Parth A Chodavadia1, Corbin D Jacobs2, Frances Wang3, Laura J Havrilesky4, Junzo P Chino2, Gita Suneja5. 1. School of Medicine, Duke University, Durham, NC, USA. 2. Department of Radiation Oncology, Duke University, Durham, NC, USA. 3. Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA. 4. Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, Duke University, Durham, NC, USA. 5. Department of Radiation Oncology, Duke University, Durham, NC, USA. Electronic address: gita.suneja@icloud.com.
Abstract
OBJECTIVE: Adjuvant management of women with high-intermediate- and high-risk early-stage endometrial cancer remains controversial. Recently published results of GOG 249 revealed that vaginal brachytherapy plus chemotherapy (VBT + CT) was not superior to whole pelvic radiation therapy (WPRT) and was associated with more toxicities and higher nodal recurrences. This study examined off-study utilization of VBT + CT among women who met criteria for GOG 249 in the period prior to study publication. METHODS: Women diagnosed with FIGO IA-IIB endometrioid, serous, or clear cell uterine cancer between 2004-2015 and treated with hysterectomy and radiotherapy (RT) were identified in the National Cancer Database. Cochrane-Armitrage trend test was used to assess trends over time. Univariate and multivariate Cox analyses were performed to calculate odds ratio (OR) of VBT + CT receipt and hazard ratio (HR) of OS. Propensity-score matched analysis was conducted to account for baseline differences. RESULTS: 9956 women met inclusion criteria. 7548 women (75.8%) received WPRT while 2408 (24.2%) received VBT + CT in the study period. From 2004-2015, there was a significant increase in VBT + CT use (p < 0.001) with the largest overall increase occurring in 2009 to 22%. Factors significantly associated with VBT + CT receipt included higher socioeconomic status (p < 0.001), higher grade endometrioid cancer (p < 0.001), and aggressive histology (p < 0.001). After propensity-score matching, VBT + CT was associated with improved OS (HR 0.74, 95% CI 0.58-0.93); however, when stratified by FIGO stage, VBT + CT was only associated with improved OS for FIGO stage 1B (HR 0.62, 95% CI 0.44-0.87). CONCLUSIONS: There was significant use of experimental arm off-study treatment in the United States prior to report of GOG 249 results. Providers should be cautious when offering off-study treatment utilizing an experimental regimen given uncertainty about efficacy and toxicity.
OBJECTIVE: Adjuvant management of women with high-intermediate- and high-risk early-stage endometrial cancer remains controversial. Recently published results of GOG 249 revealed that vaginal brachytherapy plus chemotherapy (VBT + CT) was not superior to whole pelvic radiation therapy (WPRT) and was associated with more toxicities and higher nodal recurrences. This study examined off-study utilization of VBT + CT among women who met criteria for GOG 249 in the period prior to study publication. METHODS:Women diagnosed with FIGO IA-IIB endometrioid, serous, or clear cell uterine cancer between 2004-2015 and treated with hysterectomy and radiotherapy (RT) were identified in the National Cancer Database. Cochrane-Armitrage trend test was used to assess trends over time. Univariate and multivariate Cox analyses were performed to calculate odds ratio (OR) of VBT + CT receipt and hazard ratio (HR) of OS. Propensity-score matched analysis was conducted to account for baseline differences. RESULTS: 9956 women met inclusion criteria. 7548 women (75.8%) received WPRT while 2408 (24.2%) received VBT + CT in the study period. From 2004-2015, there was a significant increase in VBT + CT use (p < 0.001) with the largest overall increase occurring in 2009 to 22%. Factors significantly associated with VBT + CT receipt included higher socioeconomic status (p < 0.001), higher grade endometrioid cancer (p < 0.001), and aggressive histology (p < 0.001). After propensity-score matching, VBT + CT was associated with improved OS (HR 0.74, 95% CI 0.58-0.93); however, when stratified by FIGO stage, VBT + CT was only associated with improved OS for FIGO stage 1B (HR 0.62, 95% CI 0.44-0.87). CONCLUSIONS: There was significant use of experimental arm off-study treatment in the United States prior to report of GOG 249 results. Providers should be cautious when offering off-study treatment utilizing an experimental regimen given uncertainty about efficacy and toxicity.