Abstract 4135: Initial clinicopathologic and molecular characterization of minimal residual disease detected by second look laparoscopy after completion of frontline surgery and chemotherapy in patients with advanced stage ovarian cancer
Authors: Nitecki Roni , Dang Minghao , Lee Sanghoon , Fellman Bryan , Rauh-hain J Alejandro , Taylor Jolyn , Ramondetta Lois , Grinsfelder Michaela , Cobb Lauren , Boruta David M. , Soliman Pamela T. , Shafer Aaron , Fleming Nicole D. , Westin Shannon N. , Sood Anil K. , Tanguma Chris , Ramrez Pedro T. , Lu Karen H. , Wang Linghua , Jazaeri Amir A. 
Published: June 2022

Abstract
Background: Despite high rates of remission after frontline management, most patients with advanced stage ovarian cancer recur. Second look laparoscopy (SLL) can provide more sensitive detection of minimal residual disease (MRD) allowing for more individualized prognostication and possible therapeutic intervention. It may also assess tumor biology and microenvironment associated with undetectable chemoresistant MRD phase of ovarian cancer. The objective of this study was to determine SLL feasibility, and clinicopathologic and molecular characteristics of MRD after frontline therapy in ovarian cancer.
Methods: SLL was offered to patients with stage III-IV high grade epithelial ovarian cancer who achieved complete response after frontline surgery and 6 cycles of carboplatin and paclitaxel chemotherapy. Patients were offered standard of care or investigational management options based on homologous recombination deficiency (HRD) and MRD status at SLL. Preliminary translational studies included RNAseq for comparison of serial, matched tumor from primary or interval TRS and SLL derived MRD+ biopsies at the time of SLL. In addition, Nanostring analyses of SLL surgical biopsies both with and without residual tumor were performed. Molecular profiling employed hierarchical clustering, principle component analysis, non-parametric testing, and pathway analyses.
Results: Between 4/2017- 7/2021, 39 patients underwent SLL. The majority had stage III disease (74%), high grade serous histology (90%) and underwent neoadjuvant chemotherapy with interval tumor reductive surgery (TRS; 54%). MRD was present in 49% (n=19) of patients and was more frequent among neoadjuvant chemotherapy recipients (73% vs 26%, P=0.015) and patients with homologous recombination proficient tumors (81% vs 25%, P=0.01). Most patients without MRD were dispositioned to observation; 4 patients with HRD received a PARP inhibitor per standard of care. All other patients with MRD received bevacizumab as part of a clinical trial, except for one patient who received a PARP inhibitor. Median follow-up was 6.74 months (range 0.66 - 28.62). Presence of MRD was associated with worse PFS (HR 3.7, 95% CI 1.3- 10.9; 5.5 vs 24.6 months; P= 0.02). Based on transcriptional signature, MRD are immunologically distinct from untreated tumors or those collected at interval TRS (after 3 cycles of chemo) but also displayed heterogeneity with two distinct subclusters.
Conclusions: SLL to assess for MRD has potential to further individualize post-frontline therapy, and identify patients at high risk for progression for early intervention clinical trials. Transcriptional profiling suggests that MRD phase of ovarian cancer is characterized by a distinct, heterogeneous, and evolving tumor and immune microenvironment.
Citation Format: Roni Nitecki, Minghao Dang, Sanghoon Lee, Bryan Fellman, J Alejandro Rauh-hain, Jolyn Taylor, Lois Ramondetta, Michaela Grinsfelder, Lauren Cobb, David M. Boruta, Pamela T. Soliman, Aaron Shafer, Nicole D. Fleming, Shannon N. Westin, Anil K. Sood, Chris Tanguma, Pedro T. Ramrez, Karen H. Lu, Linghua Wang, Amir A. Jazaeri. Initial clinicopathologic and molecular characterization of minimal residual disease detected by second look laparoscopy after completion of frontline surgery and chemotherapy in patients with advanced stage ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4135.