Purpose:
Multi-staged large AVM (>10 cm3 or diameter > 3 cm) Gammaknife radiosurgery requires setting up the patient based on a pre-treatment plan over several fractions. Residual rotational errors ...cannot be compensated by translational repositioning of the patient and may adversely impact the dose distribution on the total AVM target. This study evaluates the effect of residual rotational setup error.
Methods:
The total AVM target was contoured and split into several small sub-targets. A Gammaknife plan was completed for the whole AVM target to meet the prescription goals. Shots were split and grouped according to the location of each sub-target to be delivered in separate staged sup-plans. Rotational errors of ±1-5° about the three rotational axes along with 5mm random translational errors were used to simulate head frame setup errors on different treatment days. Software was developed to compensate for translational errors to bring the shots back to the position of the original plan. Dose distributions were compared between the original planned dose and that resulting from residual rotational errors.
Results:
The volume of the target having dose differences within 3% is decreased with larger residual rotational errors (98.28%, 84.22% and 68.08% for ±1°, ±3°, and ±5° rotation, respectively). The volume of the target with dose differences within 5% (99.89%, 94.86% and 83.01% for ±1°, ±3°, and ±5° rotation, respectively) indicate that rotation less than ±3° is acceptable for treatment.
Conclusion:
Dosimetric errors increase as rotational errors increase. The dosimetric impact was shown acceptable when rotational errors are less than 3°.
Stereotactic radiosurgery has become a common treatment approach for small-to-medium size vestibular schwannomas.
To evaluate relationship between time (beam-on and treatment) and risk of hearing ...decline after stereotactic radiosurgery for vestibular schwannomas in patients with Gardner-Robertson (GR) baseline classes I and II.
This retrospective longitudinal single-center study included 213 patients with GR I and II treated between June 2010 and December 2019. Risk of passing from GR classes I and II (coded 0) to other classes III, IV, and V (coded 1) and the increase in pure tone average (continuous outcome) were evaluated using a mixed-effect regression model. Biologically effective dose (BED) was further assessed for an alpha/beta ratio of 2.47 (Gy 2.47 ).
Binary outcome analysis revealed sex, dose rate, integral dose, time beam-on time odds ratio 1.03, P = .03, 95% CI 1.00-1.06; treatment time ( P = .02) and BED ( P = .001) as relevant. Fitted multivariable model included the sex, dose rate, and BED. Pure tone average analysis revealed age, integral dose received by tumor, isocenter number, time (beam-on time odds ratio 0.20, P = .001, 95% CI 0.083-0.33) and BED ( P = .005) as relevant.
Our analysis showed that risk of hearing decline was associated with male sex, higher radiation dose rate (cutoff 2.5 Gy/minute), higher integral dose received by the tumor, higher beam-on time ≥20 minutes, and lower BED. A BED between 55 and 61 was considered as optimal for hearing preservation.
Stereotactic radiosurgery (SRS) is a useful alternative for small- to medium-sized vestibular schwannoma. To evaluate whether biologically effective dose (BED Gy2.47 ), calculated for mean (BED ...Gy2.47 mean) and maximal (BED Gy2.47 max) cochlear dose, is relevant for hearing preservation.
This is a retrospective longitudinal single-center study. Were analyzed 213 patients with useful baseline hearing. Risk of hearing decline was assessed for Gardner-Robertson classes and pure tone average (PTA) loss. The mean follow-up period was 39 months (median 36, 6-84).
Hearing decline (Gardner-Robertson class) 3 years after SRS was associated with higher cochlear BED Gy2.47 mean (odds ratio OR 1.39, P = .009). Moreover, BED Gy2.47 mean was more relevant as compared with BED Gy2.47 max (OR 1.13, P = .04). Risk of PTA loss (continuous outcome, follow-up minus baseline) was significantly corelated with BED Gy2.47 mean at 24 (beta coefficient 1.55, P = .002) and 36 (beta coefficient 2.01, P = .004) months after SRS. Risk of PTA loss (>20 dB vs ≤) was associated with higher BED Gy2.47 mean at 6 (OR 1.36, P = .002), 12 (OR 1.36, P = .007), and 36 (OR 1.37, P = .02) months. Risk of hearing decline at 36 months for the BED Gy2.47 mean of 7-8, 10, and 12 Gy 2.47 was 28%, 57%, and 85%, respectively.
Cochlear BED Gy2.47 mean is relevant for hearing decline after SRS and more relevant as compared with BED Gy2.47 max. Three years after SRS, this was sustained for all hearing decline evaluation modalities. Our data suggest the BED Gy2.47 mean cut-off of ≤8 Gy 2.47 for better hearing preservation rates .
The task group (TG) for quality assurance for robotic radiosurgery was formed by the American Association of Physicists in Medicine’s Science Council under the direction of the Radiation Therapy ...Committee and the Quality Assurance (QA) Subcommittee. The task group (TG-135) had three main charges: (1) To make recommendations on a code of practice for Robotic Radiosurgery QA; (2) To make recommendations on quality assurance and dosimetric verification techniques, especially in regard to real-time respiratory motion tracking software; (3) To make recommendations on issues which require further research and development. This report provides a general functional overview of the only clinically implemented robotic radiosurgery device, the CyberKnife®. This report includes sections on device components and their individual component QA recommendations, followed by a section on the QA requirements for integrated systems. Examples of checklists for daily, monthly, annual, and upgrade QA are given as guidance for medical physicists. Areas in which QA procedures are still under development are discussed.
There is wide variation in treatment planning strategy for central nervous system (CNS) stereotactic radiosurgery. We sought to understand what relationships exist between intratumor maximum dose and ...local control (LC) or CNS toxicity, and dosimetric effects of constraining hotspots on plan quality of multiple metastases volumetric modulated arc therapy radiosurgery plans.
We captured brain metastases from 2015 to 2017 treated with single-isocenter volumetric modulated arc therapy radiosurgery. Included tumors received single-fraction stereotactic radiosurgery, had no previous surgery or radiation, and available follow-up imaging. Our criterion for local failure was 25% increase in tumor diameter on follow-up MRI or pathologic confirmation of tumor recurrence. We defined significant CNS toxicity as Radiation Therapy Oncology Group irreversible Grade 3 or higher. We performed univariate and multivariate analyses evaluating factors affecting LC. We examined 10 stereotactic radiosurgery plans with prescriptions of 18 Gy to all targets originally planned without constraints on the maximum dose within the tumor. We replanned each with a constraint of Dmax 120%. We compared V50%, mean brain dose, and Dmax between plans.
Five hundred and thirty tumors in 116 patients were available for analysis. Median prescription dose was 18 Gy, and median prescription isodose line (IDL) was 73%. Kaplan-Meier estimate of 12-month LC only tumor volume (HR 1.43 1.22-1.68 P < .001) was predictive of local failure on univariate analysis; prescription IDL and histology were not. In multivariate analysis, tumor volume impacted local failure (HR 1.43 1.22-1.69 P < .001) but prescription IDL did not (HR 0.95 0.86-1.05 P = .288). Only a single grade 3 and 2 grade 4 toxicities were observed; tumor volume was predictive of CNS toxicity (HR 1.58 1.25-2.00; P < .001), whereas prescription IDL was not (HR 1.01 0.87-1.17 P = .940).
The prescription isodose line had no impact on local tumor control or CNS toxicity. Penalizing radiosurgery hotspots resulted in worse radiosurgery plans with poorer gradient. Limiting maximum dose in gross tumor causes increased collateral exposure to surrounding tissue and should be avoided.
OBJECTIVE Stereotactic radiosurgery (SRS) is the primary modality for treating brain metastases. However, effective radiosurgical control of brain metastases ≥ 2 cm in maximum diameter remains ...challenging and is associated with suboptimal local control (LC) rates of 37%-62% and an increased risk of treatment-related toxicity. To enhance LC while limiting adverse effects (AEs) of radiation in these patients, a dose-dense treatment regimen using 2-staged SRS (2-SSRS) was used. The objective of this study was to evaluate the efficacy and toxicity of this treatment strategy. METHODS Fifty-four patients (with 63 brain metastases ≥ 2 cm) treated with 2-SSRS were evaluated as part of an institutional review board-approved retrospective review. Volumetric measurements at first-stage stereotactic radiosurgery (first SSRS) and second-stage SRS (second SSRS) treatments and on follow-up imaging studies were determined. In addition to patient demographic data and tumor characteristics, the study evaluated 3 primary outcomes: 1) response at first follow-up MRI, 2) time to local progression (TTP), and 3) overall survival (OS) with 2-SSRS. Response was analyzed using methods for binary data, TTP was analyzed using competing-risks methods to account for patients who died without disease progression, and OS was analyzed using conventional time-to-event methods. When needed, analyses accounted for multiple lesions in the same patient. RESULTS Among 54 patients, 46 (85%) had 1 brain metastasis treated with 2-SSRS, 7 patients (13%) had 2 brain metastases concurrently treated with 2-SSRS, and 1 patient underwent 2-SSRS for 3 concurrent brain metastases ≥ 2 cm. The median age was 63 years (range 23-83 years), 23 patients (43%) had non-small cell lung cancer, and 14 patients (26%) had radioresistant tumors (renal or melanoma). The median doses at first and second SSRS were 15 Gy (range 12-18 Gy) and 15 Gy (range 12-15 Gy), respectively. The median duration between stages was 34 days, and median tumor volumes at the first and second SSRS were 10.5 cm
(range 2.4-31.3 cm
) and 7.0 cm
(range 1.0-29.7 cm
). Three-month follow-up imaging results were available for 43 lesions; the median volume was 4.0 cm
(range 0.1-23.1 cm
). The median change in volume compared with baseline was a decrease of 54.9% (range -98.2% to 66.1%; p < 0.001). Overall, 9 lesions (14.3%) demonstrated local progression, with a median of 5.2 months (range 1.3-7.4 months), and 7 (11.1%) demonstrated AEs (6.4% Grade 1 and 2 toxicity; 4.8% Grade 3). The estimated cumulative incidence of local progression at 6 months was 12% ± 4%, corresponding to an LC rate of 88%. Shorter TTP was associated with greater tumor volume at baseline (p = 0.01) and smaller absolute (p = 0.006) and relative (p = 0.05) decreases in tumor volume from baseline to second SSRS. Estimated OS rates at 6 and 12 months were 65% ± 7% and 49% ± 8%, respectively. CONCLUSIONS 2-SSRS is an effective treatment modality that resulted in significant reduction of brain metastases ≥ 2 cm, with excellent 3-month (95%) and 6-month (88%) LC rates and an overall AE rate of 11%. Prospective studies with larger cohorts and longer follow-up are necessary to assess the durability and toxicities of 2-SSRS.
The oligometastatic paradigm suggests that some patients with a limited number of metastases might be cured if all lesions are eradicated. Evidence from randomised controlled trials to support this ...paradigm is scarce. We aimed to assess the effect of stereotactic ablative radiotherapy (SABR) on survival, oncological outcomes, toxicity, and quality of life in patients with a controlled primary tumour and one to five oligometastatic lesions.
This randomised, open-label phase 2 study was done at 10 hospitals in Canada, the Netherlands, Scotland, and Australia. Patients aged 18 or older with a controlled primary tumour and one to five metastatic lesions, Eastern Cooperative Oncology Group score of 0–1, and a life expectancy of at least 6 months were eligible. After stratifying by the number of metastases (1–3 vs 4–5), we randomly assigned patients (1:2) to receive either palliative standard of care treatments alone (control group), or standard of care plus SABR to all metastatic lesions (SABR group), using a computer-generated randomisation list with permuted blocks of nine. Neither patients nor physicians were masked to treatment allocation. The primary endpoint was overall survival. We used a randomised phase 2 screening design with a two-sided α of 0·20 (wherein p<0·20 designates a positive trial). All analyses were intention to treat. This study is registered with ClinicalTrials.gov, number NCT01446744.
99 patients were randomised between Feb 10, 2012, and Aug 30, 2016. Of 99 patients, 33 (33%) were assigned to the control group and 66 (67%) to the SABR group. Two (3%) patients in the SABR group did not receive allocated treatment and withdrew from the trial; two (6%) patients in the control group also withdrew from the trial. Median follow-up was 25 months (IQR 19–54) in the control group versus 26 months (23–37) in the SABR group. Median overall survival was 28 months (95% CI 19–33) in the control group versus 41 months (26–not reached) in the SABR group (hazard ratio 0·57, 95% CI 0·30–1·10; p=0·090). Adverse events of grade 2 or worse occurred in three (9%) of 33 controls and 19 (29%) of 66 patients in the SABR group (p=0·026), an absolute increase of 20% (95% CI 5–34). Treatment-related deaths occurred in three (4·5%) of 66 patients after SABR, compared with none in the control group.
SABR was associated with an improvement in overall survival, meeting the primary endpoint of this trial, but three (4·5%) of 66 patients in the SABR group had treatment-related death. Phase 3 trials are needed to conclusively show an overall survival benefit, and to determine the maximum number of metastatic lesions wherein SABR provides a benefit.
Ontario Institute for Cancer Research and London Regional Cancer Program Catalyst Grant.
Although stereotactic radiosurgery (SRS) alone is not a standard treatment for patients with 4-5 tumors or more, a recent trend has been for patients with 5 or more, or even 10 or more, tumors to ...undergo SRS alone. The aim of this study was to reappraise whether the treatment results for SRS alone for patients with 10 or more tumors differ from those for patients with 2-9 tumors.
This was an institutional review board-approved, retrospective cohort study that gathered data from the Katsuta Hospital Mito GammaHouse prospectively accumulated database. Data were collected for 2553 patients who consecutively had undergone Gamma Knife SRS alone, without whole-brain radiotherapy (WBRT), for newly diagnosed (mostly) or recurrent (uncommonly) brain metastases during 1998-2011. Of these 2553 patients, 739 (28.9%) with a single tumor were excluded, leaving 1814 with multiple metastases in the study. These 1814 patients were divided into 2 groups: those with 2-9 tumors (Group A, 1254 patients) and those with 10 or more tumors (Group B, 560 patients). Because of considerable bias in pre-SRS clinical factors between groups A and B, a case-matched study, which used the propensity score matching method, was conducted for clinical factors (i.e., age, sex, primary tumor state, extracerebral metastases, Karnofsky Performance Status, neurological symptoms, prior procedures surgery and WBRT, volume of the largest tumor, and peripheral doses). Ultimately, 720 patients (360 in each group) were selected. The standard Kaplan-Meier method was used to determine post-SRS survival times and post-SRS neurological death-free survival times. Competing risk analysis was applied to estimate cumulative incidence for local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-induced complications.
Post-SRS median survival times did not differ significantly between the 2 groups (6.8 months for Group A vs 6.0 months for Group B; hazard ratio HR 1.133, 95% CI 0.974-1.319, p = 0.10). Furthermore, rates of neurological death were very similar: 10.0% for group A and 9.4% for group B (p = 0.89); neurological death-free survival times did not differ significantly between the 2 groups (HR 1.073, 95% CI 0.649-1.771, p = 0.78). The cumulative incidence of local recurrence (HR 0.425, 95% CI 0.0.181-0.990, p = 0.04) and repeat SRS for new lesions (HR 0.732, 95% CI 0.554-0.870, p = 0.03) were significantly lower for Group B than for Group A patients. No significant differences between the groups were found for cumulative incidence for neurological deterioration (HR 0.994, 95% CI 0.607-1.469, p = 0.80) or SRS-related complications (HR 0.541, 95% CI 0.138-2.112, p = 0.38).
Post-SRS treatment results (i.e., median survival time; neurological death-free survival times; and cumulative incidence for local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-related complications) were not inferior (neither less effective nor less safe) for patients in Group B than for those in Group A. We conclude that carefully selected patients with 10 or more tumors are not unfavorable candidates for SRS alone. A randomized controlled trial should be conducted to test this hypothesis.
Focused ultrasound (FUS-T) and stereotactic radiosurgery thalamotomy (SRS-T) targeting the ventral intermediate nucleus are effective incisionless surgeries for essential tremor (ET). However, their ...efficacy for tremor reduction and, importantly, adverse event incidence have not been directly compared.
To present a comprehensive systematic review with network meta-analysis examining both efficacy and adverse events (AEs) of FUS-T vs SRS-T for treating medically refractory ET.
We conducted a systematic review and network meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using the PubMed and Embase databases. We included all primary FUS-T/SRS-T studies with approximately 1-year follow-up, with unilateral Fahn-Tolosa-Marin Tremor Rating Scale or Clinical Rating Scale for Tremor scores prethalamotomy/post-thalamotomy and/or AEs. The primary efficacy outcome was Fahn-Tolosa-Marin Tremor Rating Scale A+B score reduction. AEs were reported as an estimated incidence.
Fifteen studies of 464 patients and 3 studies of 62 patients met inclusion criteria for FUS-T/SRS-T efficacy comparison, respectively. Network meta-analysis demonstrated similar tremor reduction between modalities (absolute tremor reduction: FUS-T: -11.6 (95% CI: -13.3, -9.9); SRS-T: -10.3 (95% CI: -14.2, -6.0). FUS-T had a greater 1-year adverse event rate, particularly imbalance and gait disturbances (10.5%) and sensory disturbances (8.3%). Contralateral hemiparesis (2.7%) often accompanied by speech impairment (2.4%) were most common after SRS-T. There was no correlation between efficacy and lesion volume.
Our systematic review found similar efficacy between FUS-T and SRS-T for ET, with trend toward higher efficacy yet greater adverse event incidence with FUS-T. Smaller lesion volumes could mitigate FUS-T off-target effects for greater safety.