Dose constraints in the rectum and bladder following carbon-ion radiotherapy for uterus carcinoma: a retrospective pooled analysis

Abstract

BackgroundCarbon-ion radiotherapy (C-ion RT) provides better dose distribution in cancer treatment compared to photons. Additionally, carbon-ion beams provide a higher biological effectiveness, and thus a higher tumor control probability. However, information regarding the dose constraints for organs at risk in C-ion RT is limited. This study aimed to determine the predictive factors for late morbidities in the rectum and bladder after carbon-ion C-ion RT for uterus carcinomas.MethodsBetween June 1995 and January 2010, 134 patients with uterus carcinomas were treated with C-ion RT with curative intent; prescription doses of 52.8–74.4 Gy (relative biological effectiveness) were delivered in 20–24 fractions. Of these patients, 132 who were followed up for > 6 months were analyzed. We separated the data in two subgroups, a 24 fractions group and a 20 fractions group. Late morbidities, proctitis, and cystitis were assessed according to the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria. The correlations of clinical and dosimetric parameters, V10–V60, D5cc, D2cc, and Dmax, with the incidence of ≥grade 1 morbidities were retrospectively analyzed.ResultsIn the 24 fractions group, the 3-year actuarial occurrence rates of ≥grade 1 rectal and bladder morbidities were 64 and 9%, respectively. In addition, in the 20 fractions group, the 3-year actuarial occurrence rates of ≥grade 1 rectal and bladder morbidities were 32 and 19%, respectively. Regarding the dose–volume histogram data on the rectum, the D5cc and D2cc were significantly higher in patients with ≥grade 1 proctitis than in those without morbidity. In addition, the D5cc for the bladder was significantly higher in patients with ≥grade 1 cystitis than in those without morbidity. Results of univariate analyses showed that D2cc of the rectum was correlated with the development of ≥grade 1 late proctitis. Moreover, D5cc of the bladder was correlated with the development of ≥grade 1 late cystitis.ConclusionsThe present study identified the dose–volume relationships in C-ion RT regarding the occurrence of late morbidities in the rectum and bladder. Assessment of the factors discussed herein would be beneficial in preventing late morbidities after C-ion RT for pelvic malignancies.Trial registrationRetrospectively registered (NIRS: 16–040).Electronic supplementary materialThe online version of this article (10.1186/s13014-018-1061-7) contains supplementary material, which is available to authorized users.

Rectum Dose Constraints for Carbon Ion Therapy: Relative Biological Effectiveness Model Dependence in Relation to Clinical Outcomes

“…From NIRS NTCP analysis, the rectum appears as a serial organ regarding late complications, in agreement with conclusions from Okonogi et al [17] Therefore, in the definition of updated constraints, focus was given to high rectum doses. The new values were expressed in cc to overcome the previously discussed differences determined by rectum size variation.…”

“…Taking these uncertainties into account, the estimated probability of late rectal complications was very low. In Okonogi et al, D MKM|2cc was found to be the most significant predictive factor for late rectal morbidities, with a threshold of 57.3 Gy(RBE) to limit the risk for a 20 fraction treatment schedule [17]. Under the hypothesis that schedules could be compared based on the biological effective dose (BED) concept, the corresponding 16 fraction threshold value, assuming an α/β ratio of 3.9 Gy for the rectum [25], would be 53.5 Gy(RBE).…”

“…The late rectal toxicity of prostate AdC patients treated at NIRS was recently reported and fitted to the Lyman-Kutcher-Burman (LKB) NTCP model [16]. Additionally, a new study showed that the dose to 2 cc of the rectum volume (D 2cc ) could represent a good predictor of CIRT rectal damage [17].…”

Dose-averaged linear energy transfer per se does not correlate with late rectal complications in carbon-ion radiotherapy

“…We previously reported that the minimal clinical doses for most irradiated volumes of 2 cm 3 (D 2cc ) is a prognostic factor of late rectal complications [23]. The patient cohort was basically the same as that used in this prior study.…”

Pelvic insufficiency fractures following carbon-ion radiotherapy for uterine carcinomas

“…To date, several studies have reported the incidence of late morbidities after C-ion RT for pelvic malignancies [10]. We previously reported dose constraints in the rectum and bladder for C-ion RT for UC [18]. However, to the best of our knowledge, there is little information on PIF after C-ion RT for UC.…”