Lilyana Angelov

Probabilities of Radiation Myelopathy Specific to Stereotactic Body Radiation Therapy to Guide Safe Practice

PURPOSE Dose-volume histogram (DVH) results for 9 cases of post spine stereotactic body radiation therapy (SBRT) radiation myelopathy (RM) are reported and compared with a cohort of 66 spine SBRT patients without RM. METHODS AND MATERIALS DVH data were centrally analyzed according to the thecal sac point maximum (Pmax) volume, 0.1- to 1-cc volumes in increments of 0.1 cc, and to the 2 cc volume. 2-Gy biologically equivalent doses (nBED) were calculated using an α/β = 2 Gy (units = Gy(2/2)). For the 2 cohorts, the nBED means and distributions were compared using the t test and Mann-Whitney test, respectively. Significance (P<.05) was defined as concordance of both tests at each specified volume. A logistic regression model was developed to estimate the probability of RM using the dose distribution for a given volume. RESULTS Significant differences in both the means and distributions at the Pmax and up to the 0.8-cc volume were observed. Concordant significance was greatest for the Pmax volume. At the Pmax volume the fit of the logistic regression model, summarized by the area under the curve, was 0.87. A risk of RM of 5% or less was observed when limiting the thecal sac Pmax volume doses to 12.4 Gy in a single fraction, 17.0 Gy in 2 fractions, 20.3 Gy in 3 fractions, 23.0 Gy in 4 fractions, and 25.3 Gy in 5 fractions. CONCLUSION We report the first logistic regression model yielding estimates for the probability of human RM specific to SBRT.

Vertebral Compression Fracture After Spine Stereotactic Body Radiotherapy: A Multi-Institutional Analysis With a Focus on Radiation Dose and the Spinal Instability Neoplastic Score

PURPOSE Vertebral compression fracture (VCF) is increasingly recognized as an adverse event after spine stereotactic body radiotherapy (SBRT). We report a multi-institutional study aimed at clarifying the risk and predictive factors associated with VCF. PATIENTS AND METHODS A total of 252 patients with 410 spinal segments treated with SBRT were included. The primary outcome was the development of VCF (a new VCF or progression of a baseline VCF). In addition to various patient-, treatment-, and tumor-specific factors, the Spinal Instability Neoplastic Scoring (SINS) system was applied to determine predictive value. RESULTS The median follow-up was 11.5 months (range, 0.03 to 113 months). The median and mean overall survival rates were 16 and 26 months, respectively. We observed 57 fractures (57 of 410, 14%), with 47% (27 of 57) new fractures and 53% (30 of 57) fracture progression. The median time to VCF was 2.46 months (range, 0.03 to 43.01 months), and 65% occurred within the first 4 months. The 1- and 2-year cumulative incidences of fracture were 12.35% and 13.49%, respectively. Multivariable analysis identified dose per fraction (greatest risk for ≥ 24 Gy v 20 to 23 Gy v ≤ 19 Gy), in addition to three of the six original SINS criteria: baseline VCF, lytic tumor, and spinal deformity, as significant predictors of VCF. CONCLUSION Caution must be observed when treating with ≥ 20 Gy/fraction, in particular, for patients with lytic tumor, spinal misalignment, and a baseline VCF. Frequent short-term follow-up is required, as nearly two thirds of all VCF occurred within the first 4 months. We also conclude that SINS may have utility in predicting patients at high risk of SBRT-induced VCF.

Spine metastases: current treatments and future directions.

Spinal metastases are the most frequently encountered spinal tumour and can affect up to 50% of cancer patients. Both the incidence and prevalence of metastases are thought to be rising due to better detection and treatment options of the systemic malignancy resulting in increased patient survival. Further, the development and access to newer imaging modalities have resulted in easier screening and diagnosis of spine metastases. Current evidence suggests that pain, neurological symptoms and quality of life are all improved if patients with spine metastases are treated early and aggressively. However, selection of the appropriate therapy depends on several factors including primary histology, extent of the systemic disease, existing co-morbidities, prior treatment modalities, patient age and performance status, predicted life expectancy and available resources. This article reviews the currently available therapeutic options for spinal metastases including conventional external beam radiation therapy, open surgical decompression and stabilisation, vertebral augmentation and other minimally invasive surgery (MIS) options, stereotactic spine radiosurgery, bisphosphonates, systemic radioisotopes and chemotherapy. An algorithm for the management of spine metastases is also proposed. It outlines a multidisciplinary and integrated approach to these patients and it is hoped that this along with future advances and research will result in improved patient care and outcomes.

Salvage stereotactic radiosurgery effectively treats recurrences from whole-brain radiation therapy.

The purpose of the current study was to examine overall survival (OS) and time to local failure (LF) in patients who received salvage stereotactic radiosurgery (SRS) for recurrent brain metastases (BM) after initial management that included whole‐brain radiation therapy (WBRT).

Results of a survey of neurosurgical practice patterns regarding the prophylactic use of anti-epilepsy drugs in patients with brain tumors

SummaryIntroduction: The American Association of Neurology issued guidelines discouraging the prophylactic use of anti-epilepsy drugs (AEDs) in patients with brain tumors. We surveyed neurosurgeons to evaluate practice patterns with regard to using AEDs in neurosurgical patients with brain tumors. Methods: The survey consisted of 18 questions. Two group email blasts containing an internet link to the survey were sent to members of the American Association of Neurological Surgeons with email addresses. Uni- and multi-variate analysis of the responses was performed using t-test, Fisher’s exact test, or chi-squared test, where appropriate. Results: The response rate was 15.5% (386/2491). The majority of respondents (270/386; 70.0%) had more than 5 years of experience in neurosurgery. Most respondents described their practices as general (224/379; 59.1%); about one-third were members of the Joint Section on Tumors (136/381; 35.7%). More than 70% of respondents reported routine use of AED prophylaxis for patients with intra-axial gliomas or brain metastases. AED prophylaxis was also routinely used for extra-axial benign tumors or stereotactic biopsies by 53.8% and 21.4%, respectively. On multivariate analysis, the number of years in practice of ABNS certified neurosurgeons was the strongest predictor for the use of AED prophylaxis. Conclusions: Routine use of AED prophylaxis in patients with brain tumors undergoing neurosurgical procedures remains the prevailing practice pattern among members of the AANS. Additional larger prospective studies with appropriate patient stratification culminating in development of neurosurgical guidelines on AED prophylaxis in brain tumor patients is warranted.

Recursive Partitioning Analysis Index Is Predictive for Overall Survival in Patients Undergoing Spine Stereotactic Body Radiation Therapy for Spinal Metastases

PURPOSE To generate a prognostic index using recursive partitioning analysis (RPA) for patients undergoing spine stereotactic body radiation therapy (sSBRT) for spinal metastases (sMet). METHODS & MATERIALS From an institutional review board-approved database, 174 patients were treated for sMet with sSBRT between February 2006 and August 2009. Median dose was 14 Gy (range, 8-24 Gy), typically in a single fraction (range, 1-5). Kaplan-Meier analysis was performed to detect any correlation between survival and histology. Histologies were divided into favorable (breast and prostate), radioresistant (renal cell, melanoma and sarcoma), and other (all other histologies). RPA was performed to identify any association of the following variables with overall survival (OS) following sSBRT: histology, gender, age, Karnofsky performance status (KPS), control of primary, extraosseous metastases, time from primary diagnosis (TPD), dose of sSBRT (≤14 Gy vs. >14 Gy), extent of spine disease (epidural only, bone and epidural, bone only), upfront or salvage treatment, presence of paraspinal extension, and previous surgery. RESULTS Median follow-up was 8.9 months. Median OS time from sSBRT was 10.7 months. Median OS intervals for favorable histologies were 14 months, 11.2 months for radioresistant histologies, and 7.3 months for other histologies (p = 0.02). RPA analysis resulted in three classes (p < 0.0001). Class 1 was defined as TPD of >30 months and KPS of >70; Class 2 was TPD of >30 months and KPS of ≤70 or a TPD of ≤30 months and age <70 years old; Class 3 was TPD of ≤30 months and age ≥70 years old. Median OS was 21.1 months for Class 1 (n = 59), 8.7 months for Class 2 (n = 104), and 2.4 months for Class 3 (n = 11). CONCLUSION sSBRT patients treated for sMet have a wide variability in OS. We developed an RPA classification system that is predictive of OS. While many patients are treated for palliation of pain or to avoid symptomatic progression, this index may be used to predict which patients may benefit most from sSBRT.

Single-fraction stereotactic body radiotherapy for spinal metastases from renal cell carcinoma

OBJECT Stereotactic body radiotherapy (SBRT) has emerged as an important treatment option for spinal metastases from renal cell carcinoma (RCC) as a means to overcome RCCs inherent radioresistance. The authors reviewed the outcomes of SBRT for the treatment of RCC metastases to the spine at their institution, and they identified factors associated with treatment failure. METHODS Fifty-seven patients (88 treatment sites) with RCC metastases to the spine received single-fraction SBRT. Pain relief was based on the Brief Pain Inventory and was adjusted for narcotic use according to the Radiation Therapy Oncology Group protocol 0631. Toxicity was scored according to Common Toxicity Criteria for Adverse Events version 4.0. Radiographic failure was defined as infield or adjacent (within 1 vertebral body [VB]) failure on follow-up MRI. Multivariate analyses were performed to correlate outcomes with the following variables: epidural, paraspinal, single-level, or multilevel disease (2-5 sites); neural foramen involvement; and VB fracture prior to SBRT. Kaplan-Meier analysis and Cox proportional hazards modeling were used for statistical analysis. RESULTS The median follow-up and survival periods were 5.4 months (range 0.3-38 months) and 8.3 months (range 1.5-38 months), respectively. The median time to radiographic failure and unadjusted pain progression were 26.5 and 26.0 months, respectively. The median time to pain relief (from date of simulation) and duration of pain relief (from date of treatment) were 0.9 months (range 0.1-4.4 months) and 5.4 months (range 0.1-37.4 months), respectively. Multivariate analyses demonstrated that multilevel disease (hazard ratio [HR] 3.5, p = 0.02) and neural foramen involvement (HR 3.4, p = 0.02) were correlated with radiographic failure; multilevel disease (HR 2.3, p = 0.056) and VB fracture (HR 2.4, p = 0.046) were correlated with unadjusted pain progression. One patient experienced Grade 3 nausea and vomiting; no other Grade 3 or 4 toxicities were observed. Twelve treatment sites (14%) were complicated by subsequent vertebral fractures. CONCLUSIONS Stereotactic body radiotherapy for RCC metastases to the spine offers fast and durable pain relief with minimal toxicity. Stereotactic body radiotherapy seems optimal for patients who have solitary or few spinal metastases. Patients with neural foramen involvement are at an increased risk for failure.

Treatment of five or more brain metastases with stereotactic radiosurgery.

PURPOSE To examine the outcomes of patients with five or more brain metastases treated in a single session with stereotactic radiosurgery (SRS). METHODS AND MATERIALS Sixty-four patients with brain metastases treated with SRS to five or more lesions in a single session were reviewed. Primary disease type, number of lesions, Karnofsky performance score (KPS) at SRS, and status of primary and systemic disease at SRS were included. Patients were treated using dosing as defined by Radiation Therapy Oncology Group Protocol 90-05, with adjustments for critical structures. We defined prior whole-brain radiotherapy (WBRT) as WBRT completed >1 month before SRS and concurrent WBRT as WBRT completed within 1 month before or after SRS. Kaplan-Meier estimates and Cox proportional hazard regression were used to determine which patient and treatment factors predicted overall survival (OS). RESULTS The median OS after SRS was 7.5 months. The median KPS was 80 (range, 60-100). A KPS of ≥ 80 significantly influenced OS (median OS, 4.8 months for KPS ≤ 70 vs. 8.8 months for KPS ≥ 80, p = 0.0097). The number of lesions treated did not significantly influence OS (median OS, 6.6 months for eight or fewer lesions vs. 9.9 months for more than eight, p = nonsignificant). Primary site histology did not significantly influence median OS. On multivariate Cox modeling, KPS and prior WBRT significantly predicted for OS. Whole-brain radiotherapy before SRS compared with concurrent WBRT significantly influenced survival, with a risk ratio of 0.423 (95% confidence interval 0.191-0.936, p = 0.0338). No significant differences were observed when no WBRT was compared with concurrent WBRT or when the no WBRT group was compared with prior WBRT. A KPS of ≤ 70 predicted for poorer outcomes, with a risk ratio of 2.164 (95% confidence interval 1.157-4.049, p = 0.0157). CONCLUSIONS Stereotactic radiosurgery to five or more brain lesions is an effective treatment option for patients with metastatic cancer, especially for patients previously treated with WBRT. A KPS of ≥ 80 predicts for an improved outcome.

Multidisciplinary management of colorectal brain metastases: A retrospective study

The incidence of brain metastases (BM) from colorectal cancer (CRC) is increasing, and the management of this previously rare complication at a single institution is reported.

Stereotactic Radiosurgery for Single Brainstem Metastases: The Cleveland Clinic Experience

PURPOSE To assess the imaging and clinical outcomes of patients with single brainstem metastases treated with stereotactic radiosurgery (SRS). MATERIALS AND METHODS We retrospectively reviewed the data from patients with single brainstem metastases treated with SRS. Locoregional control and survival were calculated using the Kaplan-Meier method. Prognostic factors were assessed using a Cox proportional hazards model. RESULTS Between 1997 and 2007, 43 patients with single brainstem metastases were treated with SRS. The median age at treatment was 59 years, the median Karnofsky performance status was 80, and the median follow-up was 5.3 months. The median dose was 15 Gy (range, 9.6-24), and the median conformality and heterogeneity index was 1.7 and 1.9, respectively. The median survival was 5.8 months from the procedure date. Of the 33 patient with post-treatment imaging available, a complete radiographic response was achieved in 2 (4.7%), a partial response in 8 (18.6%), and stable disease in 23 (53.5%). The 1-year actuarial rate of local control, distant brain control, and overall survival was 85%, 38.3%, and 31.5%, respectively. Of the 43 patients, 8 (19%) died within 2 months of undergoing SRS, and 15 (36%) died within 3 months. On multivariate analysis, greater performance status (hazard ratio [HR], 0.95, p = .004), score index for radiosurgery (HR, 0.7; p = .004), graded prognostic assessment score (HR, 0.48; p = .003), and smaller tumor volume (HR, 1.23, p = .002) were associated with improved survival. No Grade 3 or 4 toxicities were observed. CONCLUSION The results of our study have shown that SRS is a safe and effective local therapy for patients with brainstem metastases.