The association of the chemotherapy response score and homologous recombination deficiency in patients undergoing interval tumor reductive surgery following neoadjuvant chemotherapy

Objectives In patients undergoing interval tumor reductive surgery, a good response to neoadjuvant chemotherapy may limit available tumor for homologous recombination deficiency testing. The objective of this study was to assess whether the chemotherapy response score predicts homologous recombination status. Methods We identified patients with advanced epithelial ovarian cancer (diagnosed January 2019 to 20 June 2023) who received neoadjuvant chemotherapy, underwent interval surgery, and for whom a chemotherapy response score was reported (1=no or minimal tumor response, 2=appreciable tumor response, 3=complete or near complete response with no residual tumor). Comparisons were made using ANOVAs or Kruskal-Wallis test for continuous variables and χ 2 or Fisher’s exact test for categorical variables. Results The cohort consisted of 234 patients with advanced ovarian cancer who underwent interval surgery following neoadjuvant chemotherapy. Of those who underwent germline genetic testing, 22% (51/232) had a pathogenic BRCA1 or BRCA2 mutation and of those with tumors sent for testing, 65% were found to have homologous recombination deficiency (66/146). With increasing chemotherapy response scores, a higher likelihood of a complete gross resection was observed (50% (chemotherapy response score, CRS 1) vs 77% (CRS 2) vs 88% (CRS 3), p<0.001). On multivariable analysis, CRS 2 (adjusted odds ratio=3.28, 95% CI 1.12 to 9.60, p=0.03) and CRS 3 (5.83, 1.79 to 18.93, p=0.003) were independently associated with homologous recombination deficiency compared with CRS 1. Conclusion A positive response to chemotherapy at the time of interval tumor reductive surgery defined by the chemotherapy response score was associated with homologous recombination status and the likelihood of achieving a complete gross resection.