Recent trends in the anesthetic management of craniotomy for supratentorial tumor resection.

PURPOSE OF REVIEW: The article reviews the recent evidence on the anesthetic management of patients undergoing craniotomy for supratentorial tumor resection. RECENT FINDINGS: A rapid recovery of neurological function after craniotomy for supratentorial tumor allows for the prompt diagnosis of intracranial complications and possibly an early hospital discharge. Intraoperative esmolol infusion was shown to reduce the anesthetic requirements, and may facilitate a more rapid recovery of neurological function. Outpatient craniotomy for supratentorial tumor resection has been associated with several clinical and economic benefits, but has not gained widespread use because of skepticism and medical-legal concerns. Awake craniotomy is associated with advantageous outcomes compared with surgery under general anesthesia, and is regarded as the standard of care for tumors that reside in or in close proximity to the eloquent brain. Recent studies have demonstrated that intraoperative electroacupuncture, dexmedetomidine, pregabalin, and lidocaine may facilitate postcraniotomy pain management. The use of volatile anesthetic agents in cancer surgery is associated with a worse survival compared with intravenous anesthetics, possibly by hindering immunologic defenses against cancer cells. SUMMARY: Recent evidence has yielded valuable information regarding anesthetic management of patients undergoing supratentorial tumor craniotomy. Despite a plethora of studies that compare short-term outcomes using different anesthetic and analgesic regimens, randomized controlled trials that examine the long-term outcomes (i.e., neurocognitive function, quality of life, tumor recurrence, and survival) that are of particular interest to patients are needed.

Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas. Results of a prospective phase II study.

PURPOSE: Dose escalations above 60 Gy based on MRI have not led to prognostic benefits in glioblastoma patients yet. With positron emission tomography (PET) using [(18)F]fluorethyl-L-tyrosine (FET), tumor coverage can be optimized with the option of regional dose escalation in the area of viable tumor tissue. METHODS AND MATERIALS: In a prospective phase II study (January 2008 to December 2009), 22 patients (median age 55 years) received radiochemotherapy after surgery. The radiotherapy was performed as an MRI and FET-PET-based integrated-boost intensity-modulated radiotherapy (IMRT). The prescribed dose was 72 and 60 Gy (single dose 2.4 and 2.0 Gy, respectively) for the FET-PET- and MR-based PTV-FET((72 Gy)) and PTV-MR((60 Gy)). FET-PET and MRI were performed routinely for follow-up. Quality of life and cognitive aspects were recorded by the EORTC-QLQ-C30/QLQ Brain20 and Mini-Mental Status Examination (MMSE), while the therapy-related toxicity was recorded using the CTC3.0 and RTOG scores. RESULTS: Median overall survival (OS) and disease-free survival (DFS) were 14.8 and 7.8 months, respectively. All local relapses were detected at least partly within the 95% dose volume of PTV-MR((60 Gy)). No relevant radiotherapy-related side effects were observed (excepted alopecia). In 2 patients, a pseudoprogression was observed in the MRI. Tumor progression could be excluded by FET-PET and was confirmed in further MRI and FET-PET imaging. No significant changes were observed in MMSE scores and in the EORTC QLQ-C30/QLQ-Brain20 questionnaires. CONCLUSION: Our dose escalation concept with a total dose of 72 Gy, based on FET-PET, did not lead to a survival benefit. Acute and late toxicity were not increased, compared with historical controls and published dose-escalation studies.

Phase II trial of radiotherapy after hyperbaric oxygenation with multiagent chemotherapy (procarbazine, nimustine, and vincristine) for high-grade gliomas: long-term results.

PURPOSE: To analyze the long-term results of a Phase II trial of radiotherapy given immediately after hyperbaric oxygenation (HBO) with multiagent chemotherapy in adults with high-grade gliomas. METHODS AND MATERIALS: Patients with histologically confirmed high-grade gliomas were administered radiotherapy in daily 2 Gy fractions for 5 consecutive days per week up to a total dose of 60 Gy. Each fraction was administered immediately after HBO, with the time interval from completion of decompression to start of irradiation being less than 15 minutes. Chemotherapy consisting of procarbazine, nimustine, and vincristine and was administered during and after radiotherapy. RESULTS: A total of 57 patients (39 patients with glioblastoma and 18 patients with Grade 3 gliomas) were enrolled from 2000 to 2006, and the median follow-up of 12 surviving patients was 62.0 months (range, 43.2-119.1 months). All 57 patients were able to complete a total radiotherapy dose of 60 Gy immediately after HBO with one course of concurrent chemotherapy. The median overall survival times in all 57 patients, 39 patients with glioblastoma and 18 patients with Grade 3 gliomas, were 20.2 months, 17.2 months, and 113.4 months, respectively. On multivariate analysis, histologic grade alone was a significant prognostic factor for overall survival (p < 0.001). During treatments, no patients had neutropenic fever or intracranial hemorrhage, and no serious nonhematologic or late toxicities were seen in any of the 57 patients. CONCLUSIONS: Radiotherapy delivered immediately after HBO with multiagent chemotherapy was safe, with virtually no late toxicities, and seemed to be effective in patients with high-grade gliomas.

A phase I factorial design study of dose-dense temozolomide alone and in combination with thalidomide, isotretinoin, and/or celecoxib as postchemoradiation adjuvant therapy for newly diagnosed glioblastoma.

External beam radiation therapy (XRT) with concomitant temozolomide and 6 cycles of adjuvant temozolomide (5/28-day schedule) improves survival in patients with newly diagnosed glioblastoma compared with XRT alone. Studies suggest that dose-dense temozolomide schedules and addition of cytostatic agents may further improve efficacy. This factorial design phase I/II protocol tested dose-dense temozolomide alone and combined with cytostatic agents. Patients with newly diagnosed glioblastoma received fractionated XRT to 60 Gy concomitant with temozolomide (75 mg/m²)/day for 42 days). In the phase I portion, patients with stable disease or radiologic response 1 month after chemoradiation were randomized to adjuvant temozolomide alone (150 mg/m²/day, 7/14-day schedule) or with doublet combinations of thalidomide (400 mg/day), isotretinoin (100 mg/m²/day), and/or celecoxib (400 mg twice daily), or all 3 agents. Toxicity was assessed after 4 weeks. Among 54 patients enrolled (median age, 52 years; median Karnofsky performance status, 90), adjuvant treatment was not administered to 12 (22%), primarily because of disease progression (n = 10). All combinations were well tolerated. Grade 3/4 lymphopenia developed in 63% of patients, but no related infections occurred. One patient treated with temozolomide plus isotretinoin plus thalidomide had dose-limiting grade 3 fatigue and rash, and 1 patient receiving all 4 agents had dose-limiting grade 4 neutropenia. Venous thrombosis occurred in 7 patients, 4 of whom received thalidomide. From study entry, median survival was 20 months and the 2-year survival rate was 40%. Multiple cytostatic agents can be safely combined with dose-dense temozolomide. The factorial-based phase II portion of this study is currently ongoing.

Improvement, clinical course, and quality of life after palliative radiotherapy for recurrent glioblastoma.

The purpose of this review is to assess the palliative effect of re-irradiation in adult patients with recurrent supratentorial glioblastoma (GBM) previously treated with adjuvant or primary radiation therapy, with or without chemotherapy. From a comprehensive literature search, studies were identified reporting on survival, progression, and quality of life endpoints including, but not limited to, EORTC QLQ-C30 questionnaire, clinical symptoms, and ability to reduce dexamethasone. Data from more than 300 GBM patients (grade 3 anaplastic gliomas were excluded) demonstrate that re-irradiation yields 6-month PFS of 28% to 39% and 1-year overall survival of 18% to 48%, without additional chemotherapy (median value 26%). Patients with Karnofsky performance status <70 appeared to be at higher risk of early progression and apparently had lesser benefit from re-irradiation. Clinical improvement was observed in 24% to 45% of the patients. Most studies suggest that stabilization of the performance status is a realistic aim. In the studies reporting on corticosteroid usage during and after re-irradiation, 20% to 60% of the patients achieved a reduction in steroid dependency. Serious late toxicity was uncommon, especially after conventional treatment and fractionated stereotactic radiotherapy (FSRT). In light of recent technological advances such as FSRT and intensity modulated radiotherapy, which permit maximal sparing of normal brain, re-treatment seems attractive, and deserves scientific validation. Even fraction sizes of 3 to 5 Gy seem to be well tolerated in limited-volume recurrences as long as the total dose is limited to 30 to 35 Gy. Salvage chemotherapy or targeted agents should be prospectively tested against re-irradiation alone.

[Pediatric supratentorial oligodendrogliomas: Marseilles and Lyons experiences]. / Les oligodendrogliomes supratentoriels de l'enfant. A propos des séries arseillaises et lyonnaises.

BACKGROUND AND PURPOSE: The goal of this study was to analyze the main aspects of oligodendrogliomas observed in children. METHOD: The records of 35 children aged 15 years or younger (23 from Marseilles and 12 from Lyons) were reviewed. Clinical signs and symptoms, imaging findings (CT scan and pre- and post-operative MRI), extent of surgical resection, histology according to the WHO and Ste-Anne grading and survival were analysed. Considering all these factors, a statistical analyzis was undertaken in order to identify prognostic factors. DISCUSSION AND CONCLUSION: Oligodendrogliomas are rare tumors in children. The most important differential diagnosis to discuss is dysembryoplastic neuroepithelial tumor. Our study allowed us to distinguish several subgroups of patients with a different prognosis: thalamic tumors with a dismal prognosis versus hemispheric tumors. A group of cortical tumors we called "DNT-like" (hemispheric cortical tumor, isolated epilepsy, without neurological deficit and reased ICP, without edema and mass effect on MRI) with an excellent prognosis like the group with epilepsy. Histological grading (grade A/grade B and grade II/grade III) is also a prognostic factor.

A phase II study of concurrent temozolomide and cis-retinoic acid with radiation for adult patients with newly diagnosed supratentorial glioblastoma.

PURPOSE: This Phase II study was designed to determine the median survival time of adults with supratentorial glioblastoma treated with a combination of temozolomide (TMZ) and 13-cis-retinoic acid (cRA) given daily with conventional radiation therapy (XRT). METHODS AND MATERIALS: This was a single arm, open-labeled, Phase II study. Patients were treated with XRT in conjunction with cRA and TMZ. Both drugs were administered starting on Day 1 of XRT, and chemotherapy cycles continued after the completion of XRT to a maximum of 1 year. RESULTS: Sixty-one patients were enrolled in the study. Time to progression was known for 55 patients and 6 were censored. The estimated 6-month progression-free survival was 38% and the estimated 1-year progression-free survival was 15%. Median time to progression was estimated as 21 weeks. The estimated 1-year survival was 57%. The median survival was 57 weeks. CONCLUSIONS: The combined therapy was relatively well tolerated, but there was no survival advantage compared with historical studies using XRT either with adjuvant nitrosourea chemotherapy, with TMZ alone, or with the combination of TMZ and thalidomide. Based on this study, cRA does not seem to add a significant synergistic effect to TMZ and XRT.

Management strategies and surgical techniques for deep-seated supratentorial arteriovenous malformations.

The therapeutic options for arteriovenous malformations (AVMs) of the thalamus and the basal ganglia have expanded to include preoperative embolization, stereotactic radiation, and microsurgery. Adjuncts to surgery such as stereotactic guidance, electrophysiological monitoring, intraoperative ultrasound, intraoperative angiography, and induced hypotension have significantly reduced postoperative morbidity. We review the management and outcome of 65 consecutive patients who were treated for deep-seated supratentorial vascular malformations; 45 patients (69%) were treated surgically, 10 patients (15%) were treated conservatively, and 10 patients (15%) underwent radiosurgery. This retrospective study (1976-1993) includes 51 AVMs (78%), 14 cavernous angiomas (22%), and 10 associated vascular anomalies (15%). Initially, 59 (91%) of 65 patients presented with hemorrhage; 23 patients (39%) suffered recurrent hemorrhages. Malformations ranged in size from 1 to 7.5 cm (mean, 2.8 cm). AVMs were fed principally by the anterior and posterior choroidal, thalamoperforate, and lenticulostriate arteries. Venous drainage was uniform via the deep venous system. Among 39 patients who underwent surgery for AVMs, 26 (67%) improved, 7 (18%) remained unchanged, 5 (13%) worsened, and 1 (3%) died. Among six patients who underwent surgery for cavernous angiomas, four (66%) improved, one (17%) remained unchanged, and one (17%) worsened. Operative complications included transient neurological deficits in seven patients (16%), permanent neurological deficits in six patients (13%), and new bleeding from residual AVMs in four patients (9%). Among 10 patients treated conservatively, 3 (30%) had repeat hemorrhages, 2 (20%) had progressive neurological deficits, and 1 (10%) died.(ABSTRACT TRUNCATED AT 250 WORDS)