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In particle radiotherapy, range uncertainty is an important issue that needs to be overcome. Because high-dose conformality can be achieved using a particle beam, a small uncertainty can affect tumor control or cause normal-tissue complications. From this perspective, the treatment planning system (TPS) must be accurate. However, there is a well-known inaccuracy regarding dose computation in heterogeneous media. This means that verifying the uncertainty level is one of the prerequisites for TPS commissioning. We evaluated the range accuracy of the dose computation algorithm implemented in a commercial TPS, and Monte Carlo (MC) simulation against measurement using a CT calibration phantom. A treatment plan was produced for eight different materials plugged into a phantom, and two-dimensional doses were measured using a chamber array. The measurement setup and beam delivery were simulated by MC code. For an infinite solid water phantom, the gamma passing rate between the measurement and TPS was 97.7%, and that between the measurement and MC was 96.5%. However, gamma passing rates between the measurement and TPS were 49.4% for the lung and 67.8% for bone, and between the measurement and MC were 85.6% for the lung and 100.0% for bone tissue. For adipose, breast, brain, liver, and bone mineral, the gamma passing rates computed by TPS were 91.7%, 90.6%, 81.7%, 85.6%, and 85.6%, respectively. The gamma passing rates for MC for adipose, breast, brain, liver, and bone mineral were 100.0%, 97.2%, 95.0%, 98.9%, and 97.8%, respectively. In conclusion, the described procedure successfully evaluated the allowable range uncertainty for TPS commissioning. The TPS dose calculation is inefficient in heterogeneous media with large differences in density, such as lung or bone tissue. Therefore, the limitations of TPS in heterogeneous media should be understood and applied in clinical practice.

Despite the benefits from adjuvant chemotherapy or chemoradiotherapy, approximately one-third of stage II gastric cancer (GC) patients developed recurrences. The aim of this study was to develop and validate a prognostic algorithm for gastric cancer (GCPS) that can robustly identify high-risk group for recurrence among stage II patients. A multi-step gene expression profiling study was conducted. First, a microarray gene expression profiling of archived paraffin-embedded tumor blocks was used to identify candidate prognostic genes (N=432). Second, a focused gene expression assay including prognostic genes was used to develop a robust clinical assay (GCPS) in stage II patients from the same cohort (N=186). Third, a predefined cut off for the GCPS was validated using an independent stage II cohort (N=216). The GCPS was validated in another set with stage II GC who underwent surgery without adjuvant treatment (N=300). GCPS was developed by summing the product of Cox regression coefficients and normalized expression levels of 8 genes (LAMP5, CDC25B, CDK1, CLIP4, LTB4R2, MATN3, NOX4, TFDP1). A prospectively defined cut-point for GCPS classified 22.7% of validation cohort treated with chemoradiotherapy (N=216) as high-risk group with 5-year recurrence rate of 58.6% compared to 85.4% in the low risk group (hazard ratio for recurrence=3.16, p=0.00004). GCPS also identified high-risk group among stage II patients treated with surgery only (hazard ratio=1.77, p=0.0053).

Radiation therapy is an indispensable therapeutic modality for various brain diseases. Though endogenous neural stem cells (NSCs) would provide regenerative potential, many patients nevertheless suffer from radiation-induced brain damage. Accordingly, we tested beneficial effects of exogenous NSC supplementation using in vivo mouse models that received whole brain irradiation. Systemic supplementation of primarily cultured mouse fetal NSCs inhibited radiation-induced brain atrophy and thereby preserved brain functions such as short-term memory. Transplanted NSCs migrated to the irradiated brain and differentiated into neurons, astrocytes, or oligodendrocytes. In addition, neurotrophic factors such as NGF were significantly increased in the brain by NSCs, indicating that both paracrine and replacement effects could be the therapeutic mechanisms of NSCs. Interestingly, NSCs also differentiated into brain endothelial cells, which was accompanied by the restoration the cerebral blood flow that was reduced from the irradiation. Inhibition of the VEGF signaling reduced the migration and trans-differentiation of NSCs. Therefore, trans-differentiation of NSCs into brain endothelial cells by the VEGF signaling and the consequential restoration of the cerebral blood flow would also be one of the therapeutic mechanisms of NSCs. In summary, our data demonstrate that exogenous NSC supplementation could prevent radiation-induced functional loss of the brain. Therefore, successful combination of brain radiation therapy and NSC supplementation would provide a highly promising therapeutic option for patients with various brain diseases. [ABSTRACT FROM AUTHOR]