Clinical and Imaging Outcomes After Trigeminal Schwannoma Radiosurgery: Results From a Multicenter, International Cohort Study.

BACKGROUND AND OBJECTIVES: An international, multicenter, retrospective study was conducted to evaluate the long-term clinical outcomes and tumor control rates after stereotactic radiosurgery (SRS) for trigeminal schwannoma. METHODS: Patient data (N = 309) were collected from 14 international radiosurgery centers. The median patient age was 50 years (range 11-87 years). Sixty patients (19%) had prior resections. Abnormal facial sensation was the commonest complaint (49%). The anatomic locations were root (N = 40), ganglion (N = 141), or dumbbell type (N = 128). The median tumor volume was 4 cc (range, 0.2-30.1 cc), and median margin dose was 13 Gy (range, 10-20 Gy). Factors associated with tumor control, symptom improvement, and adverse radiation events were assessed. RESULTS: The median and mean time to last follow-up was 49 and 65 months (range 6-242 months). Greater than 5-year follow-up was available for 139 patients (45%), and 50 patients (16%) had longer than 10-year follow-up. The overall tumor control rate was 94.5%. Tumors regressed in 146 patients (47.2%), remained unchanged in 128 patients (41.4%), and stabilized after initial expansion in 20 patients (6.5%). Progression-free survival rates at 3 years, 5 years, and 10 years were 91%, 86%, and 80 %. Smaller tumor volume (less than 8 cc) was associated with significantly better progression-free survival ( P = .02). Seventeen patients with sustained growth underwent further intervention at a median of 27 months (3-144 months). Symptom improvement was noted in 140 patients (45%) at a median of 7 months. In multivariate analysis primary, SRS ( P = .003) and smaller tumor volume ( P = .01) were associated with better symptom improvement. Adverse radiation events were documented in 29 patients (9%). CONCLUSION: SRS was associated with long-term freedom (10 year) from additional management in 80% of patients. SRS proved to be a valuable salvage option after resection. When used as a primary management for smaller volume tumors, both clinical improvement and prevention of new deficits were optimized.

Neurosurgery at the University of Miami.

The Department of Neurological Surgery at the University of Miami/Jackson Memorial Hospital's legacy of patient care, teaching, and research in the neurosciences extends over a period of 50 years. The department's founder was Dr. David Reynolds. The subsequent chairman, Dr. Hubert Rosomoff, formed a solid foundation that helped put the department on the map. Drs. Barth Green and Roberto Heros, the immediate past chair and co-chairman, garnered both national and international attention for the department. Dr. Green focused his career on complex spine and spinal cord disorders, and was pivotal in creating the world's largest research center for spinal cord injuries. Dr. Heros is a master educator and pioneer neurovascular surgeon, as well as a former president of several neurosurgical national and international organizations. In aggregate, the department has made major contributions to the foundations of neurosurgery.

Deep brain stimulation complicated by bilateral large cystic cavitation around the leads in a patient with Parkinson's disease.

Deep brain stimulation (DBS) is an approved and effective therapy for patients suffering from advanced Parkinson's disease (PD). Several clinical trials have indicated significant motor function improvement in patients undergoing subthalamic nucleus stimulation. This therapy is, rarely, associated with complications, mostly related to infections, seizures or stimulation-induced side effects. We report a case of a 71-year-old man with a 10-year history of PD who underwent bilateral placement of subthalamic nucleus DBS. As a complication, the patient showed subjective postoperative cognitive decline, and subsequent MRI showed peri-lead oedema, which progressed to large cystic cavitation around the leads without indication of infection. The patient received steroid therapy and the cavitations regressed without surgical intervention.

Outcomes and management strategies after nondiagnostic stereotactic biopsies of brain lesions.

BACKGROUND/AIMS: A significant minority of stereotactic biopsies (SBs) of brain lesions is nondiagnostic, yet there are no optimal strategies for preventing nondiagnostic SB (NDSB) and for managing patients after NDSB. We performed this study in order to identify risk factors for NDSB, to determine how diagnoses are eventually reached in these patients, and to ascertain whether NDSB affects clinical outcomes. METHODS: Retrospective chart review of patients at our institution who underwent SB of brain lesions. RESULTS: Twenty-four out of 100 SBs were nondiagnostic. NDSB was less likely in contrast-enhancing brain lesions in immunocompetent patients, with larger lesions and in the setting of diagnostic findings on intraoperative frozen section analysis. Of 16 patients with adequate postoperative follow-up, a diagnosis was eventually reached in 11, via further review of the pathology, retrieval of additional tissue specimens or additional noninvasive testing. Survival times for patients with NDSB and eventual tumor diagnoses were within expected ranges for patients with similar tumors. Three of the 5 patients who never received a final diagnosis enjoyed prolonged survival without progressive symptoms. CONCLUSIONS: Surgeons should consider taking additional specimens in the case of nondiagnostic intraoperative frozen section during SB. If a tumor is suspected and final pathology is nondiagnostic, outside review of the slides may be helpful, and sampling further tissue should be considered. For diseases other than tumors, the diagnosis will generally be made without a repeat biopsy. The delays in diagnosis resulting from NDSB do not appear to affect survival, at least in patients eventually found to have brain tumors.

Clinical trial of CPT-11 and VM-26/VP-16 for patients with recurrent malignant brain tumors.

CPT-11 is a potent inhibitor of topoisomerase I and has shown antitumor activity in brain xenografts and in clinical trials in recurrent/progressive malignant glioma. VM-26 and VP-16 are topoisomerase II inhibitors and have also shown activity in phase II trials. We performed a phase II trial of intravenous CPT-11 (125 mg/m2) followed 24 h later by VM-26 (125 mg/m2). VP-16 (125 mg/m2) was later substituted for VM-26 due to drug shortage. For patients on anticonvulsants, the starting dose for all drugs was 150 mg/m2. Drugs were given weekly for 3 weeks followed by 1-week rest. Twenty-five patients were entered into the study. Three patients (12%) had improvement in CAT/MRI brain scans (95% confidence interval 3-31%). Fatigue and myelosuppression, mainly leukopenia, were the main toxicities. This combination of the topoisomerase I inhibitor CPT-11 followed by the topoisomerase II inhibitor, VM-26 or VP-16, has shown modest antitumor activity comparable to that reported for each drug singly. Myelosuppression is the main toxicity when topoisomerase I and II inhibitors are combined together.

Extended remission of a recurrent median nerve malignant peripheral nerve sheath tumor after multimodal treatment. Case report.

Malignant peripheral nerve sheath tumors (MPNSTs) are difficult to control despite aggressive treatment. In this report the authors describe the treatment and follow-up review of a patient with neurofibromatosis Type I who harbored a recurrent median nerve MPNST. The man underwent preoperative intraarterial and intravenous chemotherapy followed by additional surgery for gross-total removal and postoperative radiotherapy. Two courses of preoperative intraarterial cisplatin and intravenous Adriamycin produced significant tumor shrinkage. Gross-total removal of the remaining tumor without amputation of the arm was followed by fractionated radiotherapy (total minimum tumor dose 6485 cGy, maximal dose 6575 cGy). The patient is alive 9.5 years after treatment without evidence of tumor recurrence and with only focal median nerve functional deficits. A review of the patient's treatment is warranted to provide a description of a regimen that may be useful in the treatment of similar patients in the future.

Procollagen alpha 1 type 1: a potential aide in histopathological grading of glioma.

Collagen type I production has been shown to play a role in malignant transformation. We examined procollagen type I expression in brain tumors and with histopathological grading. Expression levels of procollagen alpha 1 type 1 were determined in 5 glioma cell lines by RT-PCR, Northern, and Western blot analysis. In addition, 41 primary brain tumors and 2 metastatic lung cancers to the brain were examined by PCR. Of the 5 glioma cell line analyzed, 3 (glioma 1, SW-1783 and U-118) expressed procollagen alpha 1 type I and were sensitive to vitamin D3 (VD3). In contrast, 2 of the cell lines (U-373 and T-98G) lacked procollagen alpha 1 type 1 expression. In patients' samples, 14 of 15 anaplastic and low grade gliomas expressed procollagen alpha 1 type I, and 12 of the 14 expressed high levels. In contrast, only 12 of 21 high grade gliomas from patients expressed procollagen alpha 1 type1 and among these, only 4 of the 12 expressed high levels. Thus, there is an inversed correlation between procollagen alpha 1 type 1 expression and histopathological grading (R2=- 0.56, p=0.0005). Our data suggest that procollagen alpha 1 type I expression occurs more commonly in intermediate and low grade gliomas and may assist in histopathological grading.

Safety and efficacy of tiered limited-dose gamma knife stereotactic radiosurgery for unilateral acoustic neuroma.

Stereotactic radiosurgery has become a more widely employed modality of treatment for acoustic neuromas, but controversy still arises regarding the safety and efficacy of the technique. In general, radiation doses have been reduced over time. Since beginning treatments of acoustic neuromas with the Gamma Knife at the University of Miami/Jackson Memorial Medical Center in 1994, a dose regimen was adopted by the first author employing limited doses selected on the basis of tumor size with the anterior and medial regions of the prescription isodose surface kept just inside the gadolinium-enhanced limit of the tumor, in order to protect the facial nerve and brainstem. The records of patients treated for unilateral tumors were retrospectively reviewed. Fifty-two patients, aged 23-83 years, were treated with peripheral tumor doses of 10-14 Gy at the 45-70% isodoses. No patient developed new facial weakness or sensory loss; 3 patients had minor transient facial twitching within a few months of treatment. Of 34 patients followed more than 1 year (range 14-100 months, mean 43.4 months, median 37 months), 17 tumors reduced in size, 16 remained unchanged, and 1 increased in size. One patient, who had radiosurgery as planned postoperative adjuvant treatment after partial resection of a large tumor, developed an enlarging peritumoral arachnoid cyst that required surgical resection 79 months after radiosurgery. Patients with good pretreatment hearing retained approximately the same subjective level of hearing. Very good control of unilateral acoustic neuroma has been achieved by a limited-dose scheme that produces minimal complications, but due to the frequently indolent course of these tumors, continued long-term monitoring will be necessary.

Pilot study of estramustine added to radiosurgery and radiotherapy for treatment of high grade glioma.

Patients with high grade glioma generally have poor prognoses. Addition of radiosensitizing agents might improve the response to irradiation. The chemotherapeutic agent estramustine sensitizes experimental gliomas to radiation. Gliomas express estramustine binding proteins, and cytotoxic concentrations of estramustine metabolites are found in gliomas after oral administration. Twenty three patients, aged 25-78, with new or recurrent high grade glioma were treated with estramustine and radiosurgery and/or radiotherapy. Patients with recurrent tumors were treated with estramustine and Gamma Knife stereotactic radiosurgery; eligible tumors were limited to 4 cm maximal diameter. Patients with newly diagnosed tumors were treated with estramustine and fractionated radiotherapy, with radiosurgery also performed if the tumor was less than 4 cm maximal diameter. Estramustine (16 mg/kg per day orally) was started three days prior to radiosurgery, or, if only radiotherapy was performed, on the first day of radiotherapy. Estramustine was continued until the completion of radiosurgery and/or radiotherapy (72 Gy, 60 fractions, 1.2 Gy bid over 6 weeks). Of the 13 patients treated for newly diagnosed glioblastoma, median survival was 16 months with 38% 2-year survival. Of five patients treated for recurrent glioblastoma, survival was 3, 8, 9, 15, and 23 + months. Two patients with recurrent anaplastic astrocytoma survived for 24 and 48+ months. One patient with recurrent anaplastic mixed glioma survived 5+ months. Two patients with newly diagnosed anaplastic oligodendroglioma survived 20 and 42+ months. Four of the new glioblastoma patients developed deep vein thrombosis. The results of this pilot study indicate some benefit, and further investigation incorporating estramustine into clinical trials is suggested.