Faculty Bibliography

PURPOSE/OBJECTIVE:Stereotactic radiosurgery (SRS) has become an important modality in the treatment of brain metastases. The purpose of this study is to investigate the potential of radiomic features from planning magnetic resonance (MR) images and dose maps to predict local failure after SRS for brain metastases. MATERIALS/METHODS/METHODS:Twenty-eight patients who received Gamma Knife (GK) radiosurgery for brain metastases were retrospectively reviewed in this IRB-approved study. 179 irradiated tumors included 42 that locally failed within one-year follow-up. Using SRS tumor volumes, radiomic features were calculated on T1-weighted contrast-enhanced MR images acquired for treatment planning and planned dose maps. 125 radiomic features regarding tumor shape, dose distribution, MR intensities and textures were extracted for each tumor. Logistic regression with automatic feature selection was built to predict tumor progression from local control after SRS. Feature selection and model evaluation using receiver operating characteristic (ROC) curves were performed in a nested cross validation (CV) scheme. The associations between selected radiomic features and treatment outcomes were statistically assessed by univariate analysis. RESULTS:The logistic model with feature selection achieved ROC AUC of 0.82 ± 0.09 on 5-fold CV, providing 83% sensitivity and 70% specificity for predicting local failure. A total of 10 radiomic features including 1 shape feature, 6 MR images and 3 dose distribution features were selected. These features were significantly associated with treatment outcomes (p < 0.05). The model was validated on independent holdout data with an AUC of 0.78. CONCLUSIONS:Radiomic features from planning MR images and dose maps provided prognostic information in SRS for brain metastases. A model built on the radiomic features shows promise for early prediction of tumor local failure after treatment, potentially aiding in personalized care for brain metastases.

Purpose: This study investigated the accuracy of two dose calculation algorithms (AAA version 15.6.05 and AcurosXB (AXB) version 15.6.05) in lung, fat, and bone regions of a lung phantom using 2D Gamma analysis.
Method(s): A commercial thorax phantom (CIRS) was marked and CT simulated with 1.5 mm slice thickness then planned in Eclipse v15.6 (Varian) using an oblique 3x3 cm field traversing soft tissue, lung, and spine regions. Dose was calculated using AAA and AXB algorithms at 1.0 mm resolution for four different beam energies with the same number of monitor units: 6X, 6X-FFF, 10X and 10X-FFF. Each field was separately delivered to the phantom with Gafchromic EBT3 film placed in the axial plane through the beam isocenter. Film alignment was performed using built-in phantom pins as registration marks. Gamma analysis was performed in SNC Patient 8.2 (Sun Nuclear Corp.) software using distanceto- agreement (DTA) to compare AAA and AXB calculated doses against one another and against measured dose.
Result(s): Considerable dosimetric differences occurred between AAA and AXB especially at tissue interfaces and in the beam penumbra within the lung. About 10% and 30% of analyzed points had dose differences larger than 3% for 6X and 10X, respectively. The differences were a few percentages smaller for non-flattened beams. In comparison of calculation with measurement, the 3%/2mm-DTA passing rate for AAA was 3.7% higher than AXB for the 6X beam (3.9% for 6X-FFF), but -15.9% lower for 10X (- 24.9% for 10X-FFF).
Conclusion(s): Dose calculation algorithm accuracy was assessed in a heterogeneous thorax phantom using 2D gamma analysis and Gafchromic film. Large differences in the passing rate, especially at 10X(FFF), suggest to verify that clinical plan evaluation metrics such as coverage and dose constrains are not compromised by the choice of dose calculation algorithm

Purpose: Modern linear accelerators (LINACs) are equipped with kV-imaging systems for 2D-images and 3D-cone-beam CT (CBCT). The delivered single kV-CBCT-dose is small compared to the treatment dose but can add up to a cumulative dose of 1-3% for multi-fraction courses according to TG180. Thus, TG142 recommends an annual assessment of the imaging dose. The purpose of this project was to review the current practice, compare approaches suggested in recent literature and standardize annual kV-CBCT dose measurements.
Method(s): Current institutional practice is to measure the CBCT dose with the 10cmlong RaySafe X2 pencil-ion-chamber inserted in the center position of a CIRS lung phantom. We introduced the PMMA-CTDI phantom in a satellite-location for all measurements. Dose was measured at 3/6/9/12 o'clock and center positions of a 32cm-wide CTDI phantom to determine max dose heterogeneity for a half-trajectory imaging protocol and at the 12 o'clock and center position of either the head or abdomen phantom for 11 protocols ranging from 80kVp/100mAs to 140kVp/1688mAs using the Raysafe X2, the Standard Imaging A101 pencil-ion-chamber, and the A12 Farmer-ion-chamber. Measurements were repeated with decreased kV-tube-collimator opening as suggested by Varian.
Result(s): The dose discrepancy due to chamber position was largest between the 6 and 3 o'clock positions (10%) and the average was close to the peripheral measurement at 12 o'clock. All three detectors showed a linear dependency. Reducing CBCT beam collimation increased measurement complexity with only minimally improved agreement between measured and displayed CTDIw values. The standard deviation for dose measurements at different machines reduced from 22%/12% for the lung phantom to 7%/3% (max/mean) for the CTDI phantom.
Conclusion(s): Dose measurements at 12 o'clock and center position of CTDI-phantom have been defined as our new standard using un-modified treatment imaging protocols; conversion factors for center-only or lung-phantom measurements have been provided

PURPOSE/OBJECTIVE:Dosimetric and clinical predictors of radiation-induced optic nerve/chiasm neuropathy (RION) after single-fraction stereotactic radiosurgery (SRS) or hypofractionated (2-5 fractions) radiosurgery (fSRS) were analyzed from pooled data that were extracted from published reports (PubMed indexed from 1990 to June 2015). This study was undertaken as part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, investigating normal tissue complication probability (NTCP) after hypofractionated radiation. METHODS AND MATERIALS/METHODS:Eligible studies described dose delivered to optic nerve/chiasm and provided crude or actuarial toxicity risks, with visual endpoints (ie, loss of visual acuity, alterations in visual fields, and/or blindness/complete vision loss). Studies of patients with optic nerve sheath tumors, optic nerve gliomas, or ocular/uveal melanoma were excluded to obviate direct tumor effects on visual outcomes, as were studies not specifying causes of vision loss (ie, tumor progression vs RION). RESULTS:Thirty-four studies (1578 patients) were analyzed. Histologies included pituitary adenoma, cavernous sinus meningioma, craniopharyngioma, and malignant skull base tumors. Prior resection (76% of patients) did not correlate with RION risk (P = .66). Prior irradiation (6% of patients) was associated with a crude 10-fold increased RION risk versus no prior radiation therapy. In patients with no prior radiation therapy receiving SRS/fSRS in 1-5 fractions, optic apparatus maximum point doses resulting in <1% RION risks include 12 Gy in 1 fraction (which is greater than our recommendation of 10 Gy in 1 fraction), 20 Gy in 3 fractions, and 25 Gy in 5 fractions. Omitting multi-fraction data (and thereby eliminating uncertainties associated with dose conversions), a single-fraction dose of 10 Gy was associated with a 1% RION risk. Insufficient details precluded modeling of NTCP risks after prior radiation therapy. CONCLUSIONS:Optic apparatus NTCP and tolerance doses after single- and multi-fraction stereotactic radiosurgery are presented. Additional standardized dosimetric and toxicity reporting is needed to facilitate future pooled analyses and better define RION NTCP after SRS/fSRS.

PURPOSE/OBJECTIVE:As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy investigating normal tissue complication probability (NTCP) after hypofractionated radiation therapy, data from published reports (PubMed indexed 1995-2018) were pooled to identify dosimetric and clinical predictors of radiation-induced brain toxicity after single-fraction stereotactic radiosurgery (SRS) or fractionated stereotactic radiosurgery (fSRS). METHODS AND MATERIALS/METHODS:Eligible studies provided NTCPs for the endpoints of radionecrosis, edema, or symptoms after cranial SRS/fSRS and quantitative dose-volume metrics. Studies of patients with only glioma, meningioma, vestibular schwannoma, or brainstem targets were excluded. The data summary and analyses focused on arteriovenous malformations (AVM) and brain metastases. RESULTS:were associated with <10% risk of radionecrosis. CONCLUSIONS:The risk of radionecrosis after SRS and fSRS can be modeled as a function of dose and volume treated. The use of fSRS appears to reduce risks of radionecrosis for larger treatment volumes relative to SRS. More standardized dosimetric and toxicity reporting is needed to facilitate future pooled analyses that can refine predictive models of brain toxicity risks.

PURPOSE/OBJECTIVE:We sought to investigate the tumor control probability (TCP) of vestibular schwannomas after single-fraction stereotactic radiosurgery (SRS) or hypofractionated SRS over 2 to 5 fractions (fSRS). METHODS AND MATERIALS/METHODS:Studies (PubMed indexed from 1993-2017) were eligible for data extraction if they contained dosimetric details of SRS/fSRS correlated with local tumor control. The rate of tumor control at 5 years (or at 3 years if 5-year data were not available) were collated. Poisson modeling estimated the TCP per equivalent dose in 2 Gy per fraction (EQD2) and in 1, 3, and 5 fractions. RESULTS:Data were extracted from 35 publications containing a total of 5162 patients. TCP modeling was limited by the absence of analyzable data of <11 Gy in a single-fraction, variability in definition of "tumor control," and by lack of significant increase in TCP for doses >12 Gy. Using linear-quadratic-based dose conversion, the 3- to 5-year TCP was estimated at 95% at an EQD2 of 25 Gy, corresponding to 1-, 3-, and 5-fraction doses of 13.8 Gy, 19.2 Gy, and 21.5 Gy, respectively. Single-fraction doses of 10 Gy, 11 Gy, 12 Gy, and 13 Gy predicted a TCP of 85.0%, 88.4%, 91.2%, and 93.5%, respectively. For fSRS, 18 Gy in 3 fractions (EQD2 of 23.0 Gy) and 25 Gy in 5 fractions (EQD2 of 30.2 Gy) corresponded to TCP of 93.6% and 97.2%. Overall, the quality of dosimetric reporting was poor; recommended reporting guidelines are presented. CONCLUSIONS:With current typical SRS doses of 12 Gy in 1 fraction, 18 Gy in 3 fractions, and 25 Gy in 5 fractions, 3- to 5-year TCP exceeds 91%. To improve pooled data analyses to optimize treatment outcomes for patients with vestibular schwannoma, future reports of SRS should include complete dosimetric details with well-defined tumor control and toxicity endpoints.

PURPOSE/OBJECTIVE:We sought to investigate the tumor control probability (TCP) of spinal metastases treated with stereotactic body radiation therapy (SBRT) in 1 to 5 fractions. METHODS AND MATERIALS/METHODS:PubMed-indexed articles from 1995 to 2018 were eligible for data extraction if they contained SBRT dosimetric details correlated with actuarial 2-year local tumor control rates. Logistic dose-response models of collected data were compared in terms of physical dose and 3-fraction equivalent dose. RESULTS:Data were extracted from 24 articles with 2619 spinal metastases. Physical dose TCP modeling of 2-year local tumor control from the single-fraction data were compared with data from 2 to 5 fractions, resulting in an estimated α/β = 6 Gy, and this was used to pool data. Acknowledging the uncertainty intrinsic to the data extraction and modeling process, the 90% TCP corresponded to 20 Gy in 1 fraction, 28 Gy in 2 fractions, 33 Gy in 3 fractions, and (with extrapolation) 40 Gy in 5 fractions. The estimated TCP for common fractionation schemes was 82% at 18 Gy, 90% for 20 Gy, and 96% for 24 Gy in a single fraction, 82% for 24 Gy in 2 fractions, and 78% for 27 Gy in 3 fractions. CONCLUSIONS:Spinal SBRT with the most common fractionation schemes yields 2-year estimates of local control of 82% to 96%. Given the heterogeneity in the tumor control estimates extracted from the literature, with variability in reporting of dosimetry data and the definition of and statistical methods of reporting tumor control, care should be taken interpreting the resultant model-based estimates. Depending on the clinical intent, the improved TCP with higher dose regimens should be weighed against the potential risks for greater toxicity. We encourage future reports to provide full dosimetric data correlated with tumor local control to allow future efforts of modeling pooled data.

PURPOSE/OBJECTIVE:Dose-volume data for injury to carotid artery and other major vessels in stereotactic body radiation therapy (SBRT)/SABR head and neck reirradiation were reviewed, modeled, and summarized. METHODS AND MATERIALS/METHODS:A PubMed search of the English-language literature (stereotactic and carotid and radiation) in April 2018 found 238 major vessel maximum point doses in 6 articles that were pooled for logistic modeling. Two subsequent studies with dose-volume major vessel data were modeled separately for comparison. Attempts were made to separate carotid blowout syndrome from other bleeding events (BE) in the analysis, but we acknowledge that all except 1 data set has some element of BE interspersed. RESULTS:Prior radiation therapy (RT) dose was not uniformly reported per patient in the studies included, but a course on the order of conventionally fractionated 70 Gy was considered for the purposes of the analysis (with an approximately ≥6-month estimated interval between prior and subsequent treatment in most cases). Factors likely associated with reduced risk of BE include nonconsecutive daily treatment, lower extent of circumferential tumor involvement around the vessel, and no surgical manipulation before or after SBRT. CONCLUSIONS:Initial data pooling for reirradiation involving the carotid artery resulted in 3 preliminary models compared in this Hypofractionated Treatment Effects in the Clinic (HyTEC) report. More recent experiences with alternating fractionation schedules and additional risk-reduction strategies are also presented. Complications data for the most critical structures such as spinal cord and carotid artery are so limited that they cannot be viewed as strong conclusions of probability of risk, but rather, as a general guideline for consideration. There is a great need for better reporting standards as noted in the High Dose per Fraction, Hypofractionated Treatment Effects in the Clinic introductory paper.