ABSTRACT
Purpose: Genetic variants affecting the radiation response protein ataxia-telangiectasia mutated (ATM) have been associated with increased adverse effects of radiation but also with improved local control after conventional radiation therapy. However, it is unknown whether ATM variants affect rates of radionecrosis (RN) and local intracranial progression (LIP) after stereotactic radiosurgery (SRS) for brain metastases. Methods and Materials: Patients undergoing an initial course of SRS for non-small cell lung cancer (NSCLC) brain metastases at a single institution were retrospectively identified. Kaplan-Meier estimates were calculated and Cox proportional hazards testing was performed based on ATM variant status. Results: A total of 541 patients completed SRS for brain metastasis secondary to NSCLC, of whom 260 completed molecular profiling. Variants of ATM were identified in 36 cases (13.8%). Among patients who completed molecular profiling, RN incidence was 4.9% (95% CI, 1.6%-8.2%) at 6 months and 9.9% (95% CI, 4.8%-15.0%) at 12 months. Incidence of RN was not significantly increased among patients with ATM variants, with an RN incidence of 5.3% (95% CI, 0.0%-15.3%) at both 6 and 12 months (P = .46). For all patients who completed genomic profiling, LIP was 5.4% (95% CI, 2.4%-8.4%) at 6 months and 9.8% (5.5%-14.1%) at 12 months. A significant improvement in LIP was not detected among patients with ATM variants, with an LIP incidence of 3.1% (0.0%-9.1%) at both 6 and 12 months (P = .26). Although differences according to ATM variant type (pathologic variant or variant of unknown significance) did not reach significance, no patients with ATM pathologic variants experienced LIP. Conclusions: We did not detect significant associations between ATM variant status and RN or LIP after SRS for NSCLC brain metastases. The current data set allows estimation of patient cohort sizes needed to power future investigations to identify genetic variants that associate with significant differences in outcomes after SRS.
ABSTRACT
PURPOSE: To examine the effectiveness and safety of single-isocenter multitarget stereotactic radiosurgery using a volume-adapted dosing strategy in patients with 4 to 10 brain metastases. METHODS AND MATERIALS: Adult patients with 4 to 10 brain metastases were eligible for this prospective trial. The primary endpoint was overall survival. Secondary endpoints were local recurrence, distant brain failure, neurologic death, and rate of adverse events. Exploratory objectives were neurocognition, quality of life, dosimetric data, salvage rate, and radionecrosis. Dose was prescribed in a single fraction per RTOG 90-05 or as 5 Gy × 5 fractions for lesions ≥3 cm diameter, lesions involving critical structures, or single-fraction brain V12Gy >20 mL. RESULTS: Forty patients were treated with median age of 61 years, Karnofsky performance status 90, and 6 brain metastases. Twenty-two patients survived longer than expected from the time of protocol SRS, with 1 living patient who has not reached that milestone. Median overall survival was 8.1 months with a 1-year overall survival of 35.7%. The 1-year local recurrence rate was 5% (10 of 204 of evaluable lesions) in 12.5% (4 of 32) of the patients. Distant brain failure was observed in 19 of 32 patients with a 1-year rate of 35.8%. Grade 1-2 headache was the most common complaint, with no grade 3-5 treatment-related adverse events. Radionecrosis was observed in only 5 lesions, with a 1-year rate of 1.5%. Rate of neurologic death was 20%. Neurocognition and quality of life did not significantly change 3 months after SRS compared with pretreatment. CONCLUSIONS: These results suggest that volume-adapted dosing single-isocenter multitarget stereotactic radiosurgery is an effective and safe treatment for patients with 4 to 10 brain metastases.
ABSTRACT
PURPOSE: In this study, we evaluate and compare single isocenter multiple target VMAT (SIMT) and Conformal Arc Informed VMAT (CAVMAT) radiosurgery's sensitivity to uncertainties in dosimetric leaf gap (DLG) and treatment delivery. CAVMAT is a novel planning technique that uses multiple target conformal arcs as the starting point for limited inverse VMAT optimization. METHODS: All VMAT and CAVMAT plans were recalculated with DLG values of 0.4, 0.8, and 1.2 mm. DLG effect on V6Gy [cc], V12Gy [cc], and V16Gy [cc], and target dose was evaluated. Plans were delivered to a Delta4 (ScandiDos, Madison, WI) phantom and gamma analysis performed with varying criteria. Log file analysis was performed to evaluate MLC positional error. Sixteen targets were delivered to a SRS MapCHECK (Sun Nuclear Corp., Melbourne, FL) to evaluate VMAT and CAVMAT's dose difference (DD) as a function of DLG. RESULTS: VMAT's average maximum and minimum target dose sensitivity to DLG was 9.08 ±3.50%/mm and 9.50 ± 3.30%/mm, compared to 3.20 ± 1.60%/mm and 4.72 ± 1.60%/mm for CAVMAT. For VMAT, V6Gy [cc], V12Gy [cc], and V16Gy [cc] sensitivity was 35.83 ± 9.50%/mm, 34.12 ± 6.60%/mm, and 39.23 ± 8.40%/mm. In comparison, CAVMAT's sensitivity was 23.19 ± 4.50%/mm, 22.45 ± 4.40%/mm, and 24.88 ± 4.90%/mm, respectively. Upon delivery to the Delta4 , CAVMAT offered superior dose agreement compared to VMAT. For a 1%/1 mm gamma analysis, VMAT and CAVMAT had a passing rate of 94.53 ± 4.40% and 99.28 ± 1.70%, respectively. CAVMAT was more robust to DLG variation, with the SRS MapCHECK plans yielding an absolute average DD sensitivity of 2.99 ± 1.30%/mm compared to 5.07 ± 1.10%/mm for VMAT. Log files demonstrated minimal differences in MLC positional error for both techniques. CONCLUSIONS: CAVMAT remains robust to delivery uncertainties while offering a target dose sensitivity to DLG less than half that of VMAT, and 65% of that of VMAT for V6Gy [cc], V12Gy [cc], and V16Gy [cc]. The superior dose agreement and reduced sensitivity of CAVMAT to DLG uncertainties indicate promise as a robust alternative to VMAT for SIMT SRS.
Subject(s)
Radiosurgery , Radiotherapy, Intensity-Modulated , Humans , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , UncertaintyABSTRACT
Linac based radiosurgery to multiple metastases is commonly planned with volumetric modulated arc therapy (VMAT) as it effectively achieves high conformality to complex target arrangements. However, as the number of targets increases, VMAT can struggle to block between targets, which can lead to highly modulated and/or nonconformal multi-leaf collimator (MLC) trajectories that unnecessarily irradiation of healthy tissue. In this study we introduce, describe, and evaluate a treatment planning technique called Conformal Arc Informed VMAT (CAVMAT), which aims to reduce the dose to healthy tissue while generating highly conformal treatment plans. CAVMAT is a hybrid technique which combines the conformal MLC trajectories of dynamic conformal arcs with the MLC modulation and versatility of inverse optimization. CAVMAT has 3 main steps. First, targets are assigned to subgroups to maximize MLC blocking between targets. Second, arc weights are optimized to achieve the desired target dose, while minimizing MU variation between arcs. Third, the optimized conformal arc plan serves as the starting point for limited inverse optimization to improve dose conformity to each target. Twenty multifocal VMAT cases were replanned with CAVMAT with 20Gy applied to each target. The total volume receiving 2.5Gy[cm3], 6Gy[cm3], 12Gy[cm3], and 16Gy[cm3], conformity index, treatment delivery time, and the total MU were used to compare the VMAT and CAVMAT plans. In addition, CAVMAT was compared to a broad range of planning strategies from various institutions (108 linear accelerator based plans, 14 plans using other modalities) for a 5-target case utilized in a recent plan challenge. For the linear accelerator-based plans, a plan complexity metric based on aperture opening area and perimeter, total monitor units (MU), and MU for a given aperture opening was utilized in the plan challenge scoring algorithm to compare the submitted plans to CAVMAT. After re-planning the 20 VMAT cases, CAVMAT reduced the average V2.5Gy[cm3] by 25.25 ± 19.23%, V6Gy[cm3] by 13.68 ± 18.97%, V12Gy[cm3] by 11.40 ± 19.44%, and V16Gy[cm3] by 6.38 ± 19.11%. CAVMAT improved conformity by 3.81 ± 7.57%, while maintaining comparable target dose. MU for the CAVMAT plans increased by 24.35 ± 24.66%, leading to an increased treatment time of 2 minutes. For the plan challenge case, CAVMAT was 1 of 12 linac based plans that met all plan challenge scoring criteria. Compared to the average submitted VMAT plan, CAVMAT increased the V10%Gy[%] of healthy tissue (Brain-PTV) by roughly 3.42%, but in doing so was able to reduce the V25%Gy[%] by roughly 3.73%, while also reducing V50%Gy[%], V75%Gy[%], and V100%Gy[%]. The CAVMAT technique successfully eliminated insufficient MLC blocking between targets prior to the inverse optimization, leading to less complex treatment plans and improved tissue sparing. Tissue sparing, improved conformity, and decreased plan complexity at the cost of slight increase in treatment delivery time indicates CAVMAT to be a promising method to treat brain metastases.
