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.

Varied Photon Radiation Sources Produce Differences in Cellular Response.

In vitro studies allow evaluation of normal or cancer cell responses to radiation, either alone or in combination with agents used to modify these biological responses. Ionizing radiation can be produced by a variety of particles and sources, with varying energy spectra, interaction probabilities, linear energy transfer, dose uniformity, dose rates, and delivery methods. Multiple radiation sources have been used to irradiate cells in the published literature. However, the equivalence of response in cell culture models across radiation sources has not been rigorously established. Moreover, current reporting of radiation source parameters lacks consistency and rigor which may impact the reproducibility of pre-clinical data between laboratories. Relevant choices of radiation source are also of high importance due to growing interest in comparing photon versus particle radiation effect on biological responses. Therefore, this study robustly evaluates the cellular response (cell survival, apoptosis, and DNA damage) of three distinct cell lines using four unique photon generating radiation sources. We hypothesize there may be subtle differences across the radiation sources, without an appreciable difference in cellular response. The four photon irradiation energies investigated, 662 keV, 100 kVp, 220 kVp, 6 MV, did produce subtle differences in DNA damage and cell survival when treating three distinct tumor cell lines. These variations in cellular response emphasize the need to carefully consider irradiation source, energy, and dose rate depending on study goal and endpoint.

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.

Evaluation of a conventionally shielded proton treatment room for FLASH radiotherapy.

PURPOSE: FLASH radiotherapy (FLASH-RT) is the potential for a major breakthrough in cancer care, as preclinical results have shown significantly reduced toxicities to healthy tissues while maintaining excellent tumor control. However, FLASH conditions were not considered in the current proton facilities' shielding designs. The purpose of this study is to validate the adequacy of conventionally shielded proton rooms used for FLASH-RT. METHODS: Clinical FLASH irradiations typically take place in a few 100 ms, orders of magnitude shorter than the response time of the wide-energy neutron detector (WENDI-II). The nozzle beam current (representing the dose rate) dependence of the WENDI-II detector response was empirically determined to stabilize with a beam current of ≤10 nA at the measurement point with the highest dose rate. A large, predefined proton transmission FLASH plan (250 MeV, 7 × 20 cm2 , 8 Gy at isocenter) was commissioned as part of a FLASH clinical trial. For purpose of this study, that field was adjusted from 250 to 244 MeV, allowing a lower beam current of 10 nA to provide reliable detector response. Radiation surveys were performed for the proton beams with/without extra beam stopper (30 × 30 × 40-cm3 solid water slabs) at 0°, 90°, 180°, and 270° gantry angles. RESULTS: Ambient doses were recorded at seven different locations. A 170-nA beam current, commonly used for clinical FLASH plans, was chosen to normalize the average ambient dose rate to FLASH conditions. Assuming 200-Gy/h workload (25 FLASH beams, 8 Gy/beam), annual occupational dose at controlled areas was calculated. For all gantry angles, ≤0.4 mSv/year is expected at treatment room door. The highest ambient dose, 2.46 mSv/year, ∼5% of the maximum annual permissible occupational dose, was identified at the isocenter of the adjacent treatment room with 90° gantry. CONCLUSION: These survey results indicate that our conventionally shielded proton rotating gantry rooms result in acceptable occupational and public doses when the transmission FLASH beams delivered at four cardinal gantry angles based on 200-Gy/h workload assumption. These findings support that FLASH clinical trials in our conventionally shielded proton facilities can be safely implemented.

Chromatin structure predicts survival in glioma patients.

The pathological changes in epigenetics and gene regulation that accompany the progression of low-grade to high-grade gliomas are under-studied. The authors use a large set of paired atac-seq and RNA-seq data from surgically resected glioma specimens to infer gene regulatory relationships in glioma. Thirty-eight glioma patient samples underwent atac-seq sequencing and 16 samples underwent additional RNA-seq analysis. Using an atac-seq/RNA-seq correlation matrix, atac-seq peaks were paired with genes based on high correlation values (|r2| > 0.6). Samples clustered by IDH1 status but not by grade. Surprisingly there was a trend for IDH1 mutant samples to have more peaks. The majority of peaks are positively correlated with survival and positively correlated with gene expression. Constructing a model of the top six atac-seq peaks created a highly accurate survival prediction model (r2 = 0.68). Four of these peaks were still significant after controlling for age, grade, pathology, IDH1 status and gender. Grade II, III, and IV (primary) samples have similar transcription factors and gene modules. However, grade IV (recurrent) samples have strikingly few peaks. Patient-derived glioma cultures showed decreased peak counts following radiation indicating that this may be radiation-induced. This study supports the notion that IDH1 mutant and IDH1 wildtype gliomas have different epigenetic landscapes and that accessible chromatin sites mapped by atac-seq peaks tend to be positively correlated with expression. The data in this study leads to a new model of treatment response wherein glioma cells respond to radiation therapy by closing open regions of DNA.

Normal tissue exposure and second malignancy risk in vertebral-body-sparing craniospinal irradiation.

The purpose of this study was to compare dose to anterior organs at risk (OARs) and quantify the risk of developing secondary malignancy (SMN) in pediatric patients treated with vertebral-body-sparing (VBS) vs vertebral body (VB) pencil beam scanning proton craniospinal irradiation (CSI). Comparative plans of VBS and VB CSI were created for 10 previously treated patients. Dose-volume histograms were used to evaluate dose to OARs. Absolute excess risk of SMN was calculated according to the organ-specific, radiation-induced cancer incidence based on the organ equivalent dose. OAR dosimetric parameters and absolute excess risk of SMN were compared for VBS and VB plans using the Kruskal-Wallis H test (α = 0.05). VBS CSI leads to significantly lower radiation dose to the heart, esophagus, kidney, liver and bowel. Excluding the vertebral body also significantly decreases the absolute excess risk of SMN for liver, esophagus and bowel. For these reasons, implementation of VBS pencil beam scanning proton CSI should be considered.

Radio-Fluorogenic Gel Dosimetry with Coumarin.

Gel dosimeters are attractive detectors for radiation therapy, with properties similar to biological tissue and the potential to visualize volumetric dose distributions. Radio-fluorogenesis is the yield of fluorescent chemical products in response to energy deposition from ionizing radiation. This report shares the development of a novel radio-fluorogenic gel (RFG) dosimeter, gelatin infused with coumarin-3-carboxlyic acid (C3CA), for the quantification of imparted energy. Aqueous solutions exposed to ionizing radiation result in the production of hydroxyl free radicals through water radiolysis. Interactions between hydroxyl free radicals and coumarin-3-carboxylic acid produce a fluorescent product. 7-hydroxy-coumarin-3-carboxylic acid has a blue (445 nm) emission following ultra-violet (UV) to near UV (365⁻405 nm) excitation. Effects of C3CA concentration and pH buffers were investigated. The response of the RFG was explored with respect to strength, type, and exposure rate of high-energy radiation. Results show a linear dose response relationship independent of energy and type, with a dose-rate dependency. This report demonstrates increased photo-yield with high pH and the utility of gelatin-RFG for phantom studies of radiation dosimetry.

Dose-volume metrics and their relation to memory performance in pediatric brain tumor patients: A preliminary study.

BACKGROUND: Advances in radiation treatment (RT), specifically volumetric planning with detailed dose and volumetric data for specific brain structures, have provided new opportunities to study neurobehavioral outcomes of RT in children treated for brain tumor. The present study examined the relationship between biophysical and physical dose metrics and neurocognitive ability, namely learning and memory, 2 years post-RT in pediatric brain tumor patients. PROCEDURE: The sample consisted of 26 pediatric patients with brain tumor, 14 of whom completed neuropsychological evaluations on average 24 months post-RT. Prescribed dose and dose-volume metrics for specific brain regions were calculated including physical metrics (i.e., mean dose and maximum dose) and biophysical metrics (i.e., integral biological effective dose and generalized equivalent uniform dose). We examined the associations between dose-volume metrics (whole brain, right and left hippocampus), and performance on measures of learning and memory (Children's Memory Scale). RESULTS: Biophysical dose metrics were highly correlated with the physical metric of mean dose but not with prescribed dose. Biophysical metrics and mean dose, but not prescribed dose, correlated with measures of learning and memory. CONCLUSIONS: These preliminary findings call into question the value of prescribed dose for characterizing treatment intensity; they also suggest that biophysical dose has only a limited advantage compared to physical dose when calculated for specific regions of the brain. We discuss the implications of the findings for evaluating and understanding the relation between RT and neurocognitive functioning.

Evolution of brachytherapy treatment planning to deterministic radiation transport for calculation of cardiac dose.

Brachytherapy was among the first methods of radiotherapy and has steadily continued to evolve. Here we present a brief review of the progression of dose calculation methods in brachytherapy to the current state-of-the art computerized methods for heterogeneity correction. We further review the origin and development of the BrachyVision (Varian Medical Systems, Inc., Palo Alto, CA) treatment planning system and evaluate dosimetric results from 12 patients implanted with the strut-assisted volumetric implant (SAVI) applicator (Cianna Medical, Aliso Viejo, CA) for accelerated partial breast irradiation (APBI). Dosimetric results from plans calculated using homogenous and heterogeneous algorithms have been compared to investigate the impact of heterogeneity corrections. Our study showed large percent difference between mean cardiac doses 11.8 ± 6.2% (p = 0.0007) calculated with and without heterogeneity corrections. Our findings are consistent with those of others, indicating an overestimation of the distal dose to organs-at-risk by traditional methods, especially at interfaces between air and tissue.

Radiation Dose to the Breast by 64-slice CT: Effects of Scanner Model and Study Protocol.

RATIONALE AND OBJECTIVES: This work aimed to study the effects of scanner model and study protocol on radiation dose received by breast tissues from 64-slice computed tomography (CT) studies. MATERIALS AND METHODS: Four scanner models and three study protocols were used in scanning an anthropomorphic phantom with breast modules. Each protocol follows recommendations or guidelines from the American Association of Physicists in Medicine and the American College of Radiology. Twenty thermoluminescent dosimeters were placed inside the breast modules to measure breast tissue doses. Both the absolute and the normalized breast tissue doses were analyzed. RESULTS: The mean glandular doses of a lung cancer screening CT, a chest/abdomen/pelvis CT, and a virtual colonoscopy CT are equivalent to less than 1, 5-7, and 1-3 two-view digital mammograms, respectively, for a standard-sized patient. The normalized breast dose differs significantly (P < 0.01) between lung cancer screening CT and chest/abdomen/pelvis CT; however, it shows less than ±10% variation among scanner models for the same protocol. In virtual colonoscopy CT, breast tissue dose decreases with the distance between local tissues to the edge of the x-ray field, although the decreasing trend varies for different scanner models and protocol settings. CONCLUSIONS: When breasts are entirely included in the primary x-ray field, breast dose by 64-slice CT is mainly protocol dependent, with the normalized breast dose about 15% lower for protocols with modulated mA than for those with constant mA; when breasts are only partially included in the primary beam field, breast dose by 64-slice CT is dependent on both the scanner model and the protocol settings.

Iodine-125 seed migration within brain parenchyma after brachytherapy for brain metastasis: case report.

This case report documents the migration of 3 iodine-125 (125I) seeds from the tumor resection cavity into brain parenchyma over a 7-year period. A 66-year-old woman had a history of metastatic ovarian carcinoma, nickel allergy, and reaction to a titanium hip implant that required reoperation for hardware removal. In this unique case of parenchymal migration, the seed paths seemed to follow white matter tracts, traveling between 18.5 and 35.5 mm from the initial implant site. The patient's initial neurological decline, which was thought to be related to radiation necrosis, appeared to stabilize with medical therapy. She subsequently developed progressive right hemispheric edema that resulted in neurological deterioration and death. Considering her previous reactions to nickel and titanium, the authors now speculate that her later clinical course reflected an allergic reaction to the titanium casing of the 125I seeds. Containing a trace amount of nickel, 125I seeds can elicit a delayed hypersensitivity reaction in patients with a history of nickel dermatitis. Preoperative patch testing is recommended in these patients, and 125I seed implantation should be avoided in those who test positive.

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.

A comparison of HDR near source dosimetry using a treatment planning system, Monte Carlo simulation, and radiochromic film.

This study aimed to investigate the high-dose rate Iridium-192 brachytherapy, including near source dosimetry, of a catheter-based applicator from 0.5mm to 1cm along the transverse axis. Radiochromic film and Monte Carlo (MC) simulation were used to generate absolute dose for the catheter-based applicator. Results from radiochromic film and MC simulation were compared directly to the treatment planning system (TPS) based on the American Association of Physicists in Medicine Updated Task Group 43 (TG-43U1) dose calculation formalism. The difference between dose measured using radiochromic film along the transverse plane at 0.5mm from the surface and the predicted dose by the TPS was 24%±13%. The dose difference between the MC simulation along the transverse plane at 0.5mm from the surface and the predicted dose by the TPS was 22.1%±3%. For distances from 1.5mm to 1cm from the surface, radiochromic film and MC simulation agreed with TPS within an uncertainty of 3%. The TPS under-predicts the dose at the surface of the applicator, i.e., 0.5mm from the catheter surface, as compared to the measured and MC simulation predicted dose. MC simulation results demonstrated that 15% of this error is due to neglecting the beta particles and discrete electrons emanating from the sources and not considered by the TPS, and 7% of the difference was due to the photon alone, potentially due to the differences in MC dose modeling, photon spectrum, scoring techniques, and effect of the presence of the catheter and the air gap. Beyond 1mm from the surface, the TPS dose algorithm agrees with the experimental and MC data within 3%.

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.

Effect of breast volume on treatment reproducibility on a tomotherapy unit in the treatment of breast cancer.

PURPOSE: To determine whether the volume of a patient's breast is correlated with reliable daily setup in treatment of breast cancer with a helical tomotherapy treatment unit. METHODS AND MATERIALS: Thirty-six consecutive patients with breast cancer were treated on a helical tomotherapy unit. During simulation, kilovoltage CT images were obtained for treatment planning. These were fused with daily megavoltage CT scans, and after setup based on skin marks and laser alignment the necessary shifts were carried out. The magnitude of daily shifts (in millimeters) was retrospectively obtained from the daily image fusions, and the breast volume was obtained from the treatment plan. A total of 873 fusion scans were reviewed. Random error for absolute and directional daily shifts was evaluated for correlation to volume. Variation over time was also evaluated. RESULTS: Mean (SD) random shift for all patients in the lateral, longitudinal, and vertical directions was 2.7 (2.0), 3.1 (1.5), and 3.2 (2.6) mm, respectively. Mean (SD) absolute distance shifted was 6.0 (3.5) mm. There was no significant correlation between mean absolute or mean directional daily shift and breast volume (0.08, 0.08, 0.22, and 0.07, respectively). There was no correlation between setup variation and time. CONCLUSIONS: In this cohort, there was no correlation between breast volume and degree of daily shift. There was no correlation between time course and setup variation. Therefore, setup variation does not improve or degrade with repeated treatment setups.

Assessment of aggressiveness of prostate cancer: correlation of apparent diffusion coefficient with histologic grade after radical prostatectomy.

OBJECTIVE: The purpose of this article is to evaluate the relationship between apparent diffusion coefficient (ADC) values, tumor volume, and total Gleason grade in patients with prostate cancer before radical prostatectomy. MATERIALS AND METHODS: A total of 110 patients with prostate cancer who had undergone endorectal prostate MRI at 1.5 T before radical prostatectomy were included. ADC values were derived by drawing a region of interest on the histologically confirmed tumors. Tumor volume was obtained by manual segmentation on T2-weighted images (T2WIs) and ADC maps. The relationship between the ADC value or tumor volume and the Gleason grade was assessed by using multivariate mixed linear and effect models. Multivariate analysis was performed to evaluate the accuracy of ADC and tumor volume in determining the aggressiveness of prostate cancer. RESULTS: A total of 197 tumors were studied; 128 (65%) tumors were found in the peripheral zone and 69 (35%) were found in the central gland. The ADC value was found to be negatively correlated with the Gleason grade (r = -0.39 for peripheral zone cancer). Higher ADC values were found to be associated with lower Gleason grades in the peripheral zone prostate cancers. No association was found in the central zone prostate cancers. Both ADC values and tumor volumes were found to significantly predict tumor aggressiveness, specifically in the peripheral zone (area under the curve, 0.78). CONCLUSION: ADC values were found to be negatively correlated with the postsurgical Gleason grade in patients with prostate cancer. Our results show that ADC values might help to predict prostate cancer, especially for tumors in the peripheral zone. Given the substantial overlap in the ADC values, the addition of other MR parameters, such as volumetry, and technical improvements in diffusion-weighted imaging might improve accuracy in the stratification of patients.

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.