TY - JOUR
T1 - The genomic landscape of low-grade serous ovarian/peritoneal carcinoma and its impact on clinical outcomes
AU - Gershenson, David M.
AU - Sun, Charlotte C.
AU - Westin, Shannon N.
AU - Eyada, Mostafa
AU - Cobb, Lauren P.
AU - Nathan, Lisa C.
AU - Sood, Anil K.
AU - Malpica, Anais
AU - Hillman, Robert T.
AU - Wong, Kwong K.
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2022/6
Y1 - 2022/6
N2 - Objective: Low-grade serous carcinoma (LGSOC) is a rare epithelial ovarian/peritoneal cancer characterized by younger age at diagnosis, relative chemoresistance, prolonged overall survival (OS), and mutations in the mitogen activated protein kinase (MAPK) pathway compared to high-grade serous carcinoma. We describe the genomic profile of LGSOC by next generation sequencing (NGS) and evaluated its potential relationship to clinical outcomes. Methods: The study included 215 women with LGSOC with: 1) pathologically confirmed LGSOC, 2) availability of NGS data, and 3) adequate clinical data. Clinical subgroups were compared for progression-free survival (PFS) and OS. Multivariable Cox regression analysis was performed. Results: Median age at diagnosis was 46.6 years. The majority had a stage III ovarian primary. One or more mutations were identified in 140 (65.1%) cases; 75 (34.9%) had none. The most common mutations were KRAS (n = 71; 33.0%), NRAS (n = 24; 11.2%), and BRAF (n = 18; 8.4%). Patients with MAPK-mutated tumors (n = 113) (52.6%) had a significantly longer OS compared to those with tumors lacking MAPK pathway mutations (n = 102) (47.4%) [median OS, 147.8 months (95% CI,119.0–176.6) versus 89.5 months (95% CI, 61.4–117.7) (p = 0.01)], respectively. Median OS for patients with MAPK-mutated tumors was also significantly better than for patients whose tumors had no mutations (n = 75) [median OS, 147.8 months (95% CI, 119.0–176.6) versus 78.0 months (95% CI, 57.6–98.3)], respectively (p = 0.001). Median OS for patients with non-MAPK-mutated tumors (n = 27) was 125.1 months (95% CI, 83.9–166.3). In multivariable analysis, having a MAPK mutation was associated with improved OS. Conclusions: Patients with MAPK-mutated tumors have a significantly improved OS compared to those without MAPK-mutated tumors.
AB - Objective: Low-grade serous carcinoma (LGSOC) is a rare epithelial ovarian/peritoneal cancer characterized by younger age at diagnosis, relative chemoresistance, prolonged overall survival (OS), and mutations in the mitogen activated protein kinase (MAPK) pathway compared to high-grade serous carcinoma. We describe the genomic profile of LGSOC by next generation sequencing (NGS) and evaluated its potential relationship to clinical outcomes. Methods: The study included 215 women with LGSOC with: 1) pathologically confirmed LGSOC, 2) availability of NGS data, and 3) adequate clinical data. Clinical subgroups were compared for progression-free survival (PFS) and OS. Multivariable Cox regression analysis was performed. Results: Median age at diagnosis was 46.6 years. The majority had a stage III ovarian primary. One or more mutations were identified in 140 (65.1%) cases; 75 (34.9%) had none. The most common mutations were KRAS (n = 71; 33.0%), NRAS (n = 24; 11.2%), and BRAF (n = 18; 8.4%). Patients with MAPK-mutated tumors (n = 113) (52.6%) had a significantly longer OS compared to those with tumors lacking MAPK pathway mutations (n = 102) (47.4%) [median OS, 147.8 months (95% CI,119.0–176.6) versus 89.5 months (95% CI, 61.4–117.7) (p = 0.01)], respectively. Median OS for patients with MAPK-mutated tumors was also significantly better than for patients whose tumors had no mutations (n = 75) [median OS, 147.8 months (95% CI, 119.0–176.6) versus 78.0 months (95% CI, 57.6–98.3)], respectively (p = 0.001). Median OS for patients with non-MAPK-mutated tumors (n = 27) was 125.1 months (95% CI, 83.9–166.3). In multivariable analysis, having a MAPK mutation was associated with improved OS. Conclusions: Patients with MAPK-mutated tumors have a significantly improved OS compared to those without MAPK-mutated tumors.
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U2 - 10.1016/j.ygyno.2021.11.019
DO - 10.1016/j.ygyno.2021.11.019
M3 - Article
C2 - 35606067
AN - SCOPUS:85130485829
SN - 0090-8258
VL - 165
SP - 560
EP - 567
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 3
ER -