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Stereotactic radiotherapy for managing ovarian cancer oligoprogression under poly (ADP-ribose) polymerase inhibitors (PARPi)
  1. Stefano Durante1,
  2. Francesco Cuccia2,
  3. Michele Rigo3,
  4. Giovanni Caminiti4,
  5. Federico Mastroleo1,5,
  6. Roberta Lazzari1,
  7. Giulia Corrao1,5,
  8. Giuseppe Caruso6,7,
  9. Sabrina Vigorito8,
  10. Federica Cattani8,
  11. Giuseppe Ferrera2,
  12. Vito Chiantera9,10,
  13. Filippo Alongi3,11,
  14. Nicoletta Colombo12,13 and
  15. Barbara Alicja Jereczek-Fossa1,5
    1. 1Division of Radiation Oncology, European Institute of Oncology, IEO, IRCCS, Milan, Italy
    2. 2Radiation Oncology, ARNAS Civico Hospital, Palermo, Italy
    3. 3Advanced Radiation Oncology Department, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, Veneto, Italy
    4. 4UOC Radioterapia, ASP 7 Ragusa, Ragusa, Sicilia, Italy
    5. 5Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
    6. 6Department of Experimental Medicine, University of Rome La Sapienza, Rome, Lazio, Italy
    7. 7Divison of Gynecologic Oncology, European Institute of Oncology, IEO, IRCCS, Milan, Italy
    8. 8Unit of Medical Physics, European Institute of Oncology IRCCS, Milan, Italy
    9. 9Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Sicilia, Italy
    10. 10Department of Gynecologic Oncology, Istituto Nazionale Tumori – IRCCS Fondazione G. Pascale, Naples, Italy
    11. 11University of Brescia, Brescia, Italy
    12. 12Gynecology Program, European Institute of Oncology, IEO, IRCCS, Milan, Italy
    13. 13Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
    1. Correspondence to Dr Stefano Durante, Division of Radiation Oncology, European Institute of Oncology, Milano 20141, Italy; stefano.durante{at}ieo.it

    Abstract

    Objective Poly (ADP-ribose) polymerase inhibitors (PARPi) have become a new standard of care for the maintenance treatment of advanced epithelial ovarian cancer. This study aims to evaluate the efficacy and safety of combining stereotactic body radiotherapy with PARPi continuation as a strategy to treat ovarian cancer oligoprogression on PARPi.

    Methods This is a multicenter retrospective study including ovarian cancer patients treated with stereotactic body radiotherapy and PARPi continuation for oligoprogression under PARPi maintenance therapy between June 2012 and May 2023 in three Italian centers. PARPi treatment was continued until further disease progression or unacceptable toxicity. The primary endpoint was the next-line systemic therapy-free interval. The Kaplan-Meier method was used to assess local control, progression-free survival, and overall survival. Univariate and multivariate Cox regression analyses were performed to evaluate potential clinical outcomes predictors.

    Results 46 patients were included, with a total of 89 lesions treated over 63 radiotherapy treatments. Lymph nodes were the most frequently treated lesions (80, 89.9%), followed by visceral lesions (8, 9%) and one case with a bone lesion (1.1%). Median follow-up was 25.9 months (range 2.8–122). The median next-line systemic therapy-free interval was 12.4 months (95% CI 8.3 to 19.5). A number of prior chemotherapy lines greater than five was significantly associated with a reduced next-line systemic therapy-free interval (HR 3.21, 95% CI 1.11 to 9.32, p=0.032). At the time of analysis, 32 (69.6%) patients started a new systemic therapy regimen, while 14 (30.4%) remained on the PARPi regimen. The 2-year progression-free survival, local failure-free survival, and overall survival rates were 10.7%, 78.1%, and 76.5%, respectively. Four patients (8.7%) experienced acute toxicity with G1 gastrointestinal events.

    Conclusion Stereotactic body radiotherapy combined with PARPi continuation may be an effective and safe strategy for managing ovarian cancer patients with oligoprogression on PARPi maintenance therapy. Prospective research is warranted to shed more light on this approach.

    • Ovarian Cancer
    • Radiotherapy, Image-Guided
    • Neoplasm Metastasis

    Data availability statement

    Data are available upon reasonable request.

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    Data availability statement

    Data are available upon reasonable request.

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    • Contributors SD: Guarantor. SD, FC: Conceptualization, data curation, investigation, methodology, resources, software, validation, visualization, writing - original draft, writing - review and editing. MR, GC, FM, RL, GC, SV, FC, GF, VC, FA, NC: Validation, writing - review and editing. BAJ-F: Conceptualization, project administration, validation, supervision, writing - review and editing. All authors have read and agreed to the published version of the manuscript.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests BAJ-F has received speakers fees from Roche, Bayer, Janssen, Carl Zeiss, Ipsen, Accuray, Astellas, Elekta, and IBA Astra Zeneca, all outside the current project.

    • 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.