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TERT promoter mutations and survival outcomes in adult-type granulosa cell tumors
    1. 1Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
    2. 2Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
    3. 3The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
    1. Correspondence to Dr Robert Tyler Hillman; rthillman{at}mdanderson.org

    Abstract

    Objectives T0 evaluate survival outcomes among patients with adult-type granulosa cell tumors who have telomerase reverse transcriptase (TERT) promoter mutations.

    Methods This is a retrospective cohort study using the MD Anderson Rare Gynecologic Malignancy Registry. Patients with adult granulosa cell tumors who underwent molecular testing for TERT promoter and FOXL2 c.C402G mutations were included. We used descriptive statistics to compare demographic and clinical variables and estimated progression-free and overall survival with Kaplan-Meier curves. Cox proportional hazards regression and log-rank tests were employed for comparisons, with multivariable analyses adjusting for various factors.

    Results Among 70 patients, 28 (40%) had TERT+ tumors. The median age at diagnosis was 40 years (range 12–71) for TERT− patients and 46 years (range 25–76) for TERT+ patients. At diagnosis, 22 (63%) of 35 TERT− patients were stage I, 10 (29%) stage II, and 3 (9%) stage III, while in the TERT+ group, 17/23 (74%) were stage I, 3 (13%) stage II, and 3 (13%) stage II. Univariable analysis showed no difference in time from diagnosis to first recurrence (p=0.19) and from first recurrence to second recurrence (p=0.24) based on tumor TERT status. The median time from first to second recurrence in the TERT− group was 27.3 months (95% CI 14.1 to 40.0) and in the TERT+ group was 14.8 months (95% CI 8.1 to 21.0). There was no observed difference in overall survival between the groups (HR=0.53; 95% CI 0.19 to 1.45; p=0.21). Multivariable analysis adjusting for age at diagnosis, TERT promoter mutation status, systemic chemotherapy, and stage demonstrated a significant difference in progression-free survival based on TERT mutation status (HR=2.89; 95% CI 1.32 to 6.36).

    Conclusions After adjustment for covariates, patients with adult granulosa cell tumors and TERT+ tumors had shorter progression-free survival after first recurrence. TERT promoter mutations may identify a subset of patients with recurrent adult granulosa cell tumors and less favorable outcomes.

    • Granulosa Cell Tumor
    • Retrospective Study

    Data availability statement

    Data are available upon reasonable request. If data were to be made available, it would need to be done under material transfer agreement through MD Anderson Cancer Center.

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    Data availability statement

    Data are available upon reasonable request. If data were to be made available, it would need to be done under material transfer agreement through MD Anderson Cancer Center.

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    Footnotes

    • X @jahow514, @RTylerHillmanMD

    • Contributors ALB: data curation, formal analysis, writing - original draft; AFL: data curation; BMF: statistical analysis; DG, JH: data curation, writing - reviewing and editing; VV, AKS, LMR, DG: writing - reviewing and editing; RTH: conceptualization, formal analysis, writing - original draft, supervision, guarantor.

    • Funding This research was in part supported by the National Institutes of Health through MD Anderson's Cancer Center Support Grant CA016672. This research was supported in part by Cancer Prevention & Research Institute of Texas grants RR2000045 (R.T.H.). This work was also supported by the NIH/NCI under award numbers T32 CA101642 (D.G. and A.L.B.). Additional funding sources include the Jennifer “Jenny” Song Fund for Granulosa Cell Tumor Research, Alisha B. Smith GCT Hope Fund, The University of Texas MD Anderson Cancer Center Ovarian Cancer SPORE (NIH grant CA281701), the American Cancer Society (AKS), the Ovarian Cancer Research Alliance (AKS), and the Frank McGraw Memorial Chair in Cancer Research (AKS).

    • Disclaimer These aforementioned funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

    • Competing interests AKS reports consulting fees from Merck, Iylong, Astra Zeneca, Onxeo, ImmunoGen, GSK and participation on a data safety monitoring board for Advenchen.

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