Roy Kessous1, David Octeau1, Kathleen Klein2, Patricia N Tonin3, Celia M T Greenwood4, Manuela Pelmus5, Ido Laskov1, Liron Kogan1, Shannon Salvador1, Susie Lau1, Amber Yasmeen6, Walter H Gotlieb7. 1. Division of Gynecologic Oncology, Segal Cancer Center, Lady Davis Institute of Research, Jewish General Hospital, McGill University, Montreal, Canada. 2. Division of Gynecologic Oncology, Segal Cancer Center, Lady Davis Institute of Research, Jewish General Hospital, McGill University, Montreal, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada. 3. Cancer Research Program, The Research Institute of the McGill University Health Centre, Montreal, QC, Canada; Departments of Medicine and Human Genetics, McGill University, Montreal, QC, Canada. 4. Division of Gynecologic Oncology, Segal Cancer Center, Lady Davis Institute of Research, Jewish General Hospital, McGill University, Montreal, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada; Cancer Research Program, The Research Institute of the McGill University Health Centre, Montreal, QC, Canada; Departments of Medicine and Human Genetics, McGill University, Montreal, QC, Canada. 5. Division of Pathology, Jewish General Hospital, Montréal, Canada. 6. Division of Gynecologic Oncology, Segal Cancer Center, Lady Davis Institute of Research, Jewish General Hospital, McGill University, Montreal, Canada. Electronic address: amber.yasmeen@mail.mcgill.ca. 7. Division of Gynecologic Oncology, Segal Cancer Center, Lady Davis Institute of Research, Jewish General Hospital, McGill University, Montreal, Canada. Electronic address: walter.gotlieb@mcgill.ca.
Abstract
OBJECTIVE: The expression of homologous recombination (HR) genes in high grade ovarian cancer (HGOC) samples from debulking surgeries were correlated to outcomes in patients selected for chemotherapy treatment regimens. STUDY DESIGN: RNA was extracted from 96 fresh frozen tumor samples from debulking surgeries from chemotherapy naïve patients with HGOC (primary derived surgeries (PDS), n = 55) or following neoadjuvant chemotherapy treatment (NACT), n = 41). The samples were selected for high tumor content by a gynecological pathologist, and cancer cell content was further confirmed using a percent tumor content covariate, and mutation score covariate analysis. Gene expression analysis was performed using a tailored NanoString-based Pancancer Pathway Panel. Cox proportional hazard regression models were used to assess the associations between the expression of 19 HR genes and survival. RESULTS: In the PDS group, over-expression of six HR genes (C11orf30, NBN, FANCF, FANCC, FANCB, RAD50) was associated with improved outcome, in contrast to the NACT group where four HR genes (BRCA2, TP53, FANCB, RAD51) were associated with worse outcome. With the adding extent of debulking as a covariate, three HR genes (NBN, FANCF, RAD50), and only one HR gene (RAD51) remained significantly associated with survival in PDS and NACT groups, respectively. CONCLUSION: Distinct HR expression profiles define subgroups associated with overall outcome in patients that are exposed to neoadjuvant chemotherapy and not only chemotherapy-naïve patients.
OBJECTIVE: The expression of homologous recombination (HR) genes in high grade ovarian cancer (HGOC) samples from debulking surgeries were correlated to outcomes in patients selected for chemotherapy treatment regimens. STUDY DESIGN: RNA was extracted from 96 fresh frozen tumor samples from debulking surgeries from chemotherapy naïve patients with HGOC (primary derived surgeries (PDS), n = 55) or following neoadjuvant chemotherapy treatment (NACT), n = 41). The samples were selected for high tumor content by a gynecological pathologist, and cancer cell content was further confirmed using a percent tumor content covariate, and mutation score covariate analysis. Gene expression analysis was performed using a tailored NanoString-based Pancancer Pathway Panel. Cox proportional hazard regression models were used to assess the associations between the expression of 19 HR genes and survival. RESULTS: In the PDS group, over-expression of six HR genes (C11orf30, NBN, FANCF, FANCC, FANCB, RAD50) was associated with improved outcome, in contrast to the NACT group where four HR genes (BRCA2, TP53, FANCB, RAD51) were associated with worse outcome. With the adding extent of debulking as a covariate, three HR genes (NBN, FANCF, RAD50), and only one HR gene (RAD51) remained significantly associated with survival in PDS and NACT groups, respectively. CONCLUSION: Distinct HR expression profiles define subgroups associated with overall outcome in patients that are exposed to neoadjuvant chemotherapy and not only chemotherapy-naïve patients.
Authors: Panagiotis A Konstantinopoulos; Barbara Norquist; Christina Lacchetti; Deborah Armstrong; Rachel N Grisham; Paul J Goodfellow; Elise C Kohn; Douglas A Levine; Joyce F Liu; Karen H Lu; Dorinda Sparacio; Christina M Annunziata Journal: J Clin Oncol Date: 2020-01-27 Impact factor: 44.544
Authors: Michele Moschetta; Stergios Boussios; Elie Rassy; Eleftherios P Samartzis; Gabriel Funingana; Mario Uccello Journal: Ann Transl Med Date: 2020-12