Volumetric Radiosurgery for 1 to 10 Brain Metastases: A Multicenter, Single-Arm, Phase 2 Study.

PURPOSE: Interest is growing in treating multiple brain metastases with radiosurgery. We report on the effectiveness and tolerability of volumetric radiosurgery (VRS). METHODS AND MATERIALS: We enrolled patients with a ≥6-month estimated life expectancy and 1 to 10 brain metastases with a diameter of ≤3 cm at 5 cancer centers. Volumetric radiosurgery was delivered in 5 fractions with 98% target coverage, prescribed as 95% of 50 Gy (47.5 Gy in 5 fractions) to the metastases with no margin and 95% of 40 Gy (38 Gy in 5 fractions) to their 2-mm planning target volumes, concurrent with 20 Gy to the whole brain planning target volume. The treatment was delivered with daily image guidance using conventional linear accelerators and volumetric modulated arc therapy. A magnetic resonance imaging scan was obtained every 3 months. The primary endpoint was the 3-month objective response in the brain according to the Response Evaluation Criteria in Solid Tumors, version 1.1. The principal secondary endpoint was 1-year actuarial control of treated metastases. Toxicities were graded using the Common Terminology Criteria for Adverse Events, version 4.0. The present study is registered with ClinicalTrials.gov (clinicaltrials.gov identifier NCT01046123). RESULTS: From July 2010 to May 2013, 60 patients underwent VRS with 47.5 Gy in 5 fractions for 12 metastases in the thalamus and basal ganglia (deep metastases) and 207 non-deep metastases. The median follow-up period was 30.5 months, and the median survival was 10.1 months. For the 43 patients assessable at 3 months, the objective response in the brain was 56%. The treated metastases were controlled in 88% of patients at 1 year and 84% at 3 years. Overall survival did not differ for patients with 4 to 10 versus 1 to 3 metastases (hazard ratio 1.18, P=.6). The crude incidence of severe radionecrosis (grade 3-5) was 25% (3 of 12) per deep metastasis, 1.9% (4 of 219) per non-deep metastasis, and 10% (6 of 60) per patient. CONCLUSIONS: For non-deep brain metastases, 47.5 Gy in 5 fractions was tolerable. Volumetric radiosurgery was effective for long-term control of treated brain metastases.

Liver toxicity prediction with stereotactic body radiation therapy: The impact of accounting for fraction size.

PURPOSE: Current liver SBRT protocols rely on the calculation of "effective volume" without accounting for the biologic effect of fraction size to estimate the risk of liver toxicity, which subsequently defines tumor prescription doses. This study compared effective volume and liver toxicity predictions with and without correction for fraction size. METHODS AND MATERIALS: The effective volume was determined for 18 liver SBRT plans with and without biologic normalization using the linear quadratic formula. Lyman-Kutcher-Burman normal tissue complication probability models estimated the risk of liver toxicity. Effective volumes and corresponding toxicity predictions were compared with and without biologic normalization. RESULTS: Accounting for the biologic difference of larger fraction size reduced the effective volume in all treatment plans compared with the unadjusted effective volume (median effective volume 0.21 vs 0.32). The lower effective volume with biologic normalization substantially reduced the estimated risk of liver toxicity (average risk of toxicity 32% vs 4.5%). CONCLUSIONS: This study demonstrates that accounting for the biologic effect of fraction size with effective volume significantly decreases predicted hepatic toxicity, which suggests that the risk of liver toxicity may be overestimated in clinical practice if biologic normalization is omitted. The effective volume toxicity model has proven safe in prospective clinical trials, though safe dose escalation with liver SBRT may be feasible.

A radiotherapy planning study of RapidArc, intensity modulated radiotherapy, three-dimensional conformal radiotherapy, and parallel opposed beams in the treatment of pediatric retroperitoneal tumors.

BACKGROUND: This planning study compared RapidArc, fixed-field IMRT (cIMRT), 3D conformal radiotherapy (3D-CRT), and a parallel-opposed pair (POP) for children with retroperitoneal tumors. PROCEDURE: Plans were generated in eight patients to treat the PTV (dose range 19.8-45 Gy) while limiting kidney and liver doses. In selected patients, vertebral body (VB) dose heterogeneity was minimized. Cumulative DVH parameters, monitor units (MU), and treatment times were compared for the four techniques using the Wilcoxon matched pairs test. RESULTS: RapidArc and cIMRT covered target volumes more conformally than 3D-CRT and POP (P = 0.012). There was no difference in the ability to meet kidney dose constraints. A significantly lower volume of the liver received 12 Gy with cIMRT or RapidArc compared with 3D-CRT (P = 0.028). Where VB was included in PTV, VB dose homogeneity was generally within 94-104% of the prescription dose. Time to deliver a single fraction with RapidArc, POP, 3D-CRT, and cIMRT was 1.25 ± 0.01, 1.38 ± 0.10, 2.6 ± 0.45, and 4.02 ± 1.12 min, respectively (P = 0.012). Monitor units for a single fraction with POP, 3D-CRT, RapidArc, and cIMRT were 203 ± 26, 235 ± 32, 325 ± 71, and 665 ± 215, respectively (P < 0.05). CONCLUSIONS: POP resulted in favorable MU, treatment time and dosimetry but had poor conformality. 3D-CRT was more conformal but had higher MU and treatment time. RapidArc and cIMRT were generally no better dosimetrically than conformal techniques. RapidArc was dosimetrically very similar to cIMRT, but resulted in a major reduction in time and MU used to deliver the radiation.

A comparison of volumetric modulated arc therapy and conventional intensity-modulated radiotherapy for frontal and temporal high-grade gliomas.

PURPOSE: Volumetric modulated arc therapy (VMAT), the predecessor to Varian's RapidArc, is a novel extension of intensity-modulated radiotherapy (IMRT) wherein the dose is delivered in a single gantry rotation while the multileaf collimator leaves are in motion. Leaf positions and the weights of field samples along the arc are directly optimized, and a variable dose rate is used. This planning study compared seven-field coplanar IMRT (cIMRT) with VMAT for high-grade gliomas that had planning target volumes (PTVs) overlapping organs at risk (OARs). METHODS AND MATERIALS: 10 previously treated patients were replanned to 60 Gy in 30 fractions with cIMRT and VMAT using the following planning objectives: 98% of PTV covered by 95% isodose without violating OAR and hotspot dose constraints. Mean OAR doses were maximally decreased without reducing PTV coverage or violating hotspot constraints. We compared dose-volume histogram data, monitor units, and treatment times. RESULTS: There was equivalent PTV coverage, homogeneity, and conformality. VMAT significantly reduced maximum and mean retinal, lens, and contralateral optic nerve doses compared with IMRT (p < 0.05). Brainstem, chiasm, and ipsilateral optic nerve doses were similar. For 2-Gy fractions, mean monitor units were as follows: cIMRT = 789 +/- 112 and VMAT = 363 +/- 45 (relative reduction 54%, p = 0.002), and mean treatment times (min) were as follows: cIMRT = 5.1 +/- 0.4 and VMAT = 1.8 +/- 0.1 (relative reduction 65%, p = 0.002). CONCLUSIONS: Compared with cIMRT, VMAT achieved equal or better PTV coverage and OAR sparing while using fewer monitor units and less time to treat high-grade gliomas.

Optimization of stereotactic radiotherapy treatment delivery technique for base-of-skull meningiomas.

This study compares static conformal field (CF), intensity modulated radiotherapy (IMRT), and dynamic arcs (DA) for the stereotactic radiotherapy of base-of-skull meningiomas. Twenty-one cases of base-of-skull meningioma (median planning target volume [PTV] = 21.3 cm3) previously treated with stereotactic radiotherapy were replanned with each technique. The plans were compared for Radiation Therapy Oncology Group conformity index (CI) and homogeneity index (HI), and doses to normal structures at 6 dose values from 50.4 Gy to 5.6 Gy. The mean CI was 1.75 (CF), 1.75 (DA), and 1.66 (IMRT) (p < 0.05 when comparing IMRT to either CF or DA plans). The CI (IMRT) was inversely proportional to the size of the PTV (Spearman's rho = -0.53, p = 0.01) and at PTV sizes above 25 cm3, the CI (IMRT) was always superior to CI (DA) and CI (CF). At PTV sizes below 25 cm3, there was no significant difference in CI between each technique. There was no significant difference in HI between plans. The total volume of normal tissue receiving 50.4, 44.8, and 5.6 Gy was significantly lower when comparing IMRT to CF and DA plans (p < 0.05). There was significantly improved dose sparing for the brain stem and ipsilateral temporal lobe with IMRT but no significant difference for the optic chiasm or pituitary gland. These results demonstrate that stereotactic IMRT should be considered to treat base-of-skull meningiomas with a PTV larger than 25 cm3, due to improved conformity and normal tissue sparing, in particular for the brain stem and ipsilateral temporal lobe.

Volumetric modulated arc therapy for delivery of prostate radiotherapy: comparison with intensity-modulated radiotherapy and three-dimensional conformal radiotherapy.

PURPOSE: Volumetric modulated arc therapy (VMAT) is a novel form of intensity-modulated radiotherapy (IMRT) optimization that allows the radiation dose to be delivered in a single gantry rotation of up to 360 degrees , using either a constant dose rate (cdr-VMAT) or variable dose rate (vdr-VMAT) during rotation. The goal of this study was to compare VMAT prostate RT plans with three-dimensional conformal RT (3D-CRT) and IMRT plans. PATIENTS AND METHODS: The 3D-CRT, five-field IMRT, cdr-VMAT, and vdr-VMAT RT plans were created for 10 computed tomography data sets from patients undergoing RT for prostate cancer. The parameters evaluated included the doses to organs at risk, equivalent uniform doses, dose homogeneity and conformality, and monitor units required for delivery of a 2-Gy fraction. RESULTS: The IMRT and both VMAT techniques resulted in lower doses to normal critical structures than 3D-CRT plans for nearly all dosimetric endpoints analyzed. The lowest doses to organs at risk and most favorable equivalent uniform doses were achieved with vdr-VMAT, which was significantly better than IMRT for the rectal and femoral head dosimetric endpoints (p < 0.05) and significantly better than cdr-VMAT for most bladder and rectal endpoints (p < 0.05). The vdr-VMAT and cdr-VMAT plans required fewer monitor units than did the IMRT plans (relative reduction of 42% and 38%, respectively; p = 0.005) but more than for the 3D-CRT plans (p = 0.005). CONCLUSION: The IMRT and VMAT techniques achieved highly conformal treatment plans. The vdr-VMAT technique resulted in more favorable dose distributions than the IMRT or cdr-VMAT techniques, and reduced the monitor units required compared with IMRT.

Hearing preservation following fractionated stereotactic radiotherapy for vestibular schwannomas: prognostic implications of cochlear dose.

OBJECT: The goal in this study was to evaluate hearing preservation rates and to determine prognostic factors for this outcome following fractionated stereotactic radiotherapy (FSRT) of vestibular schwannoma. METHODS: Thirty-four consecutive patients with serviceable hearing who received FSRT between May 1998 and December 2003 were identified. Clinical and audiometry data were collected prospectively. The prescription dose was 45 Gy in 25 fractions prescribed to the 90% isodose line. The median follow-up duration was 36.5 months (range 12-85 months). The actuarial 2- and 4-year local control rates were 100 and 95.7%, respectively. Permanent trigeminal and facial nerve complications were 0 and 6%, respectively. The actuarial 2- and 3-year serviceable hearing preservation rates were both 63%. The median loss in speech reception threshold was 15 dB (range--10 to 65 dB). The radiotherapy dose to the cochlea was the only significant prognostic factor for hearing deterioration. Radiotherapy dose to the cochlear nucleus, patient age, sex, pre-FSRT hearing grade, tumor volume, and intracanalicular tumor volume failed to show any significance as prognostic factors. RESULTS: Five cases were replanned with four different radiotherapy techniques (namely arcs, dynamic arcs, static conformal fields, and intensity-modulated radiotherapy), with the cochlea defined as an organ at risk. In all cases, replanning resulted in statistically significant reduction in radiation to the cochlea (p = 0.001); however, no single replanning technique was found to be superior. CONCLUSIONS: The radiation dose to the cochlea is strongly predictive for subsequent hearing deterioration. It is essential for the cochlea to be outlined as an organ at risk, and for radiation techniques to be optimized, to improve long-term hearing preservation.

Does intensity modulation improve healthy tissue sparing in stereotactic radiosurgery of complex arteriovenous malformations?

This planning study evaluates the potential of intensity modulated treatment fields and inverse planning techniques in stereotactic radiosurgery to reduce healthy tissue dose. Twenty patients previously treated with stereotactic radiosurgery for arteriovenous malformation (AVM) were replanned with each of 4 techniques: circular non-coplanar arcs, dynamic arcs, static conformal fields, and intensity modulated radiosurgery (IMRS). Patients were selected having a maximum AVM dimension at least 20 mm, or volume greater than 10 cm(3). Target volumes ranged from 2.12 cm(3) to 13.87 cm(3) with a median of 6.03 cm(3). Resulting dose distributions show a statistically significant improvement in target conformality between circular arcs and all other techniques (p