Adverse radiation effect after stereotactic radiosurgery for brain metastases

Adverse radiation effect after stereotactic radiosurgery for brain metastases- incidence, time course, and risk factors

J Neurosurg 123:373–386, 2015

The authors sought to determine the incidence, time course, and risk factors for overall adverse radiation effect (ARE) and symptomatic ARE after stereotactic radiosurgery (SRS) for brain metastases.

Methods All cases of brain metastases treated from 1998 through 2009 with Gamma Knife SRS at UCSF were considered. Cases with less than 3 months of follow-up imaging, a gap of more than 8 months in imaging during the 1st year, or inadequate imaging availability were excluded. Brain scans and pathology reports were reviewed to ensure consistent scoring of dates of ARE, treatment failure, or both; in case of uncertainty, the cause of lesion worsening was scored as indeterminate. Cumulative incidence of ARE and failure were estimated with the Kaplan-Meier method with censoring at last imaging. Univariate and multivariate Cox proportional hazards analyses were performed.

Results Among 435 patients and 2200 brain metastases evaluable, the median patient survival time was 17.4 months and the median lesion imaging follow-up was 9.9 months. Calculated on the basis of 2200 evaluable lesions, the rates of treatment failure, ARE, concurrent failure and ARE, and lesion worsening with indeterminate cause were 9.2%, 5.4%, 1.4%, and 4.1%, respectively. Among 118 cases of ARE, approximately 60% were symptomatic and 85% occurred 3–18 months after SRS (median 7.2 months). For 99 ARE cases managed without surgery or bevacizumab, the probabilities of improvement observed on imaging were 40%, 57%, and 76% at 6, 12, and 18 months after onset of ARE. The most important risk factors for ARE included prior SRS to the same lesion (with 20% 1-year risk of symptomatic ARE vs 3%, 4%, and 8% for no prior treatment, prior whole brain radiotherapy [WBRT], or concurrent WBRT) and any of these volume parameters: target, prescription isodose, 12-Gy, or 10-Gy volume. Excluding lesions treated with repeat SRS, the 1-year probabilities of ARE were < 1%, 1%, 3%, 10%, and 14% for maximum diameter 0.3–0.6 cm, 0.7–1.0 cm, 1.1–1.5 cm, 1.6–2.0 cm, and 2.1–5.1 cm, respectively. The 1-year probabilities of symptomatic ARE leveled off at 13%–14% for brain metastases maximum diameter > 2.1 cm, target volume > 1.2 cm3, prescription isodose volume > 1.8 cm3, 12-Gy volume > 3.3 cm3, and 10-Gy volume > 4.3 cm3, excluding lesions treated with repeat SRS. On both univariate and multivariate analysis, capecitabine, but not other systemic therapy within 1 month of SRS, appeared to increase ARE risk. For the multivariate analysis considering only metastases with target volume > 1.0 cm3, risk factors for ARE included prior SRS, kidney primary tumor, connective tissue disorder, and capecitabine.

Conclusions Although incidence of ARE after SRS was low overall, risk increased rapidly with size and volume, leveling off at a 1-year cumulative incidence of 13%–14%. This study describes the time course of ARE and provides risk estimates by various lesion characteristics and treatment parameters to aid in decision-making and patient counseling.

Anatomic features of glioblastoma and their potential impact on survival

Anatomic features of glioblastoma and their potential impact on survival

Acta Neurochir (2015) 157:179–186

Many reports on glioblastoma multiforme discuss the prognostic impact of anatomical features such as cysts, necrotic changes, extent of edema or subependymal spread of tumor cells. In the present study, we examined different growth patterns and their possible relations to patient survival.

Methods To analyze whether anatomical characteristics are related to prognosis, we reviewed the prospectively collected pre- and postoperative MRIs of 83 patients in the 5-ALA study, provided by the 5-ALA Glioma Study Group. Following a standardized analytic work flow, the tumor volume and site, presence of necrosis or cysts, and perifocal edema were assessed preoperatively. In the same way, postoperative MRI and the MRI at first recurrence were analyzed. In addition, survival time of the patients was documented.

Results Median survival time of all 83 patients was 15.1 months (range 1.5 to 70.1, mean 18). The site or volume of glioblastoma, as well as the presence of intratumoral necrosis or cysts, did not exert a significant effect on survival time; 96.4 % of recurrences occurred within the former resection margin. Tumors with initial contact with the subependymal zone had multifocal or ventricular recurrences significantly more often. In patients with residual tumor on early postoperative MRI, the follow-up images displayed enlargement of the remnants in 91.9 % of these cases.

Conclusions A merely anatomical analysis of the glioblastoma growth pattern cannot reliably provide prognostic information. The occurrence of most recurrences next to the resection margin and the high percentage of growing residual tumors underline the importance of complete resections.

Effect of bupivacaine on intervertebral disc cell viability

The Spine Journal 10 (2010) 159–166

Bupivacaine is a local anesthetic commonly used to relieve or control pain in interventional spine procedures. Bupivacaine has been shown to be toxic to articular cartilage, which has similarities to intervertebral disc (IVD) cartilage, raising concern over a potentially negative effect of bupivacaine on the disc.

PURPOSE: To determine bupivacaine’s effect on cell viability of IVD cells in vitro and to elucidate whether this is through apoptosis or necrosis.

STUDY DESIGN: In vitro controlled study of bupivacaine effect on cell viability in human and rabbit IVD cells.

SUBJECTS: Rabbit annulus fibrosus (AF) tissue, nucleus pulposus (NP) cells, and knee articular chondrocytes were isolated from New Zealand white rabbits. Human AF and NP cells were isolated from stage 3 to 4 degenerative disc surgical specimens.

OUTCOME MEASURES: Cell viability was assessed after exposure to bupivacaine via trypan blue staining or flow cytometry.

METHODS: Annulus fibrosus and NP cells were grown in monolayer and alginate beads, respectively, to simulate their physiologic environment. The cells were then exposed to bupivacaine or saline control at 60 and 120 minutes and examined for cell viability. RESULTS: Rabbit NP cell death demonstrated a time and dose dependence in response to bupivacaine. In addition, cell death was greater than that observed for articular chondrocytes. Rabbit AF tissue also demonstrated increased cell death in response to bupivacaine exposure. Human NP cells demonstrated time-dependent cell death, with greater necrosis than apoptosis. Annulus fibrosus cells grown in monolayers also resulted in similar effects, with greater necrosis rather than apoptosis.

CONCLUSIONS: Despite its pain relieving properties, bupivacaine decreases cell viability in rabbit and human disc cells in a time-dependent manner. In addition, the changes observed are greater than that seen for articular chondrocytes. This increase in cell death appears to be related to an increase in necrosis rather than apoptosis. Whether bupivacaine exerts similar effects in vivo or how this relates to overall clinical outcome remains to be explored.