Symptomatic Adverse Radiation Effects Research Articles

Multi-institutional study of reirradiation for recurrent high grade glioma.

2063 Background: Treatment options are limited for recurrent WHO Grade 3-4 glioma (HGG). Reirradiation (ReRT) is an option, but the ideal treatment regimen and the benefit of concurrent and adjuvant systemic therapy in the recurrent setting remains unclear. Methods: A retrospective review of patients with recurrent HGG treated with reRT was conducted at 12 institutions. Eligible patients were treated with two courses of fractionated RT (>3 fractions) for glioma with the second course being for HGG. To estimate overall and progression free survival times, the Kaplan-Meier method was used. To assess the relationship between survival times and study variables, Cox proportional hazard regression models were used to calculate hazard ratios and the corresponding 95% confidence interval along with the p-value. SAS (version 9.4, Cary, NC, USA) was used for all analyses. P values < 0.05 were assumed to be statistically significant. Results: 482 eligible patients were identified from 1997 to 2023. 235 (54%) had histologic confirmation of glioblastoma at reRT. The median age at reRT was 53.1 years and median KPS was 80. 196 patients (51%) were treated with reRT at their initial recurrence and 122 (30%) had an IDH mutation. The most common reRT dose and number of fractions were 35 Gy and 10 fractions. 192 patients (44%) and 95 (24%) received concurrent (conc) and adjuvant (adj) temozolomide (TMZ) respectively and 116 (27%) and 110 (28%) received conc and adj bevacizumab (BEV) respectively with reRT. Median OS and PFS were 9.8 and 5.3 months. OS (16.6 vs 7.8 months, HR 2.44 p < 0.01) and PFS (8.6 vs 4.6 months, HR 1.85 p < 0.01) were longer in patients with IDH mutations. Receipt of conc and adj TMZ with reRT was associated with improved OS (HR 0.67 p < 0.01 and HR 0.49 p < 0.01 respectively) and PFS (HR 0.66 p <0.01 and HR 0.47 p < 0.01 respectively). Receipt of concBEV with reRT was associated with worse OS (HR 1.66 p < 0.01) but not PFS (HR 1.15 p = 0.28). AdjBEV was not associated with OS or PFS. Concurrent and adjTMZ were associated with improved OS ( p = 0.04 and <0.01) and PFS ( p = 0.01 and <0.01) for IDHwt tumors. In IDHmt tumors, concTMZ was associated with improved OS but not PFS ( p = 0.03 and 0.11), while adjTMZ was associated with improved OS and PFS ( p = 0.05 and <0.01). Symptomatic adverse radiation effects and Grade 3 or greater neurologic toxicity were seen in 107 (25%) and 86 (20%) of patients respectively. Neither conc nor adjBEV nor TMZ were associated with symptomatic ARE. ConcBEV was associated with lower (13% vs 23%, p = 0.03) and concTMZ was associated with higher rates (25% vs 15%, p = 0.01) of Grade 3 or greater neurologic toxicity. Conclusions: The use of concurrent and adjuvant TMZ with reRT are associated with improved OS and PFS in recurrent HGG. OS and PFS are improved with conc and adjTMZ for IDHwt tumors, while there was no PFS benefit to concTMZ in IDHmt tumors. The rate of high grade neurologic toxicity was decreased with the use of concurrent BEV and increased with the use of concTMZ.

Local control and survival after stereotactic radiosurgery for colorectal cancer brain metastases: an international multicenter analysis.

The goal of this study was to characterize local tumor control (LC), overall survival (OS), and safety of stereotactic radiosurgery for colorectal brain metastasis (CRBM). Ten international institutions participating in the International Radiosurgery Research Foundation provided data for this retrospective case series. This study included 187 patients with CRBM (281 tumors), with a median age of 62 years and 56.7% being male. Most patients (53.5%) had solitary tumors, although 10.7% had > 5 tumors. The median tumor volume was 2.7 cm3 (IQR 0.22-8.1 cm3), and the median margin dose was 20 Gy (IQR 18-22 Gy). The 3-year LC and OS rates were 72% and 20%, respectively. Symptomatic adverse radiation effects occurred in 1.6% of patients. In the multivariate analysis, age > 65 years and tumor volume > 4.0 cm3 were significant predictors of tumor progression (hazard ratio [HR] 2.6, 95% CI 1.4-4.9; p = 0.003 and HR 3.4, 95% CI 1.7-6.9; p < 0.001, respectively). Better performance status (Karnofsky Performance Scale score > 80) was associated with a reduced risk of tumor progression (HR 0.38, 95% CI 0.19-0.73; p = 0.004). Patient age > 62 years (HR 1.6, 95% CI 1.1-2.3; p = 0.03) and the presence of active extracranial disease (HR 1.7, 95% CI 1.1-2.4; p = 0.009) were significantly associated with worse OS. Stereotactic radiosurgery offers a high LC rate and a low rate of symptomatic adverse radiation effects for the majority of CRBMs. The OS and LC favored younger patients with high functional performance scores and inactive extracranial disease.

Outcomes of Gamma Knife Radiosurgery for Brain Metastases in the Motor Cortex.

To study the clinical, imaging, and survival outcomes in patients with motor cortex brain metastases treated with stereotactic radiosurgery (SRS). Imaging and clinical data were obtained from our prospective patient registry. Tumor volumes were obtained from serial imaging data. The outcomes of 208 patients with metastases involving the motor cortex who underwent SRS between 2012 and 2021 were analyzed. A total of 279 metastases (0.01 cm 3 -12.18 cm 3 , mean 0.74 cm 3 ) were irradiated. The SRS margin dose varied from 10 to 20 Gy (mean 16.9 Gy). The overall tumor control rate was 97.8%. Perilesional edema was noted in 69 (25%) tumors at presentation. Adverse radiation effects (ARE) were noted in 6% of all tumors but were symptomatic in only 1.4%. Median time to appearance of symptomatic ARE was 8 months. Edema without ARE was observed in 13%. New focal seizures were noted in 5 patients (2%) and new generalized seizures in 1 patient (0.3%). Thirty-six patients (17%) presented with motor deficits. At final follow-up, 32 (85%) were improved or unchanged, 13 (41%) had a normal examination, 10 (31%) had mild deficits, and 9 (28%) still had moderate deficits. New remote brain metastases were found in 31% of patients at a median of 8 months. After treatment, the Karnofsky performance score distribution of the population showed an overall right shift and a median survival of 10 months. Patients with incidentally found brain metastases had significantly better survival than those presenting with deficits (median 13 vs 9 months) ( P = .048). Absence of a neurological deficit, recursive partitioning analysis Class I and II, and dose >18 Gy were each associated with a significant survival advantage. SRS for motor cortex metastases is safe in most patients and effective in providing tumor control. Patients treated before neurological deficits develop show better outcomes.

Fractionated Radiosurgery in Large Volume Relapsed Glioblastoma Multiforme

Relapse is part of the natural history in glioblastoma (GBM) and there are limited advances in surgical, alternating electric field therapy (TTF), chemotherapy (CTX), immunotherapy or radiotherapeutic treatments. Radiosurgery (SRS) and Fractionated Stereotactic Radiosurgery (FSRS) may be an option, but remains controversial. We performed a review of our patients with recurrent large volume glioblastoma treated with FSRS over the last 5 years. Since January 2017 to December 2021, we reviewed our experience with large volume FSRS for the treatment of selected patients with large volume GBM recurrence. Indications and treatment planning were done according RANO criteria MR images. Overall survival (OS) and progression-free survival (PFS) after salvage FSRS were the primary endpoints evaluated. Response to FSRS was assessed with clinical evaluation and using brain MR. A total of 15 patients with GBM recurrence were treated in our institution after surgery plus adjuvant radio-chemotherapy treatment with Stupp regimen. Median age was 58 (53-74) years old. Prescription dose was 24 Gy in 4 fractions in consecutive days. Selected patients for FSRS had a good PS with large volume relapse and edema. The target volume (CTV) was the enhanced volume in MR T2 classically known has edema and the relapsed T1 volume with gadolinium uptake. The median PTV was 118.5 cc (50-244cc). 33% of the patients received concurrent chemotherapy or biological therapy with or after FSRS. No patient developed G3 symptomatic adverse radiation effect. Median follow-up was 28.6 (10-82) months from diagnosis. PFS after salvage FSRS was 11 (4-55) months. Median overall survival was 12.4 months after FSRS. Our experience and results suggest that reirradiation provides encouraging disease control and survival rates in GBM relapsed patients. The large volume FSRS associated or not with systemic treatment had good tolerance and can improve survival of patients with relapsed large volume GBM. Randomized controlled trials are needed to establish the optimal management strategy for recurrent GBM.

Treatment of adverse radiation effects with Boswellia serrata after failure of pentoxifylline and vitamin E: illustrative cases.

Adverse radiation effects (AREs) can occur after stereotactic radiosurgery (SRS), and symptomatic cases are often treated with corticosteroids, pentoxifylline, and vitamin E. The supplement 5-Loxin (Boswellia serrata) is an extract of Indian frankincense that inhibits vascular endothelial growth factor expression and has been shown to reduce perilesional edema in brain tumor patients undergoing fractionated radiation. Three patients underwent SRS for meningioma or metastasis and developed symptomatic AREs at 4 to 8 months. They were initially treated with corticosteroids, pentoxifylline, and vitamin E with transient improvement followed by recurrent neurological symptoms and imaging findings as steroids were tapered off. All patients were rescued by the administration of 5-Loxin with resolution of neurological symptoms and imaging changes, discontinuation of steroids, and no medication side effects. The author's early experience with 5-Loxin has been encouraging, and this supplement has become the author's first-line treatment for acute radiation effects after SRS. The author reserves bevacizumab for significant mass effect or failure of oral therapy. 5-Loxin has many advantages including low cost, ease of use, and patient tolerability. More experience is needed to confirm the role of 5-Loxin in the upfront treatment of AREs.

Adverse radiation effect and freedom from progression following repeat stereotactic radiosurgery for brain metastases.

The authors previously evaluated risk and time course of adverse radiation effects (AREs) following stereotactic radiosurgery (SRS) for brain metastases, excluding lesions treated after prior SRS. In the present analysis they focus specifically on single-fraction salvage SRS to brain metastases previously treated with SRS or hypofractionated SRS (HFSRS), evaluating freedom from progression (FFP) and the risk and time course of AREs. Brain metastases treated from September 1998 to May 2019 with single-fraction SRS after prior SRS or HFSRS were analyzed. Serial follow-up magnetic resonance imaging (MRI) and surgical pathology reports were reviewed to score local treatment failure and AREs. The Kaplan-Meier method was used to estimate FFP and risk of ARE measured from the date of repeat SRS with censoring at the last brain MRI. A total of 229 retreated brain metastases in 124 patients were evaluable. The most common primary cancers were breast, lung, and melanoma. The median interval from prior SRS/HFSRS to repeat SRS was 15.4 months, the median prescription dose was 18 Gy, and the median duration of follow-up imaging was 14.5 months. At 1 year after repeat SRS, FFP was 80% and the risk of symptomatic ARE was 11%. The 1-year risk of imaging changes, including asymptomatic RE and symptomatic ARE, was 30%. Among lesions that demonstrated RE, the median time to onset was 6.7 months (IQR 4.7-9.9 months) and the median time to peak imaging changes was 10.1 months (IQR 5.6-13.6 months). Lesion size by quadratic mean diameter (QMD) showed similar results for QMDs ranging from 0.75 to 2.0 cm (1-year FFP 82%, 1-year risk of symptomatic ARE 11%). For QMD < 0.75 cm, the 1-year FFP was 86% and the 1-year risk of symptomatic ARE was only 2%. Outcomes were worse for QMDs 2.01-3.0 cm (1-year FFP 65%, 1-year risk of symptomatic ARE 24%). The risk of symptomatic ARE was not increased with tyrosine kinase inhibitors or immunotherapy before or after repeat SRS. RE on imaging was common after repeat SRS (30% at 1 year), but the risk of a symptomatic ARE was much less (11% at 1 year). The results of repeat single-fraction SRS were good for brain metastases ≤ 2 cm. The authors recommend an interval ≥ 6 months from prior SRS and a prescription dose ≥ 18 Gy. Alternatives such as HFSRS, laser interstitial thermal therapy, or resection with adjuvant radiation should be considered for recurrent brain metastases > 2 cm.

Adverse Radiation Effects Following Gamma Knife Radiosurgery.

Gamma Knife Radiosurgery (GKRS) is now an established standard of treatment for the small-sized arteriovenous malformations (AVMs), meningiomas, schwannomas, metastasis, and other benign diseases. With an exponential rise in the indications for GKRS, we have witnessed an increase in the adverse radiation effects (ARE) following GKRS. The common AREs and associated risk factors following GKRS have been described for pathologies including vestibular schwannomas, arteriovenous malformations, meningiomas, and metastases based on the authors' experience, and a simplified management protocol has been provided for radiation-induced changes based on clinical and radiologic parameters. The dose, volume, location, and repeat stereotactic radiosurgery (SRS) are implied as the risk factors for ARE. Clinically symptomatic AREs require oral steroids for weeks to alleviate symptoms. In refractory cases, bevacizumab and surgical resection can be offered as a treatment modality. Appropriate dose planning strategy and hypofractionation for larger lesions help in mitigating the AREs.

Frameless Cobalt60-Based Hypofractionated Stereotactic Radiosurgery (HSRS) for Brain Metastases: Impact of Dose and Volume

<h3>Purpose/Objective(s)</h3> Frameless, gated, image-guided, Cobalt⁶⁰-based hypofractionated stereotactic radiosurgery (Co⁶⁰-HSRS) is a novel technical paradigm in the treatment of brain metastases that allows for both the dosimetric benefits of the Co⁶⁰ based stereotactic radiosurgery (SRS) platform as well as the biologic benefits of fractionation. We report mature local control (LC) and adverse radiation effects (ARE) outcomes following 5 fraction Co⁶⁰-HSRS for intact brain metastases. <h3>Materials/Methods</h3> All patients with intact brain metastases treated with 5-fraction Co⁶⁰-HSRS between 2017-2020 were retrospectively reviewed. Patients were typically selected for HSRS as opposed to single fraction SRS if the metastases were larger (>2cm diameter), were in eloquent areas, or were in proximity to another lesion receiving HSRS. Survival estimates were determined per patient using Kaplan Meier methods, and LC as well as symptomatic ARE rates were determined per lesion using competing risk methods. Univariable competing risk regression using Fine and Gray's methods were performed, and subsequent multivariable (MVA) regression using a backwards step-wise selection technique generated the final adjusted models. <h3>Results</h3> In total 299 metastases in 146 patients were identified. The median clinical and radiologic follow-up was 10.6 (range 0.5-49.9) and 10.7 months (range 0.5-47.6), respectively. The median maximum tumor diameter and volume were 1.7 cm (range, 0.2-3.9 cm) and 2.38 cc (range, 0.004-24.92 cc), respectively. The median total dose and prescription isodose was 27.5 Gy (range, 20-27.5 Gy) in 5 daily fractions and 52% (range, 45%-93%), respectively. The median overall survival (OS) was 12.7 months and the 1-year LC rate was 85%. MVA identified a total dose of 27.5 Gy vs. ≤25 Gy (hazard ratio [HR] 0.59, p = 0.042), and prior chemotherapy exposure (HR 1.99, p = 0.015), as significant predictors of LC. The 1-year ARE rate was 10.8% and the symptomatic ARE rate was 1.8%. MVA identified a gross tumor volume of ≥4.5cc (HR 7.29, p < 0.001) and a mean intra-tumoral dose of ≥39 Gy (HR 3.17, p = 0.034) as significant predictors of symptomatic ARE. <h3>Conclusion</h3> Moderate total doses in 5 daily fractions of Co⁶⁰-HSRS were associated with high rates of LC and a low incidence of symptomatic ARE. A prescription dose of 27.5 Gy was superior with respect to local control versus ≤25 Gy in 5 daily fractions. Target volumes of 4.5cc or larger as well as mean dose >39 Gy, were associated with higher rates of symptomatic necrosis. Further study will help refine the optimal dosimetric constraints for Co⁶⁰-HSRS.

Resection with intraoperative cesium-131 brachytherapy as salvage therapy for recurrent brain tumors.

The authors' objective was to examine the safety and efficacy of salvage intracranial cesium-131 brachytherapy in combination with resection of recurrent brain tumors. The authors conducted a retrospective chart review of consecutive patients treated with intraoperative intracranial cesium-131 brachytherapy at a single institution. Permanent suture-stranded cesium-131 seeds were implanted in the resection cavity after maximal safe tumor resection. The primary outcomes of interest were local, locoregional (within 1 cm), and intracranial control, as well as rates of overall survival (OS), neurological death, symptomatic adverse radiation effects (AREs), and surgical complication rate graded according to Common Terminology Criteria for Adverse Events version 5.0. Between 2016 and 2020, 36 patients received 40 consecutive cesium-131 implants for 42 recurrent brain tumors and received imaging follow-up for a median (interquartile range [IQR]) of 17.0 (12.7-25.9) months. Twenty patients (55.6%) with 22 implants were treated for recurrent brain metastasis, 12 patients (33.3%) with 16 implants were treated for recurrent atypical (n = 7) or anaplastic (n = 5) meningioma, and 4 patients (11.1%) were treated for other recurrent primary brain neoplasms. All except 1 tumor (97.6%) had received prior radiotherapy, including 20 (47.6%) that underwent 2 or more prior radiotherapy treatments and 23 (54.8%) that underwent prior resection. The median (IQR) tumor size was 3.0 (2.3-3.7) cm, and 17 lesions (40.5%) had radiographic evidence of ARE prior to salvage therapy. Actuarial 1-year local/locoregional/intracranial control rates for the whole cohort and patients with metastases and meningiomas were 91.6%/83.4%/47.9%, 88.8%/84.4%/45.4%, and 100%/83.9%/46.4%, respectively. No cases of local recurrence of any histology (0 of 27) occurred after gross-total resection (p = 0.012, log-rank test). The 1-year OS rates for the whole cohort and patients with metastases and meningiomas were 82.7%, 79.1%, and 91.7%, respectively, and the median (IQR) survival of all patients was 26.7 (15.6-36.4) months. Seven patients (19.4%) experienced neurological death from progressive intracranial disease (7 of 14 total deaths [50%]), 5 (13.9%) of whom died of leptomeningeal disease. Symptomatic AREs were observed in 9.5% of resection cavities (n = 4), of which 1 (2.4%) was grade 3 in severity. The surgical complication rate was 16.7% (n = 7); 4 (9.5%) of these patients had grade 3 or higher complications, including 1 patient (2.4%) who died perioperatively. Cesium-131 brachytherapy resulted in good local control and acceptable rates of symptomatic AREs and surgical complications in this heavily pretreated cohort, and it may be a reasonable salvage adjuvant treatment for this patient population.

Gamma knife icon based hypofractionated stereotactic radiosurgery (GKI-HSRS) for brain metastases: impact of dose and volume.

Gamma Knife Icon-based hypofractionated stereotactic radiosurgery (GKI-HSRS) is a novel technical paradigm in the treatment of brain metastases that allows for both the dosimetric benefits of the GKI stereotactic radiosurgery (SRS) platform as well as the biologic benefits of fractionation. We report mature local control and adverse radiation effect (ARE) outcomes following 5 fraction GKI-HSRS for intact brain metastases. Patients with intact brain metastases treated with 5-fraction GKI-HSRS were retrospectively reviewed. Survival, local control, and adverse radiation effect rates were determined. Univariable and multivariable regression (MVA) were performed on potential predictive factors. Two hundred and ninety-nine metastases in 146 patients were identified. The median clinical follow-up was 10.7months (range 0.5-47.6). The median total dose and prescription isodose was 27.5Gy (range, 20-27.5) in 5 daily fractions and 52% (range, 45-93), respectively. The median overall survival (OS) was 12.7months, and the 1-year local failure rate was 15.2%. MVA identified a total dose of 27.5Gy vs. ≤ 25Gy (hazard ratio [HR] 0.59, p = 0.042), and prior chemotherapy exposure (HR 1.99, p = 0.015), as significant predictors of LC. The 1-year ARE rate was 10.8% and the symptomatic ARE rate was 1.8%. MVA identified a gross tumor volume of ≥ 4.5cc (HR 7.29, p < 0.001) as a significant predictor of symptomatic ARE. Moderate total doses in 5 daily fractions of GKI-HSRS were associated with high rates of LC and a low incidence of symptomatic ARE.

The Impact of Dose on Treatment Outcomes in Patients Treated for Brain Metastases With a Hypofractionated Technique on Gamma Knife

Purpose: Brain metastases are the most common type of diagnosed central nervous system tumours, occurring in approximately 40% of all cancer patients. Historically, treatment consisted of whole brain radiotherapy (WBRT), however current practice for patients with limited intracranial disease, is to offer stereotactic radiosurgery (SRS). In 2016, our centre acquired a Gamma Knife (GK) unit, designed to treat brain metastases with a stereotactic approach, using an invasive frame based immobilization system. In 2017, a mask based frameless system was introduced, expanding indications for patients and allowing for the treatment of hypofractionated courses on this unit. Given the unique dosimetric characteristics of the GK, our research focused on patients treated for intact brain metastases, with hypofractionated doses, and aimed to report adverse radiation effects and local control. Methods: This was a retrospective study, including all patients with intact brain metastases, treated on the GK unit, with hypofractionated (5 fraction) treatments, between 2017-2020. Hypofractionated treatments are generally given to larger lesions (≥2cm) or those lesions situated in eloquent areas of the brain, such as the motor cortex or brainstem. Patients were excluded if the specific metastases received prior SRS or hypofractionated treatment, however those who received previous whole brain radiotherapy were included. Those without post -treatment imaging follow up were also excluded from the analyses. Competing risk methods were used to determine local control and symptomatic adverse radiation effect (ARE) rates per lesion and Kaplan Meier methods were used to determine survival estimates. The Common Terminology Criteria for Adverse events (CTCAE) v 5.0 was used to determine symptomatic ARE. Results: A total of 146 patients and 299 metastases were identified. The most frequent histologies were lung (38.5%), breast (31.4%) and melanoma (13.7%). 53.4% of patients had a KPS > 70% and the majority had multiple lesions treated at the time of their hypofractionated radiosurgery (62.3%). Only 18% had received prior WBRT. Prescribed doses ranged from 20-27.5Gy with the median being 27.5Gy in 5 fractions prescribed in 54.2% of cases. The median volume of the treated lesions was 2.54cc (range 0.004-24.92cc). Clinical follow-up ranged from 0.5 to 49.9 months, with the median being 13.8 months. The 1 year local control was 84.8%, and on multivariable analyses, 1 year local failure rates increased (8.3% (95% CI, 4.6-13.2) vs 23.5% (95%CI,16.6-31)) with decreasing prescribed doses (27.5Gy vs 20-25Gy) respectively. In terms of adverse radiation effects, there were 32 (10.7%) incidents identified, of which 14 (44%) were symptomatic. For symptomatic AREs, the 1 and 2 year rates were 1.7% (95% CI, 0.7-3.8) and 4.5% (95% CI, 2.4-7.7), respectively. Overall survival for this patient population was 12.7 months, with the 1 and 2 year rates being 51.3% (95% CI 42.6-59.2) and 36.8% (95%, CI 28.5-45.1), respectively. Conclusion: For patients with intact brain metastases, GK hypofractionated treatments are a safe and effective treatment modality. A 27.5Gy prescription dose in 5 fractions is associated with improved local control and a low risk of symptomatic ARE at one year.

Adverse radiation effects in volume-staged radiosurgery for large arteriovenous malformations: a multiinstitutional study.

The optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. One approach is volume-staged stereotactic radiosurgery (VS-SRS). The authors previously reported efficacy of VS-SRS for large AVMs in a multiinstitutional cohort; here they focus on risk of symptomatic adverse radiation effects (AREs). This is a multicentered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM, with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. The authors evaluated permanent, transient, and total ARE events that were symptomatic. Patients received 2-4 total volume stages. The median age was 33 years at the time of the first SRS volume stage, and the median follow-up was 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cm3 (range 7.7-94.4 cm3), with a median margin dose per stage of 17 Gy (range 12-20 Gy). A total of 64 patients (25%) experienced an ARE, of which 19 were permanent. Rather than volume, maximal linear dimension in the Z (craniocaudal) dimension was associated with toxicity; a threshold length of 3.28 cm was associated with an ARE, with a 72.5% sensitivity and a 58.3% specificity. In addition, parietal lobe involvement for superficial lesions and temporal lobe involvement for deep lesions were associated with an ARE. Size remains the dominant predictor of toxicity following SRS, but overall rates of AREs were lower than anticipated based on baseline features, suggesting that dose and size were relatively dissociated through volume staging. Further techniques need to be assessed to optimize outcomes.

Salvage Resection and Intracranial Cesium-131 Brachytherapy for Brain Tumors

Management of progressive brain tumors following high dose radiotherapy is controversial. In select cases, surgical resection can provide rapid relief of regional mass effect and edema, and highly focal adjuvant re-irradiation can be administered in the form of brachytherapy. Permanent low-dose rate cesium-131 brachytherapy may offer dosimetric and radiobiologic advantages over other isotopes. The purpose of this study was to examine the safety and efficacy of intracranial cesium-131 brachytherapy after surgical resection in a heavily pre-treated patient cohort.A retrospective chart review was conducted of all patients treated with intraoperative intracranial cesium-131 brachytherapy from an institutional database. Treatment consisted of maximal safe resection followed by implantation of suture-stranded cesium-131 seeds, maintaining approximately 10mm spacing between seeds, with a planned target dose of 80 Gy to 5mm depth. Local failure was defined as recurrence in or contacting the resection cavity after salvage resection and brachytherapy. Regional failure was defined as recurrence within 10mm of the resection cavity. Recurrence was defined as a new lesion or growth of ≥25% in any axial dimension on interval MRI. Toxicity was collected based on CTCAE 4.0.A total of 35 patients with a median imaging follow up of 17.0 months (interquartile range [IQR] 9.7-25.9) underwent 41 consecutive cesium-131 implants between 2016 and 2020. 20 patients (59%; N = 22 implants) were treated for recurrent brain metastasis, 12 patients (34%; N = 16 implants) were treated for recurrent atypical (N = 8) or anaplastic meningioma (N = 4), and 3 patients (9%) were treated for recurrent glioma (N = 2) or hemangiopericytoma (N = 1). A majority of lesions had received prior surgery (N = 28, 66.7%, range 0-3 prior surgeries) and 34 patients had received prior high dose radiation. 34 of 41 (82.9%) tumors had received prior radiosurgery, and 12 (29.2%) had undergone prior external beam radiation (range 50-60 Gy). 17 of 41 lesions (41.5%) had radiologic evidence of adverse radiation/treatment effect (ARE) prior to salvage therapy. Median tumor size was 3.0cm (IQR 2.3-3.7). Overall actuarial local/loco-regional control at 1-year was 91.6%/84.7% (89.8%/88.9% for metastases and 100%/82.5% for meningiomas). Crude loco-regional control was 86.3% for metastases, 75% for meningiomas, and 66.7% for other lesions. Symptomatic ARE following treatment was observed in 9.8% (N = 4) resection cavities. The surgical complication rate was 14.6% (N = 6 total, N = 3 [7.3%] grade 3-5) including 1 peri-operative death.Cesium-131 brachytherapy in this heavily pre-treated cohort resulted in good local control and an acceptable rate of symptomatic adverse radiation effect and toxicity and may be a reasonable treatment option for this select population.W.C. Chen: None. M. Lafreniere: None. C. Phuong: None. M. Lometti: None. O. Morin: None. B.P. Ziemer: None. H. Vasudevan: Research Grant; Children's Tumor Foundation. Patent/License Fees/Copyright; Genentech, Eli Lilly. S. Hervey-Jumper: None. P.V. Theodosopoulos: None. S. Magill: None. S.E. Fogh: Independent Contractor; Accuray. J.L. Nakamura: None. L. Boreta: None. P.K. Sneed: None. M.W. McDermott: Chair; Miami Baptist. D. Raleigh: None. S.E. Braunstein: Advisory Board; Radiation Oncology Questions, LLC.

Stereotactic Radiosurgery for Choroid Plexus Tumors: A Report of the International Radiosurgery Research Foundation

Choroid plexus tumors (CPT) are rare epithelial tumors of the choroid plexus. Gross total resection (GTR) may be curative, but it is not always possible. To evaluate the role of Gamma Knife stereotactic radiosurgery (GKSRS) as either a primary or adjuvant management option for WHO grade I-III CPT through a multicenter project. A total of 32 patients (20 females) with a total of 43 treated tumors were included in the analysis. A total of 25 patients (78%) had undergone initial surgical resection. The median total tumor volume was 2.2 cc, and the median margin and maximum doses were 13 and 25.5 Gy, respectively. Local tumor control was achieved in 69% of cases. Local tumor progression-free survival (PFS) rate for low-grade tumors at 1, 3, and 5 yr was 90%, 77%, 58%, respectively. The actuarial local tumor PFS rate for high-grade tumors at 1, 3, and 5 yr was 77%, 62%, and 62%, respectively. There was no significant difference in local tumor control rates between low- and high-grade CPT (P=.3). Gender, age, and degree of resection were not associated with treated tumor PFS. Distant intracranial spread developed in 6 patients at a median of 22 mo after initial SRS. Actuarial distant brain tumor PFS rate at 1, 2, 5, and 10 yr was 93%, 88%, 78%, and 65%, respectively. Three patients (9%) developed persistent symptomatic adverse radiation effects at a median of 11 mo after the procedure. GKSRS represents a minimally invasive alternative management strategy for imaging defined or surgically recurrent low- and high-grade CPT.

RADT-15. PREOPERATIVE SINGLE FRACTION RADIOSURGERY VERSUS POSTOPERATIVE FRACTIONATED RADIOSURGERY FOR RESECTED BRAIN METASTASES: A BI-INSTITUTIONAL ANALYSIS OF SAFETY AND CLINICAL OUTCOMES

Abstract BACKGROUND Preoperative single fraction radiosurgery (SRS) and postoperative fractionated SRS delivered over 3–5 fractions have been shown to have favorable outcomes compared to postoperative single fraction SRS for resected brain metastases. No study has directly compared these 2 treatment approaches. METHODS Records for patients with resected brain metastases treated with either single fraction preoperative SRS or fractionated (3-5 fractions) postoperative SRS were reviewed. Preoperative SRS was 10-20% dose reduced compared to standard and surgery generally followed within 48 hours. Eligibility criteria included solid tumor metastases, 1 brain metastasis resected, and no previous cranial RT. Fine-Gray and Cox multivariable (MVA) and propensity score matched (PSM) analyses were used. RESULTS A total of 330 patients (137 preoperative; 193 postoperative) were included. Median dose was 15 Gy in 1 fraction and 24 Gy in 3 fractions, respectively. In MVA, preoperative SRS was significantly associated with higher risk of cavity local recurrence (LR, hazard ratio (HR) 2.04, p=0.002) and lower risk of leptomeningeal disease (LMD, HR 0.41, p=0.05). There was no difference in adverse radiation effect (ARE) or overall survival (OS) between groups. In the PSM analysis (65 matched pairs), 1-year outcomes for preoperative vs. postoperative SRS were as follows - cavity LR: 22.9% vs. 3.1%, p&amp;lt; 0.001, LMD: 4.2% vs. 15.5%, p=0.04, ARE: 3.2% vs. 7.9%, p=0.73, composite endpoint (cavity LR, symptomatic ARE, or LMD): 27.6% vs. 20.1%, p=0.33, OS: 56.3% vs. 62.3%, p=0.8. CONCLUSIONS Preoperative single fraction SRS and postoperative fractionated (3-5 fractions) SRS demonstrate distinct patterns of failure. Compared to postoperative SRS, preoperative SRS was associated with increased risk of cavity LR and lower risk of LMD in both multivariable and PSM analyses. There was no difference in risk of ARE or OS. Methods to reduce preoperative SRS cavity LR, such as with higher dose fractionated regimens, should be considered.

Clinical and Imaging Response to Trigeminal Schwannoma Radiosurgery: A Retrospective Analysis of a 28-Year Experience.

Objective The purpose of this study was to evaluate long-term clinical outcomes and tumor control after stereotactic radiosurgery (SRS) for trigeminal schwannoma (TS). Methods During a 28-year period (1989-2017), 50 patients underwent SRS for TS. The median patient age was 51 years (range: 15-87 years). A total of 17 patients had a previous tumor resection: 10 had a single procedure, 5 had two procedures, and 2 had three procedures. The median and mean times between tumor resection and SRS were 12 and 24 months (range: 1-90 months), respectively. Four patients had neurofibromatosis II (NF2). Based on location, tumors were classified as root type (7), ganglion type (22), or dumbbell type (21). The median radiosurgery target volume was 3.4 cm 3 (range: 0.10-18 cm 3 ), median target dose was 14 Gy (range: 12-20 Gy), and the median number of isocenters was 6 (range: 1-15). The median and mean times to last follow-up was 36.9 and 55.2 months (range: 4-205 months), respectively. Eighteen patients (36%) had longer than 5-year follow-up, and seven patients (14%) had longer than 10-year follow-up. Results The tumor control rate was 92% and the clinical improvement or stabilization rate was 94%. After SRS, the rates of progression free survival (PFS) at 1, 5, and 10 years were 98, 84, and 84%, respectively. Factors associated with improved PFS were female sex ( p = 0.014) and smaller tumor volume ( p = 0.022). In this series, we did not find that tumor type (root, ganglion, and dumbbell) had a statistically significant correlation to PFS. Forty-seven patients had neurological signs or symptoms at presentation. At last follow-up, neurological signs or symptoms improved in 22/47 (47%), remained unchanged in 24/50 (48%), and worsened due to tumor progression in 3/50 (6%). One patient (2%) developed temporary symptomatic adverse radiation effect (ARE) and three additional patients (6%) had transient imaging evidence of peritumoral reactive edema but no new symptoms. Conclusion As a single outpatient procedure, SRS was associated with long-term freedom from additional management in 84% of patients. Nearly half the treated patients experienced improvement in neurological symptoms or signs.

Evaluation of radiological recurrence patterns following gamma knife radiosurgery for solitary meningioma previously treated via cranial surgery

The use of gamma knife radiosurgery (GKS) for meningiomas after cranial surgery has been extensively evaluated; however, studies on tumor progression, including recurrence out of the margin dose line, are scarce. Hence, we aimed to evaluate the meningioma recurrence after GKS within and out of the margin dose. We included 37 consecutive patients with World Health Organization (WHO) grade 1 meningiomas who were treated with GKS following cranial surgery. Radiologically indicated recurrences were classified into three patterns by their relationship to the margin dose and tumor. The median follow-up was 58.9 months; 2 (5.4%) patients died. Only 2 (5.4%) patients did not keep active daily lives because of tumor progression. Cumulative local control at 5 years was 85.2%. Local recurrence and recurrence out of the margin dose occurred in 5 (13.5%) and 13 (35.1%) patients, respectively. A larger preoperative maximum diameter was a risk factor for local recurrence (hazard ratio [HR]: 2.118; P = 0.033), adjacent progression (HR: 1.633; P = 0.015), and remote progression (HR: 2.016; P = 0.003). Symptomatic adverse radiation effects occurred in 1 patient. Salvage GKS and cranial surgery were performed in 9 (24.3%) and 8 (21.6%) patients, respectively. Progression to WHO grade 2–3 occurred in 5 (13.5%) patients. A larger preoperative maximum diameter was a risk factor for progression of WHO grade (HR: 2.016, P = 0.033). Progression out of the margin dose was associated with a larger preoperative tumor size.

Adverse Radiation Effect After Hypofractionated Stereotactic Radiosurgery in 5 Daily Fractions for Surgical Cavities and Intact Brain Metastases

Limited data exist quantifying the risk of adverse radiation effect (ARE) specific to hypofractionated stereotactic radiosurgery (HSRS). We present our analyses of the risk of ARE after 5 daily fractions of HSRS to surgical cavities and intact metastases. One hundred and eighty-seven consecutively treated patients with 118 surgical cavities and 132 intact metastases were retrospectively reviewed. All patients were treated with 5 daily fractions with a 2 mm planning target volume applied. Clinical and dosimetric variables were assessed to identify predictors of ARE. The median total prescribed dose was 30 Gy (range, 20-35 Gy) and median follow-up was 12 months. One hundred forty-four patients (77%) received treatment to a single target. Median planning target volumes for resection cavity and intact metastases were 24.9 cm3 and 7.7 cm3, respectively. ARE and symptomatic ARE were observed 21.2% and 10.8% of targets, respectively, and the median time to ARE was 8 months. Time to ARE was <6 months for 38%, 6 to 12 months for 43%, and >12 months for 19% of targets. Multivariable analysis identified intact metastases versus cavities (odds ratio [OR], 3.65; 95% confidence interval [CI], 1.33-10) as a significant predictor of symptomatic ARE. Specific to cavity HSRS, prior whole brain radiation therapy (OR 7.73; 95% CI, 1.67-35.69) and prior stereotactic radiosurgery (OR 8.66; 95% CI, 1.14-65.7) were significant predictors of symptomatic ARE. For intact metastases, the total brain minus gross tumor volume (GTV) receiving 30 Gy (BMC30) was a significant predictor of symptomatic ARE (OR, 1.21; 95% CI, 1.02-1.43), and a volume-based BMC30 threshold of 10.5 cm3 was significant with an OR of 7.21 (95% CI, 1.31-39.45). The risk of ARE was greater for intact metastases compared with cavities after HSRS. For intact lesions, the BMC30 was predictive for symptomatic necrosis, and a threshold of 10.5 cm3 may guide treatment planning.

RADI-21. STEREOTACTIC RADIOSURGERY FOR 10 OR MORE BRAIN METASTASES PROVIDES EXCELLENT RATES OF INTRACRANIAL DISEASE CONTROL WITH SUPERIOR HIPPOCAMPAL SPARING

BACKGROUND: Recent evidence supports hippocampal sparing during whole brain radiotherapy (HS-WBRT) to improve neurocognitive outcomes in patients with brain metastases (BM). This study sought to quantify the hippocampal dosimetry and treatment efficacy of stereotactic radiosurgery (SRS) to 10 or greater BM to clarify the roles of SRS and WBRT. METHODS: Patients at a single institution treated with SRS to 10 or more BM without WBRT from 1999 to 2016 were retrospectively reviewed. Treatment-related outcomes including overall survival (OS), freedom from progression (FFP), freedom from new metastases (FFNM), and adverse radiation effect (ARE) were quantified. Hippocampal volumes were retrospectively delineated and dosimetry was evaluated in patients treated with upfront SRS. RESULTS: 143 patients with a total of 2198 lesions met criteria for inclusion with 75 patients treated with upfront SRS and 68 treated as salvage from prior WBRT. Median age was 57 (IQR: 46–65) and median KPS 80 (IQR: 70–90). Histologies included breast (n=52), lung (n=49), melanoma (n=30), and other (n=12). Median number of lesions per patient was 13 (IQR 11–17) with median total volume of treatment of 4.1 cc (IQR 2.0–9.9). 12-month FFP per lesion for upfront and salvage treatment was 96.8% (95% CI: 95.5–98.1) and 83.6% (95% CI: 79.9–87.5) respectively (p < 0.001). 12-month FFNM for upfront and salvage FFSRS was 18.8% (95% CI: 10.9–32.3) versus 19.2% (95% CI: 9.7–37.8) respectively (p = 0.90). Mean hippocampal dose was 150 cGy (IQR 100–202). Symptomatic ARE was observed in 2% of patients or 1% of treated lesions. CONCLUSIONS: High rates of local control can be achieved when treating patients with greater than 10 BM with hippocampal doses that are dramatically lower than for HS-WBRT. Hippocampal sparing is readily achievable with expected rates of new metastatic lesions developing in treated patients with low rates of symptomatic ARE.

Stereotactic Radiosurgery for Brainstem Cavernous Malformations: An Updated Systematic Review and Meta-Analysis

This study was conducted to achieve more conclusive evidence for the efficacy of stereotactic radiosurgery (SRS) for brainstem cavernous malformations (BSCMs). A literature search of PubMed, EMBASE, and Web of Science was performed and studies reporting the outcomes of SRS for BSCMs were included. The primary outcome was the pre-SRS and post-SRS hemorrhage rates; the pooled incidence rate ratio (IRR) with 95% confidence interval was chosen as effect size. Lesion control, symptom change, and radiation-related complications were evaluated. A total of 576 patients across 14 studies were included in this meta-analysis. The post-SRS hemorrhage rate was significantly decreased compared with the pre-SRS rate (IRR, 0.123; P < 0.001), and the hemorrhage rate 2 years after SRS was significantly lower than that within 2 years after SRS (IRR, 0.317; P < 0.001). Ten among 14 studies have shown that the symptoms were improved or stationary after SRS. Lesion volume was reduced in 47.3% of the patients and was stationary in 49.4% on the last follow-up images. Symptomatic adverse radiation effects (AREs) developed in 7.3% and permanent AREs were observed in 2.2%. In subgroup analysis, studies having mean marginal dose of ≤13 Gy showed statistically significantly lower development of symptomatic AREs than those having mean marginal dose of >13Gy (2.0% vs. 10.8%; P= 0.008). SRS using a relatively low marginal dose can be a safe and effective treatment for BSCM. Further prospective studies are necessary to confirm the optimal radiation dose and efficacy of SRS for BSCMs.