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The aim of the present study was to report the feasibility of proton beam reirradiation for patients with locally recurrent rectal cancer (LRRC) with prior pelvic irradiation. The study population included patients who were treated with proton beam therapy (PBT) for LRRC between 2008 and December 2019 in our institution. Those who had a history of distant metastases of LRRC, with or without treatment, before reirradiation, were excluded. Overall survival (OS), progression-free survival (PFS) and local control (LC) were estimated using the Kaplan–Meier method. Ten patients were included in the present study. The median follow-up period was 28.7 months, and the median total dose of prior radiotherapy (RT) was 50 Gy (range, 30 Gy–74.8 Gy). The median time from prior RT to reirradiation was 31.5 months (range, 8.1–96.6 months), and the median reirradiation dose was 72 Gy (relative biological effectiveness) (range, 56–77 Gy). The 1-year/2-year OS, PFS and LC rates were 100%/60.0%, 20.0%/10.0% and 70.0%/58.3%, respectively, with a median survival time of 26.0 months. Seven patients developed a Grade 1 acute radiation dermatitis, and no Grade ≥ 2 acute toxicity was recorded. Grade ≥ 3 late toxicity was recorded in only one patient, who had developed a colostomy due to radiation-related intestinal bleeding. Reirradiation using PBT for LRRC patients who had previously undergone pelvic irradiation was feasible. However, the indications for PBT reirradiation for LRRC patients need to be considered carefully due to the risk of severe late GI toxicity. [ABSTRACT FROM AUTHOR]

We attempted to re-evaluate the efficacy of prophylactic cranial irradiation (PCI) in limited-stage small cell lung cancer (LS-SCLC) with more recent data. A total of 179 patients with LS-SCLC received radical thoracic radiotherapy and chemotherapy at our institution between 1998 and 2018. One hundred twenty-eight patients who achieved complete response (CR), good partial response (PR), and PR without progression for at least for one year after initial therapy were enrolled in this study. These patients were divided into a PCI group (group A, n = 43), and a non-PCI group (group B, n = 85). Survival outcomes were retrospectively evaluated. Because several background factors differed significantly between groups A and B, propensity score (PS) matching was performed as 1:1 match of the two groups. Finally, we analyzed 64 patients (group A/B = 32/32). Median follow-up periods were 53 and 31 months in groups A and B, respectively. There were no significant differences between the groups' backgrounds. Two-year overall survival (OS) rates were 77% in group A and 62% in group B (p = 0.224). Two-year brain metastasis free survival (BMFS) rates were 85% in group A and 57% in group B (p = 0.008). The number of patients who underwent a brain imaging test for confirmation of no brain metastasis (BM) after radical thoracic radiotherapy and chemotherapy (before PCI) was 84 (group A/B = 32/52). A PS matched analysis for cases of pre-PCI brain imaging group, two-year OS rates for group A/B were 73/59% (p = 0.446). Two-year BMFS rates for group A/B were 91/52% (p = 0.021). Retrospectively, PS matched analysis revealed that adding PCI to LS-SCLC patients who achieved good thoracic control significantly improved BMFS, but OS did not improve. [ABSTRACT FROM AUTHOR]

This study aimed to determine the maximum tolerance dose (MTD) and to estimate the recommended dose (RD) of concomitant S-1 with carbon-ion radiotherapy (RT) for sinonasal squamous cell carcinoma (SCC). Nine patients with sinonasal SCC received carbon-ion RT with escalating doses of S-1 according to phase I methods. Doses of 40, 60 and 80 mg/m2/day were administered twice daily in dose levels 1, 2 and 3, respectively, from days 1 to 14 and 22 to 35. Carbon-ion RT was administered at a dose of 70.4 Gy (relative biological effectiveness) in 32 fractions, 5 days a week. Two patients developed grade 3 acute dermatitis. However, none developed dose-limiting toxicities. Therefore, the MTD of S-1 could not be determined; the RD was estimated to be 80 mg/m2/day with concurrent carbon-ion RT. Partial response and stable disease were noted in 5 and 4 patients, respectively. The 2-year overall survival and local control rates were 56 and 74%, respectively. Overall, 2 patients developed ≥grade 3 late toxicities; among them, 1 patient developed grade 3 cataract and the other developed grade 4 cataract, optic nerve disorder and hearing impairment. To the best of our knowledge, this phase I study is the first clinical trial to evaluate concomitant S-1 with carbon-ion RT for sinonasal SCC. The MTD of S-1 could not be determined, and the RD was estimated to be 80 mg/m2/day. This study demonstrated a manageable safety profile for this combination. The observed outcomes may facilitate further evaluation of this novel therapy. [ABSTRACT FROM AUTHOR]

Our observational study aimed to verify the safety of our original titanium fiducial markers in gynecological cancer by using a simple insertion method. We prospectively evaluated the safety in patients with gynecological cancer who had undergone our insertion procedure of the titanium markers. The decision to implant a titanium marker was at the discretion of each radiation oncologist. The fiducial markers were manufactured by severing ligating clips for surgery into 3–6 mm pieces and were sterilized thereafter. We inserted an 18-gauge injection needle containing the marker before the marker was extruded by a 22-gauge Cattelan needle or shape memory alloy wire into the tumor or tissues close to the tumor. Severe complications within 3 months after implantation were scored according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.0. Between August 2016 and December 2018, we enrolled 46 patients. Of 46, 44 underwent implantation. The median age was 58.5 years. The most common primary site was the cervix. Two patients experienced detachment of the markers after implantation. No Grade 3 or higher level of complications was observed. Our simple insertion technique for original titanium fiducial markers was well-tolerated. [ABSTRACT FROM AUTHOR]

Aim To evaluate the treatment results of radiotherapy (RT) in children and adults with brainstem gliomas (BSGs) and review the previous literature. Methods Thirty patients (14 children, 16 adults) with BSG treated using RT were retrospectively evaluated. The median ages of the children and adults were 8 years (range: 2-16 years) and 49 years (range: 19-75 years), respectively. A histological diagnosis was obtained in 11 patients. The median total radiation dose was 56 Gy (range: 50-70 Gy) with a single fraction size of 1.8-2.0 Gy. Temozolomide was administered concurrently with RT in 14 patients. Results Tumor progression after RT occurred in 26 patients (14 children and 12 adults). Four adults survived without tumor progression. The median survival times for children and adults were 8.5 and 39 months, respectively. The 1-, 2- and 3-year overall survival rates for children/adults were 29%/75%, 14%/68% and 0%/53%, respectively ( P = 0.001), and the 1-, 2- and 3-year progression-free survival rates for children/adults were 14%/69%, 0%/49% and 0%/35%, respectively ( P < 0.001). Grade 3 or higher acute and late toxicities did not occur. Conclusion In this study, the prognosis of children with BSGs was considerably poorer than that of adults, and our results are consistent with those of previous studies. Efforts should be made to improve the survival outcomes of patients with BSGs, especially children. [ABSTRACT FROM AUTHOR]

• Space-making particle therapy provides a rational combination treatment. • Effectiveness of space-making particle therapy has been demonstrated. The primary definitive treatment for abdominopelvic sarcomas (APSs) is resection, although incomplete resection has a negative prognostic impact. Although the effectiveness of particle therapy (PT) as a treatment for APS has already been demonstrated, its application for tumors adjacent to the gastrointestinal tract is frequently restricted, due to extremely low tolerance. Space-making PT, consisting of surgical spacer placement and subsequent PT, has been developed to overcome this limitation. Between June 2006 and June 2018, a total of 75 patients with 12 types of APS underwent space-making PT. The 3-year local control rate of all patients was 90.3%. Fourteen surgery-related complications were observed in 12 patients (16%), and complications of Grade 3b or higher were observed in 3 patients. Ninety-five PT-related complications were seen in 66 patients (88.0%), and 13 patients (17.3%) had complications of Grade 3 or higher. The median V95% (volume irradiated with 95% of the treatment planning dose) of the gross tumor volume and clinical target volume were 99.9% and 99.5%, respectively. The median D95% (dose intensity covering 95% of the target volume) of the gross tumor volume/planned dose and clinical target volume/planned dose were 99.4%, and 99.1%, respectively. The feasibility and effectiveness of space-making PT have been demonstrated via dosimetric evaluation, and our results indicate that this new strategy may potentially provide an effective and innovative treatment option for advanced APS. [ABSTRACT FROM AUTHOR]

Background: A study was undertaken to analyze the efficacy and feasibility of particle beam radiation therapy (PBRT) using carbon ions and protons for the treatment of patients with oligometastatic lung tumors.Methods: A total of 47 patients with 59 lesions who underwent PBRT for oligometastatic lung tumors between 2003 and 2011 were included in this study. Patient median age was 66 (range, 39-84) years. The primary tumor site was the colorectum in 11 patients (23.4%), lung in 10 patients (21.3%) and a variety of other sites in 26 patients (55.3%). Thirty-one patients (66%) received chemotherapy prior to PBRT. Thirty-three lesions were treated with 320-MeV carbon ions and 26 were treated with 150- or 210-Mev protons in 1-4 portals. A median total dose of 60 (range, 52.8-70.2) GyE was delivered at the isocenter in 8 (range, 4-26) fractions.Results: The median follow-up time was 17 months. The local control, overall survival and progression-free survival rates at 2 years were 79%, 54 and 27% respectively. PBRT-related toxicities were observed; six patients (13%) had grade 2 toxicity (including grade 2 radiation pneumonitis in 2) and six patients (13%) had grade 3 toxicity. Univariate analysis indicated that patients treated with a biologically equivalent dose of 10 (BED10) <110 GyE10, had a significantly higher local recurrence rate. Local control rates were relatively lower in the subsets of patients with the colorectum as the primary tumor site. No local progression was observed in metastases from colorectal cancer irradiated with a BED10 ≥ 110 GyE10. There was no difference in treatment results between proton and carbon ion therapy.Conclusions: PRBT is well tolerated and effective in the treatment of oligometastatic lung tumors. To further improve local control, high-dose PBRT with a BED10 ≥ 110 GyE10 may be promising. Further investigation of PBRT for lung oligometastases is warranted. [ABSTRACT FROM AUTHOR]

• Carbon ion radiotherapy (CIRT) is useful to treat head and neck tumors. • Radiation-induced brain injury (RIBI) is an adverse effect of irradiation. • The tolerance dose of the brain in CIRT is unclear. • Risk factors for RIBI in long-term survivors following CIRT were determined. • CIRT variables were used to generate a probability profile for RIBI treatment. We aimed to determine the risk factors for radiation-induced brain injury (RIBI 1 1 Abbreviations: RIBI, radiation-induced brain injury; CIRT, carbon ion radiotherapy; HNC/SBT, head and neck cancers and skull base tumors; AE, adverse event; DVH, dose volume histogram; LQ, linear–quadratic; MRI, magnetic resonance imaging; CT, computed tomography; GTV, gross tumor volume; CTV, clinical target volume; OAR, organs at risk; RBE, relative biological effectiveness; CTCAE, Common Terminology Criteria for Adverse Events; EUD, equivalent uniform dose; AIC, Akaike Information Criterion; SOBP, Spread-Out Bragg Peak; IMRT, intensity-modulated radiotherapy) after carbon ion radiotherapy (CIRT) to predict their probabilities in long-term survivors. We evaluated 104 patients with head, neck, and skull base tumors who underwent CIRT in a regimen of 32 fractions and were followed up for at least 24 months. RIBI was assessed using the Common Terminology Criteria for Adverse Events. The median follow-up period was 45.5 months; 19 (18.3 %) patients developed grade ≥2 RIBI. The maximal absolute dose covering 5 mL of the brain (D5ml) was the only significant risk factor for grade ≥2 RIBI in the multivariate logistic regression analysis (p = 0.001). The tolerance doses of D5ml for the 5% and 50% probabilities of developing grade ≥2 RIBI were estimated to be 55.4 Gy (relative biological effectiveness [RBE]) and 68.4 Gy (RBE) by a logistic model, respectively. D5ml was most significantly associated with grade ≥2 RIBI and may enable the prediction of its probability. [ABSTRACT FROM AUTHOR]

Purpose: This retrospective study aimed to determine the clinical outcomes following particle monotherapy (ie, proton therapy [PT] or carbon ion therapy [CIT]) in patients with sinonasal squamous cell carcinoma at a single institution.Methods and Materials: Between August 2001 and March 2012, 59 patients were treated with definitive PT or CIT; none underwent chemotherapy or surgery. Of the patients, 22 (37%) had unresectable disease. PT was used in 38 patients (64%); CIT, 21 patients (36%). Almost half of the patients (n = 29, 47%) received 65.0 Gy (relative biological effectiveness) in 26 fractions.Results: The median follow-up period was 30 months (range, 8-127 months) for all patients and 65 months (range, 9-127 months) for the survivors. The 3- and 5-year overall survival rates were 56.2% and 41.6%, respectively; progression-free survival rates, 42.9% and 34.7%, respectively; and local control rates, 54.0% and 50.4%, respectively. Late toxicities of grade ≥3 occurred in 13 patients (22%).Conclusions: To our knowledge, this is the largest retrospective study of sinonasal squamous cell carcinoma treated with particle therapy alone. The efficacy of PT and CIT indicated that particle therapy can serve an important role in treating this disease. [ABSTRACT FROM AUTHOR]

Objective: The management of low-grade glioma (LGG) still remains controversial because the effectiveness of early and extensive resection is unclear, and the use of radiation therapy or chemotherapy is not well-defined. In particular, the importance of prognostic factors for survival remains a matter of discussion. The purpose of this study was to validate prognostic factors for survival in patients with LGG., Materials and Methods: A consecutive series of 55 patients with WHO grade II LGG treated in our institute between 1983 and 2013 were retrospectively reviewed to determine the prognostic factors for survival. All data were retrospectively analyzed from the aspect of baseline characteristics, pathological findings, genetic change, surgical treatments, adjuvant therapies, and survival time. Cox multivariate analysis was performed to determine the prognostic factors for survival., Results: There were 28 patients with diffuse astrocytoma (DA), 21 patients with oligodendroglioma (OG), and 6 patients with oligoastrocytoma (OA) diagnosed on initial surgery. The median overall survival was 193 months and fifteen patients (27.3%) died. A mutation in isocitrate dehydrogenase-1 (IDH1) was found in 72.9% of LGG, and this mutation was positively correlated with methylation of O6-methylguanine-DNA methyltransferase (MGMT) (p=0.02). A better prognosis was significantly associated with combined IDH1 mutation and MGMT methylation status (both positive vs both negative, HR 0.079 [95% CI 0.008-0.579], p=0.012), as well as histology (OG vs DA and OA, HR 0.158 [95% CI 0.022-0.674], p=0.011) and tumor size (<6 cm vs ≥6 cm, HR 0.120 [95% CI 0.017-0.595], p=0.008)., Conclusions: Tumor histology, size and IDH-mutation status are important predictors for prolonged overall survival in patients with LGG and may provide a reliable tool for standardizing future treatment strategies., (Copyright © 2015 Elsevier B.V. All rights reserved.)