Fraction Stereotactic Radiosurgery Research Articles

Stereotactic radiosurgery for non-functioning pituitary adenomas: meta-analysis and International Stereotactic Radiosurgery Society practice opinion.

BackgroundThis systematic review reports on outcomes and toxicities following stereotactic radiosurgery (SRS) for non-functioning pituitary adenomas (NFAs) and presents consensus opinions regarding appropriate patient management.MethodsUsing the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, a systematic review was performed from articles of ≥10 patients with NFAs published prior to May 2018 from the Medline database using the key words “radiosurgery” and “pituitary” and/or “adenoma.” Weighted random effects models were used to calculate pooled outcome estimates.ResultsOf the 678 abstracts reviewed, 35 full-text articles were included describing the outcomes of 2671 patients treated between 1971 and 2017 with either single fraction SRS or hypofractionated stereotactic radiotherapy (HSRT). All studies were retrospective (level IV evidence). SRS was used in 27 studies (median dose: 15 Gy, range: 5–35 Gy) and HSRT in 8 studies (median total dose: 21 Gy, range: 12–25 Gy, delivered in 3–5 fractions). The 5-year random effects local control estimate after SRS was 94% (95% CI: 93.0–96.0%) and 97.0% (95% CI: 93.0–98.0%) after HSRT. The 10-year local control random effects estimate after SRS was 83.0% (95% CI: 77.0–88.0%). Post-SRS hypopituitarism was the most common treatment-related toxicity observed, with a random effects estimate of 21.0% (95% CI: 15.0–27.0%), whereas visual dysfunction or other cranial nerve injuries were uncommon (range: 0–7%).ConclusionsSRS is an effective and safe treatment for patients with NFAs. Encouraging short-term data support HSRT for select patients, and mature outcomes are needed before definitive recommendations can be made. Clinical practice opinions were developed on behalf of the International Stereotactic Radiosurgery Society (ISRS).

A Retrospective Cohort Study of Longitudinal Audiologic Assessment in Single and Fractionated Stereotactic Radiosurgery for Vestibular Schwannoma.

Fractionated stereotactic radiosurgery (SRS) for vestibular schwannomas (VS) has been theorized to allow for tumor control with higher rates of hearing preservation in selected patients with useful hearing. However, there is a paucity of literature with formal audiologic measures of hearing preservation to support the standard use of fractionated SRS in VS. We hypothesized that fractionation would diminish the amount of hearing damage. To evaluate the relationship between audiologic performance and SRS fractionation scheme. We performed an IRB-approved retrospective review of patients treated with 1, 3, or 5 fraction SRS for VS at our institution from 1998 to 2016. Pre- and post-SRS audiograms with speech awareness threshold (SAT) in treated and contralateral ears were obtained. Contralateral ear measurements were used for hearing normalization to account for presbycusis. Fifty-six patients with median audiologic follow-up 2.0 yr (mean 2.66 yr, min-max 0.50-9.45 yr) were included. Patients treated with single fractionation had a significantly worsened SAT (dB) compared to patients treated with 5 fractions (P=.008) and compared to all multifraction patients (P=.009) at 12 to 24 mo follow-up. This retrospective analysis supports the use of fractionated SRS to preserve hearing in patients with VS. SAT can be used as an objective metric of hearing response to radiosurgery.

Single Fraction Stereotactic Radiosurgery Compared With Fractionated Stereotactic Radiosurgery in Treating Patients With Resected Metastatic Brain Disease

Single Fraction Stereotactic Radiosurgery Compared With Fractionated Stereotactic Radiosurgery in Treating Patients With Resected Metastatic Brain Disease

Hypofractionated Radiosurgery Plus Bevacizumab for Locally Recurrent Brain Metastasis with Previously High-Dose Irradiation

Selection of appropriate treatment for patients with recurrent brain metastasis (BM) remains uncertain. Recent studies have demonstrated a significant response rate and acceptable toxicity using fractionated stereotactic radiosurgery (FSRS) in patients with locally recurrent large BM. The aim of this study was to evaluate efficacy and toxicity of FSRS with bevacizumab as a new salvage treatment for locally recurrent BM with previous high-dose irradiation. Patients with recurrent BM previously irradiated were enrolled. Salvage FSRS dose was 9.5-29 Gy (2-5 fractions) with 62%-75% isodose line by CyberKnife according to the brain tumor volume, site, and previous dose. Bevacizumab was prescribed for 4 cycles (5 mg/kg, every 3 weeks). The primary objective was to identify the overall survival after salvage treatment. Secondary objectives included clinical response (Karnofsky performance scale), imaging response (magnetic resonance imaging) and treatment-related adverse events. From December 2009 to October 2016, 24 patients were enrolled. The 1-year overall survival after salvage stereotactic radiosurgery was 87.5%. Twenty-three (96%) patients had a positive imaging response with a T2 volume reduction range of 6-22 cm3 (median 14 cm3, P= 0.032, paired t test). Significant clinical improvement was achieved (best Karnofsky performance scale score, P < 0.05, paired t test). Grade 1/2 fatigue was observed in 8 (33%) patients. Grade 3 fatigue and headache occurred in 1 patient. FSRS with adjuvant bevacizumab treatment showed favorable clinical and radiologic control as a salvage treatment regimen. The diagnoses of radiation necrosis and local recurrence after salvage FSRS warrant further study.

Multifraction Stereotactic Radiosurgery to Large Brain Metastases: Is This Scheme Effective and Safe?

Many fractionation regimens have been described for the treatment of large brain metastases with stereotactic radiosurgery (SRS). The purpose of this analysis is to demonstrate the efficacy and the tolerance of multifraction stereotactic radiosurgery (mSRS), 3 fractions, in patients with large brain metastases. Were reviewed all patients with brain metastases treated with mSRS (3 fractions) at a single institution. Patients with large brain metastases were the majority population, but patients who were not appropriate candidates for single fraction SRS were treated with mSRS and included as well. Prognostic factors including Ds-GPA, Score Index for Radiosurgery (SIR), number of lesions, systemic disease status, primary site, PTV volume, dose (3 schemes were used due a constraint of the organ at risk - 7 Gy, 8 Gy or 9 Gy/fraction), use of whole brain radiotherapy (WBRT) either pre or post SRS, surgery and the use of systemic therapy were all evaluated. The toxicity was graded using the CTCAE V. 4.0. Kaplan- Mayer and Log-Rank test were used for survival curve calculations. Chi-square test was used for comparative analysis with a significance level of 0.05. Between March 2015 and November 2018, 86 patients were enrolled, of which 2 were excluded due to loss to follow-up and 144 lesions treated. The median follow-up was 9.0 months. The patient characteristics are shown in Table 1. The overall survival (OS) at 12 and 24 months was 43% and 21.6%, respectively, with a median overall survival of 10 months. Death due to neurological failure was 14.5%. Local control at 12 months was 81.3%, with 47.6% developing new lesions after the first mSRS. There wasn’t a correlation between local control and dose/fraction, PTV volume and the other factors. There were 4 patients with acute grade 3 toxicity (paresthesia), reversible with corticosteroids. The most common symptom was headache, grade 1 and 2, (23.5%). Eight patients had grade 1-2 seizures. The radionecrosis rate was 9.5%, and four patients had symptomatic radionecrosis. The PTV volume average was 20.87 cc (1-140 cc). In multivariate analysis, Ds-GPA, SIR, KPS, primary site (melanoma and breast were better) and systemic progression status had a statistically significant effect on OS. The dose/fraction and PTV volume did not correlate with toxicity or radionecrosis. This mSRS scheme of 3 fractions to large brain metastases showed good local control with low complication rates, in the studied population. In our retrospective analysis of 84 patients, we conclude that this 3 fraction mSRS is safe and effective. A prospective trial is warranted to compare and evaluate the best SRS regimens for this approach.Abstract 2160; Table 1Patients CharacteristicsAge (median)54.5 y (22-81)Numb. Lesions: 1 - 3; >3;91.6%/ 8.4%Ds-GPA 0-1; 1.5 - 2.5; >2.5;23.8%/ 29.8%/ 46.4%/Primary Lung; Breast; Melanoma; Others;39.3%/ 28.6%/ 8.3%/ 23.8%Fractionation 7 Gy x 3; 8 Gy x 3; 9 Gy x 3;8.3%/ 29.8%/ 61.9%/WBRT Pre mSRS; Pos mSRS; No;13.1%/ 23.8%/ 63.1%/ Open table in a new tab

RADI-25. REPEAT STEREOTACTIC RADIOSURGERY FOR RECURRENT BRAIN METASTASES

INTRODUCTION: Mainstream modality of treatment of oligo-metastatic disease is stereotactic radiosurgery (SRS). While the local control rate is nearing 90%, 7% of lesions and 10 to 15% of patients develop radiation necrosis post treatment. In the face of increasing lesion size and evidence of recurrence, re-treatment of the enlarging lesion with radiosurgery can be attempted. The aim of the project is to evaluate outcomes of lesions treated with repeat SRS. METHODS: We conducted a retrospective review of all patients that were treated with Gamma Knife radiosurgery at our institution from 2000 to 2018. Fifty-one lesions in 39 patients were identified that had recurrence during follow-up period and were treated with a second single-fraction SRS. RESULTS: A combination of imaging studies, such as PET and/or perfusion studies, lesion biopsy, and clinical course were used to make the diagnosis of lesion recurrence. The average radiation dose at first treatment was 21 Gy, and the average dose at second treatment was 19 Gy. The median time between treatments was 16.8 months, ranging from 2.5 to 75.3 months, and the median follow-up after second treatment was 10.2 months. Of 51 lesions that received two SRS treatments, 49% (25 lesions) continued to progress at a median interval of 4.8 months post treatment, of which 35% (18 lesions) were diagnosed as radiation necrosis based on biopsy results or advanced brain imaging. The overall rate of radiation necrosis post second SRS treatment was determined to be 16% per lesion and 21% per patient. CONCLUSION: Recurrent brain metastases that are re-treated with single fraction SRS are associated with a higher risk of radiation necrosis. Alternative treatment strategies, including fractionation of subsequent SRS treatments, radiation dose reduction, and combination with laser ablation could be considered to ensure symptom and disease control to reduce the rate of subsequent radiation necrosis.

Stereotactic radiosurgery combined with immune checkpoint inhibitors or kinase inhibitors for patients with multiple brain metastases of malignant melanoma.

The aim was to evaluate toxicity and oncological outcome of combined stereotactic radiosurgery (SRS) and immunotherapy or targeted therapy in patients with multiple brain metastases originating from malignant melanoma. Despite the fact that both SRS and kinase inhibitors or immune checkpoint inhibitors are considered standard treatment options for this indication, the optimal combination and sequence of these modalities remains largely unknown, especially for patients with a high number of brain metastases. For this retrospective analysis, conducted in two large SRS dedicated centers, we identified patients with brain metastases from malignant melanoma and simultaneous application of immunotherapy or targeted therapy within 30 days of SRS. Forty-eight patients with a total of 250 lesions (median: 3) were treated in 65 single fraction SRS sessions from 2012 to 2018. After a median follow-up of 8.3 months (range: 1.2-43.6 months), the 6-month and 1-year overall survival rates were 75.3 and 50.8%, respectively. The local control rate at one year was 89.5%. Immunotherapy and the application of systemic treatment directly before or concomitant to SRS were both associated with improved overall survival (P=0.037 and 0.045, respectively). We observed four grade III toxicities, of which only two can be clearly attributed to the combined treatment. Various combinations of SRS and kinase inhibitors or immune checkpoint inhibitors appear feasible and provide promising oncological results and safety profiles for treating few (n=1-4) and also multiple (n≥5) melanoma brain metastases.

Stereotactic Radiosurgery of Cavernous Sinus Meningiomas.

Objective Microsurgical resection of cavernous sinus meningiomas (CSM) is associated with a high rate of incomplete resection, recurrence, and the risk for permanent, severe cranial nerve deficits. Stereotactic radiosurgery (SRS) has evolved as alternative treatment for primary and recurrent CSM. Here, we report about the long-term clinical and radiological follow-up (FU) of a unique cohort of patients with CSM treated with LINAC or Cyberknife based SRS. Methods In this single-center retrospective analysis, we include all patients with CSM who underwent single fraction SRS between 1993 and 2016. Clinical and radiological tumor control were evaluated by the Kaplan-Meier method. Additionally, patient data were analyzed in terms of symptom control and incidence of side effects rated by the common terminology criteria for adverse events (CTCAE; v4.03). Results 116 patients (female/male = 91/25; median age, 54 years; range, 33-82 years) were included. Mean tumor volume was 5.7 ± 3.3 cm 3 (range, 0.6-16.2 cm 3 ), the median marginal dose was 12.6 Gy applied to isodose levels of 75%. Median clinical FU was 55 months (range, 3-226 months). Tumor control was 98% after 2 and 5 years and 90% after 10 years. Twelve patients (10.3%) had permanent or transient radiation related toxicity (CTCAE I-III). An improvement of symptoms was observed in 26.7% of the symptomatic patients ( n = 20 of 75). Conclusion SRS for CSM provides excellent long-term tumor and symptom control without considerable permanent side effects. Thus, SRS should be considered when counseling patients suffering from CSM.

Treatment-Plan Comparison of Three Advanced Radiation Treatment Modalities for Fractionated Stereotactic Radiotherapy to the Head and Neck

Purpose: Fractionated stereotactic radiosurgery (FSRS) can be given with at least three modalities: Gamma Knife, with the noninvasive frameless extend system (GKE); linear accelerator-based volumetric modulated arc therapy (VMAT); and intensity-modulated proton therapy (IMPT). We extracted treatment plans for patients who had received FSRS with GKE for recurrent skull base or intracranial tumors, created corresponding plans for VMAT and IMPT, and compared the quality of the three sets of plans. Methods and materials: Plans were extracted for 9 patients with recurrent malignant skull-base tumors (n = 6) or large intracranial tumors (n = 3) who had received FSRS with GKE (median dose 24 Gy in 3 fractions) in 2013 through 2015. Plans for VMAT were generated with a TrueBeam STx LINAC machine using 6-MV photons, and plans for IMPT were generated with multi-field optimization. The optimized VMAT and IMPT plans were normalized to achieve the best possible target coverage while meeting the same dose-volume constraints on organs at risk (OARs) as the GKE plans. Plans were evaluated on the basis of target coverage, conformity index, homogeneity index, gradient index, and treatment efficiency. Results: The median target volume was 10.2 cm3 (range 1.9 - 33.8 cm3). The VMAT and IMPT plans met all OAR constraints, and target coverage and conformity were comparable among all plans. VMAT and IMPT plans showed significantly better target uniformity and treatment delivery efficiency (P P

Clinical evidence for dose tolerance of the central nervous system in hypofractionated radiotherapy

Stereotactic radiosurgery (SRS), stereotactic body radiotherapy (SBRT), and stereotactic ablative body radiotherapy (SABR) are commonly used in the treatment of central nervous system (CNS) disease. This study has refined the radiation toxicity estimates for some normal tissues of the CNS based on review and analysis of the clinical evidence for single fraction radiosurgery, hypofractionated SBRT, and conventionally fractionated radiation therapy. Published guidelines and protocols are reviewed. In the past, many normal tissue tolerances were compiled based on the experience of the investigators and publications in the literature. Some tolerances were determined by modeling or calculation using the existing biological formulas, in particular the linear quadratic (LQ) model. In the present study, the estimate of risk for each dose tolerance limit in some CNS tissues is provided exclusively with normal tissue complication probability (NTCP). The clinical outcomes are compared to understand the difference in biological effect between radiosurgery and radiotherapy. Normal tissue dose tolerances and the corresponding complication rates are provided for brainstem, optic nerves, cochlea, and spinal cord, including single fraction SRS, five-fraction SBRT, and conventional radiation therapy. Calculation of biologically effective dose (BED) or single fraction equivalent dose (SFED) alone using the LQ model conveys no consensus on the biological effect across different fractionations. Comparison of conventional radiation therapy to brain and spinal cord with single fraction equivalent dose leads to even conflicting clinical outcomes. Effective differences between single fraction SRS and conventional radiotherapy need to be better understood. The existing biological model might not be valid to predict the radiosurgical outcomes based on conventionally fractionated radiotherapy. However, application of the statistical dose response models of clinical SRS and SBRT outcomes data to selected current dose tolerance guidelines into simple tables can be a clinically useful resource.

Radiotherapy as a means of treating meningiomas

Meningiomas are reasonably common benign intracranial tumours. Those treated surgically are not necessarily the same as those addressed by radiotherapy, in terms of patient factors and anatomical location. Using “lack of progression” as the criterion of benefit, in this population of 612 treated lesions (541 patients), the 10 year rate is 93% by any of the radiotherapy means used. Single fraction stereotactic radiosurgery (SRS) was used for smaller meningiomas, with fractionated radiotherapy for large volume tumours, and/or those in contact with the optic chiasm/nerve. Using median volume as the variable, larger tumours were as adequately controlled as smaller tumours. Symptomatic improvement was achieved in the majority of patients with worsened neurological deficit in <5% of patients. Subtotal resection followed by radiotherapy provides little advantage over radiotherapy alone. Local control is achieved in close to two-thirds of patients with Grade 2 or 3 meningiomas. More likely amongst the patients who have radiotherapy alone there will be patients with Grade 2 or 3 tumours (but are not biopsied) who have good long-term control. Surgery is very appropriate where complete resection (with low morbidity) can be achieved, and/or to decompress those tumours with pressure features. Informed consent can include a discussion regarding the role of radiotherapy.

Stereotactic Radiosurgery for Vestibular Schwannoma: Longitudinal Radiographic Outcomes Single and Fractionated Treatments

Vestibular schwannomas (VS) are treated with fractionated stereotactic radiosurgery (SRS) to attempt hearing preservation. There are no established predictors of longitudinal effect on tumor volume, pseudoprogression or necrosis. An institutional review board approved retrospective review of patients treated with 1, 3, or 5 fraction (fx) SRS for VS at our institution from 1998-2016, with at least 2 years of follow-up was performed. Radiographic follow-up by MRI was used to calculate tumor volume based on tridimensional measurements and non-spherical tumor volume was approximated by pi/6*x*y*z. Radiologic responders were those with reduction by at least 2mm in any dimension. Radiologic non-responders had no growth or reduction. Treatment failures grew at least 2mm in any dimension by last follow-up. Pseudoprogression was defined as any interval increase in tumor volume that later normalized or reduced to below baseline tumor volume. A total of 56 patients met selection criteria. Most patients were treated with 5 fractions (32, 57%), then 3 fractions (12, 21%) and 1 fraction (12, 21%). The most common dose and fractionation regimens were 1250 cGy x 1 (7, 12.5%), 700 cGy x 3 (12, 21.4%), 500 cGy x 5 (12, 21.4%), and 450 cGy x 5 (14, 25%). Patients treated with 1 fx had a median baseline tumor volume of 1.2 cc (range 0.04-3.88), median dose 1250 cGy per fx (range 1200-1600), and median percent reduction in tumor volume of 2.7 % (range -396 to 85). Patients treated with 3 fxs had a median baseline tumor volume of 1.2 cc (range 0.4-7.7), median dose of 700 cGy (range 700-700), and a median percent reduction in tumor volume of 24 % (range -272 to 92). Patients treated with 5 fxs had a median baseline tumor volume of 2.0 cc (range 0.07-7.49), median dose of 450 cGy (range 400-550), and a median percent reduction in tumor volume of 6 % (range -290 to 89). Regardless of the number of fxs, patients had similar rates of pseudoprogression (25% in single, 33% in 3 fx and 31% in 5 fx cohorts). Patients treated with 3 fxs had lower rates of radiographic necrosis (58% with 3 fx vs 75% with 1 or 5 fx) but higher rates of radiologic response (67% with 3 fx vs 33% with 1 fx or 44% with 5 fx) and lower rates of radiologic non-response (17% with 3 fx vs 58% with 1 fx or 38% with 5 fx). Patients with more fxs had higher rates of treatment failure (8% with 1 fx vs 17% with 3 fx or 19% with 5 fx). SRS with 1, 3, or 5 fxs was safe and effective in reducing tumor volume of VS. About one-third of all patients had evidence of pseudoprogression. Patients treated with 3 fx SRS had the largest % reduction in tumor volume (median 24%) and lowest rates of necrosis.

Outcomes following Definitive Single Fraction Stereotactic Radiosurgery for Larger Brain Metastases

Limited data is available addressing the effectiveness of single fraction stereotactic radiosurgery (SRS) as a definitive treatment, without surgical resection, for larger brain metastases (LBM; largest diameter >2cm). We report the outcomes of patients treated for LBM with SRS at a single institution. We queried a prospectively maintained registry of 2059 BM treated with SRS between 2006 and 2017 to identify 280 LBMs. We analyzed demographics and treatment details descriptively. For survival analyses, we used the Kaplan-Meier method, with survival calculated from the date of LBM treatment (per lesion analyses). We performed univariate analyses using log-rank tests, and multivariate analyses with Cox regression models. We identified 255 patients with a median 1 LBM (range 1-3). Median largest diameter was 2.52 cm (range 2.01-4.64 cm); 56 LBM were >3 but <4 cm and 9 were >4 cm. Eighty-one percent of patients had an ECOG <2 and 75% of lesions had peritumoral edema. Prior to SRS for LBM(s), 15% underwent resection of other BM, 13% received SRS for smaller lesions, and 62% of patients received systemic therapy. Mean prescribed dose was 17 Gy (range 10-24 Gy) and target minimum dose 15.1 Gy (range 5.7-21.2 Gy). During SRS for LBM, 27% had concomitant lesions (<2 cm) treated with SRS and 53% had measurable extracranial disease. Median overall survival was 10 months (range 1-98 months). At a median follow up of 7 months (range 1-95 months), 63 lesions (22%) had failed locally (LF), with 24 of 63 (8% of all lesions) exhibiting synchronous intracranial distant failure. Local control (LC) for LBM was 88%, 76%, and 55% at 6-months, 1-year and 2-years, respectively. The median time to LF was 7 months (range 1 to 61 months). No disease (site of primary, size/ volume of LBM, concomitant disease, prior radiation) or treatment (prescribed dose, minimum/ maximum target dose, conformity indices) related factors tested were significantly associated with LF on univariate analysis. Radionecrosis (RN) developed in 39 lesions, with 1-year and 2-year rates of 18%, and 28%, respectively. Prescription dose, use of steroids during SRS, and V12 Gy were not associated with the rate of RN. Treatment details and LC rates according to selected variables are summarised in Table 1. Single fraction radiosurgery for LBM is associated with relatively poor rates of local control and relatively high rates of RN. Use of hypofractionated radiosurgery to deliver higher biologically effective doses more safely may expand the therapeutic index and result in improved outcomes.Abstract MO_24_2690; Table 1Factor1-year actuarial LCp valueLocation Supratentorial (223) Cerebellum (42) Brainstem (15)75% 75% 91%0.85Primary (three most common) Lung (106) Breast (60) Melanoma (34)69% 82% 65%0.18Prescribed dose 15 Gy or less (119) > 15 Gy-20 Gy (105) > 20 Gy (56)74% 75% 82%0.36Target volume 4 cc or less (119) More than 4 cc (161)78% 74%0.21 Open table in a new tab

Local Failure and Radionecrosis Following Single Fraction Stereotactic Radiosurgery for Surgical Cavities from Brain Metastases

Local Failure and Radionecrosis Following Single Fraction Stereotactic Radiosurgery for Surgical Cavities from Brain Metastases

Novel 4D-Flow MRI to Assess Quantitative Arterial Hemodynamic Response after Brain Stereotactic Radiosurgery (SRS) for Cerebral Arteriovenous Malformations (AVMs)

For unresectable cerebral AVMs, ablative SRS is standard of care. However, obliteration may take years, during which period risk of hemorrhage is uncertain. 4D-Flow MRI, a velocity-encoded phase-contrast MRI technique used to assess cardiac hemodynamics, has potential as an early marker of treatment response to SRS. Here, we assess changes in blood flow in AVM feeding arteries after brain SRS using 4D-Flow. Patients: Retrospective review of AVM patients treated with SRS at a single institution. Four patients were identified who underwent 4D-Flow MRI prior to or within 1 month of treatment (baseline) and at least one subsequent time point (first-follow up). Imaging: Imaging was performed on a 3T scanner with dedicated head coil. 4D-Flow sequences were based on a 3D spoiled gradient echo sequence with resolution 1.12 x 0.98 x 1.6-1.8 mm. Three directional velocity encoding gradients were used with Venc 100-200 cm/s. In addition, T1 post-contrast, T2, and 3D-Time of flight (TOF) angiography images were obtained to identify the AVM nidus and feeding arteries. Analysis: In each case a feeding artery was selected that could be traced distally to the AVM on both baseline and follow up images. Measurements were made in two locations within each feeding artery. A distal measurement was made as close to the AVM nidus as possible. A proximal measurement was made in the most proximal segment of the feeding artery (e.g. M1 segment of MCA). A control measurement was made in the corresponding contralateral proximal artery. Blood flow was measured using imaging software with FDA clearance for clinical 4D flow post-processing for cardiac MRI. Changes in blood flow were assessed for significance using two-tailed paired t-tests. Baseline AVM nidus volume ranged from 4.6-10.2mL. All AVMs were treated with single fraction SRS, prescription dose 16-20 Gy. Follow up time ranged from 3-17 months. Baseline and follow up blood flow measurements in L/min are displayed in table 1. In feeding arteries, blood flow decreased by a mean of 49% proximally and by 54% distally (both p<0.05). There was no detectable change in blood flow in control arteries (mean change 12%, p = 0.28). Blood flow through cerebral AVM feeding arteries decreases significantly after SRS by time of first follow up as assessed by 4D-Flow MRI. 4D-Flow is a promising early marker of AVM response to SRS. Future studies are needed to determine if this hemodynamic response correlates to decreased risk of hemorrhage prior to radiographic AVM obliteration.Abstract 232; Table 1PatientSpetzler-Martin GradeDistal BaselineDistal Follow UpProximal BaselineProximal Follow UpControl BaselineControl Follow Up130.120.040.500.210.230.24240.290.130.560.280.030.05340.160.070.410.180.080.07420.420.240.510.350.250.26meann/a0.250.120.490.250.150.16SDn/a0.130.080.070.070.100.10 Open table in a new tab

Feasibility of dose escalation using intraoperative radiotherapy following resection of large brain metastases compared to post-operative stereotactic radiosurgery

Post-operative SRS (stereotactic radiosurgery) for large brain metastases is challenged by risks of radiation necrosis that limit SRS dose. Intraoperative radiotherapy (IORT) is a potential alternative, however standard dose recommendations are lacking. Twenty consecutive brain metastases treated with post-operative SRS were retrospectively compared to IORT plans generated for 10-30Gy in 1 fraction to 0-5mm by estimating the applicator size and distance from critical organs using pre-operative and post-operative MRI. Additionally, 7 consecutive patients treated with IORT 30Gy to surface were compared to retrospectively generated SRS plans using the post-operative MRI to 15-20Gy and 30Gy in 1 fraction marginal dose. For the 20 resection cavities treated with SRS and retrospectively compared to IORT, IORT from 10 to 30Gy resulted in lower or not significantly different doses to the optic apparatus and brainstem. Comparatively for the 7 patients treated with IORT 30Gy to retrospective SRS plans to standard 15-20Gy and 30Gy marginal dose, IORT resulted in significantly lower doses to the optic apparatus and brainstem. At a median follow-up of 6.2 months, 86% of patients treated with surgery and IORT achieved local control and 0% developed radiographic or symptomatic radiation necrosis. Critical organ dosimetry for IORT remains generally lower than that achieved with single fraction SRS following resection of large brain metastases. We recommend 30Gy to surface as the preferred prescription, consistent with the dose recommendation for IORT in glioblastoma used in the ongoing INTRAGO-II phase-III trial. Early clinical outcomes appear promising for surgery and IORT.

Fractionated Stereotactic Radiosurgery for Brain Metastases Using the Novalis Tx® System.

ObjectiveTo evaluate the efficacy of fractionated stereotactic radiosurgery (FSRS) performed using the Novalis Tx® system (BrainLAB AG, Feldkirchen, Germany; Varian Medical Systems, Palo Alto, CA, USA) for brain metastases.MethodsBetween March 2013 and July 2016, 23 brain metastases patients were admitted at a single institute. Twenty-nine lesions too large for single session stereotactic radiosurgery or located in the vicinity of eloquent structures were treated by FSRS. Based on the results obtained, we reviewed the efficacy and toxicity of FSRS for the treatment of brain metastases.ResultsThe most common lesion origin was lung (55%) followed by breast (21%). Median overall survival was 10.0 months (95% confidence interval [CI], 4.9–15.0), and median progression-free survival was 10.0 months (95% CI, 2.1–13.9). Overall survival rates at 1 and 2 years were 58.6% and 36.0%, respectively. Local recurrence and neurological complications affecting morbidity each occurred in two cases. ConclusionFSRS using the Novalis-Tx® system would appear to be an effective, safe noninvasive treatment modality for large and eloquently situated brain metastases. Further investigation is required on a larger number of patients.

33 Is hypofractionation safer than single-fraction radio surgery? The effect of fractionation on radionecrosis

Introduction: Radiation-induced brain necrosis (RN) is a relatively uncommon (5-20%) but potentially severe adverse effect of stereotactic radiosurgery (SRS) for brain metastasis(BM). We attempted to establish the effect of hypo-fractionation on RN rates by reviewing patients having simultaneous multi-fraction and single fraction treatment of BM at our centre. Methods: Patients receiving simultaneous 1 (20-24Gy) or 3 fraction (21-24Gy) SRS treatments were identified in our institution’s database. Serial post-SRS MRIs were reviewed to determine the lesion quotient (LQ), or maximum cross sectional area on T1 plus gadolinium divided by T2 FLAIR sequences. LQ less than 0.3 was considered RN. Result: Twenty-two patients were followed for a median 320 days. Sixteen patients developed radionecrosis in 21 of 62 lesions (33%), four of which were symptomatic (20%). Eleven of these lesions received 3 fractions and ten received one fraction. RN risk increased with increasing tumor volume (log odds ratio=1.12, p=0.04). There was no difference in incidence of RN in patients who received whole brain radiotherapy (WBRT) (p=0.11), hypo-fractionation (p=0.98) or had a higher maximum dose (p=0.71). Radiographic RN, however, did not clear in any patients who developed it. Eight patients developed a local recurrence (12%), six of which occurred in the single fraction group. Conclusion: Radionecrosis was significantly related to tumor volume but not fractionation, WBRT, or maximum dose. Overall, our results indicate patients receiving SRS for multiple brain metastasis have a higher rate of radionecrosis than the literature and poorer survival despite having equivalent local control.

Phosphatidylinositol-3-Kinase Mutations Are Associated With Increased Local Failure in Brain Metastases Treated With Radiation

Todetermine whether phosphatidylinositol-3-kinase (PI3K) mutations confer suboptimal local control after radiation therapy (RT) for brain metastases. We retrospectively reviewed 259 patients with brain metastases treated with RT during the period 2004 to 2017 for whom tumor genetic data (MSK-IMPACT) were available for primary or metastatic lesions. Associations between clinical factors, PI3K mutations status, and local failure (LF) were evaluated with univariate and multivariate competing risks regression. A total of 112 patients received whole brain radiation therapy (WBRT) to a median dose of 30Gy in 10 fractions, and 147 patients received stereotactic radiosurgery (SRS) to 338 lesions; 276 lesions were treated with single fraction SRS (median dose 21Gy) and 76 lesions over 3 to 5 fractions SRS (median dose 30Gy). PI3K mutations were present in 36 WBRT patients (32%) and 44 SRS patients (30%). For WBRT, patients with PI3K mutations (hazard ratio 2.67, P<.001) were found to be at higher risk for LF on multivariable analysis, and the 1-year cumulative incidence of LF was 50% (95% confidence interval [CI] 32%-65%) for patients with PI3K mutations versus 26% (95% CI 17%-37%) for patients without PI3K mutations. For SRS lesions, while PI3K mutations positivity was not statistically significantly associated with LF, higher rate of LF was observed: 1-year LF cumulative incidence of 11% (95% CI 6%-17%) for patients with PI3K mutations versus 5% (95% CI 3%-9%) for patients without PI3K mutations. Patients with PI3K mutations are at higher risk for LF for brain metastases after RT. Novel therapeutic strategies to improve treatment outcomes in these patients should be considered.

To frame or not to frame? Cone-beam CT-based analysis of head immobilization devices specific to linac-based stereotactic radiosurgery and radiotherapy.

PurposeNoninvasive frameless systems are increasingly being utilized for head immobilization in stereotactic radiosurgery (SRS). Knowing the head positioning reproducibility of frameless systems and their respective ability to limit intrafractional head motion is important in order to safely perform SRS. The purpose of this study was to evaluate and compare the intrafractional head motion of an invasive frame and a series of frameless systems for single fraction SRS and fractionated/hypofractionated stereotactic radiotherapy (FSRT/HF‐SRT).MethodsThe noninvasive PinPoint system was used on 15 HF‐SRT and 21 SRS patients. Intrafractional motion for these patients was compared to 15 SRS patients immobilized with Cosman‐Roberts‐Wells (CRW) frame, and a FSRT population that respectively included 23, 32, and 15 patients immobilized using Gill‐Thomas‐Cosman (GTC) frame, Uniframe, and Orfit. All HF‐SRT and FSRT patients were treated using intensity‐modulated radiation therapy on a linear accelerator equipped with cone‐beam CT (CBCT) and a robotic couch. SRS patients were treated using gantry‐mounted stereotactic cones. The CBCT image‐guidance protocol included initial setup, pretreatment and post‐treatment verification images. The residual error determined from the post‐treatment CBCT was used as a surrogate for intrafractional head motion during treatment.ResultsThe mean intrafractional motion over all fractions with PinPoint was 0.62 ± 0.33 mm and 0.45 ± 0.33 mm, respectively, for the HF‐SRT and SRS cohort of patients (P‐value = 0.266). For CRW, GTC, Orfit, and Uniframe, the mean intrafractional motions were 0.30 ± 0.21 mm, 0.54 ± 0.76 mm, 0.73 ± 0.49 mm, and 0.76 ± 0.51 mm, respectively. For CRW, PinPoint, GTC, Orfit, and Uniframe, intrafractional motion exceeded 1.5 mm in 0%, 0%, 5%, 6%, and 8% of all fractions treated, respectively.ConclusionsThe noninvasive PinPoint system and the invasive CRW frame stringently limit cranial intrafractional motion, while the latter provides superior immobilization. Based on the results of this study, our clinical practice for malignant tumors has evolved to apply an invasive CRW frame only for metastases in eloquent locations to minimize normal tissue exposure.