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This study aimed to identify the required capabilities and workload of medical staff in accelerator-based boron neutron capture therapy (BNCT). From August to September 2022, a questionnaire related to the capabilities and workload in the accelerator-based BNCT was administered to 12 physicians, 7 medical physicists and 7 radiological technologists engaged in BNCT and 6 other medical physicists who were not engaged in BNCT to compare the results acquired by those engaged in BNCT. Only 6–21% of patients referred for BNCT received it. Furthermore, 30–75% of patients who received BNCT were treated at facilities located within their local district. The median required workload per treatment was 55 h. Considering additional workloads for ineligible patients, the required workload reached ~1.2 times longer than those for only eligible patients' treatment. With respect to capabilities, discrepancies were observed in treatment planning, quality assurance and quality control, and commissioning between medical physicists and radiological technologists. Furthermore, the specialized skills required by medical physicists are impossible to acquire from the experience of conventional radiotherapies as physicians engaged in BNCT were specialized not only in radiation oncology, but also in other fields. This study indicated the required workload and staff capabilities for conducting accelerator-based BNCT considering actual clinical conditions. The workload required for BNCT depends on the occupation. It is necessary to establish an educational program and certification system for the skills required to safely and effectively provide BNCT to patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: In post-irradiated recurrent head and neck cancer (R-HNC), the treatment safety margin is limited by accumulated toxicity. Despite the development of aggressive curative treatment methods, such as reirradiation with photon or particle beam therapy with or without chemotherapy, sufficient clinical outcomes have not been achieved in various prospective trials due to the limitations imposed by toxicity. Boron neutron capture therapy (BNCT), with its selective cell-by-cell dose delivery, may be an effective and safe treatment option for patients with a prior radiotherapy history, as the previous Phase II trial of BNCT in unresectable locally recurrent or locally R-HNC has shown encouraging results. In this study, we analyzed the results of a Japanese nationwide post-marketing surveillance of BNCT for R-HNC conducted under the national health insurance system and found that toxicity was well-tolerated with preferable efficacy. BNCT is suggested to be a promising treatment option in post-irradiated R-HNC. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: According to current guidelines, surgery is the standard treatment for stage I non-small cell lung cancer (NSCLC), despite no clear randomized trial demonstrating that surgery is superior to stereotactic body radiotherapy (SBRT). Therefore, this study aimed to provide real-world evidence of the usefulness of SBRT for medically operable patients with pathologically proven stage I NSCLC using a large Japanese multi-institutional database. A total of 399 patients from 20 institutions were included in the database. In the results, local progression-free survival was 84.2%, and the 3-year overall survival was 77.0%. The local progression-free survival rate was better in cases with tumors ≤ 20 mm in diameter and in the adenocarcinoma subgroups. Low performance status, male sex, and pulmonary interstitial changes were poor prognostic factors for overall survival. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 18F‐fluoro‐borono‐phenylalanine = 2.5 or 5.0, and 10B 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 10B concentrations. Conclusion: The DIs were largely affected by the shift in the AP direction and were influenced by the different treatment parameters. [ABSTRACT FROM AUTHOR]

The world's first accelerator based epithermal neutron source for clinical boron neutron capture therapy (BNCT) was designed, developed, and commissioned between 2008 and 2010 by Sumitomo Heavy Industries in collaboration with Kyoto University at the Kyoto University Institute for Integrated Radiation and Nuclear Science. The accelerator system is cyclotron-based and accelerates a proton up to an energy of approximately 30 MeV. The proton strikes a beryllium target, which produces fast neutrons that traverse a beam shaping assembly composed of a combination of lead, iron, aluminum, and calcium fluoride to reduce the neutron energy down to the epithermal range (∼10 keV) suitable for BNCT. The system is designed to produce an epithermal neutron flux of up to 1.4 × 10 9 n · cm − 2 · s − 1 (exiting from the moderator of a 12 cm diameter collimator) with a proton current of 1 mA. In 2017, the same type of accelerator was installed at the Kansai BNCT Medical Center and in March 2020 the system received medical device approval in Japan (Sumitomo Heavy Industries, NeuCure® BNCT system). Soon after, BNCT for unresectable, locally advanced, and recurrent carcinoma of the head and neck region was approved by the Japanese government for reimbursement covered by the national health insurance system. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Palliative therapeutic strategies in esophageal squamous cell carcinoma (ESCC) patients with dysphagia remain controversial. Only few studies have assessed therapeutic effect factors related to improvement in dysphagia score and nutrition-support-free survival (NSFS).Objective: The present study assessed the efficacy and therapeutic effect factors related to the use of palliative radiotherapy (RT) and chemoradiotherapy (CRT) in ESCC patients with dysphagia.Methods: We retrospectively evaluated 70 patients with stage IVA/B ESCC. Patients received RT of 30 Gy in 10 fractions or concurrent CRT using 5-fluorouracil plus cisplatin of 40 Gy in 20 fractions. The change in the dysphagia score from before to after treatment was assessed, and NSFS was evaluated.Results: The median follow-up duration was 6 months (range 1-41 months). The overall rate of improvement in the dysphagia score was 60%. The median NSFS was 7.5 months. Craniocaudal tumor length < 6 cm, tumor circumference < 3/4, and CRT of 40 Gy in 20 fractions were associated with a significant improvement in the dysphagia score (p = 0.0036, p = 0.0069, and p = 0.03, respectively). NSFS was significantly longer with CRT than with RT (p = 0.048).Conclusion: Palliative RT and CRT are effective treatment options for ESCC patients with dysphagia. Craniocaudal tumor length < 6 cm, tumor circumference < 3/4, and CRT of 40 Gy in 20 fractions may improve dysphagia. CRT of 40 Gy in 20 fractions may improve NSFS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: For patients with postoperative lymph node (LN) recurrent esophageal cancer, the appropriate irradiation field in chemoradiotherapy (CRT) remains controversial. We assessed the clinical outcomes and prognostic factors related to involved-field CRT for postoperative solitary LN recurrence of esophageal squamous cell carcinoma (ESCC).Methods: We retrospectively evaluated 21 patients who had received curative resection, with LN recurrence of ESCC. Patients received CRT using 5-fluorouracil plus cisplatin or docetaxel, prescribed at 60 Gy in 30 fractions. We evaluated the pattern of failure, toxicities, survivals, and prognostic factors. We defined elective nodal failure (ENF) as recurrence in a regional LN without involved-field failure.Results: The median follow-up duration was 32 months (range, 4-106 months). Nine patients experienced failure—4 (19%) within involved-field and 5 (24%) with distant metastasis. No patients had ENF. We observed no severe toxicities. The 2-year overall survival (OS) rate was 78%. In the univariate analysis of OS, two factors, the maximal diameter of the metastatic LN < 25 mm and the absence of serum p53 antibodies (s-p53-Abs), were associated with a significantly better prognosis (p = 0.025 and p = 0.01, respectively).Conclusions: Involved-field CRT for postoperative solitary LN recurrence of ESCC did not cause ENF and was without severe toxicities. Two factors, a length of the metastatic LN < 25 mm and the absence of s-p53-Abs may improve the treatment outcome. Involved-field CRT is a treatment option worthy of consideration for postoperative solitary LN recurrence of ESCC. [ABSTRACT FROM AUTHOR]

Due to recent advancements in diagnostic techniques, the incidence of multiple primary cancer has increased; however, synchronous cancer of the anal canal and cervix (SCACC) is rare, and no previous studies have investigated the treatment of this disease. The present study reports a case in which intensity‑modulated radiotherapy (IMRT) was used to treat a 64‑year‑old female with SCACC, inguinal lymphadenopathy and anal pain. The patient was diagnosed with cT3N3M0 stage IIIb anal canal squamous cell carcinoma and cT1b1N0M0 stage Ib1 cervical squamous cell carcinoma, based on biopsy and imaging study data. According to the definitive treatment for advanced‑stage anal canal cancer, outpatient treatment with chemoradiotherapy (CRT) using S‑1 for SCACC was recommended, as the patient did not want to undergo resection of the anus. Considering the lymph node regions involved in SCACC and the necessary doses, the treatment plan was as follows: Whole pelvis and inguinal lymph node region radiation (36 Gy/20 fractions); a first booster radiation dose (9 Gy/5 fractions) for the whole pelvis; and a second booster radiation dose (14.4 Gy/8 fractions) for the primary lesions. The patient was prescribed S‑1 at a dose of 60 mg/m2/day twice daily on days 1‑14 and 29‑42. The patient experienced grade 2 diarrhea and anal mucositis, but CRT was completed without discontinuation and hospitalization. The patient exhibited a complete response and remained disease‑free without any treatment‑associated complications at the 6‑month follow‑up. In conclusion, SCACC was successfully treated with IMRT in the present case. It is important to determine the treatment strategy for synchronous cancer types, taking into consideration the tumor stage, tumor location and patient situation. [ABSTRACT FROM AUTHOR]

Background: Intensity-modulated radiation therapy (IMRT) reduces the dose delivered to organs at risk. However, there have been few direct comparisons of IMRT with conventional three-dimensional conformal radiotherapy (3DCRT). The aim of this study was to evaluate the clinical benefit of IMRT in terms of toxicity and biochemical control. Methods: The medical records of 203 consecutive patients with localized to non-metastatic (stage T1a-T3bN0M0) prostate cancer between 2007 and 2011 were retrospectively reviewed. The prescribed dose was 76 Gy delivered in 38 fractions in both the 3DCRT and IMRT treatment groups. The frequency of grade 2 or greater late gastrointestinal (GI) and genitourinary toxicity and biochemical control were estimated by the log-rank test and Cox proportional hazards model with and without adjustment by the propensity score for treatment choice. Results: A total of 159 patients were included in the study (3DCRT: 70 patients, IMRT: 89 patients). The median follow-up period was 4.7 years. The estimated 5-year cumulative risk of late GI toxicity was significantly lower in the IMRT group than in the 3DCRT group (3.6 vs 13.2%, respectively, p = 0.022). After adjustment by propensity score, IMRT remained associated with a lower risk of late GI toxicity (hazard ratio 0.22; 95% confidence interval 0.058-0.85; p = 0.028). The 5-year biochemical failure-free rate was 93.2% in the 3DCRT group and 95.4% in the IMRT group (non-significant difference). Conclusions: The incidence of late GI toxicity was significantly lower in the IMRT group than in the 3DCRT group, while the biochemical control rates were no different between the two groups. These clinical data suggest the benefit of IMRT in the reduction of late GI toxicity. [ABSTRACT FROM AUTHOR]

The article offers information on the study which assumed that hepatic blood tests would offer a surrogate endpoint for liver failure death, and therefore evaluated the effects of whole-liver radiotherapy (WLRT ) for diffuse liver metastases (LM )on hepatic blood tests. Topics discussed include study investigated abnormal results from hepatic blood tests at WLRT and evaluated the effect of WLRT for diffuse LM on hepatic blood tests and concludes that more reliable data from trials are required.

We evaluated the prognostic roles of local therapy to bone metastasis (BM) in metastatic renal cell carcinoma (mRCC) patients with BM. This retrospective study included 71 mRCC patients with BM. Local therapy to BM included en bloc resection, curettage, and radiotherapy (RT). RT was classified into RT with biological effective dose (BED) ≥85 Gy and <85 Gy by its therapeutic intensity. Local therapy to BM was given for 64 patients (90 %): en bloc resection, curettage, and RT for 16, 10, and 38 patients, respectively. Fifteen patients received RT with BED ≥85 Gy. The median overall survival (OS) was 25 months (median follow-up 16 months). For 46 patients with solitary BM, patients treated with en bloc resection, curettage, and RT with BED ≥85 Gy showed significantly better OS than those treated with RT with BED <85 Gy or no local therapy ( P = 0.006). Because OS was comparable among patients treated with en bloc resection, curettage, and RT with BED ≥85 Gy, these three treatment modalities were defined as 'intensive local therapy'. Intensive local therapy to BM was also associated with favorable OS with marginal significance ( P = 0.052) in a cohort of 25 patients with multiple BM. A multivariate analysis in the whole cohort revealed that intensive local therapy to BM was independently associated with favorable OS (hazard ratio 0.23, P < 0.001) along with Memorial-Sloan Kettering Cancer Center risk category ( P < 0.001). Thus, intensive local therapy to BM might improve OS in mRCC patients with BM including multiple BM. [ABSTRACT FROM AUTHOR]

To evaluate the feasibility of amrubicin plus cisplatin ( AP) following chemoradiotherapy for limited-disease small-cell lung cancer, chemo-naïve patients aged 20-70 years with a performance status of 0 or 1 and normal organ functions were treated with etoposide 100 mg/m2 on days 1-3, cisplatin 80 mg/m2 on day 1 and concurrent thoracic radiotherapy at 45 Gy/30 fractions ( EP- TRT), followed by three cycles of amrubicin 40 mg/m2 on days 1-3 and cisplatin 60 mg/m2 on day 1 every 3 weeks. The EP- TRT could be completed in 21 patients (15 male and 6 female patients with a median age of 62 years). Of these, 2, 1 and 18 (86%) patients received one, two and three cycles of AP, respectively. Sixteen (76%) patients required granulocyte-colony stimulating factor (G- CSF) support. Grade 3/4 neutropenia occurred in all patients. Grade 3 febrile neutropenia was observed in 9 patients, lasting for 1 day in 5 patients. The incidences of grade 3/4 thrombocytopenia and anemia were 43 and 24%, respectively. Grade 3 infection and anorexia occurred in 2 and 3 patients, respectively. The response rate was 95%. The median (95% confidence interval [ CI]) progression-free survival ( PFS) was 41.9 (0-102) months, and the 5-year PFS rate ( CI) was 41.9% (20.4-63.4%). The median overall survival ( OS) has not been reached yet, and the 5-year OS rate ( CI) was 57.8% (35.2-80.4%). In conclusion, EP- TRT followed by AP therapy was well-tolerated, although a large number of patients required G- CSF support. [ABSTRACT FROM AUTHOR]

We carried out a phase I/ II trial of chemoradiotherapy concurrent with S-1 and cisplatin to determine the maximum tolerated dose and recommended dose and to evaluate the efficacy and safety of this treatment in patients with esophageal carcinoma. Thoracic esophageal cancer patients with clinical stage II/ III disease, excluding T4, were eligible. Chemotherapy consisted of S-1 at a dose of 60-80 mg/m2/day on days 1-14, and cisplatin at 75 mg/m2 on day 1, repeated twice every 4 weeks. Single daily radiation of 50.4 Gy was given in 28 fractions concurrently starting on day 1. Patients achieving an objective response after chemoradiotherapy underwent two additional cycles of chemotherapy. Patient accrual was terminated early due to slow enrolment after 44 patients were accrued. In the phase I part, two of six patients experienced dose-limiting toxicities at each level of S-1 (S-1 60 or 80 mg/m2/day). Considering treatment compliance, the recommended dose was determined to be S-1 60 mg/m2/day. The complete response rate, the primary endpoint of phase II, was 59.5% (22/37; 90% confidence interval, 44.6-73.1%; weighted threshold, 57.2%; P = 0.46 by the exact binomial test) on central review. In the phase II part, 3-year progression-free survival was 48.4%, with a 3-year overall survival of 61.9%. Grade 3 or 4 toxicity in phase II included leukopenia (57.9%), neutropenia (50%), hyponatremia (28.9%), anorexia (21.1%), anemia (18.4%), thrombocytopenia (18.4%), and febrile neutropenia (2.6%). No treatment-related deaths were observed. Although this combination showed acceptable toxicity and favorable 3-year survival, the study did not meet its primary endpoint. This trial was registered at the UMIN Clinical Trials Registry as UMIN000000710. [ABSTRACT FROM AUTHOR]

Objective: Identifying factors that predispose patients to central nervous system (CNS) metastases may hasten disease detection and improve treatment outcomes. Methods: We reviewed the records of patients who were diagnosed with clinical stage I-III primary breast cancer at the National Cancer Center Hospital East from 2003 to 2005. Cox proportional hazard models were fitted to reveal risk factors for CNS metastases. Results: The median follow-up period after the operation was 53.5 months. Among the 591 identified patients with breast cancer, 76 experienced a relapse. Seventeen patients developed CNS metastases. Multivariate analysis indicated that the triple negative (TN) subtype (hazard ratio = 5.5) and a high Ki67 labeling index (LI; hazard ratio = 3.9) were associated with a higher risk for CNS metastases. At 4 years, the TN subtype was associated with significantly worse overall and disease-free survival rates and a higher cumulative incidence of CNS metastases compared with hormone receptor-positive/ human epidermal growth factor receptor-2-negative tumors. Breast cancers with a Ki67 LI ≥30% were also associated with lower overall and disease-free survival rates and a higher cumulative incidence of CNS metastases compared with cancers with a Ki67 LI <30%. Conclusion: TN or Ki67-overexpressing breast cancer produced earlier CNS metastases and lower disease-free and overall survival rates. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: We conducted a retrospective analysis to clarify the clinical profile of a nonsurgical approach to small cell carcinoma of the esophagus (SCEC). Patients and methods: SCEC patients in our database were reviewed. Consistent with the standard approach to small cell carcinoma of the lung (SCLC), chemoradiotherapy was the first choice for limited disease (LD)-SCEC in our institution while chemotherapy was the first choice for extensive disease (ED)-SCEC. Our strategy did not include prophylactic cranial irradiation. Results: Eighteen patients were treated between January 1996 and December 2006, of whom 10 had LD-SCEC and 8 had ED-SCEC. Regarding response to chemoradiotherapy in patients with LD-SCEC, CR rate at the primary site was 90% (9/10) and total CR rate was 80% (8/10). With a median follow-up period of 55.3 months, median survival time in LD-SCEC and ED-SCEC patients was 17.3 and 13.9 months, respectively, showing no significant difference ( p = 0.57). Brain metastases occurred in only one patient. On follow-up, eight patients with LD-SCEC and seven with ED-SCEC died of disease. Only 2 patients died of local progression, while the remaining 13 died of disease progression of distant metastases. Conclusion: Despite providing good local control, chemoradiotherapy appeared to have insufficient potential to cure LD-SCEC. Prophylactic brain irradiation for SCEC is unnecessary. [ABSTRACT FROM AUTHOR]

Nedaplatin is an analogue of cisplatin with less nonhematologic toxicity. The combination of nedaplatin and 5-fluorouracil showed a promising response rate in a previous phase II study for metastatic esophageal cancer. The purpose of this study was to determine a recommended dose and to evaluate the efficacy of nedaplatin and 5-fluorouracil combined with concurrent radiotherapy. Eligibility criteria included squamous cell carcinoma of the thoracic esophagus; T4 disease without distant organ metastasis; age 20–70 years; performance status 0–2; and adequate organ functions. Patients received two cycles of nedaplatin (80 mg/m2 or 90 mg/m2) on day 1 and continuous infusion of 5-fluorouracil 800 mg/m2/day on days 1–5, every 5 weeks with concurrent radiotherapy 60 Gy in 30 fractions. Between December 1999 and April 2002, 26 patients were accrued. The recommended dose of nedaplatin was 90 mg/m2. Common grade ≥3 toxicities included leukopenia 9, neutropenia 5, thrombocytopenia 4, esophagitis 4, and esophageal fistula 3. Three of 26 patients achieved complete response (12%; 95% confidence interval, 2%–30%). With a minimum follow-up of 26 months for surviving patients, the median survival time was 12 months (95% confidence interval, 9–22 months), and the 2-year overall survival was 31% (95% confidence interval, 13%–49%). This combined therapy is active with acceptable toxicity, however, the survival figure remains poor. Further investigation into more effective treatment is needed. [ABSTRACT FROM AUTHOR]

The purpose of this study is to determine and recommend the optimal radiation source according to breast size for tangential irradiation in breast conserving therapy. Twenty-eight patients treated at our department from January 1994 to January 1996 were studied. The dose distribution within the irradiated breast was calculated using ap60Co-gamma ray and 6 MV-X ray. Then we compared 3-D dose distributions of thep60Co-gamma ray and 6 MV-X ray in differentsized breasts. Three parameters (breast volume, chest wall separation, and breast height) were adopted as representative of breast size. We also examined correlations among the three parameters. When the breast size was large (breast volume>400 cmp3, chest wall separation >19.5 cm, or breast height>6.5 cm), the average volume of normal tissue which received more than 110% of the isocenter dose (“hot spot”) was significantly greater with thep60Co-gamma ray than with the 6 MV-X ray (p<0.05). A similar result was obtained with regard to hot spots in the clinical target volume. The cold area that received less than 95% of the isocenter dose was greater using a 6 MV-X ray when the breast size was small (breast volume <200 cmp3, chest wall separation< 17.5 cm, or breast height <5.0 cm). However, the difference was not significant. There was a significant correlation between breast volume and chest wall separation (r=0.849, p< 0.001). Breast volume and breast height were also significantly correlated (r=0.813, p<0.001). Since breast volume and shape are different in each patient, the optimal energy should be selected for each case to obtain uniform dose distribution in breast-conserving therapy. Chest wall separation or breast height, which are measurable without a 3-D planning system, can substitute for breast volume as parameters for breast size. We recommend that thep60Co-gamma ray not be used for treating large breasts, those with chest wall separation>/= 19.5 cm or breast height>/=6.5 cm. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Pretreatment pulmonary interstitial change (PIC) has been indicated as a risk factor of severe radiation pneumonitis (RP) following stereotactic body radiation therapy (SBRT) for early-stage lung cancer, but details of its true effect remain unclear. This study aims to evaluate treatment outcomes of SBRT for stage I non-small cell lung cancer in patients with PIC. A total of 242 patients are included in this study (88% male). The median age is 77 years (range, 55–92 years). A total dose of 40–70 Gy is administered in 4 to 10 fractions during a 4-to-25 day period. One, two, and three-year overall survival (OS) rates are 82.1%, 57.1%, and 42.6%, respectively. Fatal RP is identified in 6.9% of all patients. The percent vital capacity <70%, mean percentage normal lung volume receiving more than 20 Gy (>10%), performance status of 2–4, presence of squamous cell carcinoma, clinical T2 stage, regular use of steroid before SBRT, and percentage predicting forced expiratory volume in one second (<70%) are associated with worse prognoses for OS. Our results indicate that fatal RP frequently occurs after SBRT for stage I lung cancer in patients with PIC. [ABSTRACT FROM AUTHOR]

Background: The aim was to study the influence of postsurgical gross residual tumor volume on local control of maxillary sinus cancer treated with radiotherapy combined with debulking surgery. Methods: Forty-three patients who underwent combined surgery and radiotherapy (50-72 Gy, median 60 Gy) for squamous cell carcinoma of the maxillary sinus were reviewed. Gross residual tumor volume (GRTV) after surgery was measured on computed tomograms obtained during the radiotherapy planning. Patients were classified according to GRTV as follows: group AA, GRTV = 0 (microscopic residual, n = 2); group A, GRTV <10 cm3 (n = 24); group B, 10-40 cm3 (n = 9); and group C, =" border=0 src="/math/ge.gif"40 cm3 (n = 8). The relationship between local control and GRTV was analyzed using univariate and multivariate analysis. Results: The 2-year local control rate for all patients was 62%. The differences in local control rates between groups AA, A and B were not significant (P > 0.05), but the rate was significantly lower in group C than in the other groups (69% at 2 years vs 31% at 1 year, P < 0.001). Multivariate analysis showed that GRTV (P = 0.002) and histological differentiation (poorly differentiated histology was favorable, P = 0.035) were independent prognostic factors and that intra-arterial chemotherapy and administered total dose were not. Local control in groups A and B significantly depended on the total dose of radiotherapy, with 2-year control rates of patients receiving 50 Gy (n = 6) and =" border=0 src="/math/ge.gif"60 Gy (n = 27) of 17% vs 79%, respectively (P < 0.001). Conclusions: Our data suggest that adequate, not complete, debulking associated with a total radiotherapy dose of =" border=0 src="/math/ge.gif"60 Gy can provide satisfactory local control for patients with squamous cell carcinoma of the maxillary sinus. [ABSTRACT FROM AUTHOR]