <.001). In conclusion, despite real-world patients sometimes being older or having inferior PS to trial cohorts, the survival outcomes achieved were consistently equal or superior to those reported for the same treatment in the trial. We suggest that this is potentially due to optimised use of each treatment over time, improved multidisciplinary care and increased postprogression options. We can reassure clinicians and patients that outcomes matching or exceeding those reported in trials are possible. The potential for survival gains over time should routinely be factored into future trial statistical plans.
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Affiliation(s)
- Louise Kostos
- Department of Medical Oncology, Western Health, Melbourne, Victoria, Australia.,Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Wei Hong
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
| | - Belinda Lee
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.,Department of Medical Oncology, Northern Health, Melbourne, Victoria, Australia
| | - Ben Tran
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
| | - Sheau Wen Lok
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
| | - Angelyn Anton
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.,Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia.,Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Grace Gard
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
| | - Yat Hang To
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
| | - Vanessa Wong
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
| | - Jeremy Shapiro
- Cabrini Haematology and Oncology Centre, Melbourne, Victoria, Australia
| | - Rachel Wong
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.,Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia.,Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Shirley Wong
- Department of Medical Oncology, Western Health, Melbourne, Victoria, Australia
| | - Richard de Boer
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Peter Gibbs
- Department of Medical Oncology, Western Health, Melbourne, Victoria, Australia.,Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
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18
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Degeling K, Wong HL, Koffijberg H, Jalali A, Shapiro J, Kosmider S, Wong R, Lee B, Burge M, Tie J, Yip D, Nott L, Khattak A, Lim S, Caird S, Gibbs P, IJzerman M. Simulating Progression-Free and Overall Survival for First-Line Doublet Chemotherapy With or Without Bevacizumab in Metastatic Colorectal Cancer Patients Based on Real-World Registry Data. PHARMACOECONOMICS 2020; 38:1263-1275. [PMID: 32803720 DOI: 10.1007/s40273-020-00951-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
BACKGROUND Simulation models utilizing real-world data have potential to optimize treatment sequencing strategies for specific patient subpopulations, including when conducting clinical trials is not feasible. We aimed to develop a simulation model to estimate progression-free survival (PFS) and overall survival for first-line doublet chemotherapy with or without bevacizumab for specific subgroups of metastatic colorectal cancer (mCRC) patients based on registry data. METHODS Data from 867 patients were used to develop two survival models and one logistic regression model that populated a discrete event simulation (DES). Discrimination and calibration were used for internal validation of these models separately and predicted and observed medians and Kaplan-Meier plots were compared for the integrated DES. Bootstrapping was performed to correct for optimism in the internal validation and to generate correlated sets of model parameters for use in a probabilistic analysis to reflect parameter uncertainty. RESULTS The survival models showed good calibration based on the regression slopes and modified Hosmer-Lemeshow statistics at 1 and 2 years, but not for short-term predictions at 0.5 years. Modified C-statistics indicated acceptable discrimination. The simulation estimated that median first-line PFS (95% confidence interval) of 219 (25%) patients could be improved from 175 days (156-199) to 269 days (246-294) if treatment would be targeted based on the highest expected PFS. CONCLUSIONS Extensive internal validation showed that DES accurately estimated the outcomes of treatment combination strategies for specific subpopulations, with outcomes suggesting treatment could be optimized. Although results based on real-world data are informative, they cannot replace randomized trials.
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Affiliation(s)
- Koen Degeling
- Health Technology and Services Research Department, Faculty of Behavioural, Management and Social Sciences, Technical Medical Centre, University of Twente, Enschede, The Netherlands.
- Cancer Health Services Research, School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia.
| | - Hui-Li Wong
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
| | - Hendrik Koffijberg
- Health Technology and Services Research Department, Faculty of Behavioural, Management and Social Sciences, Technical Medical Centre, University of Twente, Enschede, The Netherlands
| | - Azim Jalali
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia
| | - Jeremy Shapiro
- Department of Medical Oncology, Cabrini Health, Melbourne, VIC, Australia
| | - Suzanne Kosmider
- Department of Medical Oncology, Western Health, Melbourne, VIC, Australia
| | - Rachel Wong
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia
- Department of Medical Oncology, Eastern Health, Melbourne, VIC, Australia
- Eastern Health Clinical School, Monash University, Box Hill, VIC, Australia
| | - Belinda Lee
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
- Department of Medical Oncology, Northern Health, Melbourne, VIC, Australia
| | - Matthew Burge
- Department of Medical Oncology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
| | - Jeanne Tie
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
- Department of Medical Oncology, Western Health, Melbourne, VIC, Australia
| | - Desmond Yip
- Department of Medical Oncology, The Canberra Hospital, Canberra, ACT, Australia
| | - Louise Nott
- Department of Medical Oncology, Royal Hobart Hospital, Hobart, TAS, Australia
| | - Adnan Khattak
- Department of Medical Oncology, Fiona Stanley Hospital, Perth, WA, Australia
| | - Stephanie Lim
- Department of Medical Oncology, Campbelltown Hospital, Campbelltown, NSW, Australia
| | - Susan Caird
- Department of Medical Oncology, Gold Coast University Hospital, Gold Coast, QLD, Australia
| | - Peter Gibbs
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia
- Department of Medical Oncology, Western Health, Melbourne, VIC, Australia
| | - Maarten IJzerman
- Health Technology and Services Research Department, Faculty of Behavioural, Management and Social Sciences, Technical Medical Centre, University of Twente, Enschede, The Netherlands
- Cancer Health Services Research, School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
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19
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Prasanna T, Wong R, Price T, Shapiro J, Tie J, Wong HL, Nott L, Roder D, Lee M, Kosmider S, Jalali A, Burge M, Padbury R, Maddern G, Carruthers S, Moore J, Sorich M, Karapetis CS, Gibbs P, Yip D. Metastasectomy and BRAF mutation; an analysis of survival outcome in metastatic colorectal cancer. Curr Probl Cancer 2020; 45:100637. [PMID: 32826083 DOI: 10.1016/j.currproblcancer.2020.100637] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 07/14/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Resection of oligometastases improves survival in metastatic colorectal cancer (mCRC). It is unclear whether the benefit is consistent for BRAF V600E mutant (MT) and wild type (WT) mCRC. This retrospective analysis explores the influence of BRAF MT on survival after metastasectomy. METHODS Overall survival (OS) and recurrence-free survival (RFS) for BRAF MT and WT mCRC were evaluated. Survival was also analyzed in the cohort of BRAF MT with or without metastasectomy. RESULTS Five hundred and thirteen patients who had undergone metastasectomy were identified, 6% were BRAF-MT. Median age 63. Median OS in BRAF MT vs WT: 25.7 vs 48.5 months (hazard ratio [HR] 1.95; 1.18-3.22). However, difference was not significant in a multivariate model. Right primary tumor, intact primary, >1 metastatic site, non-R0 resection, peritoneal metastasis, and synchronous metastasis were independent predictors of worse OS. Among 364 patients with RFS data there was no difference between BRAF MT and WT (16 vs 19 months, p=0.09). In another cohort of 158 BRAF-MT patients, OS was significantly better after metastasectomy compared to "no metastasectomy" (HR 0.34; 0.18-0.65, P= 0.001). Proficient mismatch repair status showed a trend toward worse survival after metastasectomy in BRAF MT (HR 1.71, P = 0.08). CONCLUSION OS did not differ after metastasectomy between BRAF MT and WT in a multivariate model. Median OS was >2 years in this study after metastasectomy among BRAFV600E MT patients suggesting a survival benefit of metastasectomy in this group where systemic therapeutic options are limited. Metastasectomy may be considered in carefully selected BRAF-MT patients.
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Affiliation(s)
- Thiru Prasanna
- Department of Medical Oncology, The Canberra Hospital, Garran, ACT, Australia; ANU Medical School, Australian National University, Australia; University of Canberra, ACT, Australia.
| | - Rachel Wong
- Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Oncology, Eastern Health, Melbourne, Australia; Monash University, Faculty of Medicine, Nursing and Health Sciences, Melbourne, Australia
| | - Timothy Price
- The Queen Elizabeth Hospital and University of Adelaide, Adelaide, Australia
| | - Jeremy Shapiro
- Cabrini Haematology and Oncology Centre, Melbourne, Australia
| | - Jeanne Tie
- Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Oncology, Western Hospital, Melbourne, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Hui-Li Wong
- Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
| | - Louise Nott
- Department of Medical Oncology, Royal Hobart Hospital, Hobart, Tasmania, Australia; Menzies Research institute, Hobart, Australia
| | - David Roder
- South Australian Health & Medical Research Institute (SAHMRI), Australia; University of South Australia, Adelaide, Australia
| | - Margaret Lee
- Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Oncology, Eastern Health, Melbourne, Australia
| | - Suzanne Kosmider
- Department of Medical Oncology, Western Hospital, Melbourne, Australia
| | - Azim Jalali
- Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Oncology, Western Hospital, Melbourne, Australia
| | - Matthew Burge
- Department of Medical Oncology, Royal Brisbane Hospital, Brisbane, Australia
| | - Robert Padbury
- Flinders University, Bedford Park, Australia; Department of Surgery, Flinders Medical Centre, Australia
| | - Guy Maddern
- University of Adelaide Discipline of Surgery, The Queen Elizabeth Hospital, Adelaide, Australia
| | - Scott Carruthers
- Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, Australia
| | - James Moore
- Department of Surgery, Royal Adelaide Hospital, Adelaide, Australia
| | - Michael Sorich
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Christos S Karapetis
- Flinders University, Bedford Park, Australia; Department of Medical Oncology, Flinders Medical Centre, Australia
| | - Peter Gibbs
- Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Oncology, Western Hospital, Melbourne, Australia
| | - Desmond Yip
- Department of Medical Oncology, The Canberra Hospital, Garran, ACT, Australia; ANU Medical School, Australian National University, Australia
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20
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Travers A, Jalali A, Begbie S, Semira C, Kosmider S, Ananda S, Wong R, Lee M, Shapiro J, Burge M, Yip D, Torres J, Ma B, Nott L, Dean A, Tie J, Khattak A, Lim S, Wong HL, Gibbs P. Real-World Treatment and Outcomes of Metastatic Colorectal Cancer Patients With a Poor or Very Poor Performance Status. Clin Colorectal Cancer 2020; 20:e21-e34. [PMID: 32919889 DOI: 10.1016/j.clcc.2020.08.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 08/05/2020] [Accepted: 08/09/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND The management of metastatic colorectal cancer patients with a poor performance status (PS) continues to be a clinical dilemma, with the potential activity and safety of treating this population remaining poorly understood. Few of these patients are enrolled onto clinical trials, and poor PS is often multifactorial. PATIENTS AND METHODS We analyzed the Treatment of Recurrent and Advanced Colorectal Cancer registry to describe treatment practices and outcomes in poor (Eastern Cooperative Oncology Group [ECOG] PS 2) and very poor PS (ECOG PS > 2) patients to explore the relationship between age, tumor burden, comorbidities, and PS, and to evaluate the benefit of systemic therapy. Standard descriptive statistical methods, Kaplan-Meier analysis, and a multivariate Cox regression model were used. RESULTS Of 2769 registry patients (diagnosed January 2009 to June 2018), 329 (12%) and 182 (7%) patients had a poor and very poor PS, respectively. Good PS patients were more likely to receive systemic therapy than poor and very poor PS patients (85%, 55%, and 21.5%, P < .0001), but clinician assessed response was observed in all subsets (53%, 41%, and 29%, P = .0003). Treatment with chemotherapy was associated with longer median overall survival across PS groups. Exploratory analysis based on comorbidity score and tumor burden subgroups demonstrated a consistently positive overall survival association with treatment. Benefit was observed where poor overall survival was attributable to medical comorbidities and to tumor burden. CONCLUSION In routine clinical care, a substantial proportion of poor and very poor PS patients receive active treatment, which is often associated with meaningful clinical benefit.
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Affiliation(s)
- Avraham Travers
- Department of Medical Oncology, Calvary Mater Newcastle, Waratah, Australia.
| | - Azim Jalali
- Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Western Health, Footscray, Australia
| | - Stephen Begbie
- Mid North Coast Cancer Institute, Port Macquarie, Australia
| | - Christine Semira
- Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
| | | | - Sumitra Ananda
- Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Western Health, Footscray, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Dentistry and Health Sciences, Faculty of Medicine, University of Melbourne, Parkville, Australia
| | - Rachel Wong
- Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Eastern Health, Box Hill, Australia; Eastern Health Clinical School, Monash University, Box Hill, Australia; Epworth Healthcare, Box Hill, Australia
| | - Margaret Lee
- Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Western Health, Footscray, Australia; Eastern Health, Box Hill, Australia; Eastern Health Clinical School, Monash University, Box Hill, Australia
| | - Jeremy Shapiro
- Haematology and Medical Oncology Unit, Cabrini Hospital, Malvern, Australia; Department of Medicine, Monash University, Clayton, Australia
| | - Matthew Burge
- Royal Brisbane and Women's Hospital, Herston, Australia; University of Queensland, St Lucia, Australia
| | - Desmond Yip
- Department of Medical Oncology, Canberra Hospital, Garran, Australia; ANU Medical School, Australian National University, Canberra, Australia
| | - Javier Torres
- Goulburn Valley Health, Shepparton, Australia; Dentistry and Health Sciences-Shepparton Campus, Faculty of Medicine, University of Melbourne, Shepparton, Australia
| | - Brigette Ma
- Chinese University of Hong Kong Prince of Wales Hospital, Department of Clinical Oncology, State Key Laboratory of Translational Oncology, Shatin, New Territories, Hong Kong SAR, China
| | | | - Andrew Dean
- Bendat Cancer Centre, St John of God Subiaco Hospital, Subiaco, Australia
| | - Jeanne Tie
- Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Western Health, Footscray, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Dentistry and Health Sciences, Faculty of Medicine, University of Melbourne, Parkville, Australia
| | | | - Stephanie Lim
- Macarthur Cancer Therapy Centre, Campbelltown Hospital, Campbelltown, Australia
| | - Hui-Li Wong
- Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Peter Gibbs
- Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Western Health, Footscray, Australia
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21
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Degeling K, Vu M, Koffijberg H, Wong HL, Koopman M, Gibbs P, IJzerman M. Health Economic Models for Metastatic Colorectal Cancer: A Methodological Review. PHARMACOECONOMICS 2020; 38:683-713. [PMID: 32319026 DOI: 10.1007/s40273-020-00908-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
OBJECTIVE The aim of this systematic review was to provide a comprehensive and detailed review of structural and methodological assumptions in model-based cost-effectiveness analyses of systemic metastatic colorectal cancer (mCRC) treatments, and discuss their potential impact on health economic outcome estimates. METHODS Five databases (EMBASE, MEDLINE, Cochrane Library, Health Technology Assessment and National Health Service Health Economic Evaluation Database) were searched on 26 August 2019 for model-based full health economic evaluations of systemic mCRC treatment using a combination of free-text terms and subject headings. Full-text publications in English were eligible for inclusion if they were published in or after the year 2000. The Consolidated Health Economic Evaluation Reporting Standards checklist was used to assess the reporting quality of included publications. Study selection, appraisal and data extraction were performed by two reviewers independently. RESULTS The search yielded 1418 publications, of which 54 were included, representing 51 unique studies. Most studies focused on first-line treatment (n = 29, 57%), followed by third-line treatment (n = 13, 25%). Model structures were health-state driven (n = 27, 53%), treatment driven (n = 19, 37%), or a combination (n = 5, 10%). Cohort-level state-transition modelling (STM) was the most common technique (n = 33, 65%), followed by patient-level STM and partitioned survival analysis (both n = 6, 12%). Only 15 studies (29%) reported some sort of model validation. Health economic outcomes for specific strategies differed substantially between studies. For example, survival following first-line treatment with fluorouracil, leucovorin and oxaliplatin ranged from 1.21 to 7.33 years, with treatment costs ranging from US$8125 to US$126,606. CONCLUSIONS Model-based cost-effectiveness analyses of systemic mCRC treatments have adopted varied modelling methods and structures, resulting in substantially different outcomes. As models generally focus on first-line treatment without consideration of downstream treatments, there is a profound source of structural uncertainty implying that the cost-effectiveness of treatments across the mCRC pathway remains uncertain.
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Affiliation(s)
- Koen Degeling
- Cancer Health Services Research, Centre for Cancer Research, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia.
- Cancer Health Services Research, Centre for Health Policy, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia.
| | - Martin Vu
- Cancer Health Services Research, Centre for Cancer Research, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia
- Cancer Health Services Research, Centre for Health Policy, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia
| | - Hendrik Koffijberg
- Health Technology and Services Research, Technical Medical Centre, Faculty of Behavioural, Management and Social Sciences, University of Twente, Enschede, The Netherlands
| | - Hui-Li Wong
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Miriam Koopman
- Department of Medical Oncology, University Medical Centre Utrecht and Utrecht University, Utrecht, The Netherlands
| | - Peter Gibbs
- Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
- Department of Medical Oncology, Western Health, Melbourne, Australia
| | - Maarten IJzerman
- Cancer Health Services Research, Centre for Cancer Research, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia
- Cancer Health Services Research, Centre for Health Policy, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia
- Health Technology and Services Research, Technical Medical Centre, Faculty of Behavioural, Management and Social Sciences, University of Twente, Enschede, The Netherlands
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
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22
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Foroughi S, Hutchinson RA, Wong HL, Christie M, Batrouney A, Wong R, Lee M, Tie J, Burgess AW, Gibbs P. Immunohistochemical evaluation of the prognostic and predictive power of epidermal growth factor receptor ligand levels in patients with metastatic colorectal cancer. Growth Factors 2020; 38:127-136. [PMID: 33775193 DOI: 10.1080/08977194.2021.1878166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
For patients with metastatic colorectal cancer (mCRC), epidermal growth factor receptor (EGFR) inhibitors are limited to patients with RAS wild-type tumours. Not all patients will benefit from treatment and better predictive biomarkers are needed. Here we investigated the prognostic and predictive impact of the EGFR ligands amphiregulin (AREG) and epiregulin (EREG). Expression levels were assessed by immunohistochemistry on 99 KRAS wild-type tumours. AREG and EREG positivity was seen in 49% and 50% of cases, respectively. No difference in expression was observed by primary tumour side. There was no significant difference in OS by AREG or EREG expression. In the subset of patients who received an EGFR inhibitor, EREG positivity was associated with longer OS (median 34.0 vs. 27.0 months, p = 0.033), driven by a difference in patients with a left-sided primary (HR 0.37, p = 0.015). Our study supports further investigation into EREG as a predictive biomarker in mCRC.
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Affiliation(s)
- Siavash Foroughi
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
| | - Ryan A Hutchinson
- Colorectal Oncogenomics Group, The University of Melbourne, Victorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia
- Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia
- University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia
| | - Hui-Li Wong
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Michael Christie
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
- Department of Pathology, Royal Melbourne Hospital, Parkville, Victoria, Australia
| | - Ahida Batrouney
- Department of Pathology, Royal Melbourne Hospital, Parkville, Victoria, Australia
| | - Rachel Wong
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
- Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia
- Eastern Health Clinical School, Monash University, Box Hill, Victoria, Australia
| | - Margaret Lee
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
- Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia
- Eastern Health Clinical School, Monash University, Box Hill, Victoria, Australia
- Department of Medical Oncology, Western Health, St Albans, Victoria, Australia
| | - Jeanne Tie
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Department of Medical Oncology, Western Health, St Albans, Victoria, Australia
| | - Antony Wilks Burgess
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
- Department of Surgery, Royal Melbourne Hospital, Parkville, Victoria, Australia
| | - Peter Gibbs
- Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
- Department of Medical Oncology, Western Health, St Albans, Victoria, Australia
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23
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Lok SW, De Boer R, Cordwell C, Marx G, Fox P, Hasovits C, Rutovitz J, Harold M, Tran B, Wong HL, Gibbs P. Demonstrating the feasibility of collecting secondary, de-identified data on Australian patients receiving treatment as part of a Medicine Access Programme. Intern Med J 2020; 50:99-104. [PMID: 30816606 DOI: 10.1111/imj.14265] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2018] [Revised: 02/18/2019] [Accepted: 02/18/2019] [Indexed: 11/29/2022]
Abstract
BACKGROUND In Australia, data generated from the carefully selected, treated and monitored patients enrolled in clinical trials largely inform routine care and funding approvals. Medicine Access Programmes (MAP) enable drug access and while potentially a rich source of data, historically have not collected data beyond a participant list. AIMS To explore the feasibility of using MAP to identify patient populations for inclusion in non-interventional studies. METHODS Clinicians affiliated with the Walter and Eliza Hall Institute engaged with Roche to implement PeRSIA, a secondary data use non-interventional study of patients receiving neoadjuvant pertuzumab for non-metastatic HER2+ breast cancer. The study utilised a pre-existing Roche-sponsored MAP to identify clinicians as data contributors. Data security, ownership and reporting issues were addressed utilising the BioGrid platform and standards developed for existing Walter and Eliza Hall Institute registries. Disease experts developed project-specific Case Report Forms documenting treatment, surgical and cancer-specific outcomes, and adverse events. RESULTS To date, 12 of 16 (75%) clinicians approached to participate in PeRSIA are contributing de-identified data. From February through September 2018, data on 41 patients from seven centres were collected. Median patient age is 56 years (range 36-81), 36 (88%) had Stage 2 to 3 disease and 27 (66%) were node positive. The median number of cycles of neoadjuvant pertuzumab planned was 4. CONCLUSIONS This initial report is, to our knowledge, the first description of a secondary data use non-interventional study collecting comprehensive data on patients enrolled, independently, in a MAP. This effort continues and opportunities with other industry partners are being pursued.
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Affiliation(s)
- Sheau W Lok
- Walter and Eliza Hall Institute, Melbourne, Victoria, Australia.,Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Richard De Boer
- Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | | | - Gavin Marx
- The University of Sydney and Sydney Adventist Hospital, Sydney, New South Wales, Australia
| | - Peter Fox
- Orange Health Service, Orange, New South Wales, Australia
| | - Csilla Hasovits
- The University of Sydney and Sydney Adventist Hospital, Sydney, New South Wales, Australia
| | - Joseph Rutovitz
- Northern Haematology and Oncology Group, Sydney, New South Wales, Australia
| | - Michael Harold
- Walter and Eliza Hall Institute, Melbourne, Victoria, Australia
| | - Ben Tran
- Walter and Eliza Hall Institute, Melbourne, Victoria, Australia.,Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Hui-Li Wong
- Walter and Eliza Hall Institute, Melbourne, Victoria, Australia.,Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Peter Gibbs
- Walter and Eliza Hall Institute, Melbourne, Victoria, Australia.,University of Melbourne, Melbourne, Victoria, Australia
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24
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Semira C, Wong H, Field K, Lee M, Lee B, Nott L, Shapiro J, Wong R, Tie J, Tran B, Richardson G, Zimet A, Lipton L, Tamjid B, Burge M, Ma B, Johns J, Harold M, Gibbs P. Chemotherapy and biologic use in the routine management of metastatic colorectal cancer in Australia: is clinical practice following the evidence? Intern Med J 2019; 49:446-454. [DOI: 10.1111/imj.14115] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Revised: 08/28/2018] [Accepted: 08/30/2018] [Indexed: 01/09/2023]
Affiliation(s)
- Christine Semira
- Systems Biology and Personalised Medicine DivisionThe Walter and Eliza Hall Institute of Medical Research Melbourne Victoria Australia
- Department of Medical BiologyThe University of Melbourne Melbourne Victoria Australia
| | - Hui‐Li Wong
- Systems Biology and Personalised Medicine DivisionThe Walter and Eliza Hall Institute of Medical Research Melbourne Victoria Australia
- Department of Medical BiologyThe University of Melbourne Melbourne Victoria Australia
| | - Kathryn Field
- Department of Medical BiologyThe University of Melbourne Melbourne Victoria Australia
- Department of Medical OncologyThe Royal Melbourne Hospital Melbourne Victoria Australia
| | - Margaret Lee
- Systems Biology and Personalised Medicine DivisionThe Walter and Eliza Hall Institute of Medical Research Melbourne Victoria Australia
- Department of Medical BiologyThe University of Melbourne Melbourne Victoria Australia
- Department of Medical OncologyWestern Health Melbourne Victoria Australia
- Department of Medical OncologyEastern Health Melbourne Victoria Australia
| | - Belinda Lee
- Systems Biology and Personalised Medicine DivisionThe Walter and Eliza Hall Institute of Medical Research Melbourne Victoria Australia
- Department of Medical BiologyThe University of Melbourne Melbourne Victoria Australia
| | - Louise Nott
- Department of Medical OncologyRoyal Hobart Hospital Hobart Tasmania Australia
| | - Jeremy Shapiro
- Department of Medical OncologyCabrini Health Melbourne Victoria Australia
| | - Rachel Wong
- Systems Biology and Personalised Medicine DivisionThe Walter and Eliza Hall Institute of Medical Research Melbourne Victoria Australia
- Department of Medical BiologyThe University of Melbourne Melbourne Victoria Australia
- Department of Medical OncologyEastern Health Melbourne Victoria Australia
| | - Jeanne Tie
- Systems Biology and Personalised Medicine DivisionThe Walter and Eliza Hall Institute of Medical Research Melbourne Victoria Australia
- Department of Medical BiologyThe University of Melbourne Melbourne Victoria Australia
- Department of Medical OncologyWestern Health Melbourne Victoria Australia
- Department of Medical OncologyPeter MacCallum Cancer Centre Melbourne Victoria Australia
| | - Ben Tran
- Systems Biology and Personalised Medicine DivisionThe Walter and Eliza Hall Institute of Medical Research Melbourne Victoria Australia
- Department of Medical BiologyThe University of Melbourne Melbourne Victoria Australia
- Department of Medical OncologyPeter MacCallum Cancer Centre Melbourne Victoria Australia
| | - Gary Richardson
- Department of Medical OncologyCabrini Health Melbourne Victoria Australia
| | - Allan Zimet
- Department of Medical OncologyEpworth Hospital Melbourne Victoria Australia
| | - Lara Lipton
- Department of Medical OncologyCabrini Health Melbourne Victoria Australia
| | - Babak Tamjid
- Department of Medical OncologyGoulburn Valley Health Shepparton Victoria Australia
| | - Matthew Burge
- Department of Medical OncologyRoyal Brisbane Hospital Brisbane Queensland Australia
| | - Brigette Ma
- Department of Clinical Oncology, Prince of Wales HospitalChinese University of Hong Kong Sha Tin Hong Kong
| | - Julie Johns
- Systems Biology and Personalised Medicine DivisionThe Walter and Eliza Hall Institute of Medical Research Melbourne Victoria Australia
| | - Michael Harold
- Systems Biology and Personalised Medicine DivisionThe Walter and Eliza Hall Institute of Medical Research Melbourne Victoria Australia
| | - Peter Gibbs
- Systems Biology and Personalised Medicine DivisionThe Walter and Eliza Hall Institute of Medical Research Melbourne Victoria Australia
- Department of Medical BiologyThe University of Melbourne Melbourne Victoria Australia
- Department of Medical OncologyWestern Health Melbourne Victoria Australia
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25
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Foroughi S, Wong H, Gately L, Lee M, Simons K, Tie J, Burgess AW, Gibbs P. Registry‐based randomized clinical trials as a method to improve cancer care in Australia. Asia Pac J Clin Oncol 2019; 15:188-189. [DOI: 10.1111/ajco.13122] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Accepted: 12/07/2018] [Indexed: 11/28/2022]
Affiliation(s)
- Siavash Foroughi
- Systems Biology and Personalised Medicine DivisionThe Walter and Eliza Hall Institute of Medical Research Parkville Victoria Australia
- Department of Medical BiologyThe University of Melbourne Parkville Victoria Australia
| | - Hui‐li Wong
- Systems Biology and Personalised Medicine DivisionThe Walter and Eliza Hall Institute of Medical Research Parkville Victoria Australia
- Department of Medical BiologyThe University of Melbourne Parkville Victoria Australia
- Department of Medical OncologyPeter MacCallum Cancer Centre Melbourne Victoria Australia
| | - Lucy Gately
- Systems Biology and Personalised Medicine DivisionThe Walter and Eliza Hall Institute of Medical Research Parkville Victoria Australia
- Department of Medical BiologyThe University of Melbourne Parkville Victoria Australia
| | - Margaret Lee
- Systems Biology and Personalised Medicine DivisionThe Walter and Eliza Hall Institute of Medical Research Parkville Victoria Australia
- Department of Medical BiologyThe University of Melbourne Parkville Victoria Australia
- Department of Medical OncologyEastern Health Box Hill Victoria Australia
- Department of Medical OncologyWestern Health St Albans Victoria Australia
| | - Koen Simons
- Centre for Epidemiology and BiostatisticsMelbourne School of Population and Global HealthThe University of Melbourne Parkville Victoria Australia
- Western Centre for HealthResearch and EducationWestern Health St Albans Victoria Australia
| | - Jeanne Tie
- Systems Biology and Personalised Medicine DivisionThe Walter and Eliza Hall Institute of Medical Research Parkville Victoria Australia
- Department of Medical BiologyThe University of Melbourne Parkville Victoria Australia
- Department of Medical OncologyPeter MacCallum Cancer Centre Melbourne Victoria Australia
- Department of Medical OncologyWestern Health St Albans Victoria Australia
| | - Antony Wilks Burgess
- Department of Medical BiologyThe University of Melbourne Parkville Victoria Australia
- Department of SurgeryRoyal Melbourne HospitalThe University of Melbourne Parkville Victoria Australia
- Structural Biology DivisionThe Walter and Eliza Hall Institute of Medical Research Parkville Victoria Australia
| | - Peter Gibbs
- Systems Biology and Personalised Medicine DivisionThe Walter and Eliza Hall Institute of Medical Research Parkville Victoria Australia
- Department of Medical BiologyThe University of Melbourne Parkville Victoria Australia
- Department of Medical OncologyWestern Health St Albans Victoria Australia
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26
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Prasanna T, Karapetis CS, Roder D, Tie J, Padbury R, Price T, Wong R, Shapiro J, Nott L, Lee M, Chua YJ, Craft P, Piantadosi C, Sorich M, Gibbs P, Yip D. The survival outcome of patients with metastatic colorectal cancer based on the site of metastases and the impact of molecular markers and site of primary cancer on metastatic pattern. Acta Oncol 2018. [DOI: 10.1080/0284186x.2018.1487581 10.1080/0284186x.2018.1487581] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Affiliation(s)
- Thiru Prasanna
- Department of Medical Oncology, The Canberra Hospital, Garran, Canberra, Australia
| | - Christos S. Karapetis
- Department of Medical Oncology, Flinders Medical Centre, Bedford Park, Australia
- Flinders Clinical and Molecular Medicine, Surgery, Flinders University, Bedford Park, Australia
| | - David Roder
- South Australian Health & Medical Research Institute (SAHMRI), Adelaide, Australia
- School of Health Sciences, University of South Australia, Adelaide, Australia
| | - Jeanne Tie
- Department of Medical Oncology, Western Hospital, Melbourne, Australia
- Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Robert Padbury
- Flinders Clinical and Molecular Medicine, Surgery, Flinders University, Bedford Park, Australia
- Department of Surgery, Flinders Medical Centre, Adelaide, Australia
| | - Timothy Price
- The Queen Elizabeth Hospital and University of Adelaide, Adelaide, Australia
| | - Rachel Wong
- Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
- Department of Medical Oncology, Eastern Health, Melbourne, Australia
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia
| | - Jeremy Shapiro
- Cabrini Haematology and Oncology Centre, Melbourne, Australia
| | - Louise Nott
- Department of Medical Oncology, Royal Hobart Hospital, Tasmania, Australia
- Menzies Research Institute, Hobart, Australia
| | - Margaret Lee
- Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
- Department of Medical Oncology, Eastern Health, Melbourne, Australia
| | - Yu Jo Chua
- Department of Medical Oncology, The Canberra Hospital, Garran, Canberra, Australia
- ANU Medical School, Australian National University, Canberra, Australia
| | - Paul Craft
- Department of Medical Oncology, The Canberra Hospital, Garran, Canberra, Australia
- ANU Medical School, Australian National University, Canberra, Australia
| | | | - Michael Sorich
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Peter Gibbs
- Department of Medical Oncology, Western Hospital, Melbourne, Australia
- Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
| | - Desmond Yip
- Department of Medical Oncology, The Canberra Hospital, Garran, Canberra, Australia
- ANU Medical School, Australian National University, Canberra, Australia
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27
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Prasanna T, Karapetis CS, Roder D, Tie J, Padbury R, Price T, Wong R, Shapiro J, Nott L, Lee M, Chua YJ, Craft P, Piantadosi C, Sorich M, Gibbs P, Yip D. The survival outcome of patients with metastatic colorectal cancer based on the site of metastases and the impact of molecular markers and site of primary cancer on metastatic pattern. Acta Oncol 2018; 57:1438-1444. [PMID: 30035653 DOI: 10.1080/0284186x.2018.1487581] [Citation(s) in RCA: 70] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Pattern of spread in patients with metastatic colorectal cancer (mCRC) is variable and may reflect different biology in subsets of patients. This is a retrospective study to explore the outcome of patients with mCRC based on their site of metastasis at diagnosis and to explore the association between tumor characteristics [KRAS/RAS, BRAF, mismatch repair (MMR) status, site of primary] and the site of metastasis. METHODS Patients from two Australian databases were divided into six groups based on site of metastasis at time of diagnosis of metastatic disease; lung-only, liver-only, lymph node-only or any patients with brain, bone or peritoneal metastases. Primary endpoint was overall survival (OS) of each cohort compared with the rest of the population. A Mantel-Haenszel chi-squared test used to explore the association between site of metastasis and selected tumor characteristics. RESULTS Five thousand nine hundred and sixty-seven patients were included. In a univariate analysis, median OS was significantly higher when metastases were limited to lung or liver and shorter for those with brain, bone or peritoneal metastases (p < .001) in both datasets. BRAF mutation was strongly associated with peritoneal metastases (relative risk = 1.8, p < .001) with lower incidence of lung (RR = 0.3, p = .004) and liver (RR = 0.7, p = .005) limited metastases. Lung-only metastases were more frequent with KRAS/RAS mutation (RR = 1.4, p = .007). Left colon tumors were associated with bone (RR = 1.6, p < .001) and lung-only metastases (RR = 2.3, p = .001) while peritoneal spread was less frequent compared with right colon tumors (RR = 0.6, p < .001). Rectal cancer was associated with brain, bone and lung metastases (RR = 1.7; p = .002, 1.7; p < .001, 2.0; p < .001). Liver-only metastases were less frequent in deficient MMR tumors (RR = 0.7, p = .01). CONCLUSION Survival duration with mCRC is related to the site of metastases with lung limited disease showing a more favorable survival outcome compared to other single metastatic site disease. The BRAF mutation and primary rectal cancer were associated with poor prognostic metastatic sites.
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Affiliation(s)
- Thiru Prasanna
- Department of Medical Oncology, The Canberra Hospital, Garran, Canberra, Australia
| | - Christos S. Karapetis
- Department of Medical Oncology, Flinders Medical Centre, Bedford Park, Australia
- Flinders Clinical and Molecular Medicine, Surgery, Flinders University, Bedford Park, Australia
| | - David Roder
- South Australian Health & Medical Research Institute (SAHMRI), Adelaide, Australia
- School of Health Sciences, University of South Australia, Adelaide, Australia
| | - Jeanne Tie
- Department of Medical Oncology, Western Hospital, Melbourne, Australia
- Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Robert Padbury
- Flinders Clinical and Molecular Medicine, Surgery, Flinders University, Bedford Park, Australia
- Department of Surgery, Flinders Medical Centre, Adelaide, Australia
| | - Timothy Price
- The Queen Elizabeth Hospital and University of Adelaide, Adelaide, Australia
| | - Rachel Wong
- Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
- Department of Medical Oncology, Eastern Health, Melbourne, Australia
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia
| | - Jeremy Shapiro
- Cabrini Haematology and Oncology Centre, Melbourne, Australia
| | - Louise Nott
- Department of Medical Oncology, Royal Hobart Hospital, Tasmania, Australia
- Menzies Research Institute, Hobart, Australia
| | - Margaret Lee
- Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
- Department of Medical Oncology, Eastern Health, Melbourne, Australia
| | - Yu Jo Chua
- Department of Medical Oncology, The Canberra Hospital, Garran, Canberra, Australia
- ANU Medical School, Australian National University, Canberra, Australia
| | - Paul Craft
- Department of Medical Oncology, The Canberra Hospital, Garran, Canberra, Australia
- ANU Medical School, Australian National University, Canberra, Australia
| | | | - Michael Sorich
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Peter Gibbs
- Department of Medical Oncology, Western Hospital, Melbourne, Australia
- Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
| | - Desmond Yip
- Department of Medical Oncology, The Canberra Hospital, Garran, Canberra, Australia
- ANU Medical School, Australian National University, Canberra, Australia
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28
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Wong HL, Christie M, Gately L, Tie J, Lee B, Semira C, Lok SW, Wong R, Gibbs P. Mismatch repair deficiency assessment by immunohistochemistry: for Lynch syndrome screening and beyond. Future Oncol 2018; 14:2725-2739. [DOI: 10.2217/fon-2018-0319] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
While mismatch repair (MMR) deficiency has been studied extensively, the assessment of MMR status in colorectal and other cancers remains highly relevant, particularly in light of recent data demonstrating that MMR deficiency is a strong predictor for treatment benefit with immune checkpoint inhibitors across multiple tumor types. In colorectal cancer, there is a growing consensus in support of routine MMR testing for Lynch syndrome screening, to inform prognosis and adjuvant chemotherapy use in early stage disease, and to predict response to immunotherapy in advanced disease. Here, we provide a review of the Ventana MMR Immunohistochemistry Panel, which was recently approved by the US FDA for use in Lynch syndrome screening.
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Affiliation(s)
- Hui-li Wong
- Systems Biology & Personalised Medicine Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
| | - Michael Christie
- Systems Biology & Personalised Medicine Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
- Department of Pathology, The Royal Melbourne Hospital, Parkville, Victoria, Australia
| | - Lucy Gately
- Systems Biology & Personalised Medicine Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
- Department of Medical Oncology, St. Vincent's Health, Fitzroy, Victoria, Australia
| | - Jeanne Tie
- Systems Biology & Personalised Medicine Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia
- Department of Medical Oncology, Western Health Medical School, University of Melbourne, Footscray, Victoria, Australia
| | - Belinda Lee
- Systems Biology & Personalised Medicine Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia
- Department of Medical Oncology, Northern Health, Epping, Victoria, Australia
| | - Christine Semira
- Systems Biology & Personalised Medicine Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
| | - Sheau Wen Lok
- Systems Biology & Personalised Medicine Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia
| | - Rachel Wong
- Systems Biology & Personalised Medicine Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
- Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia
| | - Peter Gibbs
- Systems Biology & Personalised Medicine Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
- Department of Medical Oncology, Western Health Medical School, University of Melbourne, Footscray, Victoria, Australia
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29
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Foroughi S, Wong HL, Gately L, Lee M, Simons K, Tie J, Burgess AW, Gibbs P. Re-inventing the randomized controlled trial in medical oncology: The registry-based trial. Asia Pac J Clin Oncol 2018; 14:365-373. [PMID: 29947051 DOI: 10.1111/ajco.12992] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Accepted: 04/29/2018] [Indexed: 01/09/2023]
Abstract
Substantial progress has recently been made in optimizing the management of cancer patients, resulting in major gains in survival and quality of life. Much of this progress has resulted from the serial testing of promising treatment strategies, typically using prospective randomized controlled trials to compare outcomes achieved with the new approach versus the current standard(s) of care. However, there is an ever-expanding list of important questions that are difficult to investigate, particularly with respect to determining the optimal sequencing and combination of proven active agents. With the rapidly growing list of clinical, pathologic and molecular characteristics that promise to predict treatment benefit and/or risk for defined patient subsets, many new questions regarding how best to personalize our approach to treatment selection are emerging. These questions can be investigated in the context of registry-based randomized clinical trials. Recently, the potential of registry-based randomized clinical trials was demonstrated in cardiology, highlighting the ability to rapidly recruit large numbers of patients to a trial addressing an important clinical question, with minimal cost and high external validity. In this review, we discuss the challenges and limitations of conventional clinical trials in multidisciplinary cancer care, describe the potential advantages of registry-based randomized trials, and highlight several registry-based oncology studies that are already underway to demonstrate the feasibility of this approach.
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Affiliation(s)
- Siavash Foroughi
- Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.,Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
| | - Hui-Li Wong
- Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.,Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
| | - Lucy Gately
- Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.,Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
| | - Margaret Lee
- Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.,Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.,Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia.,Department of Medical Oncology, Western Health, St Albans, Victoria, Australia
| | - Koen Simons
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.,Western Centre for Health, Research and Education, Western Health, St Albans, Victoria, Australia
| | - Jeanne Tie
- Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.,Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.,Department of Medical Oncology, Western Health, St Albans, Victoria, Australia.,Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Antony Wilks Burgess
- Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.,Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia.,Structural Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
| | - Peter Gibbs
- Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.,Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.,Department of Medical Oncology, Western Health, St Albans, Victoria, Australia
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Burge M, Semira C, Lee B, Lee M, Kosmider S, Wong R, Shapiro J, Ma B, Dean AP, Zimet AS, Steel SA, Lok SW, Torres J, Eastgate M, Wong HL, Gibbs P. Previous Bevacizumab and Efficacy of Later Anti-Epidermal Growth Factor Receptor Antibodies in Metastatic Colorectal Cancer: Results From a Large International Registry. Clin Colorectal Cancer 2018; 17:e593-e599. [PMID: 29958812 DOI: 10.1016/j.clcc.2018.05.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Revised: 05/03/2018] [Accepted: 05/24/2018] [Indexed: 12/21/2022]
Abstract
BACKGROUND The FIRE-3 [5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) plus cetuximab versus FOLFIRI plus bevacizumab in first line treatment colorectal cancer (CRC)] study reported that first-line FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab resulted in similar progression-free survival (PFS) but improved overall survival (OS). A potential explanation is that the initial biologic agent administered in metastatic CRC (mCRC) affects later line efficacy of the other treatments. We sought to test this hypothesis. MATERIALS AND METHODS We interrogated our mCRC registry (Treatment of Recurrent and Advanced Colorectal Cancer) regarding treatment and outcome data for RAS wild-type patients receiving epidermal growth factor receptor inhibitors (EGFRIs) in second and subsequent lines. Survival outcomes from the beginning of EGFRI use were determined as a function of previous bevacizumab use and the interval between ceasing bevacizumab and beginning EGFRI use. RESULTS Of 2061 patients, 222 eligible patients were identified, of whom 170 (77%) had received previous bevacizumab and 52 (23%) had not. PFS and OS from the start of EGFRIs did not differ by previous bevacizumab use (3.8 vs. 4.2 months; hazard ratio [HR], 1.12; P = .81; 9.0 vs. 9.2 months; HR, 1.19; P = .48, respectively) for the whole cohort or when analyzed by the primary tumor side (HR for left side, 1.07; P = .57; HR for right side, 1.2; P = .52). PFS was significantly shorter with right-sided primary tumors when the interval between bevacizumab and EGFRI use was < 6 versus > 6 months (median, 2.2 vs. 6 months; HR, 2.23; P = .01) but not with left-sided tumors (median, 4.2 vs. 5.5 months; HR, 1.12; P = .26). CONCLUSION Previous bevacizumab use had no effect on the activity of subsequent EGFRIs. The apparent effect of time between biologic agents in right-sided tumors might reflect patient selection.
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Affiliation(s)
- Matthew Burge
- Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia; University of Queensland, St Lucia, Brisbane, Queensland, Australia.
| | - Christine Semira
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia
| | - Belinda Lee
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia; Department of Surgery, Royal Melbourne Hospital, Parkville, Victoria, Australia
| | - Margaret Lee
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia; Department of Medical Oncology, Western Health, St Albans, Victoria, Australia; Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia
| | - Suzanne Kosmider
- Department of Medical Oncology, Western Health, St Albans, Victoria, Australia
| | - Rachel Wong
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia; Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia
| | - Jeremy Shapiro
- Department of Medical Oncology, Cabrini Health, Malvern, Victoria, Australia; Department of Medicine, Monash University, Clayton, Victoria, Australia
| | - Brigette Ma
- Department of Clinical Oncology, Chinese University of Hong Kong, New Territories, Hong Kong
| | - Andrew P Dean
- Department of Medical Oncology, St John of God Subiaco Hospital, Subiaco, Western Australia, Australia
| | - Allan S Zimet
- Department of Medical Oncology, Epworth Hospital, Richmond, Victoria, Australia
| | - Simone A Steel
- Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia
| | - Sheau Wen Lok
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia; Victoriatorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia
| | - Javier Torres
- Department of Medical Oncology, Goulburn Valley Health, Shepparton, Victoria, Australia
| | - Melissa Eastgate
- Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia; University of Queensland, St Lucia, Brisbane, Queensland, Australia
| | - Hui-Li Wong
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia; Department of Surgery, Royal Melbourne Hospital, Parkville, Victoria, Australia
| | - Peter Gibbs
- Systems Biology and Personalised Medicine Division, Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia; Department of Surgery, Royal Melbourne Hospital, Parkville, Victoria, Australia; Department of Medical Oncology, Western Health, St Albans, Victoria, Australia
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31
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Au L, Turner N, Wong HL, Field K, Lee B, Boadle D, Cooray P, Karikios D, Kosmider S, Lipton L, Nott L, Parente P, Tie J, Tran B, Wong R, Yip D, Shapiro J, Gibbs P. How accurate are medical oncologists' impressions of management of metastatic colorectal cancer in Australia? Asia Pac J Clin Oncol 2017; 14:e167-e174. [PMID: 28299879 DOI: 10.1111/ajco.12671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Accepted: 01/12/2017] [Indexed: 11/29/2022]
Abstract
AIM Current efforts to understand patient management in clinical practice are largely based on clinician surveys with uncertain reliability. The TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database is a multisite registry collecting comprehensive treatment and outcome data on consecutive metastatic colorectal cancer (mCRC) patients at multiple sites across Australia. This study aims to determine the accuracy of oncologists' impressions of real-word practice by comparing clinicians' estimates to data captured by TRACC. METHODS Nineteen medical oncologists from nine hospitals contributing data to TRACC completed a 34-question survey regarding their impression of the management and outcomes of mCRC at their own practice and other hospitals contributing to the database. Responses were then compared with TRACC data to determine how closely their impressions reflected actual practice. RESULTS Data on 1300 patients with mCRC were available. Median clinician estimated frequency of KRAS testing within 6 months of diagnosis was 80% (range: 20-100%); the TRACC documented rate was 43%. Clinicians generally overestimated the rates of first-line treatment, particularly in patients over 75 years. Estimate for bevacizumab in first line was 60% (35-80%) versus 49% in TRACC. Estimated rate for liver resection varied substantially (5-35%), and the estimated median (27%) was inconsistent with the TRACC rate (12%). Oncologists generally felt their practice was similar to other hospitals. CONCLUSIONS Oncologists' estimates of current clinical practice varied and were discordant with the TRACC database, often with a tendency to overestimate interventions. Clinician surveys alone do not reliably capture contemporary clinical practices in mCRC.
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Affiliation(s)
- Lewis Au
- Department of Medical Oncology, Western Hospital, Melbourne, Australia
| | - Natalie Turner
- Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
| | - Hui-Li Wong
- Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.,The Royal Melbourne Hospital, Melbourne, Australia
| | - Kathryn Field
- The Royal Melbourne Hospital, Melbourne, Australia.,Department of Medicine, University of Melbourne, Melbourne, Australia
| | - Belinda Lee
- Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.,The Royal Melbourne Hospital, Melbourne, Australia.,Department of Medicine, University of Melbourne, Melbourne, Australia
| | | | - Prasad Cooray
- Department of Medical Oncology, Eastern Health, Melbourne, Australia
| | | | - Suzanne Kosmider
- Department of Medical Oncology, Western Hospital, Melbourne, Australia
| | | | | | - Phillip Parente
- Department of Medical Oncology, Eastern Health, Melbourne, Australia.,Faculty of Medicine, Nursing and Health Sciences, Eastern Health Clinical School, Monash University, Box Hill, Australia
| | - Jeanne Tie
- Department of Medical Oncology, Western Hospital, Melbourne, Australia.,Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.,The Royal Melbourne Hospital, Melbourne, Australia
| | - Ben Tran
- Department of Medical Oncology, Western Hospital, Melbourne, Australia.,Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.,The Royal Melbourne Hospital, Melbourne, Australia
| | - Rachel Wong
- Department of Medical Oncology, Eastern Health, Melbourne, Australia
| | - Desmond Yip
- Canberra and Calvary Hospitals and ANU Medical School, Canberra, Australia
| | | | - Peter Gibbs
- Department of Medical Oncology, Western Hospital, Melbourne, Australia.,Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.,The Royal Melbourne Hospital, Melbourne, Australia.,BioGrid Australia, Melbourne, Australia
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Bai L, Wang F, Li ZZ, Ren C, Zhang DS, Zhao Q, Lu YX, Wang DS, Ju HQ, Qiu MZ, Wang ZQ, Wang FH, Xu RH. Chemotherapy plus bevacizumab versus chemotherapy plus cetuximab as first-line treatment for patients with metastatic colorectal cancer: Results of a registry-based cohort analysis. Medicine (Baltimore) 2016; 95:e4531. [PMID: 28002313 PMCID: PMC5181797 DOI: 10.1097/md.0000000000004531] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
The present observational cohort study was designed to elucidate the efficacy and safety profile of bevacizumab or cetuximab with chemotherapy as the first-line treatment in Chinese patients with metastatic colorectal cancer (mCRC). Clinical data were collected from a single-center registry study where mCRC patients received first-line fluoropyrimidine-based chemotherapy combined with either bevacizumab (188 patients with KRAS wild-type or mutated tumors) or cetuximab (101 patients with KRAS wild-type tumors) between January 2009 and December 2013. The Kaplan-Meier method was used for survival analysis. Cox proportional hazards model was used for estimating the prognostic and predictive values of clinicopathological characteristics. No statistically significant difference was observed between the bevacizumab and cetuximab groups in terms of median progression-free survival (PFS) (10.6 vs 8.7 months, P = 0.317), median overall survival (OS) (27.7 vs 28.3 months, P = 0.525), or overall response rate (43.1% vs 53.5%, P = 0.108). For the subset of patients with peritoneal dissemination, bevacizumab-based triplet appears to be superior to cetuximab-based triplet as measured by PFS (9.6 vs 6.1 months) and OS (26.3 vs 12.7 months), but not for patients without peritoneal dissemination (PFS, 10.6 vs 9.1 months; OS, 27.9 vs 30.7 months) (all unadjusted and adjusted interaction P < 0.05). Our study suggests that bevacizumab- or cetuximab-based regimens have similar effectiveness as first-line treatment of mCRC in Chinese population. Patients with peritoneal dissemination were likely to gain more benefit from bevacizumab than cetuximab treatment. Future prospective studies are required to further confirm these results.
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Affiliation(s)
- Long Bai
- Department of Medical Oncology, Sun Yat-sen University Cancer Center
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou
| | - Feng Wang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou
| | - Zhe-zhen Li
- Department of Medical Oncology, Sun Yat-sen University Cancer Center
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou
| | - Chao Ren
- Department of Medical Oncology, Sun Yat-sen University Cancer Center
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou
| | - Dong-sheng Zhang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou
| | - Qi Zhao
- State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Yun-xin Lu
- Department of Medical Oncology, Sun Yat-sen University Cancer Center
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou
| | - De-shen Wang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou
| | - Huai-qiang Ju
- Department of Medical Oncology, Sun Yat-sen University Cancer Center
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou
| | - Miao-zhen Qiu
- Department of Medical Oncology, Sun Yat-sen University Cancer Center
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou
| | - Zhi-qiang Wang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou
| | - Feng-hua Wang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou
| | - Rui-hua Xu
- Department of Medical Oncology, Sun Yat-sen University Cancer Center
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou
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Lee B, Wong HL, Tacey M, Tie J, Wong R, Lee M, Nott L, Shapiro J, Jennens R, Turner N, Tran B, Ananda S, Yip D, Richardson G, Parente P, Lim L, Stefanou G, Burge M, Iddawela M, Power J, Gibbs P. The impact of bevacizumab in metastatic colorectal cancer with an intact primary tumor: Results from a large prospective cohort study. Asia Pac J Clin Oncol 2016; 13:314-321. [PMID: 27885818 DOI: 10.1111/ajco.12639] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/23/2016] [Indexed: 11/30/2022]
Abstract
BACKGROUND Debate continues regarding the benefits versus risks of initial resection of the primary tumor in metastatic colorectal cancer (mCRC) patients with an asymptomatic primary tumor. Although the benefit of the anti-vascular endothelial growth factor agent bevacizumab alongside first-line chemotherapy in mCRC is established, the impact of bevacizumab on the intact primary tumor (IPT) is less well understood. METHODS Data from an Australian mCRC registry were used to assess the impact of bevacizumab-based regimens in the presence of an IPT, to see if this differs from effects in resected primary tumor (RPT) patients and to understand the safety profile of bevacizumab in patients with IPT. Progression-free survival (PFS), overall survival (OS) and safety endpoints were analyzed. RESULTS Of 1204 mCRC patients, 826 (69%) were eligible for inclusion. Bevacizumab use was similar in both arms (IPT (64%) versus RPT (70%)); compared with chemotherapy alone, bevacizumab use was associated with significantly longer PFS (IPT: 8.5 months vs 4.7 months, P = 0.017; RPT: 10.8 months vs 5.8 months, P < 0.001) and OS (IPT: 20 months vs 14.8 months, P = 0.005; RPT: 24.4 months vs 17.3 months, P = 0.004)).1 Bevacizumab use in an IPT was associated with more GI perforations (4.5% vs 1.8%, P = 0.210) but less frequent bleeding (1.5% vs 5.3%, P = 0.050) and thrombosis (1.5% vs 2.7%, P = 0.470), versus chemotherapy alone. Median survival was equivalent between patients that did or did not experience bevacizumab-related adverse events - 20.0 months versus 19.9 months, hazard ratio = 0.98, P = 0.623.1 CONCLUSIONS: The addition of bevacizumab significantly improved survival outcomes in mCRC with an IPT. The occurrence of bevacizumab-related adverse events did not significantly impact survival outcomes.
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Affiliation(s)
- Belinda Lee
- Systems Biology & Personalized Medicine Division, Walter & Eliza Hall Institute (WEHI), Melbourne, VIC, Australia.,Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia.,Faculty of Medicine, Dentistry & Health Sciences University of Melbourne, Melbourne, VIC, Australia
| | - Hui-Li Wong
- Systems Biology & Personalized Medicine Division, Walter & Eliza Hall Institute (WEHI), Melbourne, VIC, Australia.,Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia.,Faculty of Medicine, Dentistry & Health Sciences University of Melbourne, Melbourne, VIC, Australia
| | - Mark Tacey
- Faculty of Medicine, Dentistry & Health Sciences University of Melbourne, Melbourne, VIC, Australia.,Melbourne EpiCenter, The Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia
| | - Jeanne Tie
- Systems Biology & Personalized Medicine Division, Walter & Eliza Hall Institute (WEHI), Melbourne, VIC, Australia.,Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia.,Western Health, Department of Medical Oncology, Boxhill, TAS, Australia
| | - Rachel Wong
- Systems Biology & Personalized Medicine Division, Walter & Eliza Hall Institute (WEHI), Melbourne, VIC, Australia.,Eastern Health, Department of Medical Oncology, Boxhill, TAS, Australia.,Monash University, Department of Medicine, Nursing and Health Sciences, Hobart, TAS, Australia
| | - Margaret Lee
- Systems Biology & Personalized Medicine Division, Walter & Eliza Hall Institute (WEHI), Melbourne, VIC, Australia.,Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia.,Eastern Health, Department of Medical Oncology, Boxhill, TAS, Australia
| | - Louise Nott
- Royal Hobart Hospital, Department of Medical Oncology, Hobart, TAS, Australia
| | - Jeremy Shapiro
- Monash University, Department of Medicine, Nursing and Health Sciences, Hobart, TAS, Australia.,Cabrini Health, Department of Medical Oncology, Malvern, VIC, Australia
| | - Ross Jennens
- Epworth Hospital, Department of Medical Oncology, Richmond, VIC, Australia
| | - Natalie Turner
- Systems Biology & Personalized Medicine Division, Walter & Eliza Hall Institute (WEHI), Melbourne, VIC, Australia.,Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia
| | - Ben Tran
- Systems Biology & Personalized Medicine Division, Walter & Eliza Hall Institute (WEHI), Melbourne, VIC, Australia.,Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia
| | - Sumitra Ananda
- Western Health, Department of Medical Oncology, Boxhill, TAS, Australia
| | - Desmond Yip
- Canberra and Calvary Hospitals, Department of Medical Oncology, Garran, ACT, Australia
| | - Gary Richardson
- Cabrini Health, Department of Medical Oncology, Malvern, VIC, Australia
| | - Phillip Parente
- Eastern Health, Department of Medical Oncology, Boxhill, TAS, Australia.,Monash University, Department of Medicine, Nursing and Health Sciences, Hobart, TAS, Australia
| | - Lionel Lim
- Eastern Health, Department of Medical Oncology, Boxhill, TAS, Australia
| | - Greg Stefanou
- John Fawkner Hospital, Department of Medical Oncology, Coburg, VIC, Australia
| | - Matthew Burge
- Royal Brisbane Hospital, Department of Medical Oncology, Brisbane, QLD, Australia
| | - Mahesh Iddawela
- Goulburn Valley Health, Department of Medical Oncology, Shepparton, VIC, Australia
| | - Jeremy Power
- Launceston General Hospital, Department of Medical Oncology, Launceston, TAS, Australia
| | - Peter Gibbs
- Systems Biology & Personalized Medicine Division, Walter & Eliza Hall Institute (WEHI), Melbourne, VIC, Australia.,Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia.,Faculty of Medicine, Dentistry & Health Sciences University of Melbourne, Melbourne, VIC, Australia.,Western Health, Department of Medical Oncology, Boxhill, TAS, Australia
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Malouf P, Gibbs P, Shapiro J, Sockler J, Bell S. Australian contemporary management of synchronous metastatic colorectal cancer. ANZ J Surg 2016; 88:71-76. [PMID: 27122066 DOI: 10.1111/ans.13619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2016] [Revised: 03/23/2016] [Accepted: 03/28/2016] [Indexed: 11/30/2022]
Abstract
INTRODUCTION This article outlines the current Australian multidisciplinary treatment of synchronous metastatic colorectal adenocarcinoma and assesses the factors that influence patient outcome. METHODS This is a retrospective analysis of the prospective 'Treatment of Recurrent and Advanced Colorectal Cancer' registry, describing the patient treatment pathway and documenting the extent of disease, resection of the colorectal primary and metastases, chemotherapy and biological therapy use. Cox regression models for progression-free and overall survival were constructed with a comprehensive set of clinical variables. Analysis was intentionn-ton-treat, quantifying the effect of treatment intent decided at the multidisciplinary team meeting (MDT). RESULTS One thousand one hundred and nine patients presented with synchronous metastatic disease between July 2009 and November 2015. Median follow-up was 15.8 months; 4.4% (group 1) had already curative resections of primary and metastases prior to MDT, 22.2% (group 2) were considered curative but were referred to MDT for opinion and/or medical oncology treatment prior to resection and 70.2% were considered palliative at MDT (group 3). Overall, 83% received chemotherapy, 55% had their primary resected and 23% had their metastases resected; 13% of resections were synchronous, 20% were staged with primary resected first and 62% had only the colorectal primary managed surgically. Performance status, metastasis resection (R0 versus R1 versus R2 versus no resection), resection of the colorectal primary and treatment intent determined at MDT were the most significant factors for progression-free and overall survival. CONCLUSIONS This is the largest Australian series of synchronous metastatic colorectal adenocarcinoma and offers insight into the nature and utility of contemporary practice.
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Affiliation(s)
- Phillip Malouf
- Department of Colorectal Surgery, St George Hospital, Sydney, New South Wales, Australia
| | - Peter Gibbs
- Department of Oncology, Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Jeremy Shapiro
- Department of Medicine, Monash University, Melbourne, Victoria, Australia
| | - Jim Sockler
- Programming and Statistics, Datapharm Australia, Sydney, New South Wales, Australia
| | - Stephen Bell
- Cabrini Monash University Department of Surgery, Cabrini Hospital, Melbourne, Victoria, Australia
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Wong SF, Wong HL, Field KM, Kosmider S, Tie J, Wong R, Tacey M, Shapiro J, Nott L, Richardson G, Cooray P, Jones I, Croxford M, Gibbs P. Primary Tumor Resection and Overall Survival in Patients With Metastatic Colorectal Cancer Treated With Palliative Intent. Clin Colorectal Cancer 2015; 15:e125-32. [PMID: 26803709 DOI: 10.1016/j.clcc.2015.12.010] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2015] [Revised: 12/11/2015] [Accepted: 12/17/2015] [Indexed: 12/31/2022]
Abstract
BACKGROUND The survival impact of primary tumor resection in patients with metastatic colorectal cancer (mCRC) treated with palliative intent remains uncertain. In the absence of randomized data, the objectives of the present study were to examine the effect of primary tumor resection (PTR) and major prognostic variables on overall survival (OS) of patients with de novo mCRC. PATIENTS AND METHODS Consecutive patients from the Australian 'Treatment of Recurrent and Advanced Colorectal Cancer' registry were examined from June 2009 to March 2015. Univariate and multivariate Cox proportional hazards regression analyses were used to identify associations between multiple patient or clinical variables and OS. Patients with metachronous mCRC were excluded from the analyses. RESULTS A total of 690 patients de novo and 373 metachronous mCRC patients treated with palliative intent were identified. The median follow-up period was 30 months. The median age of de novo patients was 66 years; 57% were male; 77% had an Eastern Cooperative Oncology Group performance status of 0 to 1; and 76% had a colon primary. A total of 216 de novo mCRC patients treated with palliative intent underwent PTR at diagnosis and were more likely to have a colon primary (odds ratio [OR], 15.4), a lower carcinoembryonic antigen level (OR, 2.08), and peritoneal involvement (OR, 2.58; P < .001). On multivariate analysis, PTR at diagnosis in de novo patients was not associated with significantly improved OS (hazard ratio [HR], 0.82; 99% confidence interval [CI], 0.62-1.09; P = .068). PTR at diagnosis did not correlate with outcome in de novo patients with a colon primary (HR, 0.74; 99% CI, 0.54-1.01; P = .014) or a rectal primary (HR, 0.81; 99% CI, 0.27-2.44; P = .621). CONCLUSION For de novo mCRC patients treated with palliative intent, PTR at diagnosis does not significantly improve OS when adjusting for known major prognostic factors. The outcomes of randomized trials examining the survival impact of PTR are awaited.
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Affiliation(s)
- Shu Fen Wong
- Andrew Love Cancer Centre, University Hospital Geelong, Geelong, VIC, Australia; Deakin University School of Medicine, Waurn Ponds, VIC, Australia.
| | - Hui Li Wong
- Department of Medical Oncology, Royal Melbourne Hospital, Parkville, VIC, Australia; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; University of Melbourne, Parkville, VIC, Australia
| | - Kathryn M Field
- Department of Medical Oncology, Royal Melbourne Hospital, Parkville, VIC, Australia
| | - Suzanne Kosmider
- Department of Medical Oncology, Royal Melbourne Hospital, Parkville, VIC, Australia; Department of Medical Oncology, Western Health, Footscray, VIC, Australia
| | - Jeanne Tie
- Department of Medical Oncology, Royal Melbourne Hospital, Parkville, VIC, Australia; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; University of Melbourne, Parkville, VIC, Australia; Department of Medical Oncology, Western Health, Footscray, VIC, Australia
| | - Rachel Wong
- Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Oncology, Eastern Health, Box Hill, VIC, Australia; Monash University Faculty of Medicine, Nursing and Health Sciences, Clayton, VIC, Australia
| | - Mark Tacey
- Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Melbourne EpiCentre, Parkville, VIC, Australia
| | | | - Louise Nott
- Department of Medical Oncology, Royal Hobart Hospital, Hobart, TAS, Australia
| | | | - Prasad Cooray
- Department of Medical Oncology, Eastern Health, Box Hill, VIC, Australia
| | - Ian Jones
- Department of Surgery, Colorectal Surgery Unit, University of Melbourne, Royal Melbourne Hospital, Parkville, VIC, Australia
| | - Matthew Croxford
- Department of Surgery, Western Hospital, Footscray, VIC, Australia
| | - Peter Gibbs
- Department of Medical Oncology, Royal Melbourne Hospital, Parkville, VIC, Australia; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; University of Melbourne, Parkville, VIC, Australia; Department of Medical Oncology, Western Health, Footscray, VIC, Australia
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Patterns of care and outcomes for elderly patients with metastatic colorectal cancer in Australia. J Geriatr Oncol 2015; 6:387-94. [PMID: 26190441 DOI: 10.1016/j.jgo.2015.06.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2015] [Revised: 05/03/2015] [Accepted: 06/25/2015] [Indexed: 12/30/2022]
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Roohullah A, Wong HL, Sjoquist KM, Gibbs P, Field K, Tran B, Shapiro J, Mckendrick J, Yip D, Nott L, Gebski V, Ng W, Chua W, Price T, Tebbutt N, Chantrill L. Gastrointestinal perforation in metastatic colorectal cancer patients with peritoneal metastases receiving bevacizumab. World J Gastroenterol 2015; 21:5352-5358. [PMID: 25954110 PMCID: PMC4419077 DOI: 10.3748/wjg.v21.i17.5352] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2014] [Revised: 01/27/2015] [Accepted: 03/12/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the safety and efficacy of adding bevacizumab to first-line chemotherapy in metastatic colorectal cancer patients with peritoneal disease.
METHODS: We compared rates of gastrointestinal perforation in patients with metastatic colorectal cancer and peritoneal disease receiving first-line chemotherapy with and without bevacizumab in three distinct cohorts: (1) the AGITG MAX trial (Phase III randomised clinical trial comparing capecitabine vs capecitabine and bevacizumab vs capecitabine, bevacizumab and mitomycinC); (2) the prospective Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry (any first-line regimen ± bevacizumab); and (3) two cancer centres in New South Wales, Australia [Macarthur Cancer Therapy Centre and Liverpool Cancer Therapy Centre (NSWCC) from January 2005 to Decenber 2012, (any first-line regimen ± bevacizumab). For the AGITG MAX trial capecitabine was compared to the other two arms (capecitabine/bevacizumab and capecitabine/bevacizumab/mitomycinC). In the AGITG MAX trial and the TRACC registry rates of gastrointestinal perforation were also collected in patients who did not have peritoneal metastases. Secondary endpoints included progression-free survival, chemotherapy duration, and overall survival. Time-to-event outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test.
RESULTS: Eighty-four MAX, 179 TRACC and 69 NSWCC patients had peritoneal disease. There were no gastrointestinal perforations recorded in either the MAX subgroup or the NSWCC cohorts. Of the patients without peritoneal disease in the MAX trial, 4/300 (1.3%) in the bevacizumab arms had gastrointestinal perforations compared to 1/123 (0.8%) in the capecitabine alone arm. In the TRACC registry 3/126 (2.4%) patients who had received bevacizumab had a gastrointestinal perforation compared to 1/53 (1.9%) in the chemotherapy alone arm. In a further analysis of patients without peritoneal metastases in the TRACC registry, the rate of gastrointestinal perforations was 9/369 (2.4%) in the chemotherapy/bevacizumab group and 5/177 (2.8%) in the chemotherapy alone group. The addition of bevacizumab to chemotherapy was associated with improved progression-free survival in all three cohorts: MAX 6.9 m vs 4.9 m, HR = 0.64 (95%CI: 0.42-1.02); P = 0.063; TRACC 9.1 m vs 5.5 m, HR = 0.61 (95%CI: 0.37-0.86); P = 0.009; NSWCC 8.7 m vs 6.8 m, HR = 0.75 (95%CI: 0.43-1.32); P = 0.32. Chemotherapy duration was similar across the groups.
CONCLUSION: Patients with peritoneal disease do not appear to have an increased risk of gastrointestinal perforations when receiving first-line therapy with bevacizumab compared to systemic therapy alone.
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Turner NH, Wong HL, Field K, Wong R, Shapiro J, Yip D, Nott L, Tie J, Kosmider S, Tran B, Desai J, McKendrick J, Zimet A, Richardson G, Iddawela M, Gibbs P. Novel quality indicators for metastatic colorectal cancer management identify significant variations in these measures across treatment centers in Australia. Asia Pac J Clin Oncol 2015; 11:262-71. [PMID: 25871458 DOI: 10.1111/ajco.12355] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/21/2014] [Indexed: 12/24/2022]
Affiliation(s)
- Natalie Heather Turner
- The Walter and Eliza Hall Institute of Medical Research; Melbourne Victoria Australia
- Department of Medical Oncology; Royal Melbourne Hospital; Melbourne Victoria Australia
| | - Hui-li Wong
- The Walter and Eliza Hall Institute of Medical Research; Melbourne Victoria Australia
| | - Kathryn Field
- Department of Medical Oncology; Royal Melbourne Hospital; Melbourne Victoria Australia
| | - Rachel Wong
- Department of Medical Oncology; Eastern Health; Melbourne Victoria Australia
- Eastern Health Medical School; Monash University; Melbourne Victoria Australia
| | | | - Desmond Yip
- The Canberra Hospital; Canberra Australian Capital Territory Australia
- Calvary Hospital; Canberra Australian Capital Territory Australia
- ANU Medical School; Australian National University; Canberra Australian Capital Territory Australia
| | - Louise Nott
- Royal Hobart Hospital; Hobart Tasmania Australia
| | - Jeanne Tie
- The Walter and Eliza Hall Institute of Medical Research; Melbourne Victoria Australia
- Department of Medical Oncology; Royal Melbourne Hospital; Melbourne Victoria Australia
- Department of Medical Oncology; Western Hospital; Melbourne Victoria Australia
| | - Suzanne Kosmider
- Department of Medical Oncology; Western Hospital; Melbourne Victoria Australia
| | - Ben Tran
- The Walter and Eliza Hall Institute of Medical Research; Melbourne Victoria Australia
- Department of Medical Oncology; Royal Melbourne Hospital; Melbourne Victoria Australia
- Department of Medical Oncology; Western Hospital; Melbourne Victoria Australia
| | - Jayesh Desai
- The Walter and Eliza Hall Institute of Medical Research; Melbourne Victoria Australia
- Department of Medical Oncology; Royal Melbourne Hospital; Melbourne Victoria Australia
| | - Joseph McKendrick
- Department of Medical Oncology; Eastern Health; Melbourne Victoria Australia
| | - Allan Zimet
- Epworth Hospital; Melbourne Victoria Australia
| | | | - Mahesh Iddawela
- Goulburn Valley Health; Shepparton Victoria Australia
- University of Melbourne Rural Health Academic Centre; Shepparton Victoria Australia
| | - Peter Gibbs
- The Walter and Eliza Hall Institute of Medical Research; Melbourne Victoria Australia
- Department of Medical Oncology; Royal Melbourne Hospital; Melbourne Victoria Australia
- Royal Hobart Hospital; Hobart Tasmania Australia
- BioGrid Australia; Melbourne Victoria Australia
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Field K, Shapiro J, Wong HL, Tacey M, Nott L, Tran B, Turner N, Ananda S, Richardson G, Jennens R, Wong R, Power J, Burge M, Gibbs P. Treatment and outcomes of metastatic colorectal cancer in Australia: defining differences between public and private practice. Intern Med J 2015; 45:267-74. [DOI: 10.1111/imj.12643] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2014] [Accepted: 11/05/2014] [Indexed: 11/26/2022]
Affiliation(s)
- K. Field
- Department of Medical Oncology; Royal Melbourne Hospital; Melbourne Victoria Australia
| | - J. Shapiro
- Department of Medical Oncology; Cabrini Health; Melbourne Victoria Australia
- Faculty of Medicine; Monash University; Melbourne Victoria Australia
| | - H.-L. Wong
- Systems Biology and Personalised Medicine Division; Walter and Eliza Hall Institute; Melbourne Victoria Australia
- Faculty of Medicine; The University of Melbourne; Melbourne Victoria Australia
| | - M. Tacey
- Department of Statistics; Melbourne EpiCentre; Melbourne Victoria Australia
| | - L. Nott
- Department of Medical Oncology; Royal Hobart Hospital; Hobart Australia
| | - B. Tran
- Department of Medical Oncology; Royal Melbourne Hospital; Melbourne Victoria Australia
- Systems Biology and Personalised Medicine Division; Walter and Eliza Hall Institute; Melbourne Victoria Australia
- Faculty of Medicine; The University of Melbourne; Melbourne Victoria Australia
| | - N. Turner
- Department of Medical Oncology; Royal Melbourne Hospital; Melbourne Victoria Australia
- Systems Biology and Personalised Medicine Division; Walter and Eliza Hall Institute; Melbourne Victoria Australia
| | - S. Ananda
- Department of Medical Oncology; Western Hospital; Melbourne Victoria Australia
| | - G. Richardson
- Department of Medical Oncology; Cabrini Health; Melbourne Victoria Australia
| | - R. Jennens
- Department of Medical Oncology; Epworth Health; Hobart Australia
| | - R. Wong
- Department of Medical Oncology; Box Hill Hospital; Hobart Australia
| | - J. Power
- Department of Medical Oncology; Launceston Hospital; Launceston Tasmania Australia
| | - M. Burge
- Department of Medical Oncology; Royal Brisbane Hospital; Brisbane Queensland Australia
| | - P. Gibbs
- Department of Medical Oncology; Royal Melbourne Hospital; Melbourne Victoria Australia
- Systems Biology and Personalised Medicine Division; Walter and Eliza Hall Institute; Melbourne Victoria Australia
- Faculty of Medicine; The University of Melbourne; Melbourne Victoria Australia
- Department of Medical Oncology; Western Hospital; Melbourne Victoria Australia
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