Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Stratification of Homologous Recombination Deficiency-Negative High-Grade Ovarian Cancer by the Type of Peritoneal Spread into Two Groups with Distinct Survival Outcome

Simon Schnaiter
* ORCID logo ,
Esther Schamschula
,
Juliane Laschtowiczka
,
Heidelinde Fiegl
,
Johannes Zschocke
,
Alain Zeimet
,
Katharina Wimmer
ORCID logo ,
Daniel Reimer
Version 1 : Received: 12 April 2024 / Approved: 12 April 2024 / Online: 12 April 2024 (21:20:09 CEST)

How to cite: Schnaiter, S.; Schamschula, E.; Laschtowiczka, J.; Fiegl, H.; Zschocke, J.; Zeimet, A.; Wimmer, K.; Reimer, D. Stratification of Homologous Recombination Deficiency-Negative High-Grade Ovarian Cancer by the Type of Peritoneal Spread into Two Groups with Distinct Survival Outcome. Preprints 2024, 2024040867. https://doi.org/10.20944/preprints202404.0867.v1 Schnaiter, S.; Schamschula, E.; Laschtowiczka, J.; Fiegl, H.; Zschocke, J.; Zeimet, A.; Wimmer, K.; Reimer, D. Stratification of Homologous Recombination Deficiency-Negative High-Grade Ovarian Cancer by the Type of Peritoneal Spread into Two Groups with Distinct Survival Outcome. Preprints 2024, 2024040867. https://doi.org/10.20944/preprints202404.0867.v1

Abstract

Background Homologous recombination deficiency (HRD) evolved into a major diagnostic marker in high grade ovarian cancer (HGOC) predicting the response to poly (Adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and also platinum-based therapy. In addition to HRD, the type of peritoneal tumor spread influences treatment response and patient survival; miliary type tumor spread has poorer predicted outcome than non-miliary type tumor spread. Methods Known methods for HRD assessment were adapted for our technical requirements and the Predictive-value Integrated Genomic Instability Score (PIGIS) for HRD assessment evolved as an outcome. PIGIS was validated in HGOC samples from 122 patients. We used PIGIS to analyze whether the type of tumor spread correlated with HRD status and whether this had an impact on survival. Results We demonstrated that PIGIS can discriminate HRD positive from HRD negative samples. Tumors with miliary tumor spread are HRD negative and have a very bad prognosis with a progression free survival (PFS) of 15.6 months and an overall survival (OS) of 3.9 years. However, HRD negative non-miliary spreading tumors in our cohort had a much better prognosis (PFS 35.4 months, OS 8.9 years), similar to HRD positive tumors (PFS 34.7 months, OS 8.9 years). Conclusions Our results indicate that in a predominantly PARPi naïve cohort the type of tumor spread might be a better predictor of response to platinum sensitivity than HRD. It remains to be determined, whether this also applies for sensitivity to PARPi.

Keywords

Personalized medicine; genomic instability; Miliary disease; epithelial ovarian cancer; PARP inhibitor; staging

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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