Study protocol of Elective Para-aortic and pelvic versus Pelvic only Irradiation in pelvic node positive Cervical cancer: a multicentric open labelled phase III randomised controlled trial (EPIC Study)

Abstract

Introduction The revision of International Federation of Gynaecology and Obstetrics staging in 2018 with recommendations to include cross-sectional imaging and a separate stage for node positive disease have opened a lot of uncertainties in implementing the correct treatment approach in these patients. While studies have suggested higher chances of occult para-aortic lymph node (PALN) even with advanced imaging, especially in pelvic node positive disease which tend to recur after pelvic radiation therapy. This study intends to study these patients and isolate the subset who will benefit most from elective PALN irradiation.Methods and analysis This is an ongoing multicentric phase III randomised controlled trial with a sample size of 274 subjects in two arms (137 in each arm) to determine the superiority of limited elective para-aortic irradiation compared with no irradiation. Arm one includes radiation to the lower PALN and pelvis; Arm two includes radiation to the pelvis. Concurrent chemotherapy followed by brachytherapy is standard in both arms. Patients with cervical cancer and radiologically positive pelvic LNs aged>18 years and<70 years are screened for the study. The primary endpoint of this study is 3-year disease-free survival. The secondary endpoints include 3-year para-aortic recurrence-free survival, 3-year distant metastasis-free survival, 3-year overall survival, acute and late toxicity, quality of life. Translational study to evaluate systemic immune response by FAPI-PETCT (fibroblast activator protein inhibitor positron emission tomography) and assessment of p16, L1 cell adhesion molecule (L1CAM) and protein death ligand-1 (PDL-1) expression by immunohistochemistry.Ethics and dissemination The study has been approved by the institutional ethics committee and will be routinely monitored according to standard guidelines. The results of the study will be published in peer-reviewed scientific journals, presented at conferences and submitted to regulatory authorities.Trial registration number The study was registered on 17 January 2022 under CTRI/2022/01/039495 (http://ctri.nic.in).