Significance of Concurrent Use of Weekly Cisplatin in Carbon-ion Radiotherapy for Locally Advanced Adenocarcinoma of the Uterine Cervix: A Propensity Score-Matched Analysis

Abstract

In recent decades, concurrent chemoradiotherapy (CCRT) including three-dimensional image-guided brachytherapy (3D-IGBT) has become the standard modality for uterine cervical cancer. However, several recent studies show that CCRT including 3D-IGBT did not appreciably improve the poor local control (LC) or overall survival (OS) rates for adenocarcinoma (AC) of the uterine cervix. As an alternative approach, we previously examined the effectiveness of carbon-ion RT (C-ion RT) for AC of the uterine cervix, and showed that C-ion RT was a promising treatment for adenocarcinoma (AC) of the uterine cervix. In this study, we evaluated significance of concurrent weekly cisplatin and C-ion RT for locally advanced AC of the uterine cervix. We performed a pooled analysis of patients with stage IIB–IVA AC of the uterine cervix who underwent C-ion RT alone or chemo-C-ion RT between September 2007 and December 2018 at our institution. All patients received 74.4 Gy relative biological effectiveness (RBE) in 20 fractions with or without cisplatin (40 mg/m2/week for up to 5 weeks), underwent no prior pelvic RT or systemic therapy, and had a performance status of 0–2. Late toxicity was graded according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme. To compare clinical outcomes between C-ion RT alone and chemo-C-ion RT groups, propensity score matching was used, basing on the year of diagnosis, regional lymph node metastasis, and stage. LC, OS, and distant metastatic (DM)-free rates were calculated by using the Kaplan-Meier method. Log-rank, Mann-Whitney U, and chi-square tests were performed for comparison. A two-sided p-value <0.05 was considered statistically significant in all tests. The matched cohort contained 26 patients who underwent C-ion RT and 26 who underwent chemo-C-ion RT. The median age and follow-up period were 57 (range, 28–79) years and 34 (range, 2–126) months, respectively. The incidence of grade ≥3 late toxicities was comparable between the two groups. The 5-year LC rates were 49% in both the chemo-C-ion RT and C-ion RT groups. The differences in the LC rates between the groups were not significant (p = 0.886). The 5-year OS rate was significantly better in the chemo-C-ion RT group (72%) than in the C-ion RT group (46%) (p = 0.041). The 5-year distant metastatic-free rate was also significantly better in the chemo-C-ion RT group (66%) than in the C-ion RT group (41%) (p = 0.048). For FIGO stage IIB, the OS and DM-free rates were higher (although not significantly so) in the chemo-C-ion RT group than in the C-ion RT group. However, for FIGO stage IIIB, OS (p = 0.029) and DM-free (p = 0.043) rates were significantly higher in the chemo-C-ion group. Chemo-C-ion RT for locally advanced AC of the uterine cervix is associated with a long-term survival benefit.