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Purpose: In order for radiotherapy to enter the realm of personalized medicine it will be necessary to model and predict individual patient responses to radiotherapy. Methods and Materials: Here we model tumor dynamics as logistic growth and the effect of radiation as a reduction in the tumor carrying capacity, motivated by the impact of radiation on the tumor microenvironment. The model was assessed on weekly tumor volume data collected for two independent cohorts of head and neck cancer patients from XXXX1 and XXXX2 that received 66-70 Gy in standard daily fractions or with accelerated fractionation. To predict response to radiotherapy for individual patients, we developed a new forecasting framework that combined the learned tumor growth rate and carrying capacity reduction fraction (δ) distribution with weekly measurements of tumor volume reduction for a given test patient to estimate δ, which was used to predict patient-specific outcomes. Results: The model fit data from XXXX1 with high accuracy with patient-specific δ and a fixed tumor growth rate across all patients. The model fit data from an independent cohort from XXXX2 with comparable accuracy using the tumor growth rate learned from the XXXX1 cohort, demonstrating transferability of the growth rate. The forecasting framework predicted patient-specific outcomes with 76% sensitivity and 83% specificity for locoregional control and 68% sensitivity and 85% specificity for disease-free survival with the inclusion of four on-treatment tumor volume measurements. Conclusions: These results show that our simple mathematical model can describe a variety of tumor volume dynamics. Further, combining historically observed patient responses with a few patient-specific tumor volume measurements allows for the accurate prediction of patient outcomes, which may inform treatment adaptation and personalization.

PURPOSE: Radiotherapy (RT) is a mainstay of cancer care and accumulating evidence suggests the potential for synergism with components of the immune response. However, little data describes the tumor immune contexture in relation to RT-sensitivity. To address this challenge, we employed the radiation sensitivity index (RSI) gene signature to estimate the RT-sensitivity of >10,000 primary tumors and characterized their immune microenvironments in relation to the RSI. MATERIAL AND METHODS: We analyzed gene expression profiles of 10,469 primary tumors (31 types) within a prospective tissue collection protocol. The RT-sensitivity of each tumor was estimated by the RSI and respective distributions were characterized. The tumor biology measured by the RSI was evaluated by differentially expressed genes (DEGs) combined with single sample gene set enrichment analysis (ssGSEA). Differences in the expression of immune regulatory molecules were assessed and deconvolution algorithms were used to estimate immune cell infiltrates in relation to the RSI. A subset (n=2,368) of tumors underwent DNA sequencing for mutational frequency characterization. RESULTS: We identified a wide range of RSI values within and across various tumor types, with several demonstrating non-unimodal distributions (e.g. colon, renal, lung, prostate, esophagus, pancreas and PAM50 breast subtypes; p

Purpose/Objective(s) As current radiotherapy (RT) treatment schedules are not personalized for individual patients, with the prescribed dose being uniform for particular subtypes and stages of cancer, despite highly variable responses between patients, we performed an in silico trial to determine optimal personalized RT dose for head and neck cancer patients in order to minimize excess dose with the objective of minimizing toxicity and improving QOL without sacrificing tumor control. Materials/Methods Weekly tumor volume data were collected from two cancer centers for n = 39 head and neck cancer patients that received 66-70 Gy in 2-2.12 Gy daily fractions or with accelerated fractionation. Clinical outcome data, i.e., locoregional control (LRC) and disease-free survival (DFS), were also collected. Tumor volume reduction was connected to LRC by means of a volume reduction threshold associated with LRC. Due to limited patient numbers, the in silico trial was performed in an iterative leave-one-out fashion as follows: (1) a simple 2 parameter model of tumor growth and response to RT was calibrated to tumor volume data from 38 patients, (2) the calibrated model parameters were combined with the left-out patient's tumor volume data from weeks 1-4 of RT to simulate tumor volumes forward sampling from a patient-specific distribution of radiosensitivity parameters, (3) minimum cumulative radiation dose required for local tumor control was estimated by calculating the dose at which > 95% the simulated tumor volume trajectories were below the volume reduction threshold associated with LRC. Results The optimal minimum radiation dose required for LRC was calculated for each patient. We found that 87% of the patients (34/39) received a higher total dose than estimated as necessary by our model with an average overdose of 37 Gy/patient, while the remaining patients were estimated to have received too little dose, with an average underdose of 47 Gy/patient. Notably, our results showed that the current one-size-fits-all approach results in no patient receiving their optimal RT dose. Conclusion Here we show a method to determine a personalized minimum RT dose to achieve LRC. Such simulations and estimates may allow radiation oncologists to identify candidates for dose de-escalation, dose escalation, or additional concurrent treatments, such as chemotherapy.

Purpose: Radiation therapy (RT) is associated with high stress levels. The role of music therapy (MT) for patients receiving RT is not well described. This study evaluates the impact of MT on anxiety and distress during simulation in patients with newly diagnosed head and neck or breast cancer. Methods and Materials: This institutional review board–approved randomized trial of MT versus no MT at the time of simulation included the pre–State-Trait Anxiety Inventory (STAI-S Anxiety) questionnaire and Symptom Distress Thermometer (SDT). Patients randomized to MT received a consultation with a music therapist, during which music of the patients’ choice to be played during simulation was selected. The no-MT patients did not receive the MT consultation, nor did they hear prerecorded music during simulation. Subsequent to the simulation, all patients repeated the STAI-S Anxiety questionnaire and the SDT. Results: Of the 78 patients enrolled (39 in MT group and 39 in no-MT group), 38 had breast cancer and 40 had head and neck cancer. The male-female ratio was 27:51. The overall mean pre- and post-simulation STAI-S scores were 38.7 (range, 20–60) and 35.2 (range, 20–72), respectively. The overall mean pre- and post-simulation SDT scores were 3.2 (range, 0–10) and 2.5 (range, 0–10), respectively. The MT group had mean pre- and post-simulation STAI-S scores of 39.1 and 31.0, respectively (P, Summary Music therapy’s capacity to address anxiety in cancer patients has not been well described. This institutional review board–approved study evaluated a protocolized music therapy intervention’s impact on anxiety and distress experienced by patients undergoing computed tomography simulation. The intervention significantly reduced anxiety and distress in patients with newly diagnosed head and neck or breast cancer, with a greater effect in subgroups with higher baseline levels of anxiety and distress. Continued research on music therapy’s effects in radiation oncology is warranted.

Primary mucosal melanoma of the head and neck (MMHN) comprises approximately 1% of all malignant melanomas. It presents more commonly in an elderly population and has no significant gender predominance. Given its rarity, most evidence of the causes, behavior, and treatment approaches for MMHN originates from isolated case reports and retrospective series. Between 1945 and 2011, at least 1951 cases of MMHN have been reported in the literature. Despite numerous technological developments in surgery and radiation therapy, as well as advances in systemic modalities, MMHN is an aggressive malignancy with a very poor prognosis. Complete surgical excision with clear margins remains the primary treatment modality. Adjuvant postoperative radiation therapy may improve locoregional control but does not appear to affect survival. Definitive particle radiation therapy promises to provide high rates of local control for nonoperable patients. Recent molecular evidence suggests that proto-oncogene KIT aberrations in a subset of mucosal melanomas may represent a potential diagnostic value and serve as a therapeutic target for tyrosine kinase inhibitors in an adjuvant setting for patients with advanced MMHN.

In 1999, with direction from the American Society for TherapeuticRadiology andOncology(ASTRO) BoardofDirectors, a Steering Committee and a series of subcommittees were formed to define the scope of practice within radiation oncology. During the next several years, meetings were convened and drafts were developed to include input from the ASTRO Board of Directors, other experts within the oncology field, and the ASTRO members themselves. The result of this work was The Report of the ASTRO Working Group on the Scope of Radiation Oncology (from here on referred to as the SCOPE I Report).Thisreport‘‘outlined the current roleofRadiation Oncology and highlighted a number of issues and recommendations potentially important in preserving and enhancing the relevance and value of radiation oncology’’ (1). The SCOPE I Report illustrated issues pertaining to the amount of clinical involvement radiation oncologists have with patients and its effect on patient care. It addressed combined-modality therapy and its place within radiation oncology. The role of radiation therapy in treating nonmalignant (benign) diseases was also explored. The SCOPE I Report also discussed the knowledge and skill required to keep up with the fast pace of technologic advancement within radiation oncology. The purpose of the SCOPE I Report was to ‘‘stimulate dialogue and move the community toward development of an action plan’’ (1). Unfortunately, little action resulted from the development of this document. Today, many within radiation oncology believe that their field is at a crossroad in its path to the future, and that the choices made today will determine its future role in cancer treatment. Radiation oncology has become increasingly technologically driven, affecting both the way patients are managed and the way other oncology specialties view and behave toward it. For these reasons, ASTRO convened the

Purpose: Trains of multiple 192 Ir seeds are used in many clinical trials for intravascular brachytherapy. 192 Ir source is commonly considered as a gamma emitter, despite the understanding that this radionuclide also emits a wide range of electron and beta energies, with a similar range of energy. The high dose from betas and electrons in the submillimeter range due to unsealed ends of seed sources should be precisely quantified to fully understand the backdrop for complications associated with 192 Ir coronary artery brachytherapy. Methods and Materials: Monte Carlo simulations (MCNP4C code) were performed for a model 5-seed 192 Ir train used in SCRIPPS, GAMMA, and the Washington Radiation for In-Stent Restenosis (WRIST) randomized clinical trials. A stack of radiochromic films was also used to measure the dose distributions for an actual 6-seed train. Results: In the submillimeter range very close to the source, Monte Carlo results show that betas and electrons deposit a higher dose than 192 Ir photons (gamma and X-rays) over the interseed gap. A high luminal dose from the combined effects of betas, electrons, and photons emitted from 192 Ir can be deposited, particularly between seeds. When prescribing 15 Gy at 2 mm, the combined dose can be as high as 160 Gy at 0.5 mm. Different peak doses near the interseed gaps were noted, which may be due to variability of seed-end surfaces and nonuniformity of seed activity within a real multiseed train. Dose-volume histograms (DVH) of lumen surfaces were evaluated for an eccentric seed train. The DVH parameters indicating the extent of hot spots in the lumen wall, DV 10 , DV 5 , DV 2 , and DV 1 (dose received by 10, 5, 2, 1% respectively of the total lumen surface), can be as high as 55, 76, 81, and 155 Gy for a lumen with 3-mm diameter, and 75, 80, 110, and 158 Gy for a narrow 2-mm lumen. Conclusion: 192 Ir multiple seed trains used in the SCRIPPS, GAMMA, and WRIST trials can deposit a very high dose to the luminal wall. A particularly high electron and beta dose can be delivered near the interseed gap if the source is not centered in the catheter and lumen. The dose from 192 Ir betas and electrons may partially explain adverse outcomes reported from 192 Ir multiseed clinical trials. Improvement of the encapsulation design to filter out the betas and electrons should be seriously considered.

Purpose: The doses given to the intima, media, and adventitia are very crucial quantities in intravascular brachytherapy. To facilitate accurate computerized treatment planning calculations, we have determined dose distributions in away-and-along table format around an 192 Ir wire source and developed pertinent dosimetric parameters in cylindrical coordinates. Methods and Materials: The Monte Carlo method (MCNP4C code) was used to calculate the dose distributions for the AngioRad 192 Ir wire source (model SL-77HS, Interventional Therapies). The calculations were carried out for photon, beta, and electron (conversion and Auger) contributions for radial distances from 0.03 to 2.0 cm with 0.01-cm increments, and up to 2.24 cm from the source center in the longitudinal direction with 0.04-cm resolution. Dose rate values are determined in away-and-along format (cylindrical coordinates) and then converted to spherical coordinate format. Dosimetric parameters, such as the geometry factor, G(r, θ), and anisotropy function, F(r, θ), are generated in both cylindrical (R, Z, φ) and spherical (r, θ, φ) coordinates. The use of a cylindrical coordinate system for treatment planning parameters is proposed as a more suitable approach for accurate calculations. Results: The photon contribution to dose varies nearly inversely with radial distance (from the source center) along the perpendicular bisector with 0.199 × 10 −3 cGy U −1 s −1 (0.802 cGy Ci −1 s −1 ) at 1 cm. The beta and electron contributions start at very high values of about 35.5 × 10 −3 cGy U −1 s −1 and 11.0 × 10 −3 cGy U −1 s −1 , respectively, at 0.03 cm and fall off exponentially to negligible amount near 0.2 cm. The total dose rate at 0.2 cm is 1.428 × 10 −3 cGy U −1 s −1 (5.754 cGy Ci −1 s −1 ). The radial dose function, g(R), is nearly unity between 0.2 cm and 2 cm. Due to the beta and electron dose contributions, g(R) increases steeply to 5.5 as radial distance decreases from 0.2 cm down to 0.03 cm. The F(R, Z) values are close to unity for the majority of the region of interest. In contrast, F(r, θ) experiences a steep rise as shallow angles are approached (closer to the source), related to the beta dose contributions. Accurate treatment planning calculations would be possible with linear interpolation of F(R, Z), but difficult with F(r, θ) in the spherical coordinate system and the original normalization point as recommended in the American Association of Physicists in Medicine Task Group 60 (AAPM TG-60) formalism. Conclusion: The AngioRad 192 Ir wire source, model SL-77HS, was completely characterized dosimetrically using Monte Carlo methods. The use of cylindrical coordinates and a modified anisotropy function normalization point for dosimetric parameters of an elongated 192 Ir source is more suitable for accurate computerized treatment planning calculations in intravascular brachytherapy.