Proton Treatment Suppresses Exosome Production in Head and Neck Squamous Cell Carcinoma.

Proton therapy (PT) is emerging as an effective and less toxic alternative to conventional X-ray-based photon therapy (XRT) for patients with advanced head and neck squamous cell carcinomas (HNSCCs) owing to its clustered dose deposition dosimetric characteristics. For optimal efficacy, cancer therapies, including PT, must elicit a robust anti-tumor response by effector and cytotoxic immune cells in the tumor microenvironment (TME). While tumor-derived exosomes contribute to immune cell suppression in the TME, information on the effects of PT on exosomes and anti-tumor immune responses in HNSCC is not known. In this study, we generated primary HNSCC cells from tumors resected from HNSCC patients, irradiated them with 5 Gy PT or XRT, and isolated exosomes from cell culture supernatants. HNSCC cells exposed to PT produced 75% fewer exosomes than XRT- and non-irradiated HNSCC cells. This effect persisted in proton-irradiated cells for up to five days. Furthermore, we observed that exosomes from proton-irradiated cells were identical in morphology and immunosuppressive effects (suppression of IFN-γ release by peripheral blood mononuclear cells) to those of photon-irradiated cells. Our results suggest that PT limits the suppressive effect of exosomes on cancer immune surveillance by reducing the production of exosomes that can inhibit immune cell function.

Reconstruction of thermoacoustic emission sources induced by proton irradiation using numerical time reversal.

Objective.Mapping of dose delivery in proton beam therapy can potentially be performed by analyzing thermoacoustic emissions measured by ultrasound arrays. Here, a method is derived and demonstrated for spatial mapping of thermoacoustic sources using numerical time reversal, simulating re-transmission of measured emissions into the medium.Approach.Spatial distributions of thermoacoustic emission sources are shown to be approximated by the analytic-signal form of the time-reversed acoustic field, evaluated at the time of the initial proton pulse. Given calibration of the array sensitivity and knowledge of tissue properties, this approach approximately reconstructs the acoustic source amplitude, equal to the product of the time derivative of the radiation dose rate, mass density, and Grüneisen parameter. This approach was implemented using two models for acoustic fields of the array elements, one modeling elements as line sources and the other as rectangular radiators. Thermoacoustic source reconstructions employed previously reported measurements of emissions from proton energy deposition in tissue-mimicking phantoms. For a phantom incorporating a bone layer, reconstructions accounted for the higher sound speed in bone. Dependence of reconstruction quality on array aperture size and signal-to-noise ratio was consistent with previous acoustic simulation studies.Main results.Thermoacoustic source distributions were successfully reconstructed from acoustic emissions measured by a linear ultrasound array. Spatial resolution of reconstructions was significantly improved in the azimuthal (array) direction by incorporation of array element diffraction. Source localization agreed well with Monte Carlo simulations of energy deposition, and was improved by incorporating effects of inhomogeneous sound speed.Significance.The presented numerical time reversal approach reconstructs thermoacoustic sources from proton beam radiation, based on straightforward processing of acoustic emissions measured by ultrasound arrays. This approach may be useful for ranging and dosimetry of clinical proton beams, if acoustic emissions of sufficient amplitude and bandwidth can be generated by therapeutic proton sources.

AAPM Report 373: The content, structure, and value of the Professional Doctorate in Medical Physics (DMP).

The Professional Doctorate in Medical Physics (DMP) was originally conceived as a solution to the shortage of medical physics residency training positions. While this shortage has now been largely satisfied through conventional residency training positions, the DMP has expanded to multiple institutions and grown into an educational pathway that provides specialized clinical training and extends well beyond the creation of additional training spots. As such, it is important to reevaluate the purpose and the value of the DMP. Additionally, it is important to outline the defining characteristics of the DMP to assure that all existing and future programs provide this anticipated value. Since the formation and subsequent accreditation of the first DMP program in 2009-2010, four additional programs have been created and accredited. However, no guidelines have yet been recommended by the American Association of Physicists in Medicine. CAMPEP accreditation of these programs has thus far been based only on the respective graduate and residency program standards. This allows the development and operation of DMP programs which contain only the requisite Master of Science (MS) coursework and a 2-year clinical training program. Since the MS plus 2-year residency pathway already exists, this form of DMP does not provide added value, and one may question why this existing pathway should be considered a doctorate. Not only do we, as a profession, need to outline the defining characteristics of the DMP, we need to carefully evaluate the potential advantages and disadvantages of this pathway within our education and training infrastructure. The aims of this report from the Working Group on the Professional Doctorate Degree for Medical Physicists (WGPDMP) are to (1) describe the current state of the DMP within the profession, (2) make recommendations on the structure and content of the DMP for existing and new DMP programs, and (3) evaluate the value of the DMP to the profession of medical physics.

Target definition for malignant gliomas: no difference in radiation treatment volumes between 1.5T and 3T magnetic resonance imaging.

PURPOSE: Currently, most high-grade glioma patients undergo a 1.5T brain magnetic resonance (MR) for radiation treatment planning. We hypothesized that 3T MR imaging (MRI) scanning is superior to 1.5T due to higher signal-to-noise ratio (SNR), and thus will result in more accurate quantification of tumor volumes. The purpose of this prospective study was to determine differences in radiation planning volumes for high-grade gliomas when scanned on 3T MR versus 1.5T MR. METHODS AND MATERIALS: In this prospective controlled trial, 23 patients with high-grade gliomas underwent brain MRI scanning in both 1.5T and 3T field strengths within a 24-hour period; no steroids or treatment changes were made in-between scans. After 3 investigators contoured the T2 fast low-angle inversion recovery (FLAIR) abnormality (gross tumor volumes or [GTV]) for all patients, clinical target volume (CTV) and planning treatment volumes (PTV) were defined. Calculations by an independent investigator included volumes, standard deviations, SNRs, and contrast-to-noise ratios (CNRs); statistical analysis was performed on raw data. RESULTS: Planning treatment volume ratios (3T:1.5T) for each investigator were 0.95 ± 0.12 (range, 0.64-1.10), 0.98 ± 0.10 (range, 0.64-1.16), and 0.99 ± 0.06 (range, 0.86-1.13). By paired 2-tailed t test, these volumes were not statistically different (P = .051), although there is a trend to 3T producing smaller volumes than 1.5T. Dice similarity coefficients were 0.90 ± 0.05, 0.90 ± 0.06, and 0.91 ± 0.05 for the investigators. CONCLUSIONS: Planning target volumes for high-grade gliomas were similar at 3T and 1.5T MR using our standard imaging protocols. However, in some patients, the 3T MR may reveal substantially smaller tumor volume due to inferior conspicuity of the lesion. These findings imply that while overall the radiation target volumes are comparable, there are differences in CNR and SNR that lead to differences in individual patients. The 1.5T may be better for gaining conspicuity of the tumor.

Measurement of low-energy backscatter factors using GAFCHROMIC film and OSLDs.

Some of the lowest voltages used in radiotherapy are termed Grenz and superficial X-rays of ~ 20 and ~ 100 kVp, respectively. Dosimetrically, the surface doses from these beams are calculated with the use of a free in-air air kerma measurement combined with a backscatter factor and the appropriate ratio of mass energy absorption coefficients from the measurement material to water. Alternative tools to the standard ion chamber for measuring the BSF are GAFCHROMIC EBT2 film and optically stimulated luminescent dosimeter (OSLD) crystals made from Al2O3. The scope of this project included making three different backscatter measurements with an Xstrahl-D3100 X-ray unit on the Grenz ray and superficial settings. These measurements were with OSLDs, GAFCHROMIC EBT2 film, and a PTW ionization chamber. The varied measurement methods allowed for intercomparison to determine the accuracy of the results. The ion chamber measurement was the least accurate, as expected from previous experimental findings. GAFCHROMIC EBT2 film proved to be a useful tool which gave reasonable results, and Landauer OSLDs showed good results for smaller field sizes and an increasing overresponse with larger fields. The specific backscatter factors for this machine demonstrated values about 5% higher than the universal values suggested by the AAPM and IPEMB codes of practice for the 100 kVp setting. The 20 kvp measured data from both techniques showed general agreement with those found in the BJR Supplement No. 10, indicating that this unit's Grenz ray spectrum is similar to those used in previous experimental work.

Analysis of peripheral doses for base of tongue treatment by linear accelerator and helical TomoTherapy IMRT.

The purpose of this study was to compare the peripheral doses to various organs from a typical head and neck intensity-modulated radiation therapy (IMRT) treatment delivered by linear accelerator (linac) and helical TomoTherapy. Multiple human CT data sets were used to segment critical structures and organs at risk, fused and adjusted to an anthropomorphic phantom. Eighteen contours were designated for thermoluminescent dosimeter (TLD) placement. Following the RTOG IMRT Protocol 0522, treatment of the primary tumor and involved nodes (PTV70) and subclinical disease sites (PTV56) was planned utilizing IMRT to 70Gy and 56 Gy. Clinically acceptable treatment plans were produced for linac and TomoTherapy treatments. TLDs were placed and each treatment plan was delivered to the anthropomorphic phantom four times. Within 2.5 cm (one helical TomoTherapy field width) superior and inferior to the field edges, normal tissue doses were on average 45% lower using linear accelerator. Beyond 2.5 cm, the helical TomoTherapy normal tissue dose was an average of 52% lower. The majority of points proved to be statistically different using the Student's t-test with p > 0.05. Using one method of calculation, probability of a secondary malignancy was 5.88% for the linear accelerator and 4.08% for helical TomoTherapy. Helical TomoTherapy delivers more dose than a linac immediately above and below the treatment field, contributing to the higher peripheral doses adjacent to the field. At distances beyond one field width (where leakage is dominant), helical TomoTherapy doses are lower than linear accelerator doses.

Irradiated volume as a predictor of brain radionecrosis after linear accelerator stereotactic radiosurgery.

PURPOSE: To investigate the correlation between volume of brain irradiated by stereotactic radiosurgery (SRS) and the incidence of symptomatic and asymptomatic brain radionecrosis (RN). METHODS AND MATERIALS: A retrospective analysis was performed of patients treated with single-fraction SRS for brain metastases at our institution. Patients with at least 6-month imaging follow-up were included and diagnosed with RN according to a combination of criteria, including appearance on serial imaging and histology. Univariate and multivariate analyses were performed to determine the predictive value of multiple variables, including volume of brain receiving a specific dose (V8 Gy-V18 Gy). RESULTS: Sixty-three patients were reviewed, with a total of 173 lesions. Most patients (63%) had received previous whole-brain irradiation. Mean prescribed SRS dose was 18 Gy. Symptomatic RN was observed in 10% and asymptomatic RN in 4% of lesions treated. Multivariate regression analysis showed V8 Gy-V16 Gy to be most predictive of symptomatic RN (p < 0.0001). Threshold volumes for significant rise in RN rates occurred between the 75th and 90th percentiles, with a midpoint volume of 10.45 cm(3) for V10 Gy and 7.85 cm(3) for V12 Gy. CONCLUSIONS: Analysis of patient and treatment variables revealed V8 Gy-V16 Gy to be the best predictors for RN using linear accelerator-based single-fraction SRS for brain metastases. We propose that patients with V10 Gy >10.5 cm(3) or V12 Gy >7.9 cm(3) be considered for hypofractionated rather than single-fraction treatment, to minimize the risk of symptomatic RN.

A Monte Carlo brachytherapy study for dose distribution prediction in an inhomogeneous medium.

The purpose of this study was to present a theoretical analysis of how the presence of bone in interstitial brachytherapy affects dose rate distributions. This study was carried out using a Monte Carlo simulation of the dose distribution in homogeneous medium for 3 commonly used brachytherapy seeds. The 3 seeds investigated in this study are iridium-192 (192Ir) iodine-125 (125I), and palladium-103 (103Pd). The computer code was validated by comparing the specific dose rate (Lambda), the radial dose function g(r), and anisotropy function F(r,theta;) for all 3 seeds with the AAPM TG-43 dosimetry formalism and current literature. The 192Ir seed resulted in a dose rate of 1.115 +/- 0.001 cGy-hr(-1)-U(-1), the 125I seed resulted in a dose rate of 0.965 +/- 0.006 cGy/h(-1)/U(-1), and the 103Pd seed resulted in a dose rate of 0.671 +/- 0.002 cGy/h(-1)/U(-1). The results for all 3 seeds are in good agreement with the AAPM TG-43 and current literature. The validated computer code was then applied to a simple inhomogeneous model to determine the effect bone has on dose distribution from an interstitial implant. The inhomogeneous model showed a decrease in dose rate of 2% for the 192Ir, an increase in dose rate of 84% for 125I, and an increase in dose rate of 83% for the 103Pd at the surface of the bone nearest to the source.