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Purpose Skin collimation is a useful tool in electron beam therapy (EBT) to decrease the penumbra at the field edge and minimize dose to nearby superficial organs at risk (OARs), but manually fabricating these collimation devices in the clinic to conform to the patient's anatomy can be a difficult and time intensive process. This work compares two types of patient‐specific skin collimation (in‐house 3D printed and vendor‐provided machined brass) using clinically relevant metrics. Methods Attenuation measurements were performed to determine the thickness of each material needed to adequately shield both 6 and 9 MeV electron beams. Relative and absolute dose planes at various depths were measured using radiochromic film to compare the surface dose, flatness, and penumbra of the different skin collimation materials. Results Clinically acceptable thicknesses of each material were determined for both 6 and 9 MeV electron beams. Field width, flatness, and penumbra results between the two systems were very similar and significantly improved compared to measurements performed with no surface collimation. Conclusion Both skin collimation methods investigated in this work generate sharp penumbras at the field edge and can minimize dose to superficial OARs compared to treatment fields with no surface collimation. The benefits of skin collimation are greatest for lower energy electron beams, and the benefits decrease as the measurement depth increases. Using bolus with skin collimation is recommended to avoid surface dose enhancement seen with collimators placed on the skin surface. Ultimately, the appropriate choice of material will depend on the desire to create these devices in‐house or outsource the fabrication to a vendor.

Purpose PreOperative radiotherapy (RT) is commonly used in the treatment of brain metastasis and different cancer types but has never been used in primary glioblastoma (GBM). Here, we aim to establish, describe, and validate the use of PreOperative RT for the treatment of GBM in a preclinical model. Methods Rat brains were locally irradiated with 30-Gy, hypofractionated in five doses 2 weeks before or after the resection of intracranial GBM. Kaplan-Meier analysis determined survival. Hematoxylin-eosin staining was performed, and nuclei size and p21 senescence marker were measured in both resected and recurrent rodent tumors. Immunohistochemistry assessed microglia/macrophage markers, and RNAseq analyzed gene expression changes in recurrent tumors. Akoya Multiplex Staining on two human patients from our ongoing Phase I/IIa trial served as proof of principle. Results PreOperative RT group median survival was significantly higher than PostOperative RT ( p  < 0.05). Radiation enlarged cytoplasm and nuclei in PreOperative RT resected tumors ( p  < 0.001) and induced senescence in PostOperative RT recurrent tumors ( p  < 0.05). Gene Set Enrichment Analysis (GSEA) suggested a more proliferative profile in PreOperative RT group. PreOperative RT showed lower macrophage/microglia recruitment in recurrent tumors ( p  < 0.01) compared to PostOperative RT. Akoya Multiplex results indicated TGF-ß accumulation in the cytoplasm of TAMs and CD4 + lymphocyte predominance in PostOperative group. Conclusions This is the first preclinical study showing feasibility and longer overall survival using neoadjuvant radiotherapy before GBM resection in a mammalian model. This suggests strong superiority for new clinical radiation strategies. Further studies and trials are required to confirm our results.

Background Radiotherapy (RT) is an essential component in the treatment regimens for many cancer patients. However, the dose escalation required to improve curative results is hindered due to the normal tissue toxicity that is induced. The introduction of radiosensitizers to RT treatment is an avenue that is currently being explored to overcome this issue. By introducing radiosensitizers into tumor sites, it is possible to preferentially enhance the local dose deposited. Gold nanoparticles (GNPs) are a potential candidate that have shown great promise in increasing the radiosensitivity of cancer cells through an enhancement in DNA damage. Furthermore, docetaxel (DTX) is a chemotherapeutic agent that arrests cells in the G2/M phase of the cell cycle, the phase most sensitive to radiation damage. We hypothesized that by incorporating DTX to GNP-enhanced radiotherapy treatment, we could further improve the radiosensitization experienced by cancer cells. To assess this strategy, we analyzed the radiotherapeutic effects on monolayer cell cultures in vitro, as well as on a mice prostate xenograft model in vivo while using clinically feasible concentrations for both GNPs and DTX. Results The introduction of DTX to GNP-enhanced radiotherapy further increased the radiotherapeutic effects experienced by cancer cells. A 38% increase in DNA double-strand breaks was observed with the combination of GNP/DTX vs GNP alone after a dose of 2 Gy was administered. In vivo results displayed significant reduction in tumor growth over a 30-day observation period with the treatment of GNP/DTX/RT when compared to GNP/RT after a single 5 Gy dose was given to mice. The treatment strategy also resulted in 100% mice survival, which was not observed for other treatment conditions. Conclusions Incorporating DTX to work in unison with GNPs and RT can increase the efficacy of RT treatment. Our study suggests that the treatment strategy could improve tumor control through local dose enhancement. As the concentrations used in this study are clinically feasible, there is potential for this strategy to be translated into clinical settings.

Non‐small cell lung cancer patients with anaplastic lymphoma kinase or c‐ros oncogene 1 mutations who are treated with the tyrosine kinase inhibitor crizotinib rarely develop crizotinib‐associated renal cysts (CARCs). Here, we present a case report and review of the literature supporting the hypothesis that CARCs may correlate positively with progression‐free survival. Non‐small cell lung cancer patients with anaplastic lymphoma kinase or c‐ros oncogene 1 mutations who are treated with the tyrosine kinase inhibitor crizotinib rarely develop crizotinib‐associated renal cysts (CARCs). Here, we present a case report and review of the literature supporting the hypothesis that CARCs may correlate positively with progression‐free survival.

Spatially fractionated radiation therapy (SFRT) utilizes multiple radiation beams to combine areas of low and high dose within the treatment volume. Organ at risk (OAR) tolerance with SFRT is greater than traditional techniques, with increasing benefits as the beam size decreases. Minibeam radiation therapy (MBRT) is a form of SFRT with beam sizes on the order of 1 mm, which is achievable utilizing conventional treatment techniques, but MBRT has only recently been used in the treatment of humans.The primary objectives of this work are to develop a system to deliver minibeam radiation therapy (MBRT) using a commercially available small animal research radiation therapy platform, perform cell survival studies comparing the survival of cells irradiated with both MBRT and broad beam (BB) dose delivery, and complete an in vivo treatment planning study to determine the dosimetric differences of different MBRT treatment delivery techniques.Most work in SFRT has focused on larger beams that provide limited benefits or very small beams that are too impractical for clinical use. SFRT is an area of active research with growing clinical applications and interest. This work aims to lay the groundwork for future small animal studies and inform the development of future clinical trials in humans.