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  • Epithelial ovarian cancer and brain metastases: might the BRCA status, PARP inhibitor administration, and surgical treatment impact the survival?

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Original research
Epithelial ovarian cancer and brain metastases: might the BRCA status, PARP inhibitor administration, and surgical treatment impact the survival?
  1. Carolina Maria Sassu1,
  2. Claudia Marchetti1,2,
  3. Giorgia Russo2,
  4. Angelo Minucci3,
  5. Serena Maria Boccia1,
  6. Alberto Benato4,
  7. Camilla Nero1,
  8. Alessia Piermattei1,
  9. Pier Paolo Mattogno5,
  10. Diana Giannarelli6,
  11. Gabriella Ferrandina1,2,
  12. Alessandro Olivi4,5,
  13. Anna Fagotti1,2 and
  14. Giovanni Scambia1,2
  1. 1 Dipartimento Scienze della Salute della Donna e del Bambino, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  2. 2 Dipartimento Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia, Rome, Italy
  3. 3 Dipartimento Scienze di laboratorio e infettivologiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  4. 4 Dipartimento di Neuroscienze, Organi di Senso e Torace, Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia, Rome, Italy
  5. 5 Dipartimento di Neuroscienze, Organi di Senso e Torace, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  6. 6 Epidemiology and Biostatistics Facility, G-STeP Generator, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
  1. Correspondence to Dr Claudia Marchetti, Dipartimento Scienze della Salute della Donna e del Bambino, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Lazio, Italy; claudia.marchetti{at}policlinicogemelli.it

Abstract

Objective To evaluate disease characteristics and survival according to BRCA status, administration of poly-(ADP-ribose) polymerase inhibitors (PARPi), and surgery in patients with ovarian cancer and brain metastases.

Methods This is a monocentric retrospective cohort of patients with ovarian cancer and brain metastases treated between 2000 and 2021. Data were collected by a retrospective review of medical records and analyzed according to: (1) BRCA mutation; (2) PARPi before and after brain metastases; (3) surgery for brain metastases.

Results Eighty-five patients with ovarian cancer and brain metastasis and known BRCA status (31 BRCA mutated (BRCAm), 54 BRCA wild-type (BRCAwt)) were analyzed. Twenty-two patients had received PARPi before brain metastases diagnosis (11 BRCAm, 11 BRCAwt) and 12 after (8 BRCAm, 4 BRCAwt). Brain metastases occurred >1 year later in patients who had received previous PARPi. Survival was longer in the BRCAm group (median post-brain metastasis survival: BRCAm 23 months vs BRCAwt 8 months, p=0.0015). No differences were found based on BRCA status analyzing the population who did not receive PARPi after brain metastasis (median post-brain metastasis survival: BRCAm 8 months vs BRCAwt 8 months, p=0.31). In the BRCAm group, survival was worse in patients who had received previous PARPi (median post-brain metastasis survival: PARPi before, 7 months vs no-PARPi before, 24 months, p=0.003). If PARPi was administered after brain metastases, survival of the overall population improved (median post-brain metastasis survival: PARPi after, 46 months vs no-PARPi after, 8 months, p=0.00038).

In cases of surgery for brain metastases, the prognosis seemed better (median post-brain metastasis survival: surgery 13 months vs no-surgery 8 months, p=0.036). Three variables were significantly associated with prolonged survival at multivariate analysis: BRCA mutation, multimodal treatment, and ≤1 previous chemotherapy line.

Conclusions BRCA mutations might impact brain metastasis occurrence and lead to better outcomes. In a multimodal treatment, surgery seems to affect survival even in cases of extracranial disease. PARPi use should be considered as it seems to prolong survival if administered after brain metastasis.

  • Ovarian Cancer
  • BRCA1 Protein
  • BRCA2 Protein
  • Neoplasm Metastasis

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

https://doi.org/10.1136/ijgc-2023-004980

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    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information.

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    Footnotes

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    • Contributors All listed authors have contributed to the manuscript preparation. Conceptualization and design of the study: GS, AF, AO, CM, CMS. Data collection: CMS, SMB, GR, AB, AP, GF. Analysis and data interpretation: CM, CMS, PPM. Collection of detailed genetic data: AM, CN. Statistical analysis: DG, CM, CMS. Guarantor: CM. Writing, review, and editing: all authors. All the authors have read, reviewed, edited, and approved the manuscript before submission.

    • 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 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.