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 SABRinduced 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 CD11a high CD8 þ 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 tumorspecific 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.

The use of radiochromic film (RCF) dosimetry in radiation therapy is extensive due to its high level of achievable accuracy for a wide range of dose values and its suitability under a variety of measurement conditions. However, since the publication of the 1998 AAPM Task Group 55, Report No. 63 on RCF dosimetry, the chemistry, composition, and readout systems for RCFs have evolved steadily. There are several challenges in using the new RCFs, readout systems and validation of the results depending on their applications. Accurate RCF dosimetry requires understanding of RCF selection, handling and calibration methods, calibration curves, dose conversion methods, correction methodologies as well as selection, operation and quality assurance (QA) programs of the readout systems. Acquiring this level of knowledge is not straight forward, even for some experienced users. This Task Group report addresses these issues and provides a basic understanding of available RCF models, dosimetric characteristics and properties, advantages and limitations, configurations, and overall elemental compositions of the RCFs that have changed over the past 20 yr. In addition, this report provides specific guidelines for data processing and analysis schemes and correction methodologies for clinical applications in radiation therapy.

(18)F-DOPA PET SUV(max) may more accurately identify regions of higher-grade/higher-density disease in patients with astrocytomas and will have utility in guiding stereotactic biopsy selection. Using SUV-based thresholds to define high-grade portions of disease may be valuable in delineating radiotherapy boost volumes.

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.

Radiochromic film (RCF) is a valuable dosimetric tool, primarily due to its sub-millimeter spatial resolution. For accurate proton dosimetry, the dependence of film response on linear energy transfer (LET) must be characterized and calibrated. In this work, we characterized film under-response, or ‘quenching’, as a function of dose-weighted linear energy transfer (LETd) in several proton fields and established a simple, linear relationship with LETd. We performed measurements as a function of depth in a PMMA phantom irradiated by a spot-scanning proton beam. The fields had energies of 71.3 MeV, 71.3 MeV with filter, and 159.9 MeV. At each depth (measurements taken in depth step sizes of 0.5–1 mm in the Bragg peak), we measured dose with a PTW Markus ion chamber and EBT3 RCF. EBT3 under-response was characterized by the ratio of dose measured with film to that with ion chamber. LETd values for our experimental setup were calculated using in-house clinical Monte Carlo code. Measured film under-response increased with LETd, from approximately 10% under-response for LETd  =  5 keV µm−1 to approximately 20% for LETd  =  8 keV µm−1. The under-response for all measurements was plotted versus LETd. A linear fit to the data was performed, yielding a function for under-response, , with respect to LETd: . Finally, the linear under-response relationship was applied to a film measurement within a spread-out Bragg peak (SOBP). Without correcting for LETd-dependence in the SOBP measurement, the discrepancy between film and Monte Carlo profiles was greater than 15% at the distal edge. With correction, the corrected film profile was within 2% and 1 mm of the Monte Carlo profile. RCF response depends on LETd, potentially under-responding by  >15% in clinically-relevant scenarios. Therefore, it is insufficient to perform only a dose calibration; LET calibration is also necessary for accurate proton film dosimetry. The LETd-dependence of EBT3 can be described by a single, linear function over a range of clinically-relevant proton therapy LETd values.

The LRA of EBT-XD is greatly reduced when compared to EBT3. This in combination with its accuracy from 0 to 3000 cGy and minimal energy dependence from 6 to 18 MV makes EBT-XD film well suited for dosimetric measurements in high dose SRS/SBRT applications.

Metal implants which saturate the CT number scale may require dosimetrist and physicist involvement to manually contour and assign an appropriate value to the metal for accurate dose calculation. This study investigated dose calculation based directly on extended CT scale images for different metals and geometries. The aim was to evaluate extended CT accuracy as a suitable alternative to standard CT methods in the presence of high‐Z materials and artifacts, despite the reduced HU resolution of extended CT. Gafchromic film measurements were made for comparison to calculated doses. The method of direct dose calculation on extended CT scale was compared to our institution's standard method of manually contouring and assigning metal values on saturated CT images for each of the metal samples. Clinical patient plans with metal implants were investigated and DVHs were compared between standard CT and extended CT dose calculations. Dose calculations showed agreement within 2% between the two methods of metal characterization and the film measurement in the case of the strongest metal attenuator, cobalt‐chromium. In the clinical treatment plans, the greatest dose discrepancy between the two methods was 1.2%. This study suggests that direct dose calculation on an extended scale CT image in the presence of metal implants can produce accurate clinically viable treatment plans, thereby improving efficiency of clinical workflow and eliminating a potential source of human error by manual CT number assignment.PACS number(s): 87.55.dk

Radiochromic film (RCF) has several advantageous characteristics which make it an attractive dosimeter for many clinical tasks in radiation oncology. However, knowledge of and strict adherence to complicated protocols in order to produce accurate measurements can prohibit RCF from being widely adopted in the clinic. The purpose of this study was to outline some simple and straightforward RCF fundamentals in order to help clinical medical physicists perform accurate RCF measurements. We describe a process and methodology successfully used in our practice with the hope that it saves time and effort for others when implementing RCF in their clinics. Two RCF analysis software programs which differ in cost and complexity, the commercially available FilmQA Pro package and the freely available ImageJ software, were used to show the accuracy, consistency and limitations of each. The process described resulted in a majority of the measurements across a wide dose range to be accurate within ± 2% of the intended dose using either FilmQA Pro or ImageJ.