Germline BRCA, Chemotherapy response scores, and survival in the neoadjuvant treatment of ovarian cancer

Abstract Background To analyze the effects of BRCA1/2 mutations on chemotherapy response scores (CRS) and survival in a cohort of patients with advanced-stage ovarian cancer who were treated with neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS). Methods We retrospectively reviewed the medical records of 169 high-grade serous ovarian cancer patients who underwent a germline BRCA1/2 test and received three cycles of NAC at the Yonsei Cancer Center from 2006 to 2018. Chemotherapy response scores were compared in patients with and without BRCA1/2 mutations. The effects of BRCA1/2 mutations and CRS on survival were evaluated. Results BRCA1/2 mutations were detected in 47 (28.1%) of the 169 patients. Overall, 16 (34.0%) patients with BRCA1/2 mutations had a CRS 3 to chemotherapy compared to scores of 43 in patients (35.2%) without a mutation. Response scores of 3 in patients with BRCA1/2 mutations were not significantly associated with either improved progression-free survival (PFS) ( P = 0.949) or overall survival (OS) ( P = 0.168). However, CRS 3 in patients without BRCA mutations was significantly associated with both improved PFS ( P = 0.030) and OS ( P = 0.039). In patients with CRS1/2, carriers of BRCA1/2 mutations had better PFS ( P = 0.0344) and OS ( P = 0.043) than wild-type BRCA genotype patients. Conclusion In ovarian cancer patients treated with NAC, CRS did not predict survival for BRCA 1/2 mutation carriers but did for BRCA wild-type patients.

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Germline BRCA, Chemotherapy response scores, and survival in the neoadjuvant treatment of ovarian cancer

10.21203/rs.2.17498/v3 ◽

2020 ◽

Author(s):

Yong Jae Lee ◽

Hyun-Soo Kim ◽

John Hoon Rim ◽

Jung-Yun Lee ◽

Eun Ji Nam ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Neoadjuvant Treatment ◽

Progression Free Survival ◽

Cancer Center ◽

Chemotherapy Response ◽

Wild Type ◽

Brca Mutations ◽

Free Survival ◽

Interval Debulking Surgery

Abstract Background To analyze the effects of BRCA1/2 mutations on chemotherapy response scores (CRS) and survival in a cohort of patients with advanced-stage ovarian cancer who were treated with neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS). Methods We retrospectively reviewed the medical records of 169 high-grade serous ovarian cancer patients who underwent a germline BRCA1/2 test and received three cycles of NAC at the Yonsei Cancer Center from 2006 to 2018. Chemotherapy response scores were compared in patients with and without BRCA1/2 mutations. The effects of BRCA1/2 mutations and CRS on survival were evaluated. Results BRCA1/2 mutations were detected in 47 (28.1%) of the 169 patients. Overall, 16 (34.0%) patients with BRCA1/2 mutations had a CRS 3 to chemotherapy compared to scores of 43 in patients (35.2%) without a mutation. Response scores of 3 in patients with BRCA1/2 mutations were not significantly associated with either improved progression-free survival (PFS) ( P = 0.949) or overall survival (OS) ( P = 0.168). However, CRS 3 in patients without BRCA mutations was significantly associated with both improved PFS ( P = 0.030) and OS ( P = 0.039). In patients with CRS1/2, carriers of BRCA1/2 mutations had better PFS ( P = 0.0344) and OS ( P = 0.043) than wild-type BRCA genotype patients. Conclusion In ovarian cancer patients treated with NAC, CRS did not predict survival for BRCA 1/2 mutation carriers but did for BRCA wild-type patients.

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Germline BRCA, Chemotherapy response scores, and survival in the neoadjuvant treatment of ovarian cancer

10.21203/rs.2.17498/v2 ◽

2020 ◽

Author(s):

Yong Jae Lee ◽

Hyun-Soo Kim ◽

John Hoon Rim ◽

Jung-Yun Lee ◽

Eun Ji Nam ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Neoadjuvant Treatment ◽

Progression Free Survival ◽

Cancer Center ◽

Chemotherapy Response ◽

Wild Type ◽

Free Survival ◽

Interval Debulking Surgery ◽

Brca 1

Abstract Background: To analyze the effects of BRCA1/2 mutations on chemotherapy response scores (CRS) and survival in a cohort of patients with advanced-stage ovarian cancer who were treated with neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS).Methods: We retrospectively reviewed the medical records of 169 high-grade serous ovarian cancer patients who underwent a germline BRCA1/2 test and received three cycles of NAC at the Yonsei Cancer Center from 2006 to 2018. Chemotherapy response scores were compared in patients with and without BRCA1/2 mutations. The effects of BRCA1/2 mutations and CRS on survival were evaluated. Results: BRCA1/2 mutations were detected in 47 (28.1%) of the 169 patients. Overall, 16 (34.0%) patients with BRCA1/2 mutations had a CRS 3 to chemotherapy compared to scores of 43 in patients (35.2%) without a mutation. Response scores of 3 in patients with BRCA1/2 mutations were not significantly associated with either improved progression-free survival (PFS) (P = 0.949) or overall survival (OS) (P = 0.168). However, CRS 3 in patients without BRCA mutations was significantly associated with both improved PFS (P = 0.030) and OS (P = 0.039). In patients with CRS1/2, carriers of BRCA1/2 mutations had better PFS (P = 0.0344) and OS (P = 0.043) than wild-type BRCA genotype patients.Conclusion: In ovarian cancer patients treated with NAC, CRS did not predict survival for BRCA 1/2 mutation carriers but did for BRCA wild-type patients.

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The Prognostic and Predictive Role of Somatic BRCA Mutations in Ovarian Cancer: Results from a Multicenter Cohort Study

Diagnostics ◽

10.3390/diagnostics11030565 ◽

2021 ◽

Vol 11 (3) ◽

pp. 565

Author(s):

Angela Toss ◽

Claudia Piombino ◽

Elena Tenedini ◽

Alessandra Bologna ◽

Elisa Gasparini ◽

...

Keyword(s):

Ovarian Cancer ◽

Positive Impact ◽

Progression Free Survival ◽

Molecular Testing ◽

Wild Type ◽

Brca Mutations ◽

Multicenter Cohort Study ◽

Advanced Stages ◽

Predictive Role

Previous research involving epithelial ovarian cancer patients showed that, compared to germline BRCA (gBRCA) mutations, somatic BRCA (sBRCA) mutations present a similar positive impact with regard to overall survival (OS) and platinum and PARP (poly (ADP-ribose) polymerase) inhibitor sensitivity. Nevertheless, molecular testing in these studies did not include copy number variation (CNV) analyses of BRCA genes. The aim of this study was to explore the prognostic and predictive role of sBRCA mutations as compared to gBRCA mutations in patients who were also tested for CNVs. Among the 158 patients included in the study, 17.09% of patients carried a pathogenic or likely pathogenic gBRCA variant and 15.19% of patients presented pathogenetic or likely pathogenic sBRCA variants and/or CNVs. Overall, 81.6% of the patients included in this study were diagnosed with a serous histotype, and 77.2% were in advanced stages. Among women diagnosed in advanced stages, gBRCA patients showed better progression-free survival and OS as compared to sBRCA and wild-type patients, whereas sBRCA patients did not show any advantage in outcome as compared to wild-type patients. In this study, the introduction of CNV analyses increased the detection rate of sBRCA mutations, and the resulting classification among gBRCA, sBRCA and wild-type patients was able to properly stratify the prognosis of OC patients. Particularly, sBRCA mutation patients failed to show any outcome advantage as compared to wild-type patients.

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Prognostic nomogram for progression-free survival in patients with BRCA mutations and platinum-sensitive recurrent ovarian cancer on maintenance olaparib therapy following response to chemotherapy

European Journal of Cancer ◽

10.1016/j.ejca.2021.06.024 ◽

2021 ◽

Vol 154 ◽

pp. 190-200

Author(s):

Angelina Tjokrowidjaja ◽

Michael Friedlander ◽

Sarah J. Lord ◽

Rebecca Asher ◽

Manuel Rodrigues ◽

...

Keyword(s):

Ovarian Cancer ◽

Progression Free Survival ◽

Recurrent Ovarian Cancer ◽

Brca Mutations ◽

Free Survival ◽

Platinum Sensitive ◽

Response To Chemotherapy

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Comparison of Poly (ADP-ribose) Polymerase Inhibitors (PARPis) as Maintenance Therapy for Platinum-Sensitive Ovarian Cancer: Systematic Review and Network Meta-Analysis

Cancers ◽

10.3390/cancers12103026 ◽

2020 ◽

Vol 12 (10) ◽

pp. 3026

Author(s):

Amos Stemmer ◽

Inbal Shafran ◽

Salomon M. Stemmer ◽

Daliah Tsoref

Keyword(s):

Ovarian Cancer ◽

Maintenance Therapy ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Progression Free Survival ◽

Wild Type ◽

Brca Mutations ◽

Increased Risk ◽

Significant Difference ◽

Indirect Comparisons

Background: Three PARPis (olaparib, niraparib and rucaparib) are currently FDA-approved as maintenance therapy in newly diagnosed and recurrent ovarian cancer. However, thus far, no trial has compared the three approved PARPis in the overall population, in patients with BRCA mutations, or in those with wild-type BRCA. Methods: A frequentist network meta-analysis was used for indirect comparisons between the different PARPis with respect to progression free survival (PFS), overall survival (OS), and adverse events. Results: Overall, six randomized clinical trials involving 2,770 patients, were included in the analysis. Results from the indirect comparisons revealed no statistically significant differences between the three PARPis with respect to PFS or OS in the entire population and in patients with mutated and wild-type BRCA, separately. Niraparib showed a statistically significant increased risk for grade 3 and 4 thrombocytopenia (risk-difference [RD] from placebo: 0.3; 95% confidence interval [CI], 0.27‒0.34) and any grade neutropenia (RD from placebo: 0.22; 95% CI, 0.18‒0.25) as compared with the other PARPis. Conclusion: No statistically significant difference was found between the three PARPis with respect to PFS or OS (overall and in subpopulations by BRCA status). There is, however, a statistical difference in toxicity as niraparib is associated with a greater risk for thrombocytopenia and neutropenia.

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A descriptive report of outcomes of primary mucinous ovarian cancer patients receiving either an adjuvant gynecologic or gastrointestinal chemotherapy regimen

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2018-000150 ◽

2019 ◽

Vol 29 (5) ◽

pp. 904-909

Author(s):

Brooke A Schlappe ◽

Qin C Zhou ◽

Roisin O'Cearbhaill ◽

Alexia Iasonos ◽

Robert A Soslow ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Progression Free Survival ◽

Categorical Variables ◽

Continuous Variables ◽

Free Survival ◽

Exact Test ◽

Clinical Criteria ◽

Kaplan Meier

ObjectiveWe described progression-free survival and overall survival in patients with primary mucinous ovarian cancer receiving adjuvant gynecologic versus gastrointestinal chemotherapy regimens.MethodsWe identified all primary mucinous ovarian cancer patients receiving adjuvant gynecologic or gastrointestinal chemotherapy regimens at a single institution from 1994 to 2016. Gynecologic pathologists using strict pathologic/clinical criteria determined diagnosis. Adjuvant therapy was coded as gynecologic or gastrointestinal based on standard agents and schedules. Clinical/pathologic/treatment characteristics were recorded. Wilcoxon rank-sum test was used for continuous variables, and Fisher’s exact test for categorical variables. Progression-free and overall survival were calculated using the Kaplan-Meier method, applying landmark analysis.ResultsOf 62 patients identified, 21 received adjuvant chemotherapy: 12 gynecologic, 9 gastrointestinal. Median age (in years) at diagnosis: 58 (range 25–68) gynecologic cohort, 38 (range 32–68) gastrointestinal cohort (p=0.13). Median body mass index at first post-operative visit: 25 kg/m2(range 18–31) gynecologic cohort, 23 kg/m2(range 18–31) gastrointestinal cohort (p=0.23). History of smoking: 6/12 (50%) gynecologic cohort, 3/9 (33%) gastrointestinal cohort (p=0.66). Stage distribution in gynecologic and gastrointestinal cohorts, respectively: stage I: 9/12 (75%) and 3/9 (33%); stage II: 2/12 (17%) and 1/9 (11%); stage III: 1/12 (8%) and 5/9 (56%) (p=0.06). Grade distribution in gynecologic and gastrointestinal cohorts, respectively: grade 1: 8/12 (67%) and 1/9 (13%); grade 2/3: 4/12 (33%) and 7/9 (88%) (p=0.03). Three-year progression-free survival: 90.9% (95% CI 50.8% to 98.7 %) gynecologic, 53.3% (95% CI 17.7% to 79.6%) gastrointestinal. Three-year overall survival: 90.9% (95% CI 50.8% to 98.7%) gynecologic, 76.2% (95% CI 33.2% to 93.5%) gastrointestinal.ConclusionOngoing international collaborative research may further define associations between chemotherapy regimens and survival.

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