Positron Emission Tomography to Evaluate Response in the Cervix and Lymph Nodes after Definitive Chemoradiation and Immunotherapy for Cervical Cancer Patients Treated on GOG 9929

Abstract

Positron emission tomography (PET) has been shown to be prognostic for response and survival after standard chemoradiation (CRT) for cervical cancer. We investigated the role of PET in evaluating the primary tumor and metastatic lymph nodes after CRT and immunotherapy for locally advanced cervical cancer (LACC) patients (pts) treated with standard chemoradiation (CRT) followed by ipilimumab on GOG 9929. Node positive LACC pts were prospectively enrolled and treated with 6 weekly doses of cisplatin (40 mg/m2) and extended field radiation therapy. A pretreatment PET scan was required. Two to 6 weeks after CRT completion, pts with no evidence of disease progression initiated ipilimumab once every 3 weeks for 4 planned doses. Two dose levels were evaluated: 3mg/kg (DL1) and 10mg/kg (DL2), with an expansion at 10mg/kg. Pts had a post ipilimumab PET scan at 4-12 weeks. Further investigation of the cervix pre and post therapy PET scan used two metrics: (a) standardized uptake value (SUV), and (b) ratio of post-therapy SUVmax: pre-therapy SUVmax. We then correlated the PET response with 1-year disease free and overall survival data. All radiation plans underwent RT quality review with a radiation oncologist specializing in gynecology oncology. Thirty-two of 34 enrolled pts initiated study treatment, of whom 18 pts have complete pre and post therapy PET data, with at least 1 dose of ipilimumab. Of the 18 pts, 89% were squamous histology; all had positive pelvic lymph nodes (PVLN), and 47% had positive para-aortic lymph nodes (PALN). All pts completed CRT, with ipilimumab completion rates of 72% with 4 cycles, 11% with 3 cycles, 11% with 2 cycles and 6% with 1 cycle. There were no minor or major RT quality deviations. 18 patients have a measure of post ipilimumab PET scan response for the cervix: 13 had a complete response (CR), three had a partial response (PR), and two had stable disease (SD). 17 patients have a measure of PET scan response for PVLN: 8 had a CR, 7 had a PR, and 2 had SD. 3 patients have a measure of PET scan response for PALN, and all had a CR. In the 18 patients, the 12-month OS is 94% and the 12-month RFS is 88%. In the 18 patients, there were 2 recurrences, one of whom died: one had a CR in both cervix and PVLN, with no PALN data; the pt who recurred and died had a CR in cervix and a PR in PVLN, with no PALN data. This study is the first to describe the use of PET imaging as a prognostic imaging biomarker for cervical cancer after CRT and immunotherapy. Our data suggests that the post therapy PET could be used as an early correlate of response, and a potential biomarker tool for clinical trials and practice in cervical cancer.