Tadashi Kamada

Comparison of carbon-ion passive and scanning irradiation for pancreatic cancer

PURPOSE To compare carbon-ion beam dose distribution between passive and scanning radiation therapies for locally advanced pancreatic cancer. MATERIALS AND METHODS Thirteen pancreatic cancer patients were included in this study. Four types of treatment planning with respiratory gating were calculated for each patient: a four-field box with passive irradiation (Plan 1), scanning irradiation (Plan 2), a three-field (150°, 180° and 210°) protocol with passive irradiation (Plan 3), and scanning irradiation (Plan 4). The irradiation plans each delivered 55.2Gy (RBE) to the planning target volume (PTV) and were compared with respect to doses to the PTV and organs at risk (OARs). RESULTS Plan 3 exceeded the dose assessment metrics to the spinal cord. Scanning irradiation plans (Plan 2 and, particularly, Plan 4) offered significantly reduced dosage to the stomach and the duodenum compared with passive irradiation. CONCLUSION Three-field oblique scanning irradiation for pancreatic cancer has the potential to reduce gastrointestinal exposure and influence of peristalsis on dose distribution.

Role of glucose metabolism and cellularity for tumor malignancy evaluation using FDG-PET/CT and MRI.

ObjectiveStandardized uptake value (SUV) is affected by many factors. In that respect, the brain reference index (BRI: regions of interest of tumor/regions of interest of cerebellum) is one of the quantitative approaches to eliminate the variety of factors that affect SUV. MRI pulse sequence findings can also provide information about tissue cellularity. This information is useful for evaluating the malignancy of lesions. We evaluated the role of glucose metabolism and cellularity for the diagnosis of pancreatic tumor malignancy. MethodWe performed a radionuclide 2-18F-fluoro-2-deoxyglucose (18F-FDG) uptake analysis and a signal intensity analysis using MRI on 16 presurgery patients with either proven or suspected pancreatic cancer. The tumor glucose metabolism was evaluated with SUV and BRI in an FDG-PET study. Tumor cellularity was determined with the MRI factors, apparent diffusion coefficient (ADC), T2 value and tumor to nontumor ratio of proton density. We compared these results with the pathological findings. ResultsSUV (=0.855), BRI (=0.875), and ADC (=0.830) showed a larger the area under the curve than T2 value (=0.582) and tumor to nontumor ratio of proton density (=0.786) according to the receiver operating characteristics analysis, and we therefore considered that these three factors were better indexes for the diagnosis of tumor malignancy. SUV and BRI had a high specificity. In contrast, ADC had a high sensitivity. ConclusionThe glucose metabolism with PET/CT and cellularity with MRI are different indexes for the diagnosis of tumor malignancy. Both provide necessary information for making an accurate diagnosis. Using both types of information may therefore help in obtaining a highly accurate diagnosis.

Effects of ionic radius of redox-inactive bio-related metal ions on the radical-scavenging activity of flavonoids evaluated using photometric titration

Mg(2+) enhanced the scavenging activity of (+)-catechin and quercetin against the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH˙), while Al(3+) decreased their activity. Such effects of Mg(2+) and Al(3+) were not observed for kaempferol. Na(+) and Ca(2+) with large ionic radii showed little effect on the DPPH˙-scavenging activity of these three flavonoids.

Brain contrasting ability of blood-brain-barrier–permeable nitroxyl contrast agents for magnetic resonance redox imaging

The detailed in vivo T1‐weighted contrasting abilities of nitroxyl contrast agents, which have been used as redox responsive contrast agents in several magnetic resonance‐based imaging modalities, in mouse brain were investigated.

PU-H71, a novel Hsp90 inhibitor, as a potential cancer-specific sensitizer to carbon-ion beam therapy

PU-H71, a heat shock protein 90 (Hsp90) inhibitor, has yielded therapeutic efficacy in many preclinical models and is currently in clinical trials. Carbon-ion radiotherapy (CIRT) has provided successful tumor control; however, there is still room for improvement, particularly in terms of tumor-specific radiosensitization. The Hsp90 inhibitor PU-H71 has been shown to sensitize tumor cells to X-ray radiation. A murine osteosarcoma cell line (LM8) and a normal human fibroblast cell line (AG01522) were treated with PU-H71 before X-ray, 14- or 50-keV/µm carbon-ion beam (C-ion) irradiation. Cell survival and protein expression were evaluated with colony formation and western blot, respectively. Treatment with PU-H71 alone was shown to be non-toxic to both cell lines; however, PU-H71 was shown to significantly sensitize LM8 cells to not only X-ray, but also to C-ion irradiation, while only a minimal sensitizing effect was observed in AG01522 cells. PU-H71 treatment was found to suppress the protein expression levels of Rad51 and Ku70, which are associated with the homologous recombination pathway and the non-homologous end-joining pathway of double-strand break repair. The findings reported here suggest that PU-H71 could be a promising radiosensitizer for CIRT.

Locoregional therapy with α‐emitting trastuzumab against peritoneal metastasis of human epidermal growth factor receptor 2‐positive gastric cancer in mice

Peritoneal metastasis of gastric cancer (PMGC) is incurable and thus has an extremely poor prognosis. We have found, however, that locoregionally administered trastuzumab armed with astatine‐211 (211At‐trastuzumab) is effective against human epidermal growth factor receptor 2 (HER2)‐positive PMGC in a xenograft mouse model. We first observed that 211At‐trastuzumab can specifically bind and effectively kill NCI‐N87 (N87) cells, which are HER2‐positive human metastatic GC cells, both in vitro and in s.c. tumors. We established a PMGC mouse model using N87 xenografts stably expressing luciferase to test α‐particle radioimmunotherapy with 211At‐trastuzumab against PMGC. Biodistribution analysis in this PMGC mouse model revealed that the i.p. administration of 211At‐trastuzumab (1 MBq) was a more efficient means of delivery of 211At into metastatic tumors than i.v. injection; the maximum tumor uptake with i.p. administration was over 60% injected dose per gram of tissue (%ID/g) compared to approximately 18%ID/g with i.v. injection. Surprisingly, a single i.p. injection of 211At‐trastuzumab (1 MBq) was sufficient to completely eradicate intraperitoneally disseminated HER2‐positive GC xenografts in two of six treated mice by inducing DNA double‐strand breaks, and to drastically reduce the tumor burden in another three mice. No bodyweight loss, leukocytopenia, or significant biochemical changes in liver or kidney function were observed in the treatment group. Accordingly, locoregionally administered 211At‐trastuzumab significantly prolonged the survival time of HER2‐positive PMGC mice compared with control treatments. Our results provide a proof‐of‐concept demonstration that locoregional therapy with 211At‐trastuzumab may offer a new treatment option for HER2‐positive PMGC.

EP-1213: Changes in pulmonary function after single-fraction carbon-ion radiotherapy for stage I NSCLC

Conclusion: Our results suggest that SABR for medically inoperable NSCLC can be safely and effectively implemented in a non-academic institution with appropriate equipment and training.Clinical outcomes are comparable with internationally published series [3}, with encouraging 3yr OS rate of 56%. Toxicity is minimal. Longer term follow-up is required to confirm findings and provide data regarding longterm toxicity.