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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: 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.)

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.)

Purpose: To investigate pelvic insufficiency fractures (IF) after definitive pelvic radiation therapy for early-stage uterine cervical cancer, by analyzing subjects of a prospective, multi-institutional study., Materials and Methods: Between September 2004 and July 2007, 59 eligible patients were analyzed. The median age was 73 years (range, 37-84 years). The International Federation of Gynecologic Oncology and Obstetrics stages were Ib1 in 35, IIa in 12, and IIb in 12 patients. Patients were treated with the constant method, which consisted of whole-pelvic external-beam radiation therapy of 50 Gy/25 fractions and high-dose-rate intracavitary brachytherapy of 24 Gy/4 fractions without chemotherapy. After radiation therapy the patients were evaluated by both pelvic CT and pelvic MRI at 3, 6, 12, 18, and 24 months. Diagnosis of IF was made when the patients had both CT and MRI findings, neither recurrent tumor lesions nor traumatic histories. The CT findings of IF were defined as fracture lines or sclerotic linear changes in the bones, and MRI findings of IF were defined as signal intensity changes in the bones, both on T1- and T2-weighted images., Results: The median follow-up was 24 months. The 2-year pelvic IF cumulative occurrence rate was 36.9% (21 patients). Using Common Terminology Criteria for Adverse Events version 3.0, grade 1, 2, and 3 IF were seen in 12 (21%), 6 (10%), and 3 patients (5%), respectively. Sixteen patients had multiple fractures, so IF were identified at 44 sites. The pelvic IF were frequently seen at the sacroileal joints (32 sites, 72%). Nine patients complained of pain. All patients' pains were palliated by rest or non-narcotic analgesic drugs. Higher age (>70 years) and low body weight (<50 kg) were thought to be risk factors for pelvic IF (P=.007 and P=.013, Cox hazard test)., Conclusions: Cervical cancer patients with higher age and low body weight may be at some risk for the development of pelvic IF after pelvic radiation therapy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: The indication for postmastectomy radiotherapy (PMRT) in breast cancer patients with one to three positive lymph nodes has been in discussion. The purpose of this study was to identify patient groups for whom PMRT may be indicated, focusing on varied locoregional recurrence rates depending on lymphatic invasion (ly) status., Methods and Materials: Retrospective analysis of 1,994 node-positive patients who had undergone mastectomy without postoperative radiotherapy between January 1990 and December 2000 at our hospital was performed. Patient groups for whom PMRT should be indicated were assessed using statistical tests based on the relationship between locoregional recurrence rate and ly status., Results: Multivariate analysis showed that the ly status affected the locoregional recurrence rate to as great a degree as the number of positive lymph nodes (p < 0.001). Especially for patients with one to three positive nodes, extensive ly was a more significant factor than stage T3 in the TNM staging system for locoregional recurrence (p < 0.001 vs. p = 0.295)., Conclusion: Among postmastectomy patients with one to three positive lymph nodes, patients with extensive ly seem to require local therapy regimens similar to those used for patients with four or more positive nodes and also seem to require consideration of the use of PMRT., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To determine the current patterns of practice in Japan and to investigate factors that may make clinicians reluctant to use single-fraction radiotherapy (SF-RT)., Methods and Materials: Members of the Japanese Radiation Oncology Study Group (JROSG) completed an Internet-based survey and described the radiotherapy dose fractionation they would recommend for four hypothetical cases describing patients with painful bone metastasis (BM). Case 1 described a patient with an uncomplicated painful BM in a non-weight-bearing site from non-small-cell lung cancer. Case 2 investigated whether management for a case of uncomplicated spinal BM would be different from that in Case 1. Case 3 was identical with Case 2 except for the presence of neuropathic pain. Case 4 investigated the prescription for an uncomplicated painful BM secondary to oligometastatic breast cancer. Radiation oncologists who recommended multifraction radiotherapy (MF-RT) for Case 2 were asked to explain why they considered MF-RT superior to SF-RT., Results: A total of 52 radiation oncologists from 50 institutions (36% of JROSG institutions) responded. In all four cases, the most commonly prescribed regimen was 30 Gy in 10 fractions. SF-RT was recommended by 13% of respondents for Case 1, 6% for Case 2, 0% for Case 3, and 2% for Case 4. For Case 4, 29% of respondents prescribed a high-dose MF-RT regimen (e.g., 50 Gy in 25 fractions). The following factors were most often cited as reasons for preferring MF-RT: "time until first increase in pain" (85%), "incidence of spinal cord compression" (50%), and "incidence of pathologic fractures" (29%)., Conclusions: Japanese radiation oncologists prefer a schedule of 30 Gy in 10 fractions and are less likely to recommend SF-RT. Most Japanese radiation oncologists regard MF-RT as superior to SF-RT, based primarily on the time until first increase in pain., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To determine the efficacy of a definitive radiotherapy protocol using high-dose-rate intracavitary brachytherapy (HDR-ICBT) with a low cumulative dose schedule in nonbulky early-stage cervical cancer patients, we conducted a prospective multi-institutional study., Methods and Materials: Eligible patients had squamous cell carcinoma of the intact uterine cervix, Federation of Gynecologic Oncology and Obstetrics (FIGO) stages Ib1, IIa, and IIb, tumor size <40 mm in diameter (assessed by T2-weighted magnetic resonance imaging), and no pelvic/para-aortic lymphadenopathy. The treatment protocol consisted of whole-pelvis external beam radiotherapy (EBRT) of 20 Gy/10 fractions, pelvic EBRT with midline block of 30 Gy/15 fractions, and HDR-ICBT of 24 Gy/4 fractions (at point A). The cumulative biologically effective dose (BED) was 62 Gy(10) (α/β = 10) at point A. The primary endpoint was the 2-year pelvic disease progression-free (PDPF) rate. All patients received a radiotherapy quality assurance review., Results: Between September 2004 and July 2007, 60 eligible patients were enrolled. Thirty-six patients were assessed with FIGO stage Ib1; 12 patients with stage IIa; and 12 patients with stage IIb. Median tumor diameter was 28 mm (range, 6-39 mm). Median overall treatment time was 43 days. Median follow-up was 49 months (range, 7-72 months). Seven patients developed recurrences: 3 patients had pelvic recurrences (2 central, 1 nodal), and 4 patients had distant metastases. The 2-year PDPF was 96% (95% confidence interval [CI], 92%-100%). The 2-year disease-free and overall survival rates were 90% (95% CI, 82%-98%) and 95% (95% CI, 89%-100%), respectively. The 2-year late complication rates (according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer of Grade ≥ 1) were 18% (95% CI, 8%-28%) for large intestine/rectum, 4% (95% CI, 0%-8%) for small intestine, and 0% for bladder. No Grade ≥ 3 cases were observed for genitourinary/gastrointestinal late complications., Conclusions: These results suggest that definitive radiotherapy using HDR-ICBT with a low cumulative dose schedule (BED, 62 Gy(10) at point A) can provide excellent local control without severe toxicity in nonbulky (<4-cm) early-stage cervical cancer., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To describe patient characteristics and the process of radiotherapy (RT) for patients with esophageal cancer treated between 1999 and 2001 in Japan., Methods and Materials: The Japanese Patterns of Care Study (PCS) Working Group conducted a third nationwide survey of 76 institutions. Detailed information was accumulated on 621 patients with thoracic esophageal cancer who received RT., Results: The median age of patients was 68 years. Eighty-eight percent were male, and 12% were female. Ninety-nine percent had squamous cell carcinoma histology. Fifty-five percent had the main lesion in the middle thoracic esophagus. Fourteen percent had clinical Stage 0-I disease, 32% had Stage IIA-IIB, 43% had Stage III, and 10% had Stage IV disease. Chemotherapy was given to 63% of patients; 39% received definitive chemoradiotherapy (CRT) without surgery and 24% pre- or postoperative CRT. Sixty-two percent of the patients aged > or =75 years were treated with RT only. Median total dose of external RT was 60 Gy for definitive CRT patients, 60 Gy for RT alone, and 40 Gy for preoperative CRT., Conclusions: This PCS describes general aspects of RT for esophageal cancer in Japan. Squamous cell carcinoma accounted for the majority of patients. The standard total external RT dose for esophageal cancer was higher in Japan than in the United States. Chemoradiotherapy had become common for esophageal cancer treatment, but patients aged > or =75 years were more likely to be treated by RT only.

Purpose: To evaluate late cardiopulmonary toxicities after concurrent chemoradiotherapy (CCRT) for esophageal carcinomas., Methods and Materials: From February 2002 through April 2005, 74 patients with clinical Stage I-IVB carcinoma of the esophagus were treated with CCRT. Sixty-nine patients with thoracic squamous cell carcinoma were the core of this analysis. Patients received 60 Gy of radiation therapy in 30 fractions over 8 weeks, including a 2-week break, and received 2 cycles of fluorouracil/cisplatin chemotherapy concomitantly. Initial radiation fields included primary tumors, metastatic lymph nodes, and supraclavicular, mediastinal, and celiac nodes areas. Late toxicities were assessed with the late radiation morbidity scoring scheme of the Radiation Therapy Oncology Group/European Organiation for Research and Treatment of Cancer., Results: The median age was 67 years (range, 45-83 years). The median follow-up time was 26.1 months for all patients and 51.4 months for patients still alive at the time of analysis. Five cardiopulmonary toxic events of Grade 3 or greater were observed in 4 patients, Grade 5 heart failure and Grade 3 pericarditis in 1 patient, and Grade 3 myocardial infarction, Grade 3 radiation pneumonitis, and Grade 3 pleural effusion. The 2-year cumulative incidence of late cardiopulmonary toxicities of Grade 3 or greater for patients 75 years or older was 29% compared with 3% for younger patients (p = 0.005)., Conclusion: The CCRT used in this study with an extensive radiation field is acceptable for younger patients but is not tolerated by patients older than 75 years.

Purpose: To perform the largest in vivo dosimetry study for interstitial brachytherapy yet to be undertaken using a new radiophotoluminescence glass dosimeter (RPLGD) in patients with pelvic malignancy and to study the limits of contemporary planning software based on the results., Patients and Methods: Sixty-six patients with pelvic malignancy were treated with high-dose-rate interstitial brachytherapy, including prostate (n = 26), gynecological (n = 35), and miscellaneous (n = 5). Doses for a total of 1004 points were measured by RPLGDs and calculated with planning software in the following locations: rectum (n = 549), urethra (n = 415), vagina (n = 25), and perineum (n = 15). Compatibility (measured dose/calculated dose) was analyzed according to dosimeter location., Results: The compatibility for all dosimeters was 0.98 +/- 0.23, stratified by location: rectum, 0.99 +/- 0.20; urethra, 0.96 +/- 0.26; vagina, 0.91 +/- 0.08; and perineum, 1.25 +/- 0.32., Conclusions: Deviations between measured and calculated doses for the rectum and urethra were greater than 20%, which is attributable to the independent movements of these organs and the applicators. Missing corrections for inhomogeneity are responsible for the 9% negative shift near the vaginal cylinder (specific gravity = 1.24), whereas neglect of transit dose contributes to the 25% positive shift in the perineal dose. Dose deviation of >20% for nontarget organs should be taken into account in the planning process. Further development of planning software and a real-time dosimetry system are necessary to use the current findings and to achieve adaptive dose delivery.

Purpose: The aim of this study was to evaluate the efficacy and toxicity of moderate dose radiation therapy (RT) for mucosa-associated lymphoid tissue (MALT) lymphoma in a prospective multicenter phase II trial., Methods and Materials: The subjects in this study were 37 patients with MALT lymphoma between April 2002 and November 2004. There were 16 male and 21 female patients, ranging in age from 24 to 82 years, with a median of 56 years. The primary tumor originated in the orbit in 24 patients, in the thyroid and salivary gland in 4 patients each, and 5 in the others. The median tumor dose was 30.6 Gy (range, 30.6-39.6 Gy), depending on the primary site and maximal tumor diameter. The median follow-up was 37.3 months., Results: Complete remission (CR) or CR/unconfirmed was achieved in 34 patients (92%). The 3-year overall survival, progression-free survival, and local control probability were 100%, 91.9%, and 97.3%, respectively. Thirteen patients experienced Grade 1 acute toxicities including dermatitis, mucositis, and conjunctivitis. One patient developed Grade 2 taste loss. Regarding late toxicities, Grade 2 reactions including hypothyroidism, and radiation pneumonitis were observed in three patients, and Grade 3 cataract was seen in three patients., Conclusions: This prospective phase II study demonstrated that moderate dose RT was highly effective in achieving local control with acceptable morbidity in 37 patients with MALT lymphoma.

Purpose: Most patients who had any recurrent sites of cancer have been considered to be in their last stage of life. However, recent advances of clinical research reveal some patients achieve long-term survival even in recurrence. Furthermore, for patients who had only one recurrent region, radiation therapy could play an important role. As for uterine cervical carcinoma, the most common recurrent site other than the pelvis is the para-aortic lymph nodes. Thus we conducted the current study., Patients and Methods: Between 1994 and 2003, more than 5,000 uterine cervical carcinoma patients were treated with curative intended treatments at 13 Japanese hospitals. Of these patients, 84 developed para-aortic lymph node recurrence as the only site of initial tumor progression. These patients were treated with external beam radiation therapy. Radiation therapy protocol was as follows: 1.7-2.0 Gy per fraction, 5 fractions per week, and the mean total dose was 50.8 Gy (25-60 Gy)., Results: Three- and 5-year overall survival rates of all patients were 49.5% and 31.3%, respectively. Stratified by symptom sign, 3-year overall survival rate of symptom positive was 27.6% and those of the negative was 56.1% (p = 0.018). Three-year overall survival rates of the total dose > or =51 Gy and that of < or =50 Gy were 58.0% and 42.8%, respectively (p = 0.07). As for morbidity, no patients received Grade 3 or greater late toxicity., Conclusions: The current study suggested that radiation therapy for isolated para-aortic lymph node recurrence in uterine cervical carcinoma could have a significant impact on survival.

Purpose: We conducted a multicenter prospective study to evaluate the efficacy and safety of reduced-dose three-course CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) followed by involved-field radiotherapy for elderly patients with localized aggressive non-Hodgkin's lymphoma. The primary endpoint was compliance with the combined modality., Methods and Materials: This study included untreated patients, > or =70 years old, with diffuse aggressive lymphoma, Stage IA or contiguous nonbulky Stage IIA. 80%-CHOP (cyclophosphamide 600 mg/m(2), doxorubicin 40 mg/m(2), vincristine 1.1 mg/m(2), and prednisolone at 80 mg/day for 5 days) was repeated every 3 weeks. After three cycles of chemotherapy, involved-field radiotherapy was performed with a radiation dose of 30-50 Gy in 15-28 fractions., Results: Twenty-four patients with a median age of 75 years (range, 70-84 years) were enrolled. The compliance rate of the protocol study was 87.5% (95% confidence interval [CI], 67.6-97.3). Three patients received only two cycles of chemotherapy because of toxicity or second neoplasm. There were no deaths caused by severe toxicity. The 3-year progression-free and overall survival rates were 83.1% (95% CI, 75.4-90.8) and 82.9% (95% CI, 75.1-90.6), respectively., Conclusion: Three-course 80%-CHOP followed by involved-field radiotherapy may be safe for administration to elderly patients over 70 years old. The next step is to evaluate three-course 80%-CHOP and rituximab followed by radiotherapy in elderly patients with localized disease.

Purpose: To evaluate the quality of radiotherapy (RT) in Japan, we have been carrying out a national survey through patterns-of-care studies (PCSs) since 1996. We present the preliminary results of surgery combined with RT with or without chemotherapy for thoracic esophageal cancer., Methods and Materials: A Japanese PCS data format for esophageal cancer was established based on one used in the United States and including information used in the surgical registration system in Japan, so that the results in both countries could be compared. An independent panel of radiation oncologists surveyed randomly selected institutions and patients between September 1998 and March 2001. There were 767 esophageal cancer patients, of whom 220 had undergone preoperative or postoperative RT., Results: The median age of the 220 patients was 62.3 years (range 31-89); of them, 88.1% were men. Pathologically, 218 patients (99.5%) had squamous cell carcinoma, predominantly located in the middle and lower thoracic esophagus, 41.7% of the patients had Stage III disease; they accounted for 52.6% of patients in nonacademic institutions and for 37.7% of those in academic institutions (p = 0.016). Sixty-nine patients received preoperative RT; of them, 60.9% received chemotherapy; 145 patients received postoperative RT with or without chemotherapy. The spinal cord of 23 (11.7%) of 196 patients was irradiated with >/=50 Gy. In academic institutions, extended radical "three-field" lymphatic dissection was performed for 72 (48.7%) of 148 patients; however, this sophisticated surgical procedure was done in only 13 (25.5%) of 51 patients in nonacademic settings (p = 0.004). In all large academic institutions (those treating >/=300 patients annually), >/=6 MV of photon energy was used; 30.5% of nonacademic institutes had linear accelerators of <6 MV photon (p = 0.001). No deviations occurred in the radiation dose (median 46 Gy), fractionations, or fields between the two types of institutions. Univariate analyses showed that the statistically significant prognostic factors affecting overall survival were stage (p = 0.001), extended radical "three-field" lymphatic dissection (p = 0.001), no residual tumor (p = 0.001), supraclavicular RT (p = 0.001), mediastinal RT (p = 0.025), Karnofsky performance status (p = 0.006) photon energy (p = 0.011), and stratification of the institutions (p = 0.001). Multivariate analysis showed that the type of institution (p = 0.045, risk ratio = 0.604), stage (p 0.029, risk ratio = 0.572), no residual tumor (p = 0.006, risk ratio = 0.487), photon energy (p = 0.043, risk ratio = 0.579), and use of chemotherapy (p = 0.012, risk ratio = 1.907) significantly affected overall survival., Conclusion: This PCS showed that in Japan important issues are present regarding RT for esophageal cancer that should be solved immediately, namely, treatment strategy, photon energy, and dose applied to the spinal cord. The PCS provided important information on how much improvement in structure and process would be required nationwide for RT of esophageal cancer.