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. 2022 Jun;165(3):560-567.
doi: 10.1016/j.ygyno.2021.11.019. Epub 2022 Mar 30.

The genomic landscape of low-grade serous ovarian/peritoneal carcinoma and its impact on clinical outcomes

David M Gershenson  1 , Charlotte C Sun  2 , Shannon N Westin  3 , Mostafa Eyada  4 , Lauren P Cobb  5 , Lisa C Nathan  6 , Anil K Sood  7 , Anais Malpica  8 , Robert T Hillman  9 , Kwong K Wong  10
Affiliations

The genomic landscape of low-grade serous ovarian/peritoneal carcinoma and its impact on clinical outcomes

David M Gershenson et al. Gynecol Oncol. 2022 Jun.

Abstract

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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Conflict of interest statement

Declaration of competing interest Dr. Gershenson reported being a shareholder in Johnson & Johnson, Procter and Gamble, Biogen, Inc., and Bristol Myers Squibb; receiving royalties from Elsevier and UpToDate; consulting for Genentech and Springworks; and research support from Novartis and NRG Oncology, all of which are outside the submitted work. Dr. Westin reported consulting for AstraZeneca, Circulogene, Clovis Oncology, Eisai, GSK/Tesaro, Merck, Novartis, Pfizer, Roche/Genentech, and Zentalis. She reported research support from AstraZeneca, Bayer, Bio-Path, Clovis Oncology, Continga Pharmaceuticals, Mereo, Novartis, Roche/Genentech, and GSK/Tesaro. Dr. Sood reported consulting for AstraZeneca, Kiyatec, and Merck, research; support from M-Trap; and being a shareholder in BioPath. Drs. Sun, Hillman, Eyada, Wong, Malpica, and Cobb and Ms. Nathan report no conflicts of interest.

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