IMRT With Image-Guided Brachytherapy in Non-metastatic Locally Advanced Cervical Cancer

Abstract

Intensity modulated radiotherapy (IMRT) and image-guided adaptive brachytherapy (IGABT) have been only recently introduced in the treatment of locally advanced cervical cancer (LACC). We retrospectively assessed the overall clinical outcomes, patterns of failure, and toxicity in LACC patients from a single institution in a modern treatment era. A cohort of 138 patients with cervical squamous cell carcinoma or adenocarcinoma was treated with IMRT to a dose of 45 Gy and a boost of 5.4 to 14.4 Gy for involved lymph nodes, with concomitant chemotherapy, and IGABT. D2cc of the rectum, bladder and bowel were converted into the equivalent dose in 2 Gy fractions (EQD2) using a linear quadratic model (α/β=3 Gy). PET-scan was done for all patients at diagnosis and in the majority of patients (N=127) to assess treatment response. We reported late toxicity using RTOG/EORTC scoring system. Kaplan-Meier analyses for overall survival (OS), disease-free survival (DFS), pelvic control (PC) and local control (LC) were performed. Of 138 patients identified and treated between March 2011 and November 2015, 50 had stage IB, 62 had stage II, 21 had stage III and 5 had stage IVA. The median age was 51 years (range, 28-93). Histology was squamous cell carcinoma in 118 patients (85.5%). All patients had a staging PET-scan and 97% had an MRI at diagnosis. MRI tumor volume was >30 cm3 in 47% of cases. Nodal involvement was reported in 82 patients (59.4%). The median follow-up was 28 months. Endocavitary high-dose rate (HDR) IGABT was used for all patients. The median prescribed dose to the tumor was 84.3 Gy. The median D2cc to the bladder, rectum and bowel was 82.2 Gy, 67.6 Gy and 78.9 Gy, respectively. Complete PET response was observed in 113 out of 127 patients (89%). Three-year OS and DFS were 85.3% and 78.9%, respectively. Local control and pelvic control rates at 3 years were 94.8% and 91.9%, respectively. Twenty-seven patients (19.6%) were diagnosed with recurrent disease. Of these, 20 had evidence of distant recurrence and 3 had isolated local relapse. Four patients had only regional nodal recurrence, 3 of which were para-aortic recurrences that were not included in the original treatment field. Median time to relapse was 8 months (range, 2.5-45). Grade ≥ 3 late toxicities for bladder, vagina and bowel were observed in 4%, 3% and 2% of patients, respectively. Contemporary treatment of LACC with chemoradiation using IMRT and IGABT yields to higher rates of OS and DFS compared to previously published series. These good outcomes can be attributed to thorough clinical staging using PET-scan and MRI, the use of IMRT as well as the use of IGABT which allow dose escalation to involved lymph nodes and to the primary tumor without major impact on toxicity. As the majority of recurrences are distant, future trials should focus on optimizing systemic therapy.