Feasibility Study of 3D-VMAT-Based GRID Therapy.

Background: Spatially fractionated radiotherapy (GRID) could effectively de-bulk tumor volumes for shallow and deep-seated locally advanced tumors. A new treatment planning method using the three-dimensional-volumetric modulated arc therapy (VMAT) technique combined with a novel, software-generated, virtual GRID block (VGB) was developed which allows better conformity plans (VMAT-GRID) and maintain the GRID dosimetric characteristics. The dosimetric metrics calculated via the valley/peak ratio (Dmin/Dmax), D90/D10, gross tumor volume (GTV) mean dose (Dmean), GTV equivalent uniform dose (EUD), and normal tissue maximum dose. Methods: Twenty-five patients with tumor volumes ranging between 71.6 cc and 4683 cc at various tumor sites were retrospectively studied. The prescription was 20 Gy to the maximum point of GTV in a single fraction, and the VMAT-GRID plan was generated using 6 MV/10 MV flattening-filter-free beams. Results: The optimized VGB was designed with the median center-to-center distance of 27 mm, and 9 mm for the median diameter of the opening area in this study. These 2 values can be used to design any optimized VGB, the final VGB may be modified to generate a patient-specific VGB. The median GTV mean dose was 918 (877- 938) cGy, and the median GTV EUD dose was 818 (597-916) cGy. In terms of dose inhomogeneity, the median valley-to-peak dose ratio was 0.07 (0.02-0.26); and the median ratio of D90/D10 was 0.70 (0.38-0.94). For the organ-at-risk doses, there was a rapid dose drop-off in the normal tissue area immediately adjacent to the target, and the maximum global doses were all located inside the GTV. Conclusion: Our results indicated that the VMAT-GRID planning approach could successfully deliver dose with acceptable GRID dose metric while sparing the normal tissue especially in the region near the target due to the rapid dose drop-off and restricting maximum dose inside the target.

Evidence for Early Stage Anti-Tumor Immunity Elicited by Spatially Fractionated Radiotherapy-Immunotherapy Combinations.

The combination of radiotherapy and immunotherapy may generate synergistic anti-tumor host immune responses and promote abscopal effects. Spatial fractionation of a radiation dose has been found to promote unique physiological responses of tumors, which might promote synergy with immunotherapy. To determine whether spatial fractionation may augment immune activity, whole-tumor or spatial fractionation grid radiation treatment (GRID) alone or in combination with antibodies against immune checkpoints PD1 and CTLA-4 were tested in an immunocompetent mouse model using a triple negative breast tumor (4T1). Tumor growth delay, immunohistochemistry and flow cytometry were used to characterize the effects of each treatment type. Whole-beam radiation with immune checkpoint inhibition significantly restrained tumor growth in the irradiated tumor, but not abscopal tumors, compared to either of these treatments alone. In mice that received spatially fractionated irradiation, evidence of abscopal immune responses were observed in contralateral tumors with markedly enhanced infiltration of both antigen-presenting cells and activated T cells, which were preceded by increased systemic IFNγ production and led to eventual tumor growth delay. These studies suggest that systemic immune activation may be triggered by employing GRID to a primary tumor lesion, promoting anti-tumor immune responses outside the treatment field. Interestingly, PD-L1 was found to be upregulated in abscopal tumors from GRID-treated mice. Combined radio-immunotherapy therapy is becoming a validated and novel approach in the treatment of cancer. With the potential increased benefit of GRID to augment both local and metastatic disease responses, further exploration of GRID treatment as a part of current standards of care is warranted.

Neurosurgical management of perineural metastases: A case series and review of the literature.

BACKGROUND: Perineural invasion (PNI) and spread are one of the grimmest prognostic factors associated with primary skin and head-and-neck cancers, yet remain an often confused, and underreported, phenomenon. Adding complexity to reaching a diagnosis and treating perineural spread (PNS) is the finding that patients may have no known primary tumor, history of skin cancer, and/or incidental PNI in the primary tumor. These delays in diagnosis and treatment are further compounded by an already slow disease process and often require multidisciplinary care with combinations of stereotactic radiosurgery, surgical resection, and novel treatments such as checkpoint inhibitors. METHODS: Six patients with metastatic cancer to the cranial nerves who underwent Gamma Knife radiosurgery (GKRS) treatment were chosen for retrospective analysis. This information included age, gender, any past surgeries (both stereotactic and regular surgery), dose of radiation and volume of the tumor treated in the GKRS, date of PNS, comorbidities, the patient follow-up, and pre- and post-GKRS imaging. The goal of the follow-up with radiographing imaging was to assess the efficacy of GKSS. RESULTS: The clinical course of six patients with PNS is presented. Patients followed variable courses with mixed outcomes: two patients remain living, one was lost to follow-up, and three expired with a median survival of 12 months from date of diagnosis. Patients at our institution are ideally followed for life. CONCLUSION: Given the morbidity and mortality of PNS of cancer, time is limited, and further understanding is required to improve outcomes. Here, we provide a case series of patients with PNS treated with stereotactic radiosurgery, discuss their clinical courses, and review the known literature.

Comparaçäo entre sistemas Tandem para raios-x de baixas energias / Comparison between Tandem system to x-rays of low energy

Sistemas Tandem, constituídos por pares de câmaras comerciais e por um par de câmaras de placas paralelas desenvolvidas no IPEN, foram testados em campos padrões de radiação X de baixa energias (14 a 21keV), para comparação de resultados.

Tandem systems using commercial ionization chambers as well as the parallelplates chambers developed at IPEN were tested in standard low energy X radiation fields (14 -21keV) for comparative purposes.