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Sequencing chemotherapy before radiotherapy for women with stage IIIC endometrial cancer
  1. Deepa Maheswari Narasimhulu1,
  2. Matthew S Block2,
  3. Amy L Weaver3,
  4. Michaela McGree3,
  5. Amanika Kumar1,
  6. Carrie Langstraat1,
  7. Ivy Petersen4,
  8. Andrea Mariani1 and
  9. Gretchen Glaser1
  1. 1Gynecologic Surgery, Mayo Clinic Rochester, Rochester, Minnesota, USA
  2. 2Department of Medical Oncology, Mayo Clinic Rochester, Rochester, Minnesota, USA
  3. 3Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic Rochester, Rochester, Minnesota, USA
  4. 4Radiation Oncology, Mayo Clinic Rochester, Rochester, Minnesota, USA
  1. Correspondence to Dr Gretchen Glaser, Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota, USA; glaser.gretchen{at}


Objective It is unclear how to best sequence adjuvant chemotherapy and radiotherapy for advanced endometrial cancer. We studied the outcomes for women treated with chemotherapy before radiotherapy in a chemotherapy-first (chemotherapy for 6 cycles followed radiotherapy) or ‘sandwich’ approach (chemotherapy for 3 cycles followed by radiotherapy and subsequently chemotherapy for 3 cycles).

Methods Women with stage IIIC endometrial cancer and no gross residual disease treated with chemotherapy before radiotherapy between April 2003 and April 2016 were included. The Kaplan-Meier method was used to estimate recurrence and survival. We performed a meta-analysis of endometrial cancer trials comparing chemotherapy and radiotherapy versus radiotherapy alone.

Results A total of 102 patients were included. The mean (SD) age was 63.8 (10.6) years; 84 patients received the chemotherapy-first approach and 18 patients received the ‘sandwich’ approach. Pelvic and para-aortic nodes were removed in 99% and 88.2%, respectively. Among all the patients, we observed 1 pelvic (1%), 1 para-aortic (1%), and 5 vaginal (4.9%) recurrences. At 3 years, for the ‘sandwich’ and chemotherapy-first approaches, the vaginal recurrence was 11.8% and 4.2%, pelvic recurrence was 0% and 1.5%, para-aortic recurrence was 0% and 1.2%, distant recurrence was 42.9% and 24.4%, and overall survival was 70.3% and 81.7%, respectively. With ‘chemotherapy before radiotherapy’ 94.9% completed 4+ chemotherapy cycles (vs 71–90% reported in the literature for ‘radiotherapy before chemotherapy’). In a meta-analysis of endometrial cancer trials, distant recurrence rates were reduced with 4+ chemotherapy cycles but not with 3 cycles (p=0.01).

Conclusion Chemotherapy before radiation sequencing for stage IIIC endometrial cancer was associated with a high proportion of patients completing 4+ chemotherapy cycles and low locoregional lymphatic recurrence rate, despite delaying radiotherapy until after 3–6 cycles of chemotherapy and not administering concurrent cisplatin.

  • uterine cancer
  • radiation

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  • Contributors Study conception and design: MSB, GEG, AM, DN, IAP and ALW. Acquisition of data: DN. Analysis and interpretation of data: MSB, GEG, AM, MMM, DN, IAP and ALW. Drafting of manuscript: DN. Critical revision: MSB, GEG, AK, CLL, AM, MEM, DN, IAP and ALW.

  • Funding This work was supported by a grant from the National Center for Advancing Translational Sciences (CTSA Grant Number UL1 TR002377), a component of the National Institutes of Health (NIH).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Mayo Clinic IRB # 07-002816.

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

  • Data availability statement De-identified data are available upon reasonable request.

  • 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.