Kotaro Terashima

Carbon Ion Radiation Therapy With Concurrent Gemcitabine for Patients With Locally Advanced Pancreatic Cancer.

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.

Decreased Expression of Fructose-1,6-bisphosphatase Associates with Glucose Metabolism and Tumor Progression in Hepatocellular Carcinoma

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.

A clinical evaluation of visual feedback-guided breath-hold reproducibility of tumor location

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.

Esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer: Frequency and prediction

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.

Percutaneous osteoplasty for hypervascular bone metastasis

We report three cases of percutaneous osteoplasty for the treatment of hypervascular bone metastasis. Four hypervascular bone metastases were treated in three consecutive patients by percutaneous osteoplasty under fluoroscopic or computed tomographic guidance. Primary malignant tumors included pheochromocytoma and renal cell carcinoma. Pain relief after osteoplasty was achieved in all three patients. There was no major complication. Projectile bleeding and subcutaneous hematoma were noted during or after osteoplasty but were easily controlled conservatively. Percutaneous osteoplasty for hypervascular bone metastases is not only a highly effective but also a minimally invasive technique that provides immediate pain relief without major complication.

Recent advances in radiation oncology: intensity-modulated radiotherapy, a clinical perspective

Radiotherapy plays an important role in the treatment of various malignancies, and intensity-modulated radiotherapy (IMRT) is an attractive option because it can deliver precise conformal radiation doses to the target while minimizing the dose to adjacent normal tissues. IMRT provides a highly conformal dose distribution by modulating the intensity of the radiation beam. A number of malignancies have been targeted by IMRT; this work reviews published data on the major disease sites treated with IMRT. The dosimetric advantage of IMRT has resulted in the significant reduction of adverse effects in some tumors. However, there are few clinical trials comparing IMRT and three-dimensional conformal radiotherapy (3D-CRT), and no definite increase in survival or the loco-regional control rate by IMRT has been demonstrated in many malignancies. IMRT also requires greater time and resources to complete compared to 3D-CRT. In addition, the cost–effectiveness of IMRT versus 3D-CRT has not yet been established.

Effective palliative radiotherapy in primary malignant melanoma of the esophagus: a case report

IntroductionPrimary 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 presentationWe report on a case of advanced inoperable primary malignant melanoma of the esophagus treated with palliative radiotherapy. The patients dysphagia resolved with radiotherapy.ConclusionMalignant 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.

A Case of Radiation Fibrosis Appearing as Mass-Like Consolidation after SBRT with Elevation of Serum CEA

We report a case of radiation fibrosis appearing as mass-like consolidation, which was difficult to distinguish from local 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 follow-up 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.