Boron neutron capture therapy as a larynx-preserving treatment for locally recurrent laryngeal carcinoma after conventional radiation therapy: A preliminary report.

OBJECTIVE: Laryngeal preservation and a radical cure are the treatment goals for laryngeal carcinoma, and larynx-preserving therapy is generally preferred for early-stage laryngeal carcinoma. When laryngeal carcinoma recurs locally, patients are often forced to undergo total laryngectomy, resulting in loss of vocal function. However, many patients with laryngeal carcinoma who have residual or recurrent disease after radiotherapy wish to preserve their voice. The purpose of this study was to investigate the possibility of using BNCT as a larynx-preserving treatment for residual or recurrent laryngeal carcinomas following radical irradiation. PATIENTS AND METHODS: This study included 15 patients who underwent BNCT for residual or recurrent laryngeal carcinoma after radical laryngeal carcinoma irradiation. The number of treatment sessions for all patients was one irradiation. Before BNCT, the recurrent laryngeal carcinoma stage was rT1aN0, rT2N0, rT2N1, rT3N0, rT3N1, and rT4aN0 in one, six, one, three, one, and three patients, respectively. The median maximum tumor diameter before BNCT was 15 mm (8-22 mm). All patients underwent a tracheostomy before BNCT to mitigate the risk of upper airway stenosis due to laryngeal edema after BNCT. Treatment efficacy was evaluated retrospectively using monthly laryngoscopy after BNCT and contrast-enhanced CT scans at 3 months. The safety of treatment was evaluated based on examination findings and interviews with patients. RESULTS: The median hospital stay after BNCT was 2 days (1-6). The response rate at three months after BNCT in 15 patients with locally recurrent laryngeal carcinoma was 93.3 %, and the CR rate was 73.3 %. The most frequent adverse event associated with BNCT was laryngeal edema, which occurred in nine patients the day after BNCT. The average course of laryngeal edema peaked on the second day after BNCT and almost recovered after 1 week in all patients. One patient had bilateral vocal fold movement disorders. None had dyspnea because of prophylactic tracheostomy. No grade four or higher adverse events occurred. Other grade 2 adverse events included pharyngeal mucositis, diarrhea, and sore throat. Three months after BNCT, tracheostomy tubes were removed in nine patients, retinal cannulas were placed in three patients, and voice cannulas were placed in three patients. CONCLUSIONS: BNCT for locally recurrent laryngeal carcinoma can safely deliver radical irradiation to tumor tissues, even in patients undergoing radical irradiation. BNCT has shown antitumor effects against recurrent laryngeal carcinoma. However, further long-term observations of the treatment outcomes are required.

Preliminary outcomes of boron neutron capture therapy for head and neck cancers as a treatment covered by public health insurance system in Japan: Real-world experiences over a 2-year period.

PURPOSE: Since June 2020, boron neutron capture therapy (BNCT) has been a health care service covered by health insurance in Japan to treat locally advanced or recurrent unresectable head and neck cancers. Therefore, we aimed to assess the clinical outcomes of BNCT as a health insurance treatment and explore its role among the standard treatment modalities for head and neck cancers. MATERIALS AND METHODS: We retrospectively analyzed data from patients who were treated using BNCT at Kansai BNCT Medical Center, Osaka Medical and Pharmaceutical University, between June 2020 and May 2022. We assessed objective response rates based on the Response Evaluation Criteria in Solid Tumors version 1.1, and adverse events based on the Common Terminology Criteria for Adverse Events, version 5.0. Additionally, we conducted a survival analysis and explored the factors that contributed to the treatment results. RESULTS: Sixty-nine patients (72 treatments) were included in the study, with a median observation period of 15 months. The objective response rate was 80.5%, and the 1-year locoregional control, progression-free survival, and overall survival rates were 57.1% (95% confidence interval [CI]: 43.9%-68.3%), 42.2% (95% CI: 30.1%-53.8%), and 75.4% (95% CI: 62.5%-84.5%), respectively. Locoregional control was significantly longer in patients with earlier TNM staging and no history of chemotherapy. CONCLUSIONS: BNCT may be an effective treatment option for locally advanced or recurrent unresectable head and neck cancers with no other definitive therapies. If definitive surgery or radiation therapy are not feasible, BNCT should be considered at early disease stages.

A Japanese multi-institutional phase II study of moderate hypofractionated intensity-modulated radiotherapy with image-guided technique for prostate cancer.

BACKGROUND: The aim of this multi-institutional phase II study was to confirm the safety and the potential efficacy of moderately hypofractionated intensity-modulated radiotherapy (IMRT) with prostate-based image-guidance for Japanese patients. METHODS: Patients with low- or intermediate-risk localized prostate cancer were eligible. Patients with a part of high risk (having only one of the following factors, cT3a, 20 < PSA ≤ 30, or GS = 8 or 9) were also included. Hypofractionated IMRT using daily image-guided technique with prostate matching was performed with a total dose of 70 Gy in 28 fractions. Neoadjuvant hormonal therapy for 4-8 months was mandatory for patients with intermediate or high-risk prostate cancer. RESULTS: From 20 institutions, 134 patients enrolled. The median follow-up was 5.16 years (range, 1.43-6.47 years). The number of patients with low, intermediate, and high-risk prostate cancer was 20, 80, and 34, respectively. The 5-year overall, biochemical failure-free, and clinical failure-free survival was 94.5%, 96.0%, and 99.2%, respectively. The 5-year biochemical failure-free survival for patients with low-, intermediate-, and high-risk disease was 94.1%, 97.4%, and 93.9%, respectively. The incidences of grade 2 gastrointestinal (GI) and genitourinary (GU) late toxicities at 5 years were 5.3% and 5.3%, respectively. There are no acute or late toxicities ≥ grade 3. Of 124 patients who were followed for up to 5 years, the grade 2 late GU or GI toxicities were 10.5% (90% confidence intervals, 6.3-16.2%, p = 0.0958). CONCLUSION: The safety and efficacy of moderately hypofractionated IMRT with prostate-based image-guidance was confirmed among Japanese patients with prostate cancer.

Application of stoichiometric CT number calibration method for dose calculation of tissue heterogeneous volumes in boron neutron capture therapy.

BACKGROUND: Monte Carlo simulation code is commonly used for the dose calculation of boron neutron capture therapy. In the past, dose calculation was performed assuming a homogeneous mass density and elemental composition inside the tissue, regardless of the patient's age or sex. Studies have shown that the mass density varies with patient to patient, particularly for those that have undergone surgery or radiotherapy. A method to convert computed tomography numbers into mass density and elemental weights of tissues has been developed and applied in the dose calculation process using Monte Carlo codes. A recent study has shown the variation in the computed tomography number between different scanners for low- and high-density materials. PURPOSE: The aim of this study is to investigate the effect of the elemental composition inside each calculation voxel on the dose calculation and the application of the stoichiometric CT number calibration method for boron neutron capture therapy planning. METHODS: Monte Carlo simulation package Particle and Heavy Ion Transport code System was used for the dose calculation. Firstly, a homogeneous cubic phantom with the material set to ICRU soft tissue (four component), muscle, fat, and brain was modelled and the NeuCure BNCT system accelerator-based neutron source was used. The central axis depth dose distribution was simulated and compared between the four materials. Secondly, a treatment plan of the brain and the head and neck region was simulated using a dummy patient dataset. Three models were generated; (1) a model where only the fundamental materials were considered (simple model), a model where each voxel was assigned a mass density and elemental weight using (2) the Nakao20 model, and (3) the Schneider00 model. The irradiation conditions were kept the same between the different models (irradiation time and irradiation field size) and the near maximum (D1%) and mean dose to the organs at risk were calculated and compared. RESULTS: A maximum percentage difference of approximately 5% was observed between the different materials for the homogeneous phantom. With the dummy patient plan, a large dose difference in the bone (greater than 12%) and region near the low-density material (mucosal membrane, 7%-11%) was found between the different models. CONCLUSIONS: A stoichiometric CT number calibration method using the newly developed Nakao20 model was applied to BNCT dose calculation. The results indicate the importance of calibrating the CT number to elemental composition for each individual CT scanner for the purpose of BNCT dose calculation along with the consideration of heterogeneity of the material composition inside the defined region of interest.

Safety of Boron Neutron Capture Therapy with Borofalan(10B) and Its Efficacy on Recurrent Head and Neck Cancer: Real-World Outcomes from Nationwide Post-Marketing Surveillance.

BACKGROUND: This study was conducted to evaluate the real-world safety and efficacy of boron neutron capture therapy (BNCT) with borofalan(10B) in Japanese patients with locally advanced or locally recurrent head and neck cancer (LA/LR-HNC). METHODS: This prospective, multicenter observational study was initiated in Japan in May 2020 and enrolled all patients who received borofalan(10B) as directed by regulatory authorities. Patient enrollment continued until at least 150 patients were enrolled, and adverse events attributable to drugs, treatment devices, and BNCT were evaluated. The patients with LA/LR-HNC were systematically evaluated to determine efficacy. RESULTS: The 162 patients enrolled included 144 patients with squamous cell carcinoma of the head and neck (SCCHN), 17 patients with non-SCCHN (NSCCHN), and one patient with glioblastoma. Treatment-related adverse events (TRAEs) were hyperamylasemia (84.0%), stomatitis (51.2%), sialoadenitis (50.6%), and alopecia (49.4%) as acute TRAEs, and dysphagia (4.5%), thirst (2.6%), and skin disorder (1.9%) as more common late TRAEs. In patients with LA/LR-HNC, the overall response rate (ORR) was 72.3%, with a complete response (CR) in 63 (46.0%) of 137 patients with SCCHN. Among 17 NSCCHN patients, the ORR was 64.7%, with eight cases (47.1%) of CR. One- and two-year OS rates in patients with recurrent SCCHN were 78.8% and 60.7%, respectively. CONCLUSIONS: This post-marketing surveillance confirmed the safety and efficacy of BNCT with borofalan(10B) in patients with LA/LR-HNC in a real-world setting.

Out-of-field dosimetry using a validated PHITS model and computational phantom in clinical BNCT.

BACKGROUND: The out-of-field radiation dose for boron neutron capture therapy (BNCT), which results from both neutrons and γ-rays, has not been extensively evaluated. To safely perform BNCT, the neutron and γ-ray distributions inside the treatment room and the whole-body dose should be evaluated during commissioning. Although, certain previous studies have evaluated the whole-body dose in the clinical research phase, no institution providing BNCT covered by health insurance has yet validated the neutron distribution inside the room and the whole-body dose. PURPOSE: To validate the Monte Carlo model of the BNCT irradiation room extended for the whole-body region and evaluate organ-at-risk (OAR) doses using the validated model with a human-body phantom. METHODS: First, thermal neutron distribution inside the entire treatment room was measured by placing Au samples on the walls of the treatment room. Second, neutron and gamma-ray dose-rate distributions inside a human-body water phantom were measured. Both lying and sitting positions were considered. Bare Au, Au covered by Cd (Au+Cd), In, Al, and thermoluminescent dosimeters were arranged at 11 points corresponding to locations of the OARs inside the phantom. After the irradiation, γ-ray peaks emitted from the samples were measured by a high-purity germanium detector. The measured counts were converted to the reaction rate per unit charge of the sample. These measurements were compared with results of simulations performed with the Particle and Heavy Ion Transport code System (PHITS). A male adult mesh-type reference computational phantom was used to evaluate OAR doses in the whole-body region. The relative biological effectiveness (RBE)-weighted doses and dose-volume histograms (DVHs) for each OAR were evaluated. The median dose (D50% ) and near-maximum dose (D2% ) were evaluated for 14 OARs in a 1-h-irradiation process. The evaluated RBE-weighted doses were converted to equivalent doses in 2 Gy fractions. RESULTS: Experimental results within 60 cm from the irradiation center agreed with simulation results within the error bars except at ±20, 30 cm, and those over 70 cm corresponded within one digit. The experimental results of reaction rates or γ-ray dose rate for lying and sitting positions agreed well with the simulation results within the error bars at 8, 4, 11, 7 and 7, 4, 7, 6, 5, 6 out of 11 points, respectively, for Au, Au+Cd, In, Al, and TLD. Among the detectors, the discrepancies in reaction rates between experiment and simulation were most common for Au+Cd, but were observed randomly for measurement points (brain, lung, etc.). The experimental results of γ-ray dose rates were systematically lower than simulation results at abdomen and waist regions for both positions. Extending the PHITS model to the whole-body region resulted in higher doses for all OARs, especially 0.13 Gy-eq increase for D50% of the left salivary gland. CONCLUSION: The PHITS model for clinical BNCT for the whole-body region was validated, and the OAR doses were then evaluated. Clinicians and medical physicists should know that the out-of-field radiation increases the OAR dose in the whole-body region.

Real-World Results of Stereotactic Body Radiotherapy for 399 Medically Operable Patients with Stage I Histology-Proven Non-Small Cell Lung Cancer.

Surgery is the standard treatment for stage I non-small cell lung cancer (NSCLC); however, no clear randomized trial demonstrates its superiority to stereotactic body radiotherapy (SBRT) regarding survival. We aimed to retrospectively evaluate the treatment outcomes of SBRT in operable patients with stage I NSCLC using a large Japanese multi-institutional database to show real-world outcome. Exactly 399 patients (median age 75 years; 262 males and 137 females) with stage I (IA 292, IB 107) histologically proven NSCLC (adenocarcinoma 267, squamous cell carcinoma 96, others 36) treated at 20 institutions were reviewed. SBRT was prescribed at a total dose of 48-70 Gy in 4-10 fractions. The median follow-up period was 38 months. Local progression-free survival rates were 84.2% in all patients and 86.1% in the T1, 78.6% in T2, 89.2% in adenocarcinoma, and 70.5% in squamous cell subgroups. Overall 3-year survival rates were 77.0% in all patients: 90.7% in females, 69.6% in males, and 41.2% in patients with pulmonary interstitial changes. Fatal radiation pneumonitis was observed in two patients, all of whom had pulmonary interstitial changes. This real-world evidence will be useful in shared decision-making for optimal treatment, including SBRT for operable stage I NSCLC, particularly in older patients.

KORTUC, a novel hydrogen peroxide­based radiosensitizer for the enhancement of brachytherapy in patients with unresectable recurrent uterine cervical cancer.

Kochi Oxydol Radiation Therapy for Unresectable Carcinoma (KORTUC) is a novel radiosensitizer invented by Professor Ogawa at Kochi University (Japan) in 2006. The current study aimed to report the experience of the present authors with the use of KORTUC treatment in combination with interstitial brachytherapy (ISBT), with or without external beam (EB) radiotherapy (RT), in patients with locally recurrent cervical cancer (LRCC), who were likely to have a high risk of poor prognosis. Between April 2012 and January 2020, 14 female patients (15 tumoral lesions) with LRCC underwent KORTUC with ISBT. Their previous treatments included surgery (n=4), radiation therapy (n=8) and surgery plus RT (n=3). The primary lesions were located in the vaginal stump (n=5), pelvic wall (n=3), cervix (n=3), vaginal wall (n=2) and lymph nodes (n=2). At 2 h before RT, KORTUC was injected intratumorally via direct colposcopy. The dose of KORTUC ranged from 4-12 ml, adjusted for the tumor size. For patients who underwent ISBT, KORTUC was administered before and after insertion of the applicator before irradiation. Intratumoral injection of KORTUC was completed without any technical or safety issues in all 15 patients; it was well tolerated with no adverse events observed. KORTUC also showed preferable efficacy; a clinical complete response was observed in 87% of patients and the initial response rate was 100%. The 2-year local control rate in patients who underwent ISBT + KORTUC was 79%, whereas it was 63% in the re-irradiation group which was significantly lower (P=0.02) than that in the non-irradiation group (100%). Based on this finding, KORTUC with external irradiation is considered to be an optimal treatment strategy for patients with newly diagnosed LRCC this disease. Additionally, KORTUC may be an effective radiation response enhancer in multiple cancer types in which locoregional control after RT alone remains poor.

Efficacy and Safety of Bladder Preservation Therapy in Combination with Atezolizumab and Radiation Therapy (BPT-ART) for Invasive Bladder Cancer: Interim Analysis from a Multicenter, Open-label, Prospective Phase 2 Trial.

PURPOSE: To evaluate the safety and pathologic complete response (pCR) rate of radiation therapy with atezolizumab as bladder-preserving therapy for invasive bladder cancer. METHODS AND MATERIALS: A multicenter, phase 2 study was conducted with patients with clinically T2-3 or very-high-risk T1 bladder cancer who were poor candidates for or refused radical cystectomy. The interim analysis of pCR is reported as a key secondary endpoint ahead of the progression-free survival rate primary endpoint. Radiation therapy (41.4 Gy to the small pelvic field and 16.2 Gy to the whole bladder) was given in addition to 1200 mg intravenous atezolizumab every 3 weeks. After 24 treatment weeks, response was assessed after transurethral resection, and tumor programmed cell death ligand-1 (PD-L1) expression was assessed using tumor-infiltrating immune cell scores. RESULTS: Forty-five patients enrolled from January 2019 to May 2021 were analyzed. The most common clinical T stage was T2 (73.3%), followed by T1 (15.6%) and T3 (11.1%). Most tumors were solitary (77.8%), small (<3 cm) (57.8%), and without concurrent carcinoma in situ (88.9%). Thirty-eight patients (84.4%) achieved pCR. High pCR rates were achieved in older patients (90.9%) and in patients with high PD-L1-expressing tumors (95.8% vs 71.4%). Adverse events (AEs) occurred in 93.3% of patients, with diarrhea being the most common (55.6%), followed by frequent urination (42.2%) and dysuria (20.0%). The frequency of grade 3 AEs was 13.3%, whereas no grade 4 AEs were observed. CONCLUSIONS: Combination therapy with radiation therapy and atezolizumab provided high pCR rates and acceptable toxicity, indicating it could be a promising option for bladder preservation therapy.

Exploration of the threshold SUV for diagnosis of malignancy using 18F-FBPA PET/CT.

BACKGROUND: The goal of the study was to evaluate the diagnostic ability of 18F-FBPA PET/CT for malignant tumors. Findings from 18F-FBPA and 18F-FDG PET/CT were compared with pathological diagnoses in patients with malignant tumors or benign lesions. METHODS: A total of 82 patients (45 males, 37 females; median age, 63 years; age range, 20-89 years) with various types of malignant tumors or benign lesions, such as inflammation and granulomas, were examined by 18F-FDG and 18F-FBPA PET/CT. Tumor uptake of FDG or FBPA was quantified using the maximum standardized uptake value (SUVmax). The final diagnosis was confirmed by cytopathology or histopathological findings of the specimen after biopsy or surgery. A ROC curve was constructed from the SUVmax values of each PET image, and the area under the curve (AUC) and cutoff values were calculated. RESULTS: The SUVmax for 18F-FDG PET/CT did not differ significantly for malignant tumors and benign lesions (10.9 ± 6.3 vs. 9.1 ± 2.7 P = 0.62), whereas SUVmax for 18F-FBPA PET/CT was significantly higher for malignant tumors (5.1 ± 3.0 vs. 2.9 ± 0.6, P < 0.001). The best SUVmax cutoffs for distinguishing malignant tumors from benign lesions were 11.16 for 18F-FDG PET/CT (sensitivity 0.909, specificity 0.390) and 3.24 for 18F-FBPA PET/CT (sensitivity 0.818, specificity 0.753). ROC analysis showed significantly different AUC values for 18F-FDG and 18F-FBPA PET/CT (0.547 vs. 0.834, p < 0.001). CONCLUSION: 18F-FBPA PET/CT showed superior diagnostic ability over 18F-FDG PET/CT in differential diagnosis of malignant tumors and benign lesions. The results of this study suggest that 18F-FBPA PET/CT diagnosis may reduce false-positive 18F-FDG PET/CT diagnoses.

Successful salvage surgery of the residual tumor after boron neutron capture therapy (BNCT): A case report.

Salvage surgery after radiation therapy is known to be associated with a high incidence of postoperative complications. We describe a case of a successful salvage surgery after BNCT. In our patient with head and neck carcinoma, cervical lymph node recurrence with adhesion to a large vessel occurred after conventional radiotherapy. This lesion responded well to BNCT. Salvage surgery was subsequently performed to remove the residual tumor. Histopathologically, the isolated tissue contained tumor cells in its center and the surrounding tissue showed severe fibrosis. However, the tissue outside of the irradiation area had almost no fibrosis. BNCT may facilitate salvage surgery after radiotherapy because it causes less injury to the surrounding tissue than conventional radiotherapy. Our experience suggests that BNCT may be a feasible preoperative treatment in patients with inoperable lesions or in those who strongly desire preservation of function.

Improvement in the neutron beam collimation for application in boron neutron capture therapy of the head and neck region.

In June 2020, the Japanese government approved boron neutron capture therapy for the treatment of head and neck cancer. The treatment is usually performed in a single fraction, with the neutron irradiation time being approximately 30-60 min. As neutrons scatter in air and loses its intensity, it is preferable to bring the patient as close to the beam port as possible to shorten the irradiation time. However, this can be a challenge, especially for patients with head and neck cancer, as the shoulders are an obstacle to a clean positioning. In this study, a novel neutron collimation system for an accelerator based neutron source was designed to allow for a more comfortable treatment, without compromising the irradiation time. Experimental measurements confirmed the simulation results and showed the new collimator can reduce the irradiation time by approximately 60% (under the same condition where the distance between the source and the patient surface was kept the same). The dose delivered to the surrounding healthy tissue was reduced with the new collimator, showing a 25% decrease in the D50 of the mucosal membrane. Overall, the use of the newly designed collimator will allow for a more comfortable treatment of the head and neck region, reduce the treatment time, and reduce the dose delivered to the surrounding healthy tissue.

Comprehensive evaluation of dosimetric impact against position errors in accelerator-based BNCT under different treatment parameter settings.

BACKGROUND: Patients who undergo accelerator-based (AB) boron neutron capture therapy (BNCT) for head and neck cancer in the sitting position are generally uncomfortably immobilized, and patient motion during this treatment may be greater than that in other radiotherapy techniques. Furthermore, the treatment time of BNCT is relatively long (up to approximately 1 h), which increases the possibility of patient movement during treatment. As most BNCT irradiations are performed in a single fraction, the dosimetric error due to patient motion is of greater consequence and needs to be evaluated and accounted for. Several treatment parameters are required for BNCT dose calculation. PURPOSE: To investigate the dosimetric impacts (DIs) against position errors using a simple cylindrical phantom for an AB-BNCT system under different treatment parameter settings. METHODS: The treatment plans were created in RayStation and the dose calculation was performed using the NeuCure® dose engine. A cylindrical phantom (16 cm diameter × 20 cm height) made of soft tissue was modeled. Dummy tumors in the form of a 3-cm-diameter sphere were arranged at depths of 2.5 and 6.5 cm (denoted by T2.5 and T6.5 , respectively). Reference plans were created by setting the following parameters: collimator size = 10, 12, or 15 cm in diameter, collimator-to-surface distance (CSD) = 4.0 or 8.0 cm, tumor-to-blood ratio (T/B ratio) using 18 F-fluoro-borono-phenylalanine = 2.5 or 5.0, and 10 B concentration in blood = 20, 25, or 30 ppm. The prescribed dose was D95%  ≥ 20 Gy-eq for both T2.5 and T6.5 . Based on the reference plans, phantom-shifted plans were created in 26 directions [all combinations of left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions) and three distances (1.0, 2.0, and 3.0 cm). The DIs were evaluated at D80% of the tumors. The shift direction dependency of the DI in the LR, AP, and SI directions was evaluated by conducting a multiple regression analysis (MRA) and other analyses where required. RESULTS: The coefficients of the MRA of the DIs for LR, AP, and SI shifts were -0.08, 2.16, and -0.04 (p-values = 0.084, <0.01, and 0.334) for T2.5 and -0.05, 2.08, and 0.15 (p-values = 0.526, <0.01, and 0.065) for T6.5 , respectively. The analysis of variance showed that DIs due to the AP shift were significantly greater for smaller collimator sizes on T2.5 and smaller CSD on T6.5 . Dose reduction due to SI or LR (lateral) shifts was significantly greater for smaller collimator sizes on both T2.5 and T6.5 and smaller CSD on T2.5 , according to the Student's t-test. There were no significant differences in the DIs against both the AP shift and the lateral shift between the different T/B ratios and 10 B concentrations. CONCLUSION: The DIs were largely affected by the shift in the AP direction and were influenced by the different treatment parameters.

Effect of a lead block on alveolar bone protection in image-guided high-dose-rate interstitial brachytherapy for tongue cancer: using model-based dose calculation algorithms to correct for inhomogeneity.

PURPOSE: The purpose of this study was to evaluate the effect of a lead block for alveolar bone protection in image-guided high-dose-rate interstitial brachytherapy for tongue cancer. MATERIAL AND METHODS: We treated 6 patients and delivered 5,400 cGy in 9 fractions using a lead block. Effects of lead block (median thickness, 4 mm) on dose attenuation by distance were visually examined using TG-43 formalism-based dose distribution curves to determine whether or not the area with the highest dose is located in the alveolar bone, where there is a high-risk of infection. Dose re-calculations were performed using TG-186 formalism with advanced collapsed cone engine (ACE) for inhomogeneity correction set to cortical bone density for the whole mandible and alveolar bone, water density for clinical target volume (CTV), air density for outside body and lead density, and silastic density for lead block and its' silicon replica, respectively. RESULTS: The highest dose was detected outside the alveolar bone in five of the six cases. For dose-volume histogram analysis, median minimum doses delivered per fraction to the 0.1 cm3 of alveolar bone (D0.1cm3 TG-43, ACE-silicon, and ACE-lead) were 344.3 (range, 262.9-427.4) cGy, 336.6 (253.3-425.0) cGy, and 169.7 (114.9-233.3) cGy, respectively. D0.1cm3 ACE-lead was significantly lower than other parameters. No significant difference was observed between CTV-related parameters. CONCLUSIONS: The results suggested that using a lead block for alveolar bone protection with a thickness of about 4 mm, can shift the highest dose area to non-alveolar regions. In addition, it reduced D0.1cm3 of alveolar bone to about half, without affecting tumor dose.

Narrative review of local prostate and metastasis-directed radiotherapy in the treatment of metastatic prostate cancer.

The role of local treatment in patients with de novo metastatic prostate cancer is controversial. In population-based retrospective studies, metastatic prostate cancer patients who received local treatment with prostate radiotherapy showed a better prognosis than those who did not. In addition, several prospective randomized studies demonstrated that prostate radiotherapy achieves a survival benefit for patients with oligo-metastasis. Moreover, the efficacy of metastasis-directed radiotherapy was evaluated, revealing a potential benefit for patients with oligo-metastasis. Importantly, these radiotherapies may reduce the occurrence of symptomatic local events. In this review, the rationale, efficacy and future perspectives for local prostate and metastasis-directed radiotherapy in the treatment of metastatic prostate cancer were described and summarized.

Evaluation of a treatment planning system developed for clinical boron neutron capture therapy and validation against an independent Monte Carlo dose calculation system.

Boron neutron capture therapy (BNCT) for the treatment of unresectable, locally advanced, and recurrent carcinoma of the head and neck cancer has been approved by the Japanese government for reimbursement under the national health insurance as of June 2020. A new treatment planning system for clinical BNCT has been developed by Sumitomo Heavy Industries, Ltd. (Sumitomo), NeuCure® Dose Engine. To safely implement this system for clinical use, the simulated neutron flux and gamma ray dose rate inside a water phantom was compared against experimental measurements. Furthermore, to validate and verify the new planning system, the dose distribution inside an anthropomorphic head phantom was compared against a BNCT treatment planning system SERA and an in-house developed Monte Carlo dose calculation program. The simulated results closely matched the experimental results, within 5% for the thermal neutron flux and 10% for the gamma ray dose rate. The dose distribution inside the head phantom closely matched with SERA and the in-house developed dose calculation program, within 3% for the tumour and a difference of 0.3 Gyw for the brain.

New enzyme-targeting radiosensitizer (KORTUC II) treatment for locally advanced or recurrent breast cancer.

Kochi oxydol radiation therapy for unresectable carcinomas II (KORTUC II) is currently the most widely used radiosensitizer in Japan. This sensitizer is a solution consisting of 0.83% sodium hyaluronate and 0.5% hydrogen peroxide. The mixture is injected intratumorally just before radiation therapy (RT) several times. KORTUC II has the effect of neutralizing antioxidant enzymes, while increasing the oxygen tension into the tumor tissue, and achieves marked local effects without notable adverse events. The present report describes cases in which KORTUC II was used to treat patients with locally advanced breast cancer (LABC) or recurrent breast cancer (LRBC). The present study included 30 patients with LABC (n=9) or LRBC (n=21) aimed at local control of tumors, who were followed up for ≥3 months after treatment. The irradiation dose and extent fields were determined by the attending physicians considering various patient factors, such as a performance status, prognosis and presence or absence of adjuvant therapy. The median irradiation dose was 60.4 Gy3.5 (43.6-76.1 Gy3.5) based on the calculation of equivalents of 2 Gy fractions, and the median total number of sensitizer injections was 5 (2-7) times. The median maximum tumor shrinkage was 97.0% and 15 patients (50%) were assessed to have achieved a clinical complete response. The proportion with loco-regional control at 1, 2 and 3 years was 100, 94.7 and 75.4%, respectively, and progression free survival after RT at 1 and 2 years was 59.0 and 24.1%, respectively. KORTUC II exhibited high rates of local tumor control for LABC and LRBC. KORTUC II is expected to be an inexpensive and promising RT method because it is safe and has an excellent radio-sensitizing effect.

High-dose-rate interstitial brachytherapy with hypoxic radiosensitizer KORTUC II for unresectable pelvic sidewall recurrence of uterine cervical cancer: a case report.

In order to improve oncologic outcomes in radiotherapy treatments of patients with unresectable pelvic sidewall recurrences of uterine cervical cancer, we combined high-dose-rate interstitial brachytherapy (HDR-ISBT) with newly tested hypoxic radiosensitizer Kochi oxydol-radiation therapy for unresectable carcinomas (KORTUC II), an enzyme-targeting radiosensitization treatment involving intra-tumoral injection of sodium hyaluronate mixed with hydrogen peroxide. We report on a 63-year-old patient referred to our department with an extensive pelvic sidewall recurrence of uterine cervical cancer after initial hysterectomy. The tumor size was 55 × 25 × 80 mm, with a calculated volume of 89.7 cc. Whole pelvic irradiation of 50 Gy in 25 fractions was administered, combined with weekly cisplatin injections. KORTUC II injections were given two times: at day 21 (42 Gy) and at day 24 (48 Gy). After finishing whole pelvic irradiation, HDR-ISBT of 25 Gy in 5 fractions b.i.d. over 3 days was administered. KORTUC II was also injected at the time of implantation. Dose-volume histogram (DVH) values for clinical target volume were D90, D98, and D100 of 6.0, 5.0, and 3.5 Gy per fraction, respectively. D2cc values were 2.1, 4.1, 3.2, and 2.0 Gy per fraction for the bladder, rectum, sigmoid colon, and small bowel, respectively. No acute adverse events ≥ grade 3 were observed. Repeated grade 3 pyelonephritis occurred as a late complication at 11, 24, and 26 months after the treatment, and was successfully resolved with antibiotics. Moreover, grade 2 late toxicity was documented, including sciatic neuralgia, lower limb lymphedema, and urinary incontinence. At present, 32 months after HDR-ISBT, the patient remains free of disease, with no toxicity-related deterioration in physical condition.