Simulation study of comparative dosimetric analysis of coplanar horizontal-port scanned carbon-ion beam therapy in the head and neck.

OBJECTIVE: Carbon-ion radiotherapy (CIRT) has demonstrated success in treating radioresistant disease within the head and neck, owing to its unique physical and radiobiological properties. Construction cost remains prohibitive; a center offering only a horizontal port may bridge this difficulty, but removal of the vertical port may prohibit treatment of disease near critical organs-at-risk. Building a center only containing a horizontal treatment port has been proposed as one method for cost savings. METHODS: 20 complex cases of head and neck cancer previously treated with conventional CIRT were retrospectively planned using horizontal-port-only treatment incorporating non-coplanar treatment angles to achieve greater degrees of freedom. These were dosimetrically compared with the previous plans. RESULTS: Comparable D95 coverage of both planning target volume and gross tumor volume with ability to meet organ-at-risk constraints were feasible with horizontal-port-only treatment. Collectively differences were noted in PTV D95, brain stem Dmax, contralateral eye Dmax and V10 Gy (RBE); further qualitative differences were noted on a plan-by-plan basis dependent on disease location. CONCLUSION: Horizontal-port-only treatment employing non-coplanar angles was feasible for complicated head and neck disease typically treated with CIRT, though careful consideration is necessary on a plan-by-plan basis. ADVANCES IN KNOWLEDGE: It is worth noting that non-coplanar approaches are not typically used with the current treatment gantry and may extend further the difference between horizontal port planning and a gantry-based gold-standard.

Comparison of dosimetries of carbon-ion pencil beam scanning, proton pencil beam scanning and volumetric modulated arc therapy for locally recurrent rectal cancer.

We compared the dose distributions of carbon-ion pencil beam scanning (C-PBS), proton pencil beam scanning (P-PBS) and Volumetric Modulated Arc Therapy (VMAT) for locally recurrent rectal cancer. The C-PBS treatment planning computed tomography (CT) data sets of 10 locally recurrent rectal cancer cases were randomly selected. Three treatment plans were created using identical prescribed doses. The beam angles for C-PBS and P-PBS were identical. Dosimetry, including the dose received by 95% of the planning target volume (PTV) (D95%), dose to the 2 cc receiving the maximum dose (D2cc), organ at risk (OAR) volume receiving > 15Gy (V15) and > 30Gy (V30), was evaluated. Statistical significance was assessed using the Wilcoxon signed-rank test. Mean PTV-D95% values were > 95% of the volume for P-PBS and C-PBS, whereas that for VMAT was 94.3%. However, PTV-D95% values in P-PBS and VMAT were < 95% in five and two cases, respectively, due to the OAR dose reduction. V30 and V15 to the rectum/intestine for C-PBS (V30 = 4.2 ± 3.2 cc, V15 = 13.8 ± 10.6 cc) and P-PBS (V30 = 7.3 ± 5.6 cc, V15 = 21.3 ± 13.5 cc) were significantly lower than those for VMAT (V30 = 17.1 ± 10.6 cc, V15 = 55.2 ± 28.6 cc). Bladder-V30 values with P-PBS/C-PBS (3.9 ± 4.8 Gy(RBE)/3.0 ± 4.0 Gy(RBE)) were significantly lower than those with VMAT (7.9 ± 8.1 Gy). C-PBS provided superior dose conformation and lower OAR doses compared with P-PBS and VMAT. C-PBS may be the best choice for cases in which VMAT and P-PBS cannot satisfy dose constraints. C-PBS could be another choice for cases in which VMAT and P-PBS cannot satisfy dose constraints, thereby avoiding surgical resection.

Effects of dose and dose-averaged linear energy transfer on pelvic insufficiency fractures after carbon-ion radiotherapy for uterine carcinoma.

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.

Pelvic insufficiency fractures following carbon-ion radiotherapy for uterine carcinomas.

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 <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.

Four-dimensional carbon-ion pencil beam treatment planning comparison between robust optimization and range-adapted internal target volume for respiratory-gated liver and lung treatment.

We investigated the dose differences between robust optimization-based treatment planning (4DRO) and range-adapted internal target volume (rITV). We used 4DCT dataset of 20 lung cancer and 20 liver cancer patients, respectively, who had been treated with respiratory-gated carbon-ion pencil beam scanning therapy. 4DRO and rITV plans were created with the same clinical target volume (CTV) and organs at risk (OAR) contours. Four-dimensional dose distribution was calculated using deformable image registration. Dose metrics (e.g. D95, V20) were analyzed. Statistical significance was assessed by the Wilcoxon signed-rank test. For the lung cases, the mean CTV-D95 value for the rITV plan (=98.5%) was same as that for the 4DRO plan (=98.5%, P = 0.106), while the mean D95 value for the CTV + setup margin contour for the rITV plan (=98.2%) was higher than that for the 4DRO plan (95.2%, P < 0.001). For the liver cases, the mean CTV-D95 value for the rITV plan (=98.1%) was slightly lower than that for the 4DRO plan (=98.5%, P < 0.01), while the mean D95 value for the CTV + setup margin contour for the rITV plan (=98.0%) was higher than that for the 4DRO plan (94.1%, P < 0.001). For the doses to the organs at risk (OARs), the ipsilateral lung-V20/liver-V20 values for the rITV plan (=10.1%/19.7%) was significantly higher than that for the 4DRO plan (=8.6%/17.6, P < 0.001). Although the target coverage for 4DRO plan may be worse than that for rITV plan in the presence of the setup error, the 4DRO plan can improve OAR dose while preserving acceptable target dose coverage.

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

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.

Association of Chronotypes and Sleep Disturbance with Perceived Job Stressors and Stress Response: A Covariance Structure Analysis.

BACKGROUND: Chronotype, which is a person's circadian characteristics throughout a day, greatly influences a person's lifestyle, health, and sleep pattern; however, the association between job stress and chronotype remains unknown to date. Therefore, in this study, we analyzed the effects of chronotype on the job stress response, and the mediating effects of sleep disturbance using path analysis. METHODS: A cross-sectional survey was conducted on 535 adult volunteers (239 men and 296 women; average age, 41.2 ± 11.9 years) from the community. Participants were evaluated using the Diurnal Type Scale for chronotype, Pittsburg Sleep Quality Index for sleep disturbance, Brief Job Stress Questionnaire for job stressors, and the psychological and physical stress response (PPSR). To investigate the association between chronotype, sleep disturbance, perceived job stressors, and PPSR, a covariance structure analysis was performed. RESULTS: The eveningness chronotype had a significant weak direct effect on sleep disturbance, perceived job stressors, and PPSR, and had a significant indirect effect through sleep disturbance. The perceived job stressors indirectly increased PPSR through sleep disturbance. Sleep disturbance mediated the effects of the eveningness chronotype and perceived job stressors on PPSR. This model accounted for 37.3% of the variability in PPSR of adult workers. CONCLUSION: Chronotype affected PPSR through sleep disturbance. Therefore, improving the sleep disturbance of workers with the eveningness chronotype may reduce their stress response.

Influence of Parenting Quality and Neuroticism on Perceived Job Stressors and Psychological and Physical Stress Response in Adult Workers from the Community.

BACKGROUND: The complex interaction between parenting styles, job stressors, and the stress response has not been clarified to date. We hypothesized that neuroticism acts as a mediator in the effects of parenting quality on perceived job stressors and the psychological and physical stress response (PPSR), and tested this hypothesis using covariance structure analysis. SUBJECTS AND METHODS: We conducted research between April 2017 and April 2018 on 597 adult from the community, and 69 subjects were excluded owing to missing data or nonworkers. Finally, a total of 528 participants were analyzed using the following self-administered questionnaires: the Parental Bonding Instrument, the shortened Eysenck Personality Questionnaire-Revised, and the Brief Job Stress Questionnaire (BJSQ). The data were analyzed by single regression analyses and covariance structure analyses. Job stress was assessed by the BJSQ and 2 subscales, ie, perceived job stressors and the PPSR. This study was approved by the Ethics Committee of Tokyo Medical University. RESULTS: On covariance structure analysis, high parental overprotection was associated with high neuroticism and high PPSR directly, but had no significant effect on perceived job stressors. High parental overprotection was associated with high-perceived job stressors and the high PPSR indirectly through enhanced neuroticism. High parental overprotection was also associated with the high PPSR indirectly through 2 combined paths of neuroticism and perceived job stressors. This model accounted for 40% of the variability of the PPSR. On the other hand, parental care had opposite effects to parental overprotection, and this model of parental care accounted for 39% of the variability of PPSR. The model fits of the 2 models were good. CONCLUSION: Our results suggest that the quality of parenting in childhood is associated with perceived job stressors and the PPSR indirectly through neuroticism.

Effects of Job Stressors, Stress Response, and Sleep Disturbance on Presenteeism in Office Workers.

BACKGROUND: Occupational mental health, work environment, sleep health, presenteeism, and loss of work productivity caused by health problems are all public health concerns. Although sleep affects mental health and presenteeism, the associations between sleep disturbance, job stressors, stress responses, and presenteeism have remained unclear. We hypothesized that job stressors affect the presenteeism of office workers through sleep disturbance and analyzed the association among these factors. SUBJECTS AND METHODS: In 2017, a cross-sectional survey of adult office workers was performed. A total of 2899 subjects who provided written consent were included in the analysis. The survey collected demographic information, as well as the Work Limitation Questionnaire (WLQ), Pittsburgh Sleep Quality Index (PSQI), and Brief Job Stress Questionnaire (BJSQ). Associations between each of the variables were analyzed by path analysis (covariance structure analysis). This study was approved by the Ethics Committee of Tokyo Medical University. RESULTS: The path analysis demonstrated that job stressors, psychological and physical stress response (PPSR) in the BJSQ, and sleep disturbance in the PSQI had direct effects on presenteeism in the WLQ. Both job stressors and social support in the BJSQ indirectly affected presenteeism through effects on sleep disturbance and PPSR. Sleep disturbance indirectly affected presenteeism via PPSR. This model accounted for the variation of presenteeism (R 2 = 0.322). CONCLUSION: In the workplace, job stressors and low social support increase presenteeism through psychological and physical stress responses, as well as sleep disturbance. Evaluating and resolving work problems and sleep disturbance would hence be beneficial from the aspects of public health and socioeconomics.

Evaluation of patient positional reproducibility on the treatment couch and its impact on dose distribution using rotating gantry system in scanned carbon-ion beam therapy.

PURPOSE: The daily variations in patient setup may cause beam range uncertainties. We evaluated the reproducibility of relative position between the patient and the treatment couch throughout the treatment course and assessed its effects on dose distributions when a beam passes through treatment couch using rotating gantry system. METHODS: We enrolled 1023 patients (=13072 fractions) treated by carbon-ion pencil beam scanning therapy. Seven treatment sites including prostate, head and neck, bone and soft tissue, rectum, liver, lung, and pancreas were investigated. Inter-fractional changes in couch position relative to the patient were defined as translational errors. Changes in couch rotation were defined as rotational errors. Treatment planning was performed for 4 patients in each of the treatment sites. Dose distributions were then re-calculated after the couch was shifted according to average, 95th percentile, and maximum values of translational error. RESULTS: Large positional errors (>1.5 cm) were observed in 5% of treatment fractions. Positional errors were largest in prostate and pancreas patients, while smallest in head and neck and lung patients. There were no or only small changes in PTV-D95 and CTV-D95 values for almost all treatment sites. Clinically significant changes were observed in the duodenum (difference in D2cc values ranged from -55% to 28% with maximum couch shift) in pancreas treatment. CONCLUSIONS: Although underdosage to the PTV or CTV was limited, significant overdoses to organs at risk were found. The improvement of immobilization technique and appropriate selection of gantry angles could reduce the uncertainties due to changes in patient position.

Commissioning of a fluoroscopic-based real-time markerless tumor tracking system in a superconducting rotating gantry for carbon-ion pencil beam scanning treatment.

PURPOSE: To perform the final quality assurance of our fluoroscopic-based markerless tumor tracking for gated carbon-ion pencil beam scanning (C-PBS) radiotherapy using a rotating gantry system, we evaluated the geometrical accuracy and tumor tracking accuracy using a moving chest phantom with simulated respiration. METHODS: The positions of the dynamic flat panel detector (DFPD) and x-ray tube are subject to changes due to gantry sag. To compensate for this, we generated a geometrical calibration table (gantry flex map) in 15° gantry angle steps by the bundle adjustment method. We evaluated five metrics: (a) Geometrical calibration was evaluated by calculating chest phantom positional error using 2D/3D registration software for each 5° step of the gantry angle. (b) Moving phantom displacement accuracy was measured (±10 mm in 1-mm steps) with a laser sensor. (c) Tracking accuracy was evaluated with machine learning (ML) and multi-template matching (MTM) algorithms, which used fluoroscopic images and digitally reconstructed radiographic (DRR) images as training data. The chest phantom was continuously moved ±10 mm in a sinusoidal path with a moving cycle of 4 s and respiration was simulated with ±5 mm expansion/contraction with a cycle of 2 s. This was performed with the gantry angle set at 0°, 45°, 120°, and 240°. (d) Four types of interlock function were evaluated: tumor velocity, DFPD image brightness variation, tracking anomaly detection, and tracking positional inconsistency in between the two corresponding rays. (e) Gate on/off latency, gating control system latency, and beam irradiation latency were measured using a laser sensor and an oscilloscope. RESULTS: By applying the gantry flex map, phantom positional accuracy was improved from 1.03 mm/0.33° to <0.45 mm/0.27° for all gantry angles. The moving phantom displacement error was 0.1 mm. Due to long computation time, the tracking accuracy achieved with ML was <0.49 mm (=95% confidence interval [CI]) for imaging rates of 15 and 7.5 fps; those at 30 fps were decreased to 1.84 mm (95% CI: 1.79 mm-1.92 mm). The tracking positional accuracy with MTM was <0.52 mm (=95% CI) for all gantry angles and imaging frame rates. The tumor velocity interlock signal delay time was 44.7 ms (=1.3 frame). DFPD image brightness interlock latency was 34 ms (=1.0 frame). The tracking positional error was improved from 2.27 ± 2.67 mm to 0.25 ± 0.24 mm by the tracking anomaly detection interlock function. Tracking positional inconsistency interlock signal was output within 5.0 ms. The gate on/off latency was <82.7 ± 7.6 ms. The gating control system latency was <3.1 ± 1.0 ms. The beam irradiation latency was <8.7 ± 1.2 ms. CONCLUSIONS: Our markerless tracking system is now ready for clinical use. We hope to shorten the computation time needed by the ML algorithm at 30 fps in the future.

Comparison of passive and scanning irradiation methods for carbon-ion radiotherapy for breast cancer.

The dose distribution of passive and scanning irradiation for carbon-ion radiotherapy for breast cancer was compared in order to determine the preferred treatment method. Eleven Japanese patients who received carbon-ion radiotherapy for breast cancer were retrospectively analyzed. The original clinical plans were used for the passive irradiation method, while the plans for the scanning irradiation method were more recently made. Statistical analysis suggested that there was no significant difference in superiority in terms of dose distribution between the passive and scanning irradiation methods. The present study found that the scanning irradiation method was not always superior to the passive method, despite a previous study having reported the superiority of scanning irradiation. The present result is considered to arise from characteristics of breast cancer treatment, such as the simplicity of the organ at risk and the shallow depth point of the target from the skin. It is noteworthy that the present study suggests that the passive irradiation method can provide better dose distribution, depending on the case.