Hypofractionated Stereotactic Radiosurgery Research Articles

Upfront stereotactic radiosurgery versus adjuvant radiosurgery for parasagittal and parafalcine meningiomas: a systematic review and meta-analysis.

Parafalcine and parasagittal (PFPS) are common locations for meningiomas. Surgical resection for these tumors, the first-line treatment, poses challenges due to their proximity to critical structures. This systematic review investigates the use of stereotactic radiosurgery (SRS) as a treatment for PFPS meningiomas, aiming to elucidate its safety and efficacy. The review adhered to PRISMA guidelines. Searches were conducted on MEDLINE, Embase, and Cochrane. Inclusion criteria involved studies on SRS for PFPS meningiomas, reporting procedure outcomes and complications. Tumors were presumed or confirmed to be WHO grade 1. Data was systematically extracted. Meta-analysis was performed where applicable. The review included data from eight studies, 821 patients with 878 lesions. Tumor control was achieved in greater than 80% of cases. Adverse radiation effects were reported in 7.3% of them. Recurrence and further surgical approach were observed in 17.1% and 9.2% of cases, respectively. Symptom improvement was noted in 33.2% of patients. Edema occurred in approximately 25.1% of patients. A subgroup of 283 patients had upfront SRS, achieving tumor control in approximately 97% of such cases. SRS is a safe and effective treatment for PFPS meningiomas, both as an adjuvant therapy and as an upfront treatment for often smaller tumors. Post-SRS edema can typically be managed medically and usually does not require further surgical intervention. Further studies should provide more specific data on PFPS meningiomas. The use of single and hypofractionated SRS for larger volume PFPS meningiomas should be more explored to better define the risks and benefits.

LMAP-19 THE ROLE OF STEREOTACTIC RADIOSURGERY IN PATIENTS WITH BRAIN METASTASES FROM COLORECTAL CANCERS

Abstract BACKGROUND AND OBJECTIVES The role of stereotactic radiosurgery (SRS) for patients with brain metastases from colorectal cancers (CRC) has not been established. The authors present a single-institution experience of CRC patients who underwent SRS with metastatic brain spread. METHODS We retrospectively analyzed 112 metastatic CRC patients (64 female, 57.14%) with 450 brain metastases that were treated with Gamma Knife SRS between 2000-2022. The median age at SRS was 63 years (range: 28-86) and the median Karnofsky Performance Score (KPS) was 80 (range: 60-100). The primary sites were colon (86 patients, 76.79%) and rectal (26 patients, 21%). Three patients underwent hypo-fractionated SRS (3 sessions) with a median margin dose of 27 Gy (range: 27- 30). All other patients underwent single-session SRS with a median margin dose of 18 Gy (range: 11-20). RESULTS The median patient survival after SRS was 7 months (range: 1-174). Ninety-eight (87.5%) patients expired at last follow up and 15 patients (15.31%) died related to progressive intracranial disease. KPS < 80 at SRS presentation (p=0.03, HR: 0.63, 95% CI: 0.41-0.96) was associated with inferior overall survival using multivariate analysis. Seventeen patients (15.18%) had documented local tumor progression after SRS, at a median time of 7 months (range: 3-34) between SRS and progression. Twenty-six patients (23.21%) developed new brain metastases at a median of 5 months (range: 2-26) between SRS and new tumor detection. KPS ≥ 80 (p=0.05, HR: 0.96, 95% CI: 0.93-0.99), and < 3 brain metastases at SRS presentation (p<0.01, HR: 3.62, 95% CI: 1.53-8.56) were associated with better distant tumor control on multivariate analysis. The incidence of adverse radiation effects was 5.36%. CONCLUSIONS SRS effectively controls brain metastases from CRC with a low risk of treatment-related toxicity, allowing patients to focus on primary disease management. During follow-up, the development of progressive or additional metastases can be safely treated by repeat SRS.

Hypofractionated stereotactic radiosurgery (HSRS) as a salvage treatment for brain metastases failing prior stereotactic radiosurgery (SRS)

Various treatment options exist to salvage stereotactic radiosurgery (SRS) failures for brain metastases, including repeat SRS and hypofractionated SRS (HSRS). Our objective was to report outcomes specific to salvage HSRS for brain metastases that failed prior HSRS/SRS. Patients treated with HSRS to salvage local failures (LF) following initial HSRS/SRS, between July 2010 and April 2020, were retrospectively reviewed. The primary outcomes were the rates of LF, radiation necrosis (RN), and symptomatic radiation necrosis (SRN). Univariable (UVA) and multivariable (MVA) analyses using competing risk regression were performed to identify predictive factors for each endpoint. 120 Metastases in 91 patients were identified. The median clinical follow up was 13.4 months (range 1.1-111.1), and the median interval between SRS courses was 13.1 months (range 3.0-56.5). 115 metastases were salvaged with 20-35Gy in 5 fractions and the remaining five with a total dose ranging from 20 to 24Gy in 3-fractions. 67 targets (56%) were postoperative cavities. The median re-treatment target volume and biological effective dose (BED10) was 9.5cc and 37.5Gy, respectively. The 6- and 12- month LF rates were 18.9% and 27.7%, for RN 13% and 15.6%, and for SRN were 6.1% and 7.0%, respectively. MVA identified larger re-irradiation volume (hazard ratio [HR] 1.02, p = 0.04) and shorter interval between radiosurgery courses (HR 0.93, p < 0.001) as predictors of LF. Treatment of an intact target was associated with a higher risk of RN (HR 2.29, p = 0.04). Salvage HSRS results in high local control rates and toxicity rates that compare favorably to thosesingle fraction SRS re-irradiationexperiences reported in the literature.

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.

Outcomes in Intact and Resected Brain Metastasis Patients Treated with Five-Fraction Stereotactic Radiosurgery

<h3>Purpose/Objective(s)</h3> Stereotactic radiosurgery (SRS) is the preferred local treatment for many brain metastasis patients (pts), often combined with surgical resection for larger and/or symptomatic lesions. Advances in SRS technology now permit hypofractionated regimens to mitigate toxicity without compromising efficacy. Optimal target volumes and planning parameters for hypofractionated SRS (HF-SRS), however, remain a matter of debate. Herein, we report clinical outcomes and predictive factors following HF-SRS. <h3>Materials/Methods</h3> Pts undergoing HF-SRS for intact (iHF-SRS) or resected (rHF-SRS) brain metastases from 2008 to 2018 at our institution were retrospectively identified. They received linear accelerator-based image-guided HF-SRS in 5 fractions at 5, 5.5, or 6 Gy/fraction. Planning target volumes were created by expanding contrast-enhancing lesions and/or resection cavity by 1 mm and 2mm in iHF-SRS and rHF-SRS, respectively. Actuarial rates of local progression (LP), distant brain progression (DBP), leptomeningeal disease (LMD), and overall survival (OS) were calculated. Uni- (UVA) and multivariate (MVA) Cox models assessed the impact of clinical factors on OS. Fine and Gray's cumulative incidence model for competing events examined the effect of factors on LP and DBP. Logistic regression examined predictors of LMD. <h3>Results</h3> Among 445 pts, median age at HF-SRS was 63.5 years; 87% had KPS ≥70. Common primary tumor sites were lung (43%), breast (16%), GI (11%), and skin (11%). 77% of pts had evidence of systemic disease at time of HF-SRS, and 70% received immunotherapy or small molecule inhibitors (IT/SMI) following HF-SRS. 53% of pts underwent surgical resection, with ≥2 brain metastases present in 32% of rHF-SRS and 84% of iHF-SRS cases. 75% of pts received 5 Gy/fraction. Median OS was 5.1 (95% CI 4.3 - 6.0) months following iHF-SRS and 12.8 (95% CI 10.8 - 16.2) months following rHF-SRS. On MVA for iHF-SRS, OS was associated with receipt of IT/SMI (HR 0.48, 95% CI 0.33 – 0.69). For rHF-SRS, OS was associated with neurologic symptoms (HR 1.91, 95% CI 1.29 – 2.83), IT/SMI use (HR 0.43, 95% CI 0.28 – 0.65), and dural contact (HR 0.69, 95% CI 0.47 – 0.99). For LP, the cumulative incidence (CI) was 14.5% (95% CI 11.4 – 18.0%) at 18 months. On UVA, LP was not associated with any tumor or patient specific factors. For DBP, MVA showed CI to be significantly greater with rHF-SRS than iHF-SRS (p=0.01), with respective 24-month CI rates of 50.0% (95% CI 43.3 – 56.3%) and 35.7% (95% CI 29.2 – 42.2%). LMD (57 events: 33% nodular, 67% diffuse) was observed in 17.1% of rHF-SRS and 8.1% of iHF-SRS cases (OR 2.46, 95% CI 1.34 – 4.53), and was associated with primary site (lung versus breast OR 0.40, 95% CI 0.20 – 0.80; other versus breast OR 0.28, 95% CI 0.13 – 0.60). Biopsy-proven radionecrosis was observed in 17 (3.8%) pts. <h3>Conclusion</h3> 5-fraction HF-SRS demonstrated favorable rates of LC in post-operative and intact settings. Corresponding LMD rates are comparable to those of other studies.

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.

117: Frameless COBALT60-Based Hypofractionated Stereotactic Radiosurgery (HSRS) for Brain Metastases: Impact of Dose and Volume

117: Frameless COBALT60-Based Hypofractionated Stereotactic Radiosurgery (HSRS) for Brain Metastases: Impact of Dose and Volume

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 Treatment Outcome of CyberKnife-Based Stereotactic Radiotherapy for Intracranial and Extracranial Nonvestibular Schwannomas: A Single-Center Experience

Data on the outcomes of CyberKnife-based hypofractionated stereotactic radiosurgery (hSRS) for intracranial and extracranial nonvestibular schwannomas (nVSs) are not sufficient. Patients who underwent hSRS for nVSs between 2010 and 2019 were retrospectively reviewed. A total of 39 patients with 39 nVSs were identified. The mean age was 53 (±18) years, and 20 patients (51%) were women. Twenty-five patients (64%) had previous surgeries. Seventeen patients (44%) had nVSs extending outside the cranium. The mean prescribed dose covering 95% of the planning target volume was 22Gy (±3.7 Gy), the mean fractionation was 4 (±2), and the mean target volume was 13cm3 (±16cm3). The radiological tumor control rate was 100% during the mean follow-up period of 67months (±37months). Thirty-seven patients (95%) were clinically stable during the mean follow-up period of 72months (±35months). Nine patients (23%) suffered from transient adverse radiation effects (AREs), including transient tumor expansion, and 2 (5%) suffered from permanent AREs. We summarized the treatment outcomes of hSRS for nVSs. Although all patients achieved radiological tumor control, the risk of either transient or permanent ARE was high. Therefore, it is necessary to monitor patients for clinical deterioration due to AREs.

Single- and hypofractionated stereotactic radiosurgery for large (> 2cm) brain metastases: a systematic review.

Since frameless stereotactic radiosurgery (SRS) techniques have been recently introduced, hypofractionated SRS (HF-SRS) for large brain metastases (BMs) is gradually increasing. To verify the efficacy and safety of HF-SRS for large BMs, we aimed to perform a systematic review and compared them with SF-SRS. We systematically searched the studies regarding SF-SRS or HF-SRS for large (> 2cm) BM from databases including PubMed, Embase, and the Cochrane Library on July 31, 2018. Biologically effective dose with the α/β ratio of 10 (BED10), 1-year local control (LC), and radiation necrosis (RN) were compared between the two groups, with the studies being weighted by the sample size. The 15 studies with 1049 BMs that described 1-year LC and RN were included. HF-SRS tended to be performed in larger tumors; however, higher mean BED10 (50.1 Gy10 versus 40.4 Gy10, p < 0.0001) was delivered in the HF-SRS group, which led to significantly improved 1-year LC (81.6 versus 69.0%, p < 0.0001) and 1-year overall survival (55.1 versus 47.2%, p < 0.0001) in the HF-SRS group compared to the SF-SRS group. In contrast, the incidence of radiation toxicity was significantly decreased in the HF-SRS group compared to the SF-SRS group (8.0 versus 15.6%, p < 0.0001). HF-SRS results in better LC of large BMs while simultaneously reducing RN compared to SF-SRS. Thus, HF-SRS should be considered a priority for SF-SRS in patients with large BMs who are not suitable to undergo surgical resection.

Hypofractionated versus single-fraction stereotactic radiosurgery for the treatment of brain metastases: A systematic review and meta-analysis

ObjectiveThis systematic review and meta-analysis aimed to synthesize the latest evidence on the hypofractionated stereotactic radiosurgery (HF-SRS) compared to single-fraction stereotactic radiosurgery (SF-SRS) for the treatment of brain metastases. MethodsWe systematically searched PubMed, Scopus, EuropePMC, ProQuest, and Cochrane Central Databases. Original research articles investigating patients with brain metastasis receiving HF-SRS or SF-SRS reporting the local control/failure and/or radionecrosis during follow-up were included. ResultsThere were 1100 patients from 7 studies. 616 lesions were allocated to HF-SRS group and 777 lesions were allocated to SF-SRS group. Pooled rate of local control was 88% (95% CI 84%, 91%) in HF-SRS group and 81% (95% CI 74%, 88%) in the SF-SRS groups. Local control was higher in patients receiving HF-SRS compared to SF-SRS (OR 1.53 [95% CI 1.08, 2.18], p = 0.018; I2: 0%). Pooled rate of radionecrosis was 7% (95% CI 3%, 12%) in HF-SRS group and 15% (95% CI 8%, 23%) in the SF-SRS groups. Similar rate of radionecrosis was observed in both HF-SRS and SF-SRS (OR 0.82 [95% CI 0.31, 2.21], p = 0.698; I2: 61.3%). Grading of Recommendations, Assessment, Development and Evaluations (GRADE) qualification showed a low level of certainty for the higher local control in patients receiving HF-SRS compared to SF-SRS and a very low level of certainty for similar risk of radionecrosis between the two groups. ConclusionThis meta-analysis showed that HF-SRS was associated with higher local control and similar rate of radionecrosis compared to SF-SRS in patients with brain metastases.PROSPERO ID: CRD42020210469

Safety and efficacy of Hypofractionated stereotactic radiosurgery for high-grade Gliomas at first recurrence: a single-center experience

BackgroundThe optimal treatment for recurrent high-grade gliomas (rHGGs) remains uncertain. This study aimed to investigate the efficacy and safety of hypofractionated stereotactic radiosurgery (HSRS) as a first-line salvage treatment for in-field recurrence of high-grade gliomas.MethodsBetween January 2016 and October 2019, 70 patients with rHGG who underwent HSRS were retrospectively analysed. The primary endpoint was overall survival (OS), and secondary endpoints included both progression-free survival (PFS) and adverse events, which were assessed according to Common Toxicity Criteria Adverse Events (CTCAE) version 5. The prognostic value of key clinical features (age, performance status, planning target volume, dose, use of bevacizumab) was evaluated.ResultsA total of 70 patients were included in the study. Forty patients were male and 30 were female. Forty-nine had an initial diagnosis of glioblastoma (GBM), and the rest (21) were confirmed to be WHO grade 3 gliomas. The median planning target volume (PTV) was 16.68 cm3 (0.81–121.96 cm3). The median prescribed dose was 24 Gy (12–30 Gy) in 4 fractions (2–6 fractions). The median baseline of Karnofsky Performance Status (KPS) was 70 (40–90). With a median follow-up of 12.1 months, the median overall survival after salvage treatment was 17.6 months (19.5 and 14.6 months for grade 3 and 4 gliomas, respectively; p = .039). No grade 3 or higher toxicities was recorded. Multivariate analysis showed that concurrent bevacizumab with radiosurgery and KPS > 70 were favourable prognostic factors for grade 4 patients with HGG.ConclusionsSalvage HSRS showed a favourable outcome and acceptable toxicity for rHGG. A prospective phase II study (NCT04197492) is ongoing to further investigate the value of hypofractionated stereotactic radiosurgery (HSRS) in rHGG.

Redistributing Central Target Dose Hot Spots for Hypofractionated Radiosurgery of Large Brain Tumors: A Proof-of-Principle Study.

The present proof-of-principle study investigated radiobiological effects of redistributing central target dose hot spots across different treatment fractions during hypofractionated stereotactic radiosurgery (HSRS) of large intracranial tumors. Redistribution of central target dose hot spots during HSRS was simulated, and its effects were evaluated in eight cases of brain metastases. To assess dose variations in the target across N number of treatment fractions, a generalized biologically effective dose (gBED) was formulated. The gBED enhancement ratio was defined as the ratio of gBED in the tested treatment plan (with central target dose hot spot redistributions across fractions) to gBED in the conventional treatment plan (without central target dose hot spot redistributions). At a median αvalue of 0.3/Gy, the tested treatment plans resulted in average gBED increases of 15.6±3.5% and 8.3±1.8% for α/β ratios of 2 and 10Gy, respectively. In comparison with conventional treatment plans, the differences in the Paddick conformity index and gradient index did not exceed 2%. Redistributing central target dose hot spots across different treatment fractions during HSRS may be considered promising for enhancing gBED in the target. It may be beneficial for management of large intracranial neoplasms; thus, it warrants further clinical testing.

Possible Overcoming of Tumor Hypoxia with Adaptive Hypofractionated Radiosurgery of Large Brain Metastases: A Biological Modeling Study.

The present biological modeling study evaluated possible application of adaptive hypofractionated stereotactic radiosurgery (HSRS), which involves escalation of the prescription dose according to the gradual decrease in the tumor volume between treatment sessions separated by 2- to 3-week intervals, in the management of large brain metastases. To investigate the effects of dose escalation during three-stage adaptive HSRS, a generalized biologically effective dose (gBED) model was applied. Accounting for both a nonuniform dose distribution inside the target and tumor hypoxia was implemented, and normal brain radiation dose distributions were assessed. In comparison with conventional three-stage HSRS (with an identical prescription dose of 10 Gy at each treatment session), adaptive HSRS resulted in a 30-40% increase in gBED. This effect was especially prominent in late-responding targets (with α/βratios from 3 to 10Gy) and in neoplasms containing a high percentage of hypoxic cells. Despite dose escalation in the target, irradiation of the adjacent normal brain tissue was kept within safe limits at a level similar to that applied in conventional three-stage HSRS. Adaptive HSRS theoretically results in significant enhancement of gBED in the target and may possibly overcome resistance to irradiation, which is caused by tumor hypoxia. These advantages may translate into higher treatment efficacy in cases of large brain metastases.

Five-Fraction Stereotactic Radiosurgery (SRS) For Resected Brain Metastases

Randomized trials have demonstrated improved rates of local control (LC) in patients who undergo postoperative stereotactic radiosurgery (SRS) compared to observation following resection of brain metastases. However, for larger tumors, dose reduction is commonly required for single-fraction SRS in order to minimize toxicity, potentially compromising LC. Hypofractionated SRS (HF-SRS) may improve LC with minimal toxicity, in particular radionecrosis (RN). In this IRB-approved retrospective study, patients who received 5-fraction HF-SRS at Duke University Medical Center from 2008 to 2018 were identified. GTVs were contoured per consensus guidelines; PTV expansions were 2mm. Patients were treated with 5 or 5.5 Gy per fraction, the latter typically utilized for tumor histologies considered to be radioresistant. Treatment consisted of linear-accelerator-based image-guided SRS with HD-MLC. Data collected included demographics, primary disease characteristics and treatment details. For patients with sufficient radiographic follow up, rates of LC, distant brain failure (DBF), RN, overall survival (OS), and leptomeningeal disease (LMD) were calculated. 250 patients were identified. Lung was the most common primary site (43%), followed by breast (16%) and GI (13%). 69% had evidence of active systemic disease at time of treatment. Of 144 patients with recorded Karnofsky performance status (KPS), 90% had a KPS of 70 or greater. Median age at time of craniotomy was 63 years. Median time interval between craniotomy and start of SRS was 4 weeks (range 1-16). 86% of patients had at least 1 subsequent brain MRI post SRS. 3-year LC was 84% and median OS was 12.8 months (95% CI 10.9-15.5). 24-month incidence of DBF was 50% (95% CI 44%-56%). 24-month incidence of RN was 4% (95% CI 2% to 7%). 14% of patients developed LMD. On univariate analysis (UVA), a dose of 5.5 Gy/fraction was associated with improved LC, HR 0.25 (0.08, 0.82), as was no prior treatment, HR 0.40 (0.20, 0.82). Location, receipt of immunotherapy or small molecule inhibitor, dural contact, and cavity volume were not significant for LC on UVA. Compared to historical standards of single fraction SRS, post-operative, five-fraction HF-SRS results in low rates of LC and RN. The use of 5.5 Gy per fraction and the absence of prior treatment were associated with improved LC. Rates of LMD in this patient population are comparable to other studies in the postoperative setting.

Brain metastases from primary colorectal cancer: is radiosurgery an effective treatment approach? Results of a multicenter study of the radiation and clinical oncology Italian association (AIRO).

The prognosis of brain metastatic colorectal cancer patients (BMCRC) is poor. Several local treatments have been used, but the optimal treatment choice remains an unresolved issue. We evaluated the clinical outcomes of a large series of BMCRC patients treated in several Italian centers using stereotactic radiosurgery (SRS). 185 BMCRC patients for a total of 262 lesions treated were evaluated. Treatments included surgery followed by post-operative SRS to the resection cavity, and SRS, either single-fraction, then hypofractionated SRS (HSRS). Outcomes was measured in terms of local control (LC), toxicities, brain distant failure (BDF), and overall survival (OS). Prognostic factors influencing survival were assed too. The median follow-up time was 33 months (range 3-183 months). Surgery plus SRS have been performed in 28 (10.7%) cases, SRS in 141 (53.8%), and HSRS in 93 (35.5%). 77 (41.6%) patients received systemic therapy. The main total dose and fractionation used were 24 Gy in single fraction or 24 Gy in three daily fractions. Local recurrence occurred in 32 (17.3%) patients. Median, 6 months,1-year-LC were 86 months (95%CI 36-86), 87.2% ± 2.8, 77.8% ± 4.1. Median,6 months,1-year-BDF were 23 months (95%CI 9-44), 66.4% ± 3.9, 55.3% ± 4.5. Median,6 months,1-year-OS were 7 months (95% CI 6-9), 52.7% ± 3.6, 33% ± 3.5. No severe neurological toxicity occurred. Stage at diagnosis, Karnofsky Performance Status (KPS), presence and number of extracranial metastases, and disease-specific-graded-prognostic-assessment (DS-GPA) score were observed as conditioning survival. SRS/HSRS have proven to be an effective local treatment for BMCRC. A careful evaluation of prognostic factors as well as a multidisciplinary evaluation is a valid aid to manage the optimal therapeutic strategy for CTC patients with BMs. The prognosis of BMCRC is poor. Several local treatments was used, but optimal treatment choice remains undefined. Radiosurgery has proven to be an effective local treatment for BMCRC. A careful evaluation of prognostic factors and a multidisciplinary evaluation needed.

Abstract TP491: Hypofractionated Stereotactic Radiosurgery for Brain AVM Post Aruba: Obliteration, Complication, and Hemorrhage Rates

Introduction: Patients harboring brain AVMs associated with moderate-high surgical morbidity (large lesions, deep location and eloquent cortex) are increasingly undergoing hypofractionated stereotactic radiosurgery (SRS) at our institution. Most published literature is based on a single fraction SRS technique. In this review we sought to evaluate/present our hypofractionated SRS experience using the Accuray Cyberknife device. Hypothesis: Cyberknife Stereotactic Radiosurgery (C-SRS) can be used for a high risk brain arteriovenous malformations (AVMs) with high rates of successful complete obliteration and low rates of hemorrhagic, death and major disability. Methods: We performed a retrospective analysis of all patients having undergone Cyberknife SRS for brain AVMs between 2013-2019 at a large community based tertiary care health system and identified 33 patients. Of these patients 12 had a minimum of 2 year follow-up. We divided the patients into hemorrhagic and non-hemorrhagic presentations, prior endovascular treatment with embolization and based on Spetzler Martin grades. Results: 58% males with median age of 44 and 9% presenting with hemorrhage. Median planning target volume (PTV) was 7.2 cc (range 1.25-15.56 cc) and median HFSRT dose was three fractions (range 3-5) of 10.25 Gy (range 8.5-11 Gy) each. Complete obliteration was achieved in 100% of patients after salvage SRS 21 Gy x1 fraction to a residual AVM volume in 2 patients. The median time to obliteration was 747 days. 3 of 12 patients suffered radiation necrosis1 patient with a large AVM (maximum diameter of 4 cm and PTV of 12.6 cc) suffered re-hemorrhage and radiation necrosis, but ultimately completely obliterated after 402 days and was left with mRS ≤2). Conclusion: Although we have a small sample size, fractionated SRS with Cyberknife resulted in 100% obliteration, low rates recurrent hemorrhage and low morbidity (no mortality). These outcomes are superior to published single fraction radiosurgery results in high risk patients. Further study with a prospective multicenter registry or as part of a larger RCT is warranted.

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.

Assessment of the alpha/beta ratio of the optic pathway to adjust hypofractionated stereotactic radiosurgery regimens for perioptic lesions

Hypofractionation has been recently considered as an alternative to improve stereotactic radiosurgery treatments of lesions close to the optic pathways. To estimate the intrinsic benefit from fractionation versus single-dose radiosurgery for perioptic lesions, the value of the alpha/beta ratio of the optic pathways needs to be known. Based on the linear quadratic (LQ) model, hypofractionation versus single-fraction SRS can be justified in cases where parts of the optic apparatus necessarily receive the full therapeutic peripheral dose, if there is a positive difference between α/s of the lesion and the α/s of the surrounding organs at risk. Furthermore, the knowledge of α/s ratios is required to calculate radiobiological dose parameters, such as the biologically effective dose (BED) and single fraction equivalent dose (SFED), and helps estimate normal tissue complication probability (NTCP), dose constraints, and retreatment doses. Only 3 alpha/beta ratios for the visual system have been published so far, varying between -0.6 and 3.06 Gy. The alpha/beta ratio of the optic pathways was estimated from a fraction equivalent plot based on a meta-analysis of 429 studies published between 2000 and June 2018. We included 15 studies with fraction sizes between 1 and 31, considering the following inclusion criteria: at least one well-documented RION case with detailed dosimetric analysis for the visual system, follow-up period (FUP) of at least 24 months, no tumor progression, no prior radiation. Additionally, we included results from our center on 68 hypofractionated treatments and 161 single-fraction SRS treatments for perioptic lesions. The fraction equivalent (FE) plot method revealed an alpha/beta ratio of the optic pathway of 1.03 Gy, confidence interval [-0.38–1.60]. Well-documented RION cases are rare in the literature; there is still not enough data to distinguish between alpha/beta ratios of the optic chiasm, the nerves, and the tracts. Optimized hypofractionation schedules were calculated for the treatment of meningiomas, chordomas, and brain metastases. Compared to single-fraction SRS, a significant intrinsic benefit from hypofractionation can be achieved, not only for perioptic malignant tumors, but for benign lesions as well, because of the very low alpha/beta ratio of the optic system of 1.03 Gy. An increased single fraction equivalent dose of up to 10% for perioptic meningiomas and of more than 25% for malignant tumors can be reached with optimized hypofractionated stereotactic radiosurgery schedules.

Experience with hypofractionated stereotactic radiosurgery in a series of patients with skull base tumors

Introduction and objective Although the effectiveness of single-fraction brain stereotactic radiosurgery has been extensively demonstrated, recent evidence is suggesting that when skull base lesions are the targets, radiation near critical structures (e.g., optic nerves, and brainstem) should be reduced to avoid radiotoxic effects, with the risk of treatment inefficacy. Hence, in these tumors, hypofractionated stereotactic radiosurgery (HSRS) would offer a therapeutical opportunity. Here, we present our experience with this modality in the management of patients with skull base tumors.