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Background and Purpose: The correlation between dose-averaged linear energy transfer (LETd) and its therapeutic or adverse effects, especially in carbon-ion radiotherapy (CIRT), remains controversial. This study aimed to investigate the effects of LETd and dose on pelvic insufficiency fractures after CIRT., Material and Methods: Among patients who underwent CIRT for uterine carcinoma, 101 who were followed up for > 6 months without any other therapy were retrospectively analyzed. The sacrum insufficiency fractures (SIFs) were graded according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity criteria. The correlations between the relative biological effectiveness (RBE)-weighted dose, LETd, physical dose, clinical factors, and SIFs were evaluated. In addition, we analyzed the association of SIF with LETd, physical dose, and clinical factors in cases where the sacrum D50% RBE-weighted dose was above the median dose., Results: At the last follow-up, 19 patients developed SIFs. Receiver operating characteristic curve analysis revealed that the sacrum D50% RBE-weighted dose was a valuable predictor of SIF. Univariate analyses suggested that LETd V10 keV/µm, physical dose V5 Gy, and smoking status were associated with SIF. Cox regression analysis in patients over 50 years of age validated that current smoking habit was the sole risk factor for SIF. Therefore, LETd or physical dose parameters were not associated with SIF prediction., Conclusion: The sacrum D50% RBE-weighted dose was identified as a risk factor for SIF. Additionally, neither LETd nor physical dose parameters were associated with SIF prediction., Competing Interests: Declaration of interest Nobuyuki Kanematsu reports relationships with the Japan Society of Medical Physics (which includes board membership and travel reimbursement), Japan Radiology Congress (which includes board membership and travel reimbursement), Kanagawa Cancer Center (which includes consulting or advisory), Osaka International Cancer Treatment Foundation (which includes travel reimbursement), and the Association for Nuclear Technology in Medicine (which includes speaking and lecture fees). In addition, Nobuyuki Kanematsu has patents: #JP2020-044286A (pending), #JP6383429 (issued), #JP5954705 (with royalties paid), #JP5521225 (with royalties paid), and #JP4456045 (with royalties paid), all to the National Institutes for Quantum Science and Technology., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: There is growing evidence on the role of carbon-ion radiotherapy (C-ion RT) for gynaecological tumours. Pelvic insufficiency fracture (PIF) decreases the quality of life after photon beam radiotherapy (RT). However, there is little information on PIF after C-ion RT. This study retrospectively assessed incidence of PIF after C-ion RT for uterine carcinomas (UCs) and the associations of clinical and dosimetric parameters with PIF incidence., Material and Methods: We performed a pooled analysis of 102 patients with UCs who underwent definitive C-ion RT alone and were followed up for >6 months without any additional RT in the pelvic region. PIF occurrence was surveyed using magnetic resonance imaging and/or computed tomography. Associations of clinical and dosimetric parameters with PIF incidence were analysed., Results: The 2- and 5-year actuarial incidences of ≥grade 1 PIF in all pelvic regions were 22.3% and 42.4%, respectively. The most frequent site of involvement was the sacrum. Log-rank tests showed that higher volumes receiving >10 Gy (relative biological effectiveness) (V10), V20, V30, and V40, body mass index (BMI) under 18.5, and current smoking were associated with increased incidence of ≥grade 1 PIF in the sacrum., Conclusions: We clarified the actuarial incidence of PIF after C-ion RT for UCs. Higher V10, V20, V30, V40, D 50% , D mean , current smoking, BMI <18.5, and using the anterior-posterior direction in whole pelvic irradiation were associated with higher incidences of PIF in the sacrum. The present results may lead to further improvement of C-ion RT for UCs., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Several studies have focused on increasing the linear energy transfer (LET) within tumours to achieve higher biological effects in carbon-ion radiotherapy (C-ion RT). However, it remains unclear whether LET affects late complications. We assessed whether physical dose and LET distribution can be specific factors for late rectal complications in C-ion RT., Materials and Methods: Overall, 134 patients with uterine carcinomas were registered and retrospectively analysed. Of 134 patients, 132 who were followed up for >6 months were enrolled. The correlations between the relative biological effectiveness (RBE)-weighted dose based on the Kanai model (the ostensible "clinical dose"), dose-averaged LET (LETd), or physical dose and rectal complications were evaluated. Rectal complications were graded according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria., Results: Nine patients developed grade 3 or 4 late rectal complications. Linear regression analysis found that D 2cc in clinical dose was the sole risk factor for ≥grade 3 late rectal complications (p = 0.012). The receiver operating characteristic analysis found that D 2cc of 60.2 Gy (RBE) was a suitable cut-off value for predicting ≥grade 3 late rectal complications. Among 35 patients whose rectal D 2cc was ≥60.2 Gy (RBE), no correlations were found between severe rectal toxicities and LETd alone or physical dose per se., Conclusion: We demonstrated that severe rectal toxicities were related to the rectal D 2cc of the clinical dose in C-ion RT. However, no correlations were found between severe rectal toxicities and LETd alone or physical dose per se., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Radiation-induced cancer is a serious late effect that may follow radiotherapy. A considerable uncertainty is associated with carcinogenesis from photon-based treatment, and even less established when including relative biological effectiveness (RBE) for particle therapy. The aim of this work was therefore to estimate and in particular explore relative risks (RR) of secondary cancer (SC) following particle therapy as applied in treatment of prostate cancer., Material and Methods: RRs of radiation-induced SC in the bladder and rectum were estimated using a bell-shaped dose-response model incorporating RBE and fractionation effects. The risks from volumetric modulated arc therapy (VMAT) were compared to intensity-modulated proton therapy (IMPT) and scanning carbon ions for ten patients., Results: The mean estimated RR (95% CI) of SC for VMAT/C-ion was 1.31 (0.65-2.18) for the bladder and 0.58 (0.41-0.80) for the rectum. Corresponding values for VMAT/IMPT were 1.72 (1.06-2.37) and 1.10 (0.78-1.43). The radio-sensitivity parameter α had the strongest influence on the results with decreasing RR for increasing values of α., Conclusion: Based on the wide spread in RR between patients and variations across the included parameter values, the risk profiles of the rectum and bladder were not dramatically different for the investigated radiotherapy techniques., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The aim of this study was to estimate normal tissue complication probability (NTCP) parameters for late rectal complications after carbon ion radiotherapy (C-ion RT) for prostate cancer., Methods and Materials: A total of 163 patients were used to derive NTCP parameters. These patients were treated with relative biological effectiveness (RBE)-weighted dose ranging from 57.6 Gy (RBE) up to 72 Gy (RBE) and included in dose escalation trials. The Lyman-Kutcher-Burman (LKB) model was used and the model parameters were fit to the relation between dose and complication observed after C-ion RT., Results: The resulting NTCP parameters were the volume effect parameter; n=0.035 (95% CI: 0.024-0.047), the steepness of the NTCP curve; m=0.10 (0.084-0.13), the tolerance dose associated with 50% probability of complication; TD50=63.6 Gy (RBE) (61.8-65.4 Gy (RBE)) for Grade⩾1, n=0.012 (0.0050-0.023), m=0.046 (0.033-0.062), TD50=69.1 Gy (RBE) (67.6-70.9 Gy (RBE)) for Grade⩾2., Conclusion: A new set of rectal NTCP parameters in C-ion RT was determined. The rather small n values suggest that the rectum was consistent with being strictly serial organ. The new derived parameter values facilitate estimation of rectal NTCP in C-ion RT., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)