Outcomes of radiation-induced meningiomas treated with stereotactic radiosurgery.

PURPOSE: Data on the efficacy and safety of stereotactic radiosurgery (SRS) for treatment of radiation-induced meningiomas (RIMs) are limited. METHODS: A single institution database of Cobalt-60 SRS cases from 08/1999 to 10/2020 was reviewed. Radiation-induced meningiomas were identified using Cahan's criteria. Endpoints included overall survival (OS), progression free survival (PFS), local control (LC), treatment failure, and treatment toxicity. Univariate and multivariate analyses were performed using cox proportional hazard models. RESULTS: A total of 29 patients with 86 RIM lesions were identified. Median follow-up after SRS was 59 months. The median dose prescribed to the 50% isodose line was 14 Gy (range 12-20 Gy). The actuarial 5-yr OS and PFS were 96% and 68%, respectively. Patients treated for recurrent RIMs had a significantly lower PFS (45% vs 94% at 3 yr, p < 0.005) than patients treated in the upfront setting. Patients with presumed or WHO grade I RIMs had a significantly greater PFS (3-year PFS 96% vs 20%) than patients with WHO grade II RIMs (p < 0.005). On a per-lesion basis, local control (LC) at 1-, 3-, and 5-yrs was 82%, 76%, 74%, respectively. On multivariate analysis, female gender was associated with improved LC (p < 0.001), while marginal doses > 14 Gy were associated with worse local control (p < 0.001). Grade I-III toxicity following treatment was 9.0%. CONCLUSIONS: Stereotactic radiosurgery is a safe and effective treatment option for radiographic RIMs, WHO grade I RIMs, or lesions treated in the upfront setting. WHO grade II lesions and recurrent lesions are at increased risk for disease progression.

Long term survivors of stereotactic radiosurgery for brain metastases: do distant brain failures reach a plateau and what factors are associated with a brain metastasis velocity of zero?

PURPOSE: Life expectancy continues to increase for patients with brain metastases treated with stereotactic radiosurgery (SRS). The present study sought to retrospectively analyze brain metastasis patients who have survived 2 years or more, and assess for what factors may predict for a final brain metastasis velocity (BMV) of zero. METHODS: This was a single-institution retrospective study of 300 patients treated with SRS from 2001 to 2019 for brain metastases who survived greater than 2 years after first SRS. Final BMV is calculated by summing all metastases through the observed time divided by the total time in years. A BMV of zero is defined as at least 2 years of imaging follow-up without distant brain failure (DBF). RESULTS: Median age at first SRS is 61 (IQR: 53, 70). Kaplan-Meier estimated median overall survival is 4.9 years and time to DBF is 1.5 years (95% CI 1.2, 2.0). Twenty-eight (9.3%) patients underwent subsequent WBRT. One hundred and one (33.7%) patients never had any further brain metastases (BMV = 0) at a median follow-up time of 3.3 years. Median BMV is 0.4 (IQR: 0, 1.4). Distant brain failures reach a plateau at 4 years where the cumulative incidence of DBF is 82%. 70% of first time DBFs have occurred by 2 years. Factors significantly associated with a BMV of zero include fewer brain metastases at first SRS (HR 1.1; p = 0.0004) and Caucasian race (HR 1.5; p = 0.03). CONCLUSION: Approximately one third of brain metastasis patients who live beyond 2 years after initial SRS have a BMV of zero. DBFs appear to reach a plateau at 4 years. Factors significantly associated with a BMV of zero include Caucasian race and having had a single brain metastasis at first SRS.

Local control outcomes for combination of stereotactic radiosurgery and immunotherapy for non-small cell lung cancer brain metastases.

BACKGROUND: Previous series have demonstrated CNS activity for immune checkpoint inhibitors, yet no prior data exists regarding whether this activity can improve outcomes of stereotactic radiosurgery. METHODS: In this single institution retrospective series, the clinical outcomes of 80 consecutive lung cancer patients treated with concurrent immune checkpoint inhibitors and stereotactic radiosurgery were compared to 235 in the historical control cohort in which patients were treated prior to immune checkpoint inhibition being standard upfront therapy. Overall survival was estimated using the Kaplan Meier method. Cumulative incidence of local progression was estimated using a competing risk model. RESULTS: Median overall survival time was improved in patients receiving upfront immunotherapy compared to the historical control group (40 months vs 8 months, p < 0.001). Factors affected overall survival include concurrent immunotherapy (HR 0.23, p < 0.0001) and KPS (HR 0.97, p = 0.0001). Cumulative incidence of local failure in the historical control group was 10% at 1 year, compared to 1.1% at 1 year in the concurrent immunotherapy group (p = 0.025). Factors affected local control included use of concurrent immunotherapy (HR 0.09, p = 0.012), and lowest margin dose delivered to a metastasis (HR 0.8, p = 0.0018). CONCLUSION: Local control and overall survival were both improved in patients receiving concurrent immune checkpoint inhibitors with radiosurgery compared to historical controls. While these data remain to be validated, they suggest that brain metastasis patients may benefit from concurrent use of immunotherapy with SRS.

Impact of brain metastasis velocity on neurologic death for brain metastasis patients experiencing distant brain failure after initial stereotactic radiosurgery.

PURPOSE: Patients with high rates of developing new brain metastases have an increased likelihood of dying of neurologic death. It is unclear, however, whether this risk is affected by treatment choice following failure of primary stereotactic radiosurgery (SRS). METHODS: From July 2000 to March 2017, 440 patients with brain metastasis were treated with SRS and progressed to have a distant brain failure (DBF). Eighty-seven patients were treated within the immunotherapy era. Brain metastasis velocity (BMV) was calculated for each patient. In general, the institutional philosophy for use of salvage SRS vs whole brain radiotherapy (WBRT) was to postpone the use of WBRT for as long as possible and to treat with salvage SRS when feasible. No further treatment was reserved for patients with poor life expectancy and who were not expected to benefit from salvage treatment. RESULTS: Two hundred and eighty-five patients were treated with repeat SRS, 91 patients were treated with salvage WBRT, and 64 patients received no salvage radiation therapy. One-year cumulative incidence of neurologic death after salvage SRS vs WBRT was 15% vs 23% for the low- (p = 0.06), 30% vs 37% for the intermediate- (p < 0.01), and 31% vs 48% (p < 0.01) for the high-BMV group. Salvage WBRT was associated with increased incidence of neurologic death on multivariate analysis (HR 1.64, 95% CI 1.13-2.39, p = 0.01) when compared to repeat SRS. One-year cumulative incidence of neurologic death for patients treated within the immunotherapy era was 9%, 38%, and 38% for low-, intermediate-, and high-BMV groups, respectively (p = 0.01). CONCLUSION: Intermediate and high risk BMV groups are predictive of neurologic death. The association between BMV and neurologic death remains strong for patients treated within the immunotherapy era.

Mild cognitive impairment in long-term brain tumor survivors following brain irradiation.

INTRODUCTION: There is no accepted classification of cognitive impairment in cancer survivors. We assess the extent of mild cognitive impairment (MCI) syndrome in brain tumor survivors using criteria adapted from the National Institute on Aging and the Alzheimer's Association (NIA-AA). METHODS: We retrospectively reviewed the cognitive data of brain tumor survivors post-radiation therapy (RT) enrolled from 2008 to 2011 in a randomized trial of donepezil versus placebo for cognitive impairment. One hundred and ninety eight adult survivors with primary or metastatic brain tumors who were ≥ 6 months post RT were recruited at 24 sites in the United States. Cognitive function was assessed at baseline, 12 and 24 weeks post-randomization. For this analysis, we used baseline data to identify MCI and possible dementia using adapted NIA-AA criteria. Cases were subtyped into four groups: amnestic MCI-single domain (aMCI-sd), amnestic MCI-multiple domain (aMCI-md), non-amnestic MCI-single domain (naMCI-sd), and non-amnestic MCI-multiple domain (naMCI-md). RESULTS: One hundred and thirty one of 197 evaluable patients (66%) met criteria for MCI. Of these, 13% were classified as aMCI-sd, 58% as aMCI-md, 19% as naMCI-sd, and 10% as naMCI-md. Patients with poorer performance status, less education, lower household income and those not working outside the home were more likely to be classified as MCI. CONCLUSION: Two-thirds of post-RT brain tumor survivors met NIA-AA criteria for MCI. This taxonomy may be useful when applied to brain tumor survivors because it defines cognitive phenotypes that may be differentially associated with course, treatment response, and risk factor profiles.

Cognitive functioning following brain irradiation as part of cancer treatment: Characterizing better cognitive performance.

OBJECTIVE: Although brain radiation therapy (RT) impacts cognitive function, little is known about the subset of survivors with minimal cognitive deficits. This study compares the characteristics of patients receiving brain irradiation as part of cancer treatment with minimal cognitive deficits to those with poorer cognitive functioning. METHODS: Adults at least 6 months postbrain RT (N = 198) completed cognitive measures of attention, memory, and executive functions. Cognitive functioning was categorized into better- and poorer-performing groups, with better-performing survivors scoring no worse than 1.5 standard deviations below the published normative mean on all cognitive measures. Logistic regression was used to identify variables associated with better-performing group membership. RESULTS: Approximately 25% of the sample met the criteria for the better-performing group. In unadjusted analyses, RT type (whole brain irradiation and partial brain irradiation), sedating medications, and fatigue were independently associated with cognition. Sociodemographic and other clinical characteristics were not significant. In adjusted analyses, only fatigue remained significantly associated with group membership (OR = 1.05, 95% CI = 1.01-1.09, P = .009). CONCLUSIONS: There is a subgroup of survivors with minimal long-term cognitive deficits despite undergoing a full course of brain RT as part of cancer treatment. Lower fatigue had the strongest association with better cognitive performance. Interventions targeting cancer-related fatigue may help buffer the neurotoxic effects of brain RT.

Treatment of Radiation-Induced Cognitive Decline in Adult Brain Tumor Patients.

OPINION STATEMENT: Patients with either primary or metastatic brain tumors quite often have cognitive impairment. Maintaining cognitive function is important to brain tumor patients and a decline in cognitive function is generally accompanied by a decline in functional independence and performance status. Cognitive decline can be a result of tumor progression, depression/anxiety, fatigue/sleep dysfunction, or the treatments they have received. It is our opinion that providers treating brain tumor patients should obtain pre-treatment and serial cognitive testing in their patients and offer mitigating and therapeutic interventions when appropriate. They should also support cognition-focused clinical trials.

Surgical resection and postoperative radiosurgery versus staged radiosurgery for large brain metastases.

PURPOSE: The purpose of this study was to retrospectively evaluate the new treatment paradigm of staged stereotactic radiosurgery (SRS) for the treatment of large brain metastases (BM) compared to the standard of surgical resection followed by SRS. METHODS: We evaluated 78 patients with large BM treated 2012-2017 with surgical resection and postoperative SRS (surgery + SRS) or staged SRS separated by 1 month. Overall survival (OS) was estimated using the Kaplan Meier method and compared across groups using the log-rank test. Cumulative incidence of neurologic death and local and distant brain failure (LF, DBF) were estimated using competing risk methodology. RESULTS: Forty patients were treated with surgery + SRS and 38 patients were treated with staged SRS. Median follow-up was 23.2 months (95% CI 20.5-39.3). Median OS was 13.2 months for staged SRS compared to surgery + SRS 9.7 months (p = 0.53). Cumulative incidence of neurologic death at 1 year was 23% after surgery + SRS, 27% after staged SRS (p = 0.69); cumulative incidence of LF at 1 year was 6% and 8% (p = 0.65) and 1-year DBF was 59% and 21% (p ≤ 0.01). Overall rates of leptomeningeal failure and radiation necrosis were similar between the groups (p = 0.63 and p = 1.0). CONCLUSIONS: Though surgery and postoperative SRS is the standard, staged SRS represents an attractive treatment paradigm for treating large BM without sacrificing LC or survival, and potentially decreases DBF. Prospective studies are needed to validate these findings.

Initial brain metastasis velocity: does the rate at which cancers first seed the brain affect outcomes?

PURPOSE/OBJECTIVE(S): Brain metastasis velocity (BMV) is a metric that describes the rate of development of new brain metastases (BM) after initial stereotactic radiosurgery (SRS). A limitation in the application of BMV is it cannot be applied until time of first BM failure after SRS. We developed initial BM velocity (iBMV), a new metric that accounts for the number of BM at first SRS and the time since initial cancer diagnosis. MATERIALS/METHODS: We reviewed patients with BM treated at our institution with upfront SRS without WBRT. iBMV was calculated as the number of BM at initial SRS divided by time (years) from initial cancer diagnosis to first SRS. We performed a linear regression to correlate BMV as a continuous variable and with low, intermediate, and high BMV risk groups. Kaplan-Meier estimation of OS was calculated from time of first SRS to death. iBMV was not calculated for patients who presented with BM at initial cancer diagnosis. RESULTS: 994 patients were treated with upfront SRS without WBRT between 2000 and 2017. Median OS was 8.5 mos. 595 (60%) patients developed BM after cancer diagnosis and median time to first SRS from time of initial diagnosis was 2.2 years. Median iBMV was 0.79 BM/year. iBMV correlated with BMV (ß = 1.57 p = 0.021) and independently predicted for mortality [Cox proportional hazard ratio (HR) 1.11, p = 0.036] after accounting for histology, number of initial brain metastases (HR 1.03, p = 0.32), time from cancer diagnosis to SRS (HR 0.98, p = 0.157) in a multivariate model. CONCLUSION: iBMV correlates with BMV and OS. With further validation, iBMV could serve as a metric to risk stratify patients for WBRT or SRS at time of first BM presentation.

Glioblastoma radiomics: can genomic and molecular characteristics correlate with imaging response patterns?

PURPOSE: For glioblastoma (GBM), imaging response (IR) or pseudoprogression (PSP) is frequently observed after chemoradiation and may connote a favorable prognosis. With tumors categorized by the Cancer Genome Atlas Project (mesenchymal, classical, neural, and proneural) and by methylguanine-methyltransferase (MGMT) methylation status, we attempted to determine if certain genomic or molecular subtypes of GBM were specifically associated with IR or PSP. METHODS: Patients with GBM treated at two institutions were reviewed. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Mantel-cox test determined effect of IR and PSP on OS and PFS. Fisher's exact test was utilized to correlate IR and PSP with genomic subtypes and MGMT status. RESULTS: Eighty-two patients with GBM were reviewed. The median OS and PFS were 17.9 months and 8.9 months. IR was observed in 28 (40%) and was associated with improved OS (median 29.4 vs 14.5 months p < 0.01) and PFS (median 17.7 vs 5.5 months, p < 0.01). PSP was observed in 14 (19.2%) and trended towards improved PFS (15.0 vs 7.7 months p = 0.08). Tumors with a proneural component had a higher rate of IR compared to those without a proneural component (IR 60% vs 28%; p = 0.03). MGMT methylation was associated with IR (58% vs 24%, p = 0.032), but not PSP (34%, p = 0.10). CONCLUSION: IR is associated with improved OS and PFS. The proneural subtype and MGMT methylated tumors had higher rates of IR.

Gamma Knife Stereotactic Radiosurgery for the Treatment of Brain Metastases from Primary Tumors of the Urinary Bladder.

BACKGROUND/AIMS: Brain metastases from bladder cancer are rare and published outcomes data are sparse. To date, no institutions have reported a series of patients with brain metastases from bladder cancer treated with stereotactic radiosurgery (SRS). Our aim was to identify patients with brain metastases from bladder primaries treated with SRS with or without surgical resection and report the clinical outcomes. METHODS: Patients meeting eligibility criteria at our institution between 2000 and 2017 were included. The clinical variables of interest, including overall survival (OS), local recurrence, V12, distant brain failure (DBF), and initial brain metastases velocity, were calculated. Cox proportional hazards analysis was performed to identify predictors of time-to-event outcomes. RESULTS: A total of 14 patients were included. The median OS from the time of treatment was 2.1 months. Factors predictive of OS include intracranial resection (HR 0.21, p = 0.03). The cumulative incidence of local failure was 21% at 6 months and 30% at 12 months. The cumulative incidence of DBF at 6 and 12 months was 23 and 31%, respectively. CONCLUSIONS: The prognosis in this patient population remains guarded. Factors associated with improved survival include intracranial resection. Future, prospective work is needed to further define optimal management.

The Impact of Telemedicine on Pediatric Critical Care Triage.

OBJECTIVE: To examine the relationship between pediatric critical care telemedicine consultation to rural emergency departments and triage decisions. We compare the triage location and provider rating of the accuracy of remote assessment for a cohort of patients who receive critical care telemedicine consultations and a similar group of patients receiving telephone consultations. DESIGN: Retrospective evaluation of consultations occurring between April 2012 and March 2016. SETTING: Pediatric critical care telemedicine and telephone consultations in 52 rural healthcare settings in South Carolina. PATIENTS: Pediatric patients receiving critical care telemedicine or telephone consultations. INTERVENTION: Telemedicine consultations. MEASUREMENTS AND MAIN RESULTS: Data were collected from the consulting provider for 484 total consultations by telephone or telemedicine. We examined the providers' self-reported assessments about the consultation, decision-making, and triage outcomes. We estimate a logit model to predict triage location as a function of telemedicine consult age and sex. For telemedicine patients, the odds of triage to a non-ICU level of care are 2.55 times larger than the odds for patients receiving telephone consultations (p = 0.0005). Providers rated the accuracy of their assessments higher when consultations were provided via telemedicine. When patients were transferred to a non-ICU location following a telemedicine consultation, providers indicated that the use of telemedicine influenced the triage decision in 95.7% of cases (p < 0.001). For patients transferred to a non-ICU location, an increase in transfers to a higher level of care within 24 hours was not observed. CONCLUSION: Pediatric critical care telemedicine consultation to community hospitals is feasible and results in a reduction in PICU admissions. This study demonstrates an improvement in provider-reported accuracy of patient assessment via telemedicine compared with telephone, which may produce a higher comfort level with transporting patients to a lower level of care. Pediatric critical care telemedicine consultations represent a promising means of improving care and reducing costs for critically ill children in rural areas.

Analysis of perioperative radiation therapy in the surgical treatment of primary and recurrent retroperitoneal sarcoma.

BACKGROUND: Radiation therapy (RT) is increasingly utilized in conjunction with surgery for the treatment of retroperitoneal soft tissue sarcomas (RPS). Despite multiple theoretical advantages of RT, its role in the surgical management of this disease remains ill defined. METHODS: Patients undergoing surgery for RPS from 1990 to 2011 were identified. Patients were classified as having primary or recurrent disease, and then further stratified by the use of perioperative RT. Primary outcomes, including overall survival (OS) and recurrence-free survival (RFS), were estimated using the Kaplan-Meier method with comparisons based on the log rank test. Cox-proportional hazards modeling was used to estimate the independent effect of RT on survival. RESULTS: Ninety-four patients met final inclusion criteria. After adjusting for confounding variables, perioperative RT remained independently associated with a reduced risk of recurrence (HR 0.34, P < 0.01) and death (HR 0.30, P = 0.02). CONCLUSIONS: In this retrospective series, perioperative RT is an independent predictor of improved OS and RFS. These results provide additional support for the use of RT in the multimodality treatment of retroperitoneal sarcoma.

Delayed Imaging Changes 18 Months or Longer After Stereotactic Radiosurgery for Brain Metastases: Necrosis or Progression.

OBJECTIVE: Imaging changes after stereotactic radiosurgery (SRS) can occur for years after treatment, although the available data on the incidence of tumor progression and adverse radiation effects (ARE) are generally limited to the first 2 years after treatment. METHODS: A single-institution retrospective review was conducted of patients who had >18 months of imaging follow-up available. Patients who had ≥1 metastatic brain lesions treated with Gamma Knife SRS were assessed for the time to radiographic progression. Those with progression ≥18 months after the initial treatment were included in the present study. The lesions that progressed were characterized as either ARE or tumor progression based on the tissue diagnosis or imaging characteristics over time. RESULTS: The cumulative incidence of delayed imaging radiographic progression was 35% at 5 years after the initial SRS. The cumulative incidence curves of the time to radiographic progression for lesions determined to be ARE and lesions determined to be tumor progression were not significantly different statistically. The cumulative incidence of delayed ARE and delayed tumor progression was 17% and 16% at 5 years, respectively. Multivariate analysis indicated that the number of metastatic brain lesions present at the initial SRS was the only factor associated with late radiographic progression. CONCLUSIONS: The timing of late radiographic progression does not differ between ARE and tumor progression. The number of metastatic brain lesions at the initial SRS is a risk factor for late radiographic progression.

Brain metastases from renal cell carcinoma: Effects of novel systemic agents on brain metastasis outcomes.

OBJECTIVE: The objective of this study was to examine survival outcomes in 136 patients with renal cell carcinoma with metastases to the brain who were treated with radiation combined with immunotherapy or tyrosine kinase inhibitor compared to those who were treated with radiation therapy alone. METHODS: The Wake Forest Gamma Knife prospective database was searched for all patients with renal cell carcinoma brain metastases. Outcome measurements included overall survival, determined via the Kaplan-Meier Method, and cumulative incidence of local and distant failure, determined using the Fine Gray competing risks analysis with death as a competing risk for the 136 patients included. RESULTS: Overall survival for the entire population at 6 months, 12 months, and 24 months was 67%, 47% and 30%, respectively. For the TKI (non-immunotherapy-treated) population (n = 37), overall survival was 75%, 61%, and 40% at 6 months, 12 months, and 24 months, respectively. For the immunotherapy-treated population (n = 35), overall survival was 85%, 64%, and 50% at 6 months, 12 months, and 24 months, respectively. Overall survival was significantly increased for patients who received radiation with either immunotherapy or TKI (p < 0.0001). CONCLUSION: Prior series of patients with brain metastases of multiple histologies have demonstrated an improvement in the local efficacy of stereotactic radiosurgery when combined with systemic agents. We found that patients treated with targeted agents and patients treated with immunotherapy demonstrated a trend towards improvement over patients treated in the era prior to the advent of either classes of novel therapies.

Low contralateral neck recurrence risk with ipsilateral neck radiotherapy in N2b tonsillar squamous cell carcinoma.

OBJECTIVES: To characterize factors including nodal burden, pre-treatment imaging, and other patient factors which may influence the role of ipsilateral neck radiotherapy (IRT) in tonsillar squamous cell carcinoma (SCC) with multiple involved ipsilateral nodes. METHODS: Patients with cT1-2N0-2bM0 (AJCC 7th edition) tonsillar SCC treated with definitive radiation therapy (RT) at Duke University Medical Center from 1/1/1990-10/1/2019 were identified. Patient, tumor, and treatment characteristics were compared between those that received bilateral neck RT (BRT) versus IRT. Recurrence-free survival (RFS) was estimated with Kaplan-Meier method. A subset analysis of patients with N2b disease was performed. Patterns of recurrence were analyzed. RESULTS: 120 patients with cT1-2N0-2b tonsillar SCC were identified, including 71 with N2b disease (BRT: n = 30; IRT: n = 41). Median follow-up was 80 months (range: 7-209). No N2b patients who received IRT had > 1 cm of soft palate/base of tongue extension. N2b patients treated with IRT had a median of 3 (range 2-9) involved lymph nodes, with median largest nodal dimension of 2.8 cm (range 1.3-4.8 cm). 93 % of N2b patients who received IRT had staging by PET/CT, and 100 % received IMRT. For N2b patients treated with IRT, there were no contralateral neck recurrences, and 10 year RFS was 95 % (95 % CI 82 %-98 %). CONCLUSIONS: For patients treated with IRT for well-lateralized N2b tonsillar SCC, we observed high rates of local control with no observed contralateral neck recurrence. These data suggest that BRT is not universally necessary for patients with multiple involved ipsilateral nodes, particularly in the setting of baseline staging with PET/CT.

Five-year survivors from brain metastases treated with stereotactic radiosurgery: Biology, improving treatments, or just plain luck?

Background: Improvements in therapies have led to an increasing number of long-term survivors of brain metastases. The present series compares a population of 5-year survivors of brain metastases to a generalized brain metastases population to assess for factors attributable to long-term survival. Methods: A single institution retrospective review was performed to identify 5-year survivors of brain metastases who received stereotactic radiosurgery (SRS). A historical control population of 737 patients with brain metastases was used to assess similarities and differences between the long-term survivor population and the general population treated with SRS. Results: A total of 98 patients with brain metastases were found to have survived over 60 months. No differences between long-term survivors and controls were identified with regards to the age at first SRS (P = .19), primary cancer distribution (P = .80), and the number of metastases at first SRS (P = .90). Cumulative incidence of neurologic death at 6, 8 and 10 years for the long-term survivor cohort was 4.8%, 16%, and 16% respectively. In the historical controls, cumulative incidence of neurologic death reached a plateau at 40% after 4.9 years. A significant difference in the distribution of burden of disease at the time of the first SRS was found between the 5-year survivors and the control (P = .0049). 58% of 5-year survivors showed no evidence of clinical disease at the last follow-up. Conclusion: Five-year survivors of brain metastases represent a diverse histologic population, suggesting a small population of oligometastatic and indolent cancers exist for each cancer type.

Triple negative breast cancer is associated with an increased risk of residual invasive carcinoma after lumpectomy.

BACKGROUND: To assess the potential mechanisms that may underlie increased local failure in triple negative (TN) breast cancers, an analysis was performed of the risk of residual carcinoma after lumpectomy with correlation to pathologic factors, including molecular phenotype. METHODS: A review of pathologic specimens was performed for women with invasive breast cancer treated with lumpectomy followed by reexcision. Data were collected on age; tumor size, grade, and nodal stage; estrogen receptor, progesterone receptor, and human endothelial growth factor receptor 2 (Her2); extensive intraductal component; lymphovascular invasion; margins; and reexcision findings. Univariate and multivariate logistic regression analyses were performed to evaluate for associations between pathologic features of the lumpectomy specimen and reexcision findings. Molecular phenotypes were defined by conventionally used immunohistochemical pattern. RESULTS: Data were collected on 369 patients with breast cancer. The median age was 57 years, median tumor size was 1.5 cm, 36% had positive margins, 32% had positive lymph nodes, 73.5% had the luminal A subtype, 9.5% had the luminal B subtype, 4.5% were Her2-enriched, and 12.5% were TN. Overall, 32% of patients had invasive cancer in their reexcision specimens, and 51% of those with the TN subtype had residual invasive disease on reexcision compared with 30% to 31% for other subtypes. On univariate analysis, age, tumor size, margin status, lymphovascular invasion, nodal status, and TN subtype were associated with elevated risk of residual invasive cancer. On multivariate analysis using a forward stepwise model, TN subtype maintained significance, with an odds ratio of 3.28 (P = .002). CONCLUSION: TN subtype has a statistically significant association with an increased risk of residual tumor. This suggests the putative increase in the risk of local failure in TN patients may be related to increased residual tumor burden.

Brain metastasis prognostic nomograms and brain metastasis velocity: a narrative review.

OBJECTIVE: To provide a review of the current status of predictive nomograms and brain metastasis velocity (BMV) in the prognostication of brain metastasis outcomes. BACKGROUND: Statistical analyses have been used for many years in an attempt to predict clinical outcomes of brain metastasis patients. Such models have attempted to predict such endpoints as survival and which patients would most benefit from stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT). METHODS: This narrative review includes documents the history of statistical models and nomograms through the stage migration of the brain metastasis population from a population with large symptomatic brain metastases to the modern population with small asymptomatic metastases found on surveillance imaging. It also tells the history of the derivation and validation of BMV, a recently identified biomarker for survival and neurologic death in the brain metastasis population treated with SRS. CONCLUSIONS: Statistical models predicting brain metastasis behavior continue to evolve with the changing landscape of systemic therapy and the more aggressive use of SRS. Previous models with ultimately need to integrate biologic data and will continue to be updated.

Upfront immunotherapy leads to lower brain metastasis velocity in patients undergoing stereotactic radiosurgery for brain metastases.

Background: While immunotherapy has been shown to improve survival and decrease neurologic death in patients with brain metastases, it remains unclear whether this improvement is due to prevention of new metastasis to the brain. Method: We performed a retrospective review of patients presenting with brain metastases simultaneously with the first diagnosis of metastatic disease and were treated with upfront immunotherapy as part of their treatment regimen and stereotactic radiosurgery (SRS) to the brain metastases. We compared this cohort with a historical control population (prior to the immunotherapy era) who were treated with pre-immunotherapy standard of care systemic therapy and with SRS to the brain metastases. Results: Median overall survival time was improved in the patients receiving upfront immunotherapy compared to the historical cohort (48 months vs 8.4 months, p=0.001). Median time to distant brain failure was statistically equivalent (p=0.3) between the upfront immunotherapy cohort and historical control cohort (10.3 vs 12.6 months). Brain metastasis velocity was lower in the upfront immunotherapy cohort (median 3.72 metastases per year) than in the historical controls (median 9.48 metastases per year, p=0.001). Cumulative incidence of neurologic death at one year was 12% in the upfront immunotherapy cohort and 28% in the historical control cohort (p=0.1). Conclusions: Upfront immunotherapy appears to improve overall survival and decrease BMV compared to historical controls. While these data remain to be validated, they suggest that brain metastasis patients may benefit from concurrent immunotherapy with SRS.