- Email: [email protected]
Immunoscore predicts significant differences in time to recurrence in stage I colon cancer patients
Annals of Oncology 30 (Supplement 9): ix30–ix41, 2019 doi:10.1093/annonc/mdz421
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Immunoscore predicts significant differences in time to recurrence in stage I colon cancer patients
J. Galon1, F. Hermitte2, B. Mlecnik1, F. Marliot3, C. Bifulco4, A. Lugli5, I. Nagtegaal6, A. Hartmann7, M. van den Eynde8, M. Roehrl9, P. Ohashi10, E. Zavadova11, T. Torigoe12, P. Patel13, Y. Wang14, Y. Kawakami15, F. Marincola16, P. Ascierto17, B. Fox18, F. Page`s3 1 Laboratory of Integrative Cancer Immunology, INSERM, Sorbonne Universite´, Sorbonne Paris Cite´, Universite´ Paris Descartes, Universite´ Paris Diderot, Centre de Recherche des Cordeliers, Paris, France, 2Medical Affairs, HalioDx, Marseille, France, 3Laboratory of Immunology, AP-HP, Georges Pompidou European Hospital, Paris, France, 4Department of Pathology, Providence Portland Medical Center, Portland, OR, USA, 5Institute of Pathology, University of Bern, Bern, Switzerland, 6Pathology, Radboud University Medical Centre Nijmegen, Nijmegen, Netherlands, 7Department of Surgery, University Erlangen-Nu¨rnberg, Erlangen, Germany, 8Department of Medical Oncology, Cliniques Universitaires St. Luc, Brussels, Belgium, 9Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA, 10Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, 11Pathology, General Faculty Hospital, VFN Charles University, Prague, Czech Republic, 12Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan, 13Cancer Biology, The Gujarat Cancer & Research Institute, Ahmedabad, India, 14Institute for Cancer Research, School of Basic Medical Science, Department of Pathology of the First Affiliated Hospital, Health Science Center of Xi’an Jiaotong University, Xian, China, 15Cellular Signaling Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan, 16Refuge Biotechnologies, Refuge Biotechnologies, Menlo Park, USA, 17 Melanoma, Cancer Immunotherapy and Innovative Therapy Unit, Instituto Nazionale Tumori – I.R.C.C.S - Fondazione Pascale, Naples, Italy, 18Laboratory of Molecular and Tumor Immunology, Earle A. Chiles Research Institute at the Robert W. Franz Cancer Center, Portland, OR, USA R is an in vitro diagnostic test that predicts the risk of Background: ImmunoscoreV relapse in patients with Colon Cancer (CC) by measuring the host immune response at the tumor site. It is an immune risk-assessment tool providing independent and superior prognostic value than traditional histopathological risk parameters, and is intended to be used as an adjunct to the TNM classification. Currently, Immunoscore plays a critical role to guide post-surgery decisions in stage II & III CC patients. In stage I, survival rates are high and adjuvant chemotherapy is not typically recommended. However, approximately 10% of stage I CC tumors will recur even after surgical resection. Methods: A subgroup analysis was performed on the stage I patients (n ¼ 451) from the Immunoscore international validation study (Page`s et al. The Lancet 2018). Patients were classified by Immunoscore based on pre-defined cutoffs, either in 5 (IS 04) or in 3 categories: IS Low (IS0-1), Intermediate (IS 2), High (IS 3-4). Time to recurrence (TTR) was compared between Immunoscore categories. Results: Immunoscore Low, Intermediate and High were observed in 14%, 47% and 39% of the cohort, respectively. Immunoscore was positively and significantly correlated with TTR. When adjusting the model with Immunoscore, age, gender, T-stage sidedness and MSI, Immunoscore remained the sole significant parameter (stratified by participating center HRlow vs high¼7.82; 95% CI 1.49 41.01; p ¼ 0.015). In multivariate analysis, the variable with the most important relative contribution to the risk (Chi2) was Immunoscore. The robust correlation between Immunoscore classification and TTR was further corroborated by a separate analysis of the same cohort distributed into five IS categories. In MSS stage I patients, TTR rates at 5 years were 100%, 98.1%, 93.5%, 85.4%, 87.5% for IS4, IS3, IS2, IS1, IS0, respectively. R is a robust prognostic indicator of the risk of recurrence Conclusions: ImmunoscoreV in stage I CC. This risk assessment tool reliably identifies a sub-group of patients with an increased risk of relapse for whom a more intensive surveillance program after curative resection may be recommended. Legal entity responsible for the study: SITC (Society for ImmunoTherapy of Cancer) / INSERM. Funding: Grants from National Institute of Health and Medical Research (INSERM), the LabEx Immuno-oncology, the Transcan ERAnet European project, Association pour la Recherche contre le Cancer, CARPEM, AP-HP, INCA translationnel, JapanAMED (P-DIRECT) and MEXT (Grants-in-aid for Scientific Research-S), and Ministry of Health of the Czech Republic (AZV CR 15-28188A) Progres Q25-LF1. Disclosure: J. Galon: Advisory / Consultancy, Shareholder / Stockholder / Stock options, Co-
founder : HalioDx; Research grant / Funding (institution): Perkin-Elmer; Advisory / Consultancy, Research grant / Funding (institution): IObiotech; Advisory / Consultancy, Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Imcheck Therapeutics; Advisory / Consultancy: BMS; Advisory / Consultancy: Northwest Biotherapeutics; Advisory / Consultancy: Amgen; Advisory / Consultancy: Gilead; Advisory / Consultancy: CatalYm GmbH; Advisory / Consultancy: Sanofi; Licensing / Royalties, Patent holder: INSERM. F. Hermitte: Shareholder / Stockholder / Stock options, Full / Part-time employment, Co-founder : HalioDx. B.
Mlecnik: Licensing / Royalties, Patent holder: INSERM. F. Page`s: Licensing / Royalties, Patent holder: INSERM. All other authors have declared no conflicts of interest.
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A multicenter phase II study of neoadjuvant FOLFOXIRI followed by concurrent capecitabine and radiotherapy for high risk rectal cancer: A final report
G. Lam1, M. Tong2, J. Lee3, S. Chu3, D.C. Ng4, D.C.M. Lam2, C. Cho5, E.H. Hung5, L. Li2, W.M. Ho2, E.P. Hui2, A.W. Chan6, S. Hon7, T. Mak3, S. Ng3, J. Suen2, F. Mo2, B.B.Y. Ma2 1 Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China, 2 Department of Clinical Oncology, State Key Laboratory of Translational Oncology, Sir YK Pao Cancer Center, Hong Kong Cancer Institute, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China, 3Department of Surgery, Prince of Wales Hospital, Hong Kong, China, 4Department of Surgery, North District Hospital, Hong Kong, China, 5Dept of Imaging & Interventional Radiology, Prince of Wales Hospital, Hong Kong, China, 6Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China, 7Department of Surgery, Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China Background: We investigated the feasibility of adding FOLFOXIRI to neoadjuvant chemoradiotherapy for patients (pts) with high risk rectal adenocarcinoma (T3-4 þ/node positivity, threatened margin and/or sphincter involvement). Methods: Eligible patients were treated with 4 cycles of modified FOLFOXIRI (D1: CPT-11 165mg/m2, D1: oxaliplatin 85mg/m2, D1-2 200mg/m2 leucovorin, D1-2 5FU 400mg/m2 30min, then D1-2 5FU 600mg/m2 over 22hrs, with GCSF support), followed by capecitabine (825mg/m2 b.d) given concurrently during pre-operative radiotherapy (CRT, 50.4 Gy, 28 fr, 5 wks). Pts underwent surgery at planned 8-10 weeks after CRT, followed by adjuvant chemo. The primary endpoints were pathologic complete response rate (pCR) and objective response rate (ORR, RECIST ver 1.1). Results: 40 eligible pts were enrolled (median age 60 yrs; male:female¼82%:18%), 1 pt was excluded before starting treatment. Baseline stage distribution was stage II (10.2%), IIIB (64.1%) and IIIC (25.7%). Of the 39 pts evaluated for response (ITT), ORR to FOLFOXIRI was 38.5% (15 PRs, 24 SDs); ORR to CRT was 64.1% (25 PRs, 9 SDs, 1 PD, 4NA). Total of 28 pt (out of 38 evaluated, 73.7%) had a reduced overall TNM stage. Of the 27 pts who underwent surgery (18.5% had permanent stoma), pCR rate was 25.9%, 26 pts had negative and 1 pt had close margin, respectively. At median follow-up of 30.2 months, the 2-yr overall survival and relapse-free rates were 79.3% and 82.8%, respectively. The top three most common grade 3-4 toxicities: (1) To FOLFOXIRI were diarrhea (12%), neutropenia (7.7%) and hyponatremia (5.1%); (2) To CRT – diarrhea (2.5%), RT-dermatitis (2.5%) and rectal hemorrhage (2.5%). No treatment-related deaths or perioperative mortality were encountered. Conclusions: In summary, neoadjuvant FOLFOXIRI followed by Cape-RT for high risk rectal cancer is feasible and the pCR rate compares favorably with the historic rate of 13.8% with CRT alone (Yeung et al. Hong Kong Med J 2016;22) This strategy is being evaluated in a randomized study. Clinical trial identification: NCT01941641. Legal entity responsible for the study: The Chinese University of Hong Kong. Funding: Hong Kong Research Grant Council General Research Fund 471613. Disclosure: All authors have declared no conflicts of interest.
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The clinical usefulness of a new fat-dissociation method to detect lymph nodes from surgically resected specimen in colorectal cancer: Prospective randomized study
S. Fujino1, N. Miyoshi1, M. Ohue2, M. Yasui2, M. Sakon2, N. Matsuura2 Gastroenterological Surgery, Osaka Univ. / OICI, Suita, Japan, 2Surgery, Osaka International Cancer Institute, Osaka, Japan
1
Background: Pathological examination is essential to determine the cancer stage in colorectal cancer (CRC) patients, and histological examination of lymph nodes plays a pivotal role in the staging process. We previously reported a new fat-dissociation method (FM) to detect lymph nodes from surgically resected mesentery. It can reduce a fat volume of the mesentery and visualize a structure of vessels and lymph nodes. In this study we examined the effectiveness of the FM compared with a conventional palpation method in CRC. Methods: A single center, open-label, randomized controlled study was performed at Osaka International Cancer Institute (OICC) in Japan from January, 2014, to December, 2014. Randomization was done via a computer-generated permuted-block sequence, and was stratified by surgical procedures and the dissection area of lymph
C European Society for Medical Oncology 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V
All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_9/mdz421/5638386 by Jean and Alexander Heard Library user on 01 January 2020
GASTROINTESTINAL TUMOURS, COLORECTAL
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Immunoscore predicts significant differences in time to recurrence in stage I colon cancer patients
J. Galon1, F. Hermitte2, B. Mlecnik1, F. Marliot3, C. Bifulco4, A. Lugli5, I. Nagtegaal6, A. Hartmann7, M. van den Eynde8, M. Roehrl9, P. Ohashi10, E. Zavadova11, T. Torigoe12, P. Patel13, Y. Wang14, Y. Kawakami15, F. Marincola16, P. Ascierto17, B. Fox18, F. Page`s3 1 Laboratory of Integrative Cancer Immunology, INSERM, Sorbonne Universite´, Sorbonne Paris Cite´, Universite´ Paris Descartes, Universite´ Paris Diderot, Centre de Recherche des Cordeliers, Paris, France, 2Medical Affairs, HalioDx, Marseille, France, 3Laboratory of Immunology, AP-HP, Georges Pompidou European Hospital, Paris, France, 4Department of Pathology, Providence Portland Medical Center, Portland, OR, USA, 5Institute of Pathology, University of Bern, Bern, Switzerland, 6Pathology, Radboud University Medical Centre Nijmegen, Nijmegen, Netherlands, 7Department of Surgery, University Erlangen-Nu¨rnberg, Erlangen, Germany, 8Department of Medical Oncology, Cliniques Universitaires St. Luc, Brussels, Belgium, 9Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA, 10Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, 11Pathology, General Faculty Hospital, VFN Charles University, Prague, Czech Republic, 12Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan, 13Cancer Biology, The Gujarat Cancer & Research Institute, Ahmedabad, India, 14Institute for Cancer Research, School of Basic Medical Science, Department of Pathology of the First Affiliated Hospital, Health Science Center of Xi’an Jiaotong University, Xian, China, 15Cellular Signaling Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan, 16Refuge Biotechnologies, Refuge Biotechnologies, Menlo Park, USA, 17 Melanoma, Cancer Immunotherapy and Innovative Therapy Unit, Instituto Nazionale Tumori – I.R.C.C.S - Fondazione Pascale, Naples, Italy, 18Laboratory of Molecular and Tumor Immunology, Earle A. Chiles Research Institute at the Robert W. Franz Cancer Center, Portland, OR, USA R is an in vitro diagnostic test that predicts the risk of Background: ImmunoscoreV relapse in patients with Colon Cancer (CC) by measuring the host immune response at the tumor site. It is an immune risk-assessment tool providing independent and superior prognostic value than traditional histopathological risk parameters, and is intended to be used as an adjunct to the TNM classification. Currently, Immunoscore plays a critical role to guide post-surgery decisions in stage II & III CC patients. In stage I, survival rates are high and adjuvant chemotherapy is not typically recommended. However, approximately 10% of stage I CC tumors will recur even after surgical resection. Methods: A subgroup analysis was performed on the stage I patients (n ¼ 451) from the Immunoscore international validation study (Page`s et al. The Lancet 2018). Patients were classified by Immunoscore based on pre-defined cutoffs, either in 5 (IS 04) or in 3 categories: IS Low (IS0-1), Intermediate (IS 2), High (IS 3-4). Time to recurrence (TTR) was compared between Immunoscore categories. Results: Immunoscore Low, Intermediate and High were observed in 14%, 47% and 39% of the cohort, respectively. Immunoscore was positively and significantly correlated with TTR. When adjusting the model with Immunoscore, age, gender, T-stage sidedness and MSI, Immunoscore remained the sole significant parameter (stratified by participating center HRlow vs high¼7.82; 95% CI 1.49 41.01; p ¼ 0.015). In multivariate analysis, the variable with the most important relative contribution to the risk (Chi2) was Immunoscore. The robust correlation between Immunoscore classification and TTR was further corroborated by a separate analysis of the same cohort distributed into five IS categories. In MSS stage I patients, TTR rates at 5 years were 100%, 98.1%, 93.5%, 85.4%, 87.5% for IS4, IS3, IS2, IS1, IS0, respectively. R is a robust prognostic indicator of the risk of recurrence Conclusions: ImmunoscoreV in stage I CC. This risk assessment tool reliably identifies a sub-group of patients with an increased risk of relapse for whom a more intensive surveillance program after curative resection may be recommended. Legal entity responsible for the study: SITC (Society for ImmunoTherapy of Cancer) / INSERM. Funding: Grants from National Institute of Health and Medical Research (INSERM), the LabEx Immuno-oncology, the Transcan ERAnet European project, Association pour la Recherche contre le Cancer, CARPEM, AP-HP, INCA translationnel, JapanAMED (P-DIRECT) and MEXT (Grants-in-aid for Scientific Research-S), and Ministry of Health of the Czech Republic (AZV CR 15-28188A) Progres Q25-LF1. Disclosure: J. Galon: Advisory / Consultancy, Shareholder / Stockholder / Stock options, Co-
founder : HalioDx; Research grant / Funding (institution): Perkin-Elmer; Advisory / Consultancy, Research grant / Funding (institution): IObiotech; Advisory / Consultancy, Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Imcheck Therapeutics; Advisory / Consultancy: BMS; Advisory / Consultancy: Northwest Biotherapeutics; Advisory / Consultancy: Amgen; Advisory / Consultancy: Gilead; Advisory / Consultancy: CatalYm GmbH; Advisory / Consultancy: Sanofi; Licensing / Royalties, Patent holder: INSERM. F. Hermitte: Shareholder / Stockholder / Stock options, Full / Part-time employment, Co-founder : HalioDx. B.
Mlecnik: Licensing / Royalties, Patent holder: INSERM. F. Page`s: Licensing / Royalties, Patent holder: INSERM. All other authors have declared no conflicts of interest.
79O
A multicenter phase II study of neoadjuvant FOLFOXIRI followed by concurrent capecitabine and radiotherapy for high risk rectal cancer: A final report
G. Lam1, M. Tong2, J. Lee3, S. Chu3, D.C. Ng4, D.C.M. Lam2, C. Cho5, E.H. Hung5, L. Li2, W.M. Ho2, E.P. Hui2, A.W. Chan6, S. Hon7, T. Mak3, S. Ng3, J. Suen2, F. Mo2, B.B.Y. Ma2 1 Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China, 2 Department of Clinical Oncology, State Key Laboratory of Translational Oncology, Sir YK Pao Cancer Center, Hong Kong Cancer Institute, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China, 3Department of Surgery, Prince of Wales Hospital, Hong Kong, China, 4Department of Surgery, North District Hospital, Hong Kong, China, 5Dept of Imaging & Interventional Radiology, Prince of Wales Hospital, Hong Kong, China, 6Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China, 7Department of Surgery, Alice Ho Miu Ling Nethersole Hospital, Hong Kong, China Background: We investigated the feasibility of adding FOLFOXIRI to neoadjuvant chemoradiotherapy for patients (pts) with high risk rectal adenocarcinoma (T3-4 þ/node positivity, threatened margin and/or sphincter involvement). Methods: Eligible patients were treated with 4 cycles of modified FOLFOXIRI (D1: CPT-11 165mg/m2, D1: oxaliplatin 85mg/m2, D1-2 200mg/m2 leucovorin, D1-2 5FU 400mg/m2 30min, then D1-2 5FU 600mg/m2 over 22hrs, with GCSF support), followed by capecitabine (825mg/m2 b.d) given concurrently during pre-operative radiotherapy (CRT, 50.4 Gy, 28 fr, 5 wks). Pts underwent surgery at planned 8-10 weeks after CRT, followed by adjuvant chemo. The primary endpoints were pathologic complete response rate (pCR) and objective response rate (ORR, RECIST ver 1.1). Results: 40 eligible pts were enrolled (median age 60 yrs; male:female¼82%:18%), 1 pt was excluded before starting treatment. Baseline stage distribution was stage II (10.2%), IIIB (64.1%) and IIIC (25.7%). Of the 39 pts evaluated for response (ITT), ORR to FOLFOXIRI was 38.5% (15 PRs, 24 SDs); ORR to CRT was 64.1% (25 PRs, 9 SDs, 1 PD, 4NA). Total of 28 pt (out of 38 evaluated, 73.7%) had a reduced overall TNM stage. Of the 27 pts who underwent surgery (18.5% had permanent stoma), pCR rate was 25.9%, 26 pts had negative and 1 pt had close margin, respectively. At median follow-up of 30.2 months, the 2-yr overall survival and relapse-free rates were 79.3% and 82.8%, respectively. The top three most common grade 3-4 toxicities: (1) To FOLFOXIRI were diarrhea (12%), neutropenia (7.7%) and hyponatremia (5.1%); (2) To CRT – diarrhea (2.5%), RT-dermatitis (2.5%) and rectal hemorrhage (2.5%). No treatment-related deaths or perioperative mortality were encountered. Conclusions: In summary, neoadjuvant FOLFOXIRI followed by Cape-RT for high risk rectal cancer is feasible and the pCR rate compares favorably with the historic rate of 13.8% with CRT alone (Yeung et al. Hong Kong Med J 2016;22) This strategy is being evaluated in a randomized study. Clinical trial identification: NCT01941641. Legal entity responsible for the study: The Chinese University of Hong Kong. Funding: Hong Kong Research Grant Council General Research Fund 471613. Disclosure: All authors have declared no conflicts of interest.
80P
The clinical usefulness of a new fat-dissociation method to detect lymph nodes from surgically resected specimen in colorectal cancer: Prospective randomized study
S. Fujino1, N. Miyoshi1, M. Ohue2, M. Yasui2, M. Sakon2, N. Matsuura2 Gastroenterological Surgery, Osaka Univ. / OICI, Suita, Japan, 2Surgery, Osaka International Cancer Institute, Osaka, Japan
1
Background: Pathological examination is essential to determine the cancer stage in colorectal cancer (CRC) patients, and histological examination of lymph nodes plays a pivotal role in the staging process. We previously reported a new fat-dissociation method (FM) to detect lymph nodes from surgically resected mesentery. It can reduce a fat volume of the mesentery and visualize a structure of vessels and lymph nodes. In this study we examined the effectiveness of the FM compared with a conventional palpation method in CRC. Methods: A single center, open-label, randomized controlled study was performed at Osaka International Cancer Institute (OICC) in Japan from January, 2014, to December, 2014. Randomization was done via a computer-generated permuted-block sequence, and was stratified by surgical procedures and the dissection area of lymph
C European Society for Medical Oncology 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V
All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_9/mdz421/5638386 by Jean and Alexander Heard Library user on 01 January 2020
GASTROINTESTINAL TUMOURS, COLORECTAL