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This single-arm confirmatory study (JCOG1305) aimed to evaluate the utility of interim positron emission tomography (iPET)-guided therapy for newly diagnosed advanced-stage classic Hodgkin lymphoma (cHL). Patients aged 16-60 years with cHL received two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and then underwent an iPET scan (PET2), which was centrally reviewed using a five-point Deauville scale. PET2-negative patients continued an additional four cycles of ABVD, whereas PET2-positive patients switched to six cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP). The co-primary endpoints were 2-year progression-free survival (PFS) among all eligible and PET2-positive patients. Ninety-three patients were enrolled between January 2016 and December 2019. One patient was ineligible because of a diagnostic error. The median age of the 92 eligible patients was 35 (interquartile range, 28-48) years. Forty (43%) patients had stage III disease, and 43 (47%) had stage IV disease. The remaining nine (10%) patients had stage IIB disease with risk factors. Nineteen PET2-positive (21%) patients received eBEACOPP, 18 completed six cycles of eBEACOPP, 73 PET2-negative (79%) patients continued ABVD, and 70 completed an additional four cycles of ABVD. With a median follow-up period of 41.1 months, the 2-year PFS of 92 eligible patients and 19 PET2-positive patients were 84.8% (80% confidence interval [CI], 79.2-88.9) and 84.2% (80% CI, 69.7-92.1), respectively. Both primary endpoints were met at the prespecified threshold. This study demonstrates that iPET-guided therapy is a useful treatment option for younger patients with newly diagnosed advanced-stage cHL. Registration number: jRCTs031180218., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objective: This study evaluated the prognostic impact of the quality of dose distribution using dosiomics in patients with prostate cancer, stratified by pretreatment prostate-specific antigen (PSA) levels and Gleason grade (GG) group., Methods: A total of 721 patients (Japanese Foundation for Cancer Research [JFCR] cohort: N = 489 and Tokyo Radiation Oncology Clinic [TROC] cohort: N = 232) with localized prostate cancer treated by intensity-modulated radiation therapy were enrolled. Two predictive dosiomic features for biochemical recurrence (BCR) were selected and patients were divided into certain groups stratified by pretreatment PSA levels and GG. Freedom from biochemical failure (FFBF) was estimated using the Kaplan-Meier method based on each dosiomic feature and univariate discrimination was evaluated using the log-rank test. As an exploratory analysis, a dosiomics hazard (DH) score was developed and its prognostic power for BCR was examined., Results: The dosiomic feature extracted from planning target volume (PTV) significantly distinguished the high- and low-risk groups in patients with PSA levels >10 ng/mL (7-year FFBF: 86.7% vs 76.1%, P < .01), GG 4 (92.2% vs 76.9%, P < .01), and GG 5 (83.1% vs 77.8%, P = .04). The DH score showed significant association with BCR (hazard score: 2.04; 95% confidence interval: 1.38-3.01; P < .001)., Conclusion: The quality of planned dose distribution on PTV may affect the prognosis of patients with poor prognostic factors, such as PSA levels >10 ng/mL and higher GGs., Advances in Knowledge: The effects of planned dose distribution on prognosis differ depending on the patient's clinical background., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: We investigated if PD-L1 expression can be predicted by machine learning using clinical and imaging features., Methods: We included 117 patients with c-stage I/II non-small cell lung cancer who underwent radical resection. A total of 3951 radiomic features were extracted by defining the tumor (within tumor contour), rim (contour ±3 mm) and exterior (contour +10 mm) on preoperative contrast computed tomography. After feature selection by Boruta algorithm, prediction models of tumor PD-L1 expression (22C3: ≥1%, <1%) of resected specimens were constructed using Random Forest: radiomics, clinical, and combined models. Their performance was evaluated by 5-fold cross-validation, and AUCs were compared using Delong test. Next, study groups were categorized as patients without biopsy (training set), and those with biopsy (test set). Predictive ability of biopsy was compared to each prediction model., Results: Of 117 patients (66 ± 10 years old, 48% male), 33 (28.2%) had PD-L1≥1%. Mean AUC of PD-L1≥1% for the validation set in radiomics, clinical, and combined models were 0.80, 0.80, and 0.83 (P = .32 vs. clinical model), respectively. The diagnosis of malignancy was made in 22 of 38 (58%) patients with attempted biopsies, and PD-L1 was measurable in 19 of 38 (50%) patients. Diagnostic accuracies of PD-L1≥1% from 19 determinable biopsies and 38 all attempted biopsies were 0.68 and 0.34, respectively. These were out performed by machine learning: 0.71, 0.71, and 0.74 for radiomics, clinical, and combined models, respectively., Conclusions: Our machine learning could be an adjunctive tool in estimating PD-L1 expression prior to neoadjuvant treatment, particularly when PD-L1 is indeterminable with biopsy., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: This study aimed to investigate the effect of androgen deprivation therapy (ADT) on the survival of intermediate-risk prostate cancer (IR-PCA) patients treated with dose-escalated external beam radiation therapy (DE-EBRT), and to determine the group that will benefit from ADT., Methods: We analysed 620 IR-PCA patients treated with DE-EBRT at two institutions. Variables were adjusted using the stabilised inverse probability of treatment weighting method (sIPTW) between radiation therapy (RT) and RT plus ADT groups. Biochemical relapse-free survival (bRFS) rate and overall survival (OS) rate were compared using Kaplan-Meier analysis and log-rank test. Cox proportional hazard analysis (CPH) was conducted to detect unfavorable risk factors., Results: This study included 405 patients; with 217 and 188 patients in the RT and RT plus ADT groups, respectively. The prescribed radiation dose was 78 Gy in 39 fractions. The median follow-up time was 82.0 months. After sIPTW-adjustment, 214.3 and 189.7 patients were assigned to the RT and RT plus ADT groups, respectively. The 7-year bRFS and OS were 89.3% and 94.6% in RT group and 92.3% and 91.0% in RT plus ADT group, respectively. Before and after sIPTW adjustment, no statistically significant differences were found in these endpoints between treatment groups. Multivariate CPH for bRFS revealed Gleason score (GS) 4 + 3 as an unfavorable risk factor, and ADT improved biochemical control of them., Conclusion: ADT may not always be effective in all Japanese IR-PCA patients treated with DE-EBRT, but it can improve biochemical control in patients with GS 4 + 3., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: We hypothesized that epidermal growth factor receptor ( EGFR ) mutations could be detected in early-stage lung adenocarcinoma using radiomics., Methods: This retrospective study included consecutive patients with clinical stage I/II lung adenocarcinoma who underwent curative-intent pulmonary resection from March-December 2016. Using preoperative enhanced chest computed tomography, 3,951 radiomic features were extracted in total from the tumor (area within the tumor boundary), tumor rim (area within ±3 mm of the tumor boundary), and tumor exterior (area between +10 mm outside the tumor and tumor boundary). A machine learning-based radiomics model was constructed to detect EGFR mutations. The combined model incorporated both radiomic and clinical features (gender and smoking history). The performance was validated with five-fold cross-validation and evaluated using the mean area under the curve (AUC)., Results: Of 99 patients (mean age, 66±11 years; female, 66.6%; clinical stage I/II, 89.9%/10.1%), EGFR mutations in the surgical specimen were detected in 46 (46.5%). A median of 4 (range, 2 to 8) radiomic features was selected for each validation session. The mean AUCs in the radiomics and combined models were 0.75 and 0.83, respectively. The two top-ranked features in the combined model were the radiomic features extracted from the tumor exterior and the tumor, indicating a higher impact of radiomic features over relevant clinical features., Conclusions: Radiomic features, including those in the peri-tumoral area, may help detect EGFR mutations in lung adenocarcinomas in preoperative settings. This non-invasive image-based technology could help guide future precision neoadjuvant therapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-2683/coif). The authors have no conflicts of interest to declare., (2023 Translational Cancer Research. All rights reserved.)

To elucidate the long-term outcomes of non-anthracycline-containing therapies and central nervous system (CNS) events in patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL), the clinical data of 313 patients with ENKTL diagnosed between 2000 and 2013 in a nationwide retrospective study in Japan were updated and analyzed. At a median follow-up of 8.4 years, the 5-year overall survival (OS) and progression-free survival (PFS) were 71% and 64%, respectively, in 140 localized ENKTL patients who received radiotherapy-dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) in clinical practice. Nine (6.4%) patients experienced second malignancies. In 155 localized ENKTL patients treated with RT-DeVIC, 10 (6.5%) experienced CNS relapse (median, 12.8 months after diagnosis). In five of them, the events were confined to the CNS. Nine of the 10 patients who experienced CNS relapse died within 1 year after CNS relapse. Multivariate analysis identified gingival (hazard ratio [HR], 54.35; 95% confidence interval [CI], 8.60-343.35) and paranasal involvement (HR, 7.42; 95% CI, 1.78-30.89) as independent risk factors for CNS relapse. In 80 advanced ENKTL patients, 18 received steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy as first-line treatment. Patients who received SMILE as their first-line treatment tended to have better OS than those who did not (p = 0.071). Six (7.5%) advanced ENKTL patients experienced isolated CNS relapse (median, 2.6 months after diagnosis) and died within 4 months of relapse. No second malignancies were documented in advanced ENKTL patients. In the entire cohort, the median OS after first relapse or progression was 4.6 months. 12 patients who survived 5 years after PFS events were disease-free at the last follow-up. Of those, 11 (92%) underwent hematopoietic stem cell transplantation. Our 8-year follow-up revealed the long-term efficacy and safety of RT-DeVIC and SMILE. The risk of CNS relapse is an important consideration in advanced ENKTL., (© 2022 John Wiley & Sons Ltd.)

Background: We carried out the first multi-institutional prospective study on accelerated partial breast irradiation (APBI) via multicatheter interstitial brachytherapy in a shorter period for early breast cancer in Japan., Methods: Patient eligibility criteria included positive hormone receptors, tumors ≤ 3 cm and TNM stage pN0M0. After breast-conserving surgery (Japanese cylindrical resection) and histological confirmation of negative surgical margins and the absence of lymph node metastasis, applicator implantation was performed either postoperatively or intraoperatively. High-dose-rate brachytherapy of 36 Gy in 6 fractions was delivered., Results: Forty-six patients from six institutions received this treatment regimen, and the median follow-up time was 60 months (range 57-67 months). The median resected breast tissue volume was 81 cm 3 (range 28-260 cm 3 ). No Grade 4 late sequela, local recurrence nor death due to breast cancer were observed. Grade 2-3 sequelae such as rib fracture (2%), soft tissue necrosis (9%), fibrosis (20%), and breast pain (9%) were observed. The resected breast tissue volumes of the patients who had Grade ≥ 2 fibrosis and Grade < 2 fibrosis were 105.9 ± 32.3 cm 3 and 76.3 ± 45.6 cm 3 , respectively, p = 0.02. The overall cosmetic outcome score of Excellent/Good was 74% at 60 months after APBI. Grade ≥ 1 fibrosis was observed in 44% and 92% of patients who scored Excellent/Good and Fair/Poor, respectively, p = 0.004., Conclusions: This study showed excellent local control and survival results with minimal late sequelae., (© 2022. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Purpose: We aimed to compare dosimetric parameters between three-dimensional conformal radiation therapy followed by electron beam boost (3D-CRT + EB) and volumetric modulated arc therapy using simultaneous integrated boost (SIB-VMAT) in left-sided breast cancer patients., Methods: This study included 57 patients with left-sided breast cancer who underwent SIB-VMAT. All patients had a computed tomography-based maximum heart distance of ≥ 1 cm and were prescribed a dose of 42.56 Gy/16 fractions to the planning target volume and a concomitant-boosted target dose of 53.2 Gy or 51.2 Gy. The 3D-CRT + EB plan was retrospectively created for the purpose of comparison using tangential fields with field-in-field technique followed by electron beam irradiation., Results: The doses to the clinical target volume significantly improved in the SIB-VMAT plans. All dosimetric parameters for the left anterior descending coronary artery (LAD) and LAD middle position (LAD mid) in the SIB-VMAT plans were significantly lower than those for 3D-CRT + EB plans (P < 0.01), while the doses to the heart, lung, contralateral breast and non-target tissue were decreased in the 3D-CRT + EB plans compared with those in the SIB-VMAT plans (e.g., 1.9 Gy vs. 2.9 Gy; P < 0.001 for the mean dose of heart)., Conclusions: SIB-VMAT significantly improved the dose to the target while reducing the doses to the LAD and LAD mid, whereas 3D-CRT + EB significantly decreased the doses to the heart and other organs at risk in patients with left-sided breast cancer at risk for radiation-induced coronary artery disease., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: There are few reports from Japan about the outcomes of intensity-modulated radiation therapy for localized prostate cancer. This study was aimed at assessing the efficacy and toxicity of intensity-modulated radiation therapy in patients with intermediate- or high-risk prostate cancer., Methods: We conducted a review of the data, retrieved from our institutional database, of patients who had received intensity-modulated radiation therapy for localized prostate cancer at a radiation dose of 78 Gy in 39 fractions. Data of 201 patients with intermediate-risk prostate cancer and 311 patients with high-risk prostate cancer were analyzed., Results: The median follow-up period after the completion of intensity-modulated radiation therapy was 100 months (range, 24-154). The rates of cause-specific survival, overall survival, metastasis-free survival and biochemical recurrence-free survival in the intermediate-risk patients were 99, 95, 95 and 94% at 5 years and 99, 91, 90 and 86% at 8 years, respectively; the corresponding rates in the high-risk patients were 100, 97, 91 and 84% at 5 years and 96, 92, 84 and 76% at 8 years, respectively. The crude incidence of late grade 2-3 genitourinary toxicity was 28.1%, and that of late grade 3 genitourinary toxicity was 2.0%. The crude incidence of late grade 2 gastrointestinal toxicity was 5.1%, and there were no cases of late grade 3 gastrointestinal toxicity., Conclusions: Our data demonstrated that intensity-modulated radiation therapy is effective for patients with localized intermediate-risk or high-risk prostate cancer while having minimal toxicity., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Although radiation therapy is one of the most significant treatment modalities for localized prostate cancer, the prognostic factors for biochemical recurrence (BCR) regarding the treatment plan are unclear. We aimed to develop a novel dosiomics-based prediction model for BCR in patients with prostate cancer and clarify the correlations between the dosimetric factors and BCR., Methods and Materials: This study included 489 patients with localized prostate cancer (BCR: 96; no-BCR: 393) who received intensity modulated radiation therapy. A total of 2475 dosiomic features were extracted from the dose distributions on the prostate, clinical target volume (CTV), and planning target volume. A prediction model for BCR was trained on a training cohort of 342 patients. The performance of this model was validated using the concordance index (C-index) in a validation cohort of 147 patients. Another model was constructed using clinical variables, dosimetric parameters, and radiomic features for comparisons. Kaplan-Meier curves with log-rank analysis were used to assess the univariate discrimination based on the predictive dosiomic features., Results: The dosiomic feature derived from the CTV was significantly associated with BCR (hazard ratio, 0.73; 95% CI, 0.57-0.93; P = .01). Although the dosiomics model outperformed the dosimetric and radiomics models, it did not outperform the clinical model. The performance significantly improved by combining the clinical variables and dosiomic features (C-index: 0.67; 95% CI, 0.65-0.68; P < .0001). The predictive dosiomic features were used to distinguish high-risk and low-risk patients (P < .05)., Conclusions: The dosiomic feature extracted from the CTV was significantly correlated with BCR in patients with prostate cancer, and the dosiomics model outperformed the model with conventional dose indices. Hence, new metrics for evaluating the quality of a treatment plan are warranted. Moreover, further research should be conducted to determine whether dosiomics can be incorporated in a clinical workflow or clinical trial., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In the multidisciplinary management of early-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTCL), with curative intent, radiation therapy is the most efficacious modality and is an essential component of a combined-modality regimen. In the past decade, utilization of upfront radiation therapy and non-anthracycline-based chemotherapy has improved treatment and prognosis. This guideline mainly addresses the heterogeneity of clinical features, principles of risk-adapted therapy, and the role and appropriate design of radiation therapy. Radiation therapy methods (including target volume definition, dose and delivery methods) are crucial for optimizing cure for patients with early-stage ENKTCL. The application of the principles of involved site radiation therapy in this lymphoma entity often leads to a more extended clinical target volume (CTV) than in other lymphoma types because it usually presents with primary tumor invasion, multifocal lesions, or extensive submucosal infiltration beyond the macroscopic disease. The CTV varies across different primary sites and is classified mainly into nasal, nonnasal upper aerodigestive tract (UADT), and extra-UADT entities. This review is a consensus of the International Lymphoma Radiation Oncology Group regarding the approach to radiation therapy, target-volume definition, optimal dose, and dose constraints in ENKTCL treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To compare long-term outcomes and late toxicity between patients treated with 3-dimensional conformal radiation therapy (3D-CRT) and with dose-escalated intensity modulated radiation therapy (IMRT) as salvage radiation therapy (SRT) after prostatectomy., Methods and Materials: A total of 110 patients who had been treated at our institution between 2010 and 2018 with SRT for biochemical recurrence after radical prostatectomy were included. The patients were treated either by 3D-CRT with 64 Gy (59 patients) or by IMRT with 70 Gy (51 patients). The irradiation target was the prostate bed only (106 patients) or the prostate bed and pelvic region (4 patients). Twelve patients (11%) received concurrent androgen deprivation therapy. The differences in clinical outcomes and late gastrointestinal (GI) and genitourinary (GU) toxicity between the 3D-CRT and IMRT groups were retrospectively assessed. Toxicities were recorded using the Common Terminology Criteria for Adverse Events, version 5.0. Prostate-specific antigen (PSA) progression after SRT was defined as an increase in the serum PSA level of 0.2 ng/mL from the PSA nadir after SRT and confirmed by a second PSA measurement that was higher than the first., Results: The median follow-up time was 7.8 years for 3D-CRT (range:,0.3-9.2 years) and 3.1 years for IMRT (range, 0.4-7.2 years). There was no significant difference in the 4-year biochemical no-evidence-of-disease (bNED) rate between the 3D-CRT and IMRT groups (43.5% vs 52.1%; P  = .20). Toxicity analysis showed no significant difference in late GI or GU toxicities of grade 2 or greater between the 3D-CRT and IMRT groups. The respective 4-year cumulative rates of toxicity in the 3D-CRT and IMRT groups were as follows: grade ≥2 GI toxicity, 8.8% and 4.4% ( P  = .42); grade ≥2 GU toxicity, 19.1% and 20.3% ( P  = .93); and grade ≥2 hematuria, 5.3% and 8.0% ( P  = .67). In the 3D-CRT group, the 8-year cumulative rates of GI toxicity, GU toxicity, and hematuria of grade 2 or greater were 8.8%, 28.4%, and 12.6%, respectively., Conclusions: Dose-escalated IMRT showed no improvements in bNED or late toxicity compared with 3D-CRT. In addition, the results suggest that GU toxicity can occur after a long period (even after 6 years), whereas GI toxicity is seldom newly observed after 4 years., (© 2021 The Author(s).)

Background/aim: To compare five radiotherapy methods for prostate cancer., Patients and Methods: During 2005-2018, the data of patients with non-metastatic prostate cancer were retrospectively analysed. Patients were treated with high-dose-rate brachytherapy (HDR-BT); low-dose-rate brachytherapy (LDR-BT); or external-beam radiotherapy (EBRT), including conventionally fractionated radiotherapy (CFRT), moderate-hypofractionated radiotherapy (MHRT), and ultra-hypofractionated radiotherapy (UHRT)., Results: In total, 496 patients (149, HDR-BT; 100, LDR-BT; 100, CFRT; 97, MHRT, and 50, UHRT) with a median follow-up of 4.3 years were enrolled. The incidence of grade ≥2 acute genitourinary toxicities was significantly lower with HDR-BT (p<0.001) than with any other radiotherapy. The cumulative incidence of late grade ≥2 genitourinary toxicities was the highest with UHRT and significantly higher (p=0.005) with UHRT than with HDR-BT. Higher symptom score peaks were noted 4 weeks after therapy for LDR-BT than for EBRT., Conclusion: Physician-recorded toxicities were slightly lower with HDR-BT and patient-reported outcomes tended to be worse with LDR-BT., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Because non-anthracycline-based chemotherapy with l-asparaginase has improved survival outcomes in patients with extranodal natural killer/T-cell lymphoma (ENKTL), the incidence of central nerve system (CNS) relapse can be different when compared with that in previous reports. In this research, we sought to identify the incidence of and predictors for CNS relapse and to evaluate the necessity of CNS prophylaxis with intermediate-dose methotrexate (ID-MTX). The records of 399 patients in the training cohort and 253 patients in the validation cohort with ENKTL who received non-anthracycline-based chemotherapy were reviewed. Patients were divided into 2 groups according to whether the chemotherapy regimen included ID-MTX above 2 g/m2. A new central nervous system-prognostic index of natural killer (CNS-PINK) model was developed using 1-point powerful predictors of CNS relapse (PINK; hazard ratio [HR], 2.908; P = .030 and extranodal involvement [≥2]; HR, 4.161; P = .001) and was calculated as a sum of scores. The high-risk group of CNS-PINK was defined as 2 points. The cumulative incidence of CNS relapse was different between the CNS-PINK risk groups in the training (P < .001) and validation (P = .038) cohorts. Patients in the high-risk CNS-PINK group who were treated with SMILE or SMILE-like regimens with ID-MTX (S-ID-MTX) displayed a lower incidence rate of CNS relapse than did those who received other regimens without ID-MTX in the training cohort (P = .029). The CNS-PINK was demonstrated its strong predictability of CNS relapse in ENKTL patients. The effectiveness of S-ID-MTX in preventing CNS events in high-risk CNS-PINK patients should be verified in future studies., (© 2020 by The American Society of Hematology.)

This study was aimed at assessing the feasibility and toxicity of using stereotactic body radiation therapy (SBRT) for reirradiation of spinal metastatic tumors. We conducted a retrospective review, from our institutional database, of the data of patients who received reirradiation, with overlap of some prescribed isodose lines to the vertebra from the initial radiation therapy, between 2007 and 2019. We identified 40 patients with spinal metastatic tumors, of whom 2 had 2 metastatic vertebral lesions each, totaling up to 42 target lesions. The median dose to spinal cord at the initial radiation therapy was 30 Gy. SBRT based on the intensity-modulated radiation therapy (IMRT) technique was used for reirradiation to spare the spinal cord. All patients received a prescription dose of 25 Gy in 5 fractions to the planning target volume (PTV). Among the 40 cases who had pain, pain relief was obtained in 24 (60%) after reirradiation. Neurologic improvement was obtained in 8 of 15 cases (53%). The adverse events were evaluated using the Common Terminology Criteria for Adverse Events Version 5.0. Reirradiation was well-tolerated, with only 2 patients experiencing adverse events ≥grade 2 in severity, including 1 patient with grade 3 pain, and another patient with grade 3 spinal fracture. None of the patients developed radiation myelopathy. Our data demonstrated that reirradiation of spinal metastasis using SBRT provided effective pain relief and neurologic improvement, with minimal toxicity., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Objective: The aim of this study was to investigate the influence of chemoradiotherapy (CRT) on nutritional status and the association between changes in nutritional status and clinical outcomes (treatment completion, adverse events, perioperative complications, and relapse-free survival [RFS]) in patients with locally advanced rectal cancer (LARC)., Methods: In this multicenter, phase II study, 41 patients with LARC underwent CRT for 5 wk, followed by a 6- to 8-wk interval before surgery. Body weight, body mass index (BMI), lean body mass, serum albumin, and prealbumin levels were measured before (pre-), during, and after CRT, and before surgery. Changes in these data and scores on the Malnutrition Universal Screening Tool (MUST) were calculated based on pre-CRT status., Results: Twelve patients (29.3%) experienced body weight loss (BWL) ≥5% (defined as malnutrition) after CRT (P < 0.001) and before surgery (P = 0.035). Significant changes were seen in serum albumin levels and BMI during and after CRT (P < 0.001), and in MUST scores after CRT (P = 0.003) and before surgery (P = 0.035). Treatment completion was significantly associated with BWL (P = 0.028), MUST score (P = 0.013), and decreased serum albumin level (P = 0.001) after CRT. Regarding adverse events, MUST score before surgery (P = 0.009) and serum albumin level after CRT (P = 0.002) were significantly associated with diarrhea severity. Serum albumin level during CRT was associated with the onset of neutropenia (P = 0.005). No association was found between BWL and RFS., Conclusions: These findings suggest that malnutrition and changes in nutritional status are not only commonly observed after CRT, but also associated with treatment completion and adverse events., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Many patients with positive margins following breast-conserving surgery (BCS) undergo re-excisions that aim to remove residual disease from the breast, which brings a tremendous emotional burden in addition to financial consequences. We sought to determine whether re-excisions could be safely avoided without compromising local control and survival by using whole-breast radiation therapy (WBRT) with a tumor bed boost in patients with early-stage breast cancer with focally positive, tumor-exposed margins after BCS. All patients with ductal carcinoma in situ (DCIS) and/or invasive breast cancer (IBC) who had pathologically tumor-exposed margins following BCS, without re-excision and treated with WBRT with tumor bed boost between March 2005 and December 2011, were included. The radiotherapy consisted of WBRT at a dose of 50 Gy in 25 fractions, followed by a tumor bed boost with an additional dose of 16 Gy in eight fractions. A total of 125 patients fulfilled the eligibility criteria; of the 125 patients, 1 had bilateral breast cancer, resulting in 126 cases. Invasive disease was found in 102 (81%) cases and purely ductal carcinoma in situ (DCIS) disease in 24 (19%) cases. The 10-year ipsilateral breast tumor recurrence (IBTR) -free survival, progression-free survival (PFS), and 10-year overall survival (OS) rates were 95%, 92.5% and 96%, respectively. Patients with early-stage breast cancer who receive BCS and have focally positive, tumor-exposed margins can avoid re-excision by undergoing WBRT followed by a sufficient dose of tumor bed boost, without negatively impacting local control and survival., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: Although dose prediction for intensity modulated radiation therapy (IMRT) has been accomplished by a deep learning approach, delineation of some structures is needed for the prediction. We sought to develop a fully automated dose-generation framework for IMRT of prostate cancer by entering the patient CT datasets without the contour information into a generative adversarial network (GAN) and to compare its prediction performance to a conventional prediction model trained from patient contours., Methods: We propose a synthetic approach to translate patient CT datasets into a dose distribution for IMRT. The framework requires only paired-images, i.e., patient CT images and corresponding RT-doses. The model was trained from 81 IMRT plans of prostate cancer patients, and then produced the dose distribution for 9 test cases. To compare its prediction performance to that of another trained model, we created a model trained from structure images. Dosimetric parameters for the planning target volume (PTV) and organs at risk (OARs) were calculated from the generated and original dose distributions, and mean differences of dosimetric parameters were compared between the CT-based model and the structure-based model., Results: The mean differences of all dosimetric parameters except for D98% and D95% for PTV were within approximately 2% and 3% of the prescription dose for OARs in the CT-based model, while the differences in the structure-based model were within approximately 1% for PTV and approximately 2% for OARs, with a mean prediction time of 5 seconds per patient., Conclusions: Accurate and rapid dose prediction was achieved by the learning of patient CT datasets by a GAN-based framework. The CT-based dose prediction could reduce the time required for both the iterative optimization process and the structure contouring, allowing physicians and dosimetrists to focus their expertise on more challenging cases., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Various brachytherapy options are available for treating cervical cancer. This study investigated whether pre-brachytherapy magnetic resonance imaging (MRI) findings could help identify the appropriate brachytherapy technique for cervical cancer., Methods: We retrospectively evaluated patients with cervical cancer who underwent pre-brachytherapy MRI within 7 days before their first high-dose rate brachytherapy treatment between December 2009 and September 2015. Patients who could not undergo MRI at pre-treatment and/or pre-brachytherapy and complete radical radiotherapy were excluded. Conventional intracavitary brachytherapy was the preferred treatment for ≤4 cm and symmetrical tumors. Non-conventional intracavitary brachytherapy, including interstitial brachytherapy, was the preferred treatment for bulky tumors, asymmetrical tumors, tumors with severe vaginal invasion, or bulky barrel-shaped tumors. The 3-year rates of overall survival, disease-free survival, and local control were compared using the Kaplan-Meier method and the log-rank test. Overall survival and local control rates were assessed using Cox regression analysis to identify risk factors for poor overall survival and local control outcomes., Results: A total of 146 patients were included in the study. The median tumor sizes were 52 mm (range 17-85) at the pre-treatment MRI and 30 mm (range 0-78) at the pre-brachytherapy MRI. Six patients had International Federation of Gynecology and Obstetrics (FIGO) stage IB2, 67 patients had stage II, 64 patients had stage III, and nine patients had stage IVA disease. A total of 124 (85%) patients had squamous cell carcinoma and 22 (15%) patients had adenosquamous cell carcinoma or adenocarcinoma. The MRI findings showed severe vaginal invasion (pre-treatment: 19 patients, pre-brachytherapy: 10 patients), asymmetrical bulky tumors (pre-treatment: 28 patients, pre-brachytherapy: 16 patients), and severe corpus invasion (pre-treatment: 39 patients, pre-brachytherapy: 18 patients). Based on the pre-brachytherapy MRI findings, non-conventional intracavitary brachytherapy was administered to 34 (23.3%) patients. Brachytherapy seemed to be appropriate for 133 (91.1%) patients and inappropriate for 13 (8.9%) patients. The 3-year rates were 84.2% for overall survival and 90.1% for local control. Grade 3 late rectal complications occurred in two (1%) patients. Multivariate analysis showed that tumor characteristics (size, shape, and extent of invasion) were not risk factors, although inappropriate brachytherapy was significantly related to poor local control (p<0.001)., Conclusion: Pre-brachytherapy MRI may help to select appropriate brachytherapy for cervical cancer and reduce the likelihood of inappropriate brachytherapy leading to poor local control., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aim: We aimed to evaluate the efficacy of high-dose-rate brachytherapy techniques selected according to pre-brachytherapy magnetic resonance imaging (MRI) findings in asymmetrical cervical cancer (ACC)., Patients and Methods: We analyzed 33 ACC patients. Asymmetric tumors were defined as those in which the difference between the distance from the cervical canal to the farthest end of the tumor [long distance (LD)] and the distance from the cervical canal to the contralateral tumor edge [short distance (SD)] is equal to or greater than 2 cm on the basis of MRI prior to treatment. On pre-treatment and pre-brachytherapy MRI, the median LDs were 40 mm and 21 mm, respectively. Patients with LD≥2 cm and LD - SD≥1 cm on pre-brachytherapy MRI received non-conventional intracavitary brachytherapy (ICBT)., Results: Sixteen patients (48%) received non-conventional ICBT. There was no significant difference in 3-year local control between the two treatment groups (100% vs. 81.2%, p=0.07); two patients had grade 2 radiation proctitis., Conclusion: Brachytherapy techniques selected according to pre-brachytherapy MRI findings were effective for ACC treatment., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The Japanese Breast Cancer Society (JBCS) Clinical Practice Guideline was revised in 2018. This article describes the revise points in the section on radiation therapy (RT)., Methods and Materials: The JBCS formed task force to update the JBCS Clinical Practice Guideline 2015 edition. Background questions (BQs) deal with standard treatments of breast cancer in clinical practice. Clinical questions (CQs) highlight the important treatments in which controversy remains. The task force for RT section addressed the 10 BQs, the 10 CQs, and the 4 Future reseach questions (FQs). For each CQ, systematic literature reviews and meta-analyses were conducted, and recommendations, strength of recommendation and strength of evidence were determined according to the protocol in Morizane et al. (Minds Handbook for Clinical Practice Guideline Development, 2014)., Results: The recommendations, the strength of recommendation and the strength of evidence were determined based on the systematic literature reviews and the meta-analyses for each CQ., Conclusion: The JBCS updated the Clinical Practice Guideline. RT represents a significant portion of the breast cancer treatment, and these recommendations regarding RT will be useful in individualized, shared decision making between physicians and patients.

Reduced-intensity stem cell transplantation (RIST) minimizes the adverse effects of traditional hematopoietic stem cell transplantation, and low-dose total-body irradiation (TBI) is administered over a short period prior to RIST (TBI-RIST). Different institutes adopt different approaches for the administration of TBI-RIST, and since no study had previously investigated this issue, a survey of the TBI schedules in Japan was conducted. In October 2015, the Japanese Radiation Oncology Study Group initiated a national survey of TBI-RIST procedures conducted between 2010 and 2014. Of 186 institutions performing TBI, 90 (48%) responded to the survey, 78 of which performed TBI-RIST. Of 2488 patients who underwent TBI for malignant disease at these institutions, 1412 (56.8%) patients were treated for leukemia, 477 (19.2%) for malignant lymphoma, 453 (18.2) for myelodysplastic syndrome, 44 (1.8%) for multiple myeloma, and 102 (4.1%) for other malignant diseases. Further, 206 (52.0%) of 396 patients (a high proportion of patients) who underwent TBI for benign disease had aplastic anemia. The TBI-RIST equipment and treatment methods were similar to those used for myeloablative regimens. Routinely shielded organs included the lungs (43.6%), eyes (50.0%) and kidneys (10.2%). The ovaries (14.1%), thyroid (6.4%) and testicles (16.7%) were also frequently shielded, possibly reflecting an emphasis on shielding reproductive organs in children. TBI-RIST was performed more frequently than myeloablative conditioning in patients with benign disease. Genital and thyroid shielding were applied more frequently in patients treated with TBI-RIST than in patients treated with myeloablative conditioning. In conclusion, this study indicates the status of TBI-RIST in Japan and can assist future efforts to standardize TBI-RIST treatment methods and to design a future multicenter collaborative research study., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Purpose: The aim of this study is to evaluate the safety and efficacy of induction modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus bevacizumab followed by S- 1-based chemoradiotherapy in magnetic resonance imaging (MRI)-defined poor-risk locally advanced low rectal cancer., Patients and Methods: This was a prospective phase II trial at a single comprehensive cancer center. The primary endpoint was the pathological complete response (pCR) rate. Eligible patients had clinical stage II-III low rectal adenocarcinoma with any of the following MRI-defined poor-risk features: circumferential resection margin (CRM) ≤ 1 mm, cT4, positive lateral nodes, mesorectal N2 disease, and/or requiring abdominoperineal resection. Patients received six cycles of mFOLFOX6 with 5 mg/kg bevacizumab followed by oral S-1 (80 mg/m 2 /day on days 1-14 and 22-35) plus radiotherapy (50.4 Gy). Surgery was conducted through a laparoscopic approach. Lateral node dissection was selectively added when the patient had enlarged lateral nodes., Results: A total of 43 patients were enrolled. Grade 3-4 adverse events occurred in nine patients during induction chemotherapy and in five patients during chemoradiotherapy. One patient declined surgery with a clinical complete response. Forty-two patients underwent surgery, and 16 had pCR [37.2%, 95% confidence interval (CI) 24.4-52.1%]. All underwent R0 resection without conversion, including combined resection of adjacent structures (n = 14) and lateral node dissection (n = 30). Clavien-Dindo grade 3-4 complications occurred in six patients (14.3%). With median follow-up of 52 months, six developed recurrences (lung n = 5, local n = 1; 3-year relapse-free survival 86.0%)., Conclusions: This study achieved a high pCR rate with favorable toxicity and postoperative complications in poor-risk locally advanced low rectal cancer. Multicenter study is warranted to evaluate this regimen.

Purpose: We previously reported that ∼30% of patients with localized follicular lymphoma (FL) staged by 18 F-fluorodeoxyglucose positron emission tomography-computed tomography receiving primary radiation therapy (RT) will relapse within 5 years. We sought to report outcomes for those who relapsed., Methods and Materials: We conducted a multicenter, retrospective study of patients aged ≥18 years who received RT ≥ 24 Gy for stage I to II, grade 1 to 3A FL, staged with 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography-computed tomography. Observation was defined as >6 months without treatment from relapse. Overall survival (OS) and freedom from progression (FFP) were estimated with Kaplan-Meier analysis and univariable and multivariable analyses with Cox regression., Results: Of 512 patients with median follow-up of 52 months, 149 (29.1%) developed recurrent lymphoma at a median of 23 months (range, 1-143) after primary RT. Median follow-up was 33 months after relapse. Three-year OS was 91.4% after recurrence. OS was significantly worse for those with relapse ≤12 months from date of diagnosis versus all others-88.7% versus 97.6%, respectively (P = .01)-and remained significantly worse on multivariable analyses (follicular lymphoma international prognostic index-adjusted hazard ratio, 3.61; P = .009). Histology at relapse included 93 indolent (grade 1-3A), 3 FL grade 3B/not otherwise specified, and 18 diffuse large B-cell lymphoma; 35 patients did not undergo biopsy. Of those with follow-up ≥3 months who underwent biopsy (n = 74) or had presumed (n = 23) indolent recurrence, 58 patients (59.8%) were observed, 19 (19.6%) had systemic therapy, 16 (16.5%) had RT, and 4 (4.1%) had systemic therapy + RT. For patients with indolent recurrences that were observed, 3-year FFP or freedom from treatment was 56.6% (median, 48 months). For all patients with biopsied/presumed indolent recurrence receiving salvage treatment (n = 59, including 20 initially observed) 3-year FFP was 73.9%., Conclusions: Prognosis for patients with relapsed FL after primary radiation therapy is excellent, supporting the role of primary radiation in the management of early stage disease. Patients with localized FL treated with primary RT who experience early relapse (<12 months) have inferior survival compared with those with longer disease-free interval., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Extranodal NK/T cell lymphoma (NKTCL), nasal type (ENKL) that shows no apparent nasal involvement, is termed extranasal NKTCL or non-nasal NKTCL. In this study, we aimed to explore therapeutic approaches and outcomes in patients with extranasal NKTCL in current clinical practice. A data set of patients with newly diagnosed NKTCL who were diagnosed at 31 institutes in Japan between 2000 and 2013 was used for analysis. The patients' fitness for steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy was assessed using the major inclusion criteria of the SMILE phase 2 study. Of 358 patients, 47 (13%) had extranasal NKTCL. The most frequent extranodal sites of involvement in extranasal NKTCL were skin/subcutaneous tissue (n = 18). Six (13%) of the patients with extranasal NKTCL had localized disease and were diagnosed before 2010. With a median follow-up of 5.8 years, the 2-year overall survival (OS) in patients with nasal and extranasal NKTCL was 70% (95% confidence interval [CI], 65-75%) and 34% (95% CI, 21-47%), respectively. OS in patients with nasal NKTCL had a trend toward better according to treatment era (P = 0.063). In contrast, no obvious improvement of OS was observed in extranasal NKTCL (P = 0.43). The major inclusion criteria of the SMILE-P2 were met in 21% (10/47) of patients with extranasal NKTCL and 60% (188/311) of those with nasal NKTCL (P < 0.001). Despite the advent of new treatments for ENKL, OS remains unfavorable in extranasal NKTCL. A more effective therapy is needed for extranasal NKTCL.

Purpose: The study was designed to evaluate the safety and efficacy of adding oxaliplatin to py (CRT) with S-1 in patients with locally advanced rectal carcinoma (LARC). We report here the final results of the study., Patients and Methods: Patients with histopathologically confirmed LARC (cT3-T4, any N) were eligible. They received oral S-1 (80 mg/m 2 /day on days 1-5, 8-12, 22-26, and 29-33) and infusional oxaliplatin (60 mg/m 2 /day on days 1, 8, 22, 29) plus radiotherapy (1.8 Gy/day, total dose of 50.4 Gy in 28 fractions), with a chemotherapy gap in the third week of radiotherapy. Primary endpoint of the study was pathological complete response (pCR) rate. Secondary endpoints were rates of R0 resection, down-staging, cumulative 3-year local recurrence, 3-year disease-free survival (DFS), and toxicity., Results: Forty-five patients were enrolled at six centers in Japan. All patients received CRT, and 44 underwent operation. The pCR rate was 27.3% (12/44). The R0 resection rate was 95.5% (42/44). T-down-staging rate was 59.1% (26/44), and N-down staging rate was 65.9% (29/44); the combined pathological down-staging rate was 79.5% (35/44). There were no grade 4 adverse events, but 11.1% of the patients had grade 3 adverse events. Cumulative 3-year local recurrence rate was 0%. However, 13 (30.0%) patients suffered from distant metastasis, and one patient suffered from secondary esophageal cancer that was unrelated to rectal cancer. Eight patients had lung metastasis, 4 had liver metastasis, and 3 patients died of the metastatic disease. The 3-year DFS rate of the 44 patients was 67.5% (median follow-up 36.3 months), and the 3-year overall survival (OS) rate was 93.0% (median follow-up 39.6 months). The patients were then divided into the pCR (12 patients) group and non pCR (32 patients) group. The 3-year rate of DFS for each group was 91.7% and 58.1% and that of OS was 100% and 90.3%, respectively., Conclusions: The study showed a high pCR rate with no severe toxicity, good follow-up results, and good loco-regional control. Therefore, addition of oxaliplatin to preoperative CRT with S-1 in patients with LARC might be feasible and lead to better local control than standard treatment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: (i) to investigate the capability of organ-at-risk (OAR) dose reduction with the jaw tracking (JT) technique in flattening filter-free (FFF) beams in lung stereotactic body radiation therapy (SBRT), (ii) to propose a novel metric to quantify the jaw movements during JT, and (iii) to examine the relationships between the quantified jaw movements and reduction rate of OAR doses., Methods: The individual SBRT plans with volumetric modulated arc therapy using the JT technique (JT-VMAT) and VMAT plans with a fixed jaw (FJ-VMAT) were created for 15 patients, and dosimetric parameters were compared. A jaw tracking complexity score (JTCS) was defined and compared with the multi-leaf collimator (MLC) modulation complexity score (MCS). The correlations between the JTCS and reduction rate of OAR doses were examined., Results: The decrease of OARs doses was statistically significant in the JT-VMAT plans (1.2% in V20 of the lung and <1% in all other OARs). The correlations between the JTCS and MCS were not significant. There were significant correlations between the JTCS and the reduction rates in V 20 , V 2.5 , and D mean of the lung, D 1% of the spinal cord, and D 90% of the body., Conclusions: A significant decrease of dosimetric parameters of OARs was found with JT-VMAT in FFF beams. This reduction is very small and probably not clinically relevant. JTCS, a novel metric to quantify the jaw movements during JT, was proposed, and the complexity of jaw movements did not correlate with that of the movements of MLC leaves. There were significant correlations between the JTCS and some dosimetric parameters of OARs., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Radiotherapy (RT) can be curative in patients with localized follicular lymphoma (FL), with historical series showing a 10-year disease-free survival of 40 to 50%. As 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography with computerized tomography (PET-CT) upstages 10 to 60% of patients compared to CT, we sought to evaluate outcomes in patients staged by PET-CT, to determine if more accurate staging leads to better patient selection and results. We conducted a multicenter retrospective study under the direction of the International Lymphoma Radiation Oncology Group (ILROG). Inclusion criteria were: RT alone for untreated stage I to II FL (grade 1-3A) with dose equivalent ≥24 Gy, staged by PET-CT, age ≥18 years, and follow-up ≥3 months. End points were freedom from progression (FFP), local control, and overall survival (OS). A total of 512 patients treated between 2000 and 2017 at 16 centers were eligible for analysis; median age was 58 years (range, 20-90); 410 patients (80.1%) had stage I disease; median RT dose was 30 Gy (24-52); and median follow-up was 52 months (3.2-174.6). Five-year FFP and OS were 68.9% and 95.7%. For stage I, FFP was 74.1% vs 49.1% for stage II ( P < .0001). Eight patients relapsed in-field (1.6%). Four had marginal recurrences (0.8%) resulting in local control rate of 97.6%. On multivariable analysis, stage II (hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.44-3.10) and BCL2 expression (HR, 1.62; 95% CI, 1.07-2.47) were significantly associated with less favorable FFP. Outcome after RT in PET-CT staged patients appears to be better than in earlier series, particularly in stage I disease, suggesting that the curative potential of RT for truly localized FL has been underestimated., (© 2019 by The American Society of Hematology.)

Background: We evaluated the effectiveness of visual feedback (VF) on radiotherapy with deep inspiration breath-holding (DIBH), and reviewed the dose for organs at risk (OARs)., Methods: Respiratory motions during DIBH for 15 s were monitored during planning computed tomography (CT)-scanning and simulation for 40 patients after breast-conserving surgery from June 2007 to February 2008. For 22 of 40 patients, a goggle-type liquid crystal display monitor was used for VF. The opposing tangential field was planned. The prescribed dose was 50.0 Gy in 25 fractions., Results: The mean differences of the chest wall respiratory movement in DIBH between planning CT-scanning and simulation were 4.7 ± 2.6 mm for the patients without VF and 1.0 ± 0.9 mm for those with VF (p < 0.01). The mean chest wall excursion as a whole in DIBH using VF (2.0 ± 1.0 mm) was smaller than in those without VF (4.1 ± 2.4 mm) (p < 0.01). According to reproducibility and stability parameters, 4 mm was added as a posterior margin to the clinical target volume for RT with VF, and 10 mm for those without VF. The mean heart doses were 1.3 ± 0.5 Gy with VF and 2.4 ± 1.1 Gy without VF (p < 0.01). Mean dose and max dose of right breast were significantly reduced in procedures with VF use vs. in those without VF (p < 0.01 and < 0.01, respectively)., Conclusions: VF increases the accuracy of postoperative radiotherapy with DIBH, and also helps reduce the dose for OARs.

Objectives: American Brachytherapy Society (ABS)-recommended interstitial brachytherapy (IBT) should be considered for bulky vaginal tumor thicker than 5 mm. The aim of this study was to evaluate the ABS consensus guideline for patients with severe vaginal invasion based on our long-term follow-up results., Methods/materials: The study included 7 patients with vaginal cancer and 14 patients with cervical cancer invading to the lower vagina. Based on prebrachytherapy magnetic resonance imaging findings, patients received intracavitary brachytherapy (ICT) for vaginal tumors 5 mm or less or IBT for vaginal tumors less than 5 mm. Nine patients received ICT and the remaining 12 patients received IBT. For dosimetric comparison, an experimental recalculation as the virtual IBT for patients actually treated by ICT, and vice versa, was performed., Results: The 5-year local control rate for all tumors was 89.4%. No differences in local control between ICT- and IBT-treated groups were observed (P = 0.21). One patient experienced a grade 3 rectal complication. There were no significant differences in the CTV D90 and rectum D2cc between the 2 groups (P = 0.13 and 0.39, respectively). In the dosimetric study of ICT-treated patients, neither the actual ICT plans nor the experimental IBT plans exceeded the limited dose for organs at risk, which were recommended in the guideline published from the ABS. In the IBT-treated patients, D2cc for bladder and rectum of the experimental ICT plans was significantly higher than for the actual IBT plans (P < 0.001 and <0.001, respectively), and 11 experimental ICT plans (92%) exceeded the limited dose for bladder and/or rectum D2cc., Conclusions: Tumor control and toxicity after selected brachytherapy according to vaginal tumor thickness were satisfactory; IBT instead of ICT is recommended for patients with vaginal tumor thickness greater than 5 mm to maintain bladder and/or rectum D2cc.

Extranodal NK/T-cell lymphoma, nasal type (ENKL), is a rare lymphoma subtype of peripheral T/NK-cell lymphoma that is very common in East Asia and Latin America. Two-thirds of patients have localized disease in the nasal cavity or adjacent sites. Large retrospective studies have revealed the clinicopathologic features of ENKL patients, identified risk factors for short survival time, and developed prognostic models. Next-generation sequencing studies have provided a comprehensive list of recurrent mutations in ENKL. Since the early 2000s, disease-specific therapeutic approaches have been developed, and the standard of care for ENKL has markedly changed. Non-anthracycline-containing chemotherapy with or without radiotherapy is the current standard approach for ENKL treatment. Emerging therapies, including the use of immune checkpoint inhibitors, are being investigated., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A myeloablative regimen that includes total-body irradiation (TBI) before hematopoietic stem cell transplantation results in higher patient survival rates than achieved with regimens without TBI. The TBI protocol, however, varies between institutions. In October 2015, the Japanese Radiation Oncology Study Group initiated a national survey of myeloablative TBI (covering 2010-2014). Among the 186 Japanese institutions performing TBI, 90 (48%) responded. The 82 institutions that had performed myeloablative TBI during this period treated 2698 patients with malignant disease [leukemia (2082 patients, 77.2%), malignant lymphoma (378, 14%)] and 37 with non-malignant disease [severe aplastic anemia (20, 54%), inborn errors of metabolism (5, 14%)]. A linear accelerator was used at all institutions. The institutions were divided into 41 large and 41 small institutions based on the median number of patients. The long source-surface distance technique was the method of choice in the 34 institutions (82.9%) and the moving-couch technique in the 7 (17.1%) in the large institutions. The schedules most routinely used by the participating institutions consisted of 12 Gy/6 fractions/3 days (26 institutions, 63.5%) in the large institutions. The dose rate varied from 5 to 26 cGy/min. The lungs and lenses were routinely shielded in 23 large institutions (56.1%), and only the lungs in 9 large institutions (21.9%). At lung-shielding institutions, the most frequent maximum acceptable total dose for the lungs was 8 Gy (19 institutions, 27.5%). Our results reveal considerable differences in the TBI methods used by Japanese institutions and thus the challenges in designing multicenter randomized trials based on TBI.

Extranodal natural killer/T-cell lymphoma, nasal type (ENKL) is a subtype of mature T- and natural killer cell lymphomas characterized by its association with Epstein-Barr virus and extranodal involvement. Although there is geographic variance in the frequency of ENKL, its clinical features are similar between Western countries and endemic areas, such as East Asia. Anthracycline-containing chemotherapy is not recommended to treat ENKL. No standard treatment has been established based on the results of randomized controlled trials. In patients with localized disease, radiotherapy is a core component of the recommended first-line therapy. Radiotherapy administered at 50 to 54 Gy, extended involved-site radiotherapy considering tumor invasiveness, and the use of intensity modulated radiation therapy or volumetric modulated arc therapy are associated with efficacy of radiotherapy. Although the use of concurrent chemoradiotherapy has been supported by the results of clinical trials, accumulating evidence supports the use of sequential chemoradiotherapy with non-anthracycline-containing regimens that include l-asparaginase and/or platinum anticancer agents. l-asparaginase-containing chemotherapy is a key component of first-line treatments for systemic ENKL. Hematopoietic stem cell transplantation is recommended as a front-line consolidation therapy for newly diagnosed advanced-stage ENKL. Newer agents including immune checkpoint inhibitors are being investigated for treating ENKL. In this modern ENKL treatment era, multidisciplinary efforts are needed to identify the best timing and sequencing of radiotherapy, l-asparaginase, platinum, newer agents, and hematopoietic stem cell transplantation., (© 2018 by The American Society of Hematology.)

Prognosis of patients with localized nasal extranodal natural killer/T-cell lymphoma, nasal type (ENKL) has been improved by non-anthracycline-containing treatments such as concurrent chemoradiotherapy (CCRT). However, some patients experience early disease progression. To clarify the clinical features and outcomes of these patients, data from 165 patients with localized nasal ENKL who were diagnosed between 2000 and 2013 at 31 institutes in Japan and who received radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) were retrospectively analyzed. Progression of disease within 2 years after diagnosis (POD24) was used as the definition of early progression. An independent dataset of 60 patients with localized nasal ENKL who received CCRT at Samsung Medical Center was used in the validation analysis. POD24 was documented in 23% of patients who received RT-DeVIC and in 25% of patients in the validation cohort. Overall survival (OS) from risk-defining events of the POD24 group was inferior to that of the reference group in both cohorts (P < .00001). In the RT-DeVIC cohort, pretreatment elevated levels of serum soluble interleukin-2 receptor (sIL-2R), lactate dehydrogenase, C-reactive protein, and detectable Epstein-Barr virus DNA in peripheral blood were associated with POD24. In the validation cohort, no pretreatment clinical factor associated with POD24 was identified. Our study indicates that POD24 is a strong indicator of survival in localized ENKL, despite the different CCRT regimens adopted. In the treatment of localized nasal ENKL, POD24 is useful for identifying patients who have unmet medical needs., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

The present study compares dosimetric parameters between volumetric-modulated arc therapy (VMAT) and 3D conformal radiation therapy (3D-CRT) in lung tumors adjacent to the chest wall treated with stereotactic body radiation therapy (SBRT). The study focused on the radiation dose to the chest wall of 16 patients who had developed radiation-induced rib fractures (RIRF) after SBRT using 3D-CRT. The targets in all patients were partially overlapping with the fractured ribs, and the median overlapping rib-PTV distance was 0.4 cm. Stereotactic body radiation therapy was re-planned for all patients. The prescribed dose was 48 Gy in four fractions to cover at least 95% of the planning target volume (PTV). Evaluated dosimetric factors included D98% and the conformation number (CN) of the PTV, the D2cm3, V40 and V30 of the fractured ribs, the V30 of the chest wall, and the Dmean, V20 and V5 of the lung. A comparison of 3D-CRT with the VMAT plan for PTV revealed that CN was significantly improved in the VMAT plan, whereas D98% did not significantly differ between the two plans. Regarding organs at risk (OARs), the D2cm3, V40 and V30 of fractured ribs, the V30 of the chest wall, and the Dmean, V20 and V5 of the lung, were significantly decreased in the VMAT plan. We concluded that the dose to OARs such as ribs and chest wall could be reduced with improved target conformity using VMAT instead of 3D-CRT for SBRT to treat peripheral lung tumors.

Purpose: There are no randomized studies on the indication for postmastectomy radiation therapy (PMRT) in patients who receive neoadjuvant chemotherapy (NAC) followed by a mastectomy. The aim of this study was to determine clinical outcomes and identify reliable prognostic factors in patients with locally advanced breast cancer treated with NAC followed by a mastectomy and PMRT., Methods and Materials: We retrospectively evaluated the relationship between clinicopathological factors and outcomes in 351 patients with stage II or III breast cancer who underwent NAC followed by radical mastectomy and PMRT between March 2005 and December 2013., Results: The median follow-up duration was 81 months (Range, 12-156 months). For all patients, the 5-year locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates were 91.3 %, 69.8 %, and 83.4 %, respectively. On multivariate analysis, estrogen-receptor positivity, and complete response of cancer in axillary nodes (ypN0) were significant prognostic factors for better LRFS, while lympho-vascular invasion and clinical stage IIIC were independent prognostic factors for worse LRFS. The number of axillary node metastasesafter surgery was an independent prognostic factor of DMFS and OS. Patients with hormone receptor- and human epidermal growth factor receptor 2 positivity had significantly better 5-year LRFS rates., Conclusions: We identified several prognostic factors in our study. In particular, the number of axillary node metastases is significantly related to OS.

Approximately 30% to 40% of patients with diffuse large B-cell lymphoma (DLBCL) will have either primary refractory disease or relapse after chemotherapy. In transplant-eligible patients, those with disease sensitive to salvage chemotherapy will significantly benefit from high-dose therapy with autologous stem cell transplantation. The rationale for considering radiation therapy (RT) for selected patients with relapsed/refractory DLBCL as a part of the salvage program is based on data regarding the patterns of relapse and retrospective series showing improved local control and clinical outcomes for patients who received peritransplant RT. In transplant-ineligible patients, RT can provide effective palliation and, in selected cases, be administered with curative intent if the relapsed/refractory disease is localized. We have reviewed the indications for RT in the setting of relapsed/refractory DLBCL and provided recommendations regarding the optimal timing of RT, dose fractionation scheme, and treatment volume in the context of specific case scenarios., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The definition of complete resection of ductal carcinoma in situ (DCIS) is difficult to standardize because of the high variety of surgical breast conserving procedures, specimen handling, and pathological examinations. Using strictly controlled criteria in a single institute, the present study aimed to determine the ipsilateral breast cancer rate when radiotherapy is omitted following complete resection of DCIS., Methods: We retrospectively examined 363 consecutive DCIS patients who underwent breast-conserving surgery, and of these, 125 (34.4%) had complete resection according to the criteria. We finally included 103 patients who omitted radiotherapy. Ipsilateral and contralateral breast cancer events were assessed., Results: The median follow-up period was 118 months. The incidences of ipsilateral and contralateral breast cancer and ipsilateral invasive breast cancer at 10 years were 10.8%, 9.1%, and 3.6%, respectively. No patient died of breast cancer., Conclusion: If complete resection of DCIS can be ensured, the annual incidence of ipsilateral breast cancer, even without irradiation, can be limited to approximately 1%, which equals the incidence of contralateral breast cancer., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: We conducted a multi-institutional prospective study on accelerated partial breast irradiation (APBI) using interstitial brachytherapy. The clinical results over a minimum follow-up period of 30 months are presented here., Materials and Methods: Forty-six patients with breast cancer were treated with breast-conserving surgery and postoperative APBI. After confirmation of negative surgical margins and negative lymph nodes, a high-dose-rate brachytherapy protocol of 36 Gy/6 fractions was carried out. All clinical data were prospectively collected using the Common Terminology Criteria for Adverse Events ver. 3.0., Results: No recurrence was observed. Cumulative rates of grade 2 or higher late sequelae were 25% for fibrosis, 2% for fractures, 9% for pain, and 9% for soft tissue necrosis. Rates of excellent or good cosmetic results as assessed by the physician and patient were 93 and 89% at the 12-month follow-up and 76 and 74% at the 30-month follow-up, respectively. Large volumes of resected tissue in small breasts were associated with fibrosis of grade 2 or higher., Conclusion: APBI in Japanese women provides satisfactory clinical results except for cosmetic outcomes. There is some difficulty with the assessment of fibrosis and cosmetic outcomes, especially in patients with small breasts., Clinical Trial Registration Number: UMIN000001677.

Purpose: The present study compared the complications associated with hypofractionated intensity-modulated radiation therapy (Hypo-IMRT) of prostate cancer to conventionally fractionated IMRT (Conv-IMRT)., Materials and Methods: Hypo-IMRT delivered 70 Gy in 28 fractions, whereas Conv-IMRT delivered 78 Gy in 39 fractions. Toxicity was graded with the Common Terminology Criteria for Adverse Events, version 4.0, weekly during radiotherapy, 1 month after radiotherapy, and annually in both patient groups., Results: The median follow-ups were 39.1 and 38.7 months for patients in the Hypo- and Conv-IMRT groups, respectively. There was no significant difference in rates of acute and late adverse events. The proportions of grade 2 acute genitourinary complications were 48.4 and 51.2% in the Hypo- and Conv-IMRT groups, respectively. The presence of a baseline International Prostate Symptom Score (IPSS) of ten or more was the only significant prognostic factor for grade 2 acute genitourinary toxicity. The incidence of grade 2 late rectal hemorrhage at 3 years was 3.2 and 3.5% in the Hypo- and Conv-IMRT groups, respectively. Small rectal volume was significantly associated with grade 2 late rectal hemorrhage., Conclusion: Regarding acute and late adverse events, hypofractionated IMRT for prostate cancer was well tolerated and comparable with conventionally fractionated IMRT. Clinical trial registration no. UMIN000003218.

Purpose To elucidate the management and outcomes of patients with extranodal natural killer/T-cell lymphoma, nasal type (ENKL), who were diagnosed between 2000 and 2013 in Japan. Patients and Methods Data from 358 patients with ENKL diagnosed between 2000 and 2013 from 31 institutes were retrospectively analyzed. Results Patients' median age was 58 years, and 257 (72%) had localized disease. The most common first-line treatment was radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) (66%) for localized ENKL and L-asparaginase-containing chemotherapy (30%) for advanced ENKL. With a median follow-up of 5.8 years, overall survival (OS) rates at 5 years for localized and advanced ENKL were 68% and 24%, respectively. The prognostic index of natural killer lymphoma was validated in our study, although only 4% of patients with localized ENKL were classified as high risk. With a median follow-up of 5.6 years, OS and progression-free survival at 5 years in the 150 patients who received RT-DeVIC in clinical practice were 72% (95% CI, 63% to 78%) and 61% (95% CI, 52% to 69%), respectively. Toxicities of RT-DeVIC were comparable to those in a previous trial. Multivariate analysis in patients with localized ENKL who received RT-DeVIC identified elevated soluble interleukin-2 receptor as an independent predictive factor for worse OS and progression-free survival (adjusted hazard ratios, 2.28 and 2.46; 95% CI, 1.24 to 4.23 and 1.42 to 4.28; P = .008 and .0014, respectively). Conclusion Favorable OS in response to new treatments was demonstrated in a large number of patients. Improved treatment approaches are needed for localized ENKL exhibiting elevated pretreatment soluble interleukin-2 receptor.

Background: A Japanese prospective multi-institutional feasibility study on accelerated partial breast irradiation using interstitial brachytherapy was performed. The first clinical results were reported with a median follow-up of 26 months., Patients and Methods: Forty-six female breast cancer patients with positive hormone receptors and tumors ≤3 cm, pN0M0, completed the protocol treatment. After breast-conserving surgery and histological confirmation of negative surgical margins and pN0, brachytherapy applicators were implanted either postoperatively (n = 45) or intraoperatively (n = 1). High-dose-rate brachytherapy of 36 Gy/6 fractions was delivered. All clinical data were prospectively collected using case report forms and the Common Terminology Criteria for Adverse Events ver.3.0., Results: At the median follow-up of 26 months, no breast cancer recurrence of any type was observed. Sequelae ≥G2 were dermatitis (G2, 7 %), fibrosis (G2, 11 %; G3, 4 %), fracture (G2, 2 %), pain (G2, 7 %; G3, 2 %), and soft tissue necrosis (G2, 6 %). Cosmetic outcomes evaluated by excellent/good scores were 100 % at pre-therapy (n = 46), 94 % at 12 months (n = 46), and 81 % at 24 months (n = 36), respectively., Conclusions: Disease control and sequelae were satisfactory due to the strict eligibility and protocol-defined treatment parameters. The cosmetic outcomes were comparable to those of previous Japanese breast-conserving therapy series.

Aim: To determine the efficacy of low-dose palliative radiotherapy in patients with refractory aggressive lymphoma., Background: There are few reports on the administration of palliative radiotherapy to patients with aggressive lymphoma., Materials and Methods: The present study included 11 patients with 30 sites of aggressive lymphoma (diffuse large cell lymphoma, n = 7; mantle cell lymphoma, n = 2; follicular large cell lymphoma, n = 1; and peripheral T cell lymphoma, n = 1). The patients received local palliative radiotherapy after receiving a median of 4 chemotherapy regimens. The radiotherapy doses administered to the 30 sites were as follows: 8 Gy, single fraction (n = 27); 6 Gy, single fraction (n = 1); 4 Gy, single fraction (n = 1); and 4 Gy, 2 fractions (n = 1)., Results: The complete response rate was 45% (5/11); the partial response rate was 36% (4/11). Toxicity occurred at one irradiated site (the mandibular), which showed temporal acute gingivitis; however, medication was not required. Retreatment was required for 3 sites on the head (parotid, face and mandible) due to persistent discomfort. None of the other sites (27/30) required retreatment. A patient with refractory DLBCL underwent radiotherapy (4 Gy, single fraction) for hepatic hilar lymph node involvement but did not recover from jaundice and died of DLBCL., Conclusions: Eight Gray single fraction radiotherapy was one of meaningful options for the treatment of refractory aggressive lymphoma in terms of its efficacy and the incidence of adverse events. The use of 8 Gy single fraction radiotherapy is therefore recommended for achieving local control in patients with refractory aggressive lymphoma.

The aim of this study was to evaluate the initial treatment results and toxicities of radiation therapy for patients with early stage low-grade follicular lymphoma (FL) arising from the duodenum. We reviewed 21 consecutive patients with early stage duodenal FL treated with radiation therapy between January 2005 and December 2013 at the Cancer Institute Hospital, Tokyo. The characteristics of patients were: median age 62 years (range, 46-79 years), gender (male, 6; female, 15), clinical stage (I, 20; II1, 1), histological grade (I, 17; II, 4). All patients were treated with radiation therapy alone. The median radiation dose was 30.6 Gy (range, 30.6-39.6) in 17 fractions. The involved-site radiation therapy was delivered to the whole duodenum. The median follow-up time was 43.2 months (range 21.4-109.3). The 3-year overall survival (OS), relapse-free survival (RFS) and local control (LC) rates were 94.7%, 79.3% and 100%, respectively. There were four relapses documented outside the treated volumes: two in the gastrointestinal tract (jejunum, terminal ileum), one in an abdominal lymph node (mesenteric lymph node) and one in the bone marrow. None died of the disease; one death was due to acute myeloid leukemia. No toxicities greater than Grade 1 were observed during treatment and over the follow-up time. The 30.6 Gy of involved-site radiation therapy provided excellent local control with very low toxicities. Radiation therapy could be an effective and safe treatment option for patients with localized low grade FL arising from the duodenum., (© The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Purpose: Previous studies on reproducibility in gynecologic high-dose-rate interstitial brachytherapy (HDRIB) have reported caudal needle displacements as high as 14-27.9 mm. The needle-template units in these studies were, however, sutured to the perineum, which gradually moved away from the target due to edema. To overcome the caudal force from the edema, we have been using fully stretched elastic tapes that exert cranial force on the template. To evaluate the effectiveness of our technique, caudal needle displacements relative to the target were investigated using CT coordinates., Methods and Materials: Twenty-nine gynecologic cancer patients were treated using HDRIB. The template was pressed into the perineum using two elastic tapes. All patients underwent pretreatment and posttreatment CTs to obtain craniocaudal coordinates for the needles and the clinical target volume., Results: The median displacements for the 533 needles relative to the clinical target volume were -0.8 mm (range, -5.7 to +4.7 mm). Absolute craniocaudal displacement >3 mm was observed in only 14.4% of the needles, with a maximum displacement of only 5.7 mm., Conclusions: The use of elastic tapes achieved smaller displacements compared to those in previous reports. This was a simple but effective technique to minimize needle displacement for gynecologic HDRIB., (Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)