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To predict grade ≥ 2 radiation pneumonitis (RP) in patients with locally advanced non-small cell lung cancer (NSCLC) using multi-region radiomics analysis. Data from 77 patients with NSCLC who underwent definitive radiotherapy between 2008 and 2018 were analyzed. Radiomic feature extraction from the whole lung (whole-lung radiomics analysis) and imaging- and dosimetric-based segmentation (multi-region radiomics analysis) were performed. Patients with RP grade ≥ 2 or < 2 were classified. Predictors were selected with least absolute shrinkage and selection operator logistic regression and the model was built with neural network classifiers. A total of 49,383 radiomics features per patient image were extracted from the radiotherapy planning computed tomography. We identified 4 features and 13 radiomics features in the whole-lung and multi-region radiomics analysis for classification, respectively. The accuracy and area under the curve (AUC) without the synthetic minority over-sampling technique (SMOTE) were 60.8%, and 0.62 for whole-lung and 80.1%, and 0.84 for multi-region radiomics analysis. These were improved 1.7% for whole-lung and 2.1% for multi-region radiomics analysis with the SMOTE. The developed multi-region radiomics analysis can help predict grade ≥ 2 RP. The radiomics features in the median- and high-dose regions, and the local intensity roughness and variation were important factors in predicting grade ≥ 2 RP., (© 2021. The Author(s).)

This study aimed to investigate whether the use of molecular-targeted agents could affect gastrointestinal (GI) toxicity in palliative radiotherapy (RT) for metastatic bone tumors in the abdominopelvic region. We collected data of patients who received palliative RT for bone metastases in the abdominopelvic region between 2013 and 2014 from six institutions. Data of 395 patients were collected and184 patients received molecularly targeted therapy, of whom 80 received vascular endothelial growth factor (VEGF)-targeted agents. For 556 lesions, 410 sessions of irradiation were undergone. GI toxicity of ≥G3 was observed in 3.8% of patients. The incidence rates of ≥G3 GI toxicity in patients without targeted agents use, in those using VEGF-targeted agents and in those using non-VEGF-targeted agents were 3.8, 7.5 and 1.0%, respectively. Regarding risk factors of the occurrence of ≥G3 GI toxicity, univariate analysis in all patients showed that a history of abdominopelvic surgery was a significant risk factor (P = 0.01), and the use of VEGF-targeted agents showed a trend of high incidence (P = 0.06). In patients using VEGF-targeted agents, both univariate and multivariate analysis showed that combined anticoagulant use (P = 0.03 and 0.01) and agent use between 1 week before and after RT (P = 0.046 and 0.03) were significant risk factors. In conclusion, the history of abdominopelvic surgery was associated with ≥G3 GI toxicity and the use of VEGF-targeted agents showed a trend for high incidence. When using VEGF-targeted agents, caution should be exercised in the combined use of anticoagulants and in the agent use between 1 week before and after RT., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is defined by p16 positivity and/or HPV DNA positivity. Because survival of patients with HPV-related OPSCC after chemoradiotherapy is favorable, a de-intensified treatment is expected to lead to less morbidity while maintaining low mortality. The association of tumor p16 and HPV DNA status with survival after radiotherapy alone remains unknown., Methods: We retrospectively examined survival of 107 patients with locally advanced OPSCC after radiotherapy alone (n = 43) or chemoradiotherapy (n = 64) with respect to tumor p16 and HPV DNA status, using Cox's proportional hazard model., Results: Survival after radiotherapy alone was significantly worse in p16-positive/HPV DNA-negative locally advanced OPSCC than in p16-positive/HPV DNA-positive locally advanced OPSCC. In bivariable analyses that included T category, N category, TNM stage, and smoking history, the survival disadvantage of p16-positive/HPV DNA-negative locally advanced OPSCC remained significant. There was no significant difference in survival after chemoradiotherapy between p16-positive/HPV DNA-positive locally advanced OPSCC and p16-positive/HPV DNA-negative locally advanced OPSCC. Survival in p16-positive/HPV DNA-positive locally advanced OPSCC after radiotherapy alone was similar to that after chemoradiotherapy, which stayed unchanged in bivariable analyses after adjustment of every other covariable. Survival of p16-negative/HPV DNA-negative locally advanced OPSCC was poor irrespective of treatment modality., Conclusions: Survival in p16-positive locally advanced OPSCC differs depending on HPV DNA status. Radiotherapy alone can serve as a de-intensified treatment for p16-positive/HPV DNA-positive locally advanced OPSCC, but not for p16-positive/HPV DNA-negative locally advanced OPSCC.

Aim: To evaluate the efficacy and toxicity of external beam radiotherapy (RT) for isolated recurrent epithelial ovarian cancer (EOC)., Methods: Twenty-four isolated recurrent EOC patients treated with RT at Osaka University Hospital between January 2000 and January 2017 were included in the current study. Data regarding the primary or recurrent diseases, follow-up findings, and efficacy or toxicities of RT were collected and retrospectively analyzed. Survival rates were calculated using the Kaplan-Meier method and compared using the log-rank test., Results: Their median age was 59 years. Most patients had International Federation of Gynecology and Obstetrics stage III-IV diseases at the initial diagnosis. Histologically, serous adenocarcinoma was predominant, followed by clear cell adenocarcinoma. All patients had received at least one regimen of platinum-based chemotherapy; 8 were platinum-sensitive relapse and the others were platinum-resistant. Lymph nodes were the most common sites of recurrence, and the median tumor size was 25.5 mm. The median total dose of RT administered was 54 Gy, with a median daily dose of 2 Gy. RT was well-tolerated, and no patients experienced Grade 3/4 toxicities. The in-field overall response rate was 58.3% (14/24), the median regression rate was -40.2% (range: -100 to 0) and the median survival period after RT was 17 months. The 1-year survival and local progression-free survival rates after RT were 66.7% and 45.8%, respectively., Conclusion: RT showed significant antitumor effect against isolated recurrent EOC without causing severe toxicities. Prospective studies with sufficient statistical power are warranted to further evaluate the role of RT in this patient population., (© 2019 Japan Society of Obstetrics and Gynecology.)

Aim: An immunocomplex of interleukin-2 (IL-2) and its monoclonal antibody, S4B6 (IL-2/S4B6), contributes to antitumor immune systems. We investigated the antitumor efficacy of radiation (IR) combined with IL-2/S4B6 for osteosarcoma., Materials and Methods: LM8 mouse osteosarcoma cells were inoculated into both legs of C3H mice. For groups treated with IL-2/S4B6 alone, and those treated with IR combined with IL-2/S4B6 (COMB), IL-2/S4B6 was intraperitoneally administered on days 12 and 16 after tumor cell inoculation. For groups treated with IR alone or COMB, one side leg was irradiated at 10 Gy on day 12., Results: Although monotherapy with IL-2/S4B6 provided no significant tumor growth inhibition, combined therapy significantly reduced tumor volume in both irradiated and unirradiated tumors by 99% and 58%, respectively, compared to the no-treatment group, with significant induction of CD8 + T-cells in unirradiated tumors. Moreover, the combination therapy significantly prolonged overall survival., Conclusion: Radiation combined with IL-2/S4B6 may be a potential therapeutic option for therapy of osteosarcoma., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The purpose of this study is to evaluate dose-volume histogram (DVH) predictors for the development of chronic gastrointestinal (GI) complications in patients with cervical cancer who have undergone postoperative concurrent chemotherapy and whole-pelvic radiation therapy (WPRT). The subjects were 135 patients who had undergone postoperative WPRT with concurrent nedaplatin-based chemotherapy between 2000 and 2014. Associations between selected DVH parameters and the incidence of chronic GI complications of G3 or higher were evaluated. Chronic GI complications of severity G3 occurred in 18 (13%) patients. Patients with GI complications had significantly greater V5-V45, mean dose and the generalized equivalent uniform dose (gEUD) of the small bowel loops, compared with those without GI complications. V30-V45, mean dose and gEUD of the bowel bag also showed significant differences between patients with and without GI complications. In contrast, no parameter for the large bowel loop was correlated with GI complications. Receiver operating characteristics curve analysis indicated that V30-V45 of the small bowel loops were better predictors than these respective parameters for the bowel bag. Next, patients were divided into four groups based on the median V15 and V40 of the small bowel loops. The group with both a high V15 and a high V40 showed a significantly higher probability of chronic GI complications. In conclusion, the small bowel loops are better predictors of chronic GI complications compared with the bowel bag, and a relatively high-dose volume (e.g. V40) of the small bowel loops is a useful predictor of chronic GI complications., (© The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: The patterns of radiotherapy (RT) practice for biliary tract cancer (BTC) in Japan are not clearly established., Methods: A questionnaire-based national survey of RT used for BTC treatment between 2000 and 2011 was conducted by the Japanese Radiation Oncology Study Group. Detailed information was collected for 555 patients from 31 radiation oncology institutions., Results: The median age of the patients was 69 years old (range, 33-90) and 81% had a good performance status (0-1). Regarding RT treatment, 78% of the patients were treated with external beam RT (EBRT) alone, 17% received intraluminal brachytherapy, and 5% were treated with intraoperative RT. There was no significant difference in the choice of treatment modality among the BTC subsites. Many patients with EBRT were treated with a total dose of 50 or 50.4 Gy (~40%) and only 13% received a total dose ≥60 Gy, even though most institutions (90%) were using CT-based treatment planning. The treatment field consisted of the primary tumor (bed) only in 75% of the patients. Chemotherapy was used for 260 patients (47%) and was most often administered during RT (64%, 167/260), followed by after RT (63%, 163/260). Gemcitabine was the most frequently used drug for chemotherapy., Conclusions: This study established the general patterns of RT practice for BTC in Japan. Further surveys and comparisons with results from other countries are needed for development and optimization of RT for patients with BTC in Japan.

Aim: Severe late complications, particularly radiation enterocolitis and leg edema, remain major problems in patients with uterine cancer, who have undergone hysterectomy and postoperative external beam radiotherapy (EBRT). We carried out this retrospective analysis to identify the incidence of risk factors for such complications., Patients and Methods: The records of 228 patients, who underwent radical hysterectomy and postoperative EBRT (uterine cervix: 149 patients; uterine corpus: 79 patients) were reviewed retrospectively. The majority of the patients (90.8%) were treated with 50 to 50.4 Gy EBRT in conventional fractionations with anteroposterior fields. Intracavitary brachytherapy (ICBT) was administered to 9 patients (3.9%), and 35 patients (15.2%) received chemotherapy. The median follow-up for all 228 patients was 81.7 months (range, 1-273 months)., Results: Nineteen patients (8.3%) developed severe radiation enterocolitis with a median latency of 12.6 months, and the ileum was the most frequently affected site. On multivariate analysis, smoking was an independent predictor of severe radiation enterocolitis. Nineteen patients (8.3%) developed severe leg edema with a median latency of 32.7 months. The degree of leg edema did not improve in any of the 19 patients despite intensive treatment. On multivariate analysis, addition of ICBT was an independent predictor of severe leg edema., Conclusion: Severe radiation enterocolitis and severe leg edema were each observed in approximately 8% of patients with uterine cancer, who underwent postoperative radiotherapy. Severe radiation enterocolitis correlated strongly with smoking, and severe leg edema correlated strongly with addition of ICBT. These factors should be considered before administering postoperative radiotherapy to uterine cancer patients.

We report on 2 cases of hypothyroidism presenting clinical symptoms that occurred after radiotherapy for cancer of the head and neck and on the results of estimating thyroid function in patients with head and neck cancer who received radiotherapy. The first patient underwent total laryngectomy for laryngeal cancer without sacrificing the thyroid gland and partial gastrectomy for gastric cancer. Radiotherapy of the neck was carried out postoperatively. Two years later, the patient developed chest pain; pericardial effusion was detected, leading to a diagnosis of myxedema caused by hypothyroidism. The second patient received radiotherapy alone for laryngeal cancer. Two months later, low serum sodium concentration and anemia were detected in this patient. The cause of these changes was subsequently found to be hypothyroidism. Based on our experience with these 2 cases, we measured thyroid function in 35 patients who had undergone neck radiation for head and neck cancer at our hospital over the past 10 years. Hypothyroidism was observed in 13 of the 35 patients (37%). The prevalence of hypothyroidism was 46% (6/13) for patients treated with both radiation and surgery, as compared with 32% (7/22) for those who received radiation alone. The risk factors responsible for hypothyroidism were not evident from the statistical analysis of these cases. We believe that thyroid function should be evaluated periodically in patients who have undergone neck radiation because it is often difficult to diagnose hypothyroidism only from clinical symptoms.

We conducted a phase II trial to evaluate the efficacy and toxicity of radiotherapy immediately after hyperbaric oxygenation (HBO) with chemotherapy in adults with high-grade gliomas. Patients with histologically confirmed high-grade gliomas were administered radiotherapy in daily 2 Gy fractions for 5 consecutive days per week up to a total dose of 60 Gy. Each fraction was administered immediately after HBO with the period of time from completion of decompression to irradiation being less than 15 min. Chemotherapy consisted of procarbazine, nimustine (ACNU) and vincristine and was administered during and after radiotherapy. A total of 41 patients (31 patients with glioblastoma and 10 patients with grade 3 gliomas) were enrolled. All 41 patients were able to complete a total radiotherapy dose of 60 Gy immediately after HBO with one course of concurrent chemotherapy. Of 30 assessable patients, 17 (57%) had an objective response including four CR and 13 PR. The median time to progression and the median survival time in glioblastoma patients were 12.3 months and 17.3 months, respectively. On univariate analysis, histologic grade (P=0.0001) and Karnofsky performance status (P=0.036) had a significant impact on survival, and on multivariate analysis, histologic grade alone was a significant prognostic factor for survival (P=0.001). Although grade 4 leukopenia and grade 4 thrombocytopenia occurred in 10 and 7% of all patients, respectively, these were transient with no patients developing neutropenic fever or intracranial haemorrhage. No serious nonhaematological or late toxicities were seen. These results indicated that radiotherapy delivered immediately after HBO with chemotherapy was safe with virtually no late toxicity in patients with high-grade gliomas. Further studies are required to strictly evaluate the effectiveness of radiotherapy after HBO for these tumours.

Purpose: The aim of this study was to evaluate the efficacy and complications of self-expandable metallic stent placement for patients with inoperable esophageal carcinoma after radiotherapy and/or chemotherapy., Materials and Methods: We obtained data from 19 patients with advanced or recurrent esophageal carcinoma between 1996 and 2000. In all patients, a self-expandable metallic stent was placed under fluoroscopic guidance. Dysphagia before and after stent placement was graded. Complications after stent placement were also evaluated. Data were compared between patients with and without prior radiotherapy and/or chemotherapy., Results: The procedure was technically successful in all but one patient. The dysphagia grade improved in all patients. No life-threatening complications occurred. The other major complications such as mediastinitis occurred in two patients, and pneumonia and funnel phenomenon occurred in one patient each. These patients had a history of radiotherapy and/or chemotherapy prior to stent placement. Eight of the twelve patients with prior radiotherapy and/or chemotherapy compared with one of seven patients without prior therapy had persistent chest pain, which was a statistically significant difference (P < 0.05)., Conclusion: Placement of self-expandable metallic stents was effective for patients with advanced or recurrent esophageal carcinoma. However, prior irradiation and/or chemotherapy increased the risk of persistent chest pain after stent placement.

This retrospective study was conducted to analyze the local control and late complications in patients with squamous cell carcinoma of the maxillary sinus treated with postoperative radiation therapy following surgery. Between 1979 and 1998, 41 patients with squamous cell carcinoma of the maxillary sinus were treated with postoperative irradiation following partial or total maxillectomy. Tumor classification according to the TNM classification of the International Union Against Cancer (1997) was T2 in 6 patients, T3 in 21 patients, and T4 in 14 patients. Fourteen patients had negative surgical margins, 23 had microscopically positive margins, and 4 had grossly positive margins. Sixteen patients received preoperative intraarterial chemotherapy. The total dose to the primary tumor bed was 40-70 Gy (median: 54 Gy) with a fraction size of 2 Gy. The median follow-up time of the surviving patients was 93 months (range: 25-179 months). Local recurrence was observed in 17 patients (41%), and the 5-year actuarial overall survival and local control rates were 48% and 55%, respectively. In the univariate analysis, surgical margin status and total dose each had a statistically significant impact on local recurrence. For the patients with negative surgical margins, 8 of 9 (89%) patients achieved local control with a dose of 50-54 Gy, while 7 of 10 (70%) patients with microscopically positive margins achieved local control with a dose of 60-64 Gy. There were 11 late complications found in 9 patients; bone necrosis in 2, soft tissue necrosis in 2, trisumus: 2, cellulitis in 1, retinopathy in 1, and vision impairment in 3 patients. A total dose of 60 Gy or more was administered in all patients who suffered late complications except for 2 patients with vision impairment. These results indicated that an optimal dose of postoperative irradiation according to the surgical margin status was necessary to achieve local control for squamous cell carcinoma of the maxillary sinus following surgery. For patients with negative surgical margins, a total dose of 50-54 Gy in conventional fractionation was appropriate to achieve local control as well as to reduce late complications. On the other hand, a dose of 60 Gy or more was required for the patients with microscopic positive margins.

Ten patients with severe endocrine ophthalmopathy were treated by radiotherapy at Hyogo Medical Center for Adults from May 1984 to February 1988. All but one of the patients had poorly responded to previous systemic or topical corticosteroid therapy. The target of the radiotherapy was both retrobulbar tissues. The radiation field used was about 4 x 4 cm, excluding the pituitary gland and the brain, and was angled 5 degrees posteriorly to avoid the contralateral lens. A total of 2000 cGy was given to each patient over a 2 week-period. Eight of the ten patients showed some response, with 5 of them (50%) having a good to excellent response. Treatment was more effective for soft tissue changes, proptosis and keratopathy, while myopathy was less responsive. As for the duration of the eye signs and symptoms, those of a shorter duration (less then 12 months) responded better. It was also noted that the degree of the eye muscle enlargement on the pre-treatment orbital CT scan was directly correlated to the results of the treatment. Although three of the patients experienced transient headache, there were no serious acute reactions or long term complications. In conclusion, retrobulbar radiotherapy is a well-tolerated, safe and effective treatment for severe endocrine ophthalmopathy.

Background:Surgical-pathological risk factors were evaluated by weighting the magnitude of significance of multiple risk factors correlating to survival and treatment response in cervical cancer.Methods:Multivariate analysis was performed for survival outcomes entering seven pathological factors obtained from 540 radical hysterectomy specimens in stage IA2-IIB cervical cancer cases. Hazard ratio (HR) in each risk factor was determined, and the sum of HR scores for the corresponding risk factors was determined per case. Survival curves and postoperative treatment response (concurrent chemoradiotherapy (CCRT) vs radiotherapy alone) were evaluated based on the extent of HR-weighted scores.Results:Hazard ratios for risk factors relating to disease-free survival (DFS) was: lympho-vascular space invasion 3.95, nodal metastasis 3.88, adenocarcinoma 3.40, large tumour 2.36, positive margin 1.99, deep stromal invasion 1.29, and parametria invasion 1.21. The HR-weighted scoring method showed a high predictive value for recurrence (area-under-curve 0.836, P<0.001). Hazard ratio-weighted scores were negatively correlated to DFS, and the cases with score 12.5 showed 5-year DFS rate of 23.8%. Tumours with larger score offset the benefits of CCRT over radiotherapy alone for postoperative adjuvant treatment (P<0.001).Conclusion:Surgical-pathological risk factors provide valuable information for survival and management of early-stage cervical cancer when number and significance of risks are weighted. [ABSTRACT FROM AUTHOR]

The role of adjuvant radiotherapy to the site of the initial bulky mass in lymphoma remains to be determined. We retrospectively analyzed clinical data for 35 consecutive patients with diffuse large B-cell lymphoma who had an initial bulky mass were treated successfully by chemotherapy reaching complete remission or complete remission unconfirmed according to International Workshop Criteria. Median age was 57 years. Median follow-up period for surviving patients after completion of chemotherapy was 45 months. Twenty patients (group A) received adjuvant radiotherapy to the bulky mass, while 15 (group B) did not. Median dose of radiation in group A was 40 Gy (range, 30–60 Gy). In group A, four relapses occurred, all from other sites; group B included three relapses from bulky and one from other sites. Overall survival ( P = 0.15) and recurrence-free survival ( P = 0.48) did not differ significantly between groups. Although adjuvant radiotherapy to the initial bulky site is useful for controlling local disease, no survival benefit was seen. [ABSTRACT FROM AUTHOR]

A 57-year-old man with a history of hepatitis B virus infection was referred to our hospital for living-donor liver transplantation (LDLT). Five years earlier, right lobectomy had been performed for solitary hepatocellular carcinoma (HCC) with bile duct tumor thrombus in segments 5 and 6 in the liver. Two years later, transarterial chemoembolization and radiofrequency ablation were performed for recurrent HCC. Two years after those local therapies, another recurrent HCC was treated with transhepatic arterial infusion chemotherapy with cisplatin and conventional radiation therapy (RT) with 60 Gy in 20 fractions, because the tumor was contiguous to the trunk of the portal vein. After the completion of RT, symptoms due to liver failure and severe infection caused by multiple liver abscesses developed despite the administration of antibiotics and percutaneous transhepatic cholangiodrainage. Therefore, LDLT was performed with the use of a right lobe graft donated by his wife. Vascular anastomosis was successfully performed with the use of normal procedures. The patient recovered uneventfully, and has since been doing well for 34 months, with no evidence of vascular complications. However, the degree of injury to the anastomotic vessels caused by definitive RT before LDLT remains unclear, whereas the safety and efficacy of some forms of RT as a bridge to deceased-donor LT have been reported. Salvage LDLT is effective for patients with liver failure after multidisciplinary treatment including radiation, while carefully taking radiation-induced vessel injury as a potential late complication into consideration, especially in LDLT cases. [ABSTRACT FROM AUTHOR]

Poster: Clinical track: Head and Neck PO-0853: The effect of the smoking cessation for radiation therapy of glottis carcinoma with monitoring CO S. Tatekawa, S. Shimamoto, T. Nishi, M. Tani, T. Ohsima, S. Onosaka, Y. Komeya, Y. Yamashita, K. Tamari, K. Ogawa. [Extracted from the article]

Poster: Clinical track: Prostate PO-1164: Long-term outcomes of radiotherapy regimen of 72 Gy in 30 fractions for prostate cancer K. Tamari, R. Oh, H. Shiomi, S. Osamu, K. Ogawa. [Extracted from the article]