This study investigated the dosimetric impact of implementing heterogeneous boron distribution into dose evaluations on tumors in BNCT. The study involved 27 patients who underwent 18F-BPA PET/CT scans. Dose evaluations were performed using various methods reflecting boron concentrations on CT images. The conventional dose evaluations, which reflected uniform boron concentration in blood of 25 ppm and a constant tumor-to-blood (T/B) ratio of 3.5, were compared with individual dose evaluations, which reflected the blood boron concentration and T/B ratio calculated from 18F-BPA in each patient. The heterogeneous tumoral dose distribution was also compared, revealing the dosimetric impact of the boron distribution calculated from each voxel of 18F-BPA. The spatial correspondence between 18F-BPA and dose distribution was compared using metabolic tumor volume (MTV) from 18F-BPA and isodose volume from the heterogeneous dose distribution. Results showed that the median blood boron concentration and T/B ratio calculated from 18F-BPA were 25.57 (23.90-27.84) ppm and 3.75 (2.54-4.59), respectively, comparable to those in the conventional dose evaluations. All dose indices in the heterogeneous tumoral dose evaluations were significantly lower than those in the conventional dose evaluations (p < 0.01). However, the spatial correspondence between the 18F-BPA and the dose distribution was not observed in the dice similarity coefficients of both MTV40-40% isodose volume and MTV50-50% isodose volume. In conclusion, the study confirmed the validity of applying the boron concentration calculated from 18F-BPA to the dose evaluation for a patient in BNCT. The differences might be associated with non-inter-patient variations of 18F-BPA, but the conventional dose evaluations mainly focused on the high boron concentration area within the tumor. Furthermore, the discrepancies in the patients were also observed between the 18F-BPA distribution and the heterogeneous dose distribution. Therefore, this study suggested that the indications for BNCT should consider not only 18F-BPA but also the dose distributions, which could reflect the heterogeneous tumoral boron distribution.

To evaluate the efficacy and safety of diffusing alpha-emitter radiation therapy (DaRT) for recurrent head and neck cancer (rHNC) after radiotherapy. This study was a multicenter prospective clinical trial. Eligibility criteria included all patients with biopsy-proven rHNC and history of radiotherapy. The efficacy of DaRT was evaluated in terms of tumor shrinkage after 10 weeks of DaRT seed implantation. To assess safety of DaRT, radioactivity levels in blood and urine were measured, and incidence and grade of adverse events (AEs) were evaluated. Between 2019 and 2021, DaRT was performed in 11 patients and completed in 10 patients with 11 tumors. The tumor sites included the tongue (n = 3), buccal mucosa (2), lips (2), floor of the mouth (1), soft palate (1), nose (1), and subcutaneous layer (1). Nine tumors were confirmed to be squamous cell carcinoma, and the remaining two tumors were basal cell carcinoma and neuroblastoma. Complete response (CR) and partial response (PR) were observed in three and six patients, respectively. The response rate was 81.8

Boron neutron capture therapy (BNCT) is based on nuclear reactions between thermal neutron and boron-10 preferentially distributed in the cancer cells. 10B-boronophenylalanine (BPA) is the approved drug for treatment of oral cancers for BNCT. However, the predictive biomarkers to evaluate therapeutic efficacy and side-effects have not been clarified yet. Here we performed comprehensive analysis of mRNA expression using human oral squamous carcinoma SAS cells after BPA-BNCT. The expression of particular mRNAs including inflammatory and immune-related responses and transcription factors, namely CSF2, ATF3, MAFB, PTGS2 and TNFAIP3 was increased 24 h after neutron irradiation of therapeutic dose of BPA-BNCT. NF-κB pathway genes were also activated after BNCT. The early increase of the gene product of CSF2 gene, granulocyte-macrophage colony stimulating factor (GM-CSF), in culture supernatant of SAS cells was observed by ELISA analysis after BPA-BNCT at a setting dose of 24 Gy-eq. The GM-CSF level was also increased after equivalent dose of gamma-ray and carbon beam irradiation. GM-CSF may be involved in local and systemic early responses of BNCT for particular types of cancer.

Brain metastases from colorectal cancer are rare but carry a dismal prognosis. This study aimed to develop and externally validate a prognostic model for individualized survival prediction in affected patients. The model was constructed using a training cohort of 112 patients diagnosed with brain metastases after initial colorectal cancer treatment at our institution between 1985 and 2017, and validated in an external cohort of 114 patients referred for brain metastasis treatment between 1987 and 2017. A nomogram was developed incorporating five variables: age, performance status assessed by the Karnofsky Performance Status scale, number of brain metastases, maximum size of brain lesions, and number of prior systemic chemotherapy regimens. In the training cohort, the median survival was 6.6 months, with 1-year and 3-year survival rates of 29.0% and 7.2%. Poorer performance status, multiple metastases, and higher number of chemotherapy regimens were associated with worse prognosis. In the validation cohort, median survival was 5.8 months, with 1-year and 3-year survival rates of 27.0% and 8.4%. Harrell’s concordance index was 0.70 for internal validation and 0.63 for external validation. This model may provide a clinically useful tool for individualized survival estimation in patients with brain metastases from colorectal cancer.

Several types of accelerator-based boron neutron capture therapy (AB-BNCT) systems have been developed; however, the features of neutron beams differ among facilities depending on the target type and acceleration energy. AB-BNCT systems with both downward and horizontal beams have been developed. Preclinical evaluation of AB-BNCT is an important prerequisite for its use as basic data for clinical trials. Herein, we describe a general scheme for evaluating the safety and efficacy of BNCT systems. Cell-based assays and animal model studies were designed to assess the safety and efficiency of BNCT for preclinical evaluation. For cell-based studies, particular types of cancer and normal cells can be used depending on the planning of clinical trial designs. For animal studies, small rodents can only be used, depending on the medical regulations of countries. The preclinical experimental designs were found necessary to include following conditions; 1) The radioactivation level of animals after neutron beam irradiation is necessary to confirm in order to transfer the animals to outside facilities for long-term observations. 2) For each AB-BNCT system, determination of the value of the relative biological effect (RBE) of the neutron (hydrogen) dose, which is the dose from elastic scattering of fast and epithermal neutrons on cellular and tissue hydrogens, is necessary. 3) Cytotoxicity and genotoxicity in the absence and presence of boron drugs should be tested by assessing cell survival and micronuclei formation, respectively. 4) In animal models, local and systemic toxicities, including hematological profiles, should be evaluated in the acute and long-term phases. 5) A stable setup for irradiation geometry with optimized shielding materials for the neutron beam is also necessary. We confirmed that the designed preclinical experimental models are useful for evaluating the safety and efficacy of the AB-BNCT system from a biological perspective.

To analyze in a prospective study the long-term safety and efficacy of 3-dimensional conformal radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI) for Japanese women with early breast cancer. Breast cancer patients with pathological tumor size ≤ 3 cm, age ≥ 20 years, lumpectomy with at least a 5 mm margin, and ≤ 3 positive axillary nodes were eligible. APBI was delivered by 3D-CRT at a dose of 38.5 Gy in 10 fractions over 10 days. The primary endpoints were the frequency and severity of acute and late radiation toxicities, and secondary endpoints were local control, survival, and cosmesis. The sample size was determined based on the incidence of ≥ grade 3 acute and late radiation toxicities, which required 71 enrollments. Between 2008 and 2010, 73 patients enrolled in this trial. Twelve patients (16

BACKGROUND AND PURPOSE:Definitive radiotherapy for patients with scalp angiosarcoma has a poor prognosis, often resulting in severe skin adverse events. Additionally, malignant melanoma is known for its radioresistant nature. Boron neutron capture therapy (BNCT) may address these challenges due to the high uptake capacity of boron drugs in these cancer types. We aimed to determine the treatment dose for BNCT and evaluate the incidence of acute adverse events AEs following BNCT in patients with primary or recurrent angiosarcoma/malignant melanoma of the skin. MATERIALS AND METHODS:This was a single-center, non-randomized clinical trial with a three-step dose escalation plan, involving maximum skin doses of 12, 15, and 18 Gy-Eq following a 3 + 3 design. The patients underwent BNCT between November 2019 and April 2022. The primary endpoint was to evaluate the incidence of acute adverse events. RESULTS:Ten patients (scalp angiosarcomanine, forefinger malignant melanoma: one) were included. The median target lesion size was 46.5 (range: 20-145) mm. A transient asymptomatic increase in serum amylase level was the only grade 3 adverse event. The best overall response rate within 180 days was 70 % (median tumor shrinkage rate: 77.5 % [4.9-100 %]). CONCLUSIONS:BNCT with a dose of 18 Gy-Eq is a feasible treatment option, demonstrating a favorable safety profile and a high response rate in patients with primary or recurrent angiosarcoma or malignant melanoma of the skin.

Accelerator-based boron neutron capture therapy (BNCT) systems employing a solid-state lithium target indicated the reduction of neutron flux over the lifetime of a target, and its reduction could represent the neutron flux model. This study proposes a novel compensatory approach for delivering the required neutron fluence and validates its clinical applicability. The proposed approach relies on the neutron flux model and the cumulative sum of real-time measurements of proton charges. The accuracy of delivering the required neutron fluence for BNCT using the proposed approach was examined in five Li targets. With the proposed approach, the required neutron fluence could be delivered within 3.0%, and within 1.0% in most cases. However, those without using the proposed approach exceeded 3.0% in some cases. The proposed approach can consider the neutron flux reduction adequately and decrease the effect of uncertainty in neutron measurements. Therefore, the proposed approach can improve the accuracy of delivering the required fluence for BNCT even if a neutron flux reduction is expected during treatment and over the lifetime of the Li target. Additionally, by adequately revising the approach, it may apply to other type of BNCT systems employing a Li target, furthering research in this direction.

This study reports the first patient treatment for cutaneous malignant melanoma using a linear accelerator-based boron neutron capture therapy (BNCT) system. A single-center open-label phase I clinical trial had been conducted using the system since November 2019. A patient with a localized node-negative acral malignant melanoma and the largest diameter of the tumor ≤ 15 cm who refused primary surgery and chemotherapy was enrolled. After administering boronophenylalanine (BPA), a single treatment of BNCT with the maximum dose of 18 Gy-Eq delivered to the skin was performed. The safety and efficacy of the accelerator-based BNCT system for treating localized cutaneous malignant melanoma were evaluated. The first patient with cutaneous malignant melanoma in situ on the second finger of the left hand did not develop dose-limiting toxicity in the clinical trial. After BNCT, the treatment efficacy was gradually observed, and the patient achieved PR within 6 months and CR within 12 months. Moreover, during the follow-up period of 12 months after BNCT, the patient did not exhibit a recurrence without any treatment-related grade 2 or higher adverse events. Although grade 1 adverse events of dermatitis, dry skin, skin hyperpigmentation, edema, nausea, and aching pain were noted in the patient, those adverse events were relieved without any treatment. This case report shows that the accelerator-based BNCT may become a promising treatment modality for cutaneous malignant melanoma. We expect further clinical trials to reveal the efficacy and safety of the accelerator-based BNCT for cutaneous malignant melanoma.

This study aimed to quantify the relative biological effectiveness (RBE) for epithermal neutron beam contaminated with fast neutrons in the accelerator-based boron neutron capture therapy (BNCT) system coupled to a solid-state lithium target. The experiments were performed in National Cancer Center Hospital (NCCH), Tokyo, Japan. Neutron irradiation with the system provided by Cancer Intelligence Care Systems (CICS), Inc. was performed. X-ray irradiation, which was assigned as the reference group, was also performed using a medical linear accelerator (LINAC) equipped in NCCH. The four cell lines (SAS, SCCVII, U87-MG and NB1RGB) were utilized to quantify RBE value for the neutron beam. Before both of those irradiations, all cells were collected and dispensed into vials. The doses of 10% cell surviving fraction (SF) (D10) were calculated by LQ model fitting. All cell experiments were conducted in triplicate at least. Because the system provides not only neutrons, but gamma-rays, the contribution from the gamma-rays to the survival fraction were subtracted in this study. D10 value of SAS, SCCVII, U87-MG and NB1RGB for the neutron beam was 4.26, 4.08, 5.81 and 2.72 Gy, respectively, while that acquired by the X-ray irradiation was 6.34, 7.21, 7.12 and 5.49 Gy, respectively. Comparison of both of the D10 values, RBE value of SAS, SCCVII, U87-MG and NB1RGB for the neutron beam was calculated as 1.7, 2.2, 1.3 and 2.5, respectively, and the average RBE value was 1.9. This study investigated RBE of the epithermal neutron beam contaminated with fast neutrons in the accelerator-based BNCT system coupled to a solid-state lithium target.

Introduction: Concurrent chemoradiotherapy (CCRT) has been the standard of care for patients with locally advanced non-small cell lung cancer (LA-NSCLC). Background and Purpose: The results of the PACIFIC trial established the use of consolidative durvalumab after concurrent chemoradiotherapy (CCRT) as the standard of care for patients with locally advanced non-small cell lung cancer (LA-NSCLC). A subgroup analysis of the PACIFIC trial reported a better progression-free survival (PFS) in Asians. Although real-world data on LA-NSCLC patients who received CCRT plus durvalumab have been reported, there have been few large-scale reports on Asians. In this study, we investigated prognostic factors in the largest real-world data set in Asia of only Japanese LA-NSCLC patients treated with CCRT plus durvalumab. Materials and Methods: One hundred and thirteen LA-NSCLC patients who received definitive CCRT and consolidative durvalumab at our institution between May 2018 and April 2021 were analyzed. Overall survival (OS), cause-specific survival (CSS), PFS, distant metastasis-free survival (DMFS), and in-field progression-free survival (IFPFS) were investigated as treatment outcomes using competing risk analyses. Results: During a median follow-up of 24 months (range, 5-47) after the initiation of durvalumab ther-apy, 31 patients died, of whom 23 died of lung cancer. In the multivariate analysis, the pretreatment fac-tors that correlated with OS were ILA scores, adenocarcinoma, and performance status at the initiation of durvalumab. Furthermore, ILA score and programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) >= 1 % were significantly correlated with CSS, and PD-L1 TPS >= 1 % was significantly correlated with PFS and IFPFS. Conclusion: Pretreatment ILA, adenocarcinoma, and performance status may have an impact on OS of LA-NSCLC patients receiving CCRT plus durvalumab. (c) 2022 The Author(s). Published by Elsevier B.V. Radiotherapy and Oncology xxx (2023) xxx-xxx This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

A Japanese multi-institutional prospective study was initiated to investigate the effectiveness and safety of accelerated partial breast irradiation (APBI) using strut-adjusted volume implant (SAVI) brachytherapy, with subjects registered between 2016 and 2021. Herein, we report the preliminary results on the feasibility of this treatment modality in Japan, focusing on the registration process, dosimetry, and acute toxicities. Primary registration was conducted before breast-conserving surgery (BCS) and the eligibility criteria included the following: age ≥ 40 years, tumor unifocal and unicentric, ≤ 3 cm in diameter, cN0M0, proven ductal, mucinous, tubular, medullary, or lobular carcinoma by needle biopsy. Secondary registration was conducted after BCS had been performed leaving a cavity for device implantation and pathological evaluations, and the eligibility criteria were as follows: negative surgical margin, tumor ≤ 3 cm in diameter on gross pathological examination, histologically confirmed ductal, mucinous, tubular medullary, colloid, or lobular carcinoma, pN0, L0V0, no extensive ductal component, no initiation of chemotherapy within 2 weeks of the brachytherapy APBI planning with SAVI was performed for the patients successfully entered in the study by the secondary registration process, and the treatment was administered at the dose of 34 Gy in 10 fractions administered twice daily. Between 2016 and 2021, 64 women were enrolled in the study through primary registration, of which 19 were excluded from the secondary registration process, and in one, it was deemed impossible to comply with the dose constraints established during treatment planning. After the exclusion of these latter 20 patients, we treated the remaining 44 patients by APBI with SAVI. The dose constraints could be adhered to in all the patients, but re-planning was necessitated in 3 patients because of applicator movement during the treatment period. Grade 2 acute toxicities were observed in 18

In the original publication [...].

Abstract Background The correlation between L‐type amino acid transporter 1 (LAT1) expression and 4‐borono‐2‐18F‐fluoro‐phenylalanine (18F‐FBPA) accumulation in humans remains unclear. This study aimed to investigate the correlation between LAT1 expression in tumor tissues and 18F‐FBPA accumulation in patients with head and neck cancer who participated in a clinical trial of 18F‐FBPA positron emission tomography (PET). Methods Altogether, 28 patients with head and neck cancer who participated in a clinical trial of 18F‐FBPA PET at our institution between March 2012 and January 2018 were included. Correlations between standardized uptake values (SUVs); the maximum SUV (SUVmax), the mean SUV within a 1 cm3 sphere centered at a single point, that is, the SUVmax (SUVpeak), the minimum SUV (SUVmin), and the intensity of LAT1 expression (maximum and minimum LAT1 expressions) were investigated. Results Weak correlations were identified between SUVmax and LAT1 maximum score, SUVmin and LAT1 maximum score, and SUVmin and LAT1 minimum score (ρ = 0.427, 0.362, and 0.330, respectively). SUVmax and LAT1 minimum score, SUVpeak and LAT1 maximum score, and SUVpeak and LAT1 minimum score demonstrated moderate correlations (ρ = 0.535, 0.556, and 0.661, respectively). Boron neutron capture therapy (BNCT) was performed in 2 of the 4 patients with discrepancies between 18F‐FBPA accumulation and intensity of LAT1 expression, and the intensity of LAT1 expression was a better predictor of treatment response. Conclusion 18F‐FBPA accumulation and the intensity of LAT1 expression demonstrated a moderate correlation; however, LAT1 expression may be a better predictor of treatment response of BNCT in patients with discrepancies.

Background and purpose: Ultrahypofractionated radiation therapy is increasingly used in the treatment of prostate cancer. High-dose-rate brachytherapy (HDR-BT) and stereotactic body radiotherapy (SBRT) are representative methods of ultrahypofractionation. This study was performed to compare clinically applied treatment plans for patients who had been treated using HDR-BT vs. conventional or robotic SBRT. Materials and methods: Calculated dose-volume indices between HDR-BT without a perirectal spacer (n = 20), robotic SBRT without a spacer (n = 40), and conventional (non-robotic) SBRT with a spacer (n = 40) were compared. Percentages against the prescription dose regarding the planning target volume (PTV), bladder, rectum, and urethra were statistically compared. Results: The D50% of the PTV with HDR-BT (140.5% +/- 4.9%) was significantly higher than that with robotic or conventional SBRT (116.2% +/- 1.6%, 101.0% +/- 0.4%, p < 0.01). The D2cm3 of the bladder with HDR-BT (65.6% +/- 6.4%) was significantly lower than those with SBRT (105.3% +/- 2.9%, 98.0% +/- 1.3%, p < 0.01). The D2cm3 of the rectum with HDR-BT (60.6% +/- 6.2%) was also significantly lower than those with SBRT (85.1% +/- 8.8%, 70.4% +/- 9.6%, p < 0.01). By contrast, the D0.1cm(3) of the urethra with HDR-BT (117.1% +/- 3.6%) was significantly higher than those with SBRT (100.2% +/- 0.7%, 104.5% +/- 0.6%, p < 0.01). Conclusions: HDR-BT could administer a higher dose to the PTV and a lower dose to the bladder and rectum, at the cost of a slightly higher dose to the urethra compared with SBRT.

Objective: The purposes of this trial were to demonstrate the feasibility and effectiveness of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients in the phase I/II prospective clinical trial. Methods: Patients with FIGO stage IB2-IVA uterine cervical cancer pretreatment width of which was >= 5 cm measured by magnetic resonance imaging were eligible for this clinical trial. The protocol therapy included 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of HBT and pelvic radiotherapy with a central shield up to 50-50.4 Gy in 25-28 fractions. The primary endpoint of phase II part was 2-year pelvic progression-free survival (PPFS) rate higher than historical control of 64%. Results: Between October 2015 and October 2019, 73 patients were enrolled in the initial registration and 52 patients proceeded to the secondary registration. With the median follow-up period of 37.3 months (range, 13.9-52.9 months), the 2-PPFS was 80.7% (90% confidence interval [CI]=69.7%-88%). Because the lower range of 90% CI of 2-year PPFS was 69.7%, which was higher than the historical control ICBT data of 64%, therefore, the primary endpoint of this study was met. Conclusion: The effectiveness of HBT were demonstrated by a prospective clinical study. Because the dose goal determined in the protocol was lower than 85 Gy, there is room in improvement for local control. A higher dose might have been needed for tumors with poor responses.

Treatment of brain metastases (BMs) from colorectal cancer (CRC) has transitioned with the expansion of indications for stereotactic radiotherapy. Our study aimed to assess changes in prognosis and prognostic factors associated with changes in treatment for BMs from CRC. We retrospectively surveyed treatments for and outcomes of BMs from CRC in 208 patients treated during 1997–2018. Patients were divided into two groups according to time of BM diagnosis, i.e., 1997–2013 (“first period”) and 2014–2018 (“second period”). We compared overall survival between the periods and assessed how the transition impacted prognostic factors affecting overall survival, including the following prognostic factors such as Karnofsky performance status (KPS), volume-related factors (BM number and diameter), and BM treatment modalities as covariates. Of the 208 patients, 147 were treated in the first period and 61 in the second period. Whole-brain radiotherapy use decreased from 67 to 39

The first magnetic resonance (MR)-guided radiotherapy system in Japan was installed in May 2017. Implementation of online MR-guided adaptive radiotherapy (MRgART) began in February 2018. Online MRgART offers greater treatment accuracy owing to the high soft-tissue contrast in MR-images (MRI), compared to that in X-ray imaging. The Japanese Society for Magnetic Resonance in Medicine (JSMRM), Japan Society of Medical Physics (JSMP), Japan Radiological Society (JRS), Japanese Society of Radiological Technology (JSRT), and Japanese Society for Radiation Oncology (JASTRO) jointly established the comprehensive practical guidelines for online MRgART. These guidelines propose the essential requirements for clinical implementation of online MRgART with respect to equipment, personnel, institutional environment, practice guidance, and quality assurance/quality control (QA/QC). The minimum requirements for related equipment and QA/QC tools, recommendations for safe operation of MRI system, and the implementation system are described. The accuracy of monitor chamber and detector in dose measurements should be confirmed because of the presence of magnetic field. The ionization chamber should be MR-compatible. Non-MR-compatible devices should be used in an area that is not affected by the static magnetic field (outside the five Gauss line), and their operation should be checked to ensure that they do not affect the MR image quality. Dose verification should be performed using an independent dose verification system that has been confirmed to be reliable through commissioning. This guideline proposes the checklists to ensure the safety of online MRgART. Successful clinical implementation of online MRgART requires close collaboration between physician, radiological technologist, nurse, and medical physicist.