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Background. The purpose of the present study was to present the treatment outcomes of particle therapy for indeterminate pulmonary nodules (IPNs) diagnosed as stage I non-small cell lung cancer, including a comparative analysis involving pathologically proven lung cancer (PPLC). Material and methods. A total of 54 patients (57 lesions) who underwent particle therapy for IPNs were enrolled in this study. Median patient age was 76 (range 52-87) years. T-classification was: T1a, 30; T1b, 16; and T2a, 11. Particle therapy using protons or carbon ions was delivered at total doses of 52.8-80 Gy equivalent in 4-26 fractions. The PPLC cohort included 111 patients. Results. The median follow-up time was 41 (range 7-90) months. For all IPN patients, the three-year overall survival, progression-free survival, local control and distant progression-free survival rates were 90%, 72%, 94% and 79%, respectively. Grade 2 toxicities were radiation pneumonitis (19%), dermatitis (9%), rib fracture (2%), chest wall pain (2%) and neuropathy (2%). No ≥ grade 3 toxicities were observed. In univariate analysis, the IPN group showed significantly better survival relative to the PPLC group. However, after adjustment for baseline imbalances between these two groups in multivariate analysis, pathological confirmation did not correlate with survival. Conclusions. Particle therapy for IPNs provided favorable outcomes with minimal toxicities, which may be comparable to those for PPLC patients. Further studies are needed to clarify the optimal management of IPN patients. [ABSTRACT FROM AUTHOR]

Background: Organizing pneumonia (OP), so called bronchiolitis obliterans organizing pneumonia after postoperative irradiation for breast cancer has been often reported. There is little information about OP after other radiation modalities. This cohort study investigated the clinical features and risk factors of OP after stereotactic ablative radiotherapy of the lung (SABR). Methods: Patients undergoing SABR between 2004 and 2010 in two institutions were investigated. Blood test and chest computed tomography were performed at intervals of 1 to 3 months after SABR. The criteria for diagnosing OP were: 1) mixture of patchy and ground-glass opacity, 2) general and/or respiratory symptoms lasting for at least 2 weeks, 3) radiographic lesion in the lung volume receiving < 0.5 Gy, and 4) no evidence of a specific cause. Results: Among 189 patients (164 with stage I lung cancer and 25 with single lung metastasis) analyzed, nine developed OP. The incidence at 2 years was 5.2% (95% confidence interval; 2.6-9.3%). Dyspnea were observed in all patients. Four had fever. These symptoms and pulmonary infiltration rapidly improved after corticosteroid therapy. Eight patients had presented with symptomatic radiation pneumonitis (RP) around the tumor 2 to 7 months before OP. The prior RP history was strongly associated with OP (hazard ratio 61.7; p = 0.0028) in multivariate analysis. Conclusions: This is the first report on OP after SABR. The incidence appeared to be relatively high. The symptoms were sometimes severe, but corticosteroid therapy was effective. When patients after SABR present with unusual pneumonia, OP should be considered as a differential diagnosis, especially in patients with prior symptomatic RP. [ABSTRACT FROM AUTHOR]

Background: The treatment schedules for stereotactic body radiotherapy (SBRT) for lung cancer vary from institution to institution. Several reports have indicated that stage IB patients had worse outcomes than stage IA patients when the same dose was used. We evaluated the clinical outcomes of SBRT for stage I non-small cell lung cancer (NSCLC) treated with different doses depending on tumor diameter. Methods: Between February 2004 and November 2008, 124 patients with stage I NSCLC underwent SBRT. Total doses of 44, 48, and 52 Gy were administered for tumors with a longest diameter of less than 1.5 cm, 1.5-3 cm, and larger than 3 cm, respectively. All doses were given in 4 fractions. Results: For all 124 patients, overall survival was 71%, cause-specific survival was 87%, progression-free survival was 60%, and local control was 80%, at 3 years. The 3-year overall survival was 79% for 85 stage IA patients treated with 48 Gy and 56% for 37 stage IB patients treated with 52 Gy (p = 0.05). At 3 years, cause-specific survival was 91% for the former group and 79% for the latter (p = 0.18), and progression-free survival was 62% versus 54% (p = 0.30). The 3-year local control rate was 81% versus 74% (p = 0.35). The cumulative incidence of grade 2 or 3 radiation pneumonitis was 11% in stage IA patients and 30% in stage IB patients (p = 0.02). Conclusions: There was no difference in local control between stage IA and IB tumors despite the difference in tumor size. The benefit of increasing the SBRT dose for larger tumors should be investigated further. [ABSTRACT FROM AUTHOR]

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

• We performed a prospective phase 2 study to assess the 7-year treatment outcomes of image-guided proton therapy (IGPT) with fiducial markers in 43 operable stage I NSCLC cases. • IGPT yielded 3-year overall survival and local control rates of 95% each, with 7-year rates of 83% and 95%, respectively. • Grade 3 radiation pneumonitis was observed in one case (2.3%). • Quality of life (QOL) analysis revealed IGPT effectively maintained overall QOL; however, about 40% patients reported dyspnea after treatment. This study evaluated long-term efficacy, safety, and changes in quality of life (QOL) of patients after image-guided proton therapy (IGPT) for operable stage I non-small cell lung cancer (NSCLC). This single-institutional prospective phase 2 study enrolled patients with operable histologically confirmed stage IA or IB NSCLC (7th edition of UICC). The prescribed dose was 66 Gy relative biological effectiveness equivalents (GyRBE) in 10 fractions for peripheral lesions, or 72.6 GyRBE in 22 fractions for central lesions. The primary endpoint was the 3-year overall survival (OS). The secondary endpoints included disease control, toxicity, and changes in QOL score. We enrolled 43 patients (median age: 68 years; range, 47–79 years) between July 2013 to January 2021, of whom 41 (95 %) had peripheral lesions and 27 (63 %) were stage IA. OS, local control, and progression-free survival rates were 95 % (95 % CI: 83–99), 95 % (82–99), and 86 % (72–94), respectively, at 3 years, and 83 % (66–92), 95 % (82–99), and 77 % (60–88), respectively, at 7 years. Four patients (9 %) developed grade 2, and one patient (2 %) developed grade 3 radiation pneumonitis. No other grade 3 or higher adverse events were observed. In the QOL analysis, global QOL remained favorable; however, approximately 40 % of patients reported dyspnea at 3 and 24 months. Our findings suggest that IGPT provides effective disease control and survival in operable stage I NSCLC, particularly for peripheral lesions. Moreover, toxicity associated with IGPT was minimal, and patients reported favorable QOL. [ABSTRACT FROM AUTHOR]

A prospective multicenter registry study was started May 2016 in Japan to evaluate the efficacy and safety of proton beam therapy (PBT) for hepatocellular carcinoma (HCC). Patients who received PBT for HCC from May 2016 to June 2018 were registered in the database of the Particle Beam Therapy Committee and Subcommittee of the Japanese Society for Radiation Oncology. Overall survival (OS), progression-free survival (PFS), and local recurrence were evaluated. Of the 755 registered patients, 576 with initial PBT and no duplicate cancer were evaluated. At final follow-up, 322 patients were alive and 254 had died. The median follow-up period for survivors was 39 months (0-58 months). The median OS time of the 576 patients was 48.8 months (95% CI, 42.0-55.6 months) and the 1-, 2-, 3-, and 4-year OS rates were 83.8% (95% CI, 80.5%-86.6%), 68.5% (64.5%-72.2%), 58.2% (53.9%-62.2%), and 50.1% (44.9%-55.0%), respectively. Recurrence was observed in 332 patients, including local recurrence in 45 patients. The median PFS time was 14.7 months (95% CI, 12.4-17.0 months) and the 1-, 2-, 3-, and 4-year PFS rates were 55.2% (95% CI, 51.0%-59.2%), 37.5% (33.5%-41.5%), 30.2% (26.3%-34.2%), and 22.8% (18.5%-27.4%), respectively. The 1-, 2-, 3-, and 4-year OS rates were significantly higher for tumor size <5 versus 5 to 10 cm (P <.001) and <5 versus ≥10 cm (P <.001); Child-Pugh score A/B versus C (P <.001); and distance of the tumor from the gastrointestinal tract <1 versus 1 to 2 cm (P <.008) and <1 versus >2 cm (P <.001). At final follow-up, 27 patients (4.7%) had late adverse events of grade 3 or higher, with liver failure (n = 7), and dermatitis (n = 7) being most common. This multicenter prospective data registry indicated that PBT for HCC gives good therapeutic effects (3-year local control rate of 90%) with a low risk of severe late adverse events. [ABSTRACT FROM AUTHOR]

• Particle therapy for patients with operable early-stage lung cancer has demonstrated good progression free and overall survival. • Toxicity was very mild, with Grade 3 toxicity occurring in 1.5 % of patients. • Type of particle therapy had no effect on overall survival or progression free survival. To investigate the toxicity and survival outcomes of proton and carbon ion radiotherapy for patients with operable early-stage lung cancer who are eligible for lobectomy. This multicenter nationwide prospective cohort study included patients with operable early-stage lung cancer. Proton and carbon ion radiotherapy was performed according to the schedule stipulated in the unified treatment policy. Progression-free survival (PFS), overall survival (OS) and treatment-related toxicities were evaluated. A total of 274 patients were enrolled and included in efficacy and safety analyses. The most common tumor type was adenocarcinoma (44 %), while 105 cases (38 %) were not histologically confirmed or diagnosed clinically. Overall, 250 (91 %) of the 274 patients had tumors that were peripherally situated, while 138 (50 %) and 136 (50 %) patients were treated by proton and carbon ion radiotherapy, respectively. The median follow-up time for all censored patients was 42.8 months (IQR 36.7–49.0). Grade 3 or severe treatment-related toxicity was observed in 4 cases (1.5 %). Three-year PFS was 80.5 % (95 % CI: 75.7 %–85.5 %) and OS was 92.5 % (95 % CI: 89.3 %–95.8 %). Pathological confirmation and clinical stage were factors significantly associated with PFS, while tumor location and particle-ion type were not. Meanwhile, clinical stage was significantly associated with OS, but pathological confirmation, tumor location, and particle-ion type were not. Particle therapy for operable early-stage lung cancer resulted in excellent 3-year OS and PFS in each subset. In this disease context, proton and carbon ion beam therapies are feasible alternatives to curative surgery. [ABSTRACT FROM AUTHOR]

Purpose: To establish an ultra-high dose-rate (UHDR) radiation system using a synchrotron proton beam accelerator and to compare the effects by irradiation positions on cultured cells and chick embryos., Methods and Materials: Protons for UHDR were obtained by applying high-frequency power at much higher levels than usual to extract all protons within approximately 50 ms. Subsequently, monitoring with a Faraday cup was performed immediately after synchrotron extraction and the waveform was adjusted accordingly. Four cultured tumor lines, 2 normal cell lines, and chick embryos were used. UHDR radiation therapy (UHDR-RT) at 6 to 18 Gy (200-300 Gy/s, single exposure) and conventional dose-rate radiation therapy (Conv-RT) at 6 to 18 Gy (3 Gy/s) were administered to the 1-cm spread-out Bragg peak (SOBP) and the plateau region preceding SOBP. After irradiation, disparities in cell growth rates and cell cycle progression were assessed, and cell survival was evaluated via colony assay. Chick embryos were also examined for survival., Results: UHDR-RT was achieved at a range of 40 to 800 Gy/s, encompassing both plateau and peak phases. In vitro studies demonstrated similar cell-killing effects between UHDR-RT and Conv-RT in cancer cells. Significant apoptotic effects and G2 arrest were observed during the cell cycle under peak UHDR-RT conditions. The FLASH effect was not observed in normal single cells under normal atmospheric conditions. Stronger cell-killing effects were noted in V79 spheroids exposed to peak UHDR-RT than peak Conv-RT. Moreover, in chick embryos, an increase in survival rate, indicative of the FLASH effect, was observed., Conclusions: The FLASH effect was also achieved with UHDR-RT using a synchrotron proton beam accelerator in chick embryos. The cell-killing effects in cancer cells were higher with peak UHDR-RT that may be due to the higher linear energy transfer at the SOBP., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Proton-based, definitive chemoradiotherapy (P-CRT) for esophageal squamous cell carcinoma (ESCC) previously showed comparable survival outcomes with the surgery-based therapy, i.e., neoadjuvant chemotherapy followed by esophagectomy (NAC-S), in a single-institutional study. This study aimed to validate this message in a Japanese multicenter study., Methods: Eleven Japanese esophageal cancer specialty hospitals have participated. A total of 518 cases with clinical Stage I-IVA ESCC between 2010 and 2019, including 168 P-CRT and 350 NAC-S patients, were enrolled and long-term outcomes were evaluated. Propensity-score weighting analyses with overlap weighting for confounding adjustment were used., Results: The 3-year overall survival (OS) of the P-CRT group was equivalent to the NAC-S group (74.8% vs. 72.7%, hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.61-1.25). Although, the 3-year P-CRT group progression-free survival (PFS) was inferior to the NAC-S group (51.4% vs. 59.6%, HR 1.39, 95% CI 1.04-1.85), the progression P-CRT group cases showed better survival than the NAC-S group (HR 0.58, 95% CI 0.38-0.88), largely because of salvage surgery or endoscopic submucosal dissection for local progression. The survival advantage of P-CRT over NAC-S was more pronounced in the cT1-2 (HR 0.61, 95% CI 0.29-1.26) and cStage I-II (HR 0.50, 95% CI 0.24-1.07) subgroups, although this trend was not evident in other populations, such as cT3-4 and cStage III-IVA., Conclusions: Proton-based CRT for ESCC showed equivalent OS to surgery-based therapy. Especially for patients with cT1-2 and cStage I-II disease, proton-based CRT has the potential to serve as a first-line treatment., (© 2024. The Author(s), under exclusive licence to The Author(s) under exclusive licence to The Japan Esophageal Society.)

In radiotherapy for pediatric abdominal tumors, determining the effect of concurrent chemotherapy on polyglycolic acid (PGA) spacers is crucial; yet this effect has not been validated. Therefore, we aimed to evaluate the impact of cyclophosphamide (CPA) chemotherapy on the PGA spacer using a rat model. Twenty-four rats were implanted with the spacer, and morphological changes in the spacer were assessed on CT for both the CPA-dosed group (40 mg/kg) and the control group. The size and volume of the spacer were quantified using CT, while the degree of adhesion and microscopic examination of the tissue were determined using pathology specimens. Morphologically, the size of the spacer decreased over time in both the CPA-dosed and control groups, with no significant differences observed between groups. No significant differences in adhesion were observed between the two groups. Macrophages were observed around the PGA fibers, suggesting their involvement in the degradation of the PGA spacer. These results suggest that CPA does not cause significant clinically problematic degradation or adverse tissue reactions to the PGA spacer. This study reinforced the benefits of PGA spacers; however, future research focusing on in vivo longitudinal monitoring of individual rats, as well as on humans, is required., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)