C.K. Cramer

Early or late radiotherapy following gross or subtotal resection for atypical meningiomas: Clinical outcomes and local control

We report a single institution series of surgery followed by either early adjuvant or late radiotherapy for atypical meningiomas (AM). AM patients, by WHO 2007 definition, underwent subtotal resection (STR) or gross total resection (GTR). Sixty-three of a total 115 patients then received fractionated or stereotactic radiation treatment, early adjuvant radiotherapy (≤4months after surgery) or late radiotherapy (at the time of recurrence). Kaplan Meier method was used for survival analysis with competing risk analysis used to assess local failure. Overall survival (OS) at 1, 2, and 5years for all patients was 87%, 85%, 66%, respectively. Progression free survival (PFS) at 1, 2, and 5years for all patients was 65%, 30%, and 18%, respectively. OS at 1, 2, and 5years was 75%, 72%, 55% for surgery alone, and 97%, 95%, 75% for surgery+radiotherapy (log-rank p-value=0.0026). PFS at 1, 2, and 5years for patients undergoing surgery without early adjuvant radiotherapy was 64%, 49%, and 27% versus 81%, 73%, and 59% for surgery+early adjuvant radiotherapy (log-rank p-value=0.0026). The cumulative incidence of local failure at 1, 2, and 5years for patients undergoing surgery without early External Beam Radiation Therapy (EBRT) was 18.7%, 35.0%, and 52.9%, respectively, versus 4.2%, 13.3%, and 20.0% for surgery and early EBRT (p-value=0.02). Adjuvant radiotherapy improves OS in patients with AM. Early adjuvant radiotherapy improves PFS, likely due to the improvement in local control seen with early adjuvant EBRT.

The Effects of smoking status and smoking history on patients with brain metastases from lung cancer

There is limited data on the effects of smoking on lung cancer patients with brain metastases. This single institution retrospective study of patients with brain metastases from lung cancer who received stereotactic radiosurgery assessed whether smoking history is associated with overall survival, local control, rate of new brain metastases (brain metastasis velocity), and likelihood of neurologic death after brain metastases. Patients were stratified by adenocarcinoma versus nonadenocarcinoma histologies. Kaplan–Meier analysis was performed for survival endpoints. Competing risk analysis was performed for neurologic death analysis to account for risk of nonneurologic death. Separate linear regression and multivariate analyses were performed to estimate the brain metastasis velocity. Of 366 patients included in the analysis, the median age was 63, 54% were male and, 60% were diagnosed with adenocarcinoma. Current smoking was reported by 37% and 91% had a smoking history. Current smoking status and pack‐year history of smoking had no effect on overall survival. There was a trend for an increased risk of neurologic death in nonadenocarcinoma patients who continued to smoke (14%, 35%, and 46% at 6/12/24 months) compared with patients who did not smoke (12%, 23%, and 30%, P = 0.053). Cumulative pack years smoking was associated with an increase in neurologic death for nonadenocarcinoma patients (HR = 1.01, CI: 1.00–1.02, P = 0.046). Increased pack‐year history increased brain metastasis velocity in multivariate analysis for overall patients (P = 0.026). Current smokers with nonadenocarcinoma lung cancers had a trend toward greater neurologic death than nonsmokers. Cumulative pack years smoking is associated with a greater brain metastasis velocity.

Hippocampal dose volume histogram predicts Hopkins Verbal Learning Test scores after brain irradiation

Purpose Radiation-induced cognitive decline is relatively common after treatment for primary and metastatic brain tumors; however, identifying dosimetric parameters that are predictive of radiation-induced cognitive decline is difficult due to the heterogeneity of patient characteristics. The memory function is especially susceptible to radiation effects after treatment. The objective of this study is to correlate volumetric radiation doses received by critical neuroanatomic structures to post–radiation therapy (RT) memory impairment. Methods and materials Between 2008 and 2011, 53 patients with primary brain malignancies were treated with conventionally fractionated RT in prospectively accrued clinical trials performed at our institution. Dose-volume histogram analysis was performed for the hippocampus, parahippocampus, amygdala, and fusiform gyrus. Hopkins Verbal Learning Test-Revised scores were obtained at least 6 months after RT. Impairment was defined as an immediate recall score ≤15. For each anatomic region, serial regression was performed to correlate volume receiving a given dose (VD(Gy)) with memory impairment. Results Hippocampal V53.4Gy to V60.9Gy significantly predicted post-RT memory impairment (P < .05). Within this range, the hippocampal V55Gy was the most significant predictor (P = .004). Hippocampal V55Gy of 0%, 25%, and 50% was associated with tumor-induced impairment rates of 14.9% (95% confidence interval [CI], 7.2%-28.7%), 45.9% (95% CI, 24.7%-68.6%), and 80.6% (95% CI, 39.2%-96.4%), respectively. Conclusions The hippocampal V55Gy is a significant predictor for impairment, and a limiting dose below 55 Gy may minimize radiation-induced cognitive impairment.

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.

Potential Prognostic Markers for Survival and Neurologic Death in Patients with Breast Cancer Brain Metastases who Receive upfront SRS Alone

Purpose/Objectives Stereotactic radiosurgery (SRS) is used as a treatment option for breast cancer brain metastases. It is unclear what factors predict neurologic death for these patients. Materials/Methods A total of 128 patients with breast cancer brain metastases were treated with upfront SRS alone in this study. Survival was estimated using the Kaplan-Meier method. Clinicopathologic factors evaluated included age, ER/PR status, Her2 status, numbers of brain metastases treated, minimum SRS dose, disease-specific GPA, extracranial disease status and systemic disease burden. Results ER or PR positivity was associated with a trend towards decreased neurologic death (subdistribution hazard ratio (sHR) = 0.54, p=0.06). Factors associated with non-neurologic death include extracranial disease status (sHR = 2.02, p=0.02) and dose (sHR = 1.11, p=0.02); Her2-positivity was associated with reduced hazard of non-neurologic death (sHR 0.52, p=0.05). Conclusions ER/PR positivity was associated with a trend towards less neurologic death. HER2 positivity was associated with a trend towards less non-neurologic death.

The number of prior lines of systemic therapy as a prognostic factor for patients with brain metastases treated with stereotactic radiosurgery: Results of a large single institution retrospective analysis

OBJECTIVES It is presently unknown whether patients with brain metastases from heavily pre-treated cancers have a significantly different prognosis than those with less pre-treatment. In this study we sought to identify whether the number of prior lines of systemic therapy are associated with clinical outcomes in patients with brain metastases who received stereotactic radiosurgery (SRS). PATIENTS AND METHODS Between July 2000 and July 2017, 377 patients with brain metastases were treated with upfront SRS. We performed a large, single institution retrospective analysis of these patients. Kaplan Meier analysis was used to estimate survival times. Competing risk analysis was used to estimate times to local failure (LF) and distant brain failure (DBF). Multivariate analysis was performed to estimate the hazard ratios (HRs) for overall survival (OS), neurologic and non-neurologic death for patients with 1, 2 and 3+ lines of prior systemic therapy. RESULTS Of the 1077 patients with brain metastases treated with SRS, 377 received prior systemic therapy with a median of 1 (range: 1-9) lines of prior therapy. Median OS was 8.70 months (95% CI, 7.9-9.5). Median OS for patients with 1 prior line of therapy, 2 prior lines of therapy and 3 or greater lines of therapy were 9.93-, 9.05-, and 6.18-months, respectively (log rank p = .04). Lines of therapy as a continuous variable was not associated with LF or DBF on competing risk analysis. The percentage of patients that died of neurological death was 36%. Greater prior lines of therapy (1 vs. 2 vs. 3 and greater) was associated with a greater likelihood of dying of non-neurologic death (grays p = .01), but was not associated with likelihood of dying of neurologic death (p = .57). CONCLUSION Lines of therapy are associated with OS and non-neurologic death but are not associated with neurologic death, LF or DBF.

Survival and Failure Outcomes Predicted by Brain Metastasis Volumetric Kinetics in Melanoma Patients Following Upfront Treatment with Stereotactic Radiosurgery Alone

Introduction The roles of early whole brain radiotherapy (WBRT) and upfront stereotactic radiosurgery (SRS) alone in the treatment of melanoma patients with brain metastasis remain uncertain. We investigated the volumetric kinetics of brain metastasis development and associations with clinical outcomes for melanoma patients who received upfront SRS alone. Methods Volumetric brain metastasis velocity (vBMV) was defined as the volume of new intracranial disease at the time of distant brain failure (DBF) for the first DBF (DBF1) and second DBF (DBF2) averaged over the time since initial or most recent SRS. Non-volumetric brain metastasis velocity (BMV) was calculated for comparison. Results Median overall survival (OS) for all patients was 7.7 months. Increasing vBMVDBF1 was associated with worsened OS (hazard ratio (HR): 1.10, confidence interval (CI): 1.02 - 1.18, p = .01). Non-volumetric BMVDBF1 was not predictive of OS after DBF1 (HR: 1.00, CI: 0.97 - 1.02, p = .77). Cumulative incidence of DBF2 at three months after DBF1 was 50.0% for vBMVDBF1 > 4 cc/yr versus (vs) 15.1% for vBMVDBF1 ≤ 4 cc/yr, (Gray’s p-value = .02). Cumulative incidence of salvage WBRT at three months after DBF1 was 50.0% for vBMVDBF1 > 4 cc/yr vs 2.3% for vBMVDBF1 ≤ 4 cc/yr (Gray’s p-value < .001). Conclusion In melanoma patients with brain metastasis, volumetric BMV was predictive of survival, shorter time to second DBF, and the need for salvage WBRT. Non-volumetric BMV, however, did not predict for these outcomes, suggesting that vBMV is a stronger predictor in melanoma.