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Efficacy of cumulative cisplatin dose on survival in patients with locally advanced cervical cancer treated with definitive chemoradiotherapy: multicenter study by Turkish Oncology Group
  1. Arif Akyildiz1,
  2. Melis Gultekin2,
  3. Ecem Yigit2,
  4. Ecem Demir3,
  5. Rashad Ismayilov4,
  6. Melin Ahmed5,
  7. Mustafa Buyukkor6,
  8. Hasan Cagri Yildirim1,
  9. Nilgun Yildirim7,
  10. Gokhan Ucar8,
  11. Efnan Algin8,
  12. Ahmet Emin Ozturk9,
  13. Sinem Akbas10,
  14. Fatih Selcukbiricik10,
  15. Seval Orman11,
  16. Nedim Turan11,
  17. Mesut Yilmaz12,
  18. Rumeysa Colak12,
  19. Esra Ozen Engin13,
  20. Nargiz Majidova14,
  21. Ibrahim Vedat Bayoglu14,
  22. Havva Beyaz15,
  23. Ozturk Ates6,
  24. Kamuran Ibıs16,
  25. Sefika Arzu Ergen3,
  26. Sezin Yuce Sari2,
  27. Yilmaz Tezcan15,
  28. Ferah Yildiz2 and
  29. Zafer Arik1
    1. 1Department of Medical Oncology, Hacettepe University Faculty of Medicine, Ankara, Turkey
    2. 2Department of Radiation Oncology, Hacettepe University Faculty of Medicine, Ankara, Turkey
    3. 3Department of Radiation Oncology, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Turkey
    4. 4Department of Internal Medicine, Hacettepe University Faculty of Medicine, Ankara, Turkey
    5. 5Department of Medical Oncology, Istanbul University Faculty of Medicine, Istanbul, Turkey
    6. 6Department of Medical Oncology, Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey
    7. 7Department of Medical Oncology, Fırat University Faculty of Medicine, Elazig, Turkey
    8. 8Department of Medical Oncology, Ankara Bilkent City Hospital, Ankara, Turkey
    9. 9Department of Medical Oncology, Prof. Dr. Cemil Tascioglu City Hospital, Istanbul, Turkey
    10. 10Department of Medical Oncology, Koc University Hospital, Istanbul, Turkey
    11. 11Department of Medical Oncology, Kartal Dr. Lufti Kirdar City Hospital, Istanbul, Turkey
    12. 12Department of Medical Oncology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey
    13. 13Department of Medical Oncology, Sakarya University Faculty of Medicine, Sakarya, Turkey
    14. 14Department of Medical Oncology, Marmara University Pendik Training and Research Hospital, Istanbul, Turkey
    15. 15Department of Radiation Oncology, Ankara Bilkent City Hospital, Ankara, Turkey
    16. 16Department of Radiation Oncology, Istanbul University Faculty of Medicine, Istanbul, Turkey
    1. Correspondence to Dr Arif Akyildiz, Hacettepe University Cancer Institute, Department of Medical Oncology, 06100 Sihhiye, Ankara, Turkey; drakyildizarif{at}gmail.com

    Abstract

    Objective To investigate the impact of cumulative cisplatin dose on clinical outcomes in locally advanced cervical cancer patients undergoing definitive chemoradiotherapy.

    Methods A retrospective analysis was conducted on 654 patients with stage IB3–IVA disease treated with definitive chemoradiotherapy. Radiotherapy was applied as external beam pelvic with or without para-aortic radiotherapy and brachytherapy. Concomitant chemotherapy was in the form of weekly or 3 weekly cisplatin. Data on demographics, treatment protocols, cumulative cisplatin dose, adverse effects, and survival outcomes were collected. Statistical analyses, including univariate and multivariate Cox regression models, were used to assess factors influencing progression free survival and overall survival.

    Results The median cumulative cisplatin dose was 210 mg (range 40–320), and ≥200 mg in 503 (76.9%) patients. Median follow-up was 35 months (range 1–150). The 5 year progression free survival and overall survival rates were 66.9% and 77.1%, respectively. Multivariate analysis identified poor performance status, non-squamous cell histology, presence of lymph node metastases, and hemoglobin <10 g/dL before chemoradiotherapy as poor prognostic factors for both progression free survival and overall survival in the whole group. When stage III cases were evaluated separately, the cumulative cisplatin dose <200 mg was found to be a significant poor prognostic factor in overall survival (hazard ratio 1.79, 95% confidence interval 1.1 to 3.0, p=0.031).

    Conclusion Our study showed that a cumulative cisplatin dose >200 mg, particularly in patients with lymph node metastases, significantly improved overall survival. Factors such as anemia, toxicity related challenges, and comorbidities were identified as critical considerations in treatment planning. These findings emphasize the balance between maximizing therapeutic efficacy and managing toxicity, guiding personalized treatment approaches for locally advanced cervical cancer.

    • Cervical Cancer
    • Cervix Uteri
    • Radiotherapy

    Data availability statement

    Data are available upon reasonable request.

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    Data availability statement

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    Footnotes

    • X @EcemYigitMD

    • Contributors Conceptualization: AA and ZA. Formal analysis: AA, EY, ED, RI, and ZA. Funding acquisition: AA. Investigation: AA, MA, MB, HCCY, NY, GU, EA, AEO, SA, FS, SO, MY, RC, EOE, NM, HB, and KI. Methodology: AA, RI, and ZA. Project administration: AA. Resources: AA, HCCY, SAE, MG, IVB, and ZA. Supervision: MG and ZA. Validation: KI, OA, and SAE. Visualization: RI. Writing-original draft: AA and RI. Writing-review and editing: EY, MG, and ZA. Responsible for the overall content as a guarantor: AA. 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 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.