Grams, Michael P.

Abstract Physicians performing x-ray guided interventional procedures have a keen interest in radiation safety. Radiation dose to tissues and organs of the head and neck are of particular interest because they are not routinely protected by wearable radiation safety devices. This study was conducted to facilitate estimation of radiation dose to tissues of the head and neck of interventional physicians based on the dose recorded by a personal dosimeter worn on the left collar. Scatter beam qualities maximum energy and HVL were measured for 40 scatter beams emitting from an anthropomorphic patient phantom. Variables of the scatter beams included scatter angle (35° and 90°), primary beam peak tube potential (60, 80, 100, and 120 kVp), and 5 Cu spectral filter thicknesses (0–0.9 mm). Four reference scatter beam qualities were selected to represent the range of scatter beams realized in a typical practice. A general radiographic x-ray tube was tuned to produce scatter-equivalent radiographic beams and used to simultaneously expose the head and neck of an anthropomorphic operator phantom and radiochromic film. The geometric relationship between the x-ray source of the scatter-equivalent beams and the operator phantom was set to mimic that between a patient and physician performing an invasive cardiovascular procedure. Dose to the exterior surface of the operator phantom was measured with both 3 × 3 cm 2 pieces of film and personal dosimeters positioned at the location of the left collar. All films were scanned with a calibrated flatbed scanner, which converted the film’s reflective density to dose. Films from the transverse planes of the operator phantom provided 2D maps of the dose distribution within the phantom. These dose maps were normalized by the dose at the left collar, providing 2D percent of left collar dose (LCD) maps. The percent LCD maps were overlain with bony anatomy CT images of the operator phantom and estimates of percent LCD to the left, right and whole brain, brain stem, lenses of the eyes, and carotid arteries were calculated. Per expectation, results indicated greater percent dose to superficial versus deep tissues and increasing percent dose to deep tissues with increasing scatter-equivalent beam energy and HVL. The results enable estimation of the scatter dose to tissues of the head and neck of interventional physicians based on occupational dose measured by a personal dosimeter worn at the collar outside the protective apron.

Abstract We investigated the influence of PD-1 expression on the systemic antitumor response (abscopal effect) induced by stereotactic ablative radiotherapy (SABR) in preclinical melanoma and renal cell carcinoma models. We compared the SABR-induced antitumor response in PD-1–expressing wild-type (WT) and PD-1–deficient knockout (KO) mice and found that PD-1 expression compromises the survival of tumor-bearing mice treated with SABR. None of the PD-1 WT mice survived beyond 25 days, whereas 20% of the PD-1 KO mice survived beyond 40 days. Similarly, PD-1–blocking antibody in WT mice was able to recapitulate SABR-induced antitumor responses observed in PD-1 KO mice and led to increased survival. The combination of SABR plus PD-1 blockade induced near complete regression of the irradiated primary tumor (synergistic effect), as opposed to SABR alone or SABR plus control antibody. The combination of SABR plus PD-1 blockade therapy elicited a 66% reduction in size of nonirradiated, secondary tumors outside the SABR radiation field (abscopal effect). The observed abscopal effect was tumor specific and was not dependent on tumor histology or host genetic background. The CD11ahigh CD8+ T-cell phenotype identifies a tumor-reactive population, which was associated in frequency and function with a SABR-induced antitumor immune response in PD-1 KO mice. We conclude that SABR induces an abscopal tumor-specific immune response in both the irradiated and nonirradiated tumors, which is potentiated by PD-1 blockade. The combination of SABR and PD-1 blockade has the potential to translate into a potent immunotherapy strategy in the management of patients with metastatic cancer. Cancer Immunol Res; 3(6); 610–9. ©2015 AACR.

Background. Radiotherapy has been utilized for metastatic and recurrent osteosarcoma and Ewing sarcoma (ES), in order to provide palliation and possibly prolong overall or progression-free survival. Stereotactic body radiotherapy (SBRT) is convenient for patients and offers the possibility of increased efficacy. We report our early institutional experience using SBRT for recurrent and metastatic osteosarcoma and Ewing sarcoma.Methods. We reviewed all cases of osteosarcoma or ES treated with SBRT between 2008 and 2012.Results. We identified 14 patients with a total of 27 lesions from osteosarcoma(n=19)or ES(n=8). The median total curative/definitive SBRT dose delivered was 40 Gy in 5 fractions (range, 30–60 Gy in 3–10 fractions). The median total palliative SBRT dose delivered was 40 Gy in 5 fractions (range, 16–50 Gy in 1–10 fractions). Two grade 2 and 1 grade 3 late toxicities occurred, consisting of myonecrosis, avascular necrosis with pathologic fracture, and sacral plexopathy. Toxicity was seen in the settings of concurrent chemotherapy and reirradiation.Conclusions. This descriptive report suggests that SBRT may be a feasible local treatment option for patients with osteosarcoma and ES. However, significant toxicity can result, and thus systematic study is warranted to clarify efficacy and characterize long-term toxicity.