3741 - Molecular Subtypes in Patients with Recurrent Endometrial Cancer Treated with Definitive Radiation
Presenter(s)
L. Bendesky1, A. H. Klopp2, S. N. Westin3, A. Jhingran2, A. Z. Kesaria2, L. Colbert2, N. Taku2, C. R. Weil2, L. L. Lin4, and M. M. Joyner2; 1MD Anderson Cancer Center, Houston, TX, 2Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 3Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 4Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s): Radiation therapy (RT) is the standard treatment for isolated pelvic recurrences of endometrial cancer. We evaluated the impact of molecular subtype, tumor volume, radiographic response and use of concurrent chemotherapy in patients undergoing RT for locally recurrent disease.
Materials/Methods: We retrospectively analyzed 52 patients treated with RT to the pelvis for recurrent endometrial cancer (2011-2022). Molecular subtype was categorized as mismatch repair deficient (dMMR), mismatch repair proficient/p53 wild type (NSMP), and p53 abnormal (p53abn). Baseline tumor volume was defined from pre-treatment MRI (preferred) or CT. Radiographic response was calculated as percent volume reduction between baseline and imaging performed after 20-25 fractions for boost planning. Progression-free survival (PFS) was measured from RT completion to recurrence or death.
Results: Median age was 63 years with median follow-up of 46 months. Subtypes included NSMP (52%), dMMR (33%; predominantly MLH1/PMS2 loss), and p53abn (15%). Concurrent chemotherapy was delivered to 69% of patients. Among evaluable patients (n=32), median tumor reduction was 50% (IQR 21-76%). dMMR tumors demonstrated greater median shrinkage (62%) compared to NSMP (41%) and p53abn (41%). Baseline tumor volume was independently associated with PFS, with a 1.6% increase in hazard rate for recurrence per cubic centimeter (p = 0.018). Five-year overall survival rate was 84% for NSMP, 52% for dMMR, and 60% for p53abn tumors. PFS was 52% in NSMP compared with 44% in both dMMR and p53abn subtypes after 5 years. No evidence for improvement in PFS was observed with concurrent chemotherapy in either dMMR or pMMR cohorts.
Conclusion: In recurrent endometrial cancer treated with RT, baseline tumor burden appears to be a dominant prognostic factor. Concurrent chemotherapy did not confer measurable benefit within molecular subgroups, highlighting the need for integrated systemic strategies, especially optimal strategies for integrating immunotherapy with RT for definitive treatment of recurrent dMMR endometrial cancers.