Presenter(s)
E. Atici1, B. J. Shelton2, L. Baldwin Branch3, and D. Fabian1; 1University of Kentucky, Department of Radiation Medicine, Lexington, KY, 2University of Kentucky, Lexington, KY, 3University of Kentucky, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Lexington, KY
Purpose/Objective(s): Endometrial cancer is the fourth most common cancer amongst women in the US. Optimal adjuvant regimen remains challenging for locally advanced or high-risk patients. 10 year data from PORTEC-3 highlighted the importance of systemic treatment added to radiation. We reviewed data from a single academic cancer center to evaluate the impact of adjuvant treatment order on clinical outcomes by stage, histologic, and pathologic features.
Materials/Methods: We performed a retrospective review of adjuvant treatment order after surgical resection at an academic cancer center from 2015-2026. Eligible patients had both definitive external beam radiation (EBRT) and chemotherapy after initial diagnosis of endometrial cancer. Adjuvant therapy was categorized as serial or sandwich. Serial therapy was defined as EBRT with/without concurrent chemotherapy, followed by additional chemotherapy. Sandwich therapy was defined as chemotherapy, then EBRT with/without concurrent chemotherapy, followed by more chemotherapy.
Results:
Of 539 cases, 86 cases matched inclusion criteria. 28 patients received serial and 58 patients received sandwich therapy. In the overall cohort, the mean follow up was 53 months. Median age was 62 years old. Most common histology was endometrial adenocarcinoma (55%). Overall, 67% had FIGO stage III disease, and 60% had grade 3 tumors. LVSI was present in 50% of patients. dMMR was identified in 17%, and 20% had p53 mutations; MMR and p53 data were unavailable in 45% and 58% of cases, respectively. In the serial arm, 55% of the patients had grade 3 disease compared to 61% in the sandwich arm. 66% of the patients had FIGO stage III disease in the serial arm versus 67% amongst patients who received sandwich treatment. LVSI was more common in the sandwich group (57% vs 30%). dMMR was more frequent in the serial group (30% vs 12%). p53 abnormalities were observed in 22% of serial and 18% of sandwich patients. There was no difference in overall survival (OS) based on adjuvant treatment sequence (p=0.53). Progression Free Survival (PFS) trended towards significance, favoring sandwich therapy (p=0.09). Kaplan-Meier (KM) estimated PFS at 60 months was 52% (95% CI, 30%-75%) for the serial group and 73% (95% CI, 60%-86%) for the sandwich group. Amongst p53wt group, PFS was significantly improved with sandwich therapy(p=0.03). Amongst the p53mut group, sandwich modality was trending towards improvement in OS (87% vs 50%, p=0.2) without statistically significant difference in PFS (p=0.9).Conclusion: Chemotherapy and EBRT are standard for high risk or locally advanced endometrial cancer. In our cohort, overall PFS showed a trend toward statistical significance favoring sandwich therapy. Sandwich sequencing was associated with improved PFS among patients with p53wt. These findings suggest molecular features such as p53 status may help guide optimal sequencing. Prospective studies are warranted to further evaluate sandwich therapy stratified by molecular risk factors.