Toxicity and Early Clinical Outcomes for Sequential and Simultaneous Integrated Nodal Boost in Patients with Locally Advanced Cervical Cancer

Abstract

Early trials demonstrated improved oncologic outcomes with extended field radiation therapy (EFRT) for patients with gynecologic malignancies and there is some evidence for a dose response in terms of lymph node control. In the pre-IMRT era, use of EFRT and dose escalation to nodal disease were limited by treatment-related toxicity, particularly GI. We evaluated the safety of dose escalated nodal boost (sequential and simultaneous integrated boost (SIB)) in patients with node-positive cervical cancer. Secondarily, we evaluated early clinical outcomes of these patients. We retrospectively identified consecutive node-positive cervical cancer patients treated with external beam radiation therapy at our institution between 2010 and 2018 who received 1) sequential boost or 2) SIB to gross nodal disease. We assessed acute and late treatment-related toxicity. Local control (LC), overall survival (OS), and freedom from distant metastasis (FFDM) at 2 years were estimated by the Kaplan-Meier method. For LC and FFDM, the alternate failure event was ignored. We identified 42 patients who met the inclusion criteria. Median follow up was 39 months. Median age for all patients was 44 (range 21-83). FIGO stage at diagnosis ranged from IB1 to IVB. The most common tumor histology was squamous cell carcinoma (71.4%). Forty patients (95.2%) had gross pelvic, 21 (50%) para-aortic, and 4 (9.5%) supraclavicular nodes at the time of diagnosis. The median total dose to nodal disease was 65 Gy in 25-30 fractions (range 60-67.6 Gy), given with either a sequential (n=22) or simultaneous (n=20) boost. Forty-one patients received concurrent chemotherapy (1 patient refusal) and all patients received brachytherapy boost. One patient in the sequential boost group experienced acute grade 3 GI toxicity (nausea/diarrhea). Otherwise, no grade 3+ acute (non-hematologic) toxicity was noted. Four patients (18.2%) in the sequential group and 1 patient (5%) in the SIB group experienced grade 3 late GI toxicity. The grade 3 late GI toxicity seen in the SIB group was distant from the nodal boost (sigmoid stricture requiring non-emergent surgical intervention). Four patients (18.2%) in the sequential group experienced grade 3 late GU toxicity. No grade 3+ late GU toxicity was seen in the patients receiving SIB. Overall LC, OS, and FFDM at 2 years (95% CIs) were 82.6% (65%, 91%), 73.6% (56%, 84%), and 70% (51%, 82%), respectively. Simultaneous integrated boost (SIB) to 60-65 Gy in 25 fractions to gross nodal disease in patients with locally advanced cervical cancer appears safe, with at least equivalent (potentially less) high grade late toxicity compared to sequential nodal boost.