Stereotactic Radiosurgery Radiation Research Articles

OUTCOMES OF STEREOTACTIC RADIOSURGERY/RADIOTHERAPY (SRST) IN MALIGNANT MELANOMA WITH CRANIAL METASTASES - THE WESSEX EXPERIENCE

Abstract AIMS To assess overall survival in malignant melanoma with cranial metastases following stereotactic radio- surgery/radiotherapy (SRST). METHOD Patients with metastatic melanoma who received SRST for their cranial metastases at the Wessex Neuro- Oncology Unit were evaluated between January 2017 and January 2023. Subtype analysis based on BRAF mutation was also performed. Their overall survival (OS) was plotted using Kaplan-Meier graph. RESULTS 121 patients were identified. The mean age at referral was 62 years (range 30-90). 50 patients had a BRAF mutation while 71 were BRAF wild type. This is a heterogenous cohort of patients, ranging from cranial-only disease to widespread disease, receiving one to two lines of systemic treatment. The median OS in patients with malignant melanoma with cranial metastases following SRST is 15 months (similar in both BRAF mutant and BRAF wildtype subgroups). The 3-year survival rate is 22.8% (BRAF mutant – 27.3%, BRAF wildtype - 20.3%). There is a small group of patients (28%) that died within six months of SRST. CONCLUSIONS Limitations were the small number of patients, short follow up period and heterogeneity in terms of systemic therapy. Our experience reveals in malignant melanoma, the median OS is 15 months after SRST to their cranial metastases. We found that BRAF mutation is non-discriminatory when predicting response to SRST and not the sole factor in predicting OS. A small cohort did not benefit from SRST as they survived for 6 months or less. Further analysis of this subgroup is needed to improve patient selection and treatment personalisation.

Morbidity of single-fraction spine radiosurgery for metastatic disease.

e24116 Background: The optimal management of metastatic spine disease involves radiation therapy, with stereotactic radiosurgery (SRS) utilization having increased in adoption while proving to be efficacious and safe. Spine SRS morbidity (fatigue, dermatitis, nausea and esophagitis) is generally mild and depends on the spinal vertebral level(s) treated. More severe adverse events such as vertebral compression fracture (VCF), radiation-induced myelopathy, and tracheoesophageal (TE) fistula have been documented. The potential benefits of single-fraction SRS (sfSRS) over multi-fraction SRS include increased patient convenience, decreased financial toxicity, and increased treatment completion rates. These benefits may potentially be overshadowed by the morbidity of sfSRS versus multifraction SRS. In this analysis, we perform the first comprehensive examination of sfSRS morbidity in the treatment of spinal lesions. Methods: An extensive search of the PubMed database was undertaken through 2/2/23 to find studies examining spinal sfSRS. Search parameters included the terms “single-fraction, spine, radiation SRS OR SBRT” Articles including multi-fractionated regimens only, reviewed sites outside of the spine, or did not report on clinical outcomes/toxicities were excluded. Results: 17 articles met initial inclusion criteria; 9 were added from references for a total of 26 articles comprising at least 2,699 patients (one study reported the number of tumors, not patients). Dose ranges for single-fraction SRS were 8-26 Gy. Commonly noted toxicities were fatigue, nausea/vomiting, and dermatitis which were no worse than moderate/minimal, not requiring invasive intervention. The overall rate of VCF was 16.2%, with an increased propensity at >20 Gy. The proportion of reported segments requiring surgical intervention (operative stabilization, vertebroplasty/kyphoplasty) for VCF after single-fraction SRS was 20.2% (33/163). The rate of TE fistula at 25 Gy was 8.3%, with an overall rate (dose range = 10-28 Gy) of 1.3% with up to 12-years of follow-up. In patients receiving median dose of 24 Gy, the rate of severe esophagitis was 6.8%, myositis was 1.3% (at 1-year) and 8.3% (at 5-years). The rate of peripheral nervous system injury was 2.5% (at 18-26 Gy) and pain flare was 8% (at 16-24 Gy). The rate of ureteral and esophageal stricture was 1.9% each in patients receiving 12-24 Gy. Conclusions: VCF is the most commonly reported severe adverse events with single-fraction spine SRS, particularly for doses > 20 Gy. 80% of VCFs can be successfully managed without invasive intervention. Other severe adverse events are rare – particularly for < 20 Gy – but require post-SRS monitoring to expediently and efficiently intervene if necessary. These findings indicate that single-fraction spine SRS to < 20 Gy is safe with minimal morbidity. Further study regarding the efficacy of such dosing is being evaluated in ongoing clinical trials.

Heterogeneity of HER2 Expression in Circulating Tumor Cells of Patients with Breast Cancer Brain Metastases and Impact on Brain Disease Control.

Simple SummaryResults from a previous study suggested that the number of circulating tumor cells (CTC) might have a role as a biomarker of early distant brain failure in patients with breast cancer brain metastases (BCBM). However, it remains largely underexplored whether heterogeneous HER2 expression in CTC may have a prognostic implication. We evaluated the status of HER2 expression in CTC before and after radiotherapy/radiosurgery for BCBM and observed that the presence of HER2 expression in any moment was associated with longer distant brain failure-free survival, irrespective of the primary immunophenotype of the breast tumor. This finding suggests that the status of HER2 expression in CTC has the potential to improve the treatment selection for patients with BCBM.HER2 expression switching in circulating tumor cells (CTC) in breast cancer is dynamic and may have prognostic and predictive clinical implications. In this study, we evaluated the association between the expression of HER2 in the CTC of patients with breast cancer brain metastases (BCBM) and brain disease control. An exploratory analysis of a prospective assessment of CTC before (CTC1) and after (CTC2) stereotactic radiotherapy/radiosurgery (SRT) for BCBM in 39 women was performed. Distant brain failure-free survival (DBFFS), the primary endpoint, and overall survival (OS) were estimated. After a median follow-up of 16.6 months, there were 15 patients with distant brain failure and 16 deaths. The median DBFFS and OS were 15.3 and 19.5 months, respectively. The median DBFFS was 10 months in patients without HER2 expressed in CTC and was not reached in patients with HER2 in CTC (p = 0.012). The median OS was 17 months in patients without HER2 in CTC and was not reached in patients with HER2 in CTC (p = 0.104). On the multivariate analysis, DBFFS was superior in patients who were primary immunophenotype (PIP) HER2-positive (HR 0.128, 95% CI 0.025–0.534; p = 0.013). The expression of HER2 in CTC was associated with a longer DBFFS, and the switching of HER2 expression between the PIP and CTC may have an impact on prognosis and treatment selection for BCBM.

Radiation Therapy for Brain Metastases: ASCO Guideline Endorsement of ASTRO Guideline.

American Society of Radiation Oncology (ASTRO) has developed a guideline on appropriate radiation therapy for brain metastases. ASCO has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations. "Radiation Therapy for Brain Metastases: An ASTRO Clinical Practice Guideline"2 was reviewed for developmental rigor by methodologists. An ASCO Endorsement Panel subsequently reviewed the content and the recommendations. The ASCO Endorsement Panel determined that the recommendations from the ASTRO guideline, published May 6, 2022, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorses "Radiation Therapy for Brain Metastases: An ASTRO Clinical Practice Guideline."2. Within the guideline, stereotactic radiosurgery (SRS) is recommended for patients with Eastern Cooperative Oncology Group performance status of 0-2 and up to four intact brain metastases, and conditionally recommended for patients with up to 10 intact brain metastases. The guideline provides detailed dosing and fractionation recommendations on the basis of the size of the metastases. For patients with resected brain metastases, radiation therapy (SRS or whole-brain radiation therapy [WBRT]) is recommended to improve intracranial disease control; if there are limited additional brain metastases, SRS is recommended over WBRT. For patients with favorable prognosis and brain metastases ineligible for surgery and/or SRS, WBRT is recommended with hippocampal avoidance where possible and the addition of memantine is recommended. For patients with brain metastases, limiting the single-fraction V12Gy to brain tissue to ≤ 10 cm3 is conditionally recommended.Additional information is available at www.asco.org/neurooncology-guidelines.

Heterogeneity of HER2 expression in circulating tumor cells of patients with breast cancer brain metastases and impact on brain disease control.

2029 Background: The HER2 expression switching in circulating tumor cells (CTC) of breast cancer is dynamic and may have prognostic and predictive clinical implications. This study aims to analyse the association between expression of HER2 in CTC of patients with breast cancer brain metastases (BCBM) and brain disease control. Methods: Exploratory analysis of a prospective assessment (NCT02941536) of CTC before (CTC1) and 4–5 weeks after (CTC2) stereotactic radiotherapy/radiosurgery (SRT). CTC were isolated and quantified by a method of isolation by size of tumors and analyzed by immunocytochemistry to evaluate the expression of HER2. Distant brain failure-free survival (DBFFS), the primary endpoint, and overall survival (OS) were estimated by Kaplan-Meier estimator. Log-rank tests were applied in order to compare the survival curves. For multivariate analysis of prognostic factors that affected DBFFS and OS, the Cox proportional model was adjusted. Results: The median age at SRT was 54 (34-70), the diagnosis-specific graded prognostic assessment (DS-GPA) was 1–2 in 17.5% and 2.5–4 in 82.5% and the primary immunophenotype (PIP) was HER2-enriched in 51%, luminal B (LB) in 31% and triple negative (TN) in 18% of the total of 39 patients. CTC were detected in all 39 patients before SRT and the median CTC1 was 2 CTC/mL. After SRT, CTC were detected in 34 of 35 patients (4 deaths between CTC1 and CTC2) and the median CTC2 was 2.33 CTC/mL. HER2 was expressed in CTC1 and/or CTC2 in 9 patients, of which only 2 patients had PIP HER2-enriched. After a median follow-up of 16.6 months, there were 15 patients with distant brain failure and 16 deaths. The median DBFFS and OS were 15.3 and 19.5 months, respectively. Median DBFFS was 7 months in patients with PIP TN and was not reached in PIP LB and HER2-enriched (p = 0.036); 14 months in patients with DS-GPA 1-2 and 7 months with DS-GPA 2.5-4 (p = 0.017); 10 months in patients without HER2 expressed in CTC and not reached in patients with HER2 expressed in CTC (p = 0.012). Median OS was 4.8 months in patients with PIP TN and was not reached in PIP LB and HER2-enriched (p = 0.0026); 19.54 months in patients with DS-GPA 1-2 and 7.6 months with DS-GPA 2.5-4 (p = 0.00088); 17 months in patients without HER2 expressed in CTC and not reached in patients with HER2 expressed in CTC (p = 0.104). On multivariate analysis, DBFFS was superior in patients with PIP HER2-enriched (HR 0.128, 95% CI 0.025–0.534; p = 0.013) and OS was superior in patients with PIP HER2-enriched (HR 0.073, 95% CI 0.018-0.288; p < 0.0001) and LB (HR 0.224, 95% CI 0.062–0.816; p = 0.023). The status of expression of HER2 in CTC was not included in Cox model for DBFFS due to lack of events in patients with HER2 expressed in CTC. Conclusions: The expression of HER2 in CTC was associated with a longer DBFFS and the switching of HER2 expression between PIP and CTC may have impact on prognosis and treatment selection of BCBM.

Ipilimumab and Stereotactic Radiosurgery with CyberKnife® System in Melanoma Brain Metastases: A Retrospective Monoinstitutional Experience.

Simple SummaryRetrospective studies have shown a survival advantage in combining ipilimumab with radiotherapy in patients with melanoma brain metastases (MBMs). However, these studies did not clarify the correct timing between the two methods. The aims of our study were to demonstrate the efficacy and toxicity of stereotactic radiotherapy/radiosurgery on MBMs in combination with ipilimumab and estimate the correct timing of treatments to improve patients’ outcomes.The median overall survival (OS) and local control (LC) of patients with melanoma brain metastases (MBMs) are poor even with immune checkpoint inhibitors and/or radiotherapy (RT). The aims of the study were to evaluate the association and timing of stereotactic radiotherapy (SRT)/radiosurgery (SRS) performed with the CyberKnife® System and ipilimumab (IPI). A total of 63 MBMs patients were analyzed: 53 received RT+IPI and 10 RT alone. Therefore, the patients were divided into four groups: RT PRE-PI (>4 weeks before IPI) (18), RT CONC-IPI (4 weeks before/between first and last cycle/within 3 months of last cycle of IPI) (20), RT POST-IPI (>3 months after IPI) (15), and NO-IPI (10). A total of 127 lesions were treated: 75 with SRS (one fraction) and 24 with SRT (three to five fractions). The median follow-up was 10.6 months. The median OS was 10.6 months for all patients, 10.7 months for RT+IPI, and 3.3 months for NO-IPI (p = 0.96). One-year LC was 50% for all patients, 56% for RT+IPI, and 18% for NO-IPI (p = 0.08). The 1-year intracranial control was 45% for all patients, 44% for RT+IPI, and 51% for NO-IPI (p = 0.73). IPI with SRS/SRT in MBMs treatment could improve LC. However, the impact and timing of the two modalities on patients’ outcomes are still unclear.

Response Rate And Local Recurrence After Concurrent Immune Checkpoint Therapy And Radiation For Non-Small Cell Lung Cancer And Melanoma Brain Metastases

Growing evidence suggests that immune checkpoint therapy (ICT) and radiation (RT) may be synergistic in the treatment of brain metastases (BrM), but the optimal timing of therapy to maximize synergy remains unclear. We evaluated the impact of treatment timing on response rate and local recurrence in patients with non-small cell lung cancer (NSCLC) or melanoma BrM. We reviewed the records of BrM patients who received ICT and brain-directed RT between 2007-2016 at our institution. ICT consisted of ipilimumab, pembrolizumab, and/or nivolumab; RT included stereotactic radiosurgery/radiotherapy (SRS/T) or whole brain RT (WBRT). We evaluated response rate and local recurrence on a per-metastasis basis (unidimensional RANO-BM). Individual metastases were included only if they underwent RT within 90 days of ICT, to minimize selection biases while analyzing the impact of treatment timing on outcomes. Within this cohort, concurrent treatment was defined as receiving RT on the same day as a dose of ICT or in between doses of an ICT course; all other treatment was non-concurrent (but still within 90 days). Multivariable Cox proportional hazards models were used to assess time to response and local recurrence on a per-metastasis basis, adjusting for confounding variables and using a sandwich estimator to account for intra-patient correlation. The final cohort included 110 patients treated for 340 BrM, with 102 BrM treated concurrently and 238 BrM treated non-concurrently. In total, 68% had melanoma and 32% had NSCLC; 59% of BrM were treated with SRS/T and 41% with WBRT; and 44% received ipilimumab, 46% received anti-PD-1 therapy, and 9% received both simultaneously. Median radiographic follow-up after RT was 6.9 months (IQR 3.5-13.3 months). Rates of any response (complete or partial) were higher with concurrent treatment (70% vs 47%, p<0.001), with correspondingly lower rates of progressive disease (5% vs 26%). On multivariable analysis, time to response was improved with concurrent treatment (HR 1.78, 95% CI 1.18-2.66, p = 0.005), and local recurrence was also decreased with concurrent treatment (HR 0.46, 95% CI 0.26-0.82, p = 0.009). Only 1/103 BrM with a complete response later progressed. In a sensitivity analysis comparing concurrent treatment (n = 102 BrM) to treatment that was non-concurrent but within 30 days (n = 110 BrM), there remained improved rates of any response with concurrent treatment (70% vs 53%, p<0.001). Concurrent brain-directed RT and ICT improves response rates and decreases local recurrence of NSCLC and melanoma BrM, even when compared to treatment that was non-concurrent but within 90 days. Further study of this combination is warranted, particularly in patients in whom rapid treatment response is needed.

Predictors of Local Control of Brain Metastasis Treated With Laser Interstitial Thermal Therapy.

Laser Interstitial Thermal Therapy (LITT) has been used to treat recurrent brain metastasis after stereotactic radiosurgery (SRS). Little is known about how best to assess the efficacy of treatment, specifically the ability of LITT to control local tumor progression post-SRS. To evaluate the predictive factors associated with local recurrence after LITT. Retrospective study with consecutive patients with brain metastases treated with LITT. Based on radiological aspects, lesions were divided into progressive disease after SRS (recurrence or radiation necrosis) and new lesions. Primary endpoint was time to local recurrence. A total of 61 consecutive patients with 82 lesions (5 newly diagnosed, 46 recurrence, and 31 radiation necrosis). Freedom from local recurrence at 6 mo was 69.6%, 59.4% at 12, and 54.7% at 18 and 24 mo. Incompletely ablated lesions had a shorter median time for local recurrence (P<.001). Larger lesions (>6 cc) had shorter time for local recurrence (P=.03). Dural-based lesions showed a shorter time to local recurrence (P=.01). Tumor recurrence/newly diagnosed had shorter time to local recurrence when compared to RN lesions (P=.01). Patients receiving systemic therapy after LITT had longer time to local recurrence (P=.01). In multivariate Cox-regression model, the HR for incomplete ablated lesions was 4.88 (P<.001), 3.12 (P=.03) for recurrent tumors, and 2.56 (P=.02) for patients not receiving systemic therapy after LITT. Complication rate was 26.2%. Incompletely ablated and recurrent tumoral lesions were associated with higher risk of treatment failure and were the major predicting factors for local recurrence. Systemic therapy after LITT was a protective factor regarding local recurrence.

SURG-02. LASER INTERSTITIAL THERMAL THERAPY FOR BRAIN METASTASES: OUTCOMES AND PREDICTORS OF LOCAL RECURRENCE

BACKGROUND: LITT has been used to treat recurrent brain metastasis after stereotactic radiosurgery (SRS). Little is known about how best to assess the efficacy of treatment, specifically the ability of LITT to control local tumor progression post-SRS. Objectives: Evaluate the predictive factors associated with local recurrence after LITT. METHODS: Retrospective study with consecutive patients with brain metastases treated with LITT. Based on radiological aspects, lesions were divided into progressive disease after SRS (recurrence or radiation necrosis) and new lesions. Primary endpoint was time to local recurrence. RESULTS: 61 consecutive patients with 82 lesions (5 newly diagnosed, 46 recurrence and 31 radiation necrosis). Freedom from local recurrence at 6 months was 69.6%, 59.4% at 12, and 54.7% at 18 and 24 months. Incompletely ablated lesions had a shorter median time for local recurrence (p< 0.001). Larger lesions (>6cc) had shorter time for local recurrence (p=0.03). Dural based lesions showed a shorter time to local recurrence (p=0.01). Tumor recurrence/newly diagnosed had shorter time to local recurrence when compared to RN lesions (p=0.01). Patients receiving systemic therapy after LITT had longer time to local recurrence (p=0.01). In multivariate Cox-regression model the HR for incomplete ablated lesions was 4.88 (p< 0.001), 3.12 (p=0.03) for recurrent tumors, and 2.56 (p=0.02) for patients not receiving systemic therapy after LITT. Complication rate was 26.2%. CONCLUSIONS: Incompletely ablated and recurrent tumoral lesions were associated with higher risk of treatment failure and were the major predicting factors for local recurrence. Systemic therapy after LITT was a protective factor regarding local recurrence.

Impact of radiation, systemic therapy and treatment sequencing on survival of patients with melanoma brain metastases

BackgroundCombining stereotactic radiosurgery (SRS) and active systemic therapies (STs) achieved favourable survival outcomes in patients with melanoma brain metastases (MBMs) in retrospective analyses. However, several aspects of this treatment strategy remain poorly understood. We report on the overall survival (OS) of patients with MBM treated with a combination of radiotherapy (RT) and ST as well as the impact of the v-Raf murine sarcoma viral oncogene homolog B (BRAF)-V600 mutation (BRAFmut) status, types of RT and ST and their sequence. Patients and methodsData of 208 patients treated with SRS or whole brain radiation therapy (WBRT) and either immunotherapy (IT) or targeted therapy (TT) within a 6-week interval to RT were analysed retrospectively. OS was calculated from RT to death or last follow-up. Univariate and multivariate Cox proportional hazard analyses were performed to determine prognostic features associated with OS. ResultsThe median follow-up was 7.3 months. 139 patients received IT, 67 received TT and 2 received IT and TT within 6 weeks to RT (WBRT 45%; SRS 55%). One-year Kaplan-Meier OS rates were 69%, 65%, 33% and 18% (P < .001) for SRS with IT, SRS with TT, WBRT with IT and WBRT with TT, respectively. Patients with a BRAFmut receiving IT combined with RT experienced higher OS rates (88%, 65%, 50% and 18%). TT following RT or started before and continued thereafter was associated with improved median OS compared with TT solely before RT (12.2 [95% confidence interval {CI} 9.3–15.1]; 9.8 [95% CI 6.9–12.6] versus 5.1 [95% CI 2.7–7.5]; P = .03). ConclusionSRS and IT achieved the highest OS rates. A BRAFmut appears to be a favourable prognostic factor for OS. For the combination of RT and TT, the sequence appears to be crucial. Combinations of WBRT and ST achieved unprecedentedly high OS rates and warrant further studies.

Clinical, radiological and toxicity evaluation of Vestibular Schwannoma patients treated with Cyberknife® stereotactic radiosurgery-radiotherapy

Clinical, radiological and toxicity evaluation of Vestibular Schwannoma patients treated with Cyberknife® stereotactic radiosurgery-radiotherapy

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.

Salvage Stereotactic Radiosurgery is Associated with Improved Overall Survival Compared to Whole Brain Radiation in the Setting of Progressive Brain Metastases

Brain metastasis velocity (BMV) is a recently defined metric that is highly prognostic for overall survival (OS) after distant brain failure (DBF) following stereotactic radiosurgery (SRS). At time of first DBF, BMV can be calculated by dividing the number of brain metastases (BrM) by the amount of time (unit of years) since initial SRS. A proposed utility for BMV has been to help triage patients to proper salvage therapy after SRS failure based on low (BMV of <4), intermediate (BMV 4-13), and high (BMV>13) risk groups. The purpose of this study was to determine the effect of salvage modality (SRS or whole brain radiation therapy [WBRT]) on OS at the time of first salvage therapy for each BMV risk group. Patients from nine academic centers were treated with upfront SRS alone for BrM. BMV was defined as the number of new BrM at first DBF divided by the time (years) since first SRS for to create a unit of BrM/year. Patients were classified by BMV into low-, intermediate-, and high-risk groups, consisting of <4, 4 to 13, and >13 new BrM/year, respectively. Time-to-event outcomes were estimated using Kaplan-Meier method. For patients in the low, intermediate, and high-risk groups, OS was calculated by stratifying by salvage SRS or WBRT. A univariate and multivariate model (MVA) was created to evaluate OS after first DBF based on patient characteristics and salvage treatment with SRS vs WBRT. Two thousand and eighty patients were included in the study. Median OS from initial SRS was 10.2 mo (95% Confidence Interval [CI] 9.7-11.0 mo). Nine hundred and thirteen (32%) had a DBF treated with salvage SRS or WBRT. The median OS after first DBF for patients who received salvage SRS was 13.1 mo (CI 11.2-16.5 mo), 9.6 mo (CI: 7.8-11.9 mo) and 6.0 mo (CI: 4.9-9.2 mo) for patients with BMV < 4, BMV 4-13, and BMV > 13, respectively. In contrast, for patients who received salvage WBRT for DBF, median OS after initial DBF was 6.6 mo (CI: 5.0-12.7), 4.7 mo (CI: 3.9-8.6) and 3.9 mo (CI: 2.8-5.2) for patients with BMV < 4, BMV 4-13, and BMV > 13, respectively. Compared to patients who received WBRT as salvage therapy, SRS was associated with improved OS after first DBF for BMV < 4 (log-rank p=0.005), BMV 4-13 (p=0.005) and BMV >13 (p=0.0006). Salvage with SRS (vs. WBRT) remained a significant predictor of survival after DBF in multivariate models that included the covariates of age, recursive partitioning analysis class, number of BrM at time of first DBF, and histology for BMV <4 (Hazard Ratio [HR] 0.56, p=0.002), BMV 4-13 (HR 0.60, p=0.005), and BMV >13 (HR 0.48 p<0.001). Salvage SRS after progressive BrM was associated with a higher OS compared to patients treated with WBRT. This was observed across all BMV risk groups and remained significant on MVA. Initial steps have been taken to validate these findings in a multi-institutional prospective randomized trial.

Survival Patterns of 5750 Stereotactic Radiosurgery-Treated Patients with Brain Metastasis as a Function of the Number of Lesions.

The number of brain metastases (BMs) plays an important role in the decision between stereotactic radiosurgery (SRS) and whole-brain radiation therapy. We analyzed the survival of 5750 SRS-treated patients with BM as a function of BM number. Survival analyses were performed with Kaplan-Meier analysis as well as univariate and multivariate Cox proportional hazards models. Patients with BMs were first categorized as those with 1, 2-4, and 5-10 BMs based on the scheme proposed by Yamamoto etal. (Lancet Oncology 2014). Median overall survival for patients with 1 BM was superior to those with 2-4 BMs (7.1 months vs. 6.4 months, P= 0.009), and survival of patients with 2-4 BMs did not differ from those with 5-10 BMs (6.4 months vs. 6.3 months, P= 0.170). The median survival of patients with >10 BMs was lower than those with 2-10 BMs (6.3 months vs. 5.5 months, P= 0.025). In a multivariate model that accounted for age, Karnofsky Performance Score, systemic disease status, tumor histology, and cumulative intracranial tumor volume, we observed a ∼10% increase in hazard of death when comparing patients with 1 versus 2-10 BMs (P<0.001) or 10 versus >10 BMs (P < 0.001). When BM number was modeled as a continuous variable rather than using the classification by Yamamoto etal., we observed a step-wise 4% increase in the hazard of death for every increment of 6-7 BM (P < 0.001). The contribution of BM number to overall survival is modest and should be considered as one of the many variables considered in the decision between SRS and whole-brain radiation therapy.

BRAIN METASTASIS FROM UTERINE MALIGNANCIES: TREATMENT MODALITIES AND PROGNOSTIC FACTORS

Isolated brain metastases from gynecologic malignancies are unusual. Advances in therapeutic modalities including surgery, whole brain radiotherapy stereotactic radiosurgery and chemotherapy improved survival and quality of life in this population. Therapeutic decision is based on patients’ specific prognostic factors. We report three cases of isolated brain metastases from gynecologic cancers and discuss treatment modalities in the light of a literature review.

Outcomes in patients with brain metastasis from esophageal carcinoma.

159 Background: Brain metastases from esophageal carcinoma have historically been rare. With improvements in systemic therapy, patients are living longer and the incidence of brain metastasis (mets) is expected to rise. However, there is no consensus on management. We present our single institution experience with brain mets from esophageal cancer. Methods: We retrospectively identified 49 patients (pts) with brain mets from primary esophageal cancer who were treated at our tertiary referral center between 1998 and 2015. Medical records were reviewed to collect demographic and clinical information. Results: Median age at diagnosis of the primary esophageal cancer was 60 years. 41 pts were male. 39 pts had adenocarcinoma, 4 had squamous cell carcinoma, 4 had poorly differentiated carcinoma, and 1 had neuroendocrine carcinoma. Stage at diagnosis ranged from I-IV. 7pts had synchronous brain mets, defined as occurring within 3 months of diagnosis. The remaining pts were found to have brain mets more than 3 months after diagnosis. 27 pts had a solitary met, 12 had two lesions, and the rest had multiple lesions. For primary treatment, 12 pts had surgery only, 8 had stereotactic radiosurgery (SRS) as a definitive treatment, and the remainder had a combination of surgery, SRS, and whole brain radiation therapy. Median survival following esophageal cancer diagnosis was 24 months (range 3-71), and median survival after the identification of brain mets was 5 months (range 1-52). Using the recursive partitioning score (RPA), 15 pts had class I disease and 28 had class II, and 6 had class III disease. Those with class I or II disease had significantly improved overall survival (p &lt; 0.001). Conclusions: Brain metastases from esophageal cancer are rare with overall poor prognosis. However, some pts can have prolonged survival. In the largest series to date, we found that pts with controlled systemic disease and limited number of brain lesions who had definitive therapy (surgery or SRS) had better outcome. Aggressive treatment may improve outcomes.

The challenge of durable brain control in patients with brain-only metastases from breast cancer.

The vast majority of patients with brain metastases from breast cancer have extracranial metastases, e.g., in the liver, lungs or bones, with serious impact on prognosis. Limited research has been performed on patients with brain-only disease. We analyzed patterns of treatment, brain control and survival in uni- and multivariate analyses. All 25 patients with brain-only disease were treated with radiotherapy (whole-brain radiotherapy (WBRT) with or without stereotactic radiotherapy/radiosurgery (SRS) or surgical resection) and most patients with systemic treatment later during the disease trajectory. Only a minority of patients remained free from brain progression at 1 year after their initial therapy, regardless of initial treatment approach (median brain progression-free survival 6.2 months). However, overall survival was significantly better after initial surgical resection/SRS as compared to upfront WBRT (median 24.1 and 5.2 months, respectively). For all patients combined, median survival was 11.7 months (2-year survival rate 28 %). Several prognostic factors for shorter survival were identified in multivariate regression analysis: lower KPS, triple-negative tumor, coordination deficit, older age, lack of upfront surgical resection or SRS, and lack of endocrine or HER2-directed therapy after brain metastases treatment. Although durable brain control and long-term survival beyond 5 years could be achieved in a subset of patients (largely after successful salvage), progression of brain metastases during the first year after diagnosis was common. Prognosis was influenced by patient-, disease- and treatment-related factors.

Treatment of Large Brain Metastases With Stereotactic Radiosurgery

We report our series of patients with large brain metastases, >3 cm in diameter, who received stereotactic radiosurgery (SRS) as a component of their treatment, focusing on survival and intracranial recurrence rates. The brain tumor database was queried for patients treated with SRS for large brain metastases. Local recurrence (LR) and distant brain recurrence (DBR) rates were calculated using cumulative incidence analysis, and overall survival (OS) was calculated using Kaplan-Meier analysis. Patients were classified into 1 of the 4 groups based on treatment strategy: SRS alone, surgery plus SRS, SRS plus whole-brain radiation therapy (WBRT), and salvage SRS from more remote WBRT and/or surgery. A total of 153 patients with 164 lesions were evaluated. The SRS alone was the treatment approach in 62 lesions, surgery followed by SRS to the resection bed (S + SRS) in 33, SRS + WBRT in 19, and salvage SRS in 50. There was no statistically significant difference in OS between the 4 treatment groups (P = .06). Median survival was highest in patients receiving surgery + SRS (12.2 months) followed by SRS + WBRT (6.9 months), SRS alone (6.6 months), and salvage SRS (6.1 months). There was also no significant difference for LR rates between the groups at 12 months. No significant variables on univariate analysis were noted for LR. The 12-month DBR rates were highest in the S + SRS group (52%), followed by salvage SRS (31%), SRS alone (28%), and SRS + WBRT (13%; P = .03). There were no significant predictors for local control. Keeping in mind that patient numbers in the SRS + WBRT group are small, the addition of WBRT to SRS did not appear to significantly improve survival or local control, supporting the delayed use of WBRT for some patients to prevent potential side effects provided regular imaging surveillance and salvage therapy are utilized. Prospective studies are needed to optimize SRS treatment regimens for patients with large brain metastases.

Unyielding progress: recent advances in the treatment of central nervous system neoplasms with radiosurgery and radiation therapy.

In the past decade, our understanding of the roles of external beam radiotherapy (EBRT) and stereotactic radiosurgery (SRS) in the management of brain tumors has dramatically improved. To highlight the changes and contemporary treatment approaches, we review the indications and outcomes of ionizing radiation for benign intracranial tumors and brain metastases. For nonfunctioning pituitary adenomas, SRS is able to achieve radiographic tumor control in at least 90 % of cases. The rate of SRS-induced endocrine remission for functioning pituitary adenomas depends on the tumor subtype, but it is generally lower than the rate of radiographic tumor control. The most common complications from pituitary adenoma SRS treatment are hypopituitarism and cranial neuropathies. SRS has become the preferred treatment modality for vestibular schwannomas and skull base meningiomas less than 3 cm in size. Large vestibular schwannomas and meningiomas remain best managed with initial surgical resection or EBRT for surgically ineligible patients. For small to moderately sized brain metastases, there has been a shift toward treatment of newly diagnosed patients with SRS alone due to similar local control rates compared with surgical resection. RCTs have shown combined SRS and whole brain radiation therapy (WBRT) for brain metastases to decrease rates of local and distant intracranial recurrence compared to SRS alone. However, the improved intracranial control comes at the expense of poorer neurocognitive outcomes and without prolonging overall survival. Therefore, WBRT is generally reserved for salvage therapy. While EBRT has been frequently supplanted by SRS for the treatment pituitary adenomas and brain metastases, it still proves useful in selected cases of large lesions which are not amenable to surgical debulking or for those with widespread disease, poor performance status, and short life expectancy. In recent years, the scope of SRS has extended beyond the intracranial space to include extradural and intradural spinal tumors.

SU-E-T-505: BrainLab Plan Comparisons: Brain Scan Pencil Beam versus IPlan Monte Carlo.

Monte Carlo (MC) dose modeling techniques are available in the newest version of Brain Lab's IPlan treatment planning system (TPS). Prior to the upgrade, at our facility, BrainLab's BrainScan was the treatment planning system available; pencil beam (PB) modeling is employed by BrainScan. As published in the literature, MC calculations, as compared to the PB algorithm, can generate differences in coverage as much as 20%. With the introduction of the new treatment planning system, treatment parameter comparisons were made with quantitative assessments. Differences due to changes in the dose calculation that could impact patient treatments and outcomes were investigated. Beam data was collected for the new BrainLab TPS IPLAN under the conditions as outlined in the manufacturer's Version 1.3 data collection, commissioning and acceptance guidelines. Utilizing BrainLab's treatment planning systems, treatment plan comparisons were made. First, PB modeling treatment plans were assessed for each treatment plan with pencil beam modeling in the BrainScan and IPlan TPS. Treatment plans with MC modeling were then compared to PB models. Differences in the dose distribution, DVH values, and monitor units were evaluated between the older version software (BrainScan) and the newer treatment planning system (IPlan). As predicted by the literature, the differences in the MC modeling versus PB modeling were significant depending upon the anatomy (tumor site). Modeling comparison for the treatment plans will be presented for SRS (Stereotactic Radiosurgery) and Stereotactic Body Radiation Therapy (SBRT). Clinical implementation of a new treatment planning system must be approached with caution and with adherence to AAPM recommendations and guidelines. Whenever a new TPS calculation model is introduced, thorough comparison between former and new models should be obtained. An additional recommended test would be to perform an independent, end-to-end check of the overall system utilizing the RPC (Radiological Physics Center) phantom.