Surgical treatment of high-grade gliomas in motor areas. The impact of different supportive technologies: a 171-patient series.

In the last few years much has been published to validate new technology in brain mapping for clinical purposes, but there have been few clinical results. In this report we describe our five-year experience in the surgical management of malignant gliomas around motor areas with an evaluation of the impact of functional magnetic resonance imaging (fMRI) plus navigator and intraoperative neurophysiology (IN). End-points were extent of removal, morbidity, and survival. Variables describing patient and tumor characteristics and treatment modalities were statistically weighted in relation to treatment outcome. Tumor depth (P = 0.01), midline shift ≥1 cm. (P = 0.05), and insular location (P = 0.001) negatively affected extent of removal, whereas IN (P < 0.001) and fMRI plus navigator (P = 0.02) contributed to increasing the rate of total removal (73%, 71% vs. 40%). Postoperative motor impairment was mild and transient in a minority of cases (20%). General complications, as defined by the Glioma Outcome Project, occurred in 23% of cases. IN was the only factor associated with acute postoperative motor deterioration (P < 0.001). IN and age >65 years (P = 0.01) were associated with the occurrence of complications. Overall survival was significantly higher in patients operated with IN or fMRI plus navigator (P < 0.01). Comparing different surgical strategies used in the same period, we observed that supportive technologies in glioma surgery have their primary impact on the quality of resection and survival. IN led to transient motor impairment and some additional complications which did not affect functional outcome.

The first successful case of hearing produced by electrical stimulation of the human midbrain.

HYPOTHESIS: Electrical stimulation of the inferior colliculus in the midbrain can provide a safe and efficacious alternative to auditory brainstem implants (ABIs). BACKGROUND: Patients with neurofibromatosis type 2 (NF2) receive limited speech recognition with ABIs. Some ABI patients without NF2 can achieve excellent speech understanding, suggesting that the limited NF2 performance is due to brainstem damage from the tumor and its removal. METHODS: An array of electrodes (Med-El ABI) was placed on the dorsal surface of the inferior colliculus in the midbrain of a human volunteer as an auditory prosthesis via an infratentorial supracerebellar median surgical approach. Electrophysiological responses, psychophysical responses, and speech recognition were measured. RESULTS: Electrical stimulation produced auditory sensations on all 12 electrodes with no nonauditory sensations. Auditory threshold levels indicated the stability of the electrode array over time. Electrophysiological measures showed activation in the contralateral auditory cortex but none in ipsilateral cortex. All electrodes demonstrated a full range of loudness sensation and electrode-specific pitch sensations. Speech recognition was significant, but limited in the first month after surgery. CONCLUSION: This approach may provide advantages for patients with brainstem damage.

The treatment of adults with medulloblastoma: a prospective study.

PURPOSE: To assess in a prospective trial the value of prognostic factors and the outcome of medulloblastoma in adults. METHODS AND MATERIALS: Patients (> or =18 years) with a histologic diagnosis of medulloblastoma were staged according to Chang et al.'s classification (low risk: T1, T2, T3a, M0, and no residual disease after surgery; high risk: T3b-T4, any M+ or postoperative presence of residual tumor). In low-risk patients, treatment consisted of 36 Gy to the craniospinal axis, supplemented by a local tumor dose of 18.8 Gy (total dose of 54.8 Gy). In high-risk patients, 2 cycles of "up-front chemotherapy" were delivered before the same radiation therapy, followed by maintenance chemotherapy if M1, M2, or M3 disease was present. RESULTS: Over a 12-year period, 36 evaluable patients were enrolled. Progression-free survival (PFS) at 5 years was higher in low-risk patients compared to the high-risk group: 76% +/- 14% (95% confidence interval [CI] = 52%-100%) vs. 61% +/- 11% (95% CI = 42%-87%). Patients with M- disease showed a significantly better outcome than M+ patients, with 75% showing PFS at 5 years vs. 45% (p = 0.01). CONCLUSION: The overall PFS observed is comparable to that obtained in pediatric series and suggests that a more effective therapy must be developed for high-risk patients.

O(6)-methylguanine DNA-methyltransferase methylation status can change between first surgery for newly diagnosed glioblastoma and second surgery for recurrence: clinical implications.

O(6)-methylguanine DNA-methyltransferase (MGMT) promoter methylation status is a prognostic factor in newly diagnosed glioblastoma patients. However, it is not yet clear whether, and if so how, MGMT methylation status may change. Moreover, it is unknown whether the prognostic role of this epigenetic feature is retained during the disease course. A retrospective analysis was made using a database of 614 glioblastoma patients treated prospectively from January 2000 to August 2008. We evaluated only patients who met the following inclusion criteria: age > or = 18 years; performance status 0-2; histological diagnosis of glioblastoma at both first and second surgery for recurrence; postoperative treatment consisting of: (i) radiotherapy (RT) followed by adjuvant temozolomide (TMZ) until 2005 and (ii) TMZ concurrent with and adjuvant to RT after 2005; a time interval > or = 3 months between first and second surgery. MGMT status was evaluated at first and second surgery in all 44 patients (M:F 32:12, median age: 49 years, range: 27-67 years). In 38 patients (86.4%), MGMT promoter status was assessable at both first and second surgery. MGMT methylation status, changed in 14 patients (37%) of second surgery samples and more frequently in methylated than in unmethylated patients (61.5% vs 24%, P = .03). The median survival was significantly influenced only by MGMT methylation status determined at first surgery (P = .04). Significant changes in MGMT methylation status during the course of GBM occur more frequently in MGMT methylated than unmethylated cases. MGMT methylation status determined at first surgery appears to be of prognostic value; however, it is not predictive of outcome following second surgery.

Dose-intensity temozolomide after concurrent chemoradiotherapy in operated high-grade gliomas.

PURPOSE: We performed a new phase II trial enrolling patients with newly diagnosed high-grade glioma (HGG) to test the efficacy of a weekly alternating temozolomide (TMZ) schedule after surgery and concomitant chemoradiotherapy. METHODS: From January 2005 to January 2007, 34 patients (21 men, 13 women; age range 30-70, mean age 53) were enrolled. There were 32 glioblastoma multiforme and two anaplastic astrocytoma. Each patient after surgery received standard concurrent chemoradiotherapy. After a 4-week break, patients were then to receive 12 cycles of 1-week-on/1-week-off TMZ, with 75 mg/m(2) for the first cycle, 100 mg/m(2) for the second, 125 mg/m(2) for the third, and 150 mg/m(2) from the fourth to the 12th. Hematological toxicity was monitored every week during concomitant chemoradiotherapy and then every 4 weeks. RESULTS: After 12 months from the end of radiotherapy, the overall survival (OS) rate was 59% (20/38), distributed as follows: 60% (18/30) for recursive partitioning analysis (RPA) class 4 patients and 33% (1/3) for RPA class 6 patients; the only RPA class 1 patient was alive and disease free at the time of writing. Median OS was 13 months [95% confidence interval (CI) 11.02-14.98 months]. Hematological toxicity was seen in six patients (18%): grade 1 neutropenia in four, grade 2 thrombocytopenia in one, and grade 4 thrombocytopenia plus grade 1 neutropenia in one. There was one case of opportunistic infection (Pneumocystis carinii pneumonitis). CONCLUSION: The toxicity of the TMZ dose-dense regimen was very low. Results seem to be encouraging for RPA lower classes (patients with good prognostic factors).

A multicenter retrospective study of chemotherapy for recurrent intracranial ependymal tumors in adults by the Gruppo Italiano Cooperativo di Neuro-Oncologia.

BACKGROUND: No data on the role of chemotherapy in recurrent ependymal tumors are available in adults. The aim of the current study was to investigate outcomes after salvage chemotherapy in this setting. METHODS: A retrospective review was made of the charts of 28 adults (> or = 18 years) with progressive or recurrent ependymal tumors after surgery and radiotherapy, who received chemotherapy between 1993 and 2003 in 3 institutions of the Gruppo Italiano Cooperativo di Neuro-Oncologia network. RESULTS: Thirteen patients (46.3%) received cisplatin-based chemotherapy (Group A) and 15 (53.7%) received regimens without cisplatin (Group B). Platinum-based chemotherapy yielded 2 complete responses (CR) (15.4%) and 2 (15.4%) partial responses (PR), whereas 7 patients (53.8%) remained stable (SD). After regimens without cisplatin, there were no CR, 2 PR (13.3%), and 11 SD (73.3%). The overall median time to progression was 9.9 months (95% confidence interval [95% CI], 7.5-21.7 months), 9.9 months (5.2-not reached) for Group A and 10.9 months (95% CI, 7.17-23.9 months) for Group B. The overall median survival (OS) was 40.7 months (95% CI, 16-not reached), 31 months (21-not reached) for Group A and 40.7 months (13.4-not reached) for Group B. CONCLUSIONS: Cisplatin-based chemotherapy achieved a higher response rate, but did not prolong disease progression-free survival or OS. More active regimens for the salvage treatment of ependymal tumors have yet to be found.

Temozolomide in patients with glioblastoma at second relapse after first line nitrosourea-procarbazine failure: a phase II study.

OBJECTIVES: To investigate the efficacy of temozolomide (TMZ) in relationship to progression free survival at 6 months (PFS-6), median time to progression (TTP), response rate and toxicity, a phase II study was conducted in patients with recurrent glioblastoma multiforme (GBM) following surgery plus radiotherapy and a first-line regimen based on nitrosourea, procarbazine and vincristine. METHODS: Forty-two patients with GBM were administered TMZ at the dose of 150 mg/m(2)/daily for 5 days every 4 weeks. RESULTS: The PFS-6 and at 12 months (PFS-12) was 24% (95% Confidence Interval [CI] = 14-42%) and 8% (CI = 2-27%), respectively, with a median TTP of 11.7 weeks (CI = 9-22 weeks). The response was assessed in all 42 patients; we observed 2 complete responses (CR) (4.7%), 6 partial responses (PR) (14.3%), and 9 stable disease (SD) (21.4%), with CR+PR = 19% (CI = 7-31%). CONCLUSION: TMZ as a second line regimen is a valid option in patients with heavily pretreated GBM.