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We report a case of radiation fibrosis appearing as mass-like consolidation, which was difficult to distinguish fromlocal recurrence. A 72-year-old woman was diagnosed as having primary lung cancer (cT1N0M0 stage IA) in the right upper lobe and was treated with SBRT of 48 Gy in 4 fractions. After 12 months, mass-like consolidation appeared around the irradiated area, and after 13 months, it had increased in size. FDG-PET revealed high uptake (SUV max = 5.61) for the consolidation. CT-guided biopsy was performed, but we could not confirm the diagnosis. Considering her poor respiratory function and her age, short-interval followup was performed. After 15 months, the consolidation enlarged at the dorsal side, and carcinoembryonic antigen (CEA) became elevated (14.6 ng/mL). Serum KL-6 (436 U/mL) and SP-D (204 ng/mL) were also elevated. However, after 16 months, serum CEA slightly decreased. The consolidation gradually retracted on follow-up CT images. CEA, KL-6, and SP-D were also decreased by degrees. After 40 months, there is no evidence of local recurrence. [ABSTRACT FROM AUTHOR]

Purpose: To determine, in the setting of locally advanced pancreatic cancer, the maximum tolerated dose of carbon ion radiation therapy (C-ion RT) and gemcitabine dose delivered concurrently and to estimate local effect and survival.Methods and Materials: Eligibility included pathologic confirmation of pancreatic invasive ductal carcinomas and radiographically unresectable disease without metastasis. Concurrent gemcitabine was administered on days 1, 8, and 15, and the dose levels were escalated from 400 to 1000 mg/m(2) under the starting dose level (43.2 GyE) of C-ion RT. The dose levels of C-ion RT were escalated from 43.2 to 55.2 GyE at 12 fractions under the fixed recommended gemcitabine dose determined.Results: Seventy-six patients were enrolled. Among the 72 treated patients, dose-limiting toxicity was observed in 3 patients: grade 3 infection in 1 patient and grade 4 neutropenia in 2 patients. Only 1 patient experienced a late grade 3 gastric ulcer and bleeding 10 months after C-ion RT. The recommended dose of gemcitabine with C-ion RT was found to be 1000 mg/m(2). The dose of C-ion RT with the full dose of gemcitabine (1000 mg/m(2)) was safely increased to 55.2 GyE. The freedom from local progression rate was 83% at 2 years using the Response Evaluation Criteria in Solid Tumors. The 2-year overall survival rates in all patients and in the high-dose group with stage III (≥45.6 GyE) were 35% and 48%, respectively.Conclusions: Carbon ion RT with concurrent full-dose gemcitabine was well tolerated and effective in patients with unresectable locally advanced pancreatic cancer. [ABSTRACT FROM AUTHOR]

Purpose: Investigation of the treatment potential of carbon-ion radiation therapy in pelvic recurrence of rectal cancer.Methods and Materials: A phase 1/2 dose escalation study was performed. One hundred eighty patients (186 lesions) with locally recurrent rectal cancer were treated with carbon-ion radiation therapy (CIRT) (phase 1/2: 37 and 143 patients, respectively). The relapse locations were 71 in the presacral region, 82 in the pelvic sidewalls, 28 in the perineum, and 5 near the colorectal anastomosis. A 16-fraction in 4 weeks dose regimen was used, with total dose ranging from 67.2 to 73.6 Gy(RBE); RBE-weighted absorbed dose: 4.2 to 4.6 Gy(RBE)/fraction.Results: During phase 1, the highest total dose, 73.6 Gy(RBE), resulted in no grade >3 acute reactions in the 13 patients treated at that dose. Dose escalation was halted at this level, and this dose was used for phase 2, with no other grade >3 acute reactions observed. At 5 years, the local control and survival rates at 73.6 Gy(RBE) were 88% (95% confidence interval [CI], 80%-93%) and 59% (95% CI, 50%-68%), respectively.Conclusion: Carbon-ion radiation therapy may be a safe and effective treatment option for locally recurrent rectal cancer and may serve as an alternative to surgery. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to clarify the incidence, the clinical risk factors, and the dose–volume relationship of radiation-induced rib fracture (RIRF) after hypofractionated stereotactic body radiation therapy (SBRT). Methods and Materials: One hundred sixteen patients treated with SBRT for primary or metastatic lung cancer at our institution, with at least 6 months of follow-up and no previous overlapping radiation exposure, were included in this study. To determine the clinical risk factors associated with RIRF, correlations between the incidence of RIRF and the variables, including age, sex, diagnosis, gross tumor volume diameter, rib–tumor distance, and use of steroid administration, were analyzed. Dose–volume histogram analysis was also conducted. Regarding the maximum dose, V10, V20, V30, and V40 of the rib, and the incidences of RIRF were compared between the two groups divided by the cutoff value determined by the receiver operating characteristic curves. Results: One hundred sixteen patients and 374 ribs met the inclusion criteria. Among the 116 patients, 28 patients (46 ribs) experienced RIRF. The estimated incidence of rib fracture was 37.7% at 3 years. Limited distance from the rib to the tumor (<2.0 cm) was the only significant risk factor for RIRF (p = 0.0001). Among the dosimetric parameters used for receiver operating characteristic analysis, the maximum dose showed the highest area under the curve. The 3-year estimated risk of RIRF and the determined cutoff value were 45.8% vs. 1.4% (maximum dose, ≥42.4 Gy or less), 51.6% vs. 2.0% (V40, ≥0.29 cm3 or less), 45.8% vs. 2.2% (V30, ≥1.35 cm3 or less), 42.0% vs. 8.5% (V20, ≥3.62 cm3 or less), or 25.9% vs. 10.5% (V10, ≥5.03 cm3 or less). Conclusions: The incidence of RIRF after hypofractionated SBRT is relatively high. The maximum dose and high-dose volume are strongly correlated with RIRF. [Copyright &y& Elsevier]

Purpose: To determine clinical factors for predicting the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer. Methods and Materials: The study group consisted of 109 patients with esophageal cancer of T1–4 and Stage I–III who were treated with definitive radiotherapy and achieved a complete response of their primary lesion at Kyushu University Hospital between January 1998 and December 2007. Esophageal stenosis was evaluated using esophagographic images within 3 months after completion of radiotherapy. We investigated the correlation between esophageal stenosis after radiotherapy and each of the clinical factors with regard to tumors and therapy. For validation of the correlative factors for esophageal stenosis, an artificial neural network was used to predict the esophageal stenotic ratio. Results: Esophageal stenosis tended to be more severe and more frequent in T3–4 cases than in T1–2 cases. Esophageal stenosis in cases with full circumference involvement tended to be more severe and more frequent than that in cases without full circumference involvement. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. In the multivariate analysis, T stage, extent of involved circumference, and wall thickness of the tumor region were significantly correlated to esophageal stenosis (p = 0.031, p < 0.0001, and p = 0.0011, respectively). The esophageal stenotic ratio predicted by the artificial neural network, which learned these three factors, was significantly correlated to the actual observed stenotic ratio, with a correlation coefficient of 0.864 (p < 0.001). Conclusion: Our study suggested that T stage, extent of involved circumference, and esophageal wall thickness of the tumor region were useful to predict the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer. [ABSTRACT FROM AUTHOR]

Fructose-1,6-bisphosphatase (FBP1), the rate-limiting enzyme in gluconeogenesis, is reduced in expression in certain cancers where it has been hypothesized to act as a tumor suppressor, including in hepatocellular carcinoma (HCC). Here, we report functional evidence supporting this hypothesis, providing a preclinical rationale to develop FBP1 as a therapeutic target for HCC treatment. Three independent cohorts totaling 594 cases of HCC were analyzed to address clinical significance. Lower FBP1 expression associated with advanced tumor stage, poor overall survival, and higher tumor recurrence rates. In HCC cell lines, where endogenous FBP1 expression is low, engineering its ectopic overexpression inhibited tumor growth and intracellular glucose uptake by reducing aerobic glycolysis. In patient specimens, promoter methylation and copy-number loss of FBP1 were independently associated with decreased FBP1 expression. Similarly, FBP1 downregulation in HCC cell lines was also associated with copy-number loss. HCC specimens exhibiting low expression of FBP1 had a highly malignant phenotype, including large tumor size, poor differentiation, impaired gluconeogenesis, and enhanced aerobic glycolysis. The effects of FBP1 expression on prognosis and glucose metabolism were confirmed by gene set enrichment analysis. Overall, our findings established that FBP1 downregulation in HCC contributed to tumor progression and poor prognosis by altering glucose metabolism, and they rationalize further study of FBP1 as a prognostic biomarker and therapeutic target in HCC patients. Cancer Res; 76(11); 3265-76. ©2016 AACR., (©2016 American Association for Cancer Research.)

Aim: The aim of this study was to investigate the clinical factors for predicting overall survival (OS) and the significance of a minute amount of ascites on computed tomography (CT) in patients with locally advanced pancreatic cancer (LAPC) treated with chemoradiotherapy (CRT)., Patients and Methods: Between 2003 and 2011, 48 consecutive patients with LAPC were treated with CRT. Various clinical factors, including ascites, were evaluated for correlation with OS. A subset analysis of 16 patients with a minute amount of ascites was also performed., Results: The median survival duration and the 1-year OS rates were 11.5 months and 50%, respectively. A minute amount of ascites on CT and elevated carbohydrate antigen 19-9 (CA19-9) level were significantly associated with poorer OS. In 16 patients with ascites, the amount of ascites increased in the course of the disease, and these were considered to be cancerous clinically, regardless of the amount., Conclusion: A minute amount of ascites and CA19-9 were important prognostic factors in CRT. Any amount of ascites was considered an early indicator of peritoneal carcinomatosis in LAPC., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: To analyze the treatment outcome of radiotherapy for localized primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (POAML) and evaluate the prognostic effect of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) clinical staging system for POAML., Patients and Methods: Seventy-three patients with Ann Arbor stage IE POAML who were treated with radiotherapy alone were analyzed. T-Factor based on the AJCC staging system was T1 in 28, T2 in 33 and T3 in 12 patients., Results: Out of nine patients with relapse, six had distant and three had contralateral ocular adnexal relapse. One patient died of lymphoma progression. The 5-year local control and progression-free survival (PFS) rates were 100% and 81.5%, respectively. T-Factor was not significantly associated with PFS., Conclusion: Radiotherapy achieved excellent local control and survival rates for stage IE POAML. The AJCC TNM clinical staging system was not significantly predictive for PFS of stage IE POAML., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (POAML) is a rare disease. The purpose of this study was to evaluate the treatment outcome and patterns of failure of patients with early-stage POAML treated with radiotherapy., Patients and Methods: From 1995 to 2008, 53 patients with early-stage POAML were reviewed. Tumors were categorized as either superficial or mass-forming type. In principle, superficial lesions (n=11) were treated with 24 Gy, while the mass-forming lesions (n=42) were irradiated with 30 Gy. The median follow-up period was 3.9 years., Results: All four cases of relapse had mass-forming lesions. The 5-year overall and progression-free survival rates were 100% and 91.5%, respectively. Although 30 patients experienced grade 2 or 3 late adverse events, no patients had radiation-related retinopathy., Conclusion: Early-stage POAML can be well-controlled with radiotherapy. However, the risk of distant relapse should be noted, in particular, for mass-forming tumors.

Aim: To retrospectively evaluate the efficacy and safety of definitive fractionated re-irradiation for local recurrence following stereotactic body radiotherapy (SBRT) for primary lung cancer., Patients and Methods: Between April 2003 and December 2011, 398 patients with primary lung tumor underwent SBRT at the Kyushu University Hospital, and 46 out of these developed local recurrence after SBRT. Definitive fractionated re-irradiation was performed for 17 out of the 46 patients. The median dose of re-irradiation was 60 Gy/ 30 fractions. Concurrent chemotherapy was given to four patients., Results: The median follow-up duration was 12.6 months. At one year post-re-irradiation, local progression-free survival was 33.8%; progression-free survival, 30.9%; cause-specific survival, 79.3%; and overall survival, 74.7%. No severe adverse events were observed during the follow-up., Conclusion: Definitive fractionated re-irradiation is thought to be a safe alternative therapy for local recurrence following SBRT, although its efficacy may be not entirely satisfactory.

Background: The efficacy of stereotactic body radiation therapy (SBRT) for patients treated with domiciliary oxygen therapy is not well-known., Patients and Methods: We collected the clinical records of 15 patients with chronic respiratory insufficiency requiring domiciliary oxygen therapy at 1-3 l/min who were treated with SBRT for stage I non-small cell lung cancer. All patients were fixed with a thermoplastic body cast system. SBRT was given in 7-8 fields with an isocenter dose of 40-60 Gy in 4-10 fractions (median, 48 Gy in 4 fractions)., Results: The overall 2-year and 5-year survival rates for all patients were 67.4% and 34.7%, while the disease-specific 2-year and 5-year survival rates were 90.0% and 72.0%, respectively. Pulmonary adverse effects were mild in the majority of the patients, although two patients had grade 2 radiation pneumonitis. The oxygen flow required increased slightly at follow-up periods greater than one year, but was still at an acceptable level., Conclusion: SBRT was feasible for patients requiring domiciliary oxygen therapy.

In this study, we evaluated the feasibility, efficacy and toxicity of concurrent chemoradiotherapy with S-1 (tegafur-gimeracil-oteracil potassium) for T2N0 glottic carcinoma. A total of 23 patients with T2N0 glottic carcinoma received chemoradiotherapy with S-1. Radiotherapy consisted of five daily fractions of 2 Gy per week, to a total median dose of 70 Gy. S-1 was administered 65 mg/m(2) per day for 4 weeks, beginning on the day therapy was started, followed by 2 weeks off the drug and twice a day until the end of radiotherapy. Initial local control rate of the primary tumor was achieved in all patients. The median follow-up period for all patients was 38 months. The 3-year local control rate was 95.4%. Regarding adverse reactions, grade 3 mucositis upon clinical examination, mucositis upon functional/symptomatic examination, dysphagia, hepatic toxicity and anemia were observed in 13, 2, 2, 1 and 1 patients, respectively. This chemoradiotherapy did not result in grade 4 acute toxicity or severe late toxicity. Chemoradiotherapy with S-1 was feasible, well tolerated and effective. This therapy is suggested as a possible regimen for improving local control of T2N0 glottic carcinoma.

The purpose of this study was to evaluate the reproducibility of visual feedback-guided breath-hold using a machine vision system with a charge-coupled device camera and a monocular head-mounted display. Sixteen patients with lung tumors who were treated with stereotactic radiotherapy were enrolled. A machine vision system with a charge-coupled device camera was used for monitoring respiration. A monocular head-mounted display was used to provide the patient with visual feedback about the breathing trace. The patients could control their breathing so that the breathing waveform would fall between the upper and lower threshold lines. Planning and treatment were performed under visual feedback-guided expiratory breath-hold. Electronic portal images were obtained during treatment. The range of cranial-caudal motion of the tumor location during each single breath-hold was calculated as the intra-breath-hold (intra-BH) variability. The maximum displacement between the two to five averaged tumor locations of each single breath-hold was calculated as the inter-breath-hold (inter-BH) variability. All 16 patients tolerated the visual feedback-guided breath-hold maneuvers well. The intra- and inter-BH variability of all patients was 1.5 +/- 0.6 mm and 1.2 +/- 0.5 mm, respectively. A visual feedback-guided breath-hold technique using the machine vision system is feasible with good breath-hold reproducibility.

Introduction: Primary malignant melanoma of the esophagus is a rare but highly aggressive tumor with poor prognosis. Surgical resection is the treatment of choice. However, some cases may be diagnosed with advanced inoperable disease. Palliative radiotherapy may be used to relieve symptoms caused by the esophageal tumor., Case Presentation: We report on a case of advanced inoperable primary malignant melanoma of the esophagus treated with palliative radiotherapy. The patient's dysphagia resolved with radiotherapy., Conclusion: Malignant melanoma of the esophagus is rare. Patients with advanced inoperable malignant melanomas of the esophagus benefit from radiation therapy. Radiation therapy is effective for palliation.