The Clinical Results in Multi-Institutional Retrospective Analysis of Carbon-Ion Radiotherapy for Patients With Locally Advanced Adenocarcinoma of the Uterine Cervix.

Purpose/Objective(s) Since the use of image-guided brachytherapy has been accepted as a treatment for cervical cancer, many studies have reported improved local control (LC) rates of cervical squamous cell carcinoma. However, recent reports indicate that patients with adenocarcinoma (AC) continue to have lower LC rates. Carbon-ion radiotherapy (CIRT), having advantages in dose-localization properties and biological effectiveness, has been applied to various types of malignancies including AC of the uterine cervix. The favorable clinical outcome of CIRT for AC of the uterine cervix has been reported in several single-institutional studies. To validate the significance, we conducted a multi-institutional survey of CIRT for locally advanced AC (LAAC) of the uterine cervix. Materials/Methods We retrospectively analyzed the clinical outcomes of patients with stage IIB–IVA LAAC of the uterine cervix who underwent chemo-CIRT or CIRT alone between April 2010 and April 2016. Patients received 74.4 Gy (relative biological effectiveness [RBE]) in 20 fractions of CIRT or 55.2 Gy (RBE) in 16 fractions of CIRT plus 3 sessions of brachytherapy. Patients aged ≤70 years with adequate bone marrow and organ function were administered cisplatin weekly (40 mg/m2 per week for up to 5 weeks). Tumor response was assessed six months post-treatment in accordance with the RECIST v1.1. The LC and overall survival (OS) rates were calculated using the Kaplan-Meier method. Acute toxicities were classified according to the CTCAEv4.0, with a maximum reaction within 3 months after initiation of therapy. Late adverse toxicities were classified according to the RTOG/EORTC scoring system. Results Fifty-five patients were enrolled in this study. The median follow-up period was 67.5 months. The 5-year OS and LC rates were 69% and 65%, respectively. A multivariate analysis based on the Cox proportional-hazards model showed that the tumor response six months post-treatment was significantly associated with LC (5-year LC: CR vs. non-CR, 77% vs. 29%, P = 0.003, hazard ratio [HR]: 0.227) and OS (5-year OS: CR vs. non-CR, 83% vs. 29%, P = 0.002, HR: 0.253). In terms of acute toxicity, only 4 patients developed Grade 3 toxicity, and none of the patients developed Grade 4 toxicity. No statistical differences were observed in the incidence of acute toxicity between the CIRT and chemo-CIRT groups. In terms of late toxicity, only one patient developed Grade 3 rectum/sigmoid toxicity in the CIRT group. Meanwhile, 3 patients developed Grade 3 or worse toxicity in rectum/sigmoid or genitourinary in chemo-CIRT group. No statistical differences were observed in the incidence of late toxicity between the CIRT and chemo-CIRT groups. Conclusion The present study represents promising outcomes of CIRT or chemo-CIRT for LAAC of the uterine cervix, especially in the cases showing favorable response at 6 months. Author Disclosure N. Okonogi: None. K. Ando: None. K. Murata: None. M. Wakatsuki: None. S. Noda: None. D. Irie: None. H. Tsuji: None. M. Shozu: None. T. Ohno: None.