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The association of the chemotherapy response score and homologous recombination deficiency in patients undergoing interval tumor reductive surgery following neoadjuvant chemotherapy
  1. Roni Nitecki Wilke1,
  2. Jinsong Liu2,
  3. Shannon Neville Westin1,
  4. Bryan M Fellman3,
  5. Travis T Sims1,
  6. Melissa Pham1,
  7. Kelly Rangel1,
  8. Esther Sey1,
  9. Jose Alejandro Rauh-Hain1,
  10. Karen H Lu1,
  11. Anil K Sood1 and
  12. Nicole D Fleming1
    1. 1Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
    2. 2Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Teaxs, USA
    3. 3Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
    1. Correspondence to Dr Roni Nitecki Wilke; rnitecki{at}mdanderson.org

    Abstract

    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 χ2 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.

    • Carcinoma, Ovarian Epithelial
    • Gynecologic Surgical Procedures
    • Homologous recombination
    • Ovarian Cancer
    • Pathology

    Data availability statement

    Data are available upon reasonable request.

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    Footnotes

    • X @Shannon.Westin, @nicoleflemingmd

    • Contributors RNW: methodology; formal analysis; writing - original draft; writing - review and editing; guarantor. JL: writing - review and editing. SNW: writing - review and editing. BMF: data curation; formal analysis; writing - review and editing. TTS: writing - review and editing. MP: writing - review and editing. KR: data curation; writing - review and editing. ES: data curation; writing - review and editing. JARH: writing - review and editing. KHL: writing - review and editing. AKS: conceptualization; writing - review and editing. NDF: conceptualization methodology; supervision; writing - review and editing. RNW is the guarantor.

    • Funding This work was supported, in part, by the MD Anderson Ovarian Cancer Moon Shot program, the NIH/NCI under award number P30CA016672, the Ovarian Cancer SPORE at MD Anderson (CA281701). The funding sources were not involved in the development of our research hypothesis.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.