Cuong P Duong1,2, Nicholas J Clemons3,4, Carlos S Cabalag5,6,7, Owen W J Prall8, John Ciciulla9, Laurence A Galea9, Niko Thio10, Madawa Jayawardana10,2, Trishe Y M Leong11,12, Julia V Milne10,2, Kenji M Fujihara10,2, Lynn Chong13,14, Michael W Hii13,14, Gisela Mir Arnau10, Paul J Neeson10,2, Wayne A Phillips10,2,13. 1. Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. 2. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia. 3. Cancer Research, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. Nicholas.Clemons@petermac.org. 4. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia. Nicholas.Clemons@petermac.org. 5. Cancer Research, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. carloscabalag@gmail.com. 6. Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. carloscabalag@gmail.com. 7. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia. carloscabalag@gmail.com. 8. Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. 9. Department of Anatomical Pathology, Melbourne Pathology, Sonic Healthcare, Melbourne, VIC, Australia. 10. Cancer Research, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. 11. Department of Anatomical Pathology, St Vincent's Hospital, Fitzroy, VIC, Australia. 12. Department of Clinical Pathology, University of Melbourne, Parkville, VIC, Australia. 13. Department of Surgery (St Vincent's Hospital), University of Melbourne, Fitzroy, VIC, Australia. 14. Department of Upper GI and Hepatobiliary Surgery, St Vincent's Hospital, Fitzroy, Victoria, Australia.
Abstract
BACKGROUND: In esophageal cancer (EC), there is a paucity of knowledge regarding the interplay between the tumor immune microenvironment and response to neoadjuvant treatment and, therefore, which factors may influence outcomes. Thus, our goal was to investigate the changes in the immune microenvironment with neoadjuvant treatment in EC by assessing the expression of immune related genes and their association with prognosis. METHODS: We examined the transcriptome of paired pre- and post-neoadjuvant treated EC specimens. Based on these findings, we validated the presence of tumor-infiltrating neutrophils using CD15+ immunohistochemistry in a discovery cohort of patients with residual pathologic disease. We developed a nomogram as a predictor of progression-free survival (PFS) incorporating the variables CD15+ cell count, tumor regression grade, and tumor grade. RESULTS: After neoadjuvant treatment, there was an increase in genes related to myeloid cell differentiation and a poor prognosis associated with high neutrophil (CD15+) counts. Our nomogram incorporating CD15+ cell count was predictive of PFS with a C-index of 0.80 (95% confidence interval [CI] 0.68-0.9) and a concordance probability estimate (CPE) of 0.77 (95% CI 0.69-0.86), which indicates high prognostic ability. The C-index and CPE of the validation cohort were 0.81 (95% CI 0.69-0.91) and 0.78 (95% CI 0.7-0.86), respectively. CONCLUSIONS: Our nomogram incorporating CD15+ cell count can potentially be used to identify patients at high risk of recurrent disease and thus stratify patients who will benefit most from adjuvant treatment.
BACKGROUND: In esophageal cancer (EC), there is a paucity of knowledge regarding the interplay between the tumor immune microenvironment and response to neoadjuvant treatment and, therefore, which factors may influence outcomes. Thus, our goal was to investigate the changes in the immune microenvironment with neoadjuvant treatment in EC by assessing the expression of immune related genes and their association with prognosis. METHODS: We examined the transcriptome of paired pre- and post-neoadjuvant treated EC specimens. Based on these findings, we validated the presence of tumor-infiltrating neutrophils using CD15+ immunohistochemistry in a discovery cohort of patients with residual pathologic disease. We developed a nomogram as a predictor of progression-free survival (PFS) incorporating the variables CD15+ cell count, tumor regression grade, and tumor grade. RESULTS: After neoadjuvant treatment, there was an increase in genes related to myeloid cell differentiation and a poor prognosis associated with high neutrophil (CD15+) counts. Our nomogram incorporating CD15+ cell count was predictive of PFS with a C-index of 0.80 (95% confidence interval [CI] 0.68-0.9) and a concordance probability estimate (CPE) of 0.77 (95% CI 0.69-0.86), which indicates high prognostic ability. The C-index and CPE of the validation cohort were 0.81 (95% CI 0.69-0.91) and 0.78 (95% CI 0.7-0.86), respectively. CONCLUSIONS: Our nomogram incorporating CD15+ cell count can potentially be used to identify patients at high risk of recurrent disease and thus stratify patients who will benefit most from adjuvant treatment.
Authors: Shona Hendry; Roberto Salgado; Thomas Gevaert; Prudence A Russell; Tom John; Bibhusal Thapa; Michael Christie; Koen van de Vijver; M V Estrada; Paula I Gonzalez-Ericsson; Melinda Sanders; Benjamin Solomon; Cinzia Solinas; Gert G G M Van den Eynden; Yves Allory; Matthias Preusser; Johannes Hainfellner; Giancarlo Pruneri; Andrea Vingiani; Sandra Demaria; Fraser Symmans; Paolo Nuciforo; Laura Comerma; E A Thompson; Sunil Lakhani; Seong-Rim Kim; Stuart Schnitt; Cecile Colpaert; Christos Sotiriou; Stefan J Scherer; Michail Ignatiadis; Sunil Badve; Robert H Pierce; Giuseppe Viale; Nicolas Sirtaine; Frederique Penault-Llorca; Tomohagu Sugie; Susan Fineberg; Soonmyung Paik; Ashok Srinivasan; Andrea Richardson; Yihong Wang; Ewa Chmielik; Jane Brock; Douglas B Johnson; Justin Balko; Stephan Wienert; Veerle Bossuyt; Stefan Michiels; Nils Ternes; Nicole Burchardi; Stephen J Luen; Peter Savas; Frederick Klauschen; Peter H Watson; Brad H Nelson; Carmen Criscitiello; Sandra O'Toole; Denis Larsimont; Roland de Wind; Giuseppe Curigliano; Fabrice André; Magali Lacroix-Triki; Mark van de Vijver; Federico Rojo; Giuseppe Floris; Shahinaz Bedri; Joseph Sparano; David Rimm; Torsten Nielsen; Zuzana Kos; Stephen Hewitt; Baljit Singh; Gelareh Farshid; Sibylle Loibl; Kimberly H Allison; Nadine Tung; Sylvia Adams; Karen Willard-Gallo; Hugo M Horlings; Leena Gandhi; Andre Moreira; Fred Hirsch; Maria V Dieci; Maria Urbanowicz; Iva Brcic; Konstanty Korski; Fabien Gaire; Hartmut Koeppen; Amy Lo; Jennifer Giltnane; Marlon C Rebelatto; Keith E Steele; Jiping Zha; Kenneth Emancipator; Jonathan W Juco; Carsten Denkert; Jorge Reis-Filho; Sherene Loi; Stephen B Fox Journal: Adv Anat Pathol Date: 2017-11 Impact factor: 3.875
Authors: Alexander R Moschen; Timon E Adolph; Romana R Gerner; Verena Wieser; Herbert Tilg Journal: Trends Endocrinol Metab Date: 2017-02-15 Impact factor: 12.015
Authors: Mark Ayers; Jared Lunceford; Michael Nebozhyn; Erin Murphy; Andrey Loboda; David R Kaufman; Andrew Albright; Jonathan D Cheng; S Peter Kang; Veena Shankaran; Sarina A Piha-Paul; Jennifer Yearley; Tanguy Y Seiwert; Antoni Ribas; Terrill K McClanahan Journal: J Clin Invest Date: 2017-06-26 Impact factor: 14.808