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Yildirim ME, Karadurmuş N, Ökten İN, Türk HM, Urakçı Z, Arslan Ç, Çelik S, Dane F, Şendur MAN, Bilir C, Karabulut B, Cicin İ, Çubukçu E, Karaca M, Ozcelik M, Artaç M, Tanrikulu E, Alacacioglu A, Açıkgöz Ö, Öven B, Geredeli Ç, Çil T, Harputluoğlu H, Kefeli U, Bozkurt O, Tural D, Sakin A, Yalçın Ş, Gumus M. Real-world treatment outcomes from nationwide Onco-colon Turkey registry in RAS wild-type patients treated with biologics second-line mCRC. J Oncol Pharm Pract 2024:10781552241241004. [PMID: 38613329 DOI: 10.1177/10781552241241004] [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: 04/14/2024]
Abstract
BACKGROUNDS AND OBJECTIVES Colorectal cancer is one of the leading causes of mortality both globally and in our country. In Turkey, we conducted a multicenter investigation into the effectiveness of second-line treatments and real-life data for patients with RAS wild-type metastatic colorectal cancer (NCT04757311). MATERIALS AND METHODS In this retrospective analysis, records from 28 centers were collected, and histopathological, molecular, and clinical characteristics were documented. Patients were categorized into groups based on their second-line biological treatments: anti-EGFR (Group A and Group B, panitumumab and cetuximab) and anti-VEGF (Group C, bevacizumab and aflibercept). They were then compared within these groups. RESULTS A total of 588 patients with documented RAS wild-type status were evaluated. The median OS was 15.7, 14.3 and 14.7 months in Group A, Group B and Group C, respectively (p = 0.764). The median PFS of the patients in second-line setting that received panitumumab, cetuximab and bevacizumab/aflibercept were 7.8, 6.6 and 7.4 months, respectively (p = 0.848). CONCLUSION According to the results of our real-life data study, there is no significant difference in efficiency between the combination of biological agent and chemotherapy used in the second-line treatments.
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Affiliation(s)
- Mahmut Emre Yildirim
- Medical Oncology Department, İstanbul Dr. Lütfi Kırdar Kartal City Hospital, Istanbu, Türkiye
| | - Nuri Karadurmuş
- Medical Oncology Department, Gulhane Training and Research Hospital, Ankara, Türkiye
| | - İlker Nihat Ökten
- Medical Oncology Department, Medeniyet University Goztepe Training and Research Hospital, Istanbul, Türkiye
| | - Hacı Mehmet Türk
- Department of Medical Oncology, Bezmialem Vakif University Faculty of Medicine, Istanbul, Türkiye
| | - Zuhat Urakçı
- Department of Medical Oncology, Dicle University Medical Faculty, Diyarbakir, Türkiye
| | - Çağatay Arslan
- Medical Oncology, Bahcesehir Universitesi Tip Fakultesi, Istanbul, Türkiye
| | - Sinemis Çelik
- Medical Oncology Department, Istanbul Oncology Hospital, Istanbul, Türkiye
| | - Faysal Dane
- Department of Internal Medicine, Division of Medical Oncology, Marmara University School of Medicine, Istanbul, Türkiye
| | | | - Cemil Bilir
- Medical Oncology Department, Sakarya University Training and Research Hospital, Sakarya, Türkiye
| | - Bülent Karabulut
- Medical Oncology, Ege University Faculty of Medicine, Izmir, Türkiye
| | - İrfan Cicin
- Department of Internal Medicine, Division of Oncology, Trakya University Faculty of Medicine, Edirne, Türkiye
| | - Erdem Çubukçu
- Faculty of Medicine, Medical Oncology, Uludag University, Bursa, Türkiye
| | - Mustafa Karaca
- Medical Oncology Department, Antalya Training and Research Hospital, Antalya, Türkiye
| | - Melike Ozcelik
- Department of Oncology, Umraniye Training and Research Hospital, Istanbul, Türkiye
| | - Mehmet Artaç
- Department of Medical Oncology, Necmettin Erbakan University Medical Faculty, Konya, Türkiye
| | - Eda Tanrikulu
- Medical Oncology, Istanbul Haydarpasa Numune Training and Research Hospital, Istanbul, Türkiye
| | - Ahmet Alacacioglu
- Medical Oncology Department, Ministry of Health İzmir Katip Çelebi University Atatürk Education and Research Hospital, Izmir, Türkiye
| | - Özgür Açıkgöz
- Medical Oncology Department, Istanbul Medipol University, İstanbul, Türkiye
| | - Başak Öven
- Medical Oncology Department, Yeditepe University Hospital, Istanbul, Türkiye
| | - Çağlayan Geredeli
- Department of Medical Oncology, Okmeydani Training and Research Hospital, Istanbul, Türkiye
| | - Timucin Çil
- Department of Medical Oncology, University of Health Sciences, Adana City Education and Research Hospital, Adana, Türkiye
| | | | - Umut Kefeli
- Medical Oncology, Kocaeli University School of Medicine, Kocaeli, Türkiye
| | - Oktay Bozkurt
- Medical Oncology Department, Erciyes Universitesi, Kayseri, Türkiye
| | - Deniz Tural
- Medical Oncology, Istanbul Bakirkoy Dr Sadi Konuk Training and Research Hospital, Istanbul, Türkiye
| | - Abdullah Sakin
- Department of Medical Oncology, Yuzuncu Yil University, Van, Türkiye
| | - Şuayip Yalçın
- Department of Medical Oncology, Hacettepe University Faculty of Medicine, Ankara, Türkiye
| | - Mahmut Gumus
- Department of Medical Oncology, Istanbul Medeniyet University Faculty of Medicine, Istanbul, Türkiye
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Pericay C, Fernández Montes A, Alonso Orduña V, Macias Declara I, Asensio Martínez E, Rodríguez Salas N, Torres E, Cacho Lavín D, Rodríguez Alonso RM, Falcó E, Oliva JC, Cirera L. Real-World Outcomes in Patients with Metastatic Colorectal Cancer in Spain: The RWD-ACROSS Study. Cancers (Basel) 2023; 15:4603. [PMID: 37760572 PMCID: PMC10526223 DOI: 10.3390/cancers15184603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 09/05/2023] [Accepted: 09/13/2023] [Indexed: 09/29/2023] Open
Abstract
The retrospective, observational RWD-ACROSS study analyzed disease characteristics, systemic treatment, and survival in patients with metastatic colorectal cancer (mCRC) in Spain. In total, 2002 patients were enrolled (mean age 65.3 years; 62.7% male). Overall median overall survival (OS) was 26.72 months, and was longer in patients with left-sided tumors (28.85 vs. 21.04 months (right-sided tumors); p < 0.0001) and in patients receiving first-line anti-epidermal growth factor receptor (EGFR) treatment (31.21 vs. 26.75 (anti-vascular endothelial growth factor (VEGF) treatment) and 24.45 months (chemotherapy); p = 0.002). Overall median progression-free survival (PFS) was 10.72 months and was longer in patients with left-sided tumors (11.24 vs. 9.31 months (right-sided tumors); p < 0.0001), and in patients receiving either first-line anti-EGFR or anti-VEGF (12.13 and 12.00 vs. 8.98 months (chemotherapy); p < 0.001). PFS was longer with anti-VEGF treatment in patients with right-sided tumors and wild-type RAS (11.24 vs. 8.78 (anti-EGFR) and 7.83 months (chemotherapy); p = 0.025). Both anti-EGFR and anti-VEGF produced longer PFS in patients with left-sided tumors and wild-type RAS than chemotherapy alone (12.39 and 13.14 vs. 9.83 months; p = 0.011). In patients with left-sided tumors and mutant RAS, anti-VEGF produced a longer PFS than chemotherapy alone (12.36 vs. 9.34 months; p = 0.001). In Spain, wild-type RAS or left-sided mCRC tumors are predictive of longer survival times.
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Affiliation(s)
- Carles Pericay
- Servicio de Oncología Médica, Hospital Universitario Mútua Terrassa, Plaça del Doctor Robert, 5., 08221 Terrassa, Spain;
| | - Ana Fernández Montes
- Servicio de Oncología Médica, Complexo Hospitalario Universitario de Ourense, Calle Ramón Puga Noguerol, 54., 32005 Ourense, Spain;
| | - Vicente Alonso Orduña
- Servicio de Oncología Médica, Hospital Universitario Miguel Servet, Instituto de Investigacion Sanitaria de Aragon, Paseo Isabel la Católica, 1-3., 50009 Zaragoza, Spain;
| | - Ismael Macias Declara
- Institut d’Investigació I Innovació I3PT, Fundació Parc Taulí, Plaça Taulí, 1., 08208 Sabadell, Spain; (I.M.D.); (J.C.O.)
| | - Elena Asensio Martínez
- Servicio de Oncología Médica, Hospital General Universitario de Elche, Carrer Almazara, 11., 03203 Elche, Spain;
| | - Nuria Rodríguez Salas
- Servicio de Oncología Médica, Hospital Universitario La Paz, Paseo de la Castellana, 261., 28046 Madrid, Spain;
| | - Esperanza Torres
- UGC Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria and Instituto de Investigación Biomédica de Málaga (IBIMA), Campus de Teatinos, S/N, 29010 Málaga, Spain;
| | - Diego Cacho Lavín
- Servicio de Oncología Médica, Hospital Universitario Marqués de Valdecilla, 39008 Santander, Spain;
| | - Rosa María Rodríguez Alonso
- Servicio de Oncología Médica, Hospital Universitario Reina Sofía-Córdoba, Avenida Menéndez Pidal s/n., 14004 Córdoba, Spain;
| | - Esther Falcó
- Servicio de Oncología Médica, Hospital de Son Llàtzer, Carretera de Manacor, 07198 Palma de-Mallorca, Spain;
| | - Joan Carles Oliva
- Institut d’Investigació I Innovació I3PT, Fundació Parc Taulí, Plaça Taulí, 1., 08208 Sabadell, Spain; (I.M.D.); (J.C.O.)
| | - Lluis Cirera
- Servicio de Oncología Médica, Hospital Universitario Mútua Terrassa, Plaça del Doctor Robert, 5., 08221 Terrassa, Spain;
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Amonkar MM, Abderhalden LA, Frederickson AM, Aksomaityte A, Lang BM, Leconte P, Zhang I. Clinical outcomes of chemotherapy-based therapies for previously treated advanced colorectal cancer: a systematic literature review and meta-analysis. Int J Colorectal Dis 2023; 38:10. [PMID: 36630020 DOI: 10.1007/s00384-022-04301-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/28/2022] [Indexed: 01/12/2023]
Abstract
PURPOSE The purpose of this study was to evaluate clinical outcomes of standard therapies in previously treated, advanced colorectal cancer (CRC) patients. METHODS A systematic literature review was conducted in Embase, MEDLINE, and CENTRAL databases (January 2000-July 2021), annual oncology conferences (2019-2021), and clinicaltrials.gov to identify studies evaluating the use of licensed interventions in second-line or later settings. The primary outcome of interest was objective response rate (ORR) and secondary outcomes included progression-free survival (PFS) and overall survival (OS). ORR was pooled using the Freeman-Tukey double arcsine transformation. For survival outcomes, published Kaplan-Meier curves for OS and PFS were digitized to re-construct individual patient-level data and pooled following the methodology described by Combescure et al. (2014). RESULTS Twenty-three trials evaluating standard chemotherapies with or without targeted therapies across 4,791 advanced CRC patients contributed to our meta-analysis. In the second-line setting, the random effects pooled estimate of ORR was 22.4% (95% confidence interval (CI): 18.0, 27.1), median PFS was 7.0 months (95% CI: 6.4, 7.4), and median OS was 14.9 months (95% CI: 13.6, 16.1). In the third-line or later setting, the random effects pooled estimate of ORR was 1.7% (95% CI: 0.8, 2.7), median PFS was 2.3 months (95% CI: 2.0, 2.8), and median OS was 8.2 months (95% CI: 7.1, 9.1). CONCLUSION Standard treatments have limited efficacy in the second-line or later setting with worsening outcomes in later lines. Given the global burden of CRC, further research into novel and emerging therapeutic options following treatment failure is needed.
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Jo H, Lee MS, Lee YP, Kim H, Hong J, Lee J, Park S, Park J, Park Y, Lim H, Kang W, Kim S. A Comparison of Folinic Acid, Fluorouracil and Irinotecan (FOLFIRI) plus Bevacizumab and FOLFIRI plus Aflibercept as Second-line Treatment for Metastatic Colorectal Cancer. Clin Oncol (R Coll Radiol) 2022; 34:e323-e328. [DOI: 10.1016/j.clon.2022.02.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 01/05/2022] [Accepted: 02/15/2022] [Indexed: 12/13/2022]
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Wilson K, Flood M, Narasimhan V, Pham T, Warrier S, Ramsay R, Michael M, Heriot A. Complete pathological response in rectal cancer utilising novel treatment strategies for neo-adjuvant therapy: A systematic review. Eur J Surg Oncol 2021; 47:1862-1874. [PMID: 33814240 DOI: 10.1016/j.ejso.2021.03.245] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 02/07/2021] [Accepted: 03/17/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Locally advanced rectal cancer is routinely treated with neo-adjuvant long course chemoradiotherapy or short course radiotherapy, followed by total mesorectal excision. Not all patients respond to this treatment and there has been an emergence of novel treatment strategies designed to improve outcomes for these patients. This systematic review aims to assess the current novel neo-adjuvant treatment strategies being utilised in the treatment of patients with rectal cancer and how these impact pathological complete response (pCR) rates. METHODS A systematic review of the literature was performed to evaluate pathological response in patients with rectal cancer receiving novel neo-adjuvant therapy. EMBASE and Medline electronic databases were searched for relevant articles. Articles published between January 2008 and February 2019 were retrieved. Included studies underwent critical appraisal and complete pathological response rates were recorded. RESULTS Of the initial 1074 articles identified, 217 articles fulfilled the inclusion criteria, of these 60 articles (4359 patients) were included. Neo-adjuvant therapy delivered included novel long course chemoradiation therapy, neoadjuvant chemotherapy alone, addition of a biological agent, total neo-adjuvant therapy, novel short course radiation therapy and studies utilising biomarkers to select patients for therapy. Complete pathological response rates ranged from 0 to 60%. CONCLUSION A validated novel neo-adjuvant therapy that significantly increases pCR rates in patients with rectal cancer has not been identified.
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Affiliation(s)
- K Wilson
- Peter MacCallum Cancer Centre, Department of Surgical Oncology, Australia; Differentiation and Transcription Laboratory, Sir Peter MacCallum Cancer Centre, Australia; Sir Peter MacCallum Dept. of Oncology, University of Melbourne, Australia.
| | - M Flood
- Peter MacCallum Cancer Centre, Department of Surgical Oncology, Australia; Differentiation and Transcription Laboratory, Sir Peter MacCallum Cancer Centre, Australia; Sir Peter MacCallum Dept. of Oncology, University of Melbourne, Australia
| | - V Narasimhan
- Peter MacCallum Cancer Centre, Department of Surgical Oncology, Australia; Differentiation and Transcription Laboratory, Sir Peter MacCallum Cancer Centre, Australia; Sir Peter MacCallum Dept. of Oncology, University of Melbourne, Australia
| | - T Pham
- Peter MacCallum Cancer Centre, Department of Surgical Oncology, Australia; Differentiation and Transcription Laboratory, Sir Peter MacCallum Cancer Centre, Australia; Sir Peter MacCallum Dept. of Oncology, University of Melbourne, Australia
| | - S Warrier
- Peter MacCallum Cancer Centre, Department of Surgical Oncology, Australia
| | - R Ramsay
- Peter MacCallum Cancer Centre, Department of Surgical Oncology, Australia; Differentiation and Transcription Laboratory, Sir Peter MacCallum Cancer Centre, Australia
| | - M Michael
- Peter MacCallum Cancer Centre, Department of Medical Oncology, Australia; Sir Peter MacCallum Dept. of Oncology, University of Melbourne, Australia
| | - A Heriot
- Peter MacCallum Cancer Centre, Department of Surgical Oncology, Australia; Sir Peter MacCallum Dept. of Oncology, University of Melbourne, Australia
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Benson AB, Venook AP, Al-Hawary MM, Arain MA, Chen YJ, Ciombor KK, Cohen S, Cooper HS, Deming D, Farkas L, Garrido-Laguna I, Grem JL, Gunn A, Hecht JR, Hoffe S, Hubbard J, Hunt S, Johung KL, Kirilcuk N, Krishnamurthi S, Messersmith WA, Meyerhardt J, Miller ED, Mulcahy MF, Nurkin S, Overman MJ, Parikh A, Patel H, Pedersen K, Saltz L, Schneider C, Shibata D, Skibber JM, Sofocleous CT, Stoffel EM, Stotsky-Himelfarb E, Willett CG, Gregory KM, Gurski LA. Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021; 19:329-359. [PMID: 33724754 DOI: 10.6004/jnccn.2021.0012] [Citation(s) in RCA: 877] [Impact Index Per Article: 219.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section. These updates include recommendations for first-line use of checkpoint inhibitors for mCRC, that is deficient mismatch repair/microsatellite instability-high, recommendations related to the use of biosimilars, and expanded recommendations for biomarker testing. The systemic therapy recommendations now include targeted therapy options for patients with mCRC that is HER2-amplified, or BRAF V600E mutation-positive. Treatment and management of nonmetastatic or resectable/ablatable metastatic disease are discussed in the complete version of the NCCN Guidelines for Colon Cancer available at NCCN.org. Additional topics covered in the complete version include risk assessment, staging, pathology, posttreatment surveillance, and survivorship.
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Affiliation(s)
- Al B Benson
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | - Alan P Venook
- UCSF Helen Diller Family Comprehensive Cancer Center
| | | | | | | | | | - Stacey Cohen
- Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
| | | | | | - Linda Farkas
- UT Southwestern Simmons Comprehensive Cancer Center
| | | | | | | | | | | | | | - Steven Hunt
- Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | | | | | - Smitha Krishnamurthi
- Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | | | | | - Eric D Miller
- The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | - Mary F Mulcahy
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | | | | | - Katrina Pedersen
- Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
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Smolenschi C, Perret A, Dall'Armellina F, Boige V, Malka D, Hollebecque A, Ducreux M. An appraisal of emerging second line therapies for metastatic colorectal cancer. Expert Rev Gastroenterol Hepatol 2021; 15:165-179. [PMID: 33085557 DOI: 10.1080/17474124.2021.1840975] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
INTRODUCTION Despite a significant improvement in overall survival over the last 15 years, colorectal cancer remains a major public health problem worldwide. Much effort has been made to develop an optimal choice of first-line treatments, but after progression the therapeutic possibilities and the criteria for choice are different. AREAS COVERED The purpose of this literature review is to discuss the different possibilities of second-line treatment and to specify the criteria for choice. Biological subgroups requiring specific therapeutic decisions will be described. We conducted a systematic review for randomized controlled trials published since 1995. A non-exhaustive review of published phase II studies, cohort studies, and international guidelines was also given and future leads were discussed. EXPERT OPINION Some choices of second-line treatments are a direct result of the option chosen in the first line. Others are necessary because of the biological specificity of the tumor: immunotherapy for tumors with microsatellite instability, or the combination encorafenib cetuximab for mutated BRAF-V600E tumors. In many other circumstances, there are several options that require extensive involvement of multidisciplinary boards and the patient in the final therapeutic decision.
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Affiliation(s)
- Cristina Smolenschi
- Department of Medical Oncology, Gustave Roussy Cancer Centre , Villejuif, France.,Departement of Therapeutic Innovation, Gustave Roussy Cancer Centre , Villejuif, France
| | - Audrey Perret
- Department of Medical Oncology, Gustave Roussy Cancer Centre , Villejuif, France
| | | | - Valerie Boige
- Department of Medical Oncology, Gustave Roussy Cancer Centre , Villejuif, France
| | - David Malka
- Department of Medical Oncology, Gustave Roussy Cancer Centre , Villejuif, France
| | - Antoine Hollebecque
- Department of Medical Oncology, Gustave Roussy Cancer Centre , Villejuif, France.,Departement of Therapeutic Innovation, Gustave Roussy Cancer Centre , Villejuif, France
| | - Michel Ducreux
- Department of Medical Oncology, Gustave Roussy Cancer Centre , Villejuif, France.,Paris-Saclay University , Saint Aubin, France
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Martin J, Petrillo A, Smyth EC, Shaida N, Khwaja S, Cheow HK, Duckworth A, Heister P, Praseedom R, Jah A, Balakrishnan A, Harper S, Liau S, Kosmoliaptsis V, Huguet E. Colorectal liver metastases: Current management and future perspectives. World J Clin Oncol 2020; 11:761-808. [PMID: 33200074 PMCID: PMC7643190 DOI: 10.5306/wjco.v11.i10.761] [Citation(s) in RCA: 120] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 05/14/2020] [Accepted: 08/31/2020] [Indexed: 02/06/2023] Open
Abstract
The liver is the commonest site of metastatic disease for patients with colorectal cancer, with at least 25% developing colorectal liver metastases (CRLM) during the course of their illness. The management of CRLM has evolved into a complex field requiring input from experienced members of a multi-disciplinary team involving radiology (cross sectional, nuclear medicine and interventional), Oncology, Liver surgery, Colorectal surgery, and Histopathology. Patient management is based on assessment of sophisticated clinical, radiological and biomarker information. Despite incomplete evidence in this very heterogeneous patient group, maximising resection of CRLM using all available techniques remains a key objective and provides the best chance of long-term survival and cure. To this end, liver resection is maximised by the use of downsizing chemotherapy, optimisation of liver remnant by portal vein embolization, associating liver partition and portal vein ligation for staged hepatectomy, and combining resection with ablation, in the context of improvements in the functional assessment of the future remnant liver. Liver resection may safely be carried out laparoscopically or open, and synchronously with, or before, colorectal surgery in selected patients. For unresectable patients, treatment options including systemic chemotherapy, targeted biological agents, intra-arterial infusion or bead delivered chemotherapy, tumour ablation, stereotactic radiotherapy, and selective internal radiotherapy contribute to improve survival and may convert initially unresectable patients to operability. Currently evolving areas include biomarker characterisation of tumours, the development of novel systemic agents targeting specific oncogenic pathways, and the potential re-emergence of radical surgical options such as liver transplantation.
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Affiliation(s)
- Jack Martin
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Angelica Petrillo
- Department of Precision Medicine, Division of Medical Oncology, University of Campania "L. Vanvitelli", Napoli 80131, Italy, & Medical Oncology Unit, Ospedale del Mare, 80147 Napoli Italy
| | - Elizabeth C Smyth
- Department of Oncology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Nadeem Shaida
- Department of Radiology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB22 0QQ, United Kingdom
| | - Samir Khwaja
- Department of Radiology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB22 0QQ, United Kingdom
| | - HK Cheow
- Department of Nuclear Medicine, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Adam Duckworth
- Department of Pathology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Paula Heister
- Department of Pathology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Raaj Praseedom
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Asif Jah
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Anita Balakrishnan
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Simon Harper
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Siong Liau
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Vasilis Kosmoliaptsis
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Emmanuel Huguet
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
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Vera R, Salgado M, Safont MJ, Gallego J, González E, Élez E, Aranda E. Controversies in the treatment of RAS wild-type metastatic colorectal cancer. Clin Transl Oncol 2020; 23:827-839. [PMID: 32789773 PMCID: PMC7979622 DOI: 10.1007/s12094-020-02475-8] [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] [Received: 06/19/2020] [Accepted: 08/03/2020] [Indexed: 01/05/2023]
Abstract
Objective To provide guidance for the management of RAS wild-type (wt) metastatic colorectal cancer (mCRC) in daily practice. Methods Nominal group and Delphi techniques were used. A steering committee of seven experts analyzed the current management of RAS wt mCRC, through which they identified controversies, critically analyzed the available evidence, and formulated several guiding statements for clinicians. Subsequently, a group of 30 experts (the expert panel) was selected to test agreement with the statements, through two Delphi rounds. The following response categories were established in both rounds: 1 = totally agree, 2 = basically agree, 3 = basically disagree, 4 = totally disagree. Agreement was defined if ≥ 75% of answers were in categories 1 and 2 (consensus with the agreement) or 3 and 4 (consensus with the disagreement). Results Overall, 71 statements were proposed, which incorporated the following areas: (1) overarching principles; (2) tumor location; (3) triplets; (4) maintenance; (5) second-line and beyond treatments; (6) Rechallenge and liquid biopsy. After the two Delphi rounds, only six statements maintained a lack of clear consensus. Conclusions This document aims to describe the expert’s attitude when dealing with several common clinical questions regarding patients with RAS wt mCRC. Electronic supplementary material The online version of this article (10.1007/s12094-020-02475-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- R Vera
- Medical Oncology Department, Complejo Hospitalario de Navarra, Pamplona, Spain
| | - M Salgado
- Medical Oncology Department, Complejo Hospitalario Universitario de Ourense, Ourense, Spain
| | - M J Safont
- Medical Oncology Department, Hospital General Universitario de Valencia, Valencia, Spain
| | - J Gallego
- Medical Oncology Department, Hospital General Universitario de Elche, Alicante, Spain
| | - E González
- Medical Oncology Department, Hospital Universitario Virgen de las Nieves, Granada, Spain
| | - E Élez
- Vall d'Hebron Institute of Oncology, Barcelona, Spain
| | - E Aranda
- Medical Oncology Department, Maimonides Institute of Biomedical Research (IMIBIC), Hospital Reina Sofía, University of Córdoba, Av. Menendez Pidal, s/n, 14004, Córdoba, Spain.
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10
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Ryu JY, Choi YJ, Won EJ, Hui E, Kim HS, Cho YS, Yoon TJ. Gene editing particle system as a therapeutic approach for drug-resistant colorectal cancer. NANO RESEARCH 2020; 13:1576-1585. [DOI: 10.1007/s12274-020-2773-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2019] [Revised: 02/27/2020] [Accepted: 03/23/2020] [Indexed: 08/29/2023]
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11
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Safety and Tolerability of Anti-Angiogenic Protein Kinase Inhibitors and Vascular-Disrupting Agents in Cancer: Focus on Gastrointestinal Malignancies. Drug Saf 2019; 42:159-179. [PMID: 30649744 DOI: 10.1007/s40264-018-0776-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Angiogenesis is an essential process for tumor growth and metastasis. Inhibition of angiogenesis as an anticancer strategy has shown significant results in a plethora of tumors. Anti-angiogenic agents are currently part of many standard-of-care options for several metastatic gastrointestinal cancers. Bevacizumab, aflibercept, ramucirumab, and regorafenib have significantly improved both progression-free and overall survival in different lines of treatment in metastatic colorectal cancer. Second-line ramucirumab and third-line apatinib are effective anti-angiogenic treatments for patients with metastatic gastric cancer. Unfortunately, the anti-angiogenic strategy has major practical limitations: resistance inevitably develops through redundancy of signaling pathways and selection for subclonal populations adapted for hypoxic conditions. Anti-angiogenic agents may be more effective in combination therapies, with not only cytotoxics but also other emerging compounds in the anti-angiogenic class or in the separate class of the so-called vascular-disrupting agents. This review aims to provide an overview of the approved and "under development" anti-angiogenic compounds as well as the vascular-disrupting agents in the treatment of gastrointestinal cancers, focusing on the actual body of knowledge available on therapy challenges, pharmacodynamic and pharmacokinetic mechanisms, safety profiles, promising predictive biomarkers, and future perspectives.
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12
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Gouverneur A, Bezin J, Jové J, Bosco-Lévy P, Fourrier-Réglat A, Noize P. Treatment Modalities and Survival in Older Adults with Metastatic Colorectal Cancer in Real Life. J Am Geriatr Soc 2019; 67:913-919. [PMID: 30840323 DOI: 10.1111/jgs.15858] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2018] [Revised: 02/05/2019] [Accepted: 02/07/2019] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Metastatic colorectal cancer (mCRC) is increasingly treated with targeted therapies, but little is known about real-life mCRC treatment in older adults. The aims were to describe the real-life first-line treatment modalities in older adult mCRC patients, to identify factors associated with treatment modalities, and to evaluate survival with regard to treatment modalities. PATIENTS AND METHODS A cohort of mCRC patients aged 65 years and older at diagnosis was identified between 2009 and 2013 using French national healthcare insurance system claims data. Treatment modalities were: treatment with one or more anticancer medication vs best supportive care and, among treated patients, treatment with targeted therapy vs conventional chemotherapy alone. Multivariate logistic regression was used to identify factors associated with treatment by anticancer medication and by targeted therapy. Cox proportional hazards models were used to assess the independent effect of treatment modalities on overall survival while adjusting for baseline covariates identified with logistic regression. RESULTS A total of 503 patients were included with a median age of 78 years (54% were men). Of these, 299 (59%) were treated with anticancer medications. Among treated patients, 131 (44%) received targeted therapy. In multivariate analysis, age 75 years or older, renal failure, malnutrition, and five or more concomitant medications were associated with a lower likelihood of treatment with anticancer medications. Among treated patients, age 75 years or older, history of cancer, lymph node metastases, and a single metastatic site were associated with a lower likelihood of treatment with targeted therapy. Multivariate Cox proportional hazards models found that treatment with any anticancer medication tended to be associated with a lower risk of death; treatment with targeted therapy was not significantly associated. CONCLUSION A more appropriate prescription of anticancer medications in the older adult will require the definition of more explicit criteria to avoid undertreatment. The real benefit of targeted therapies vs conventional chemotherapy alone needs to be confirmed in this population. J Am Geriatr Soc 67:913-919, 2019.
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Affiliation(s)
- Amandine Gouverneur
- Bordeaux Population Health Research Center, team Pharmacoepidemiology, UMR 1219, University of Bordeaux, Inserm, Bordeaux, France.,Pôle de Santé publique, Service de Pharmacologie médicale, CHU de Bordeaux, Bordeaux, France
| | - Julien Bezin
- Bordeaux Population Health Research Center, team Pharmacoepidemiology, UMR 1219, University of Bordeaux, Inserm, Bordeaux, France
| | - Jérémy Jové
- Bordeaux PharmacoEpi, INSERM CIC1401, Bordeaux, France
| | | | - Annie Fourrier-Réglat
- Bordeaux Population Health Research Center, team Pharmacoepidemiology, UMR 1219, University of Bordeaux, Inserm, Bordeaux, France.,Pôle de Santé publique, Service de Pharmacologie médicale, CHU de Bordeaux, Bordeaux, France.,Bordeaux PharmacoEpi, INSERM CIC1401, Bordeaux, France
| | - Pernelle Noize
- Bordeaux Population Health Research Center, team Pharmacoepidemiology, UMR 1219, University of Bordeaux, Inserm, Bordeaux, France.,Pôle de Santé publique, Service de Pharmacologie médicale, CHU de Bordeaux, Bordeaux, France.,Bordeaux PharmacoEpi, INSERM CIC1401, Bordeaux, France
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13
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Li J, Xu R, Qin S, Liu T, Pan H, Xu J, Bi F, Lim R, Zhang S, Ba Y, Bai Y, Fan N, Tsuji A, Yeh KH, Ma B, Wei V, Shi D, Magherini E, Shen L. Aflibercept plus FOLFIRI in Asian patients with pretreated metastatic colorectal cancer: a randomized Phase III study. Future Oncol 2018; 14:2031-2044. [PMID: 30117334 DOI: 10.2217/fon-2017-0669] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
AIM To investigate whether the benefit of combining aflibercept with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) chemotherapy could be confirmed in patients from the Asia-Pacific region (ClinicalTrials.gov: NCT01661270). Patients & methods: Asian patients with oxaliplatin-pretreated metastatic colorectal cancer were randomized to receive aflibercept or placebo, followed by FOLFIRI. The primary end point was progression-free survival. RESULTS The intention-to-treat population comprised 332 patients. A clinical supply misallocation resulted in 198/332 (60%) patients receiving at least one cycle of misallocated treatment. Nevertheless, the addition of aflibercept to FOLFIRI was shown to improve progression-free survival (hazard ratio: 0.629; 95% CI: 0.488-0.812). Adverse events were in line with expectations. CONCLUSION The beneficial treatment effect associated with the addition of aflibercept to FOLFIRI was confirmed in Asian patients with pretreated metastatic colorectal cancer.
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Affiliation(s)
- Jin Li
- Shanghai East Hospital, Tongji University School of Medicine, Shanghai, PR China
| | - Ruihua Xu
- Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, PR China
| | - Shukui Qin
- People's Liberation Army (PLA) Cancer Center, 81 Military Hospital of China, Nanjing, PR China
| | - Tianshu Liu
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, PR China
| | - Hongming Pan
- Department of Medical Oncology, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, PR China
| | - Jianming Xu
- Department of Oncology, 307 Hospital of the Chinese People's Liberation Army, Beijing, PR China
| | - Feng Bi
- Department of Medical Oncology, West China Hospital of Sichuan University, Chengdu, PR China
| | - Robert Lim
- Department of Haematology-Oncology, National University Cancer Institute, Singapore
| | - Suzhan Zhang
- Cancer Institute, Second Affiliated Hospital of Zhejiang University, Hangzhou, PR China
| | - Yi Ba
- Department of Gastrointestinal Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, PR China
| | - Yuxian Bai
- Cancer Hospital, Harbin Medical University, Harbin, PR China
| | - Nanfeng Fan
- Department of Medical Oncology, Fujian Province Cancer Hospital, Fuzhou, PR China
| | - Akihito Tsuji
- Department of Medical Oncology, Kobe City Medical Center General Hospital, Hyogo, Japan
| | - Kun-Huei Yeh
- Department of Oncology, National Taiwan University Cancer Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Brigette Ma
- Department of Clinical Oncology, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, SAR
| | - Vivian Wei
- Research and Development, Sanofi, Beijing, PR China
| | - Dongmei Shi
- Research and Development, Sanofi, Beijing, PR China
| | | | - Lin Shen
- Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, PR China
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14
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Lanera C, Minto C, Sharma A, Gregori D, Berchialla P, Baldi I. Extending PubMed searches to ClinicalTrials.gov through a machine learning approach for systematic reviews. J Clin Epidemiol 2018; 103:22-30. [PMID: 29981872 DOI: 10.1016/j.jclinepi.2018.06.015] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Revised: 06/19/2018] [Accepted: 06/29/2018] [Indexed: 12/23/2022]
Abstract
OBJECTIVES Despite their essential role in collecting and organizing published medical literature, indexed search engines are unable to cover all relevant knowledge. Hence, current literature recommends the inclusion of clinical trial registries in systematic reviews (SRs). This study aims to provide an automated approach to extend a search on PubMed to the ClinicalTrials.gov database, relying on text mining and machine learning techniques. STUDY DESIGN AND SETTING The procedure starts from a literature search on PubMed. Next, it considers the training of a classifier that can identify documents with a comparable word characterization in the ClinicalTrials.gov clinical trial repository. Fourteen SRs, covering a broad range of health conditions, are used as case studies for external validation. A cross-validated support-vector machine (SVM) model was used as the classifier. RESULTS The sensitivity was 100% in all SRs except one (87.5%), and the specificity ranged from 97.2% to 99.9%. The ability of the instrument to distinguish on-topic from off-topic articles ranged from an area under the receiver operator characteristic curve of 93.4% to 99.9%. CONCLUSION The proposed machine learning instrument has the potential to help researchers identify relevant studies in the SR process by reducing workload, without losing sensitivity and at a small price in terms of specificity.
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Affiliation(s)
- Corrado Lanera
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Via Loredan 18, Padova 35131, Italy
| | - Clara Minto
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Via Loredan 18, Padova 35131, Italy
| | - Abhinav Sharma
- Department of Biological Sciences and Bioengineering (BSBE), IIT, Kanpur, India
| | - Dario Gregori
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Via Loredan 18, Padova 35131, Italy
| | - Paola Berchialla
- Department of Clinical and Biological Sciences, University of Torino, Via Santena 5bis, Torino 10126, Italy
| | - Ileana Baldi
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Via Loredan 18, Padova 35131, Italy.
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15
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Battaglin F, Puccini A, Intini R, Schirripa M, Ferro A, Bergamo F, Lonardi S, Zagonel V, Lenz HJ, Loupakis F. The role of tumor angiogenesis as a therapeutic target in colorectal cancer. Expert Rev Anticancer Ther 2018; 18:251-266. [PMID: 29338550 PMCID: PMC7493706 DOI: 10.1080/14737140.2018.1428092] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 01/11/2018] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Angiogenesis is a complex process regulated by several pro- and anti-angiogenic factors, thus the loss of its fine equilibrium plays a key role in colorectal cancer (CRC) development and progression. Therapeutic agents targeting VEGF/VEGFR signaling, the main regulator of this process, proved to be effective across different treatment lines in metastatic CRC (mCRC) and contributed greatly to improve patients' survival in recent years. Areas covered: This review aimed to summarize the actual body of knowledge available on the VEGF pathway in CRC, including currently available anti-angiogenic drugs and treatment challenges, mechanisms of resistance, promising predictive biomarkers and future perspectives. Expert commentary: Angiogenesis inhibition in subsequent lines of treatment is a valid strategy in the continuum of care of mCRC patients. In this scenario, the availability of multiple agents warrants to tailor therapy to an individualized approach. However, the validation of predictive biomarkers to aid therapeutic decisions remains an issue. Intrinsic and adaptive resistance to anti-angiogenic agents comprises distinct and intertwined processes, eventually leading to treatment failure and disease progression. The expanding knowledge on the mechanisms underlying the angiogenesis pathway, different potential treatment targets and mechanisms of tumor resistance, may lead to promising new perspectives in this field.
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Affiliation(s)
- Francesca Battaglin
- Medical Oncology Unit 1, Clinical and Experimental Oncology Department, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
- Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Alberto Puccini
- Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
- Department of Medical Oncology 1, Ospedale Policlinico San Martino, Genova, Italy
| | - Rossana Intini
- Medical Oncology Unit 1, Clinical and Experimental Oncology Department, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Marta Schirripa
- Medical Oncology Unit 1, Clinical and Experimental Oncology Department, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Alessandra Ferro
- Medical Oncology Unit 1, Clinical and Experimental Oncology Department, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Francesca Bergamo
- Medical Oncology Unit 1, Clinical and Experimental Oncology Department, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Sara Lonardi
- Medical Oncology Unit 1, Clinical and Experimental Oncology Department, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Vittorina Zagonel
- Medical Oncology Unit 1, Clinical and Experimental Oncology Department, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Heinz-Josef Lenz
- Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Fotios Loupakis
- Medical Oncology Unit 1, Clinical and Experimental Oncology Department, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
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16
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Gulei D, Magdo L, Jurj A, Raduly L, Cojocneanu-Petric R, Moldovan A, Moldovan C, Florea A, Pasca S, Pop LA, Moisoiu V, Budisan L, Pop-Bica C, Ciocan C, Buiga R, Muresan MS, Stiufiuc R, Ionescu C, Berindan-Neagoe I. The silent healer: miR-205-5p up-regulation inhibits epithelial to mesenchymal transition in colon cancer cells by indirectly up-regulating E-cadherin expression. Cell Death Dis 2018; 9:66. [PMID: 29352232 PMCID: PMC5833765 DOI: 10.1038/s41419-017-0102-8] [Citation(s) in RCA: 69] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Revised: 10/08/2017] [Accepted: 10/23/2017] [Indexed: 12/23/2022]
Abstract
EMT represents the dominant program within advanced stages of colon cancer, where cells acquire migratory characteristics in order to invade secondary tissues and form metastasis. Where the majority of the therapeutic strategies are concentrated on the reduction of the tumor mass through different apoptotic mechanisms, the present study advocates an important role for miR-205-5p in impairment of colon cancer cells migration and restoration of the epithelial phenotype. Upon identification of a homogenous downregulated profile for miR-205-5p in colon adenocarcinoma patients, functional studies demonstrated that experimental upregulation of this sequence is able to significantly raise the levels of E-cadherin through direct inhibition of ZEB1. Moreover, the elevation in CDH1 expression was translated into functional parameters where cells lost their invasion and migratory characteristics and formed homogenous clusters through adhesion interactions. Survival analysis of colon adenocarcinoma patients revealed that low levels of miR-205-5p are associated with an unfavorable prognostic compared to those with increased expression, demonstrating the possible clinical utility of miR-205-5p replacement. Exogenous administration of miRNA mimics was not associated with significant changes in cell viability or inflammatory pathways. Therefore, the proposed strategy is aiming towards inhibition of metastasis and limitation of the tumor borders in advanced stages patients in order to prolong the survival time and to increase the efficiency of the current therapeutic strategies.
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Affiliation(s)
- Diana Gulei
- MEDFUTURE - Research Center for Advanced Medicine, "Iuliu-Hatieganu" University of Medicine and Pharmacy, Marinescu 23 Street / Louis Pasteur 4-6 Street, Cluj-Napoca, Romania
| | - Lorand Magdo
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 23 Marinescu Street, 400337, Cluj-Napoca, Romania
| | - Ancuta Jurj
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 23 Marinescu Street, 400337, Cluj-Napoca, Romania
| | - Lajos Raduly
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 23 Marinescu Street, 400337, Cluj-Napoca, Romania.,Department of Pathophysiology, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăștur 3-5 Street, 400372, Cluj-Napoca, Romania
| | - Roxana Cojocneanu-Petric
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 23 Marinescu Street, 400337, Cluj-Napoca, Romania
| | - Alin Moldovan
- MEDFUTURE - Research Center for Advanced Medicine, "Iuliu-Hatieganu" University of Medicine and Pharmacy, Marinescu 23 Street / Louis Pasteur 4-6 Street, Cluj-Napoca, Romania
| | - Cristian Moldovan
- MEDFUTURE - Research Center for Advanced Medicine, "Iuliu-Hatieganu" University of Medicine and Pharmacy, Marinescu 23 Street / Louis Pasteur 4-6 Street, Cluj-Napoca, Romania
| | - Adrian Florea
- Department of Cell and Molecular Biology, Faculty of Medicine, "Iuliu Haţieganu" University of Medicine and Pharmacy, 6 Louis Pasteur St., 400349, Cluj-Napoca, Romania
| | - Sergiu Pasca
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 23 Marinescu Street, 400337, Cluj-Napoca, Romania
| | - Laura-Ancuta Pop
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 23 Marinescu Street, 400337, Cluj-Napoca, Romania
| | - Vlad Moisoiu
- Faculty of Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 8 Victor Babes Street, Cluj-Napoca, Romania
| | - Liviuta Budisan
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 23 Marinescu Street, 400337, Cluj-Napoca, Romania
| | - Cecilia Pop-Bica
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 23 Marinescu Street, 400337, Cluj-Napoca, Romania
| | - Cristina Ciocan
- MEDFUTURE - Research Center for Advanced Medicine, "Iuliu-Hatieganu" University of Medicine and Pharmacy, Marinescu 23 Street / Louis Pasteur 4-6 Street, Cluj-Napoca, Romania
| | - Rares Buiga
- Department of Pathology, "Prof. Dr. Ion Chiricuta" Oncology Institute, Cluj-Napoca, Romania
| | - Mihai-Stefan Muresan
- 5th Surgical Department, Municipal Hospital, Cluj-Napoca, Romania.,Surgical and Gynecological Oncology Department, "Prof. Dr. Ion Chiricuta" Oncology Institute, Republicii 34 Street, 400015, Cluj-Napoca, Romania.,"Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Rares Stiufiuc
- MEDFUTURE - Research Center for Advanced Medicine, "Iuliu-Hatieganu" University of Medicine and Pharmacy, Marinescu 23 Street / Louis Pasteur 4-6 Street, Cluj-Napoca, Romania.,Department of Pharmaceutical Physics-Biophysics, Faculty of Pharmacy, "Iuliu Hatieganu" University of Medicine and Pharmacy, Pasteur 6 Street, 400349, Cluj-Napoca, Romania
| | - Calin Ionescu
- 5th Surgical Department, Municipal Hospital, Cluj-Napoca, Romania. .,"Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
| | - Ioana Berindan-Neagoe
- MEDFUTURE - Research Center for Advanced Medicine, "Iuliu-Hatieganu" University of Medicine and Pharmacy, Marinescu 23 Street / Louis Pasteur 4-6 Street, Cluj-Napoca, Romania. .,Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 23 Marinescu Street, 400337, Cluj-Napoca, Romania. .,Department of Functional Genomics and Experimental Pathology, "Prof. Dr. Ion Chiricuta" Oncology Institute, Republicii 34 Street, Cluj-Napoca, 400015, Romania.
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17
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Jiang Y, Fan H, Jiang Y, Song G, Wang F, Li X, Li G. Efficacy and safety of FOLFIRI and biotherapy versus FOLFIRI alone for metastatic colorectal cancer patients: A meta-analysis. Medicine (Baltimore) 2017; 96:e8767. [PMID: 29310351 PMCID: PMC5728752 DOI: 10.1097/md.0000000000008767] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Previous randomized controlled trials (RCTs) and meta-analyses have demonstrated the useless of FOLFIRI alone for previously treated patients with metastatic colorectal cancer (mCRC). The role of FOLFIRI regimen combined with biological therapy is unknown. The purpose of this meta-analysis is to evaluate the efficacy and safety of combining biological therapy with chemotherapy in previously treated patients with mCRC. METHODS MEDLINE, EMBASE, Web of Science, Cochrane library, and ClinicalTrials.gov were searched. Eligible studies were RCTs that evaluated the efficacy and safety of the FOLFIRI regimen with or without biological therapy for previously treated patients with mCRC. The hazard ratio (HR) or risk ratio (RR) with 95% confidence interval was estimated. The Chi-squared and I-squared tests were used to assess the statistical heterogeneity. RESULTS The literature search identified 7 RCTs that met the inclusion criteria for the meta-analysis, and 3680 patients with mCRC were included. The meta-analysis showed that combined therapy was associated with a significant improved progression-free survival (PFS) (HR = 0.78, 95% CI = 0.72-0.85, P < .001), overall survival (OS) (HR = 0.84, 95% CI = 0.77-0.92, P < .001), and overall response rate (ORR) (RR = 1.70, 95% CI = 1.25-2.31, P = .001). Sensitivity analysis suggested that combined therapy versus FOLFIRI alone might increase the risk of Grade 3/4 AEs. CONCLUSION The addition of biological therapy to the FOLFIRI regimen improved the PFS, OS, and ORR compared with FOLFIRI alone for previously treated patients with mCRC. Long-term survival outcomes are warranted.
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Affiliation(s)
| | - Hui Fan
- Department of Radiation Oncology
| | - Yongmei Jiang
- Department of Neurological Rehabilitation, the Second Affiliated Hospital of Dalian Medical University
| | - Guirong Song
- School of Public Health, Dalian Medical University, Dalian, Liaoning, P.R. China
| | - Feng Wang
- School of Public Health, Dalian Medical University, Dalian, Liaoning, P.R. China
| | - Xiaofeng Li
- School of Public Health, Dalian Medical University, Dalian, Liaoning, P.R. China
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18
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Ducreux M, Österlund P, Pignon JP. Angiogenesis inhibition in the second-line treatment of metastatic colorectal cancer-A definite conclusion? Semin Oncol 2017; 44:129-131. [PMID: 28923210 DOI: 10.1053/j.seminoncol.2017.07.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- M Ducreux
- Department of Medical Oncology, Gustave Roussy, Villejuif, France; Université Paris-Saclay, Saint-Aubin, France.
| | - P Österlund
- Department of Oncology, Tampere University Hospital, Tampere Tampere university, Faculty of medicine and life sciences Tampere, FINLAND
| | - J P Pignon
- Service de Biostatistique et d'Epidémiologie, Gustave Roussy, Villejuif, France; INSERM U1018, CESP, Villejuif, France; Ligue Nationale Contre le Cancer, Cancer Meta-Analysis Platform, Villejuif, France
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19
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Carvalho AC, Leal F, Sasse AD. Cost-effectiveness of cetuximab and panitumumab for chemotherapy-refractory metastatic colorectal cancer. PLoS One 2017; 12:e0175409. [PMID: 28403233 PMCID: PMC5389795 DOI: 10.1371/journal.pone.0175409] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Accepted: 03/24/2017] [Indexed: 11/19/2022] Open
Abstract
Background Cetuximab and panitumumab are monoclonal antibodies targeting the epidermal growth factor receptor. Both drugs are active against RAS wild type metastatic colorectal cancer after chemotherapy failure, with similar efficacy and toxicity profiles. However, their cost and limited survival benefits may compromise incorporation in the Brazilian public healthcare system, the Unified Heath System (Sistema Único de Saúde) (SUS). Methods A cost-effectiveness analysis was conducted using a Markov model from the Brazilian Public health perspective and a lifetime horizon in patients with RAS -wt mCRC. Transition probabilities and mortality rates were extracted from randomized studies. Treatment costs were obtained from price tables regulated by the Brazilian Health Ministry. The World Health Organization recommendation of three times GDP per capita was used to define the cost-effectiveness threshold. Results The use of cetuximab or panitumumab for chemotherapy-refractory mCRC patients resulted in 0.22 additional life-years relative to BSC, with incremental cost-effectiveness ratios (ICERs) of $58,240 and $52,772 per LY, respectively. That exceeds the pre-specified threshold for cost-effectiveness. Acquisition of biological agents was the major driver of increased costs. Conclusions Our economic evaluation demonstrates that both cetuximab and panitumumab are not a cost-effective approach in RAS-wt mCRC patients. Discussion about drug price should be prioritized to enable incorporation of these monoclonal antibodies in the SUS.
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Affiliation(s)
- Adriana Camargo Carvalho
- Centre for Evidence in Oncology, Department of Internal Medicine, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil
| | - Frederico Leal
- Centre for Evidence in Oncology, Department of Internal Medicine, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil
| | - Andre Deeke Sasse
- Centre for Evidence in Oncology, Department of Internal Medicine, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil
- * E-mail:
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Chebib R, Verlingue L, Cozic N, Faron M, Burtin P, Boige V, Hollebecque A, Malka D. Angiogenesis inhibition in the second-line treatment of metastatic colorectal cancer: A systematic review and pooled analysis. Semin Oncol 2017; 44:114-128. [PMID: 28923209 DOI: 10.1053/j.seminoncol.2017.07.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 04/18/2017] [Accepted: 07/31/2017] [Indexed: 12/26/2022]
Abstract
The last two decades have seen intensive efforts devoted to the development of compounds that target angiogenesis for the treatment of metastatic colorectal cancer (mCRC). In this review, we describe supporting evidence and ongoing development of angiogenesis inhibitors in the second-line treatment of mCRC, and summarize relevant randomized trials to help therapeutic decision-making in daily practice.
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Affiliation(s)
- Ralph Chebib
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Paris, France
| | - Loic Verlingue
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Paris, France
| | - Nathalie Cozic
- Service de Biostatistique et d'Epidémiologie, Gustave Roussy, Université Paris-Saclay, Paris, France; INSERM U1018, CESP, Gustave Roussy, Université Paris-Saclay, Paris, France; Ligue Nationale Contre le Cancer Meta-Analysis Platform, Gustave Roussy, Université Paris-Saclay, Paris France
| | - Matthieu Faron
- Service de Biostatistique et d'Epidémiologie, Gustave Roussy, Université Paris-Saclay, Paris, France; INSERM U1018, CESP, Gustave Roussy, Université Paris-Saclay, Paris, France; Département de Chirurgie Digestive, Gustave Roussy, Université Paris-Saclay, Paris, France
| | - Pascal Burtin
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Paris, France
| | - Valérie Boige
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Paris, France
| | - Antoine Hollebecque
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Paris, France; Département d'Innovation Thérapeutique et d'Essais Précoces (DITEP), Villejuif, France
| | - David Malka
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Paris, France.
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Yang YF, Wang GY, He JL, Wu FP, Zhang YN. Overall survival of patients with KRAS wild-type tumor treated with FOLFOX/FORFIRI±cetuximab as the first-line treatment for metastatic colorectal cancer: A meta-analysis. Medicine (Baltimore) 2017; 96:e6335. [PMID: 28328812 PMCID: PMC5371449 DOI: 10.1097/md.0000000000006335] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
The addition of cetuximab to FOLFIRI or FOLFOX as the first-line treatment for metastatic colorectal cancer (mCRC) was shown to reduce the risk of disease progression and increase the chance of response in patients with KRAS wild-type disease. An updated systematic meta-analysis was undertaken to determine the efficacy of cetuximab plus FOLFIRI or FOLFOX.Major databases were searched to identify RCTs investigating wild-type KRAS mCRC after the first-line treatment, and treatment with FOLFOX/FORFIRI ± cetuximab was compared. Data on clinical efficacy and safety were pooled and compared by ORs, HRs, and 95% CIs.Five eligible trials with 1464 patients were included in the meta-analysis. Compared to FOLFOX/FORFIRI, cetuximab as the first-line therapy has improved overall survival (OS) (hazard ratio [HR] = 0.82, 95% confidence interval [CI]: 0.72-0.93, P = 0.003), progression-free survival (PFS) (HR = 0.66, 95% CI: 0.56 -0.77, P < 0.00001), and overall response rate (ORR) (odds ratio [OR] = 2.12, 95% CI: 1.70-2.65, P < 0.00001). However, Grade 3/4 AE was increased with the OR of 2.76 (95%CI: 2.01-3.78, P < 0.00001). The most common grade 3/4 toxicity in the wild-type KRAS population was neutropenia and diarrhea. For cetuximab plus FOLFIRI, there was a higher incidence of grade 3 or 4 diarrhea (OR = 1.76, 95% CI: 1.15-2.70, P = 0.01), but there was no significant difference for neutropenia (OR = 1.35, 95% CI: 1.00-1.83, P = 0.05).The addition of cetuximab in mCRC as the first-line treatment is a potential effective approach in the improved outcomes but associated with increased toxicity.
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Affiliation(s)
| | | | | | - Feng-Peng Wu
- Department of Radiotherapy, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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22
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Pei X, Liu Y, Sun L, Zhang J, Fang Y, Liao X, Liu J, Zhang C, Yin T. Outcome of Molecular Targeted Agents Plus Chemotherapy for Second-Line Therapy of Metastatic Colorectal Cancer: A Meta-Analysis of Randomized Trials. Clin Colorectal Cancer 2016; 15:e149-e156. [DOI: 10.1016/j.clcc.2016.03.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2015] [Revised: 02/29/2016] [Accepted: 03/22/2016] [Indexed: 10/22/2022]
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Chow OS, Kuk D, Keskin M, Smith JJ, Camacho N, Pelossof R, Chen CT, Chen Z, Avila K, Weiser MR, Berger MF, Patil S, Bergsland E, Garcia-Aguilar J. KRAS and Combined KRAS/TP53 Mutations in Locally Advanced Rectal Cancer are Independently Associated with Decreased Response to Neoadjuvant Therapy. Ann Surg Oncol 2016; 23:2548-55. [PMID: 27020587 DOI: 10.1245/s10434-016-5205-4] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Indexed: 01/07/2023]
Abstract
BACKGROUND The response of rectal cancers to neoadjuvant chemoradiation (CRT) is variable, but tools to predict response remain lacking. We evaluated whether KRAS and TP53 mutations are associated with pathologic complete response (pCR) and lymph node metastasis after adjusting for neoadjuvant regimen. METHODS Retrospective analysis of 229 pretreatment biopsies from patients with stage II/III rectal cancer was performed. All patients received CRT. Patients received 0-8 cycles of FOLFOX either before or after CRT, but prior to surgical excision. A subset was analyzed to assess concordance between mutation calls by Sanger Sequencing and a next-generation assay. RESULTS A total of 96 tumors (42 %) had KRAS mutation, 150 had TP53 mutation (66 %), and 59 (26 %) had both. Following neoadjuvant therapy, 59 patients (26 %) achieved pCR. Of 133 KRAS wild-type tumors, 45 (34 %) had pCR, compared with 14 of 96 (15 %) KRAS mutant tumors (p = .001). KRAS mutation remained independently associated with a lower pCR rate on multivariable analysis after adjusting for clinical stage, CRT-to-surgery interval and cycles of FOLFOX (OR 0.34; 95 % CI 0.17-0.66, p < .01). Of 29 patients with KRAS G12V or G13D, only 2 (7 %) achieved pCR. Tumors with both KRAS and TP53 mutation were associated with lymph node metastasis. The concordance between platforms was high for KRAS (40 of 43, 93 %). CONCLUSIONS KRAS mutation is independently associated with a lower pCR rate in locally advanced rectal cancer after adjusting for variations in neoadjuvant regimen. Genomic data can potentially be used to select patients for "watch and wait" strategies.
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Affiliation(s)
- Oliver S Chow
- Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Deborah Kuk
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Metin Keskin
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - J Joshua Smith
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | | | - Chin-Tung Chen
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Zhenbin Chen
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - Karin Avila
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | | | - Sujata Patil
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Maeda K, Ohki T, Kanaoka Y, Toya N, Baba T, Hara M, Hagiwara S. Current surgical management of abdominal aortic aneurysm with concomitant malignancy in the endovascular era. Surg Today 2015; 46:985-94. [PMID: 26471508 DOI: 10.1007/s00595-015-1262-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Accepted: 09/02/2015] [Indexed: 01/09/2023]
Abstract
PURPOSE The management of abdominal aortic aneurysm (AAA) with concomitant malignancy is controversial in terms of which treatment should come first. The aim of this study was to evaluate the outcomes of endovascular aortic repair (EVAR) as the initial treatment prior to the treatment of malignancy for patients with AAA and concomitant malignancy. METHODS EVAR for AAA was performed in 1,175 cases between April 2007 and April 2014, of which 63 patients (5.4 %) who had AAAs and malignancy were identified. The clinical details and outcomes for patients with AAA and malignancy were evaluated. RESULTS The mean age of patients with AAA and malignancy was 76.6 years. Thirty-three patients underwent EVAR before surgery for their malignancies, and 30 patients received chemoradiotherapy following EVAR. No significant differences in the length of stay (LOS), 30-day mortality, and morbidities were observed in all groups. However, the overall survival rate of the patients who had AAA and malignancy was lower than those who had only AAA (P < 0.0001). The mean intervals from EVAR to surgery and chemoradiotherapy for malignancy in our institution were 13.4 days (overall 38.1 days) and 5.8 days (overall 18.2 days), respectively. CONCLUSION EVAR for patients with AAA and concomitant malignancy may be acceptable in terms of a short LOS and resulting in treatment for malignancy without delay.
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Affiliation(s)
- Koji Maeda
- Division of Vascular Surgery, Department of Surgery, Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
| | - Takao Ohki
- Division of Vascular Surgery, Department of Surgery, Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Yuji Kanaoka
- Division of Vascular Surgery, Department of Surgery, Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Naoki Toya
- Division of Vascular Surgery, Department of Surgery, Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Takeshi Baba
- Division of Vascular Surgery, Department of Surgery, Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Masayuki Hara
- Division of Vascular Surgery, Department of Surgery, Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Shin Hagiwara
- Division of Vascular Surgery, Department of Surgery, Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
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MiR expression profiles of paired primary colorectal cancer and metastases by next-generation sequencing. Oncogenesis 2015; 4:e170. [PMID: 26436952 PMCID: PMC4632090 DOI: 10.1038/oncsis.2015.29] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2015] [Revised: 08/20/2015] [Accepted: 08/27/2015] [Indexed: 02/07/2023] Open
Abstract
MicroRNAs (miRs) have been recognized as promising biomarkers. It is unknown to what extent tumor-derived miRs are differentially expressed between primary colorectal cancers (pCRCs) and metastatic lesions, and to what extent the expression profiles of tumor tissue differ from the surrounding normal tissue. Next-generation sequencing (NGS) of 220 fresh-frozen samples, including paired primary and metastatic tumor tissue and non-tumorous tissue from 38 patients, revealed expression of 2245 known unique mature miRs and 515 novel candidate miRs. Unsupervised clustering of miR expression profiles of pCRC tissue with paired metastases did not separate the two entities, whereas unsupervised clustering of miR expression profiles of pCRC with normal colorectal mucosa demonstrated complete separation of the tumor samples from their paired normal mucosa. Two hundred and twenty-two miRs differentiated both pCRC and metastases from normal tissue samples (false discovery rate (FDR) <0.05). The highest expressed tumor-specific miRs were miR-21 and miR-92a, both previously described to be involved in CRC with potential as circulating biomarker for early detection. Only eight miRs, 0.5% of the analysed miR transcriptome, were differentially expressed between pCRC and the corresponding metastases (FDR <0.1), consisting of five known miRs (miR-320b, miR-320d, miR-3117, miR-1246 and miR-663b) and three novel candidate miRs (chr 1-2552-5p, chr 8-20656-5p and chr 10-25333-3p). These results indicate that previously unrecognized candidate miRs expressed in advanced CRC were identified using NGS. In addition, miR expression profiles of pCRC and metastatic lesions are highly comparable and may be of similar predictive value for prognosis or response to treatment in patients with advanced CRC.
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Gill S, Dowden S, Colwell B, Collins LL, Berry S. Navigating later lines of treatment for advanced colorectal cancer – Optimizing targeted biological therapies to improve outcomes. Cancer Treat Rev 2014; 40:1171-81. [DOI: 10.1016/j.ctrv.2014.10.002] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2014] [Revised: 10/07/2014] [Accepted: 10/08/2014] [Indexed: 12/27/2022]
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