Influence of secondary neutrons induced by proton radiotherapy for cancer patients with implantable cardioverter defibrillators

<p>Abstract</p> <p>Background</p> <p>Although proton radiotherapy is a promising new approach for cancer patients, functional interference is a concern for patients with implantable cardioverter defibrillators (ICDs). The purpose of this study was to clarify the influence of secondary neutrons induced by proton radiotherapy on ICDs.</p> <p>Methods</p> <p>The experimental set-up simulated proton radiotherapy for a patient with an ICD. Four new ICDs were placed 0.3 cm laterally and 3 cm distally outside the radiation field in order to evaluate the influence of secondary neutrons. The cumulative in-field radiation dose was 107 Gy over 10 sessions of irradiation with a dose rate of 2 Gy/min and a field size of 10 × 10 cm². After each radiation fraction, interference with the ICD by the therapy was analyzed by an ICD programmer. The dose distributions of secondary neutrons were estimated by Monte-Carlo simulation.</p> <p>Results</p> <p>The frequency of the power-on reset, the most serious soft error where the programmed pacing mode changes temporarily to a safety back-up mode, was 1 per approximately 50 Gy. The total number of soft errors logged in all devices was 29, which was a rate of 1 soft error per approximately 15 Gy. No permanent device malfunctions were detected. The calculated dose of secondary neutrons per 1 Gy proton dose in the phantom was approximately 1.3-8.9 mSv/Gy.</p> <p>Conclusions</p> <p>With the present experimental settings, the probability was approximately 1 power-on reset per 50 Gy, which was below the dose level (60-80 Gy) generally used in proton radiotherapy. Further quantitative analysis in various settings is needed to establish guidelines regarding proton radiotherapy for cancer patients with ICDs.</p

Results of Proton Beam Therapy without Concurrent Chemotherapy for Patients with Unresectable Stage III Non-small Cell Lung Cancer

Introduction:This study was performed retrospectively to evaluate the outcome of patients with stage III non-small cell lung cancer (NSCLC) after proton beam therapy (PBT) alone.Methods:The subjects were 57 patients with histologically confirmed NSCLC (stage IIIA/IIIB: 24/33) who received PBT without concurrent chemotherapy. The cohort included 32 cases of squamous cell carcinoma, 18 adenocarcinoma, and 7 non-small cell carcinoma. Lymph node metastases were N0 7, N1 5, N2 30, and N3 15. Planned total doses ranged from 50 to 84.5 GyE (median, 74 GyE).Results:Planned treatment was completed in 51 patients (89%). At the time of analysis, 20 patients were alive, and the median follow-up periods were 16.2 months for all patients and 22.2 months for survivors. The median overall survival period was 21.3 months (95% confidence interval: 14.2–28.4 months), and the 1- and 2-year overall survival rates were 65.5% (52.9–78.0%) and 39.4% (25.3–53.5%), respectively. Disease progression occurred in 38 patients, and the 1- and 2-year progression-free survival rates were 36.2% (23.1–49.4%) and 24.9% (12.7–37.2%), respectively. Local recurrence was observed in 13 patients, and the 1- and 2-year local control rates were 79.1% (66.8–91.3%) and 64.1% (47.5–80.7%), respectively. Grade ≥3 lung toxicity was seen in six patients, esophageal toxicity occurred at grade ⩽2, and there was no cardiac toxicity.Conclusion:The prognosis of patients with unresectable stage III NSCLC is poor without chemotherapy. Our data suggest that high-dose PBT is beneficial and tolerable for these patients

Functional Regulation of Sugar Assimilation by N-Glycan-specific Interaction of Pancreatic α-Amylase with Glycoproteins of Duodenal Brush Border Membrane

Porcine pancreatic α-amylase (PPA) binds to N-linked glycans of glycoproteins (Matsushita, H., Takenaka, M., and Ogawa, H. (2002) J. Biol Chem., 277, 4680–4686). Immunostaining revealed that PPA is located at the brush-border membrane (BBM) of enterocytes in the duodenum and that the binding is inhibited by mannan but not galactan, indicating that PPA binds carbohydrate-specifically to BBM. The ligands for PPA in BBM were identified as glycoprotein N-glycans that are significantly involved in the assimilation of glucose, including sucrase-isomaltase (SI) and Na(+)/Glc cotransporter 1 (SGLT1). Binding of SI and SGLT1 in BBM to PPA was dose-dependent and inhibited by mannan. Using BBM vesicles, we found functional changes in PPA and its ligands in BBM due to the N-glycan-specific interaction. The starch-degrading activity of PPA and maltose-degrading activity of SI were enhanced to 240 and 175%, respectively, while Glc uptake by SGLT1 was markedly inhibited by PPA at high but physiologically possible concentrations, and the binding was attenuated by the addition of mannose-specific lectins, especially from Galanthus nivalis. Additionally, recombinant human pancreatic α-amylases expressed in yeast and purified by single-step affinity chromatography exhibited the same carbohydrate binding specificity as PPA in binding assays with sugar-biotinyl polymer probes. The results indicate that mammalian pancreatic α-amylases share a common carbohydrate binding activity and specifically bind to the intestinal BBM. Interaction with N-glycans in the BBM activated PPA and SI to produce much Glc on the one hand and to inhibit Glc absorption by enterocytes via SGLT1 in order to prevent a rapid increase in blood sugar on the other