Stereotactic radiosurgery for brain metastases from human epidermal receptor 2 positive breast Cancer: an international, multi-center study.

PURPOSE: To report patient outcomes and local tumor control rates in a cohort of patients with biopsy-proven HER-2 positive breast cancer treated with stereotactic radiosurgery (SRS) for brain metastases (BM). METHODS: This international, retrospective, multicenter study, included 195 female patients with 1706 SRS-treated BM. Radiologic and clinical outcomes after SRS were determined and prognostic factors identified. RESULTS: At SRS, median patient age was 55 years [interquartile range (IQR) 47.6-62.0], and 156 (80%) patients had KPS ≥ 80. The median tumor volume was 0.1 cm3 (IQR 0.1-0.5) and the median prescription dose was 16 Gy (IQR 16-18). Local tumor control (LTC) rate was 98%, 94%, 93%, 90%, and 88% at six-, 12-, 24-, 36- and 60-months post-SRS, respectively. On multivariate analysis, tumor volume (p = < 0.001) and concurrent pertuzumab (p = 0.02) improved LTC. Overall survival (OS) rates at six-, 12-, 24-, 36-, 48-, and 60-months were 90%, 69%, 46%, 27%, 22%, and 18%, respectively. Concurrent pertuzumab improved OS (p = 0.032). In this patient subgroup, GPA scores ≥ 2.5 (p = 0.038 and p = 0.003) and rare primary tumor histologies (p = 0.01) were associated with increased and decreased OS, respectively. Asymptomatic adverse radiation events (ARE) occurred in 27 (14.0%) and symptomatic ARE in five (2.6%) patients. Invasive lobular carcinoma primary (p = 0.042) and concurrent pertuzumab (p < 0.001) conferred an increased risk for overall but not for symptomatic ARE. CONCLUSION: SRS affords effective LTC for selected patients with BM from HER-2 positive breast cancer. Concurrent pertuzumab improved LTC and OS but at the same time increased the risk for overall, but not symptomatic, ARE.

Stereotactic radiosurgery for nonfunctioning pituitary tumor: A multicenter study of new pituitary hormone deficiency.

BACKGROUND: Stereotactic radiosurgery (SRS) is used to treat recurrent or residual nonfunctioning pituitary neuroendocrine tumors (NFPA). The objective of the study was to assess imaging and development of new pituitary hormone deficiency. METHODS: Patients treated with single-session SRS for a NFPA were included in this retrospective, multicenter study. Tumor control and new pituitary dysfunction were evaluated using Cox analysis and Kaplan-Meier curves. RESULTS: A total of 869 patients (male 476 [54.8%], median age at SRS 52.5 years [Interquartile range (IQR): 18.9]) were treated using a median margin dose of 14Gy (IQR: 4) for a median tumor volume of 3.4 cc (IQR: 4.3). With a median radiological follow-up of 3.7 years (IQR: 4.8), volumetric tumor reduction occurred in 451 patients (51.9%), stability in 364 (41.9%) and 54 patients (6.2%) showed tumor progression.The probability of tumor control was 95.5% (95% Confidence Interval [CI]: 93.8-97.3) and 88.8% (95%CI: 85.2-92.5) at 5 and 10 years, respectively. A margin dose >14 Gy was associated with tumor control (Hazard Ratio [HR]:0.33, 95% CI: 0.18-0.60, P < 0.001). The probability of new hypopituitarism was 9.9% (95% CI: 7.3-12.5) and 15.3% (95% CI: 11-19.4) at 5 and 10 years, respectively. A maximum point dose >10 Gy in the pituitary stalk was associated with new pituitary hormone deficiency (HR: 3.47, 95% CI: 1.95-6.19). The cumulative probability of new cortisol, thyroid, gonadotroph, and growth hormone deficiency was 8% (95% CI: 3.9-11.9), 8.3% (95% CI: 3.9-12.5), 3.5% (95% CI: 1.7-5.2), and 4.7% (95% CI: 1.9-7.4), respectively at 10 years. CONCLUSIONS: SRS provides long-term tumor control with a 15.3% risk of hypopituitarism at 10 years.

Stereotactic radiosurgery versus active surveillance for incidental, convexity meningiomas: a matched cohort analysis from the IMPASSE study.

BACKGROUND: The optimal treatment strategy of asymptomatic, convexity meningiomas, remains unclear. OBJECTIVE: The purpose of this study was to define the safety and efficacy of stereotactic radiosurgery (SRS) in the management of patients with asymptomatic convexity meningiomas. METHODS: Data of SRS-treated patients from 14 participating centers and patients managed conservatively for an asymptomatic, convexity-located meningioma were compared. Local tumor control rate and development of new neurologic deficits were evaluated in the active surveillance and in the SRS-treated cohorts. RESULTS: In the unmatched cohorts, there were 99 SRS-treated patients and 140 patients managed conservatively for an asymptomatic, convexity meningioma. Following propensity score matching for age, there were 98 patients in each cohort. In the matched cohorts, tumor control was achieved in 99% of SRS-treated, and in 69.4% of conservatively managed patients (p < 0.001). New neurological deficits occurred in 2.0% of patients in each of the matched cohorts (p = 1.00). Increasing age was predictive of tumor growth [(OR 1.1; 95% CI (1.04 - 1.2), (p < 0.001)]. CONCLUSION: This is one of the first reports to suggest that SRS is a low risk and effective treatment strategy for asymptomatic incidentally discovered convexity meningiomas. In this study, tumor control was achieved in significantly more patients after radiosurgery compared to those managed with active surveillance. SRS may be offered at diagnosis of an asymptomatic convexity meningioma and should be recommended when meningioma growth is noted on follow-up.

Semiautomatic brain region extraction: a method of parcellating brain regions from structural magnetic resonance images.

Structural MR imaging has become essential to the evaluation of regional brain changes in both healthy aging and disease-related processes. Several methods have been developed to measure structure size and regional brain volumes, but many of these methods involve substantial manual tracing and/or landmark identification. We present a new technique, semiautomatic brain region extraction (SABRE), for the rapid and reliable parcellation of cortical and subcortical brain regions. We combine the SABRE parcellation with tissue compartment segmentation [NeuroImage 17 (2002) 1087] to produce measures of gray matter (GM), white matter (WM), ventricular CSF, and sulcal CSF for 26 brain regions. Because SABRE restricts user input to a few easily identified landmarks, inter-rater reliability is high for all volumes, with all coefficients between 0.91 and 0.99. To assess construct validity, we contrasted SABRE-derived volumetric data from healthy young and older adults. Results from the SABRE parcellation and tissue segmentation showed significant differences in multiple brain regions in keeping with regional atrophy described in the literature by researchers using lengthy manual tracing methods. Our findings show that SABRE is a reliable semiautomatic method for assessing regional tissue volumes that provides significant timesavings over purely manual methods, yet maintains information about individual cortical landmarks.

Working memory in another dimension: functional imaging of human olfactory working memory.

The majority of working memory research has been carried out within the visual and auditory modalities, leaving it unclear how other modalities would map onto currently proposed working memory models. In this study we examined the previously uninvestigated area of olfactory working memory. Our aim was to investigate if olfactory working memory would engage prefrontal regions known to be involved in working memory for other sensory modalities. Using positron emission tomography we measured cerebral blood flow changes in 12 volunteers during an olfactory working memory task and a comparison visual working memory task. Our findings indicate that both olfactory and face working memory engaged dorsolateral and ventrolateral frontal cortex when the task requirements were matched; a conjunction analysis indicated overlap in the distribution of activity in the two tasks. Similarities and differences in activity were noted in parietal lobe regions, with both tasks engaging inferior areas of 40/7, but only visual working memory showing increased activity within left superior parietal cortex. The findings support the idea that working memory processes engage frontal cortical areas independent of the modality of input, but do not rule out the possibility of modality-specific neural populations within dorsolateral or ventrolateral cortex.

Face learning and memory: the twins test.

The clinical utility of current face recognition tests has been questioned. To evaluate if a new paradigm may measure this type of memory more accurately, the authors created a novel test to examine face learning (previously uninvestigated) and short- and long-term retention. For this initial investigation of test sensitivity to hemisphere of dysfunction, patients with surgical resection from a temporal lobe and healthy subjects were tested. Recognition was evaluated on 3 trials: after a single exposure, after 4 exposures (for learning), and after a 24-hr delay interval. Patients with a right resection performed significantly worse than healthy controls and patients with left resection. There was no difference between patients with a left resection and controls. Classification of individual patients to side of resection based on test results showed higher sensitivity (82%) than published for other tests and maintained good specificity (79%).

Brain metastases in patients with no known primary tumor.

BACKGROUND: The care of patients with a brain metastasis from unknown primary site is controversial. The authors reviewed the results of stereotactic radiosurgery in this group of patients to better define clinical expectations. METHODS: During an 11-year interval, radiosurgery was performed in 421 patients with brain metastases at the University of Pittsburgh. Fifteen patients had solitary or multiple (< or = 5) brain metastases without a detectable primary site at the time of initial presentation. In five patients, a histologic diagnosis of cancer was obtained from extracranial metastatic sites. In 10 patients, a diagnosis was obtained from the brain. A total of 31 tumors with a mean volume of 4.3 mL (range, 0. 05-18.6 mL) underwent radiosurgery with a mean marginal dose of 16.2 Gray (Gy) (range, 12-20 Gy). Fourteen patients (93.3%) also received whole brain fractionated radiation therapy. RESULTS: The median survival was 15 months after radiosurgery (range, 1-48 months) and 27 months after their initial diagnosis of cancer. In 4 patients (26. 7%), the primary tumor was discovered later (lung in 3 patients and liver in 1). Three of these four patients died due to progression of their primary tumor. Of the remaining 11 patients, 4 died of progression of extracranial metastases, 2 died of other systemic diseases, and 3 patients died because of progression of brain metastasis. Three patients (20%) were still living between 21-48 months after radiosurgery. The presence of active systemic disease and brain stem location both were associated with a poor outcome (P = 0.004 and 0.04). The actuarial imaging-defined local tumor control rate was 91.3 +/- 5.9% at 4 years. CONCLUSIONS: Radiosurgery was an effective strategy for patients with brain metastases from an unknown primary site. Disease progression outside of the brain was the usual cause for patient death.

Human brain function during odor encoding and recognition. A PET activation study.

In previous positron emission tomography (PET) studies we have shown significant regional cerebral blood flow (rCBF) increases during olfactory stimulation: unilaterally in the right orbitofrontal cortex, and bilaterally in the inferior frontal and temporal lobes (piriform cortex). In the present study we investigated brain function during different stages of olfactory memory processing. Subjects were scanned during four tasks: odor encoding, long-term odor recognition, short-term odor recognition and a no-odor sensorimotor control task. Subjects were 12 right-handed healthy volunteers (6 men, 6 women). Each subject underwent a training session four days prior to their PET scan to learn the six odors required for the long-term memory scan. PET scans were obtained with a Siemens Exact ECAT HR+ 3D system using H2(15)O methodology and 60-sec scanning intervals. PET images were coregistered with each subject's magnetic resonance imaging scan, averaged, and transformed into standard stereotaxic space. Paired image subtractions were analyzed for rCBF changes. Preliminary analyses have revealed significant activation of the right orbitofrontal region and bilateral piriform cortices during the long-term odor recognition task compared with the control task. Activation of the right piriform cortex was present during the short-term recognition task. Brain activity during encoding and retrieval tasks also involved prefrontal cortices. PET activation studies of memory in other modalities have led to hypotheses of a hemispheric encoding/retrieval asymmetry in frontal cortex; the generalizability of this theory to olfactory memory will be discussed.

Sodium amobarbital memory tests: what do they predict?

Severe transient postoperative memory deficits among epilepsy patients with resection from one temporal lobe may be indicative of increased risk for amnesia had more extensive removal of mesial structures occurred. Immediate postoperative testing may provide some validation for risk of amnesia as predicted by the intracarotid sodium amobarbital memory test (IAP-M). Thirty patients (24 not considered at risk for amnesia and 5 who failed the IAP-M) were tested on the first, second, and third days following resection from the right or left temporal lobe. Results suggest that the IAP-M paradigm used does not necessarily predict postoperative memory performance.