Marek Wronski

Surgical treatment of 70 patients with brain metastases from breast carcinoma.

Brain metastases are diagnosed in 15% of patients with metastatic breast carcinoma. Most patients are treated with whole‐brain radiotherapy (WBRT) and/or chemotherapy. The information on surgical results is sparse.

Resection of brain metastases from colorectal carcinoma in 73 patients

At the time of diagnosis of colorectal carcinoma, 2–3% of patients are likely to be harboring brain metastases, and another 10% of patients will develop brain lesions during the course of their disease. The purpose of this study was to examine the clinical course of a group of patients with metastatic brain disease who underwent surgical resection in a single institution. The authors believe this information will be useful for establishing prognostic factors and for clinical decision making.

Treatment of Recurrent Glioblastoma Multiforme Using Fractionated Stereotactic Radiosurgery and Concurrent Paclitaxel

Despite the progress in neurosurgery and radiotherapy, almost all patients treated with malignant gliomas develop recurrent tumors and die of their disease. Eighty-eight patients (median age 56 years) with recurrent glioblastoma (median tumor volume 32.7 cm3) were treated with noninvasive fractionated stereotactic radiosurgery and concurrent paclitaxel used as a sensitizer. The median interval between diagnosis of primary glioblastoma and salvage radiosurgery was 7.8 months. Four weekly treatments (median dose: 6.0 Gy) were delivered after the 3-hour paclitaxel infusion (median dose: 120 mg/m2). Survival was calculated by the Kaplan-Meier method from radiosurgery treatment. Overall median survival was 7.0 months, and the 1-year and 2-year actuarial survival rates were 17% and 3.4%, respectively. When grouped by performance status, there was no difference in survival between the patients with low and high Karnofsky score. Patients with tumor volume less than 30 cm3 survived significantly longer than those with tumor greater than 30 cm3 (9.4 vs. 5.7 months, p = 0.0001). Their 1-year survival rate was 40% and 8%, respectively. Eleven patients (11%) had reoperation because of expanding mass. Stable disease was seen in 40% of patients (n = 34), and increase in radiographically detected mass was observed in 41 patients (48.8%). Although the treatment of recurrent GBM is mostly palliative, the fractionated radiosurgery offers a chance for prolonged survival, especially in patients with a smaller tumor volume.

The treatment of patients with recurrent brain metastases. A retrospective analysis of 109 patients with nonsmall cell lung cancer

Background. Brain metastases represent a major source of morbidity in patients with cancer.

Acoustic Neuroma: Potential Benefits of Fractionated Stereotactic Radiosurgery

BACKGROUND Single-fraction radiosurgery of acoustic neuromas less than 3 cm in diameter is remarkable for high control but not infrequent incidence of facial and trigeminal neuropathy. Larger tumors treated surgically often result in deafness and facial neuropathy. Fractionated stereotactic radiosurgery was used in an effort to maintain effective therapy while minimizing toxicity of treatment. METHODS The authors described 38 patients with acoustic neuromas, with age range 35-89 years (mean, 60 years). 2,000 cGy in divided weekly doses of 400 or 500 cGy was most commonly prescribed. Tumors > or = 3 cm (n = 16) received the 5 fraction schema. Mean tumor volume was 6.9 cm3, with range from 0.1 to 32.0 cm3. RESULTS Median clinical follow-up was 27.1 months, while neuroimaging follow-up had a median of 16.3 months. All tumors were controlled. Of 23 tumors smaller than 3 cm, 14 (61%) decreased in size, and 9 showed cessation of growth. Thirteen of 16 (81%) large acoustic neuromas (3-5 cm) diminished in size. The remaining 3 showed cessation of growth. Median radiographic follow-up was 20 months, with a median clinical follow-up of 28 months. No patient developed fifth nerve symptoms after treatment nor did any patient require surgery for treatment failure. Only one had temporary seventh nerve palsy. CONCLUSION Fractionated stereotactic radiosurgery offers a therapeutic approach producing high control rates while avoiding morbidity frequently seen after single-fraction radiosurgery or microsurgery.

Results and prognostic factors of surgery in the management of non-small cell lung cancer with solitary brain metastasis.

Between 1975 and 1988, 37 patients with resectable non-small cell lung cancer (NSCLC) and synchronous (within 1 month, n = 10) or metachronous (n = 27) solitary brain metastasis (SBM) underwent combined excision of their lesions. Overall 5-year and median survival were 30% and 27 months (range, 3 to 125+ months), respectively. Twenty-seven patients had a relapse, and their median disease-free interval (DFI) was 17.5 months (range, 1 to 108 months). The most frequent (78%, n = 20) site of first recurrence locally was either the ipsilateral thorax (n = 14) or brain (n = 6). In univariate analysis, age, primary tumor and lymph node status; tumor histology, size, and side; type of pulmonary resection; side and location of SBM; and onset of presentation did not affect survival and DFI. By contrast, the interval (less than or equal to versus greater than 12 months) between the two operations significantly affected survival (P = 0.0096) and DFI (P = 0.046). The DFI was also affected by the administration of adjuvant chemotherapy (AC) for the primary tumor (P = 0.02). Using the Cox model, AC was the most independent predictor of DFI. These data support the inclusion of surgery in the therapeutic armamentarium for patients with NSCLC and SBM.

Resection of brain metastases from sarcoma

AbstractBackground: Brain metastases from sarcoma are rare, and data concerning the treatment and results of therapy are sparse. Methods: We retrospectively reviewed 25 patients with brain metastases from sarcoma of skeletal or soft-tissue origin, surgically treated in a single institution during 20 years. Results: In 18 patients the brain lesion was located supratentorially, and in 7 patients infratentorially. Median age at brain metastasis diagnosis was 25 years. Median time from primary diagnosis to diagnosis of brain metastasis was 26.7 months. Lung metastases were present in 19 patients and in 8 patients they were synchronous with the brain lesion. Pulmonary metastases were resected in 12 patients (48% of total, and 63% of those with pulmonary lesions). The overall median survival from diagnosis of the primary sarcoma was 38 months and from craniotomy was 7 months. The presence or absence of lung lesions did not alter the median survival as calculated from diagnosis of brain metastasis. Overall percent survival was 40% at 1 year and 16% at 2 years. Conclusions: Because brain metastases from sarcoma are refractory to alternative treatment, surgical excision is indicated when feasible. Brain metastases from sarcoma are uncommon, usually occurring with or after lung metastasis. Long-term survival is possible in some patients.

Impaired memory and behavioral performance with fentanyl at low plasma concentrations.

Fentanyl is commonly administered to conscious patients by continuous epidural or intravenous (IV) infusions, or by the transdermal route, which result in relatively constant, low, concentrations of the drug. Previous studies of memory and cognitive effects have not been performed at constant plasma concentrations of fentanyl. Based on simulated infusions using the pharmacokinetic modeling program IV-SIM, we administered fentanyl or placebo to nine healthy volunteers (aged 21–45 yr) by continuous IV infusion, targeting plasma concentrations of 1, 1.5, and 2.5 ng/mL in succession. A battery of memory and psychomotor tasks was administered at each plasma concentration of fentanyl, and at two points in the recovery phase while drug levels were decreasing. At increasing plasma concentrations of fentanyl, we found the following effects on memory (in comparison with placebo): a progressive decline in verbal learning (P < 0.03); decreased delayed recognition of words presented at different test times (P < 0.02); and decreased spontaneous recall of pictures shown during infusion (P < 0.03). Fentanyl at concentrations above 2.5 ng/mL caused a performance decrement of 15%-30% relative to baseline on all the psychomotor tests administered. Plasma concentrations less than 2.25 ng/mL had negligible effects on performance with the exception of the critical flicker fusion frequency, which decreased by 5 Hz at plasma concentrations between 1.5 and 2.25 ng/mL. Visual analog scale (VAS) measures of mental and physical sedation were significantly affected by fentanyl, but euphoria was not demonstrable. All subjects receiving fentanyl experienced severe nausea and four of six had one or more episodes of emesis (P < 0.03). We conclude that even though patients experiencing constant, low plasma concentrations of fentanyl appear to be awake, they could have significantly impaired memory.

Cerebral metastases in pleural mesothelioma: Case report and review of the literature

A case of malignant mesothelioma metastatic to the brain is described. A 52-year old woman, with no known exposure to asbestos, presented with a biphasic mesothelioma of the left parietal pleura. Following resection, the thorax was irradiated with 4000 cGy, and all symptoms subsided. Three months later, a left temporal lobe tumor was diagnosed and subsequently resected. Despite neurological improvement, she died 10 days postoperatively from constrictive pericardial disease. The authors have reviewed the 54 reported cases of brain metastases from mesothelioma and have noted that the histologic appearance of brain metastases from mesothelioma may be similar to glioblastoma multiforme. Because brain metastasis from mesothelioma is rare, procedures to clarify the nature of the tumor should be performed.

Endometrial cancer metastasis to brain: report of two cases and a review of the literature.

Two cases of brain metastases from endometrial adenocarcinoma are reported. A 70-year-old female presented with lung metastases 14 months after hysterectomy and adjuvant treatment. At 6 months later, a cerebellar metastasis was resected and followed by radiation therapy. The patient died 5.5 months later. In the second case, a 60-year-old patient developed a lung endometrial metastasis 6 years after initial treatment. At 1 year later she was diagnosed with bilateral hydrocephalus caused by a left temporal and posterior fossa tumor. A ventriculoperitoneal shunt was inserted and she received brain radiation. Two weeks later she gradually became comatose, with right hemiparesis. A metastatic, hemorrhagic temporal tumor was resected but the patient never regained consciousness and died after 7 weeks. The existing literature on brain metastases from endometrial adenocarcinoma is reviewed.