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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.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.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.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.

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 D2cc in clinical dose was the sole risk factor for ≥grade 3 late rectal complications (p = 0.012). The receiver operating characteristic analysis found that D2cc of 60.2 Gy (RBE) was a suitable cut-off value for predicting ≥grade 3 late rectal complications. Among 35 patients whose rectal D2cc 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 D2cc 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.

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, D50%, Dmean, current smoking, BMI

This study reports the commissioning methodology and results of a respiratory gating system [AZ – 733 V/733 VI (Anzai Medical Co., Japan)] using a pressure sensor in carbon‐ion scanning radiotherapy. Commissioning includes choosing a location and method for pressure sensor installation, delay time measurement of the system, and the final flow test. Additionally, we proposed a methodology for the determination of a threshold level of generating an on/off gate for the beam to the respiratory waveform, which is important for clinical application. Regarding the location and method for installation of the pressure sensor, the actual person's abdomen, back of the body position, and supine/prone positioning were checked. By comparing the motion between the pressure sensor output and the reference LED sensor motion, the chest rear surface was shown to be unsuitable for the sensor installation, due to noise in the signal caused by the cardiac beat. Regarding delay time measurement of the system, measurements were performed for the following four steps: (a). Actual motion to wave signal generation; (b). Wave signal to gate signal generation; (c). Gate signal to beam on/off signal generation; (d). Beam on/off signal to the beam irradiation. The total delay time measured was 46 ms (beam on)/33 ms (beam off); these were within the prescribed tolerance time (

Purpose Pancreatic tumor treatment dose distribution variations associated with supine and prone patient positioning were evaluated. Methods A total of 33 patients with pancreatic tumors who underwent CT in the supine and prone positions were analyzed retrospectively. Gross tumor volume (GTV), planning target volume (PTV), and organs at risk (OARs) (duodenum and stomach) were contoured. The prescribed dose of 55.2 Gy (RBE) was planned from four beam angles (0°, 90°, 180°, and 270°). Patient collimator and compensating boli were designed for each field. Dose distributions were calculated for each field in the supine and prone positions. To improve dose distribution, patient positioning was selected from supine or prone for each beam field. Results Compared with conventional beam angle and patient positioning, D2cc of 1st-2nd portion of duodenum (D1-D2), 3rd-4th portion of duodenum (D3-D4), and stomach could be reduced to a maximum of 6.4 Gy (RBE), 3.5 Gy (RBE), and 4.5 Gy (RBE) by selection of patient positioning. V10 of D1-D2, D3-D4, and stomach could be reduced to a maximum of 7.2 cc, 11.3 cc, and 11.5 cc, respectively. D95 of GTV and PTV were improved to a maximum of 6.9% and 3.7% of the prescribed dose, respectively. Conclusions Optimization of patient positioning for each beam angle in treatment planning has the potential to reduce OARs dose maintaining tumor dose in pancreatic treatment.

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 57.6Gy (RBE) up to 72Gy (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; TD 50 =63.6Gy (RBE) (61.8–65.4Gy (RBE)) for Grade⩾1, n =0.012 (0.0050–0.023), m =0.046 (0.033–0.062), TD 50 =69.1Gy (RBE) (67.6–70.9Gy (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.

Background Carbon-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. Methods Between 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. Results In 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. Conclusions The 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 registration Retrospectively registered (NIRS: 16–040). Electronic supplementary material The online version of this article (10.1186/s13014-018-1061-7) contains supplementary material, which is available to authorized users.

Challenging issues in treatment planning for scanned carbon-ion (C-ion) therapy are (i) accurate calculation of dose distribution, including the contribution of large angle-scattered fragments, (ii) reduction in the memory space required to store the dose kernel of individual pencil beams and (iii) shortening of computation time for dose optimization and calculation. To calculate the dose contribution from fragments, we modeled the transverse dose profile of the scanned C-ion beam with the superposition of three Gaussian distributions. The development of pencil beams belonging to the first Gaussian component was calculated analytically based on the Fermi-Eyges theory, while those belonging to the second and third components were transported empirically using the measured beam widths in a water phantom. To reduce the memory space for the kernels, we stored doses only in the regions of interest considered in the dose optimization. For the final dose calculation within the patient's whole body, we applied a pencil beam redefinition algorithm. With these techniques, the triple Gaussian beam model can be applied not only to final dose calculation but also to dose optimization in treatment planning for scanned C-ion therapy. To verify the model, we made treatment plans for a homogeneous water phantom and a heterogeneous head phantom. The planned doses agreed with the measurements within ±2% of the target dose in both phantoms, except for the doses at the periphery of the target with a high dose gradient. To estimate the memory space and computation time reduction with these techniques, we made a treatment plan for a bone sarcoma case with a target volume of 1.94 l. The memory space for the kernel and the computation time for final dose calculation were reduced to 1/22 and 1/100 of those without the techniques, respectively. Computation with the triple Gaussian beam model using the proposed techniques is rapid, accurate and applicable to dose optimization and calculation in treatment planning for scanned C-ion therapy.

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.