Faculty Bibliography

BACKGROUND: Patients with small-cell lung cancer have a high likelihood of developing brain metastases. Many of these patients will have prophylactic cranial irradiation (PCI) or eventually undergo whole brain radiation therapy (WBRT). Despite these treatments, a large number of these patients will have progression of their intracranial disease and require additional local therapy. Stereotactic radiosurgery (SRS) is an important treatment option for such patients. METHODS: We retrospectively reviewed the charts of 44 patients with brain metastases from small-cell lung cancer treated with gamma knife SRS. Multivariate analysis was used to determine significant prognostic factors influencing survival. RESULTS: The median follow-up from SRS in this patient population was 9 months (1-49 months). The median overall survival (OS) was 9 months after SRS. Karnofsky performance status (KPS) and combined treatment involving WBRT and SRS within 4 weeks were the two factors identified as being significant predictors of increased OS (p = 0.033 and 0.040, respectively). When comparing all patients, patients treated with a combined approach had a median OS of 14 months compared to 6 months if SRS was delivered alone. We also compared the OS times from the first definitive radiation: WBRT, WBRT and SRS if combined therapy was used, and SRS if the patient never received WBRT. The median survival for those groups was 12, 14, and 13 months, respectively, p = 0.19. Seventy percent of patients had follow-up magnetic resonance imaging available for review. Actuarial local control at 6 months and 12 months was 90% and 86%, respectively. Only 1 patient (2.2%) had symptomatic intracranial swelling related to treatment, which responded to a short course of steroids. New brain metastases outside of the treated area developed in 61% of patients at a median time of 7 months; 81% of these patients had received previous WBRT. CONCLUSIONS: Stereotactic radiosurgery for small-cell lung carcinoma brain metastases provided safe and effective local tumor control in the majority of patients.

Stereotactic radiosurgery is used for many neoplastic, vascular, and functional disorders of the nervous system. The expanded use of this technique over the past two decades is based mainly on the spectrum of clinical research performed for these disorders. From case series to randomized trials, the safety and efficacy of radiosurgery is well documented. In this report, we discuss the key indications for radiosurgery and the kinds of research performed in this field.

BACKGROUND: Approximately 20 to 40% of patients with systemic malignancies develop brain metastases. OBJECTIVE: To assess the potential role of stereotactic radiosurgery (SRS) for larger metastatic brain tumors, we reviewed our recent experience. METHODS: Between 2004 and 2008, 70 patients with a metastatic brain tumor larger than 3 cm in maximum diameter underwent Gamma knife SRS. Thirty-three patients had received previous whole brain radiation therapy (WBRT) and 37 received only SRS. RESULTS: The overall median follow-up was 8.1 months. At the first planned imaging follow-up at 2 months, 29 (41%) tumors had >50% volume reduction, 22 (31%) had 10 to 50% volume reduction, and 19 (28%) were stable or larger. We also evaluated brain edema using MRI T2 images. In 11 patients (16%) the peritumoral edema volume was reduced by more than 50%, in 25 (36%) it was reduced by 10 to 50%, in 21 (30%) it was stable, and in 13 (19%) it was increased. Twenty (36%) discontinued corticosteroids by the time of first imaging follow-up. Because of persistent symptoms, 7 patients (10%) required a craniotomy to remove the tumor. Tumor volume reduction (>50%) was associated with a single metastasis (P=.012), no previous WBRT (P=.002), and a tumor volume<16 cm3 (P=.002). The better peritumoral edema volume reduction (>50%) was associated with a single metastasis (P=.024), no previous WBRT (P=.05), and breast cancer histology (P=.044). CONCLUSION: Surgical resection remains the primary approach for larger brain metastases if feasible. Tumor volume is a better indicator than maximum diameter. Tumor volume and edema responded better in patients who underwent SRS alone.

OBJECTIVE: It is possible to judge the impact of scientific research by the number of citations a publication has received. We identified the most cited works in the field of stereotactic radiosurgery to study the evolution of this field from the perspective of publication. METHODS: A Web of Science search was performed for articles that included the word 'radiosurgery' in the title. We studied the reports with >100 citations. RESULTS: A total of 5,532 published works were available for study between 1951 and 2010. Eighty-five articles had >/= 100 citations, and these were published in 19 separate journals. The majority were published in the International Journal of Radiation Oncology, Biology and Physics, the Journal of Neurosurgery and Neurosurgery. The most common topics included brain metastasis management (n = 20), arteriovenous malformations (n = 17), vestibular schwannomas (n = 9), technologies (n = 9), meningiomas (n = 8) and dose response/radiobiology (n = 6). Fifty-seven percent of the articles were published in the last 10 years. CONCLUSIONS: The first radiosurgery report by Leksell (1951) initiated the field. The 1980s were a period of new technology development followed in the 1990s by introductory articles on specific indications that consisted mainly of retrospective case series. More sophisticated higher level evidence reports were published in the last decade. The most significant works in radiosurgery include initial technology descriptions, multicenter studies with large numbers of patients, randomized clinical trials and reports that provide dose prescription guidelines.

Gamma knife stereotactic radiosurgery (SRS) has proven to be an effective management approach for trigeminal neuralgia and as a minimally invasive alternative management option for cluster headache (CH). In CH, patients undergo single-session focused irradiation of the trigeminal nerve root (TN), sometimes coupled with irradiation of the sphenopalatine ganglion (SPG) as well. SRS provides early pain relief in most patients, but is associated with trigeminal sensory dysfunction in some patients. In the future, a prospective trial that compares a single target of TN to dual targets of both the TN and SPG may provide further understanding of the value of SRS for CH.

BACKGROUND: Obsessive compulsive disorder (OCD), in its severe form, can cause tremendous disability for affected patients. OBJECTIVE: To evaluate the results following bilateral radiosurgical anterior capsulotomy for severe medically refractory OCD. METHODS: We performed gamma knife anterior capsulotomy (GKAC) on 3 patients with extreme, medically intractable OCD. According to our protocol, all patients were evaluated by at least 2 psychiatrists who recommended surgery. The patient had to request the procedure, and had to have severe OCD according to the Yale-Brown Obsessive Compulsive Scale (YBOCS). Patient ages were 37, 55, and 40 years, and pre-radiosurgery YBOCS scores were 34/40, 39/40, and 39/40. Bilateral lesions were created with 2 4-mm isocenters to create an oval volume in the ventral internal capsule at the putaminal midpoint. A maximum dose of 140 or 150 Gy was used. RESULTS: There was no morbidity after the procedure, and all patients returned immediately to baseline function. All patients noted significant functional improvements, and reduction in OCD behavior. Follow-up was at 55, 42, and 28 months. The first patient reduced her YBOCS score from 34 to 24. One patient with compulsive skin picking and an open wound had later healing of the chronic wound and a reduction in the YBOCS score from 39 to 8. At 28 months, the third patient is living and working independently, and her YBOCS score is 18. CONCLUSION: Within a strict protocol, gamma knife radiosurgery provided improvement of OCD behavior with no adverse effects. This technique should be evaluated further in patients with severe and disabling behavioral disorders.

OBJECT: The authors report their experience of using Gamma Knife surgery (GKS) in patients with subependymal giant cell astrocytoma (SEGA). METHODS: Over a 20-year period, the authors identified 6 patients with SEGAs who were eligible for GKS. The median patient age was 16.5 years (range 7-55 years). In 4 patients, GKS was used as a primary management therapy. One patient underwent radiosurgery for recurrent tumors after prior resection, and in 1 patient GKS was used as an adjunct after subtotal resection. The median tumor volume at GKS was 2.75 cm(3) (range 0.7-5.9 cm(3)). A median radiation dose of 14 Gy (range 11-20 Gy) was delivered to the tumor margin. RESULTS: The median follow-up duration was 73 months (range 42-90 months). Overall local tumor control was achieved in 4 tumors (67%) with progression-free periods of 24, 42, 57, and 66 months. Three tumors regressed and one remained unchanged. In 2 patients the tumors progressed, and in 1 of these patients the lesion was managed by repeated GKS with subsequent tumor regression. The other relatively large tumor (5.9 cm(3)) was excised 9 months after GKS. The progression-free period for all GKS-managed tumors varied from 9 to 66 months. There were no cases of hydrocephalus or GKS-related morbidity. CONCLUSIONS: Gamma Knife surgery may be an additional minimally invasive management option for SEGA in a patient who harbors a small but progressively enlarging tumor when complete resection is not safely achievable. It may also benefit patients with a residual or recurrent tumor that has progressed after surgery.

OBJECT: To evaluate the role of stereotactic radiosurgery (SRS) in the management of brain metastases from breast cancer, the authors assessed clinical outcomes and prognostic factors for survival. METHODS: The records from 350 consecutive female patients who underwent SRS for 1535 brain metastases from breast cancer were reviewed. The median patient age was 54 years (range 19-84 years), and the median number of tumors per patient was 2 (range 1-18 lesions). One hundred seventeen patients (33%) had a single metastasis to the brain, and 233 patients (67%) had multiple brain metastases. The median tumor volume was 0.7 cm(3) (range 0.01-48.9 cm(3)), and the median total tumor volume for each patient was 4.9 cm(3) (range 0.09-74.1 cm(3)). RESULTS: Overall survival after SRS was 69%, 49%, and 26% at 6, 12, and 24 months, respectively, with a median survival of 11.2 months. Factors associated with a longer survival included controlled extracranial disease, a lower recursive partitioning analysis (RPA) class, a higher Karnofsky Performance Scale score, a smaller number of brain metastases, a smaller total tumor volume per patient, the presence of deep cerebral or brainstem metastases, and HER2/neu overexpression. Sustained local tumor control was achieved in 90% of the patients. Factors associated with longer progression-free survival included a better RPA class, fewer brain metastases, a smaller total tumor volume per patient, and a higher tumor margin dose. Symptomatic adverse radiation effects occurred in 6% of patients. Overall, the condition of 82% of patients improved or remained neurologically stable. CONCLUSIONS: Stereotactic radiosurgery was safe and effective in patients with brain metastases from breast cancer and should be considered for initial treatment.

PURPOSE: The Pittsburgh radiosurgery-based arteriovenous malformation (AVM) grading scale was developed to predict patient outcomes after radiosurgery and was later modified with location as a two-tiered variable (deep vs. other). The purpose of this study was to test the modified radiosurgery-based AVM score in a separate set of AVM patients managed with radiosurgery. METHODS AND MATERIALS: The AVM score is calculated as follows: AVM score = (0.1)(volume, cc) + (0.02)(age, years) + (0.5)(location; frontal/temporal/parietal/occipital/intraventricular/corpus callosum/cerebellar = 0, basal ganglia/thalamus/brainstem = 1). Testing of the modified system was performed on 293 patients having AVM radiosurgery from 1992 to 2004 at the University of Pittsburgh with dose planning based on a combination of stereotactic angiography and MRI. The median patient age was 38 years, the median AVM volume was 3.3 cc, and 57 patients (19%) had deep AVMs. The median modified AVM score was 1.25. The median patient follow-up was 39 months. RESULTS: The modified AVM scale correlated with the percentage of patients with AVM obliteration without new deficits (2.00, 32%; F = 11.002, R(2) = 0.8117, p = 0.001). Linear regression also showed a statistically significant correlation between outcome and dose prescribed to the margin (F = 25.815, p <0.001). CONCLUSIONS: The modified radiosurgery-based AVM grading scale using location as a two-tiered variable correlated with outcomes when tested on a cohort of patients who underwent both angiography and MRI for dose planning. This system can be used to guide choices among observation, endovascular, surgical, and radiosurgical management strategies for individual AVM patients.