299 - Influence of Cachexia in Locally Advanced Endometrial Cancer: A Secondary Analysis of NRG GOG 258/RTOG 1203

E. D. Donnelly¹, M. Kocherginsky², K. Dobinda³, L. M. Barroilhet⁴, P. Jayabalan², E. Barber⁵, D. Matei², M. E. Randall⁶, D. Mutch⁷, A. H. Klopp⁸, A. R. Yeung⁹, J. Walker¹⁰, S. F. Andrews¹¹, G. H. C. Cantuaria¹², A. Armstrong¹³, D. S. Mohan¹⁴, J. Contreras¹⁵, S. Pugh¹⁶, A. Miller¹⁷, and L. A. Kachnic¹⁸; ¹Department of Radiation Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, ²Northwestern University Feinberg School of Medicine, Chicago, IL, ³Northwestern Memorial Hospital, Chicago, IL, ⁴Department of Gynecologic Oncology, University of Wisconsin Hospital and Clinics, Madison, WI, ⁵Northwestern University, Chicago, IL, ⁶University of Kentucky, Lexington, KY, ⁷Washington University School of Medicine in St. Louis, Department of Obstetrics and Gynecology, St. Louis, MO, ⁸Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ⁹Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL, ¹⁰Oklahoma University Health Sciences Center, Oklahoma City, OK, ¹¹Carolina Regional Cancer Center, Myrtle Beach, SC, ¹²Northside Hospital Cancer Institute, Atlanta, GA, ¹³Case Western Reserve University, Cleaveland, OH, ¹⁴Kaiser Permanente Cancer Treatment Center, San Francisco, CA, ¹⁵Department of Radiation Oncology, Washington University in St. Louis, St. Louis, MO, ¹⁶NRG Oncology Statistics and Data Management Center, Philadelphia, PA, ¹⁷Roswell Park Cancer Institute, Buffalo, NY, ¹⁸Columbia University, New York, NY

Purpose/Objective(s): Cachexia is a metabolic state leading to weight loss from both muscle volume and adipose tissue loss. Cancer cachexia is believed to impact over 50% of cancer patients. Several studies have shown cachexia to be an independent prognostic indicator of worse outcomes. Endometrial cancer represents a unique patient population in which cachexia may be under-diagnosed secondary to obesity. Our aim was to assess the impact of cachexia on progression-free survival (PFS) in patients with locally advanced endometrial cancer enrolled on recent cooperative group trials. Materials/

Methods: Eligible patients were selected from those enrolled on NRG/GOG-258 and NRG/RTOG 1203. All patients underwent a hysterectomy for stages IB, grade 3 to IVA (FIGO 2009) disease. The study required patient images from the radiation (RT) planning CT scans. Several cachexia indices (skeletal muscle area [SMA], skeletal muscle index [SMI]) were assessed by measuring and averaging the volume on two consecutive axillary images at the mid-level of the L3 vertebral body. The SMA was calculated by adding and averaging the volumes of both the paraspinal muscles [PS SMA] and abdominal muscles [ABD SMA] at L3. The L3 SMI, a well-established cancer cachexia index, was calculated. Cachexia cutoffs were determined based on volume measurements of all eligible patients. PFS was estimated using the Kaplan-Meier method. Cox proportional hazards models, adjusted for treatment arm, were used to identify cachexia indices associated with PFS.
Results: In total, 422 patients had baseline characteristics available for evaluation: 119 (28%) patients in the RTOG-1203 control 3D RT arm, 110 (26%) in the IMRT arm, and 193 (46%) in the GOG-258 chemoradiation arm. The median age of the combined cohort was 62 (IQR: [55-68]). The median BMI was 32 (IQR: [26, 38]), with 20% and 59% categorized as overweight and obese, respectively. 228 (54%) patients had imaging and BMI data available to calculate cachexia indices. Cachexia based on L3 SMA (<30 vs. =30) was associated with worse PFS (HR=1.71, p=0.014), whereas L3 SMI (<12000 vs =12000) was not associated with PFS (HR=1.39; p=0.13). When evaluating individual muscle groups, cachexia in the paraspinal SMA alone was also significantly associated with worse PFS (HR=1.74, p = 0.013), but not in the abdominal SMA alone (p=0.181).
Conclusion: Endometrial cancer represents a unique cancer population, and as such, cancer cachexia is not well studied. In this secondary analysis of patients with locally advanced endometrial cancer from RTOG 1203 and GOG 258, L3 SMI cachexia was not associated with worse outcomes. However, other cachexia indices in this patient population (L3 and PSA SMA) were found to be associated with higher recurrences and significantly worse PFS. This study demonstrates that traditional measures of cachexia may not extrapolate to endometrial cancer and other indices may be required.