Faculty Bibliography

BACKGROUND:Since the inception of spinal radiosurgery decades ago, the factors influencing spinal cord recovery have remained unclear. Elucidating these factors would aid in reirradiation planning and delivery. We describe modeling reirradiation normal tissue complication probabilities (NTCP) from compiled published data, akin to the collaborative Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) and High Dose per Fraction, Hypofractionated Treatment Effects in the Clinic (HyTEC) projects. PURPOSE/OBJECTIVE:Simple dose-time recovery factors for the spinal cord serve as a basis to propose the Reirradiation Treatment Effects in the Clinic (ReTEC) project. ReTEC aims to define human organ recovery factors to convert the total composite dose to an equivalent physical dose compatible with the de novo therapy dose tolerance limits. Additionally, we present a system for automating analyses as well as clinical implementation of radiation dose-time recovery. METHODS:Published literature was queried for stereotactic voxel-wise composite reirradiation plans involving the spinal cord, but none were found. Hence, minimum reporting criteria were used instead: spinal cord maximum dose (Dmax) of each course, time interval between courses, and number of fractions or biologically effective dose, per patient or in sufficiently homogeneous groups of patients. Recovery factors and logistic model parameters were fitted with maximum likelihood techniques. RESULTS:An NTCP model was derived from 13 papers with data from 282 lesions, including six myelopathy cases. The model suggested spinal cord recovery of more than 50% in less than 1 year, which is faster and more complete than current clinical practice, but with wide confidence intervals (CI) (bootstrap 95% CI: 31%-95% when the time interval was 1 year). CONCLUSION/CONCLUSIONS:Due to limited data, we recommend remaining within current standard guidelines until more comprehensive analyses, optimally under the ReTEC initiative, refute or validate these estimates. ReTEC would require composite plans accounting for differing Dmax locations in each course. Nevertheless, this proof-of-concept Dmax model provides insight and serves as a basis to propose ReTEC.

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: 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: 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/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: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.