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Adjuvant combined-modality therapy for stage IIIC endometrioid and non-endometrioid endometrial cancer

  • Bhavana V. Chapman
    Affiliations
    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
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  • Author Footnotes
    1 Present address: Department of Radiation Oncology, Orlando Health UF Health Cancer Center, 1400 South Orange Avenue, Orlando, FL 32806, USA.
    Cameron W. Swanick
    Footnotes
    1 Present address: Department of Radiation Oncology, Orlando Health UF Health Cancer Center, 1400 South Orange Avenue, Orlando, FL 32806, USA.
    Affiliations
    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
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  • Matthew S. Ning
    Affiliations
    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
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  • Pamela K. Allen
    Affiliations
    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
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  • Pamela T. Soliman
    Affiliations
    Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
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  • Shannon N. Westin
    Affiliations
    Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
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  • Author Footnotes
    2 Present address: Department of Pathology, Wayne State University, School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201, USA.
    Vishakha Pardeshi
    Footnotes
    2 Present address: Department of Pathology, Wayne State University, School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201, USA.
    Affiliations
    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
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  • Russell R. Broaddus
    Affiliations
    Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
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  • Karen H. Lu
    Affiliations
    Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
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  • Anuja Jhingran
    Affiliations
    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
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  • Patricia J. Eifel
    Affiliations
    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
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  • Ann H. Klopp
    Correspondence
    Corresponding author at: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
    Affiliations
    Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Search for articles by this author
  • Author Footnotes
    1 Present address: Department of Radiation Oncology, Orlando Health UF Health Cancer Center, 1400 South Orange Avenue, Orlando, FL 32806, USA.
    2 Present address: Department of Pathology, Wayne State University, School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201, USA.

      Highlights

      • Adjuvant radiotherapy improves DSS for node-positive endometrial cancer.
      • Chemoradiotherapy results in the highest DSS in patients with non-endometrioid and grade 3 endometrioid tumors.
      • Pelvic and in-field paraaortic recurrence rates are low among patients who receive radiotherapy.

      Abstract

      Objective

      To identify the optimal adjuvant treatment regimen for patients with endometrioid and non-endometrioid node-positive endometrial cancer.

      Methods

      We retrospectively identified 249 women with FIGO 2009 stage IIIC endometrial cancer at our institution who underwent surgical staging from 1985 to 2015 followed by external beam radiotherapy (RT), chemotherapy (CT), or a combination of CT + RT. Survival rates were calculated using the Kaplan-Meier method.

      Results

      The 5-year disease-specific survival (DSS) rate for all patients was 65%. Adjuvant CT + RT conferred higher rates of 5-year DSS as compared to CT alone in patients with grade 3 endometrioid and non-endometrioid tumors (61% vs. 27%, P = 0.04 and 67% vs. 38%, P = 0.02, respectively). Among patients with non-endometrioid tumors, treatment with concurrent chemoradiotherapy followed by additional sequential chemotherapy had higher 5-year DSS rates than with concurrent chemoradiotherapy alone (74% vs. 50%, P = 0.02). The 3-year pelvic recurrence rate was 5% with RT ± CT and 35% with CT alone (P < 0.001) for all patients. No paraaortic nodal failures were observed following extended-field RT, but 14% of patients who received pelvic-only RT or CT alone developed recurrences in the paraaortic nodes (P < 0.001).

      Conclusions

      Combined-modality therapy including adjuvant external beam pelvic radiotherapy yields excellent outcomes for patients with all subtypes of node-positive endometrial cancer. The most pronounced DSS advantage from adjuvant chemoradiotherapy was evident in women with non-endometrioid endometrial cancer.

      Keywords

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      References

        • Siegel R.L.
        • Miller K.D.
        • Jemal A.
        Cancer statistics, 2018.
        CA Cancer J. Clin. 2018; 68: 7-30
      1. Surveillance E, and End Results (SEER) Program (www.seer.cancer.gov) Research Data (1973–2015), National Cancer Institute, DCCPS, Surveillance Research Program, (released April 2018, based on the November 2017 submission).

        • Shah P.H.
        • Kudrimoti M.
        • Feddock J.
        • Randall M.
        Adjuvant treatment for stage IIIC endometrial cancer: options and controversies.
        Gynecol. Oncol. 2011; 122: 675-683
        • Mundt A.J.
        • Murphy K.T.
        • Rotmensch J.
        • Waggoner S.E.
        • Yamada S.D.
        • Connell P.P.
        Surgery and postoperative radiation therapy in FIGO stage IIIC endometrial carcinoma.
        Int. J. Radiat. Oncol. Biol. Phys. 2001; 50: 1154-1160
        • Pecorelli S.
        Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium.
        Int. J. Gynaecol. Obstet. 2009; 105: 103-104
        • Hogberg T.
        • Signorelli M.
        • de Oliveira C.F.
        • Fossati R.
        • Lissoni A.A.
        • Sorbe B.
        • et al.
        Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer–results from two randomised studies.
        Eur. J. Cancer. 2010; 46: 2422-2431
        • Randall M.E.
        • Filiaci V.L.
        • Muss H.
        • Spirtos N.M.
        • Mannel R.S.
        • Fowler J.
        • et al.
        Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group Study.
        J. Clin. Oncol. 2006; 24: 36-44
        • Matei D.
        • Filiaci V.L.
        • Randall M.
        • Steinhoff M.
        • DiSilvestro P.
        • Moxley K.M.
        • et al.
        A randomized phase III trial of cisplatin and tumor volume directed irradiation followed by carboplatin and paclitaxel vs. carboplatin and paclitaxel for optimally debulked, advanced endometrial carcinoma.
        J. Clin. Oncol. 2017; 35: 5505
        • de Boer S.M.
        • Powell M.E.
        • Mileshkin L.
        • Katsaros D.
        • Bessette P.
        • Haie-Meder C.
        • et al.
        Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial.
        Lancet Oncol. 2018; 19: 295-309
        • Randall M.
        • Filiaci V.
        • McMeekin D.
        • Yashar C.M.
        • Mannel R.
        • Salani R.
        • et al.
        A phase 3 trial of pelvic radiation therapy versus vaginal cuff brachytherapy followed by paclitaxel/carboplatin chemotherapy in patients with high-risk, early-stage endometrial cancer: a Gynecology Oncology Group Study.
        Int. J. Radiat. Oncol. Biol. Phys. 2017; 99: 1313
        • Cancer Genome Atlas Research N
        • Kandoth C.
        • Schultz N.
        • Cherniack A.D.
        • Akbani R.
        • Liu Y.
        • et al.
        Integrated genomic characterization of endometrial carcinoma.
        Nature. 2013; 497: 67-73
        • Klopp A.
        • Smith B.D.
        • Alektiar K.
        • Cabrera A.
        • Damato A.L.
        • Erickson B.
        • et al.
        The role of postoperative radiation therapy for endometrial cancer: executive summary of an American Society for Radiation Oncology evidence-based guideline.
        Pract. Radiat. Oncol. 2014; 4: 137-144
        • Meyer L.A.
        • Bohlke K.
        • Powell M.A.
        • Fader A.N.
        • Franklin G.E.
        • Lee L.J.
        • et al.
        Postoperative radiation therapy for endometrial cancer: American Society of Clinical Oncology clinical practice guideline endorsement of the American Society for Radiation Oncology evidence-based guideline.
        J. Clin. Oncol. 2015; 33: 2908-2913
        • Lee L.J.
        • Viswanathan A.N.
        Combined chemotherapy and radiation improves survival for node-positive endometrial cancer.
        Gynecol. Oncol. 2012; 127: 32-37
        • Wong A.T.
        • Rineer J.
        • Lee Y.C.
        • Schwartz D.
        • Safdieh J.
        • Weiner J.
        • et al.
        Utilization of adjuvant therapies and their impact on survival for women with stage IIIC endometrial adenocarcinoma.
        Gynecol. Oncol. 2016; 142: 514-519
        • Klopp A.H.
        • Jhingran A.
        • Ramondetta L.
        • Lu K.
        • Gershenson D.M.
        • Eifel P.J.
        Node-positive adenocarcinoma of the endometrium: outcome and patterns of recurrence with and without external beam irradiation.
        Gynecol. Oncol. 2009; 115: 6-11
        • Rosenthal D.I.
        • Liu L.
        • Lee J.H.
        • Vapiwala N.
        • Chalian A.A.
        • Weinstein G.S.
        • et al.
        Importance of the treatment package time in surgery and postoperative radiation therapy for squamous carcinoma of the head and neck.
        Head Neck. 2002; 24: 115-126
        • Secord A.A.
        • Havrilesky L.J.
        • O'Malley D.M.
        • Bae-Jump V.
        • Fleming N.D.
        • Broadwater G.
        • et al.
        A multicenter evaluation of sequential multimodality therapy and clinical outcome for the treatment of advanced endometrial cancer.
        Gynecol. Oncol. 2009; 114: 442-447
        • Secord A.A.
        • Geller M.A.
        • Broadwater G.
        • Holloway R.
        • Shuler K.
        • Dao N.Y.
        • et al.
        A multicenter evaluation of adjuvant therapy in women with optimally resected stage IIIC endometrial cancer.
        Gynecol. Oncol. 2013; 128: 65-70
        • Greven K.
        • Winter K.
        • Underhill K.
        • Fontenesci J.
        • Cooper J.
        • Burke T.
        Final analysis of RTOG 9708: adjuvant postoperative irradiation combined with cisplatin/paclitaxel chemotherapy following surgery for patients with high-risk endometrial cancer.
        Gynecol. Oncol. 2006; 103: 155-159
        • Cosgrove C.M.
        • Cohn D.E.
        • Goodfellow P.J.
        Primum non nocere: are we ready for POLE testing in endometrial cancer?.
        Gynecol. Oncol. 2017; 147: 240-242
      2. Wortman BG, Bosse T, Nout RA, Lutgens L, van der Steen-Banasik EM, Westerveld H, et al. Molecular-integrated risk profile to determine adjuvant radiotherapy in endometrial cancer: evaluation of the pilot phase of the PORTEC-4a trial. Gynecol. Oncol.. 2018;151:69–75.