A simulation study of MR-guided proton therapy system using iron-yoked superconducting open MRI: a conceptual study.

Radiotherapy platforms integrated with magnetic resonance imaging (MRI) have been significantly successful and widely used in X-ray therapy over the previous decade. MRI provides greater soft-tissue contrast than conventional X-ray techniques, which enables more precise radiotherapy with on-couch adaptive treatment planning and direct tracking of moving tumors. The integration of MRI into a proton beam irradiation system (PBS) is still in the research stage. However, this could be beneficial as proton therapy is more sensitive to anatomical changes and organ motion. In this simulation study, we considered the integration of PBS into the 0.3-T superconducting open MRI system. Our proposed design involves proton beams traversing a hole at the center of the iron yoke, which allows for a reduced fringe field in the irradiation nozzle while maintaining a large proton scan field of the current PBS. The shape of the bipolar MRI magnets was derived to achieve a large MRI field-of-view. To monitor the beam position and size accurately while maintaining a small beam size, the beam monitor installation was redesigned from the current system. The feasibility of this system was then demonstrated by the treatment plan quality, which showed that the magnetic field did not deteriorate the plan quality from that without the magnetic field for both a rectangular target and a prostate case. Although numerous challenges remain before the proposed simulation model can be implemented in a clinical setting, the presented conceptual design could assist in the initial design for the realization of the MR-guided proton therapy.

Decision regret after curative treatment and its association with the decision-making process and quality of life for prostate cancer patients.

OBJECTIVES: To determine how the treatment decision-making process and posttreatment health-related quality of life (HRQOL) are related to regret about treatment choice for prostate cancer patients in Japan. METHODS: We invited a total of 614 patients who were treated with radiation therapy (RT), radical prostatectomy (RP), or active surveillance/watchful waiting (AS/WW) from April 2007 to March 2021. Posttreatment regret was evaluated by the Decision Regret Scale. HRQOL was evaluated by the Expanded Prostate Cancer Index Composite and the 12-item Short Form Survey. The decision-making process was assessed by patient evaluation of the decision-making process. We compared the decision regret scale scores across treatment types, HRQOL, and decision-making processes. RESULTS: Data from 371 patients were analyzed (RT: 202, RP: 149, AS/WW: 20). The median length of time since treatment was 64 (IQR: 43-93) months. The decision regret scale scores were not significantly different among the treatment groups but were significantly greater (strong regret) in patients with poor urinary summary scores, bowel summary scores, and hormonal summary scores. The decision regret scale scores were significantly lower (less regret) for patients who reported being adequately informed at the time of the treatment decision and who had adequately communicated their questions and concerns to physicians than for patients who reported less adequate communication. This result was also observed among patients who reported low HRQOL scores. CONCLUSIONS: These findings underline the important influence of posttreatment HRQOL and decision-making as an interactive process between physicians and their patients on posttreatment regret in prostate cancer patients.

Geometric target margin strategy of proton craniospinal irradiation for pediatric medulloblastoma.

In proton craniospinal irradiation (CSI) for skeletally immature pediatric patients, a treatment plan should be developed to ensure that the dose is uniformly delivered to all vertebrae, considering the effects on bone growth balance. The technical (t) clinical target volume (CTV) is conventionally set by manually expanding the CTV from the entire intracranial space and thecal sac, based on the physician's experience. However, there are differences in contouring methods among physicians. Therefore, we aimed to propose a new geometric target margin strategy. Nine pediatric patients with medulloblastoma who underwent proton CSI were enrolled. We measured the following water equivalent lengths for each vertebra in each patient: body surface to the dorsal spinal canal, vertebral limbus, ventral spinal canal and spinous processes. A simulated tCTV (stCTV) was created by assigning geometric margins to the spinal canal using the measurement results such that the vertebral limb and dose distribution coincided with a margin assigned to account for the uncertainty of the proton beam range. The stCTV with a growth factor (correlation between body surface area and age) and tCTV were compared and evaluated. The median values of each index for cervical, thoracic and lumber spine were: the Hausdorff distance, 9.14, 9.84 and 9.77 mm; mean distance-to-agreement, 3.26, 2.65 and 2.64 mm; Dice coefficient, 0.84, 0.81 and 0.82 and Jaccard coefficient, 0.50, 0.60 and 0.62, respectively. The geometric target margin setting method used in this study was useful for creating an stCTV to ensure consistent and uniform planning.

Proton and carbon ion radiotherapy for operable early-stage lung cancer; a prospective nationwide registry.

BACKGROUND AND PURPOSE: To investigate the toxicity and survival outcomes of proton and carbon ion radiotherapy for patients with operable early-stage lung cancer who are eligible for lobectomy. MATERIALS AND METHODS: This multicenter nationwide prospective cohort study included patients with operable early-stage lung cancer. Proton and carbon ion radiotherapy was performed according to the schedule stipulated in the unified treatment policy. Progression-free survival (PFS), overall survival (OS) and treatment-related toxicities were evaluated. RESULTS: A total of 274 patients were enrolled and included in efficacy and safety analyses. The most common tumor type was adenocarcinoma (44 %), while 105 cases (38 %) were not histologically confirmed or diagnosed clinically. Overall, 250 (91 %) of the 274 patients had tumors that were peripherally situated, while 138 (50 %) and 136 (50 %) patients were treated by proton and carbon ion radiotherapy, respectively. The median follow-up time for all censored patients was 42.8 months (IQR 36.7-49.0). Grade 3 or severe treatment-related toxicity was observed in 4 cases (1.5 %). Three-year PFS was 80.5 % (95 % CI: 75.7 %-85.5 %) and OS was 92.5 % (95 % CI: 89.3 %-95.8 %). Pathological confirmation and clinical stage were factors significantly associated with PFS, while tumor location and particle-ion type were not. Meanwhile, clinical stage was significantly associated with OS, but pathological confirmation, tumor location, and particle-ion type were not. CONCLUSIONS: Particle therapy for operable early-stage lung cancer resulted in excellent 3-year OS and PFS in each subset. In this disease context, proton and carbon ion beam therapies are feasible alternatives to curative surgery.

A Single-Institution Prospective Study To Evaluate the Safety and Efficacy of Real- Time Image-Gated Spot-Scanning Proton Therapy (RGPT) for Prostate Cancer.

Purpose: In real-time image-gated spot-scanning proton therapy (RGPT), the dose distribution is distorted by gold fiducial markers placed in the prostate. Distortion can be suppressed by using small markers and more than 2 fields, but additional fields may increase the dose to organs at risk. Therefore, we conducted a prospective study to evaluate the safety and short-term clinical outcome of RGPT for prostate cancer. Methods and Materials: Based on the previously reported frequency of early adverse events (AE) and the noninferiority margin of 10%, the required number of cases was calculated to be 43 using the one-sample binomial test by the Southwest Oncology Group statistical tools with the one-sided significance level of 2.5% and the power 80%. Patients with localized prostate cancer were enrolled and 3 to 4 pure gold fiducial markers of 1.5-mm diameter were inserted in the prostate. The prescribed dose was 70 Gy(relative biologic effectiveness) in 30 fractions, and treatment was performed with 3 fields from the left, right, and the back, or 4 fields from either side of slightly anterior and posterior oblique fields. The primary endpoint was the frequency of early AE (≥grade 2) and the secondary endpoint was the biochemical relapse-free survival rate and the frequency of late AE. Results: Forty-five cases were enrolled between 2015 and 2017, and all patients completed the treatment protocol. The median follow-up period was 63.0 months. The frequency of early AE (≥grade 2) was observed in 4 cases (8.9%), therefore the noninferiority was verified. The overall 5-year biochemical relapse-free survival rate was 88.9%. As late AE, grade 2 rectal bleeding was observed in 8 cases (17.8%). Conclusions: The RGPT for prostate cancer with 1.5-mm markers and 3- or 4- fields was as safe as conventional proton therapy in early AE, and its efficacy was comparable with previous studies.

Probability of normal tissue complications for hematologic and gastrointestinal toxicity in postoperative whole pelvic radiotherapy for gynecologic malignancies using intensity-modulated proton therapy with robust optimization.

This retrospective treatment-planning study was conducted to determine whether intensity-modulated proton therapy with robust optimization (ro-IMPT) reduces the risk of acute hematologic toxicity (H-T) and acute and late gastrointestinal toxicity (GI-T) in postoperative whole pelvic radiotherapy for gynecologic malignancies when compared with three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated X-ray (IMXT) and single-field optimization proton beam (SFO-PBT) therapies. All plans were created for 13 gynecologic-malignancy patients. The prescribed dose was 45 GyE in 25 fractions for 95% planning target volume in 3D-CRT, IMXT and SFO-PBT plans and for 99% clinical target volume (CTV) in ro-IMPT plans. The normal tissue complication probability (NTCP) of each toxicity was used as an in silico surrogate marker. Median estimated NTCP values for acute H-T and acute and late GI-T were 0.20, 0.94 and 0.58 × 10-1 in 3D-CRT; 0.19, 0.65 and 0.24 × 10-1 in IMXT; 0.04, 0.74 and 0.19 × 10-1 in SFO-PBT; and 0.06, 0.66 and 0.15 × 10-1 in ro-IMPT, respectively. Compared with 3D-CRT and IMXT plans, the ro-IMPT plan demonstrated significant reduction in acute H-T and late GI-T. The risk of acute GI-T in ro-IMPT plan is equivalent with IMXT plan. The ro-IMPT plan demonstrated potential clinical benefits for reducing the risk of acute H-T and late GI-T in the treatment of gynecologic malignances by reducing the dose to the bone marrow and bowel bag while maintaining adequate dose coverage to the CTV. Our results indicated that ro-IMPT may reduce acute H-T and late GI-T risk with potentially improving outcomes for postoperative gynecologic-malignancy patients with concurrent chemotherapy.

A new predictive parameter for dose-volume metrics in intensity-modulated radiation therapy planning for prostate cancer: Initial phantom study.

BACKGROUND: Organ-at-risk (OAR) sparing is often assessed using an overlap volume-based parameter, defined as the ratio of the volume of OAR that overlaps the planning target volume (PTV) to the whole OAR volume. However, this conventional overlap-based predictive parameter (COPP) does not consider the volume relationship between the PTV and OAR. PURPOSE: We propose a new overlap-based predictive parameter that consider the PTV volume. The effectiveness of proposed overlap-based predictive parameter (POPP) is evaluated compared with COPP. METHODS: We defined as POPP = (overlap volume between OAR and PTV/OAR volume) × (PTV volume/OAR volume). We generated intensity modulated radiation therapy (IMRT) based on step and shoot technique, and volumetric modulated arc therapy (VMAT) plans with the Auto-Planning module of Pinnacle3 treatment planning system (v14.0, Philips Medical Systems, Fitchburg, WI) using the American Association of Physicists in Medicine Task Group (TG119) prostate phantom. The relationship between the position and size of the prostate phantom was systematically modified to simulate various geometric arrangements. The correlation between overlap-based predictive parameters (COPP and POPP) and dose-volume metrics (mean dose, V70Gy, V60Gy, and V37.5 Gy for rectum and bladder) was investigated using linear regression analysis. RESULTS: Our results indicated POPP was better than COPP in predicting intermediate-dose metrics. The bladder results showed a trend similar to that of the rectum. The correlation coefficient of POPP was significantly greater than that of COPP in < 62 Gy (82% of the prescribed dose) region for IMRT and in < 55 Gy (73% of the prescribed dose) region for VMAT regarding the rectum (p < 0.05). CONCLUSIONS: POPP is superior to COPP for creating predictive models at an intermediate-dose level. Because rectal bleeding and bladder toxicity can be associated with intermediate-doses as well as high-doses, it is important to predict dose-volume metrics for various dose levels. POPP is a useful parameter for predicting dose-volume metrics and assisting the generation of treatment plans.

Slow-growing WNT medulloblastoma with atypical magnetic resonance imaging findings: illustrative case.

BACKGROUND: Medulloblastomas, with four molecular subgroups, are generally rapid-growing tumors with significant contrast enhancement and well-defined margins. However, each subgroup's clinical features, including disease time course and imaging characteristics, are not well defined. OBSERVATIONS: The authors describe the case of a 15-year-old female who presented with a 7-month history of impaired left-hand movement and was found to have a lesion on the dorsal side of the fourth ventricle. T2-weighted magnetic resonance imaging (MRI) at the patient's first presentation showed diffuse hyperintense signal without apparent mass, and gadolinium-enhanced T1-weighted imaging showed very slight contrast enhancement. In 1 month, her symptoms progressed, and follow-up MRI revealed an increase in the size of the lesion, showing greater diffusion restriction and contrast enhancement. She underwent gross-total resection, and pathology was consistent with classic medulloblastoma. Genetic analysis of the tumor confirmed the wingless (WNT) molecular subgroup. Adjuvant chemotherapy and proton beam therapy were performed. At the 18-month follow-up, MRI showed no recurrence of disease. LESSONS: Slow-growing medulloblastoma is very rare and not known to be associated with a specific molecular subgroup. Here, the authors report a case of slow-growing WNT medulloblastoma, indicating that slow growth may be a feature of this subgroup.

Brain metastases in Japanese NSCLC patients: prognostic assessment and the use of osimertinib and immune checkpoint inhibitors-retrospective study.

BACKGROUND: The Graded Prognostic Assessment for lung cancer using molecular markers (Lung-molGPA) has not been validated for use with Japanese non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) and the factors impacting survival need to be assessed. METHODS: We retrospectively analyzed 294 NSCLC patients who were newly diagnosed with BM between 2013 and 2020 and had received radiotherapy for BM initially at the Hokkaido Cancer Center. We evaluated the effect on the prognosis of Lung-molGPA items, the expression of PD-L1 (classified as high, low, and no expression), and the treatment history. The main outcome was the survival measured from the day of the diagnosis of BM, and log-rank tests were performed to evaluate the results. RESULTS: The median overall survival (OS) times for adenocarcinoma by groups of GPA scores (0‒1.0, 1.5‒2.0, 2.5‒3.0, and 3.5‒4.0) were 5.5, 14.8, 28.3, and 39.0 months (p < 0.0001), respectively. The median survival times for non-adenocarcinoma by groups of GPA scores (0‒1.0, 1.5‒2.0, and 2.5‒3.0) were 3.2, 11.0, and 16.0 months (p = 0.0011), respectively. In adenocarcinoma patients with gene mutations, osimertinib significantly improved the outcome (median OS: 34.2 and 17.6 months with and without osimertinib, respectively (p = 0.0164)). There was no significant difference in the OS between patients who were initially treated with tyrosine-kinase inhibitor for BM and those who initially received radiotherapy (p = 0.5337). In patients tested for PD-L1 expression, the median survival times after the diagnosis of BM were 5.6, 22.5, and 9.3 months for the high-, low- and no-expression groups (p = 0.2198), respectively. Also, in patients with high PD-L1 expressions, those with ICI had survival (median OS, 8.6 months) than those without (median OS, 3.6 months). CONCLUSIONS: We confirmed that Lung-molGPA successfully classified Japanese NSCLC patients with BM by the prognosis. Osimertinib prolonged survival of EGFR-positive NSCLC patients with BM, and ICI was effective in patients with high PD-L1 expressions.

Distribution of human papilloma virus genotypes and treatment outcomes in definitive radiotherapy for cervical cancer.

Most oncogenic human papilloma virus (HPV) genotypes stratify into two species, α-7 HPV and α-9 HPV. There are several studies that evaluate the relationship between HPV species and treatment outcomes and reports that HPV species is prognostic. The HPV genotyping was conducted using biopsy specimens which had been stored in these studies. We conducted the study using the HPV test performed by cytology specimens which is less invasive and more useful in clinical settings. This study enrolled 46 patients who received HPV genotyping before the definitive radiotherapy. The results of the HPV genotyping were classified into HPVα-7, HPVα-9 and negatives. Of the 46 patients, 10 were positive for HPVα-7, 21 positive for HPVα-9 and 15 were negative. The median follow-up period was 38 months (range 4-142). The HPVα-7, HPVα-9 and negative groups showed the 3-year overall survival (OS; 59.3%, 80.4% and 72.2% [P = 0.25]); local control (LC; 67.5%, 81% and 80% [P = 0.78]); pelvic control (PC) (50%, 81% and 72.7% [P = 0.032]); pelvic lymph node (PLN) control (78.7%, 95% and 92.3% [P = 0.012]); distant metastasis free (DMF) survival (50%, 75.4% and 42.8% [P = 0.098]); and progression free survival (PFS) rate of patients (30%, 66.7% and 38.9% [P = 0.085]), respectively. Patients with HPVα-7 showed statistically significant poorer PC than the HPVα-9 group, in multivariate analysis. This result is consistent with previous studies for HPV positive patients. The HPV negativity rate was higher in this study than in other studies and further work on this may be needed for clinical use.

Prostatic urinary tract visualization with super-resolution deep learning models.

In urethra-sparing radiation therapy, prostatic urinary tract visualization is important in decreasing the urinary side effect. A methodology has been developed to visualize the prostatic urinary tract using post-urination magnetic resonance imaging (PU-MRI) without a urethral catheter. This study investigated whether the combination of PU-MRI and super-resolution (SR) deep learning models improves the visibility of the prostatic urinary tract. We enrolled 30 patients who had previously undergone real-time-image-gated spot scanning proton therapy by insertion of fiducial markers. PU-MRI was performed using a non-contrast high-resolution two-dimensional T2-weighted turbo spin-echo imaging sequence. Four different SR deep learning models were used: the enhanced deep SR network (EDSR), widely activated SR network (WDSR), SR generative adversarial network (SRGAN), and residual dense network (RDN). The complex wavelet structural similarity index measure (CW-SSIM) was used to quantitatively assess the performance of the proposed SR images compared to PU-MRI. Two radiation oncologists used a 1-to-5 scale to subjectively evaluate the visibility of the prostatic urinary tract. Cohen's weighted kappa (k) was used as a measure of agreement of inter-operator reliability. The mean CW-SSIM in EDSR, WDSR, SRGAN, and RDN was 99.86%, 99.89%, 99.30%, and 99.67%, respectively. The mean prostatic urinary tract visibility scores of the radiation oncologists were 3.70 and 3.53 for PU-MRI (k = 0.93), 3.67 and 2.70 for EDSR (k = 0.89), 3.70 and 2.73 for WDSR (k = 0.88), 3.67 and 2.73 for SRGAN (k = 0.88), and 4.37 and 3.73 for RDN (k = 0.93), respectively. The results suggest that SR images using RDN are similar to the original images, and the SR deep learning models subjectively improve the visibility of the prostatic urinary tract.

Long-term consequences of residual lesions after chemoradiotherapy in patients with germinoma at onset.

OBJECTIVE: In patients with intracranial germ cell tumors, residual lesions are sometimes observed after completion of primary chemoradiotherapy. Although salvage resection of these end-of-treatment residual lesions is recommended for patients with nongerminomatous germ cell tumors, the necessity of early salvage resection for those with germinoma is not clear. The aim of this study was to investigate the frequency of residual germinoma lesions after primary chemoradiotherapy, as well as their management, long-term consequences, and prognosis. METHODS: The authors retrospectively reviewed patients who were primarily treated for germinoma between 2002 and 2021. Residual lesions were evaluated with MRI with and without contrast enhancement within 2 weeks after chemoradiotherapy. The decision to perform salvage resection of residual lesions was at the discretion of the treating physicians. The change in appearance of residual lesions was assessed with serial MRI. Overall survival (OS), progression-free survival (PFS), and recurrence pattern were also investigated. RESULTS: Sixty-nine patients were treated with chemoradiotherapy for germinoma, with a mean follow-up period of 108 months. Residual lesions were radiologically observed in 30 patients (43.5%). Among these, 5 patients (3 with pineal lesions and 2 with basal ganglia lesions) underwent salvage resection. Pathological examination revealed teratomatous components in 3 patients, whereas no tumoral components were identified in 2 patients. One patient with a basal ganglia lesion showed worsening of hemiparesis postoperatively. The remaining 25 patients received watchful observation without surgical intervention. Chronological periodic radiological change in residual lesions was evaluated in 21 patients. One year after primary treatment, the size of the residual lesions was stable and had decreased in 10 and 11 patients, respectively. None of the lesions increased in size. The 10-year PFS and OS rates were 96.7% and 97.3% in patients without residual lesions (n = 39), and 87.1% and 100% in patients with residual lesions (n = 30), respectively. Presence of residual lesions had no significant effect on PFS or OS. All recurrences occurred at distant sites or via dissemination without progression of the primary tumor site, regardless of the presence of residual lesion. CONCLUSIONS: End-of-treatment residual lesions are not rare in patients with germinoma, and these residual lesions seldom show progression. Because of the potential risk of surgical complications, the indication for early salvage surgery for residual lesions should be carefully determined. Watchful observation is recommended for the majority of these cases.

Dosimetric advantages of daily adaptive strategy in IMPT for high-risk prostate cancer.

PURPOSE: To evaluate the dosimetric advantages of daily adaptive radiotherapy (DART) in intensity-modulated proton therapy (IMPT) for high-risk prostate cancer by comparing estimated doses of the conventional non-adaptive radiotherapy (NART) that irradiates according to an original treatment plan through the entire treatment and the DART that uses an adaptive treatment plan generated by using daily CT images acquired before each treatment. METHODS: Twenty-three patients with prostate cancer were included. A treatment plan with 63 Gy (relative biological effectiveness (RBE)) in 21 fractions was generated using treatment planning computed tomography (CT) images assuming that all patients had high-risk prostate cancer for which the clinical target volume (CTV) needs to include prostate and the seminal vesicle (SV) in our treatment protocol. Twenty-one adaptive treatment plans for each patient (total 483 data sets) were generated using daily CT images, and dose distributions were calculated. Using a 3 mm set-up uncertainty in the robust optimization, the doses to the CTV, prostate, SV, rectum, and bladder were compared. RESULTS: Estimated accumulated doses of NART and DART in the 23 patients were 60.81 ± 3.47 Gy (RBE) and 63.24 ± 1.04 Gy (RBE) for CTV D99 (p < 0.01), 62.99 ± 1.28 Gy (RBE) and 63.43 ± 1.33 Gy (RBE) for the prostate D99 (p = 0.2529), and 59.07 ± 5.19 Gy (RBE) and 63.17 ± 1.04 Gy (RBE) for SV D99 (p < 0.001). No significant differences were observed between NART and DART in the estimated accumulated dose for the rectum and bladder. CONCLUSION: Compared with the NART, DART was shown to be a useful approach that can maintain the dose coverage to the target without increasing the dose to the organs at risk (OAR) using the 3 mm set-up uncertainty in the robust optimization in patients with high-risk prostate cancer.

Particle therapy using protons or carbon ions for cancer patients with cardiac implantable electronic devices (CIED): a retrospective multi-institutional study.

PURPOSE: To evaluate the outcomes of particle therapy in cancer patients with cardiac implantable electronic devices (CIEDs). MATERIALS AND METHODS: From April 2001 to March 2013, 19,585 patients were treated with proton beam therapy (PBT) or carbon ion therapy (CIT) at 8 institutions. Of these, 69 patients (0.4%, PBT 46, CIT 22, and PBT + CIT 1) with CIEDs (64 pacemakers, 4 implantable cardioverter defibrillators, and 1 with a cardiac resynchronization therapy defibrillator) were retrospectively reviewed. All the patients with CIEDs in this study were treated with the passive scattering type of particle beam therapy. RESULTS: Six (13%) of the 47 PBT patients, and none of the 23 CIT patients experienced CIED malfunctions (p = 0.105). Electrical resets (7) and over-sensing (3) occurred transiently in 6 patients. The distance between the edge of the irradiation field and the CIED was not associated with the incidence of malfunctions in 20 patients with lung cancer. A larger field size had a higher event rate but the test to evaluate trends as not statistically significant (p = 0.196). CONCLUSION: Differences in the frequency of occurrence of device malfunctions for patients treated with PBT and patients treated with CIT did not reach statistical significance. The present study can be regarded as a benchmark study about the incidence of malfunctioning of CIED in passive scattering particle beam therapy and can be used as a reference for active scanning particle beam therapy.

Impact of a spatially dependent dose delivery time structure on the biological effectiveness of scanning proton therapy.

PURPOSE: In the scanning beam delivery of protons, different portions of the target are irradiated with different linear energy transfer protons with various time intervals and irradiation times. This research aimed to evaluate the spatially dependent biological effectiveness of protracted irradiation in scanning proton therapy. METHODS: One and two parallel opposed fields plans were created in water phantom with the prescribed dose of 2 Gy. Three scenarios (instantaneous, continuous, and layered scans) were used with the corresponding beam delivery models. The biological dose (physical dose × relative biological effectiveness) was calculated using the linear quadratic model and the theory of dual radiation action to quantitatively evaluate the dose delivery time effect. In addition, simulations using clinical plans (postoperative seminoma and prostate tumor cases) were conducted to assess the impact of the effects on the dose volume histogram parameters and homogeneity coefficient (HC) in targets. RESULTS: In a single-field plan of water phantom, when the treatment time was 19 min, the layered-scan scenario showed a decrease of <0.2% (almost 3.3%) in the biological dose from the plan on the distal (proximal) side because of the high (low) dose rate. This is in contrast to the continuous scenario, where the biological dose was almost uniformly decreased over the target by approximately 3.3%. The simulation with clinical geometry showed that the decrease rates in D99% were 0.9% and 1.5% for every 10 min of treatment time prolongation for postoperative seminoma and prostate tumor cases, respectively, whereas the increase rates in HC were 0.7% and 0.2%. CONCLUSIONS: In protracted irradiation in scanning proton therapy, the spatially dependent dose delivery time structure in scanning beam delivery can be an important factor for accurate evaluation of biological effectiveness.

A treatment planning study of urethra-sparing intensity-modulated proton therapy for localized prostate cancer.

BACKGROUND AND PURPOSE: Urethra-sparing radiation therapy for localized prostate cancer can reduce the risk of radiation-induced genitourinary toxicity by intentionally underdosing the periurethral transitional zone. We aimed to compare the clinical impact of a urethra-sparing intensity-modulated proton therapy (US-IMPT) plan with that of conventional clinical plans without urethral dose reduction. MATERIALS AND METHODS: This study included 13 patients who had undergone proton beam therapy. The prescribed dose was 63 GyE in 21 fractions for 99% of the clinical target volume. To compare the clinical impact of the US-IMPT plan with that of the conventional clinical plan, tumor control probability (TCP) and normal tissue complication probability (NTCP) were calculated with a generalized equivalent uniform dose-based Lyman-Kutcher model using dose volume histograms. The endpoints of these model parameters for the rectum, bladder, and urethra were fistula, contraction, and urethral stricture, respectively. RESULTS: The mean NTCP value for the urethra in US-IMPT was significantly lower than that in the conventional clinical plan (0.6% vs. 1.2%, p < 0.05). There were no statistically significant differences between the conventional and US-IMPT plans regarding the mean minimum dose for the urethra with a 3-mm margin, TCP value, and NTCP value for the rectum and bladder. Additionally, the target dose coverage of all plans in the robustness analysis was within the clinically acceptable range. CONCLUSIONS: Compared with the conventional clinically applied plans, US-IMPT plans have potential clinical advantages and may reduce the risk of genitourinary toxicities, while maintaining the same TCP and NTCP in the rectum and bladder.

Cost-effectiveness analysis using lifetime attributable risk of proton beam therapy for pediatric medulloblastoma in Japan.

Compared to conventional X-ray therapy, proton beam therapy (PBT) has more clinical and physical advantages such as irradiation dose reduction to normal tissues for pediatric medulloblastoma. However, PBT is expensive. We aimed to compare the cost-effectiveness of PBT for pediatric medulloblastoma with that of conventional X-ray therapy, while focusing on radiation-induced secondary cancers, which are rare, serious and negatively affect a patient's quality of life (QOL). Based on a systematic review, a decision tree model was used for the cost-effectiveness analysis. This analysis was performed from the perspective of health care payers; the cost was estimated from medical fees. The target population was pediatric patients with medulloblastoma below 14 years old. The time horizon was set at 7.7 years after medulloblastoma treatment. The primary outcome was the incremental cost-effectiveness ratio (ICER), which was defined as the ratio of the difference in cost and lifetime attributable risk (LAR) between conventional X-ray therapy and PBT. The discount rate was set at 2% annually. Sensitivity analyses were performed to model uncertainty. Cost and LAR in conventional X-ray therapy and PBT were Japanese yen (JPY) 1 067 608 and JPY 2436061 and 42% and 7%, respectively. The ICER was JPY 3856398/LAR. In conclusion, PBT is more cost-effective than conventional X-ray therapy in reducing the risk of radiation-induced secondary cancers in pediatric medulloblastoma. Thus, our constructed ICER using LAR is one of the valid indicators for cost-effectiveness analysis in radiation-induced secondary cancer.

Visualizing the urethra by magnetic resonance imaging without usage of a catheter for radiotherapy of prostate cancer.

The urethra position may shift due to the presence/absence of the catheter. Our proposed post-urination-magnetic resonance imaging (PU-MRI) technique is possible to identify the urethra without catheter. We aimed to verify the inter-operator difference in contouring the urethra by PU-MRI. The mean values of the evaluation indices of dice similarity coefficient, mean slice-wise Hausdorff distance, and center coordinates were 0.93, 0.17 mm, and 0.36 mm for computed tomography, and 0.75, 0.44 mm, and 1.00 mm for PU-MRI. Therefore, PU-MRI might be useful for identifying the prostatic urinary tract without using a urethral catheter. Clinical trial registration: Hokkaido University Hospital for Clinical Research (018-0221).

Proton beam therapy for children and adolescents and young adults (AYAs): JASTRO and JSPHO Guidelines.

Children and adolescents and young adults (AYAs) with cancer are often treated with a multidisciplinary approach. This includes use of radiotherapy, which is important for local control, but may also cause adverse events in the long term, including second cancer. The risks for limited growth and development, endocrine dysfunction, reduced fertility and second cancer in children and AYAs are reduced by proton beam therapy (PBT), which has a dose distribution that decreases irradiation of normal organs while still targeting the tumor. To define the outcomes and characteristics of PBT in cancer treatment in pediatric and AYA patients, this document was developed by the Japanese Society for Radiation Oncology (JASTRO) and the Japanese Society of Pediatric Hematology/Oncology (JSPHO).