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Purpose: While stereotactic body radiotherapy (SBRT) can reduce tumor volumes in patients with metastatic renal cell carcinoma (mRCC), little is known regarding the immunomodulatory effects of high-dose radiation in the tumor microenvironment. The main objectives of this pilot study were to assess the safety and feasibility of nephrectomy following SBRT treatment of patients with mRCC and analyze the immunological impact of high-dose radiation.Experimental Design: Human RCC cell lines were irradiated and evaluated for immunomodulation. In a single-arm feasibility study, patients with mRCC were treated with 15 Gray SBRT at the primary lesion in a single fraction followed 4 weeks later by cytoreductive nephrectomy. RCC specimens were analyzed for tumor-associated antigen (TAA) expression and T-cell infiltration. The trial has reached accrual (ClinicalTrials.gov identifier: NCT01892930).Results: RCC cells treated in vitro with radiation had increased TAA expression compared with untreated tumor cells. Fourteen patients received SBRT followed by surgery, and treatment was well-tolerated. SBRT-treated tumors had increased expression of the immunomodulatory molecule calreticulin and TAA (CA9, 5T4, NY-ESO-1, and MUC-1). Ki67+ -proliferating CD8+ T cells and FOXP3+ cells were increased in SBRT-treated patient specimens in tumors and at the tumor–stromal interface compared with archived patient specimens.Conclusions: It is feasible to perform nephrectomy following SBRT with acceptable toxicity. Following SBRT, patient RCC tumors have increased expression of calreticulin, TAA, as well as a higher percentage of proliferating T cells compared with archived RCC tumors. Collectively, these studies provide evidence of immunomodulation following SBRT in mRCC. Clin Cancer Res; 23(17); 5055–65. ©2017 AACR.

Supplementary figure S3 shows gating strategy and isotype staining of live tumor cells used for patient samples.

Supplementary table 3 shows immunohistochemical antibodies and dilutions.

Supplementary figure S5 shows PD-1+ CD4+ T cells and CD68+ macrophages are increased in SBRT-treated specimens compared to nephrectomy controls.

Supplementary figure S2 shows immunomodulation of tumor cells following high-dose radiation.

Supplementary figure S4 shows tumors resected from RCC patients treated with SBRT have decreased CD54 and increased surface NY-ESO-1 expression.

Supplementary figure S1 shows radiation induces changes in surface expression of immunogenic molecules.

Supplementary table S2 shows flow cytometry antibodies and dilutions.

Qualified medical physicists (QMPs) are in a unique position to influence the creation and application of key performance indicators (KPIs) across diverse practices in health care. Developing KPIs requires the involvement of stakeholders in the area of interest. Fundamentally, KPIs should provide actionable information for the stakeholders using or viewing them. During development, it is important to strongly consider the underlying data collection for the KPI, making it automatic whenever possible. Once the KPI has been validated, it is important to setup a review cycle and be prepared to adjust the underlying data or action levels if the KPI is not performing as intended. Examples of specific KPIs for QMPs of common scopes of practice are provided to act as models to aid in implementation. KPIs are a useful tool for QMPs, regardless of the scope of practice or practice environment, to enhance the safety and quality of care being delivered.

During dose calculation, the Eclipse treatment planning system (TPS) retracts the multileaf collimator (MLC) leaf positions by half of the dosimetric leaf gap (DLG) value (measured at central axis) for all leaf positions in a dynamic MLC plan to accurately model the rounded leaf ends. The aim of this study is to map the variation of DLG along the travel path of each MLC leaf pair and quantify how this variation impacts delivered dose.6 MV DLG values were measured for all MLC leaf pairs in increments of 1.0 cm (from the line intersecting the CAX and perpendicular to MLC motion) to 13.0 cm off axis distance at dmax. The measurements were performed on two Varian linear accelerators, both employing the Millennium 120-leaf MLCs. The measurements were performed at several locations in the beam with both a Sun Nuclear MapCHECK device and a PTW pinpoint ion chamber.The measured DLGs for the middle 40 MLC leaf pairs (each 0.5 cm width) at positions along a line through the CAX and perpendicular to MLC leaf travel direction were very similar, varying maximally by only 0.2 mm. The outer 20 MLC leaf pairs (each 1.0 cm width) have much lower DLG values, about 0.3-0.5 mm lower than the central MLC leaf pair, at their respective central line position. Overall, the mean and the maximum variation between the 0.5 cm width leaves and the 1.0 cm width leaf pairs are 0.32 and 0.65 mm, respectively.The spatial variation in DLG is caused by the variation of intraleaf transmission through MLC leaves. Fluences centered on the CAX would not be affected since DLG does not vary; but any fluences residing significantly off axis with narrow sweeping leaves may exhibit significant dose differences. This is due to the fact that there are differences in DLG between the true DLG exhibited by the 1.0 cm width outer leaves and the constant DLG value utilized by the TPS for dose calculation. Since there are large differences in DLG between the 0.5 cm width leaf pairs and 1.0 cm width leaf pairs, there is a need to correct the TPS plans, especially those with high modulation (narrow dynamic MLC gap), with 2D variation of DLG.