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Biondo S, Frago R, Kreisler E. Primary tumor resection for asymptomatic colorectal cancer with unresectable metastasis: the end of the dilemma. Ann Oncol 2024; 35:757-759. [PMID: 38969010 DOI: 10.1016/j.annonc.2024.06.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Accepted: 06/21/2024] [Indexed: 07/07/2024] Open
Affiliation(s)
- S Biondo
- Department of General and Digestive Surgery, Colorectal Unit, Bellvitge University Hospital, and Bellvitge Biomedical Investigation Institute (IDIBELL), Barcelona; Department of Clinical Sciences, University of Barcelona, Barcelona, Spain.
| | - R Frago
- Department of General and Digestive Surgery, Colorectal Unit, Bellvitge University Hospital, and Bellvitge Biomedical Investigation Institute (IDIBELL), Barcelona; Department of Clinical Sciences, University of Barcelona, Barcelona, Spain
| | - E Kreisler
- Department of General and Digestive Surgery, Colorectal Unit, Bellvitge University Hospital, and Bellvitge Biomedical Investigation Institute (IDIBELL), Barcelona; Department of Clinical Sciences, University of Barcelona, Barcelona, Spain
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van der Kruijssen DEW, Elias SG, van de Ven PM, van Rooijen KL, Lam-Boer J', Mol L, Punt CJA, Sommeijer DW, Tanis PJ, Nielsen JD, Yilmaz MK, van Riel JMGH, Wasowiz-Kemps DK, Loosveld OJL, van der Schelling GP, de Groot JWB, van Westreenen HL, Jakobsen HL, Fromm AL, Hamberg P, Verseveld M, Jaensch C, Liposits GI, van Duijvendijk P, Oulad Hadj J, van der Hoeven JAB, Trajkovic M, de Wilt JHW, Koopman M. Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase III CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group. Ann Oncol 2024; 35:769-779. [PMID: 38852675 DOI: 10.1016/j.annonc.2024.06.001] [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: 02/05/2024] [Revised: 05/11/2024] [Accepted: 06/02/2024] [Indexed: 06/11/2024] Open
Abstract
BACKGROUND Upfront primary tumor resection (PTR) has been associated with longer overall survival (OS) in patients with synchronous unresectable metastatic colorectal cancer (mCRC) in retrospective analyses. The aim of the CAIRO4 study was to investigate whether the addition of upfront PTR to systemic therapy resulted in a survival benefit in patients with synchronous mCRC without severe symptoms of their primary tumor. PATIENTS AND METHODS This randomized phase III trial was conducted in 45 hospitals in The Netherlands and Denmark. Eligibility criteria included previously untreated mCRC, unresectable metastases, and no severe symptoms of the primary tumor. Patients were randomized (1 : 1) to upfront PTR followed by systemic therapy or systemic therapy without upfront PTR. Systemic therapy consisted of first-line fluoropyrimidine-based chemotherapy with bevacizumab in both arms. Primary endpoint was OS in the intention-to-treat population. The study was registered at ClinicalTrials.gov, NCT01606098. RESULTS Between August 2012 and February 2021, 206 patients were randomized. In the intention-to-treat analysis, 204 patients were included (n = 103 without upfront PTR, n = 101 with upfront PTR) of whom 116 were men (57%) with median age of 65 years (interquartile range 59-71 years). Median follow-up was 69.4 months. Median OS in the arm without upfront PTR was 18.3 months (95% confidence interval 16.0-22.2 months) compared with 20.1 months (95% confidence interval 17.0-25.1 months) in the upfront PTR arm (P = 0.32). The number of grade 3-4 events was 71 (72%) in the arm without upfront PTR and 61 (65%) in the upfront PTR arm (P = 0.33). Three deaths (3%) possibly related to treatment were reported in the arm without upfront PTR and four (4%) in the upfront PTR arm. CONCLUSIONS Addition of upfront PTR to palliative systemic therapy in patients with synchronous mCRC without severe symptoms of the primary tumor does not result in a survival benefit. This practice should no longer be considered standard of care.
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Affiliation(s)
- D E W van der Kruijssen
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht
| | - S G Elias
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht
| | - P M van de Ven
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht
| | - K L van Rooijen
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht
| | - J 't Lam-Boer
- Department of Surgery, Radboud University Medical Center, Nijmegen; Department of Surgery, Netherlands Cancer Institute, Amsterdam
| | - L Mol
- Clinical Research Department, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht
| | - C J A Punt
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht
| | - D W Sommeijer
- Department of Medical Oncology, Amsterdam University Medical Center, Amsterdam; Department of Medical Oncology, Flevo Hospital, Almere
| | - P J Tanis
- Department of Surgery, Amsterdam University Medical Center, Amsterdam; Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands
| | - J D Nielsen
- Department of Surgery, Aalborg University Hospital, Aalborg, Denmark
| | - M K Yilmaz
- Department of Medical Oncology, Aalborg University Hospital, Aalborg, Denmark
| | - J M G H van Riel
- Department of Medical Oncology, Elisabeth-TweeSteden Hospital, Tilburg
| | | | | | | | - J W B de Groot
- Department of Medical Oncology, Isala Hospital, Zwolle, The Netherlands
| | | | - H L Jakobsen
- Department of Surgery, Herlev and Gentofte Hospital, Herlev, Denmark
| | - A L Fromm
- Department of Medical Oncology, Herlev and Gentofte Hospital, Herlev, Denmark
| | - P Hamberg
- Department of Medical Oncology, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands
| | - M Verseveld
- Department of Surgery, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands
| | - C Jaensch
- Department of Surgery, Regional Hospital Gødstrup, Herning, Denmark
| | - G I Liposits
- Department of Medical Oncology, Regional Hospital Gødstrup, Herning, Denmark
| | | | - J Oulad Hadj
- Department of Medical Oncology, Gelre Hospital, Apeldoorn
| | | | - M Trajkovic
- Department of Medical Oncology, Albert Schweitzer Hospital, Dordrecht, The Netherlands
| | - J H W de Wilt
- Department of Surgery, Radboud University Medical Center, Nijmegen
| | - M Koopman
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht.
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Sijmons JML, Zamaray B, Veld JV, Warps AK, Dekker JWT, Tuynman JB, van Westreenen HL, Consten ECJ, Tanis PJ. Relief of Obstruction in Left-Sided Obstructive Colon Cancer: Nationwide Analysis of Applied Treatment in the Palliative Setting. J Gastrointest Cancer 2024; 55:691-701. [PMID: 38168860 DOI: 10.1007/s12029-023-01010-6] [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] [Accepted: 12/24/2023] [Indexed: 01/05/2024]
Abstract
BACKGROUND For relief of bowel obstruction in left-sided obstructive colon cancer (LSOCC), a self-expandable metal stent (SEMS) or decompressing stoma (DS) can be placed. In a curative setting, these two strategies have been extensively studied as a bridge to elective resection. Guidelines recommend SEMS as the preferred option in the palliative setting, but adherence in daily practice is unknown. Therefore, this study aimed to gain more insight into patients with LSOCC who received palliative treatment with SEMS or DS at a national level. METHODS A retrospective population-based cohort study was conducted in the Netherlands. Data from the Netherlands Cancer Registry (NCR) on all patients with LSOCC treated with DS or SEMS not followed by resection of the primary tumour between January 1, 2015, and December 31, 2019, were analysed. Type of treatment (DS or SEMS) for different clinical scenarios, was the main outcome of this study, and was also evaluated over the years (2015-2019). RESULTS Palliative treatment with SEMS or DS for LSOCC was performed in 1077 patients, of whom 79.2% had metastatic disease (M1). Patients without metastatic disease (M0) were older (≥ 80 years M0 67.4%, M1 25.3%, P < 0.001), had a worse clinical condition (ASA III 51.4% versus 36.37%, ASA IV-V 13.3% versus 4.0% P < 0.001) and presented with higher tumour stage (cT4 55.4% versus 33.5%, % P < 0.001). DS was performed in 91.5% of the patients and SEMS in 8.5%. The proportion of DS did not significantly differ between patients with M1 and M0 (91.8% vs. 90.2% respectively, P = 0.525). No increase in SEMS application was observed over the years, with a stable overall proportion of DS of 91-92% per year. In the multivariable analyses, ninety-day mortality and overall survival were not significantly different between SEMS and DS. CONCLUSIONS This study revealed that DS was the primary treatment modality for palliative management of LSOCC in the Netherlands between 2015 and 2019, while the guidelines recommended SEMS as preferred treatment. For patients with LSOCC eligible for stenting in the palliative setting, SEMS placement should become more available and accessible as the preferred treatment option, to avoid a stoma in the terminal phase of life.
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Affiliation(s)
- J M L Sijmons
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Meibergdreef 9 Amsterdam, Amsterdam, The Netherlands
- Dutch Institute for Clinical Auditing, Rijsburgerweg 10, Leiden, The Netherlands
- Cancer Center Amsterdam, Treatment and quality of life, De Boelelaan 1118, Amsterdam, The Netherlands
| | - B Zamaray
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Meibergdreef 9 Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Treatment and quality of life, De Boelelaan 1118, Amsterdam, The Netherlands
| | - J V Veld
- Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands
| | - A K Warps
- Department of Surgery, University Medical Centre Groningen, Hanzeplein 1, Groningen, The Netherlands
| | - J W T Dekker
- Department of Surgery, Reinier de Graaf Groep, Reinier de Graafweg 5, Delft, The Netherlands
| | - J B Tuynman
- Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands
| | - H L van Westreenen
- Department of Surgery, Isala Hospital, Dokter van Heesweg 2, Zwolle, The Netherlands
| | - E C J Consten
- Department of Surgery, University Medical Centre Groningen, Hanzeplein 1, Groningen, The Netherlands
- Meander Medical Centre, Department of Surgery, Maatweg 3, Amersfoort, The Netherlands
| | - P J Tanis
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Meibergdreef 9 Amsterdam, Amsterdam, The Netherlands.
- Cancer Center Amsterdam, Treatment and quality of life, De Boelelaan 1118, Amsterdam, The Netherlands.
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC, Doctor Molewaterplein 40, Rotterdam, 3015 GD, the Netherlands.
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Pécsi B, Mangel LC. The Real-Life Impact of Primary Tumor Resection of Synchronous Metastatic Colorectal Cancer-From a Clinical Oncologic Point of View. Cancers (Basel) 2024; 16:1460. [PMID: 38672540 PMCID: PMC11047864 DOI: 10.3390/cancers16081460] [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: 02/24/2024] [Revised: 04/03/2024] [Accepted: 04/09/2024] [Indexed: 04/28/2024] Open
Abstract
AIM The complex medical care of synchronous metastatic colorectal (smCRC) patients requires prudent multidisciplinary planning and treatments due to various challenges caused by the primary tumor and its metastases. The role of primary tumor resection (PTR) is currently uncertain; strong arguments exist for and against it. We aimed to define its effect and find its best place in our therapeutic methodology. METHOD We performed retrospective data analysis to investigate the clinical course of 449 smCRC patients, considering treatment modalities and the location of the primary tumor and comparing the clinical results of the patients with or without PTR between 1 January 2013 and 31 December 2018 at the Institute of Oncotherapy of the University of Pécs. RESULTS A total of 63.5% of the 449 smCRC patients had PTR. Comparing their data to those whose primary tumor remained intact (IPT), we observed significant differences in median progression-free survival with first-line chemotherapy (mPFS1) (301 vs. 259 days; p < 0.0001; 1 y PFS 39.2% vs. 26.6%; OR 0.56 (95% CI 0.36-0.87)) and median overall survival (mOS) (760 vs. 495 days; p < 0.0001; 2 y OS 52.4 vs. 26.9%; OR 0.33 (95% CI 0.33-0.53)), respectively. However, in the PTR group, the average ECOG performance status was significantly better (0.98 vs. 1.1; p = 0.0456), and the use of molecularly targeted agents (MTA) (45.3 vs. 28.7%; p = 0.0005) and rate of metastasis ablation (MA) (21.8 vs. 1.2%; p < 0.0001) were also higher, which might explain the difference partially. Excluding the patients receiving MTA and MA from the comparison, the effect of PTR remained evident, as the mOS differences in the reduced PTR subgroup compared to the reduced IPT subgroup were still strongly significant (675 vs. 459 days; p = 0.0009; 2 y OS 45.9 vs. 24.1%; OR 0.37 (95% CI 0.18-0.79). Further subgroup analysis revealed that the site of the primary tumor also had a major impact on the outcome considering only the IPT patients; shorter mOS was observed in the extrapelvic IPT subgroup in contrast with the intrapelvic IPT group (422 vs. 584 days; p = 0.0026; 2 y OS 18.2 vs. 35.9%; OR 0.39 (95% CI 0.18-0.89)). Finally, as a remarkable finding, it should be emphasized that there were no differences in OS between the smCRC PTR subgroup and metachronous mCRC patients (mOS 760 vs. 710 days, p = 0.7504, 2 y OS OR 0.85 (95% CI 0.58-1.26)). CONCLUSIONS The role of PTR in smCRC is still not professionally justified. Our survey found that most patients had benefited from PTR. Nevertheless, further prospective trials are needed to clarify the optimal treatment sequence of smCRC patients and understand this cancer disease's inherent biology.
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Affiliation(s)
- Balázs Pécsi
- Institute of Oncotherapy, Clinical Center and Medical School, University of Pécs, 7624 Pécs, Hungary
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Monahan BV, Patel T, Poggio JL. Stage IV Colorectal Cancer at Initial Presentation versus Progression during and after Treatment, Differences in Management: Management Differences for Initial Presentation versus Progression of Disease after Initial Treatment. Clin Colon Rectal Surg 2024; 37:108-113. [PMID: 38322603 PMCID: PMC10843884 DOI: 10.1055/s-0043-1761626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2024]
Abstract
Stage IV colorectal cancer is a prevalent disease and understanding the appropriate treatment options is important. Medical oncologic treatment remains the mainstay of treatment in cases where curative resection is not possible. Surgical intervention is indicated if the primary tumor and associated metastases are amenable to curative resection or if obstructive, bleeding, or perforative complications arise from the tumor. New endoscopic techniques can provide palliation and benefit for patients who cannot undergo surgery and may speed time to chemotherapy initiation. Recently, immunotherapy has shown promise at managing, controlling, and regressing advanced disease, in some cases converting it to curative with resection. For patients that progress while on treatment, continued medical therapy remains the mainstay of treatment. Further research into the benefits of asymptomatic primary tumor resection without curative intent needs to be performed. Colorectal cancer, and more specifically metastatic colorectal cancer, continues to have improved 1- and 5-year survival rates and likely will continue to do so over the coming months and years.
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Affiliation(s)
- Brian V. Monahan
- Department of Surgery, Temple University Hospital, Philadelphia, Pennsylvania
| | - Takshaka Patel
- Department of Surgery, Temple University Hospital, Philadelphia, Pennsylvania
| | - Juan Lucas Poggio
- Department of Surgery, Temple University Hospital, Philadelphia, Pennsylvania
- Division of Colorectal Surgery, Temple University Hospital, Philadelphia, Pennsylvania
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Ho MF, Lai VC, Ng DCK, Ng SSM. Prognosis of patients with unresectable stage IV Colon cancer undergoing primary tumor resection: A multicenter study of minimally symptomatic or asymptomatic primary tumor. Asian J Surg 2023; 46:3710-3715. [PMID: 36522225 DOI: 10.1016/j.asjsur.2022.11.127] [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: 10/14/2022] [Revised: 11/23/2022] [Accepted: 11/30/2022] [Indexed: 12/15/2022] Open
Abstract
AIM To determine the factors affecting survival of patients with unresectable stage IV colon cancer with Primary tumour resection (PTR) as first treatment compared with those with conventional palliative chemotherapy. METHODOLOGY Patient with minimally or asymptomatic stage IV colon cancer at diagnosis were identified from prospectively managed database in included centers from 2015 to 2020. Patient with and without PTR performed were followed up. Primary end point was overall survival. Risk factors affecting survival will be analysis by Kaplan Meier statistics and Cox regression analysis. Secondary outcome will be stoma formation, complication rate and reoperation. RESULTS 162 patients were included in analysis. 68 patients treated with systemic therapy PTR and 94 patients with tumour in-situ before systemic therapy. Baseline demographics including sex, age, functional status, tumour location, site of metastasis, RAS status were similar except there was slightly more liver metastasis on non-resection group (63.2% vs 79.8%). Cox regression analysis found PTR (HR 0.485, 0.302-0.778, p = 0.003)), bone metastasis (HR 3.163, 1.146-6.918, p = 0.004) commencement (HR 0.579, 0.345-0.971, p = 0.038) and completion of systemic therapy (HR 0.310, 0.178-0.539, p = 0.000) are independent factors predicting survival. The median overall survival after PTR vs tumour in-situ is 28 (IQR: 16-47) vs 12 (IQR:6-31) months (p<0.001). CONCLUSION Resection of primary tumour is an independent good prognostic factor in relatively asymptomatic stage IV CA colon patients with unresectable metastasis. Resection should be considered as long as the procedure is straight forward and do not impose significant morbidities with careful patient selection.
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Affiliation(s)
- Man Fung Ho
- Department of Surgery, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong Special Administrative Region; Department of Surgery, North District Hospital, Hong Kong Special Administrative Region.
| | - Victoria Cindy Lai
- Department of Surgery, North District Hospital, Hong Kong Special Administrative Region
| | - Dennis Chung Kei Ng
- Department of Surgery, North District Hospital, Hong Kong Special Administrative Region
| | - Simon Siu Man Ng
- Department of Surgery, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong Special Administrative Region
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Rijken A, van de Vlasakker VCJ, Simkens GA, Rovers KP, van Erning FN, Koopman M, Verhoef C, de Wilt JHW, de Hingh IHJT. Primary tumor resection or systemic treatment as palliative treatment for patients with isolated synchronous colorectal cancer peritoneal metastases in a nationwide cohort study. Clin Exp Metastasis 2023:10.1007/s10585-023-10212-y. [PMID: 37209222 DOI: 10.1007/s10585-023-10212-y] [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: 12/29/2022] [Accepted: 05/15/2023] [Indexed: 05/22/2023]
Abstract
Limited data are available to guide the decision-making process for clinicians and their patients regarding palliative treatment options for patients with isolated synchronous colorectal cancer peritoneal metastases (CRC-PM). Therefore, the aim of this study is to analyze the outcome of the different palliative treatments for these patients. All patients diagnosed with isolated synchronous CRC-PM between 2009 and 2020 (Netherlands Cancer Registry) who underwent palliative treatment were included. Patients who underwent emergency surgery or curative intent treatment were excluded. Patients were categorized into upfront palliative primary tumor resection (with or without additional systemic treatment) or palliative systemic treatment only. Overall survival (OS) was compared between both groups and multivariable cox regression analysis was performed. Of 1031 included patients, 364 (35%) patients underwent primary tumor resection and 667 (65%) patients received systemic treatment only. Sixty-day mortality was 9% in the primary tumor resection group and 5% in the systemic treatment group (P = 0.007). OS was 13.8 months in the primary tumor resection group and 10.3 months in the systemic treatment group (P < 0.001). Multivariable analysis showed that primary tumor resection was associated with improved OS (HR 0.68; 95%CI 0.57-0.81; P < 0.001). Palliative primary tumor resection appeared to be associated with improved survival compared to palliative systemic treatment alone in patients with isolated synchronous CRC-PM despite a higher 60-day mortality. This finding must be interpreted with care as residual bias probably played a significant role. Nevertheless, this option may be considered in the decision-making process by clinicians and their patients.
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Affiliation(s)
- Anouk Rijken
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
- Department of Research and Development, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands
| | | | - Geert A Simkens
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - Koen P Rovers
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - Felice N van Erning
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
- Department of Research and Development, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands
| | - Miriam Koopman
- Department of Medical Oncology, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Cornelis Verhoef
- Department of Surgery, Erasmus Medical Centre, Rotterdam, the Netherlands
| | - Johannes H W de Wilt
- Department of Surgery, Radboud University Medical Centre, Nijmegen, the Netherlands
| | - Ignace H J T de Hingh
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands.
- Department of Research and Development, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands.
- GROW- School for Oncology and Development Biology, Maastricht University, Maastricht, the Netherlands.
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Yin TC, Chen PJ, Yeh YS, Li CC, Chen YC, Su WC, Chang TK, Huang CW, Huang CM, Tsai HL, Wang JY. Efficacy of concurrent radiotherapy in patients with locally advanced rectal cancer and synchronous metastasis receiving systemic therapy. Front Oncol 2023; 13:1099168. [PMID: 37064097 PMCID: PMC10098206 DOI: 10.3389/fonc.2023.1099168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 03/21/2023] [Indexed: 04/03/2023] Open
Abstract
BackgroundNeoadjuvant chemoradiotherapy followed by total mesorectal excision is the standard treatment for patients with nonmetastatic locally advanced rectal cancer (LARC). However, for patients with LARC and synchronous metastasis, the optimal treatment strategy and sequence remain inconclusive. In the present study, we evaluated the efficacy and safety of concurrent radiotherapy in patients with de novo metastatic rectal cancer who received chemotherapy and targeted therapy.MethodsWe retrospectively reviewed the data of 63 patients with LARC and synchronous metastasis who received intensive therapy at the study hospital between April 2015 and November 2018. The included patients were divided into two groups: RT-CT, those who received systemic chemotherapy with targeted therapy and concurrent radiotherapy (for primary rectal cancer), and CT, those who received only systemic chemotherapy with targeted therapy.ResultsTreatment response was better in the RT-CT group than in the CT group. The rate of primary tumor resection (PTR) was higher in the RT-CT group than in the CT group (71.4% and 42.9%, respectively; P = .0286). The RT-CT group exhibited considerably longer local recurrence-free survival (P = .0453) and progression-free survival (PFS; from 13.3 to 22.5 months) than did the CT group (P = .0091); however, the groups did not differ in terms of overall survival (OS; P = .49). Adverse events were almost similar between the groups, except frequent diarrhea, the prevalence of which was higher in the RT-CT group than in the CT group (59.5% and 23.8%, respectively; P = .0075).ConclusionsIn the era of biologics, radiotherapy may increase the resectability of primary rectal tumors, reducing the risk of locoregional failure and prolonging PFS. Concurrent pelvic radiotherapy may not substantially improve OS, which is indicated by metastasis. Hence, the resection of the distant metastases may be essential for improving long-term OS. To further determine the efficacy of concurrent radiotherapy, additional prospective, randomized studies must combine preoperative pelvic radiotherapy with PTR and metastectomy to treat patients with stage IV LARC.
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Affiliation(s)
- Tzu-Chieh Yin
- Division of General and Digestive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Surgery, Kaohsiung Municipal Tatung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Jung Chen
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yung-Sung Yeh
- Division of Trauma and Surgical Critical Care, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Emergency Medicine, Faculty of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Injury Prevention and Control, College of Public Health, Taipei Medical University, Taipei, Taiwan
| | - Ching-Chun Li
- Division of General and Digestive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Surgery, Kaohsiung Municipal Hsiaokang Hospital, Kaohsiung, Taiwan
| | - Yen-Cheng Chen
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wei-Chih Su
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tsung-Kun Chang
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Surgery, Faculty of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-Wen Huang
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chun-Ming Huang
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Radiation Oncology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsiang-Lin Tsai
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- *Correspondence: Jaw-Yuan Wang, ; ; Hsiang-Lin Tsai,
| | - Jaw-Yuan Wang
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Pingtung Hospital, Ministry of Health and Welfare, Pingtung, Taiwan
- *Correspondence: Jaw-Yuan Wang, ; ; Hsiang-Lin Tsai,
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Fanotto V, Salani F, Vivaldi C, Scartozzi M, Ribero D, Puzzoni M, Montagnani F, Leone F, Vasile E, Bencivenga M, De Manzoni G, Basile D, Fornaro L, Masi G, Aprile G. Primary Tumor Resection for Metastatic Colorectal, Gastric and Pancreatic Cancer Patients: In Search of Scientific Evidence to Inform Clinical Practice. Cancers (Basel) 2023; 15:cancers15030900. [PMID: 36765854 PMCID: PMC9913845 DOI: 10.3390/cancers15030900] [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: 12/23/2022] [Revised: 01/24/2023] [Accepted: 01/28/2023] [Indexed: 02/05/2023] Open
Abstract
The management of the primary tumor in metastatic colorectal, gastric and pancreatic cancer patients may be challenging. Indeed, primary tumor progression could be associated with severe symptoms, compromising the quality of life and the feasibility of effective systemic therapy, and might result in life-threatening complications. While retrospective series have suggested that surgery on the primary tumor may confer a survival advantage even in asymptomatic patients, randomized trials seem not to definitively support this hypothesis. We discuss the evidence for and against primary tumor resection for patients with metastatic gastrointestinal (colorectal, gastric and pancreatic) cancers treated with systemic therapies and put in context the pros and cons of the onco-surgical approach in the time of precision oncology. We also evaluate current ongoing trials on this topic, anticipating how these will influence both research and everyday practice.
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Affiliation(s)
- Valentina Fanotto
- Department of Oncology, Academic Hospital of Udine, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), Piazzale Santa Maria della Misericordia, 33100 Udine, Italy
| | - Francesca Salani
- Unit of Oncology 2, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
- Institute of Interdisciplinary Research “Health Science”, Scuola Superiore Sant’Anna, Piazza Martiri della Libertà 33, 56124 Pisa, Italy
| | - Caterina Vivaldi
- Unit of Oncology 2, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
| | - Mario Scartozzi
- Unit of Medical Oncology, University Hospital, University of Cagliari, 09124 Cagliari, Italy
| | - Dario Ribero
- Division of General and Oncologic Surgery Multimedica, A.O. Santa Croce e Carle, 12100 Cuneo, Italy
| | - Marco Puzzoni
- Unit of Medical Oncology, University Hospital, University of Cagliari, 09124 Cagliari, Italy
| | - Francesco Montagnani
- Department of Oncology, Azienda Sanitaria Locale di Biella, 13900 Ponderano, Italy
| | - Francesco Leone
- Department of Oncology, Azienda Sanitaria Locale di Biella, 13900 Ponderano, Italy
| | - Enrico Vasile
- Unit of Oncology 2, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
| | - Maria Bencivenga
- General and Upper GI Surgery Division, Verona University (VR), 37134 Verona, Italy
| | - Giovanni De Manzoni
- General and Upper GI Surgery Division, Verona University (VR), 37134 Verona, Italy
| | - Debora Basile
- Department of Oncology, San Bortolo General Hospital, ULSS 8 Berica-Vicenza, 36100 Vicenza, Italy
| | - Lorenzo Fornaro
- Unit of Oncology 2, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
- Correspondence: ; Tel.: +39-050992466
| | - Gianluca Masi
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
| | - Giuseppe Aprile
- Department of Oncology, San Bortolo General Hospital, ULSS 8 Berica-Vicenza, 36100 Vicenza, Italy
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10
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Zou M, Yang ZQ, Gao F. Letter to the editor "Extramural venous invasion (EMVI) in colorectal cancer is associated with increased cancer recurrence and cancer-related death". Eur J Surg Oncol 2023; 49:298-299. [PMID: 36038430 DOI: 10.1016/j.ejso.2022.08.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 08/11/2022] [Indexed: 01/24/2023] Open
Affiliation(s)
- Min Zou
- Department of Colorectal and Anal Surgery, The 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou, 730050, Gansu Province, China
| | - Zeng-Qiang Yang
- Department of Colorectal Surgery, Gansu Provincial Central Hospital, Lanzhou, 730070, Gansu Province, China
| | - Feng Gao
- Department of Colorectal and Anal Surgery, The 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou, 730050, Gansu Province, China.
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11
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Colloca GA, Venturino A, Guarneri D. Primary tumor resection in patients with unresectable colorectal cancer with synchronous metastases could improve the activity of poly-chemotherapy: A trial-level meta-analysis. Surg Oncol 2022; 44:101820. [DOI: 10.1016/j.suronc.2022.101820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 06/12/2022] [Accepted: 07/11/2022] [Indexed: 12/24/2022]
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12
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Qiao Y, Qiao Y, Li H, Fu J, You S. Survival benefit of primary and metastatic tumor resection for colon cancer with liver metastases: A population based, propensity score-matched study. Front Surg 2022; 9:959826. [PMID: 36111222 PMCID: PMC9468248 DOI: 10.3389/fsurg.2022.959826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 08/08/2022] [Indexed: 11/16/2022] Open
Abstract
Background Colon cancer remains one of the most common malignancies and we aimed to evaluate whether surgery has an effect on the survival of metastatic colon patients. Methods We analyzed 7,583 metastatic colon patients from the Surveillance, Epidemiology, between January 2010 and December 2015. Using Cox proportional hazards models and Kaplan-Meier curves, the overall survival rate (OS) and cancer-specific survival rate and End Results (SEER) registry (CSS) months (m) were evaluated with corresponding 95% confidence intervals (95% CIs). Propensity score matching (PSM) was performed to adjust for potential baseline confounding of all comparison groups. Results In general, receiving both primary and metastatic tumor resection (PMTR) remarkably improved OS and CSS compared with only primary tumor resection (PTR) after PS matching (PSM) (P < 0.05), with a significantly improved OS (HR = 0.74, 95%CI = 0.69–0.80) and CSS (HR = 0.71, 95%CI = 0.66–0.76) in all stage M1 colon patients. The stratification analysis indicated a significant difference between OS and CSS in M1a and M1b stages. After PSM, PMTR was found to be associated with remarkably improved OS and CSS for patients with liver metastases but not associated with OS and CSS of patients with lung metastases in both M1a and M1b stage. Conclusions The results from this large SEER cohort supported PMTR might improve the survival of colon patients with liver metastases on the basis of chemotherapy.
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Affiliation(s)
- Yunfeng Qiao
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yunfeng Qiao
- Cancer Center, Faculty of Health Sciences, University of Macau, Macau, China
| | - Huijun Li
- Department of Imaging Medicine, Taikang Tongji (Wuhan) Hospital, Wuhan, China
| | - Jinge Fu
- Department of Anorectal Surgery, Weishi Central Hospital, Kaifeng, China
| | - Shuping You
- Department of Anus and Bowel Surgery, Jingmen No. 2 People's Hospital, Jingmen, China
- Correspondence: Shuping You
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13
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Mendoza-Moreno F, Diez-Alonso M, Matías-García B, Ovejero-Merino E, Gómez-Sanz R, Blázquez-Martín A, Quiroga-Valcárcel A, Vera-Mansilla C, Molina R, San-Juan A, Barrena-Blázquez S, Ortega MA, Alvarez-Mon M, Gutiérrez-Calvo A. Prognostic Factors of Survival in Patients with Peritoneal Metastasis from Colorectal Cancer. J Clin Med 2022; 11:jcm11164922. [PMID: 36013160 PMCID: PMC9410473 DOI: 10.3390/jcm11164922] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 08/17/2022] [Accepted: 08/19/2022] [Indexed: 11/16/2022] Open
Abstract
Objectives: The aim of this study was to analyze the prognostic factors of survival in patients with peritoneal metastasis (PM) from colorectal cancer (CRC). The type of relationship between survival and the PM time of detection was used to determine whether it was synchronous with the primary tumor or metachronous. Patients and Methods: Retrospective observational study. It included patients treated for colorectal adenocarcinoma diagnosed between January 2005 and December 2019 who presented PM at the time of diagnosis or during follow-up. Variables, such as sex, age, differentiation grade, positive adenopathy (pN+), tumor size (pT), tumor location, mucinous component, peritoneal carcinomatosis index (PCI), and KRAS mutational status, were analyzed. Results: During the study period, 1882 patients were surgically treated for CRC in our hospital. Of these, 240 patients (12.8%) were included in the study after evidence of PM. The mean age was 67 ± 12 years (range: 32−92 years), and 114 patients were female (47.5%). The mean follow-up was 20 ± 13 months (median 12 months). The Kaplan−Meier survival at 36 months was higher in patients with metachronous PM (24% vs. 8%; p = 0.002), WT-KRAS tumors (31% vs. 15%; p < 0.001), N0 stage (30% vs. 19%; p < 0.001), T3 stage tumors (18% vs. 19% in T4A and 3% in T4B; p > 0.001), and tumors with classic adenocarcinoma histology (18% vs. 8%; p = 0.011). Patients with a PCI of 1−10 showed a likelihood of survival at 36 months of 56%, which was longer than that found in patients with a PCI of 11−20 (8%) or a PCI of >20 (0%) (p < 0.001). In the multiple regression analysis, the factors with an independent prognostic value were: poor grade of differentiation (HR 1.995; 95% CI: 1.294−3.077), KRAS mutation (HR 1.751; 95% CI: 1.188−2.581), PCI 11−20 (HR: 9.935; 95% CI: 5.204−18.966) and PCI > 20 (HR: 4.011; 95% CI: 2.291−7.023). Conclusions: PCI should continue as the as the most useful prognostic indicator in order to assess prognostic estimations as well as therapeutic and surgical decisions, but tumor grade and KRAS mutational status may help in the treatment decision process by providing complementary information. The time of PM detection did not achieve statistical significance in the multiple regression analysis.
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Affiliation(s)
- Fernando Mendoza-Moreno
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
- Correspondence:
| | - Manuel Diez-Alonso
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
| | - Belén Matías-García
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
| | - Enrique Ovejero-Merino
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
| | - Remedios Gómez-Sanz
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
| | - Alma Blázquez-Martín
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
| | - Ana Quiroga-Valcárcel
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
| | - Cristina Vera-Mansilla
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
| | - Raquel Molina
- Oncology, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
| | - Alberto San-Juan
- Oncology, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
| | - Silvestra Barrena-Blázquez
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
| | - Miguel A. Ortega
- Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Melchor Alvarez-Mon
- Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcalá de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
- Immune System Diseases-Rheumatology and Internal Medicine Service, University Hospital Príncipe de Asturias (CIBEREHD), 28806 Alcalá de Henares, Spain
| | - Alberto Gutiérrez-Calvo
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Teaching Hospital, 28805 Alcalá de Henares, Spain
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14
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Shu Y, Xu L, Yang W, Xu X, Zheng S. Asymptomatic Primary Tumor Resection in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis. Front Oncol 2022; 12:836404. [PMID: 35425714 PMCID: PMC9001954 DOI: 10.3389/fonc.2022.836404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 03/07/2022] [Indexed: 11/18/2022] Open
Abstract
Background In patients with metastatic colorectal cancer (mCRC) with an asymptomatic primary tumor, there is no consensus on the indication for resection of the primary tumor. Methods The PubMed, Embase and the Cochrane Library databases were searched from inception to November 30,2021. A meta-analysis was performed using RevMan (version 5.3.3; The Cochrane Collaboration) on the outcome of mCRC patients with or without resection of the primary tumor in 8 selected studies. Results This meta-analysis included 2805 colorectal cancer patients with an asymptomatic primary tumor from 8 selected studies. Primary tumor resection (PTR) patients had longer overall survival (OS: MD =6.76 [3.39, 10.12], I2 = 77%, P < 0.0001), compared with non-primary tumor resection (NPTR) patients. In the subgroup, the randomized controlled trials (RCT) PTR group didn’t have longer overall survival (OS: MD =3.79 [-3.49, 11.08], I2 = 69%, P= 0.31); the Non-RCT PTR group had longer overall survival (OS: MD =8.42 [3.14, 13.70], I2 = 89%, P= 0.002). In the meanwhile, compared with NPTR group, the 2-year overall survival rate, the 3-year overall survival rate, 5-year overall survival rate in the PTR group is higher (OR=2.35 [1.74, 3.18], I2 = 0%, P < 0.00001; OR=3.61 [2.35, 5.54], I2 = 0%, P < 0.00001; OR=3.02 [1.72, 5.33], I2 = 48%, P= 0.0001, respectively). Conclusions Our results from studies demonstrate that the resection of primary tumor is a prognostic factor for survival in mCRC patients. However, 2 RCTs showed the resection of primary tumor was not related with a significant survival benefit in subgroup. Therefore, a larger RCT in the era of modern chemotherapy and liver resection techniques would be helpful.
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Affiliation(s)
- Yefei Shu
- Department of Medical Oncology, Hangzhou Cancer Hospital, Hangzhou, China
| | - Ling Xu
- Department of Oncology and Hematology, Hangzhou Red Cross Hospital, Hangzhou, China
| | - Wei Yang
- Department of Oncology and Hematology, Hangzhou Red Cross Hospital, Hangzhou, China
| | - Xiaofeng Xu
- Department of Oncology and Hematology, Hangzhou Red Cross Hospital, Hangzhou, China
| | - Song Zheng
- Department of Medical Oncology, Hangzhou Cancer Hospital, Hangzhou, China.,Department of Medical Oncology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
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15
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Huang L, Wei G, Chen N, Liu J, Wang Z, Yu Y, Qiu M. Impact of Upfront Chemotherapy on the Effect of Primary Tumour Resection for Asymptomatic Synchronous Colorectal Cancer With Unresectable Metastases: A Propensity-Score-Matched Cohort Analysis. Clin Med Insights Oncol 2022; 16:11795549221085054. [PMID: 35355515 PMCID: PMC8958687 DOI: 10.1177/11795549221085054] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 02/05/2022] [Indexed: 02/05/2023] Open
Abstract
Background: It is controversial whether primary tumour resection (PTR) and the sequencing of chemotherapy and PTR are associated with the survival of patients with incurable stage IV colorectal cancer. This study aimed to explore the effects of PTR and the sequencing of chemotherapy and PTR on asymptomatic colorectal cancer with synchronous unresectable metastases (asmCRC). Patients and Methods: Patients with asmCRC were retrospectively identified from a single centre and categorised into 3 groups: PTR followed by chemotherapy (POC), upfront chemotherapy followed by PTR (UFC), and palliative chemotherapy (PC). The primary end points included median overall survival (OS) and progression-free survival (PFS). Clinical features were analysed using χ2 test, while survival curves were generated using the Kaplan-Meier test. Propensity-score matching (PSM) was performed when comparing survival between POC and UFC groups. Results: From 2008 to 2014, 255 patients were identified and included into the POC (n = 101), UFC (n = 40), and PC (n = 114) groups. The UFC and POC groups had significantly better median OS compared with the PC group (40.7 vs 16.3 months, P < .0001; 39.7 vs 16.3 months, P < .0001). Before PSM, the UFC group had better median PFS than the POC and PC groups (18.5 vs 9.7 months, P = .038; 18.5 vs 6.1 months, P < .0001). After PSM, UFC has better PFS than POC (P = .038). And the UFC group did not have higher postoperative or preoperative morbidity compared with the POC group (P = .235). Conclusions: Primary tumour resection could improve the survival of patients with asmCRC. Compared with POC or PC, UFC was associated with a better median PFS without significantly increasing preoperative or postoperative morbidity.
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Affiliation(s)
- Lin Huang
- Lung Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Guixia Wei
- Department of Abdominal Cancer, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Nan Chen
- Department of Thoracic Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Jiewei Liu
- Lung Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Ziqiang Wang
- Department of Gastrointestinal Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Yongyang Yu
- Department of Gastrointestinal Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Meng Qiu
- Department of Abdominal Cancer, West China Hospital of Sichuan University, Chengdu, Sichuan, China
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16
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Huang M, Yang Y, Li Q, Wang C, Liang L, Zhu X, Zhang W, Chen Z, Huang D, Li W, Zhang X, Zhao X, Qiu L, Geng Q, Yu N, Du W, Sun S, Sheng X, Li X, Guo W. Induction Chemotherapy Followed by Primary Tumor Resection Did Not Bring Survival Benefits in Colon Cancer Patients With Asymptomatic Primary Lesion and Synchronous Unresectable Metastases. Front Oncol 2022; 12:747124. [PMID: 35174078 PMCID: PMC8841852 DOI: 10.3389/fonc.2022.747124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Accepted: 01/04/2022] [Indexed: 12/24/2022] Open
Abstract
BackgroundIt is still controversial whether primary tumor resection (PTR) improves survival in colorectal cancer (CRC) patients with unresectable metastases.MethodsColon cancer patients were enrolled and randomly allocated to with or without PTR after induction chemotherapy with XELOX or mFOLFOX6, and those with chemotherapy failure were excluded. The primary endpoint was TTF (time to strategy failure) on an intent-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT02291744.ResultsBetween April 2015 and July 2020, 140 patients were enrolled, and 54 patients were excluded due to colon obstruction (16), perforation (1), disease progression (22), death (1), radical resection (3), or other reasons (11). After induction chemotherapy, 86 patients were randomized into group A (the resection group, n = 42) or group B (chemotherapy-alone group, n = 44). The median TTF was 143 days (95% CI: 104.9–181.1) in group A and 196 days (95% CI: 96.5–295.5) in group B (HR: 0.930 95% CI: 0.589–1.468, p = 0.755), and there was no significant difference in PFS, OS, and incidence of chemotherapy-related adverse events between two groups. The primary lesion-related events after PTR in group A were significantly fewer than those in group B. Patients with a tumor regression grade (TRG) score of 2 had longer TTF and PFS than those with score of 3.ConclusionPTR after induction chemotherapy could not bring survival benefits for colon cancer patients with unresectable metastases, and it is not recommended routinely. However, it also requires individualized treatment as colon obstruction or perforation occurred in some patients and PTR could reduce primary tumor-related events, and the TRG score might help for selection of beneficial patients.
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Affiliation(s)
- Mingzhu Huang
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ya’nan Yang
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Qingguo Li
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Chenchen Wang
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Lei Liang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Xiaodong Zhu
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wen Zhang
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhiyu Chen
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Dan Huang
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Wenhua Li
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xiaowei Zhang
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xiaoying Zhao
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Lixin Qiu
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Qirong Geng
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Nuoya Yu
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wenfang Du
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Sijie Sun
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xuedan Sheng
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xinxiang Li
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- *Correspondence: Weijian Guo, ; Xinxiang Li,
| | - Weijian Guo
- Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- *Correspondence: Weijian Guo, ; Xinxiang Li,
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17
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Siu DHW, Ali A, Tjokrowidjaja A, De Silva M, Lee J, Clingan PR, Aghmesheh M, Brungs D, Mapagu C, Goldstein D, O'Neill S, Liauw WS, Sjoquist KM, Thomas D, Pavlakis N, Clarke SJ, Diakos C, Chantrill LA. Clinical and molecular profile of young adults with early-onset colorectal cancer: Experience from four Australian tertiary centers. Asia Pac J Clin Oncol 2022; 18:660-668. [PMID: 35098672 DOI: 10.1111/ajco.13745] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 11/16/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Patients with early-onset colorectal cancer (EO-CRC) have unique characteristics. Contemporary data on the pathological and molecular features, and survival of EO-CRC are limited in the Australian context. AIM To determine the demographic, histopathological and molecular characteristics of adults with EO-CRC, and their survival. METHODS We conducted a retrospective study of adults aged 18-49 years with EO-CRC who were referred to the Illawarra Shoalhaven Local Health District, South Eastern Sydney Local Health District and Royal North Shore Hospital in New South Wales, Australia, between 2014 and 2018. RESULTS Of 257 patients included, 94 (37%) patients presented with de novo metastatic CRC, 80% patients had near-average risk family history and 89% had a symptomatic presentation. In 159 patients with nonmetastatic disease at diagnosis, stage III disease (OR 3.88 [95% CI: 1.13-13.3]; p = .03) and the presence of perineural invasion (PNI) (OR 6.63 [95% CI: 2.21-19.84]; p = .001) were risk factors associated with the development of metastatic disease. Among 94 patients with de novo metastatic disease, 43 (43%) and 12 (14%) patients harbored a KRAS or BRAF V600E mutation, respectively. The median overall survival was 29.6 months (95% CI: 20.4-38.7). BRAF mutation was associated with inferior survival (HR 3.00 [95% CI: 1.30-6.94]; p = .01). CONCLUSION The prevalence of KRAS and BRAF mutations in our cohort is similar to the overseas experience. Stage III disease at diagnosis, presence of PNI and BRAF mutation are adverse prognostic indicators. A better understanding of the molecular landscape is needed for this patient cohort, so as to better tailor prevention strategies, screening and treatment pathways.
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Affiliation(s)
- Derrick Ho Wai Siu
- Department of Medical Oncology, Illawarra Shoalhaven Local Health District (ISLHD), New South Wales, Australia.,Department of Medical Oncology, St George Hospital, New South Wales, Australia.,National Health and Medical Research Council (NHMRC) Clinical Trial Centre, University of Sydney, New South Wales, Australia.,Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
| | - Arwa Ali
- Department of Medical Oncology, Nelune Cancer Centre, The Prince of Wales Hospital (POWH), New South Wales, Australia.,Department of Medical Oncology, South Egypt Cancer Institute, Asyut, Egypt
| | - Angelina Tjokrowidjaja
- Department of Medical Oncology, St George Hospital, New South Wales, Australia.,National Health and Medical Research Council (NHMRC) Clinical Trial Centre, University of Sydney, New South Wales, Australia
| | - Madhawa De Silva
- Department of Medical Oncology, Royal North Shore Hospital (RNSH), New South Wales, Australia
| | - Joanna Lee
- Department of Medical Oncology, St George Hospital, New South Wales, Australia
| | - Philip R Clingan
- Department of Medical Oncology, Illawarra Shoalhaven Local Health District (ISLHD), New South Wales, Australia.,School of Medicine, University of Wollongong, New South Wales, Australia
| | - Morteza Aghmesheh
- Department of Medical Oncology, Illawarra Shoalhaven Local Health District (ISLHD), New South Wales, Australia.,School of Medicine, University of Wollongong, New South Wales, Australia
| | - Daniel Brungs
- Department of Medical Oncology, Illawarra Shoalhaven Local Health District (ISLHD), New South Wales, Australia.,School of Medicine, University of Wollongong, New South Wales, Australia
| | - Cristina Mapagu
- Department of Medical Oncology, Illawarra Shoalhaven Local Health District (ISLHD), New South Wales, Australia.,Westmead Clinical School, University of Sydney, New South Wales, Australia
| | - David Goldstein
- Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.,Department of Medical Oncology, Nelune Cancer Centre, The Prince of Wales Hospital (POWH), New South Wales, Australia
| | - Siobhan O'Neill
- Department of Medical Oncology, Nelune Cancer Centre, The Prince of Wales Hospital (POWH), New South Wales, Australia
| | - Winston S Liauw
- Department of Medical Oncology, St George Hospital, New South Wales, Australia.,Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
| | - Katrin M Sjoquist
- Department of Medical Oncology, St George Hospital, New South Wales, Australia.,National Health and Medical Research Council (NHMRC) Clinical Trial Centre, University of Sydney, New South Wales, Australia
| | - David Thomas
- Department of Medical Oncology, St George Hospital, New South Wales, Australia
| | - Nick Pavlakis
- Department of Medical Oncology, Royal North Shore Hospital (RNSH), New South Wales, Australia.,Northern Clinical School, University of Sydney, New South Wales, Australia
| | - Stephen J Clarke
- Department of Medical Oncology, Royal North Shore Hospital (RNSH), New South Wales, Australia.,Northern Clinical School, University of Sydney, New South Wales, Australia
| | - Connie Diakos
- Department of Medical Oncology, Royal North Shore Hospital (RNSH), New South Wales, Australia.,Northern Clinical School, University of Sydney, New South Wales, Australia
| | - Lorraine A Chantrill
- Department of Medical Oncology, Illawarra Shoalhaven Local Health District (ISLHD), New South Wales, Australia.,Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.,The Garvan Institute of Medical Research, Sydney, New South Wales, Australia
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18
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Benavides M, Gómez-España A, García-Alfonso P, González CG, Viéitez JM, Rivera F, Safont MJ, Abad A, Sastre J, Valladares-Ayerbes M, Carrato A, González-Flores E, Robles L, Salud A, Alonso-Orduña V, Montagut C, Asensio E, Díaz-Rubio E, Aranda E. Upfront primary tumour resection and survival in synchronous metastatic colorectal cancer according to primary tumour location and RAS status: Pooled analysis of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD). Eur J Surg Oncol 2021; 48:1123-1132. [PMID: 34872775 DOI: 10.1016/j.ejso.2021.11.122] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 09/14/2021] [Accepted: 11/17/2021] [Indexed: 12/30/2022] Open
Abstract
INTRODUCTION Retrospective studies and meta-analyses suggest that upfront primary tumour resection (UPTR) confers a survival benefit in patients with asymptomatic unresectable metastatic colorectal cancer (mCRC) undergoing chemotherapy, however a consensus of its role in routine clinical practice in the current era of targeted therapies is lacking. This retrospective study aimed to analyse the survival benefit of UPTR in terms of tumour location and mutational status, in patients with synchronous mCRC receiving chemotherapy and targeted therapy. PATIENTS AND METHODS Survival was analysed in a pooled cohort of synchronous mCRC patients treated with a first-line anti-VEGF or anti-EGFR inhibitor in seven trials of the Spanish TTD group, according to UPTR, tumour-sidedness and mutational profiling. RESULTS Of 1334 eligible patients, 642 (48%) had undergone UPTR. UPTR was associated with significantly longer overall survival (OS; 25.0 vs 20.3 months; HR 1.30, 95%CI 1.15-1.48; p < 0.0001). UPTR was associated with significant OS benefit in both left-sided (HR 1.38, 95%CI 1.13-1.69; p = 0.002) and right-sided (HR 1.39, 95%CI 1.00-1.94; p = 0.049) tumours, RASwt (HR 1.29, 95%CI 1.05-1.60; p = 0.016) and BRAFwt (HR 1.49, 95%CI 1.21-1.84; p = 0.0002) tumours, and treatment with anti-EGFRs (HR 1.47, 95%CI 1.13-1.92; p = 0.004) and anti-VEGFs (HR 1.25, 95%CI 1.08-1.44; p = 0.003). Multivariate analysis identified number of metastatic sites, RAS status, primary tumour location and UPTR as independent prognostic factors for OS. CONCLUSION Considering the selection bias inherent to this study, our results support UPTR before first-line anti-EGFR or anti-VEGF targeted therapy in right and left-sided asymptomatic unresectable synchronous mCRC patients. RAS/BRAF mutational status may also influence UPTR function.
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Affiliation(s)
- Manuel Benavides
- UGC Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, IBIMA, Málaga, Spain.
| | - Auxiliadora Gómez-España
- Department of Medical Oncology, IMIBIC, Universidad de Córdoba, CIBERONC, Instituto de Salud Carlos III, Hospital Universitario Reina Sofía, Córdoba, Spain
| | - Pilar García-Alfonso
- Department of Medical Oncology, Hospital Universitario Gregorio Marañón, Madrid, Spain
| | - Cristina García González
- UGC Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, IBIMA, Málaga, Spain
| | - Jose María Viéitez
- Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Fernando Rivera
- Department of Medical Oncology, University Hospital Marqués de Valdecilla, IDIVAL, Santander, Spain
| | - María José Safont
- Department of Medical Oncology, Hospital General Universitario Valencia, Universidad de Valencia, CIBERONC, Valencia, Spain
| | - Albert Abad
- Department of Medical Oncology, Instituto Oncológico Dr. Rosell, Barcelona, Spain
| | - Javier Sastre
- Department of Medical Oncology, Hospital Clínico San Carlos, Instituto de Investigación Hospital Clínico San Carlos (IdISSC), University Complutense, CIBERONC, Madrid, Spain
| | | | - Alfredo Carrato
- Department of Medical Oncology, IRYCIS, CIBERONC, Alcalá University, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | | | - Luis Robles
- Department of Medical Oncology, Hospital 12 de Octubre, Madrid, Spain
| | - Antonieta Salud
- Department of Medical Oncology, Hospital de Lleida Arnau de Vilanova, Lérida, Spain
| | - Vicente Alonso-Orduña
- Department of Medical Oncology, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón (IISA), Zaragoza, Spain
| | - Clara Montagut
- Department of Medical Oncology, Hospital del Mar Medical Research Institute, CIBERONC, Barcelona, Spain
| | - Elena Asensio
- Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain
| | - Eduardo Díaz-Rubio
- Department of Medical Oncology, Hospital Clínico San Carlos, Instituto de Investigación Hospital Clínico San Carlos (IdISSC), University Complutense, CIBERONC, Madrid, Spain
| | - Enrique Aranda
- Department of Medical Oncology, IMIBIC, Universidad de Córdoba, CIBERONC, Instituto de Salud Carlos III, Hospital Universitario Reina Sofía, Córdoba, Spain
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19
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Stukalova OY, Polikarpov AA, Isсhenko RV. CHEMOEMBOLIZATION OF THE HEPATIC ARTERY IN THE TREATMENT OF PATIENTS WITH CHEMORESISTANT METASTASES OF COLORECTAL CANCER. REVIEW. SURGICAL PRACTICE 2021. [DOI: 10.38181/2223-2427-2021-3-61-68] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
In the structure of the incidence of malignant tumors for a number of years, colorectal cancer occupies one of the leading positions, with a steady tendency to growth. The five-year survival rate of patients with metastatic liver damage in colorectal cancer does not exceed 28%. A significant breakthrough in the study of the biology of colorectal cancer has led to a deep understanding of individual processes of carcinogenesis and a personalized approach to treatment tactics. Despite this, the problem of chemoresistance remains one of the most acute. The high toxicity of systemic chemotherapy limits its use in this group of patients. In this connection, minimally invasive and at the same time effective methods of local treatment of malignant liver tumors have been introduced into clinical practice. These methods include: hepatic artery chemoinfusion, chemoembolization, oil chemoembolization and radioembolization. At present, a large world experience has already been accumulated in the application of the above-described methods of treatment. However, the question of the application of methods of interventional surgery in the treatment of patients with chemoresistant metastases is still open. The presented review reflects the results of the analysis of scientific literature on the treatment of this group of patients. The main stages of development and improvement of X-ray endovascular methods of treatment are presented.
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Affiliation(s)
| | - A. A. Polikarpov
- Surgery and Oncology Granov Russian Research Center of Radiology and Surgical Technologies of Healthcare Ministry of the Russian Federation
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20
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van der Kruijssen DEW, Elias SG, Vink GR, van Rooijen KL, 't Lam-Boer J, Mol L, Punt CJA, de Wilt JHW, Koopman M. Sixty-Day Mortality of Patients With Metastatic Colorectal Cancer Randomized to Systemic Treatment vs Primary Tumor Resection Followed by Systemic Treatment: The CAIRO4 Phase 3 Randomized Clinical Trial. JAMA Surg 2021; 156:1093-1101. [PMID: 34613339 DOI: 10.1001/jamasurg.2021.4992] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Importance The role of primary tumor resection (PTR) in synchronous patients with metastatic colorectal cancer (mCRC) who had unresectable metastases and few or absent symptoms of their primary tumor is unclear. Studying subgroups with low postoperative mortality may identify patients who potentially benefit from PTR. Objective To determine the difference in 60-day mortality between patients randomized to systemic treatment only vs PTR followed by systemic treatment, and to explore risk factors associated with 60-day mortality. Design, Setting, and Participants CAIRO4 is a randomized phase 3 trial initiated in 2012 in which patients with mCRC were randomized to systemic treatment only or PTR followed by systemic treatment with palliative intent. This multicenter study was conducted by the Danish and Dutch Colorectal Cancer Group in general and academic hospitals in Denmark and the Netherlands. Patients included between August 2012 and December 2019 with histologically proven colorectal cancer, unresectable metastases, and a primary tumor with few or absent symptoms were eligible. Interventions Systemic treatment, consisting of fluoropyrimidine-based chemotherapy with bevacizumab vs PTR followed by fluoropyrimidine-based chemotherapy with bevacizumab. Main Outcomes and Measures The aim of the current analysis was to compare 60-day mortality rates in both treatment arms. A secondary aim was the identification of risk factors for 60-day mortality in the treatment arms. These aims were not predefined in the study protocol. Results A total of 196 patients were included in the intention-to-treat analysis (112 [57%] men; median [IQR] age, 65 [59-70] years). Sixty-day mortality was 3% (95% CI, 1%-9%) in the systemic treatment arm and 11% (95% CI, 6%-19%) in the PTR arm (P = .03). In a per-protocol analysis, 60-day mortality was 2% (95% CI, 1%-7%) vs 10% (95% CI, 5%-18%; P = .048). Patients with elevated serum levels of lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, and/or neutrophils who were randomized to PTR had a significantly higher 60-day mortality than patients without these characteristics. Conclusions and Relevance Patients with mCRC who were randomized to PTR followed by systemic treatment had a higher 60-day mortality than patients randomized to systemic treatment. Especially patients randomized to the PTR arm with elevated serum levels of lactate dehydrogenase, neutrophils, aspartate aminotransferase, and/or alanine aminotransferase were at high risk of postoperative mortality. Final study results on overall survival have to be awaited. Trial Registration ClinicalTrials.gov Identifier: NCT01606098.
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Affiliation(s)
- Dave E W van der Kruijssen
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Sjoerd G Elias
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Geraldine R Vink
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.,Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, the Netherlands
| | - Karlijn L van Rooijen
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Jorine 't Lam-Boer
- Department of Surgery, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Linda Mol
- Clinical Research Department, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, the Netherlands
| | - Cornelis J A Punt
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Johannes H W de Wilt
- Department of Surgery, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Miriam Koopman
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
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21
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Gao X, Kahl AR, Goffredo P, Lin AY, Vikas P, Hassan I, Charlton ME. Treatment of Stage IV Colon Cancer in the United States: A Patterns-of-Care Analysis. J Natl Compr Canc Netw 2021; 18:689-699. [PMID: 32502984 DOI: 10.6004/jnccn.2020.7533] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Accepted: 01/10/2020] [Indexed: 11/17/2022]
Abstract
BACKGROUND National guidelines recommend chemotherapy as the mainstay of treatment for stage IV colon cancer, with primary tumor resection (PTR) reserved for patients with symptomatic primary or curable disease. The aims of this study were to characterize the treatment modalities received by patients with stage IV colon cancer and to determine the patient-, tumor-, and hospital-level factors associated with those treatments. METHODS Patients diagnosed with stage IV colon cancer in 2014 were extracted from the SEER Patterns of Care initiative. Treatments were categorized into chemotherapy only, PTR only, PTR + chemotherapy, and none/unknown. RESULTS The total weighted number of cases was 3,336; 17% of patients received PTR only, 23% received chemotherapy only, 41% received PTR + chemotherapy, and 17% received no treatment. In multivariable analyses, compared with chemotherapy only, PTR + chemotherapy was associated with being married (odds ratio [OR], 1.9), having bowel obstruction (OR, 2.55), and having perforation (OR, 2.29), whereas older age (OR, 5.95), Medicaid coverage (OR, 2.46), higher T stage (OR, 3.51), and higher N stage (OR, 6.77) were associated with PTR only. Patients who received no treatment did not have more comorbidities or more severe disease burden but were more likely to be older (OR, 3.91) and non-Hispanic African American (OR, 2.92; all P<.05). Treatment at smaller, nonacademic hospitals was associated with PTR (± chemotherapy). CONCLUSIONS PTR was included in the treatment regimen for most patients with stage IV colon cancer and was associated with smaller, nonacademic hospitals. Efforts to improve guideline implementation may be beneficial in these hospitals and also in non-Hispanic African American and older populations.
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Affiliation(s)
- Xiang Gao
- 1Department of Surgery, Carver College of Medicine, and
| | - Amanda R Kahl
- 2Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa
| | | | - Albert Y Lin
- 3Division of Oncology, Department of Medicine, VA Palo Alto Health Care System, Palo Alto, California.,4Department of Medicine, Stanford University, Stanford, California; and
| | - Praveen Vikas
- 5Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa
| | - Imran Hassan
- 1Department of Surgery, Carver College of Medicine, and
| | - Mary E Charlton
- 2Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa
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22
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van der Kruijssen DEW, van Rooijen KL, Kurk SA, de Wilt JHW, Punt CJA, Vink GR, Elias SG, Koopman M. Role of Up-Front Primary Tumor Resection and Tumor Sidedness in the Survival of Synchronous Metastatic Colon Cancer Patients. Dig Surg 2021; 38:283-289. [PMID: 34320508 DOI: 10.1159/000517477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Accepted: 05/25/2021] [Indexed: 12/10/2022]
Abstract
INTRODUCTION Uncertainty exists about a possible survival benefit of primary tumor resection (PTR) in synchronous metastatic colon cancer (mCC). Since sidedness of the primary tumor is regarded as an important prognostic factor, our objective was to study the interaction between PTR and sidedness in synchronous mCC. METHODS In this retrospective study, we used data from 2 first-line phase 3 randomized controlled trials (RCTs). A mixed Cox regression model was used to study the multiplicative interaction between PTR and sidedness. We adjusted for age, treatment arm, WHO performance status, number of affected organs by metastases, serum lactate dehydrogenase, and year of enrollment. RESULTS We found that PTR is associated with better survival in both right-sided (hazard ratio [HR] 0.59 [95% confidence interval 0.42-0.8 2]) and left-sided mCC (HR 0.70 [95% confidence interval 0.52-0.93]). The interaction between PTR and sidedness was not significant (p = 0.45). CONCLUSION Our data suggest that the prognostic value of PTR is independent of sidedness. Validation of these results will be performed in ongoing RCTs.
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Affiliation(s)
- Dave E W van der Kruijssen
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Karlijn L van Rooijen
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Sophie A Kurk
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Johannes H W de Wilt
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Cornelis J A Punt
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Geraldine R Vink
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.,Comprehensive Cancer Organization, Utrecht, The Netherlands
| | - Sjoerd G Elias
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Miriam Koopman
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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23
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van der Kruijssen DEW, Brouwer NPM, van der Kuil AJS, Verhoeven RHA, Elias SG, Vink GR, Punt CJA, de Wilt JHW, Koopman M. Interaction Between Primary Tumor Resection, Primary Tumor Location, and Survival in Synchronous Metastatic Colorectal Cancer: A Population-Based Study. Am J Clin Oncol 2021; 44:315-324. [PMID: 33899807 DOI: 10.1097/coc.0000000000000823] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
OBJECTIVES Location of the primary tumor has prognostic value and predicts the effect of certain therapeutics in synchronous metastatic colorectal cancer. We investigated whether the association between primary tumor resection (PTR) and overall survival (OS) also depends on tumor location. METHODS Data on synchronous metastatic colorectal cancer patients from the Netherlands Cancer Registry (n=16,106) and Surveillance, Epidemiology, and End Results (SEER) registry (n=19,584) were extracted. Cox models using time-varying covariates were implemented. Median OS for right-sided colon cancer (RCC), left-sided colon cancer, and rectal cancer was calculated using inverse probability weighting and a landmark point of 6 months after diagnosis as reference. RESULTS The association between PTR and OS was dependent on tumor location (P<0.05), with a higher median OS of upfront PTR versus upfront systemic therapy in Netherlands Cancer Registry (NCR) of 1.9 (95% confidence interval: 0.9-2.8), 4.3 (3.3-5.6), and 3.4 (0.6-7.6) months in RCC, left-sided colon cancer and rectal cancer, respectively. In SEER data, the difference was 6.0 (4.0-8.0), 8.0 (5.0-10.0), and 10.0 (7.0-13.0) months, respectively. Hazard plots indicate a higher hazard of death 2 to 3 months after PTR in RCC. CONCLUSION Upfront PTR is associated with improved survival regardless of primary tumor location. Patients with RCC appear to have less benefit because of higher mortality during 2 to 3 months after PTR.
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Affiliation(s)
| | - Nelleke P M Brouwer
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | | | - Rob H A Verhoeven
- Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL)
| | - Sjoerd G Elias
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht
| | - Geraldine R Vink
- Department of Medical Oncology, University Medical Center Utrecht
- Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL)
| | - Cornelis J A Punt
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht
| | - Johannes H W de Wilt
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Miriam Koopman
- Department of Medical Oncology, University Medical Center Utrecht
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24
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Arhin ND, Shen C, Bailey CE, Matsuoka LK, Hawkins AT, Holowatyj AN, Ciombor KK, Hopkins MB, Geiger TM, Kam AE, Roth MT, Lebeck Lee CM, Lapelusa M, Dasari A, Eng C. Surgical resection and survival outcomes in metastatic young adult colorectal cancer patients. Cancer Med 2021; 10:4269-4281. [PMID: 34132476 PMCID: PMC8267130 DOI: 10.1002/cam4.3940] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 04/09/2021] [Accepted: 04/12/2021] [Indexed: 12/17/2022] Open
Abstract
Background The incidence of colorectal cancer in adults younger than age 50 has increased with rates expected to continue to increase over the next decade. The objective of this study is to examine the survival benefit of surgical resection (primary and/or metastatic) versus palliative therapy in this patient population. Methods We identified 6708 young adults aged 18–45 years diagnosed with metastatic colorectal cancer (mCRC) from 2004 to 2015 from the SEER database. Overall survival (OS) was analyzed using Kaplan–Meier estimation, log rank test, and multivariate Cox proportional hazards model. Results Sixty‐three percent of patients in our study underwent primary tumor resection (PTR), with 40% undergoing PTR alone and 23% undergoing both resection of primary disease and metastasectomy. The median OS for patients who underwent both PTR and metastasectomy was 36 months, compared to 13 months for those who did not receive any surgical intervention. The multivariate analysis showed significant OS benefit of receiving both PTR and metastasectomy (HR 0.34, 95% CI: 0.31–0.37, p < 0.001) compared to palliative therapy. Undergoing PTR only and metastasectomy only were also associated with improved OS (HR 0.46, 95% CI: 0.43–0.49, p < 0.001 and HR 0.64, 95% CI: 0.55–0.76, p < 0.001, respectively). Conclusion This is the largest observational study to evaluate survival outcomes in young‐onset mCRC patients and the role of surgical intervention of the primary and/or metastatic site. Our study provides evidence of statistically significant increase in OS for young mCRC patients who undergo surgical intervention of the primary and/or metastatic site.
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Affiliation(s)
- Nina D Arhin
- Division of Hematology and Oncology, Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Chan Shen
- Department of Surgery, Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA
| | - Christina E Bailey
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Lea K Matsuoka
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Alexander T Hawkins
- Section of Colon & Rectal Surgery, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Andreana N Holowatyj
- Department of Medicine, Vanderbilt University Medical Center/Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
| | - Kristen K Ciombor
- Division of Hematology and Oncology, Department of Internal Medicine, Vanderbilt University Medical Center/Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
| | - Michael B Hopkins
- Division of General Surgery, Colon and Rectal Surgery, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Timothy M Geiger
- Division of General Surgery, Colon and Rectal Surgery, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Audrey E Kam
- Division of Hematology, Oncology and Cell Therapy, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA
| | - Marc T Roth
- Division of Hematology and Oncology, Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | | | - Michael Lapelusa
- Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Arvind Dasari
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Cathy Eng
- Division of Hematology and Oncology, Department of Internal Medicine, Vanderbilt University Medical Center/Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
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25
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Prognostic value of regional lymph node involvement in patients with metastatic colorectal cancer: palliative versus curative resection. World J Surg Oncol 2021; 19:150. [PMID: 33985521 PMCID: PMC8120831 DOI: 10.1186/s12957-021-02260-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 05/05/2021] [Indexed: 12/11/2022] Open
Abstract
Background Approximately 20% of patients with colorectal cancer are initially diagnosed with stage IV disease. This study aims to examine the role of regional lymph node (LN) status in metastatic colorectal cancer (mCRC) with respect to clinicopathologic features and survival outcomes. Methods We investigated 1147 patients diagnosed with mCRC and had undergone surgical resection of the primary CRC. A total of 167 patients were placed in the LN-negative (LN−) group and another 980 in the LN-positive (LN+) group. Results LN+ patients exhibited a significantly higher rate of T4 tumors (p = 0.008), poorly differentiated adenocarcinoma (p < 0.001), lymphovascular invasion (p < 0.001), and perineural invasion (p < 0.001) than those in the LN− group. LN− patients had a significantly higher rate of lung metastasis (p < 0.001), whereas the rate of peritoneal seeding (p < 0.001) and systemic node metastasis (p < 0.001) was both significantly higher in the LN+ group. The 5-year overall survival (OS) in the LN+ group was significantly poorer than that in the LN− group (LN− vs. LN+ 23.2% vs. 18.1%; p = 0.040). In patients with curative resection, the 5-year OS rate has no significant difference between the two groups (LN− vs. LN+ 19.5% vs. 24.3%; p = 0.890). Conclusions Metastatic CRC patients with LN+ who underwent primary tumor resection may present with more high-risk pathological features, more peritoneal seeding, and systemic node metastasis, but less lung metastasis than LN− patients. LN+ patients had poorer long-term outcomes compared with that in LN− patients. Nevertheless, with curative resection, LN+ patients could have similar survival outcomes as LN− patients.
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Chen JN, Shoucair S, Wang Z, Habib JR, Zhao FQ, Yu J, Liu Z, Liu Q. Primary Tumor Resection for Rectal Cancer With Unresectable Liver Metastases: A Chance to Cut Is a Chance for Improved Survival. Front Oncol 2021; 11:628715. [PMID: 33791215 PMCID: PMC8006931 DOI: 10.3389/fonc.2021.628715] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 02/22/2021] [Indexed: 01/05/2023] Open
Abstract
Background: About half of the patients with rectal cancer will develop liver metastasis during the course of their illness. Unfortunately, a large proportion of these metastases are unresectable. Surgical resection of the primary tumor vs. palliative treatment in patients with unresectable synchronous liver metastases remains controversial. Methods: Patients with rectal cancer with surgically unresectable liver metastases were identified from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2015. According to different treatment modalities, patients were divided into a primary tumor resection group and a non-resection group. Rates of primary tumor resection and survival were calculated for each year. Kaplan–Meier methods and Cox regression models were used to assess long-term survival. Multivariable logistic regression models were used to evaluate factors potentially associated with primary tumor resection. Results: Among 1,957 patients, 494 (25.2%) had undergone primary tumor resection. Patients with primary tumor resection had significantly better 5-year survival rate (27.2 vs. 5.6%, P < 0.001) compared to the non-resection group. Chemoradiotherapy with primary site resection was associated with the longest mean and 5-year OS (44.7 months, 32.4%). The Cox regression analyses of the subgroup indicated that patients who underwent primary tumor resection had improved survival compared with those who did not undergo resection in all 25 subgroups. Factors associated with primary tumor resection were well or moderately differentiated tumor grade, undergoing radiation, and primary tumor size <5 cm. Conclusions: The majority of patients with rectal cancer with unresectable liver metastases did not undergo primary tumor resection. Our results indicate that resection of the primary tumor appears to offer the greatest chance of survival. Prospective studies are needed to confirm these results.
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Affiliation(s)
- Jia-Nan Chen
- Department of Colon and Rectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Sami Shoucair
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Zheng Wang
- Department of Colon and Rectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Joseph R Habib
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Fu-Qiang Zhao
- Department of Colon and Rectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun Yu
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Zheng Liu
- Department of Colon and Rectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qian Liu
- Department of Colon and Rectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Ostwal V, Kapoor A, Engineer R, Saklani A, deSouza A, Patil P, Arya S, Ankathi SK, Chopra S, Patil M, Jain S, Ramaswamy A. Systemic chemotherapy and short-course radiation in metastatic rectal cancers: A feasible paradigm in unresectable and potentially resectable cancers. South Asian J Cancer 2020; 8:92-97. [PMID: 31069186 PMCID: PMC6498721 DOI: 10.4103/sajc.sajc_174_18] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background: The optimal use and sequencing of short-course radiotherapy (SCRT) in metastatic rectal cancers (mRCs) are not well established. Materials and Methods: We retrospectively reviewed the records of mRC patients receiving SCRT followed by palliative chemotherapy between January 1, 2013, and December 31, 2016, in Tata Memorial Hospital. Patients were classified as having “potentially resectable” disease (local and metastatic) or “unresectable” disease at baseline based on prespecified criteria. Results: A total of 105 consecutive patients were available for analysis. The median age of patients was 48 years (range: 16–62 years), and 57.1% were male patients. Signet ring histology was seen in 13.3% of patients. The most common site of metastases was liver limited (29.5%), nonloco-regional nodes (12.4%), and lung limited metastases (9.5%). Chemotherapeutic regimens administered were capecitabine-oxaliplatin (70.5%), modified 5 fluorouracil (5 FU)-leucovorin-irinotecan-oxaliplatin (10.5%), and modified 5 FU-leucovorin-irinotecan (8.6%). Targeted therapy accompanying chemotherapy was administered in 27.6% of patients. About 42.1% of patients with potentially resectable disease and 11.1% with the unresectable disease at baseline underwent curative-intent resection of the primary and address of metastatic sites. With a median follow-up 18.2 months, median overall survival (OS) was 15.7 months (95% confidence interval: 10.42–20.99). Patients classified as potentially resectable had a median OS of 32.62 months while patients initially classified as unresectable had a median OS of 13.04 months (P = 0.016). The presence of signet ring morphology predicted for inferior mOS (P = 0.021). Conclusions: SCRT followed by systemic therapy in mRC is a feasible, efficacious paradigm for maximizing palliation, and achieving objective responses. The classification of patients based on resectability was predictive of actual resection rates as well as outcomes. Signet ring mRC show inferior outcomes in this cohort of patients.
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Affiliation(s)
- Vikas Ostwal
- Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Akhil Kapoor
- Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Reena Engineer
- Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Avanish Saklani
- Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Ashwin deSouza
- Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Prachi Patil
- Department of Medical Gastroenterology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Supreeta Arya
- Department of Radiology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | | | - Supriya Chopra
- Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Mangesh Patil
- Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Shanu Jain
- Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Anant Ramaswamy
- Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
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Self-expandable metal stent (SEMS) placement or emergency surgery as palliative treatment for obstructive colorectal cancer: A systematic review and meta-analysis. Crit Rev Oncol Hematol 2020; 155:103110. [DOI: 10.1016/j.critrevonc.2020.103110] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 09/09/2020] [Accepted: 09/09/2020] [Indexed: 12/11/2022] Open
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Gertsen EC, Brenkman HJF, Goense L, Mohammad NH, Weusten BLA, van Hillegersberg R, Ruurda JP. Non-curative gastrectomy for advanced gastric cancer does not result in additional risk of postoperative morbidity compared to curative gastrectomy. Surg Oncol 2020; 35:126-131. [PMID: 32871547 DOI: 10.1016/j.suronc.2020.08.018] [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: 04/03/2020] [Revised: 07/30/2020] [Accepted: 08/19/2020] [Indexed: 12/27/2022]
Abstract
BACKGROUND Non-curative gastrectomy (nCG) for gastric cancer can be considered in selected cases to relieve symptoms. The aim of this study was to evaluate postoperative morbidity and mortality in patients who underwent nCG and compare these results with an intended curative gastrectomy (CG). MATERIALS AND METHODS All patients who underwent both nCG and CG in the Netherlands were included from the Dutch Upper GI Cancer Audit (2011-2016). In this population-based cohort study postoperative morbidity, mortality, readmissions and short-term oncological outcomes were appraised. Propensity score matching (PSM) was applied to create comparable groups of patients who underwent nCG versus CG, using patient and tumor characteristics. RESULTS Of the 2202 eligible patients, 115 patients underwent nCG and 2087 underwent CG. After PSM, 115 nCG-patients were matched to 227 CG-patients. More conversions from laparoscopic to open surgery occurred during nCG (10·4 versus 2·6%, p = 0·007). Although postoperative mortality was higher after nCG in the original cohort (9·6 versus 4·8%, p = 0·026), after PSM there was no difference between groups (9·6 versus 7·0%, p = 0·415). Postoperative morbidity, re-interventions and readmission rates did not differ significantly between groups. Resection of additional organs (30·4 versus 11·5%, p < 0·001) and R+ resections (65·2 versus 12·3%, p < 0·001) occurred more frequently during nCG. CONCLUSIONS nCG does not lead to additional postoperative risks compared to CG in patients with similar characteristics, and may be considered in fit patients with advanced gastric cancer. However, randomized trials evaluating potential (survival) benefits of nCG should be awaited.
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Affiliation(s)
- Emma C Gertsen
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
| | - Hylke J F Brenkman
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
| | - Lucas Goense
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands; Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
| | - Nadia Haj Mohammad
- Department of Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
| | - Bas L A Weusten
- Department of Gastroenterology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
| | | | - Jelle P Ruurda
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
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Skelton WP, Franke AJ, Iqbal A, George TJ. Comprehensive literature review of randomized clinical trials examining novel treatment advances in patients with colon cancer. J Gastrointest Oncol 2020; 11:790-802. [PMID: 32953161 PMCID: PMC7475336 DOI: 10.21037/jgo-20-184] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Accepted: 07/20/2020] [Indexed: 12/18/2022] Open
Abstract
The treatment of colon cancer has had numerous recent advances, in terms of surgical approach, adjuvant therapies, and more. In this review, the authors examine randomized clinical trials comparing open surgery to laparoscopic surgery (including total mesocolic excision), and also examine the role of robotic surgery. Novel surgical techniques including the no-touch technique, side-to-side anastomosis, suture technique, complete mesocolic excision (CME) with central vascular ligation (CVL), and natural orifice transluminal endoscopic surgery (NOTES) are outlined. The role of placing endoscopic self-expandable metal stents (SEMS) for colonic obstruction is compared and contrasted with the surgical approach, and the effect that the anti-VEGF inhibitor bevacizumab may have on this side effect profile is further explored. The role of the resection of the primary tumor in the setting of metastatic disease is examined with respect to survival benefit. Pathways of perioperative care which can accelerate post-surgical recovery, including enhanced recovery after surgery (ERAS) are examined. The role of adjuvant chemotherapy in patients with high-risk stage II and patients with stage III disease is examined, along with the role on circulating tumor DNA (ctDNA) as well as with the biologic targeted agents cetuximab and bevacizumab. Lastly, the authors detail the postoperative surveillance schedules after surgical resection with respect to survival outcomes.
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Affiliation(s)
- William Paul Skelton
- Division of Medical Oncology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Florida, USA
| | - Aaron J. Franke
- Division of Medical Oncology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Florida, USA
| | - Atif Iqbal
- Section of Colorectal Surgery, Baylor College of Medicine, Houston, USA
| | - Thomas J. George
- Division of Hematology & Oncology, Department of Medicine, University of Florida College of Medicine, Florida, USA
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Chen X, Hu W, Huang C, Liang W, Zhang J, Wu D, Lv Z, Li Y, Luo Y, Liang Z, Wang M, Wang J, Yao X. Survival outcome of palliative primary tumor resection for colorectal cancer patients with synchronous liver and/or lung metastases: A retrospective cohort study in the SEER database by propensity score matching analysis. Int J Surg 2020; 80:135-152. [PMID: 32634480 DOI: 10.1016/j.ijsu.2020.06.024] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 06/09/2020] [Accepted: 06/13/2020] [Indexed: 01/05/2023]
Abstract
BACKGROUND There is a great matter of controversies whether some of these synchronous metastatic colorectal cancer patients can benefit from palliative primary tumor resection (pPTR) and there is still no reported randomized control trial to address this issue. METHODS Patients with microscopically proven metastatic colorectal cancer were identified within the SEER database (2010-2016). Patients were propensity matched 1:1 into pPTR and non-surgery groups and among the matched cohort, the univariable and multivariable Cox proportional hazards regression models were performed to identify predictors of survival. Median survival was calculated by using the Kaplan-Meier method. RESULTS Of 21,405 colorectal cancer patients diagnosed with synchronous liver and/or lung metastases, 7386 were identified in the matched cohort. The median overall survival was 12.0 months, 22.0 months in the non-surgery, surgery groups, respectively (p < 0.001) and the corresponding median cancer-specific survival was 13.0 months, 22.0 months, respectively (p < 0.001). Multivariable Cox regression analysis demonstrated that surgery was independently associated with improved overall survival (hazard ratio, 0.531) as well as cancer-specific survival (hazard ratio, 0.516). In stratified analyses by primary site and patterns of distant metastases, those patients with pPTR had better prognosis. In addition, stratified analysis revealed that trimodality therapy was linked with the greatest therapeutic effect followed by addition of chemotherapy to pPTR. CONCLUSIONS pPTR may offer some therapeutic benefits among carefully selected patients, and surgery-based multimodality therapy was associated with better survival.
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Affiliation(s)
- Xianzhe Chen
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China; Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China.
| | - Weixian Hu
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China; Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China.
| | - Chengzhi Huang
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China; School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510006, China.
| | - Weijun Liang
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China; Medical College of Shantou University, Shantou, Guangdong, 515000, China.
| | - Jie Zhang
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China; Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China.
| | - Deqing Wu
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China.
| | - Zejian Lv
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China.
| | - Yong Li
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China; Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China; Medical College of Shantou University, Shantou, Guangdong, 515000, China; School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510006, China.
| | - Yuwen Luo
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China; Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China.
| | - Zongyu Liang
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China; Medical College of Shantou University, Shantou, Guangdong, 515000, China.
| | - Minjia Wang
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China; School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510006, China.
| | - Junjiang Wang
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China; Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China.
| | - Xueqing Yao
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China; Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China; Medical College of Shantou University, Shantou, Guangdong, 515000, China; School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510006, China.
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Xu J, Ma T, Ye Y, Pan Z, Lu D, Pan F, Peng W, Sun G. Surgery on primary tumor shows survival benefit in selected stage IV colon cancer patients: A real-world study based on SEER database. J Cancer 2020; 11:3567-3579. [PMID: 32284753 PMCID: PMC7150453 DOI: 10.7150/jca.43518] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Accepted: 03/02/2020] [Indexed: 12/16/2022] Open
Abstract
Objectives: Most patients with stage IV colon cancer did not have the opportunity for curative surgery, only selected patients could benefit from surgery. This study aimed to determine whether surgery on the primary tumor (SPT) should be performed in patients with stage IV colon cancer and how to select patients for SPT. Methods: This study included 48,933 patients with stage IV colon cancer who were identified in the Surveillance, Epidemiology and End Results (SEER) database between 1998 and 2015. Propensity score matching (PSM) analysis was adopted to balance baseline differences between SPT and non-surgery groups. Kaplan-Meier (K-M) curves were utilized to compare the overall survival (OS). Prognostic nomograms were generated to predict survival based on pre- and post-operative risk factors. Patients were divided into low, middle, and high mortality risk subsets for OS by X-tile analyses based on scores derived from above nomograms. Results: Patients with SPT had a significantly longer OS than those without surgery, regardless of the metastatic sites and diagnostic years. Nomograms, according to the pre- and post-operative risk factors, showed moderate discrimination (all C-indexes above 0.7). Based on X-tile analyses, low mortality risk subset (post-operative score ≤ 22.3, preoperative score ≤ 9.7) recommended for SPT, and high mortality risk was not. Conclusions: SPT led to prolonged survival in stage IV colon cancer. Our nomograms would help to select suitable patients for SPT.
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Affiliation(s)
- Jing Xu
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230000, China
| | - Tai Ma
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230000, China
| | - Yuanzi Ye
- Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230000, China
| | - Zhipeng Pan
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230000, China
| | - Donghui Lu
- Department of Radiology, The 901st Hospital of the Joint Logistics Support Force of PLA, Hefei, Anhui Province 230031, China
| | - Faming Pan
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui Province 230000, China
| | - Wanren Peng
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230000, China
| | - Guoping Sun
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230000, China
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Wells SM, Boothe D, Ager BJ, Tao R, Gilcrease GW, Lloyd S. Analysis of Nonsurgical Treatment Options for Metastatic Rectal Cancer. Clin Colorectal Cancer 2020; 19:91-99.e1. [PMID: 32173281 DOI: 10.1016/j.clcc.2019.11.002] [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: 07/17/2019] [Accepted: 11/19/2019] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Using a large national registry, we investigated patterns of care and overall survival (OS) for metastatic rectal cancer patients treated with chemotherapy or radiotherapy (RT), or with a multimodal approach. PATIENTS AND METHODS Adult patients with metastatic rectal cancer who did not undergo resection diagnosed from 2004 to 2014 were included. Kaplan-Meier, log-rank, and Cox regression analyses were performed. RESULTS We identified 2385 patients. Of these, 1020 patients (43%) received chemotherapy alone, 228 (10%) received RT alone, 850 (36%) received chemotherapy and RT, and 287 (12%) received no treatment. Receipt of chemotherapy alone increased over the study period, and receipt of chemoradiotherapy decreased (P < .01). The only factor predictive of receiving any RT on multivariate analysis was clinical stage T3 disease. Factors predictive of OS on multivariate analysis included receipt of chemotherapy, Hispanic race, income greater than $46,000, and presence of lung metastasis. The OS for patients treated with chemotherapy and RT was not significantly different than chemotherapy alone. Five-year OS with chemotherapy alone, RT alone, chemoradiotherapy, and no treatment were, respectively, 84%, 56%, 79%, and 46%. CONCLUSION Metastatic rectal cancer patients with T3 tumors were more likely to receive RT. Local RT does not improve survival for patients with metastatic rectal cancer who do not also undergo surgery. The use of chemotherapy alone for metastatic rectal cancer is increasing, and chemotherapy is associated with higher OS compared to no treatment and RT alone. This remained true even in patients older than 80 years.
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Affiliation(s)
- Stacey M Wells
- Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah, Salt Lake City, UT
| | | | - Bryan J Ager
- Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah, Salt Lake City, UT
| | - Randa Tao
- Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah, Salt Lake City, UT
| | - Glynn Weldon Gilcrease
- Division of Oncology, Department of Internal Medicine, Huntsman Cancer Hospital, University of Utah, Salt Lake City, UT
| | - Shane Lloyd
- Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah, Salt Lake City, UT.
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Different variables predict the outcome of patients with synchronous versus metachronous metastases of colorectal cancer. Clin Transl Oncol 2020; 22:1399-1406. [PMID: 31916018 DOI: 10.1007/s12094-019-02277-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2019] [Accepted: 12/17/2019] [Indexed: 02/07/2023]
Abstract
PURPOSE Timing of metastasis is a controversial prognostic factor for patients with metastatic colorectal cancer (mCRC), as well as the performance of the common prognostic variables within patients with synchronous (SMs) or metachronous metastases (MMs). The aim of the current study is to evaluate outcome by the timing of metastases and to explore different tumor characteristics associated with SMs and MMs. METHODS Data were collected from the clinical records of patients with mCRC, which were referred to the Department of Oncology of the Ospedale Civile di Sanremo from 2006 to 2011. A comparison of the characteristics of tumors of patients, overall and by the timing of metastases, and a Cox regression analysis have been performed to select the most relevant prognostic factors. Finally, the characteristics of the variables associated with the outcome were analyzed through a logistic regression. RESULTS Two hundreds fifteen patients with SMs and two hundreds ten with MMs were included. Patients with SMs reported a poor prognosis (18.5 versus 62.8 months; p value < 0.001). Among patients with SMs there was a significant difference in overall survival between patients with a CEA-positive or negative disease, while no difference was present among patients with MMs. After multivariate analysis, only within the SMs group the occurrence of liver metastases was related to a CEA-positive disease. CONCLUSIONS Within the cohort of SMs high CEA levels, occurrence of liver metastases and right-sided colon tumors were associated with a very poor prognosis, whereas no relationship was detectable in the group of patients with MMs.
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Cao D, Zheng Y, Xu H, Ge W, Xu X. Bevacizumab improves survival in metastatic colorectal cancer patients with primary tumor resection: A meta-analysis. Sci Rep 2019; 9:20326. [PMID: 31889159 PMCID: PMC6937309 DOI: 10.1038/s41598-019-56528-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Accepted: 12/08/2019] [Indexed: 02/06/2023] Open
Abstract
It is not well determined whether primary tumor resection is associated with better outcomes in metastatic colorectal cancer (mCRC) patients treated with bevacizumab. In this meta-analysis, we aimed to assess the prognostic role of primary tumor resection in mCRC treated with bevacizumab. Electronic databases including the Cochrane library, Embase, and Pubmed were searched until April 2018. Clinical studies assessing the influence of primary tumor resection on the efficacy of bevacizumab in patients with mCRC were identified. The primary endpoint was overall survival (OS), and the secondary endpoint was progression-free survival (PFS). Seven studies including 2760 mCRC patients were finally included. The results of the meta-analysis were in favor of bevacizumab to patients with resected primary tumor in terms of OS (HR = 0.50, 95%CI: 0.39–0.64; p < 0.01), and PFS (HR = 0.65, 95%CI: 0.51–0.81; p < 0.01). Administration of bevacizumab in mCRC patients with resected primary tumor had a better OS (HR = 0.65, 95%CI: 0.56–0.74; p < 0.01), when compared to chemotherapy(CT). Adding bevacizumab to mCRC patients without resection of primary tumor also had a better OS (HR = 0.78, 95%CI: 0.65–0.94; p < 0.01) and PFS (HR = 0.71, 95%CI: 0.57–0.88; p < 0.01) compared to chemotherapy alone. In conclusion, mCRC patients with resected primary tumor have better survival than those without surgery of primary tumor when treated with bevacizumab. Primary tumor resection status should be taken into consideration when using bevacizumab in mCRC.
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Affiliation(s)
- Dedong Cao
- Department of Oncology, RenMin Hospital of Wuhan University, Jiefang Road #238 Wuchang District, Wuhan, 430000, China.
| | - Yongfa Zheng
- Department of Oncology, RenMin Hospital of Wuhan University, Jiefang Road #238 Wuchang District, Wuhan, 430000, China
| | - Huilin Xu
- Department of Oncology, The Fifth hospital of Wuhan, Xianzheng Street #122 Hanyang District, Wuhan, 430000, China
| | - Wei Ge
- Department of Oncology, RenMin Hospital of Wuhan University, Jiefang Road #238 Wuchang District, Wuhan, 430000, China
| | - Ximing Xu
- Department of Oncology, RenMin Hospital of Wuhan University, Jiefang Road #238 Wuchang District, Wuhan, 430000, China.
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Colloca GA, Venturino A, Guarneri D. Neutrophil-related Variables Have Different Prognostic Effect Based on Primary Tumor Location in Patients With Metastatic Colorectal Cancer Receiving Chemotherapy. Clin Colorectal Cancer 2019; 18:e343-e348. [DOI: 10.1016/j.clcc.2019.06.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Revised: 06/02/2019] [Accepted: 06/25/2019] [Indexed: 12/15/2022]
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Zhou B, Zong S, Zhong W, Tian Y, Wang L, Zhang Q, Zhang R, Li L, Wang W, Zhao J, Chen X, Feng Y, Zhai B, Sun T, Liu Y. Interaction between laminin-5γ2 and integrin β1 promotes the tumor budding of colorectal cancer via the activation of Yes-associated proteins. Oncogene 2019; 39:1527-1542. [PMID: 31676872 DOI: 10.1038/s41388-019-1082-1] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 10/16/2019] [Accepted: 10/17/2019] [Indexed: 02/07/2023]
Abstract
Colorectal cancer (CRC) is a common cancer type and a threat to human health. Tumor budding (TB) is the presence of a single cancer cell or clusters of up to five cancer cells prior to the invasive front of an aggressive carcinoma and is an independent prognosis factor for CRC. The molecular mechanism of TB is still unclear, and drugs that inhibit this process are still in the blank stage. This study found that TBs exhibit characteristics of partial EMT with a decreased expression of E-cadherin and no substantial differences in the expression of N-cadherin and vimentin. We also observed the interaction of integrin with extracellular matrix components, laminin-5γ2 (LN-5γ2), play essential roles in the TB of CRC. We then verified that the interaction between LN-5γ2 and integrin β1 promotes the TB of CRC via the activation of FAK and Yes-associated proteins (YAP). A natural drug monomer, cucurbitacin B, was screened using virtual screening methods for the interaction interface of proteins. We found that this monomer could block the interaction interface between LN-5γ2 and integrin β1 and substantially inhibit the TB of CRC cells via inactivation of YAP. This study provides new insights into the mechanism of TB mechanism and the development of drugs targeting the TB of CRC.
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Affiliation(s)
- Bijiao Zhou
- Molecular Pathology Institute of Gastrointestinal Tumors, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, 272029, Shandong, China.,State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300350, China.,Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs and Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, 300457, China
| | - Shumin Zong
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300350, China.,Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs and Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, 300457, China
| | - Weilong Zhong
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, 300052, China
| | - Yixuan Tian
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300350, China.,Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs and Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, 300457, China
| | - Lumeng Wang
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300350, China.,Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs and Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, 300457, China
| | - Qian Zhang
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300350, China.,Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs and Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, 300457, China
| | - Renya Zhang
- Molecular Pathology Institute of Gastrointestinal Tumors, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, 272029, Shandong, China
| | - Lei Li
- Molecular Pathology Institute of Gastrointestinal Tumors, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, 272029, Shandong, China
| | - Wei Wang
- Molecular Pathology Institute of Gastrointestinal Tumors, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, 272029, Shandong, China
| | - Jianmin Zhao
- Department of Pathology, Hospital of Shun Yi District, Beijing, China
| | - Xin Chen
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300350, China.,Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs and Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, 300457, China
| | - Yaju Feng
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300350, China.,Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs and Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, 300457, China
| | - Binghui Zhai
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300350, China.,Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs and Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, 300457, China
| | - Tao Sun
- State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300350, China. .,Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs and Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, 300457, China.
| | - Yanrong Liu
- Molecular Pathology Institute of Gastrointestinal Tumors, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, 272029, Shandong, China. .,State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300350, China. .,Tianjin Key Laboratory of Early Druggability Evaluation of Innovative Drugs and Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, 300457, China.
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Leijssen LGJ, Dinaux AM, Kunitake H, Bordeianou LG, Berger DL. The impact of postoperative morbidity on survival in patients with metastatic colon and rectal cancer. J Surg Oncol 2019; 120:460-472. [PMID: 31276213 DOI: 10.1002/jso.25610] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2019] [Accepted: 06/13/2019] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Avoiding postoperative morbidity is essential in patients with advanced cancer. To further improve treatment in stage IV colorectal cancer, knowledge about risk factors which effect short- and long-term outcomes is important. METHODS All stage IV colon and rectal cancer who underwent elective surgery between 2004 and 2015 were included (n = 345). We compared resectable colon and rectal patients, and unresectable colon and rectal cancer patients. RESULTS Median follow-up duration was 22.2 (unresectable) and 56.7 months (resectable) with no difference in tumor location. Colon cancer patients were more often considered unresectable (P < .001). Rectal procedures were correlated with a higher morbidity rate and a longer surgical duration (P < .001). In the resectable cohort, obese patients, open procedures and prolonged surgery were independently associated with postoperative complications. Considering the palliative group, neoadjuvant treatment and age were correlated with worse outcomes. Morbidity was not associated with long-term outcomes in the resectable cohort. However, unresectable patients who developed respiratory (hazard ratio [HR]: 7.53) or cardiac (HR: 3.75) complications and patients with an American Society of Anesthesiologists-score III to IV (HR: 1.51) had an impaired survival. CONCLUSION Our results emphasize the need for an adequate preoperative assessment to identify patients at risk for postoperative complications and impaired survival.
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Affiliation(s)
- Lieve G J Leijssen
- Department of General and Gastrointestinal Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Anne M Dinaux
- Department of General and Gastrointestinal Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Hiroko Kunitake
- Department of General and Gastrointestinal Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Liliane G Bordeianou
- Department of General and Gastrointestinal Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - David L Berger
- Department of General and Gastrointestinal Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
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Jiang C, Wang F, Guo G, Dong J, Liu S, He W, Zhang B, Xia L. Metastatic lymph node ratio as a prognostic indicator in patients with stage IV colon cancer undergoing resection. J Cancer 2019; 10:2534-2540. [PMID: 31258759 PMCID: PMC6584347 DOI: 10.7150/jca.29216] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 05/05/2019] [Indexed: 01/01/2023] Open
Abstract
Background: It has been shown that the metastatic lymph node ratio (LNR, metastatic LNs divided by the total number of retrieved LNs) significantly affects the prognosis of patients with non-stage IV and some curative stage IV colon cancer undergoing curative resection. In this study, we aimed to evaluate the role of the LNR as a predictor of prognosis in patients with stage IV colon cancer undergoing curative or palliative resection. Patients and Methods: We conducted a retrospective study of 424 patients who were initially diagnosed with stage IV colon cancer at the Sun Yat-Sen University Cancer Center from 2003 to 2014. The patients were divided into the curative and palliative primary tumor resection groups with regional lymph nodes harvest. The median value was used as the cutoff for the LNR. Overall survival (OS) was assessed with the Kaplan-Meier method and log-rank test. Multivariate analysis was performed to identify the prognostic factors for OS. Results: The cutoff value for the LNR was 0.2. A total of 71 and 353 patients were classified as being in the curative and palliative resection groups, respectively. Patients in the palliative resection group showed higher pretreatment levels of carbohydrate antigen 19-9 (CA199; P = 0.014), a deeper infiltration of the primary tumor (P = 0.049), a lower regional lymph node harvest (i.e., total lymph node yield [TLN] ≤ 11; P = 0.001), and more extensive metastasis (P = 0.006). Among all patients, initial elevated CA199 levels, a TLN≤11, a negative lymph nodes (NLN) ≤7, and a LNR ≤0.2 were significantly associated with an unfavorable prognosis. OS was significantly longer in patients with a low LNR in both groups (P = 0.008 and P = 0.001, respectively). The LNR was an independent prognostic indicator in patients with stage IV colon cancer, with a hazard ratio (HR) of 1.47 (95% confidence interval [CI] 1.14-1.91; P = 0.003) in total population, and an HR of 1.43 (95% CI 1.09-1.86; P = 0.009) in patients with palliative resection. Conclusion: The LNR can be used as an independent prognostic factor in patients with stage IV colon cancer patients undergoing resection.
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Affiliation(s)
- Chang Jiang
- VIP Region, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, R.P. China
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, R.P. China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, R.P. China
| | - Fang Wang
- Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, R.P. China
| | - Guifang Guo
- VIP Region, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, R.P. China
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, R.P. China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, R.P. China
| | - Jun Dong
- VIP Region, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, R.P. China
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, R.P. China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, R.P. China
| | - Shousheng Liu
- VIP Region, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, R.P. China
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, R.P. China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, R.P. China
| | - Wenzhuo He
- VIP Region, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, R.P. China
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, R.P. China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, R.P. China
| | - Bei Zhang
- VIP Region, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, R.P. China
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, R.P. China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, R.P. China
| | - Liangping Xia
- VIP Region, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, R.P. China
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, R.P. China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, R.P. China
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Lorimer PD, Motz BM, Kirks RC, Han Y, Symanowski JT, Hwang JJ, Salo JC, Hill JS. Frequency of unplanned surgery in patients with stage IV colorectal cancer receiving palliative chemotherapy with an intact primary: An analysis of SEER‐Medicare. J Surg Oncol 2019; 120:407-414. [DOI: 10.1002/jso.25508] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Accepted: 05/05/2019] [Indexed: 12/19/2022]
Affiliation(s)
- Patrick D. Lorimer
- Department of Surgery, Carolinas Medical CenterLevine Cancer Institute Charlotte North Carolina
| | - Benjamin M. Motz
- Department of Surgery, Carolinas Medical CenterLevine Cancer Institute Charlotte North Carolina
| | - Russell C. Kirks
- Department of Surgery, Carolinas Medical CenterLevine Cancer Institute Charlotte North Carolina
| | - Yimei Han
- Department of Biostatistics, Carolinas Medical CenterLevine Cancer Institute Charlotte North Carolina
| | - James T. Symanowski
- Department of Biostatistics, Carolinas Medical CenterLevine Cancer Institute Charlotte North Carolina
| | - Jimmy J. Hwang
- Department of Surgery, Carolinas Medical CenterLevine Cancer Institute Charlotte North Carolina
| | - Jonathan C. Salo
- Department of Surgery, Carolinas Medical CenterLevine Cancer Institute Charlotte North Carolina
| | - Joshua S. Hill
- Department of Surgery, Carolinas Medical CenterLevine Cancer Institute Charlotte North Carolina
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Xu Z, Becerra AZ, Fleming FJ, Aquina CT, Dolan JG, Monson JR, Temple LK, Jusko TA. Treatments for Stage IV Colon Cancer and Overall Survival. J Surg Res 2019; 242:47-54. [PMID: 31071604 DOI: 10.1016/j.jss.2019.04.034] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Revised: 03/21/2019] [Accepted: 04/09/2019] [Indexed: 01/05/2023]
Abstract
BACKGROUND The role of primary tumor resection (PTR) for asymptomatic stage IV colon cancer with unresectable metastases remains unclear. Increasingly there has been a trend away from resection. The aim of this study was to examine trends in the treatment of stage IV colon cancers, impact of different treatments on long-term mortality, and factors associated with receipt of postoperative chemotherapy. METHODS The 2006-2012 National Cancer Data Base was queried for stage IV colon cancer patients. Treatments were grouped into PTR and chemotherapy, PTR only, chemotherapy only, and no treatment. A descriptive analysis was performed examining patient and hospital characteristics associated with different treatments. A Cox regression analysis was used to assess the adjusted effect of different treatments on long-term survival. A multivariable logistic regression was used to examine factors associated with postoperative chemotherapy. RESULTS Of 31,310 patients, who met inclusion criteria, 22% of the patients underwent PTR and chemotherapy, 37.5% received chemotherapy only, 11.9% underwent PTR, and 28.6% received no treatment. Patients who received no treatment had the highest hazard of death at 1, 3, and 5 y, followed by PTR only, and chemotherapy only compared with PTR combined with chemotherapy. Patients who were older and had more comorbidities were less likely to receive postoperative chemotherapy. CONCLUSIONS Primary tumor resection in conjunction with postoperative chemotherapy among stage IV colon cancer patients with unresectable metastases was associated with a long-term survival benefit compared with other treatment options. Efforts should be made to increase the use of postoperative chemotherapy where feasible.
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Affiliation(s)
- Zhaomin Xu
- Department of Surgery, University of Rochester Medical Center, Rochester, New York
| | - Adan Z Becerra
- Department of Surgery, University of Rochester Medical Center, Rochester, New York; Department of Public Health Sciences, Social and Scientific Systems, Silver Spring, Maryland; Department of Public Health Sciences, University of Rochester Medical Center, Rochester, New York.
| | - Fergal J Fleming
- Department of Surgery, University of Rochester Medical Center, Rochester, New York
| | - Christopher T Aquina
- Department of Surgery, University of Rochester Medical Center, Rochester, New York
| | - James G Dolan
- Department of Public Health Sciences, University of Rochester Medical Center, Rochester, New York
| | - John R Monson
- Department of Surgery, Center for Colon and Rectal Surgery, Florida Hospital Medical Group, Orlando, Florida
| | - Larissa K Temple
- Department of Surgery, University of Rochester Medical Center, Rochester, New York
| | - Todd A Jusko
- Department of Public Health Sciences, University of Rochester Medical Center, Rochester, New York
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Simillis C, Kalakouti E, Afxentiou T, Kontovounisios C, Smith JJ, Cunningham D, Adamina M, Tekkis PP. Primary Tumor Resection in Patients with Incurable Localized or Metastatic Colorectal Cancer: A Systematic Review and Meta-analysis. World J Surg 2019; 43:1829-1840. [DOI: 10.1007/s00268-019-04984-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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43
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Kwakman JJM, van Kruijsdijk RCM, Elias SG, Seymour MT, Meade AM, Visseren FLJ, Punt CJA, Koopman M. Choosing the right strategy based on individualized treatment effect predictions: combination versus sequential chemotherapy in patients with metastatic colorectal cancer. Acta Oncol 2019; 58:326-333. [PMID: 30657353 DOI: 10.1080/0284186x.2018.1564840] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Translating results from randomized trials to individual patients is challenging, since treatment effects may vary due to heterogeneous prognostic characteristics. We aimed to demonstrate model development for individualized treatment effect predictions in cancer patients. We used data from two randomized trials that investigated sequential versus combination chemotherapy in unresectable metastatic colorectal cancer (mCRC) patients. MATERIAL AND METHODS We used data from 803 patients included in CAIRO for prediction model development and internal validation, and data from 1423 patients included in FOCUS for external validation. A Weibull model with pre-specified patient and tumour characteristics was developed for a prediction of gain in median overall survival (OS) by upfront combination versus sequential chemotherapy. Decision curve analysis with net benefit was used. A nomogram was built using logistic regression for estimating the probability of receiving second-line treatment after the first-line monochemotherapy. RESULTS Median-predicted gain in OS for the combination versus sequential chemotherapy was 2.3 months (IQR: -1.1 to 3.7 months). A predicted gain in favour of sequential chemotherapy was found in 231 patients (29%) and a predicted gain of >3 months for combination chemotherapy in 294 patients (37%). Patients with benefit from sequential chemotherapy had metachronous metastatic disease and a left-sided primary tumour. Decision curve analyses showed improvement in a net benefit for treating all patients according to prediction-based treatment compared to treating all patients with combination chemotherapy. Multiple characteristics were identified as prognostic variables which identify patients at risk of never receiving second-line treatment if treated with initial monochemotherapy. External validation showed good calibration with moderate discrimination in both models (C-index 0.66 and 0.65, respectively). CONCLUSIONS We successfully developed individualized prediction models including prognostic characteristics derived from randomized trials to estimate treatment effects in mCRC patients. In times where the heterogeneity of CRC becomes increasingly evident, such tools are an important step towards personalized treatment.
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Affiliation(s)
- Johannes J. M. Kwakman
- Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Rob C. M. van Kruijsdijk
- Department of Internal Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Sjoerd G. Elias
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Matthew T. Seymour
- Department of Medical Oncology, The Leeds Teaching Hospitals, University of Leeds, Leeds, UK
| | - Angela M. Meade
- Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UK
| | - Frank L. J. Visseren
- Department of Vascular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Cornelis J. A. Punt
- Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Miriam Koopman
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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Hidaka E, Maeda C, Nakahara K, Wakamura K, Ishiyama Y, Shimada S, Seki J, Takano Y, Oae S, Enami Y, Sawada N, Ishida F, Kudo SE. High Serum CA19-9 Concentration Predicts Poor Prognosis in Elderly Patients with Stage IV Colorectal Cancer. Gastrointest Tumors 2019; 5:117-124. [PMID: 30976583 PMCID: PMC6422141 DOI: 10.1159/000493793] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 09/17/2018] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND/AIM The optimal treatment strategy for elderly patients with stage IV colorectal cancer (CRC) remains controversial due to limited research data. The purpose of this study was to evaluate treatment results and to clarify the prognostic factors, especially poor prognosis factors, in elderly patients with stage IV CRC. METHODS We retrospectively reviewed the data of 82 elderly patients (aged ≥75 years) with stage IV CRC who underwent surgical treatment at our hospital between April 2001 and March 2017. Factors that affected prognosis and the ability to undergo treatment were analyzed via multivariate analysis. RESULTS The median overall survival (OS) in the patients with high pretreatment serum carbohydrate antigen 19-9 (CA19-9) concentration (> 370 U/mL) was significantly worse than in those with lower serum CA19-9 concentration (0-370 U/mL) (8.5 vs. 19.2 months, p = 0.0059). In univariate analysis, age (≥80 years) (p = 0.014), performance status of 1-3 (p = 0.028), and high pretreatment serum CA19-9 concentration (p = 0.014) were significant prognostic factors for poor OS. By contrast, resection of the primary tumor (p = 0.024), chemotherapy (p < 0.0001), and resection of distant metastasis (p = 0.0005) were significant prognostic factors for favorable OS. Multivariate analysis showed that a high pretreatment serum CA19-9 concentration was an independent prognostic factor for poor OS (p = 0.01). Meanwhile, resection of the primary tumor (p = 0.033), chemotherapy (p < 0.0001), and resection of distant metastasis (p = 0.0008) were prognostic factors for favorable OS. CONCLUSIONS A high pretreatment serum CA19-9 concentration (> 370 U/mL) was a reliable predictive factor for poor prognosis, and aggressive treatments should be performed carefully in these patients. Moreover, various treatments, including surgery and chemotherapy, might improve OS in elderly patients with stage IV CRC.
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Affiliation(s)
- Eiji Hidaka
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
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Lau JW, Chang HS, Lee KY, Gwee YX, Lee WQ, Chong CS. Survival outcomes following primary tumor resection for patients with incurable metastatic colorectal carcinoma: Experience from a single institution. J Dig Dis 2018; 19:550-560. [PMID: 30117288 DOI: 10.1111/1751-2980.12657] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2018] [Revised: 07/13/2018] [Accepted: 08/13/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Palliative primary tumor resection (PTR) has been used for preventing and treating tumor-related complications. We aimed to determine whether PTR can increase overall survival (OS) in patients with unresectable metastatic colorectal cancer (CRC). METHODS A retrospective review of a prospectively collected database in a single center was performed. Patients diagnosed with metastatic CRC from January 2004 to December 2014 were included. Patients who had attained curative resection or had disease recurrence were excluded. All patients were discussed at a multidisciplinary tumor board where subsequent treatment decisions were made. RESULTS Altogether 408 patients were analyzed. Of these 145 received PTR with palliative chemotherapy (PC; group A), 110 received PC only (group B), 52 received PTR only (group C), while 101 received neither PTR nor PC (group D). Undergoing PTR led to statistically significant improvement in OS (22.7 months vs 12.1 months vs 6.9 months vs 2.7 months, P < 0.001). We performed subgroup analyses to control for potential confounders and found that the influence of PTR on OS persisted. With multivariate analysis, the predictors of poor OS were no PTR (hazards ratio [HR] 2.32, 95% confidence interval [CI] 1.82-2.96, P < 0.001), no PC (HR 4.25, 95% CI 3.27-5.33, P < 0.001) and the presence of peritoneal metastases (HR 1.37, 95% CI 1.06-1.78, P = 0.018). Diversion surgery did not lead to a statistical difference in OS. CONCLUSIONS The absences of PTR and PC, and peritoneal metastases are independently associated with decreased OS in patients with unresectable metastatic CRC. Randomized controlled trials are needed to verify this observation.
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Affiliation(s)
- Joel Wl Lau
- Department of Surgery, University Surgical Cluster, National University Hospital, Singapore
| | - Heidi Sy Chang
- Department of Surgery, University Surgical Cluster, National University Hospital, Singapore
| | - Kai Y Lee
- Department of Surgery, University Surgical Cluster, National University Hospital, Singapore
| | - Yong X Gwee
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Wen Q Lee
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Choon S Chong
- Department of Surgery, University Surgical Cluster, National University Hospital, Singapore
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Korkmaz L, Coşkun HŞ, Dane F, Karabulut B, Karaağaç M, Çabuk D, Karabulut S, Aykan NF, Doruk H, Avcı N, Turhal NS, Artaç M. Kras-mutation influences outcomes for palliative primary tumor resection in advanced colorectal cancer-a Turkish Oncology Group study. Surg Oncol 2018; 27:485-489. [PMID: 30217306 DOI: 10.1016/j.suronc.2018.05.032] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Revised: 05/28/2018] [Accepted: 05/29/2018] [Indexed: 02/05/2023]
Abstract
PURPOSE We aimed to investigate the prognostic effect of primary tumor resection (PTR) prior to bevacizumab-based treatments in unresectable metastatic colorectal cancer (mCRC). METHODS We retrospectively collected 341 mCRC cases with unresectable metastases at diagnosis. PTR was performed in 210 cases (the surgery group) and the other patients (n = 131) were followed without PTR (the no-surgery group). All the patients were treated with bevacizumab combined chemotherapy regimens. RESULTS The median progression free survival (PFS) of the surgery group was 10.4 months (95% CI: 8.9-11.9), which was significantly better than that of the no-surgery group (7.6 months, 95% CI: 6.4-8.8, P=0.000). The median overall survival (OS) of the surgery group was longer than that of the no-surgery group (27.4 months vs. 18.3 months, respectively, P=0.000). The median PFS and OS of the surgery group were 10.4 months and 28.2 months, which were significantly longer than that of the no-surgery group in Kras-mutant patients (7.8 months and 18.3 months; P=0.004, P=0.028, respectively). There was no difference in terms of PFS and OS between the surgery and the no-surgery groups in Kras-wild type patients. CONCLUSION Palliative PTR may improve the survival outcomes for unresectable mCRC patients. PTR may be preferred, particularly in Kras-mutant patients.
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Affiliation(s)
- Levent Korkmaz
- Department of Medical Oncology, NecmettinErbakan University, Meram Faculty of Medicine, Konya, Turkey
| | - Hasan Şenol Coşkun
- Department of Medical Oncology, Akdeniz University Faculty of Medicine, Antalya, Turkey
| | - Faysal Dane
- Department of Medical Oncology, Marmara University Faculty of Medicine, Istanbul, Turkey
| | - Bülent Karabulut
- Department of Medical Oncology, Ege University Faculty of Medicine, Izmir, Turkey
| | - Mustafa Karaağaç
- Department of Medical Oncology, NecmettinErbakan University, Meram Faculty of Medicine, Konya, Turkey
| | - Devrim Çabuk
- Department of Medical Oncology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey
| | - Senem Karabulut
- Department of Medical Oncology, Istanbul University, Istanbul Medical Faculty, Istanbul, Turkey
| | - Nuri Faruk Aykan
- Department of Medical Oncology, Istanbul University, Istanbul Medical Faculty, Istanbul, Turkey
| | - Hatice Doruk
- Department of Medical Oncology, Acıbadem Bursa Hospital, Bursa, Turkey
| | - Nilüfer Avcı
- Department of Medical Oncology, Ali Osman Sönmez Oncology Hospital, Bursa, Turkey
| | | | - Mehmet Artaç
- Department of Medical Oncology, NecmettinErbakan University, Meram Faculty of Medicine, Konya, Turkey.
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47
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Tai YH, Chang WK, Wu HL, Chan MY, Chen HH, Chang KY. The effect of epidural analgesia on cancer progression in patients with stage IV colorectal cancer after primary tumor resection: A retrospective cohort study. PLoS One 2018; 13:e0200893. [PMID: 30028851 PMCID: PMC6054421 DOI: 10.1371/journal.pone.0200893] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Accepted: 07/05/2018] [Indexed: 01/17/2023] Open
Abstract
Retrospective clinical studies showed perioperative epidural analgesia (EA) was associated with better postoperative oncologic outcomes in patients with specific types of non-metastatic cancers. This study aimed to investigate the effects of EA on cancer prognosis after surgical intervention for stage IV colorectal cancer. In this retrospective study, patients with stage IV colorectal cancer undergoing primary tumor resection and metastasectomy between January 2005 and December 2014 were classified into two groups based on their use of perioperative EA or not and evaluated through August 2016. Primary and secondary endpoints were postoperative progression-free survival (PFS) and overall survival (OS), respectively. A total of 999 patients were included and 165 (16.5%) of them received EA. The median follow-up interval was 17.5 months and no significant difference in PFS or OS was noted between the EA and non-EA groups in the univariate analysis. Multivariable Cox proportional hazards model identified four independent risk factors both for disease progression and mortality, including American Society of Anesthesiologists (ASA) physical status ≥ 3, higher pretreatment carcinoembryonic antigen (CEA), multiple distant metastases, and pathologic lymphovascular invasion. After adjustment for the selected risk factors, the effects of EA on PFS and OS remained non-significant (hazard ratio: 1.06, 95% CI: 0.87 to 1.29, for PFS and 0.90, 95% CI: 0.68 to 1.20 for OS). Similar findings were demonstrated by propensity score analysis. Our results did not support the association between perioperative epidural analgesia and better progression-free or overall survival in patients following stage IV colorectal cancer surgery.
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Affiliation(s)
- Ying-Hsuan Tai
- Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Anesthesiology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
- Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Wen-Kuei Chang
- Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Hsiang-Ling Wu
- Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
- Department of Surgery, Taipei Veterans General Hospital, Yuli Branch, Hualien, Taiwan
| | - Min-Ya Chan
- Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Technology Application and Human Resource Development, National Taiwan Normal University, Taipei, Taiwan
| | - Hsiu-Hsi Chen
- Division of Biostatistics, Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Kuang-Yi Chang
- Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
- * E-mail:
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48
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Lau JWL, Chang HSY, Lee KY, Gwee YX, Lee WQ, Chong CS. Modern-day palliative chemotherapy for metastatic colorectal cancer: does colonic resection affect survival? ANZ J Surg 2018; 88:E772-E777. [PMID: 29938886 DOI: 10.1111/ans.14726] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Revised: 05/02/2018] [Accepted: 05/04/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Patients with metastatic colorectal cancer (mCRC) with surgically incurable metastases would be recommended for palliative chemotherapy (PC). The role of surgical intervention is debatable with no conclusive evidence for routine primary tumour resection (PTR) or stoma creation. We aimed to study if surgical intervention conferred a survival benefit in patients with mCRC who received upfront systemic therapy. METHODS A retrospective review of a prospectively collected database in a single centre was performed. Patients diagnosed with mCRC from January 2004 to December 2014 were included. We excluded patients who had an upfront surgical intervention, had no treatment with systemic therapy or had attained curative resection. The decision for surgery was based on the outcome of a multidisciplinary tumour board. Demographic, clinicopathological, treatment and follow-up data were collected. Univariate and multivariate analyses were performed. RESULTS Out of 408 patients with mCRC with incurable metastases, we analysed 124 patients who had upfront PC. Twenty-nine had PC + PTR (group A), 10 had PC + stoma (group B) and 85 had PC only (group C). Undergoing PTR led to significant improvement in overall survival (OS; 30.8 versus 13.4 versus 11.0 months, P < 0.001). With multivariate analysis, undergoing PTR and receiving biologics were independent good prognostic variables. Surgical resection was safe with minimal complications. CONCLUSIONS PTR was found to increase OS while stoma creation had no impact on OS. The benefits and safety of undergoing PTR may be a result of selection bias. Further prospective studies are required to confirm the observations of this study.
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Affiliation(s)
- Joel Wen Liang Lau
- Department of General Surgery, University Surgical Cluster, National University Hospital, Singapore
| | - Heidi Sian Ying Chang
- Department of General Surgery, University Surgical Cluster, National University Hospital, Singapore
| | - Kai Yin Lee
- Department of General Surgery, University Surgical Cluster, National University Hospital, Singapore
| | - Yong Xiang Gwee
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Wen Qiang Lee
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Choon Seng Chong
- Department of General Surgery, University Surgical Cluster, National University Hospital, Singapore
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49
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van Rooijen KL, Shi Q, Goey KKH, Meyers J, Heinemann V, Diaz-Rubio E, Aranda E, Falcone A, Green E, de Gramont A, Sargent DJ, Punt CJA, Koopman M. Prognostic value of primary tumour resection in synchronous metastatic colorectal cancer: Individual patient data analysis of first-line randomised trials from the ARCAD database. Eur J Cancer 2018; 91:99-106. [PMID: 29353165 DOI: 10.1016/j.ejca.2017.12.014] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2017] [Accepted: 12/07/2017] [Indexed: 12/11/2022]
Abstract
Indication for primary tumour resection (PTR) in asymptomatic metastatic colorectal cancer (mCRC) patients is unclear. Previous retrospective analyses suggest a survival benefit for patients who underwent PTR. The aim was to evaluate the prognostic value of PTR in patients with synchronous mCRC by analysis of recent large RCTs including systemic therapy with modern targeted agents. Individual patient data (IPD) of 3423 patients enrolled into 8 randomised controlled trials (RCTs) with first-line systemic therapy in the ARCAD (Aide et Recherche en Cancérologie Digestive) database were analysed. The number of patients with unresected synchronous mCRC, resected synchronous mCRC and metachronous mCRC was 710 (21%), 1705 (50%) and 1008 (29%), respectively. Adjusting for age, gender, performance status (PS) and prior chemotherapy, the unresected group had a significantly worse median overall survival (16.4 m) compared with the synchronous resected (22.2 m; hazard ratio [HR] 1.60, 95% CI 1.43-1.78) and metachronous (22.4 m; HR 1.81, 95% CI 1.58-2.07) groups. Similarly, median progression-free survival was significantly worse for the unresected group compared with the synchronous resected (HR 1.31, 95% CI 1.19-1.44) and metachronous (HR 1.47, 95% CI 1.30-1.66) groups. In a multivariate analysis, the observed associations remained significant. This largest IPD analysis of mCRC trials to date demonstrates an improved survival in synchronous mCRC patients after PTR. These results may be subject to bias since reasons for (non)resection were not available. Until results of ongoing RCTs are available, both upfront PTR followed by systemic treatment and upfront systemic treatment are considered appropriate treatment strategies.
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Affiliation(s)
- K L van Rooijen
- Department of Medical Oncology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands
| | - Q Shi
- Department of Health Science Research, Mayo Clinic, Rochester, USA
| | - K K H Goey
- Department of Medical Oncology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands
| | - J Meyers
- Department of Health Science Research, Mayo Clinic, Rochester, USA
| | - V Heinemann
- Department of Medical Oncology and Comprehensive Cancer Center, Munich, Germany
| | - E Diaz-Rubio
- Cancer Translational Unit, Hospital Clinico San Carlos, Universidad Complutense, Madrid, Spain
| | - E Aranda
- Department of Medical Oncology, UCO, Maimonides Institute of Biomedical Research (IMIBIC), CIBERONC, Instituto de Salud Carlos III, Córdoba, Spain
| | - A Falcone
- Department of Medical Oncology, University of Pisa, Pisa, Italy
| | - E Green
- Department of Health Science Research, Mayo Clinic, Rochester, USA
| | - A de Gramont
- Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France
| | - D J Sargent
- Department of Health Science Research, Mayo Clinic, Rochester, USA
| | - C J A Punt
- Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - M Koopman
- Department of Medical Oncology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands.
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50
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Morikawa T, Inada R, Nagasaka T, Mori Y, Kishimoto H, Kawai T, Umeda Y, Mishima H, Goel A, Fujiwara T. BRAF V600E mutation is a predictive indicator of upfront chemotherapy for stage IV colorectal cancer. Oncol Lett 2017; 15:2195-2201. [PMID: 29434925 PMCID: PMC5776948 DOI: 10.3892/ol.2017.7553] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Accepted: 02/07/2017] [Indexed: 12/16/2022] Open
Abstract
In stage IV colorectal cancer (CRC), initial resection of the primary tumor is considered to be an important strategy for improving disease outcome. However, there is no consensus on the timing as to when the surgical intervention of the primary tumor should occur. The present study hypothesizes that genetic profiles in CRC may indicate the appropriate treatment strategies for patients with stage IV CRC, and a cohort of 113 patients with stage IV CRC resected primary lesions at various periods were analyzed for the presence of mutations in the KRAS, exon 2, and BRAF genes, exon 15, and for the microsatellite instability status of the tumor. These data were additionally correlated with various clinicopathological features. Although BRAF-mutant was revealed to be an independent negative prognostic factor in stage IV CRC (HR, 8.42; 95% confidence interval, 2.72–26.02), BRAF-mutant samples exhibited better prognoses if they were treated with chemotherapy prior to tumor resection. Thus, the presence of BRAF mutations provides a compelling rationale for the establishment of intensive upfront chemotherapy to improve survival in stage IV CRC.
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Affiliation(s)
- Tatsuya Morikawa
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Chūgoku 700-8558, Japan
| | - Ryo Inada
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Chūgoku 700-8558, Japan
| | - Takeshi Nagasaka
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Chūgoku 700-8558, Japan
| | - Yoshiko Mori
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Chūgoku 700-8558, Japan
| | - Hiroyuki Kishimoto
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Chūgoku 700-8558, Japan
| | - Takashi Kawai
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Chūgoku 700-8558, Japan
| | - Yuzo Umeda
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Chūgoku 700-8558, Japan
| | - Hideyuki Mishima
- Cancer Center, Aichi Medical University, Nagakute, Aichi 480-1195, Japan
| | - Ajay Goel
- Center for Gastrointestinal Research and Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, TX 75246, USA
| | - Toshiyoshi Fujiwara
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Chūgoku 700-8558, Japan
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