Stereotactic Radiosurgery With Versus Without Neoadjuvant Endovascular Embolization for Brain Arteriovenous Malformations With Associated Intracranial Aneurysms.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) with neoadjuvant embolization is a treatment strategy for brain arteriovenous malformations (AVMs), especially for those with large nidal volume or concomitant aneurysms. The aim of this study was to assess the effects of pre-SRS embolization in AVMs with an associated intracranial aneurysm (IA). METHODS: The International Radiosurgery Research Foundation AVM database from 1987 to 2018 was retrospectively reviewed. SRS-treated AVMs with IAs were included. Patients were categorized into those treated with upfront embolization (E + SRS) vs stand-alone SRS (SRS). Primary end point was a favorable outcome (AVM obliteration + no permanent radiation-induced changes or post-SRS hemorrhage). Secondary outcomes included AVM obliteration, mortality, follow-up modified Rankin Scale, post-SRS hemorrhage, and radiation-induced changes. RESULTS: Forty four AVM patients with associated IAs were included, of which 23 (52.3%) underwent pre-SRS embolization and 21 (47.7%) SRS only. Significant differences between the E + SRS vs SRS groups were found for AVM maximum diameter (1.5 ± 0.5 vs 1.1 ± 0.4 cm3, P = .019) and SRS treatment volume (9.3 ± 8.3 vs 4.3 ± 3.3 cm3, P = .025). A favorable outcome was achieved in 45.4% of patients in the E + SRS group and 38.1% in the SRS group (P = .625). Obliteration rates were comparable (56.5% for E + SRS vs 47.6% for SRS, P = .555), whereas a higher mortality rate was found in the SRS group (19.1% vs 0%, P = .048). After adjusting for AVM maximum diameter, SRS treatment volume, and maximum radiation dose, the likelihood of achieving favorable outcome and AVM obliteration did not differ between groups (P = .475 and P = .820, respectively). CONCLUSION: The likelihood of a favorable outcome and AVM obliteration after SRS with neoadjuvant embolization in AVMs with concomitant IA seems to be comparable with stand-alone SRS, even after adjusting for AVM volume and SRS maximum dose. However, the increased mortality among the stand-alone SRS group and relatively low risk of embolization-related complications suggest that these patients may benefit from a combined treatment approach.

Patterns of Care and Data Quality in a National Registry of Black and White Patients with Merkel Cell Carcinoma.

Merkel Cell Carcinoma (MCC) is a rare cancer most commonly affecting White patients; less is known for Black patients. We aim to report presentation, treatment, and quality of registry data by race with a secondary endpoint of overall survival. We conducted a retrospective cohort analysis between 2006−2017 via the National Cancer Database of Black and White MCC patients with and without known staging information. Multivariable logistic, proportional odds logistic, and baseline category logistic regression models were used for our primary endpoint. Multivariable Cox regression was used to interrogate overall survival. Multiple imputation was used to mitigate missing data bias. 34,503 patients with MCC were included (2566 Black patients). Black patients were younger (median age 52 vs. 72, p < 0.0001), had higher rates of immunosuppression (28% vs. 14%, p = 0.0062), and were more likely to be diagnosed at a higher stage (proportional OR = 1.41, 95% CI 1.25−1.59). No differences were noted by race across receipt of definitive resection (DR), though Black patients did have longer time from diagnosis to DR. Black patients were less likely to receive adjuvant radiation. Black patients were more likely to have missing cancer stage (OR = 1.69, CI 1.52−1.88). Black patients had decreased adjusted risk of mortality (HR 0.73, 0.65−0.81). Given the importance of registry analyses for rare cancers, efforts are needed to ensure complete data coding. Paramount to ensuring equitable access to optimal care for all is the recognition that MCC can occur in Black patients.

Immune Status in Merkel Cell Carcinoma: Relationships With Clinical Factors and Independent Prognostic Value.

BACKGROUND: Immunosuppression (IS) currently is not considered in staging for Merkel cell carcinoma (MCC). An analysis of the National Cancer Database (NCDB) was performed to investigate immune status as an independent predictor of overall survival (OS) for patients with MCC and to describe the relationship between immune status and other prognostic factors. METHODS: The NCDB was queried for patients with a diagnosis of MCC from 2010 to 2016 who had known immune status. Multivariable Cox proportional hazards models were used to define factors associated with OS. Secondary models were constructed to assess the association between IS etiology and OS. Multivariable logistic regression models were used to characterize relationships between immune status and other factors. RESULTS: The 3-year OS was lower for the patients with IS (44.6%) than for the immunocompetent (IC) patients (68.7%; p < 0.0001). Immunosuppression was associated with increased adjusted mortality hazard (hazard ratio [HR], 2.36, 95% confidence interval [CI], 2.03-2.75). The etiology of IS was associated with OS (p = 0.0015), and patients with solid-organ transplantation had the lowest 3-year OS (32.7%). Immunosuppression was associated with increased odds of greater nodal burden (odds ratio [OR], 1.70; 95% CI, 1.37-2.11) and lymphovascular invasion (OR, 1.58; 95% CI, 1.23-2.03). CONCLUSIONS: Immune status was independently prognostic for the OS of patients with localized MCC. The etiology of IS may be associated with differential survival outcomes. Multiple adverse prognostic factors were associated with increased likelihood of IS. Immune status, and potentially the etiology of IS, may be useful prognostic factors to consider for future MCC staging systems.

Stereotactic Radiosurgery With Versus Without Embolization for Brain Arteriovenous Malformations.

BACKGROUND: Prior comparisons of brain arteriovenous malformations (AVMs) treated using stereotactic radiosurgery (SRS) with or without embolization were inherently flawed, due to differences in the pretreatment nidus volumes. OBJECTIVE: To compare the outcomes of embolization and SRS, vs SRS alone for AVMs using pre-embolization malformation features. METHODS: We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Patients were categorized into the embolization and SRS (E + SRS) or SRS alone (SRS-only) cohorts. The 2 cohorts were matched in a 1:1 ratio using propensity scores. Primary outcome was defined as AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiologic and symptomatic radiation-induced changes (RIC), and cyst formation. RESULTS: The matched cohorts each comprised 101 patients. Crude AVM obliteration rates were similar between the matched E + SRS vs SRS-only cohorts (48.5% vs 54.5%; odds ratio = 0.788, P = .399). Cumulative probabilities of obliteration at 3, 4, 5, and 6 yr were also similar between the E + SRS (33.0%, 46.4%, 56.2%, and 60.8%, respectively) and SRS-only (32.9%, 46.2%, 56.0%, and 60.6%, respectively) cohorts (subhazard ratio (SHR) = 1.005, P = .981). Cumulative probabilities of radiologic RIC at 3, 4, 5, and 6 yr were lower in the E + SRS (25.0%, 25.7%, 26.7%, and 26.7%, respectively) vs SRS-only (45.3%, 46.2%, 47.8%, and 47.8%, respectively) cohort (SHR = 0.478, P = .004). Symptomatic and asymptomatic embolization-related complication rates were 8.3% and 18.6%, respectively. Rates of post-SRS hemorrhage, all-cause mortality, symptomatic RIC, and cyst formation were similar between the matched cohorts. CONCLUSION: This study refutes the prevalent notion that AVM embolization negatively affects the likelihood of obliteration after SRS.

Embolization of Brain Arteriovenous Malformations With Versus Without Onyx Before Stereotactic Radiosurgery.

BACKGROUND: Embolization of brain arteriovenous malformations (AVMs) using ethylene-vinyl alcohol copolymer (Onyx) embolization may influence the treatment effects of stereotactic radiosurgery (SRS) differently than other embolysates. OBJECTIVE: To compare the outcomes of pre-SRS AVM embolization with vs without Onyx through a multicenter, retrospective matched cohort study. METHODS: We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Embolized AVMs treated with SRS were selected and categorized based on embolysate usage into Onyx embolization (OE + SRS) or non-Onyx embolization (NOE + SRS) cohorts. The 2 cohorts were matched in a 1:1 ratio using de novo AVM features for comparative analysis of outcomes. RESULTS: The matched cohorts each comprised 45 patients. Crude AVM obliteration rates were similar between the matched OE + SRS vs NOE + SRS cohorts (47% vs 51%; odds ratio [OR] = 0.837, P = .673). Cumulative probabilities of obliteration were also similar between the OE + SRS vs NOE + SRS cohorts (subhazard ratio = 0.992, P = .980). Rates of post-SRS hemorrhage, all-cause mortality, radiation-induced changes, cyst formation, and embolization-associated complications were similar between the matched cohorts. Sensitivity analysis for AVMs in the OE + SRS cohort embolized with Onyx alone revealed a higher rate of asymptomatic embolization-associated complications in this subgroup compared to the NOE + SRS cohort (36% vs 15%; OR = 3.297, P = .034), but the symptomatic complication rates were similar. CONCLUSION: Nidal embolization using Onyx does not appear to differentially impact the outcomes of AVM SRS compared with non-Onyx embolysates. The embolic agent selected for pre-SRS AVM embolization should reflect both the experience of the neurointerventionalist and target of endovascular intervention.

Stereotactic radiosurgery with versus without prior Onyx embolization for brain arteriovenous malformations.

OBJECTIVE: Investigations of the combined effects of neoadjuvant Onyx embolization and stereotactic radiosurgery (SRS) on brain arteriovenous malformations (AVMs) have not accounted for initial angioarchitectural features prior to neuroendovascular intervention. The aim of this retrospective, multicenter matched cohort study is to compare the outcomes of SRS with versus without upfront Onyx embolization for AVMs using de novo characteristics of the preembolized nidus. METHODS: The International Radiosurgery Research Foundation AVM databases from 1987 to 2018 were retrospectively reviewed. Patients were categorized based on AVM treatment approach into Onyx embolization (OE) and SRS (OE+SRS) or SRS alone (SRS-only) cohorts and then propensity score matched in a 1:1 ratio. The primary outcome was AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiological and symptomatic radiation-induced changes (RICs), and cyst formation. Comparisons were analyzed using crude rates and cumulative probabilities adjusted for competing risk of death. RESULTS: The matched OE+SRS and SRS-only cohorts each comprised 53 patients. Crude rates (37.7% vs 47.2% for the OE+SRS vs SRS-only cohorts, respectively; OR 0.679, p = 0.327) and cumulative probabilities at 3, 4, 5, and 6 years (33.7%, 44.1%, 57.5%, and 65.7% for the OE+SRS cohort vs 34.8%, 45.5%, 59.0%, and 67.1% for the SRS-only cohort, respectively; subhazard ratio 0.961, p = 0.896) of AVM obliteration were similar between the matched cohorts. The secondary outcomes of the matched cohorts were also similar. Asymptomatic and symptomatic embolization-related complication rates in the matched OE+SRS cohort were 18.9% and 9.4%, respectively. CONCLUSIONS: Pre-SRS AVM embolization with Onyx does not appear to negatively influence outcomes after SRS. These analyses, based on de novo nidal characteristics, thereby refute previous studies that found detrimental effects of Onyx embolization on SRS-induced AVM obliteration. However, given the risks incurred by nidal embolization using Onyx, this neoadjuvant intervention should be used judiciously in multimodal treatment strategies involving SRS for appropriately selected large-volume or angioarchitecturally high-risk AVMs.

The effect of omission of adjuvant radiotherapy after neoadjuvant chemotherapy and breast conserving surgery with a pathologic complete response.

OBJECTIVE(S): Neoadjuvant chemotherapy (NAC) is a standard of care for locally advanced breast cancers. Adjuvant radiotherapy (RT) after NAC is an area of active research. We hypothesize overall survival (OS) is not altered by omitting RT in women with a pathologic complete response (pCR) to NAC after breast conserving survery (BCS). METHODS: Patients from the National Cancer Database who underwent NAC, BCS, and had a pCR were included. Inflammatory disease, <6 months follow up, and unknown variables were excluded. Descriptive statistics characterized the retained cohort. Logistic regression analyzed the influence of variables on the rate of RT omission. Cox proportional hazard modeling analyzed the influence of prognostic variables on OS. RESULTS: Of 5383 women included, 364 (7%) omitted RT. 5-year OS was 94.1% with RT, 93% without. RT omission was most likely in women >70yo (adjusted OR2.4, 95%CI 1.58-3.65, p < .0001;reference 40-49 yo), Hispanic (AOR 1.73, 95%CI 1.19-2.52, p = .0044; reference non-Hispanic), ≥20 miles from treatment facility (20-49 miles; AOR 1.45, 95%CI 1.09-1.93, p = .0109: >50 miles; AOR 2.02, 95%CI 1.42-2.87, p < .0001;reference 0-19 miles), grade 1 (AOR 4.29, 95%CI 2.16-8.51, p < .0001; reference grade 3), and clinical T4 disease (AOR 3.17, 95%CI 1.74-5.79, p = .0002; reference T0/1). Women ≥60yo (60-69: AHR 2.33, 95%CI 1.41-3.83, p = .0009:70+:AHR 2.4, 95%CI 1.24-4.62, p = .0092; reference 40-49) and with N1 and N3 disease (N1: AHR 1.67, 95% CI 2.28-3.24, p = .0034; N3: AHR3.37,95%CI2.01-5.65,p < .0001) showed increased death. Triple-positive (AHR 0.18, 95%CI 0.07-0.43, p = .0002) and HER2+ patients (AHR 0.44, 95%CI 0.30-0.64, p < .0001) had improved OS compared to triple-negative disease. No survival difference was seen with omission of RT (log-rank test: p = .1783; Cox model AHR 1.33, 95%CI 0.76-2.31, p = .3181). CONCLUSION: Women ≥70, of Hispanic origin, living ≥20 miles from treatment facility, and grade 1 disease were more likely to omit RT. HER2+ patients had favorable OS, while older age and N3 disease were negative prognostic factors. Omitting RT after a pCR to NAC and BCS was not found to affect OS.

Immune status and the efficacy of radiotherapy on overall survival for patients with localized Merkel cell carcinoma: An analysis of the National Cancer Database.

BACKGROUND: Immunosuppressed (IS) patients with Merkel cell carcinoma (MCC) have worse outcomes compared to immunocompetent (IC) patients, and it is unclear if adjuvant radiotherapy (RT) is beneficial for these patients. We sought to determine the effect of immune status on adjuvant RT efficacy regarding overall survival (OS) for patients with localized MCC. METHODS: This was an observational study of National Cancer Database (NCDB) identifying patients with stage I/II or III MCC with known immune status diagnosed from 2010 to 2014. The median follow-up time was 29 months. OS was described using Kaplan-Meier methods and compared for subgroups by immune status and adjuvant RT using log-rank tests, multivariable Cox regression and interaction effect testing. RESULTS: A total of 2049 IC and 255 IS patients were included. Adjuvant RT was associated with decreased hazard of death for stage I/II MCC (HR 0.65, CI 0.54-0.78) adjusting for factors including immune status. Interaction effect testing did not demonstrate a significant difference in the effect of adjuvant RT on OS between IC and IS status in either stage I/II or III MCC (both P values > 0.05). CONCLUSIONS: In this observational study, adjuvant RT was associated with decreased hazard of death for patients with stage I/II MCC regardless of immune status. Adjuvant RT should be considered for both IS and IC patients with localized MCC.

Stereotactic radiosurgery for central neurocytomas: an international multicenter retrospective cohort study.

OBJECTIVE: Central neurocytomas (CNs) are uncommon intraventricular tumors, and their rarity renders the risk-to-benefit profile of stereotactic radiosurgery (SRS) unknown. The aim of this multicenter, retrospective cohort study was to evaluate the outcomes of SRS for CNs and identify predictive factors. METHODS: The authors retrospectively analyzed a cohort of patients with CNs treated with SRS at 10 centers between 1994 and 2018. Tumor recurrences were classified as local or distant. Adverse radiation effects (AREs) and the need for a CSF shunt were also evaluated. RESULTS: The study cohort comprised 60 patients (median age 30 years), 92% of whom had undergone prior resection or biopsy and 8% received their diagnosis based on imaging alone. The median tumor volume and margin dose were 5.9 cm3 and 13 Gy, respectively. After a median clinical follow-up of 61 months, post-SRS tumor recurrence occurred in 8 patients (13%). The 5- and 10-year local tumor control rates were 93% and 87%, respectively. The 5- and 10-year progression-free survival rates were 89% and 80%, respectively. AREs were observed in 4 patients (7%), but only 1 was symptomatic (2%). Two patients underwent post-SRS tumor resection (3%). Prior radiotherapy was a predictor of distant tumor recurrence (p = 0.044). Larger tumor volume was associated with pre-SRS shunt surgery (p = 0.022). CONCLUSIONS: Treatment of appropriately selected CNs with SRS achieves good tumor control rates with a reasonable complication profile. Distant tumor recurrence and dissemination were observed in a small proportion of patients, which underscores the importance of close post-SRS surveillance of CN patients. Patients with larger CNs are more likely to require shunt surgery before SRS.

Extrapulmonary small cell carcinoma: Prognostic factors, patterns of care, and overall survival.

BACKGROUND: Extrapulmonary small cell carcinoma is a rare malignancy with scarce data. Treatment paradigms extrapolate from pulmonary small cell carcinoma and single institution studies. We analyzed the epidemiology, patterns of care, prognostic factors, and overall survival (OS) of EPSCC patients. METHODS: The cohort included EPSCC. Patients with <2 months follow-up, unknown demographic/treatment variables were excluded. Descriptive statistics were performed to characterize the cohort. Kaplan-Meier methods were used to estimate OS. Cox proportional hazard modeling was done to analyze the influence of prognostic variables on OS. RESULTS: 5747 patients were included. Median OS was 1.2 years. Head and neck (HR: 0.60, 95% CI 0.53-0.67, p < 0.0001) and breast (HR: 0.69, 95% CI 0.53-0.89, p = .0046) were associated with improved OS; gastrointestinal (HR: 1.19, 95% CI 1.09-1.29, p < .0001) worse OS; and gynecologic (HR: 1.04, 95% CI 0.92-1.17, p = .5660) showing no difference, all compared to genitourinary (reference). Surgery was associated with improved overall survival (HR: 0.84, 95% CI 0.79-0.91, p=<.0001). Chemoradiation showed a decreased HR (HR: 0.91, 95% CI 0.83-0.99, p = .0363) when compared to chemotherapy alone (reference). CONCLUSION: EPSCC occurs throughout the body with poor survival. Anatomic subsite was predictive for survival. Surgical resection may improve survival. Concurrent chemoradiation appears to improve survival over chemotherapy alone.

Survival impact of prolonged postoperative radiation therapy for patients with glioblastoma treated with combined-modality therapy.

BACKGROUND: Though conventionally fractionated chemoradiation (CRT) is well tolerated by selected patients with newly diagnosed glioblastoma (GBM), adverse health-related and nonhealth-related factors can lead to unplanned interruptions in treatment. The effects of prolonged time to completion (TTC) of radiation therapy (RT) on overall survival (OS) for these patients are unclear. METHODS: The National Cancer Database (NCDB) was queried for all adult patients with newly diagnosed GBM undergoing surgical resection followed by adjuvant CRT with conventionally fractionated RT (6000-6600 cGy in 30-33 fractions) from 2005 to 2012. TTC was defined as the interval from first to last fraction of RT. Recursive partitioning analysis (RPA) was used to determine a threshold for TTC of adjuvant RT. Cox proportional hazards modeling was used to identify covariates associated with OS. RESULTS: A total of 13489 patients were included in our cohort. Patients who completed adjuvant RT within the RPA-defined threshold of 46 days from initiation of RT (median OS: 14.0 months, 95% confidence interval (CI) 13.7 to 14.3 months) had significantly improved OS compared to patients with TTC of 47 days or greater (median OS: 12.0 months, 95% CI 11.4 to 12.6 months, P < .001). Delays in completing adjuvant RT were relatively common, with 15.0% of patients in our cohort having a TTC of RT of 47 days or greater. CONCLUSIONS: Delays in completing adjuvant RT were associated with a worse survival outcome. Any unnecessary delays in completing adjuvant RT should be minimized while ensuring the safe delivery of therapy.

Increasing time to postoperative stereotactic radiation therapy for patients with resected brain metastases: investigating clinical outcomes and identifying predictors associated with time to initiation.

We sought to determine the impact of time to initiation (TTI) of post-operative radiosurgery on clinical outcomes for patients with resected brain metastases and to identify predictors associated with TTI. All patients with resected brain metastases treated with postoperative SRS or fractionated stereotactic radiation therapy (fSRT) from 2012 to 2016 at a single institution were reviewed. TTI was defined as the interval from resection to first day of radiosurgery. Receiver operating characteristic (ROC) curves were used to identify an optimal threshold for TTI with respect to local failure (LF). Survival outcomes were estimated using the Kaplan-Meier method and analyzed using the log-rank test and Cox proportional hazards models. Logistic regression models were used to identify factors associated with ROC-determined TTI covariates. A total of 79 resected lesions from 73 patients were evaluated. An ROC curve of LF and TTI identified an optimal threshold for TTI of 30.5 days, with an area under the curve of 0.637. TTI > 30 days was associated with an increased hazard of LF (HR 4.525, CI 1.239-16.527) but was not significantly associated with survival (HR 1.002, CI 0.547-1.823) or distant brain failure (DBF, HR 1.943, CI 0.989-3.816). Fifteen patients (20.5%) required post-operative inpatient rehabilitation. Post-operative rehabilitation was associated with TTI > 30 days (OR 1.48, CI 1.142-1.922). In our study of resected brain metastases, longer time to initiation of post-operative radiosurgery was associated with increased local failure. Ideally, post-op SRS should be initiated within 30 days of resection if feasible.

Patterns of care and predictors of adjuvant therapies in elderly patients with glioblastoma: An analysis of the National Cancer Data Base.

BACKGROUND: The objectives of this study were to characterize patterns of care and to identify predictors for adjuvant therapy in elderly patients with glioblastoma in the modern era. METHODS: The National Cancer Data Base was queried for patients aged 70 years and older with glioblastoma diagnosed from January 1, 2004 through December 31, 2012. Multinomial logistic regression was used to identify predictors for receiving adjuvant therapy. Survival outcomes were estimated using the Kaplan-Meier method and were analyzed using Cox regression models and the log-rank test. RESULTS: In total, 14,886 patients were identified. Of these, 8214 patients (55.2%) received combined-modality therapy with chemotherapy and radiation (CRT), 3955 (26.6%) received no adjuvant therapy, 2065 (13.9%) received radiation therapy (RT) alone, and 652 (4.4%) received chemotherapy (CT) alone after undergoing resection. The receipt of CRT increased in frequency over the study interval, from 40.3% in 2004 to 59.8% in 2012. Younger patients (ages 70-75 years) were more likely to receive CRT than no adjuvant therapy (P < .0001 for all other age groups) or adjuvant RT alone (P < .0001 for all other age groups). Combined-modality therapy with adjuvant CRT produced improved survival outcomes, and the highest median overall survival was 9.2 months. CONCLUSIONS: In this analysis of elderly patients who had glioblastoma diagnosed from 2004 through 2012, a significant increase in the receipt of combined-modality therapy was observed. Combined-modality treatment produces improved survival outcomes and should be considered as adjuvant treatment for carefully selected elderly patients. Cancer 2017;123:3277-84. © 2017 American Cancer Society.

Peri-SRS Administration of Immune Checkpoint Therapy for Melanoma Metastatic to the Brain: Investigating Efficacy and the Effects of Relative Treatment Timing on Lesion Response.

OBJECTIVE: To investigate the efficacy of immune checkpoint therapy (ICT) administered with stereotactic radiosurgery (SRS) and determine the effects of relative treatment timing on lesion response. METHODS: A prospective institutional database of all patients with intact brain metastases treated with SRS from 2008 to 2015 was reviewed for patients diagnosed with malignant melanoma. Lesion response was determined using a modified RECIST v1.1 criteria. Patients were grouped according to if they received ICT and the timing of ICT relative to SRS. Cox regression was used to identify predictors of lesion failure (LF) and distant brain failure (DBF). The Wilcoxon rank-sum test was used to compare median lesion regression after SRS between treatment groups. RESULTS: Fifty-one patients with 167 metastases were evaluated. Eighteen patients (59 lesions) were treated with peri-SRS ICT with anticytotoxic T-lymphocyte-associated protein 4 or antiprogrammed cell death protein 1 therapy. Peri-SRS ICT was a significant favorable predictor for reduced hazard of LF (hazard ratio, 0.131; confidence interval, 0.028-0.610). Concurrent ICT given with SRS (hazard ratio, 0.364; confidence interval, 0.161-0.825) significantly predicted freedom from DBF. When quantitative lesion response was examined, peri-SRS ICT resulted in a significantly greater median percent lesion regression than did SRS alone at 1.5 (-30.7% vs. -14.6%; P = 0.018), 4 (-42.3% vs. -18.8%; P = 0.031), and 5 months after SRS (-52.01 vs. -14.9%; P = 0.002). CONCLUSIONS: ICT combined with SRS was associated with greater lesion regression of melanoma brain metastases and decreased LF. When given concurrently, combined SRS and ICT may result in improved freedom from DBF.

A Dose-Volume Response Model for Brain Metastases Treated With Frameless Single-Fraction Robotic Radiosurgery: Seeking to Better Predict Response to Treatment.

Purpose/Objective(s): To establish a dose-volume response relationship for brain metastases treated with single-fraction robotic stereotactic radiosurgery and identify predictors of local control. MATERIALS/METHODS: We reviewed a prospective institutional database of all patients treated for intact brain metastases with stereotactic radiosurgery alone using the CyberKnife robotic radiosurgery system from 2012 to 2015. Tumor response was determined based on Response Evaluation Criteria In Solid Tumors version 1.1. Survival was estimated using the Kaplan-Meier method. Logistic regression modeling was used to identify predictors of outcome and establish a dose-volume response relationship. Receiver operating characteristic curves were constructed to evaluate the predictive capability of the relationship. RESULTS: There were 357 metastases evaluated in 111 patients with a median diameter of 8.14 mm (2.00-40.77 mm). At 6 and 12 months, local control was 86.9% and 82.2%, respectively. For lesions of similar volumes, higher maximum dose, mean dose, and minimum dose (all P values <.05) predicted for better local control. Tumor volume and diameter were strongly correlated, and a dose-volume response relationship was constructed using mean dose per lesion diameter (Gy/mm) that was predictive of local control (odds ratio: 1.34, 95% confidence interval: 1.06-1.70). Area under the receiver operating characteristic curve for local control and mean dose by volume was 0.6199 with a threshold of 2.05 Gy/mm (local failure 7.6% above and 17.3% below 2.05 Gy/mm). CONCLUSION: A dose-volume response relationship exists for brain metastases treated with robotic stereotactic radiosurgery. Mean dose per volume is strongly predictive of local control and can be potentially useful during stereotactic radiosurgery plan evaluation while respecting previously established dose constraints.

Dose-Volume Response Relationship for Brain Metastases Treated with Frameless Single-Fraction Linear Accelerator-Based Stereotactic Radiosurgery.

BACKGROUND: Our aim was to identify a dose-volume response relationship for brain metastases treated with frameless stereotactic radiosurgery (SRS). METHODS: We reviewed patients who underwent frameless single-fraction linear accelerator SRS for brain metastases between 2007 and 2013 from an institutional database. Proportional hazards modeling was used to identify predictors of outcome. A ratio of maximum lesion dose per mm-diameter (Gy/mm) was constructed to establish a dose-volume relationship. RESULTS: There were 316 metastases evaluated in 121 patients (2 - 33 mm in the largest diameter). The median peripheral dose was 18.0 Gy (range: 10.0 - 24.0 Gy). Local control was 84.8% for all lesions and was affected by location, peripheral dose, maximum dose, and lesion size (p values < 0.050). A dose-volume response relationship was constructed using the maximum dose and lesion size. A unit increase in Gy/mm was associated with decreased local failure (p = 0.005). Local control of 80%, 85%, and 90% corresponded to maximum doses per millimeter of 1.67 Gy/mm, 2.86 Gy/mm, and 4.4 Gy/mm, respectively. Toxicity was uncommon and only 1.0% of lesions developed radionecrosis requiring surgery. CONCLUSIONS: For brain metastases less than 3 cm, a dose-volume response relationship exists between maximum radiosurgical dose and lesion size, which is predictive of local control.