Category: Oncology

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Glioblastoma multiforme of the elderly: the prognostic effect of resection on survival

J Neurooncol. DOI 10.1007/s11060-010-0429-9

According to recent developments the best treatment options for glioblastoma (GBM) consist in maximum safe resection and additional adjuvant treatment with radiotherapy (RT) and alkylating chemotherapy (CHX).

These options have been evaluated for populations with a median age of approximately 58 years. We therefore addressed the issue of whether elderly patients ([65years) could also benefit from cytoreductive surgery (CS) and adjuvant treatment using alkylating chemotherapy.

Onehundred and three patients suffering from newly diagnosed, primary supratentorial glioblastoma multiforme[65 years (median 70.8 years) were identified in our single-center glioma database (2002–2007) and retrospectively divided into group A (n = 31) treated with surgery alone (biopsy, BY, n = 21, CS n = 10), group B (n = 37) surgery plus radiation (BY n = 18, CS n = 19), and group C (n = 35) surgery, RT and CHX (BY n = 4, CS n = 31). Progression- free survival (PFS) and overall survival (OAS) were determined in each group and correlated to age, Karnofsky performance score (KPS), and extent of resection (biopsy (BY), partial (PR), and complete resection (CR)). Progression was defined according the Macdonald criteria. For all patients PFS and OAS were 3.2 months and 5.1 months (m) respectively. PFS and OAS for groups A/B/C were 1.8/ 3.2/6.4 m (P = 0.000) and 2.2/4.4/15.0 m (P = 0.000), respectively. Median age for groups A/B/C was 74.4/70.6/ 68.5 years and median KPS was 60/70/80. Age (\75, C75) was inversely correlated with OAS (5.8/2.5 m, P = 0.01). KPS (\70, C70) was correlated with OAS 2.4/6.5 m (P = 0.000). Extent of resection (BY, PR, or CR) correlated with PFS (2.1/3.4/6.4 m, P = 0,000) and OS (2.2/7.0/ 13.9 m, P = 0,000), respectively.

Our study shows that elderly GBM patients can benefit from maximum treatment procedures with cytoreductive microsurgery, radiation therapy, and chemotherapy. Treatment options are obviously affected by KPS and age. The most impressive outcome predictor in this population was the extent of microsurgical resection for patients treated with adjuvant radiotherapy and chemotherapy. To conclude, elderly GBM patients should not be per se excluded from intensive treatment procedures.

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Brain surface motion imaging to predict adhesions between meningiomas and the brain surface

Neuroradiology (2010) 52:1003–1010. DOI 10.1007/s00234-010-0671-z

“Brain surface motion imaging” (BSMI) is the subtraction of pulse-gated, 3D, heavily T2-weighted image of two different phases of cerebrospinal fluid (CSF) pulsation, which enables the assessment of the dynamics of brain surface pulsatile motion. The purpose of this study was to evaluate the feasibility of this imaging method for providing presurgical information about adhesions between meningiomas and the brain surface.

Methods Eighteen cases with surgically resected meningioma in whom BSMI was presurgically obtained were studied. BSMI consisted of two sets of pulse-gated, 3D, heavily T2-weighted, fast spin echo scans. Images of the systolic phase and the diastolic phase were obtained, and subtraction was performed with 3D motion correction. We analyzed the presence of band-like texture surrounding the tumor and judged the degree of motion discrepancy as “total,” “partial,” or “none.” The correlation between BSMI and surgical findings was evaluated. For cases with partial adhesions, agreements in the locations of the adhesions were also evaluated.

Results On presurgical BSMI, no motion discrepancy was seen in eight cases, partial in six cases, and total in four cases. These presurgical predictions about adhesions and surgical findings agreed in 13 cases (72.2%). The locations of adhesions agreed in five of six cases with partial adhesions.

Conclusion In the current study, BSMI could predict brain and meningioma adhesions correctly in 72.2% of cases, and adhesion location could also be predicted. This imaging method appears to provide presurgical information about brain/meningioma adhesions.

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Intraoperative 5-aminolevulinic-acid-induced fluorescence in meningiomas

Acta Neurochir (2010) 152:1711–1719. DOI 10.1007/s00701-010-0708-4

5-aminolevulinic acid (5-ALA) has gained importance as an intraoperative photodynamic diagnostic agent for the extirpation of malignant gliomas. The application of this technique for resection of meningiomas has barely been explored. The aim of this study was to evaluate the utility of 5-ALA-induced fluorescence as a visual tool in meningioma resection and its correlation with histological findings.

Methods A total of 33 consecutive patients undergoing resection of intracranial meningiomas from December 2007 to August 2009 were included in this study. After confirmation of normal liver function, 5-ALA was administered orally (20 mg/kg) within 3–5 h prior to skin incision. All cases were operated on using standard microsurgical and neuronavigation-guided techniques. Intraoperative 440 nm fluorescence was applied periodically during and at the end of resection in order to detect tumor-infiltrated sites. The fluorescence of the tumor was evaluated intraoperatively by the surgeon and confirmed by subsequent video analysis.

Results A total of 32 (97%) patients presented with benign meningiomas (WHO I–II). In 1 (3%) patient, histological anaplastic signs (WHO III) could be demonstrated. 5-ALAinduced fluorescence of the tumor was confirmed in a total of 31 (94%) patients. The fluorescence did not correlate with the histological findings (n=30 WHO I–II, n=1 WHO grade III) or with preoperative brain edema and administration of steroids. A total resection could be postoperatively demonstrated in 25 (76%) patients. No adverse effects attributable to 5-ALA occurred.

Conclusions 5-ALA-induced fluorescence is a useful and promising intraoperative tool for the visualization of meningioma tissue. The novel findings demonstrated in this study in terms of high fluorescence and poor correlation with histological findings highlight the usefulness of this technique as a routine visual tool to achieve optimal resection of meningiomas.

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First-line treatment of malignant glioma with carmustine implants followed by concomitant radiochemotherapy: a multicenter experience

Neurosurg Rev (2010) 33:441–449. DOI 10.1007/s10143-010-0280-7

Randomized phase III trials have shown significant improvement of survival 1, 2, and 3 years after implantation of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers for patients with newly diagnosed malignant glioma. But these studies and subsequent non-phase III studies have also shown risks associated with local chemotherapy within the central nervous system. The introduction of concomitant radiochemotherapy with temozolomide (TMZ) has later demonstrated a survival benefit in a phase III trial and has become the current treatment standard for newly diagnosed malignant glioma patients. Lately, this has resulted in clinical protocols combining local chemotherapy with BCNU wafers and concomitant radiochemotherapy with TMZ although this may carry the risk of increased toxicity.

We have compiled the treatment experience of seven neurosurgical centers using implantation of carmustine wafers at primary surgery followed by 6 weeks of radiation therapy (59–60 Gy) and 75 mg/m2/day TMZ in patients with newly diagnosed glioblastoma followed by TMZ monochemotherapy. We have retrospectively analyzed the postoperative clinical course, occurrence and severity of adverse events, progression-free interval, and overall survival in 44 patients with newly diagnosed glioblastoma multiforme. All patients received multimodal treatment including tumor resection, BCNU wafer implantation, and concomitant radiochemotherapy. Of 44 patients (mean age 59±10.8 years) with glioblastoma who received Gliadel wafer at primary surgery, 28 patients (64%) had died, 16 patients (36%) were alive, and 15 patients showed no evidence of clinical or radiographic progression after a median follow-up of 15.6 months. At time of analysis of adverse events in this patient population, the median overall survival was 12.7 months and median progression-free survival was 7.0 months. Surgical, neurological, and medical adverse events were analyzed. Twenty-three patients (52%) experienced adverse events of any kind including complications that did not require treatment. Nineteen patients (43%) experienced grade 3 or grade 4 adverse events. Surgical complications included cerebral edema, healing abnormalities, cerebral spinal fluid leakage, meningitis, intracranial abscess, and hydrocephalus. Neurological adverse events included newly diagnosed seizures, alteration of mental status, and new neurological deficits. Medical complications were thromboembolic events (thrombosis, pulmonary embolism) and hematotoxicity.

Combination of both treatment strategies, local chemotherapy with BCNU wafer and concomitant radiochemotherapy, appears attractive in aggressive multimodal treatment schedules and may utilize the sensitizing effect of TMZ and carmustine on MGMT and AGT on their respective drug resistance genes. Our data demonstrate that combination of local chemotherapy and concomitant radiochemotherapy carries a significant risk of toxicity that currently appears underestimated. Adverse events observed in this study appear similar to complication rates published in the phase III trials for BCNU wafer implantation followed by radiation therapy alone, but further add the toxicity of concomitant radiochemotherapy with systemic TMZ. Save use of a combined approach will require specific prevention strategies for multimodal treatments.

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Postauricular, transpetrous, presigmoid approach for extensive skull base tumors in the petroclival region: the successes and the travails

Acta Neurochir (2010) 152:1633–1645.DOI 10.1007/s00701-010-0701-y

Postauricular, transpetrous, presigmoid approach combines a supra/infratentorial exposure with partial petrosectomy to access third to the twelfth cranial nerves and extraaxial lesions situated anterolateral to brainstem. It provides a shorter working distance to large petrosal, petroclival, cerebellopontine, and cerebellomedullary cisternal lesions and their extensions to the subtemporal–infratemporal areas. This study reviews the surgical technique, corridors of extension, and complications encountered utilizing this approach for excising extensive lesions in these locations.

Methods The lesions (n=14) included petroclival meningiomas [(n=5), including three recurrent lesions], dumbbell lower cranial nerve schwannomas (n=2), giant acoustic schwannomas (n=2), recurrent giant trigeminal nerve schwannoma (n=1), glomus jugulare (n=3), and recurrent petrous aneurysmal bone cyst (n=1). The approach was combined with a retrosigmoid suboccipital craniectomy (n=3), with an infratemporal approach (n=2), and with an extreme lateral transcondylar approach and a translabyrinthine approach in one patient each, respectively. External auditory canal was not ligated in nine patients, superior petrosal sinus and tentorial division was performed in all patients, and sigmoid sinus–internal jugular vein was excised in three patients (with a glomus jugulare (n=1) and petroclival meningioma (n=2), respectively). Repair was performed with fat–fascia, pedicled pericranium, and temporalis muscle. Lumbar drain was placed for three to five postoperative days.

Results Total excision was performed in nine patients. Small tumor remnants were left attached to the brainstem (n=3, petroclival meningioma), carotid canal and cavernous sinus (n=1, glomus jugulare), and sigmoid sinus–jugular bulb (n=1, recurrent trigeminal schwannoma). A two-staged procedure was performed in three patients. Two patients with recurrent giant petroclival meningiomas died: one with lower cranial nerve paresis due to aspiration pneumonitis and the other with cerebrospinal fluid otorrhoea and secondary meningitis.

Conclusions The approach facilitates direct tumor decompression and its retraction away from the brainstem without initially encountering the intracisternal cranial nerves and neuraxis. It provides multiple corridors for excising extensive posterior fossa tumors. Preoperative assessment of sigmoid sinus dominance, jugular bulb height, labyrinth, vein of Labbe, and space available through Trautman’s triangle considerably helps in complication avoidance.

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Prognostic factors for long-term outcome of patients with surgical resection of skull base chordomas—106 cases review in one institution

Neurosurg Rev (2010) 33:451–456. DOI 10.1007/s10143-010-0273-6

Skull base chordoma are still challenging. Between May 1993 and June 2005, 106 consecutive patients with skull base chordoma underwent surgical removal at Skull Base Division of Neurosurgery, Beijing Tiantan Hospital, China. Retrospective analysis included medical charts and images.

The age of the patients ranged from 7 to 65 years old, with an average age of 35.6 years. Sixty patients were male; the other 46 were female (1.3:1). Follow up data were available in 79 cases ranging from 10 to 158 months (average 63.9 months) after operation.

The prognostic factors for recurrence and survival were analyzed with Kaplan‐Meier, Cox regression and t‐test. Overall, 1, 3, 5 and 10 years survival rates were 87.2%, 79.4%, 67.6% and 59.5% respectively. One, 3, 5 and 10 year recurrent rates were 19.1%, 34.7%, 52.9% and 88.3%, respectively.

The long term outcome of the skull base chordomas is poor. The previous radiotherapy or surgery, dedifferentiated pathology, and less tumor resection are risk factors for longterm survival and recurrence (p<0.05). Although there is no statistic significant role of tumor adherent to vital structure for outcome (p=0.051), it can not exclude its importance for favorable outcome.

Gender, age, tumor size and staging are not independent risk factors for outcome. Surgical technique leading to radical tumor resection with less morbidity is advocatory and beneficial for patients with skull base chordoma with long term outcome, if the tumor could be exposed and resected completely, the recurrence rate was very low for most benign chordomas.

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Perioperative and Long-term Outcomes From the Management of Parasagittal Meningiomas Invading the Superior Sagittal Sinus

Neurosurgery 67:885–893, 2010 DOI: 10.1227/NEU.0b013e3181ef2a18

Parasagittal meningiomas invading the superior sagittal sinus (SSS) pose formidable obstacles to surgical management. Invasion is often considered a contraindication to surgery because of associated morbidity, such as cerebral venous thrombosis.

OBJECTIVE: We report our most recent experience with the resection of parasagittal meningiomas invading the SSS.

METHODS: Between 1992 and 2004, 110 patients with parasagittal meningiomas underwent surgery at the Johns Hopkins Medical Institutions. Clinical charts, radiological studies, pathological features, and operative notes were retrospectively analyzed; only those patients with minimum 24 months follow-up (n = 61) were further studied.

RESULTS: Tumor distribution by location along the SSS was: 21% anterior, 62% middle, and 17% posterior. All patients were managed with initial surgical resection with radiosurgery for residual/recurrent disease if indicated (19.6%). Pathological examination revealed 80% grade I meningiomas, 13% grade II meningiomas, and 7% grade III meningiomas. Simpson grade I/II resection was achieved in 81% of patients. Major complications included venous thrombosis/infarction (7%), intraoperative air embolism (1.5%), and death (1.5%); long-term outcomes assessed included recurrence (11%) and improvement in Karnofsky Performance Score (85%).

CONCLUSION: On the basis of our study, the incidence of postoperative venous sinus thrombosis is 7% in the setting of a recurrence rate of 11% with a mean follow-up of 41 months. In comparison with the published literature, the data corroborate the rationale for our treatment paradigm; lesions invading the sinus can initially be resected to the greatest extent possible without excessive manipulation of vascular structures, whereas residual/recurrent disease can be observed and managed with radiosurgery.

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Diffusion tensor imaging tractography in patients with intramedullary tumors: comparison with intraoperative findings and value for prediction of tumor resectability

J Neurosurg Spine 13:371–380, 2010. DOI: 10.3171/2010.3.SPINE09399

The aim of this retrospective study was to evaluate the predictive value of diffusion tensor (DT) imaging with respect to resectability of intramedullary spinal cord tumors and to determine the concordance of this method with intraoperative surgical findings.

Methods. Diffusion tensor imaging was performed in 14 patients with intramedullary lesions of the spinal cord at different levels using a 3-T magnet. Routine MR imaging scans were also obtained, including unenhanced and enhanced T1-weighted images and T2-weighted images. Patients were classified according to the fiber course with respect to the lesion and their lesions were rated as resectable or nonresectable. These results were compared with the surgical findings (existence vs absence of cleavage plane). The interrater reliability was calculated using the κ coefficient of Cohen.

Results. Of the 14 patients (7 male, 7 female; mean age 49.2 ± 15.5 years), 13 had tumors (8 ependymomas, 2 lymphomas, and 3 astrocytoma). One lesion was proven to be a multiple sclerosis plaque during further diagnostic workup. The lesions could be classified into 3 types according to the fiber course. In Type 1 (5 cases) fibers did not pass through the solid lesion. In Type 2 (3 cases) some fibers crossed the lesion, but most of the lesion volume did not contain fibers. In Type 3 (6 cases) the fibers were completely encased by tumor. Based on these results, 6 tumors were considered resectable, 7 were not. During surgery, 7 tumors showed a good cleavage plane, 6 did not. The interrater reliability (Cohen κ) was calculated as 0.83 (p < 0.003), which is considered to represent substantial agreement. The mean duration of follow-up was 12.0 ± 2.9. The median McCormick grade at the end of follow-up was II.

Conclusions. These preliminary data suggest that DT imaging in patients with spinal cord tumors is capable of predicting the resectability of the lesion. A further prospective study is needed to confirm these results and any effect on patient outcome.

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Image-guided frameless stereotactic biopsy without intraoperative neuropathological examination. Clinical article

Journal of Neurosurgery, August 2010 Volume 113, Number 2
DOI: 10.3171/2009.12.JNS09573
Stereotactic biopsy is a safe and effective technique for the diagnosis of brain tumors. The use of intraoperative neuropathological examination has been routinely advocated to increase diagnostic yield, but the procedure lengthens surgical time, may produce false-negative and -positive results, and current biopsy techniques have a very low nondiagnostic rate. Therefore, the authors questioned the need for intraoperative histological evaluation.
Methods
The authors prospectively studied all patients undergoing image-guided biopsy under the care of a single surgeon (P.L.G.) between July 2005 and October 2007. A Stryker neuronavigation system with a trajectory guide was used to plan a single trajectory, and, using a side-cutting biopsy cannula, multiple biopsy samples were taken from between 1 and 4 sites within the tumor. Tissue was inspected macroscopically by the surgeon and was only submitted for neuropathological assessment postoperatively.
Results
One hundred thirty-four biopsies were performed during the study. A positive diagnosis was established in 133 cases (99.3%). One biopsy was negative (0.7%) and postoperative imaging (performed because the tissue was macroscopically normal) demonstrated inaccurate targeting of the lesion. Significant complications were seen in 3 patients (2.2%) who all had preoperative WHO performance scores of III or IV. Two patients suffered delayed deterioration and died due to probable surgical complications—one with thalamic glioblastoma multiforme (GBM) and one with gliomatosis cerebri. One patient with GBM suffered an intracerebral hematoma that was managed conservatively. Postoperative seizures were seen in 4 patients (3%), and 2 patients (1.5%) experienced a transient neurological deficit. Histological diagnosis showed a GBM in 64 cases, Grade III glioma in 19, Grade I or II in 23, metastasis in 10, lymphoma in 13, and other disease in 4. There were 32 patients discharged to home on the same day as surgery. Compared with the authors’ previous retrospective audit into 127 biopsies, this technique showed improved diagnostic yield (99.3 vs 94.5%, p = 0.032) with fewer complications (2.2 vs 4.7% [not statistically significant]).
Conclusions
This technique of image-guided biopsy has high diagnostic yield with acceptably low morbidity and may be performed as a day case. Intraoperative neuropathological examination would not have increased the diagnostic yield further in this study, and its routine use may not be necessary. In the authors’ department £70,350 (UK)/$114,522 (US) would have been saved by not using intraoperative neuropathology in this series. Therefore, intraoperative neuropathology should no longer be routinely recommended.

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Functional Magnetic Resonance Imaging and Diffusion Tensor Tractography Incorporated Into an Intraoperative 3-Dimensional Ultrasound-Based Neuronavigation System: Impact on Therapeutic Strategies, Extent of Resection, and Clinical Outcome

Neurosurgery 67:251-264, 2010 DOI: 10.1227/01.NEU.0000371731.20246.AC

Functional neuronavigation with intraoperative 3-dimensional (3D) ultrasound may facilitate safer brain lesion resections than conventional neuronavigation.

OBJECTIVE: In this study, functional magnetic resonance imaging (fMRI) and diffusion tensor tractography (DTT) were used to map eloquent areas. We assessed the use of fMRI and DTT for preoperative assessments and determined whether using these data together with 3D ultrasound during surgery enabled safer lesion resection.

METHODS:We reviewed 51 consecutive patients with intracranial lesions in whom fMRI with or without DTT was used to map eloquent areas. To assess a possible impact of fMRI/DTT, we reviewed and analyzed the quality of the fMRI/DTT data, any change in therapeutic strategies, lesion to eloquent area distance (LEAD), extent of resection, and clinical outcome.

RESULTS: As a result of the fMRI/DTT mapping, the therapeutic strategies were changed in 4 patients. The median tumor residue for glioma patients was 11% (n = 33) and 0% for nonglioma lesions (n = 12). For gliomas, there was a significant correlation between decreasing LEAD and increasing tumor residue. Of the glioma patients, 42% underwent gross total resection (≥ 95%) and 12% suffered neurological worsening after surgery as a result of complications. Of glioma patients with an LEAD of ≤ 5 mm, 24% underwent gross total resection and 10% experienced neurological deterioration.

CONCLUSION: This study demonstrates that preoperative fMRI and DTT had direct consequences for therapeutic strategies and indicates their impact on intraoperative strategies to spare eloquent cortex and tracts. Functional neuronavigation combined with intraoperative 3D ultrasound can, in most patients, enable resection of brain lesions with general anesthesia without jeopardizing neurological function.

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Trigonal and peritrigonal lesions of the lateral ventricle—surgical considerations and outcome analysis of 20 patients

Neurosurg Rev DOI 10.1007/s10143-010-0271-8

The aim of this study is to review the results and clinical outcome of patients with surgically treated lesions within the trigone of the lateral ventricle.

This is a retrospective case series of 20 (eight male, 12 female) patients with lesions of the trigone of the lateral ventricle operated between 1998 and 2008. All lesions were removed via the transcortical temporal and transcortical parietal route. Surgical complications and outcome were assessed using the modified Rankin Scale (mRS).

There were four children and 16 adults with a mean age of 42±22 years (min=1, max=74). Eight (40%) lesions grew within the trigone of the dominant hemisphere. In 17 cases, the lesion was purely intraventricular, and in three cases, a slight paraventricular extension was seen. The mean size was 4.5 cm of maximal diameter. Surgical removal was achieved via the transcortical parietal route in 13 cases (65%) and the transcortical temporal route in seven cases (35%). In all cases, complete resection was possible. According to the mRS, 13 patients improved, five remained the same, and two were lost to follow-up. One patient had an increased visual field deficit postoperatively and new hemiparesis and aphasia, but returned to the preoperative level within a few weeks. In one patient, an acute myocardial infarction occurred due to previous cardiac stent placement and instent stenosis.

Even large trigonal lesions can be resected with low morbidity using a transcortical approach depending on the peritrigonal extension of the tumor.

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First-line treatment of malignant glioma with carmustine implants followed by concomitant radiochemotherapy: a multicenter experience

Neurosurg Rev DOI 10.1007/s10143-010-0280-7

Randomized phase III trials have shown significant improvement of survival 1, 2, and 3 years after implantation of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers for patients with newly diagnosed malignant glioma. But these studies and subsequent non-phase III studies have also shown risks associated with local chemotherapy within the central nervous system. The introduction of concomitant radiochemotherapy with temozolomide (TMZ) has later demonstrated a survival benefit in a phase III trial and has become the current treatment standard for newly diagnosed malignant glioma patients. Lately, this has resulted in clinical protocols combining local chemotherapy with BCNU wafers and concomitant radiochemotherapy with TMZ although this may carry the risk of increased toxicity. We have compiled the treatment experience of seven neurosurgical centers using implantation of carmustine wafers at primary surgery followed by 6 weeks of radiation therapy (59–60 Gy) and 75 mg/m2/day TMZ in patients with newly diagnosed glioblastoma followed by TMZ monochemotherapy. We have retrospectively analyzed the postoperative clinical course, occurrence and severity of adverse events, progression-free interval, and overall survival in 44 patients with newly diagnosed glioblastoma multiforme. All patients received multimodal treatment including tumor resection, BCNU wafer implantation, and concomitant radiochemotherapy. Of 44 patients (mean age 59±10.8 years) with glioblastoma who received Gliadel wafer at primary surgery, 28 patients (64%) had died, 16 patients (36%) were alive, and 15 patients showed no evidence of clinical or radiographic progression after a median follow-up of 15.6 months. At time of analysis of adverse events in this patient population, the median overall survival was 12.7 months and median progression-free survival was 7.0 months. Surgical, neurological, and medical adverse events were analyzed. Twenty-three patients (52%) experienced adverse events of any kind including complications that did not require treatment. Nineteen patients (43%) experienced grade 3 or grade 4 adverse events. Surgical complications included cerebral edema, healing abnormalities, cerebral spinal fluid leakage, meningitis, intracranial abscess, and hydrocephalus. Neurological adverse events included newly diagnosed seizures, alteration of mental status, and new neurological deficits. Medical complications were thromboembolic events (thrombosis, pulmonary embolism) and hematotoxicity. Combination of both treatment strategies, local chemotherapy with BCNU wafer and concomitant radiochemotherapy, appears attractive in aggressive multimodal treatment schedules and may utilize the sensitizing effect of TMZ and carmustine on MGMT and AGT on their respective drug resistance genes. Our data demonstrate that combination of local chemotherapy and concomitant radiochemotherapy carries a significant risk of toxicity that currently appears underestimated. Adverse events observed in this study appear similar to complication rates published in the phase III trials for BCNU wafer implantation followed by radiation therapy alone, but further add the toxicity of concomitant radiochemotherapy with systemic TMZ. Save use of a combined approach will require specific prevention strategies for multimodal treatments.

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Management of Anterolateral Foramen Magnum Meningiomas: Surgical Vs Conservative Decision Making

Neurosurgery 67[ONS Suppl 1]:ons00-ons00, 2010. DOI: 10.1227/01.NEU.0000382971.63877.DD

Anterolateral meningiomas of the foramen magnum (FMMs) represent a neurosurgical challenge because they grow in close contact with osteoarticular, nervous, and vascular structures that cannot be sacrificed or retracted. OBJECTIVE: To evaluate our strategy and results in 26 patients with FMMs and analyze factors affecting the decision-making process, resection, and outcome. METHODS: Among 26 consecutive symptomatic FMM (10 anterior, 16 lateral) patients (16 women, 10 men, ages 28-82 years), 4 older than 70 years of age were untreated. Twentytwo were operated on using a posterolateral approach, with the vertebral artery transposed in 19 and the occipital condyle drilled in 10. We analyzed the characteristics and outcome of untreated cases, the utility of THE occipital condyle drilled, the difficulties of microdissection, morbidity and total removal rates, the outcome of tumor residues, and the literature on radiosurgery. RESULTS: Three of 4 untreated patients remained clinically stable at 2 to 5 years. After systematic vertebral artery medial transposition and occipital condyle drilled in 6 cases, our technique evolved with experience in the next 16 (vertebral artery transposed in 13 of 16; occipital condyle drilled in 4 of 13) for dissecting anteriorly beyond midline (anterior FMMs). Retrocondylar access was sufficient for lateral FMMs. Tumors were totally removed in 16 of 22 (73%). One patient died, and 4 had permanent deficits. Follow-up of more than 5 years in 12 patients showed no C0-1 instability, and slight increase of tumor residue size 7 years after surgery. In the literature, 15 FMMs treated with radiosurgery are reported, 13 at diagnosis and 2 at recurrence, with short-term clinical and radiological safety and efficacy. CONCLUSION:We currently recommend (1) aiming for subtotal removal in difficult cases, (2) remaining conservative in asymptomatic or elderly patients with mild symptoms, and (3) considering radiosurgery at diagnosis for small (<30 mm) symptomatic FMMs or as an adjunct for evolving residues/recurrences in poor candidates for resection.

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Resection of malignant brain tumors in eloquent cortical areas: a new multimodal approach combining 5-aminolevulinic acid and intraoperative monitoring

J Neurosurg 113:352–357, 2010.DOI: 10.3171/2009.10.JNS09447

Object. Several studies have revealed that the gross-total resection (GTR) of malignant brain tumors has a significant influence on patient survival. Frequently, however, GTR cannot be achieved because the borders between healthy brain and diseased tissue are blurred in the infiltration zones of malignant brain tumors. Especially in eloquent cortical areas, resection is frequently stopped before total removal is achieved to avoid causing neurological deficits. Interestingly, 5-aminolevulinic acid (5-ALA) has been shown to help visualize tumor tissue intraoperatively and, thus, can significantly improve the possibility of achieving GTR of primary malignant brain tumors. The aim of this study was to go one step further and evaluate the utility and limitations of fluorescence-guided resections of primary malignant brain tumors in eloquent cortical areas in combination with intraoperative monitoring based on multimodal functional imaging data. Methods. Eighteen patients with primary malignant brain tumors in eloquent areas were included in this prospective study. Preoperative neuroradiological examinations included MR imaging with magnetization-prepared rapid gradient echo (MPRAGE), functional MR, and diffusion tensor imaging sequences to visualize functional areas and fiber tracts. Imaging data were analyzed offline, loaded into a neuronavigational system, and used intraoperatively during resections. All patients received 5-ALA 6 hours before surgery. Fluorescence-guided tumor resections were combined with intraoperative monitoring and cortical as well as subcortical stimulation to localize functional areas and fiber tracts during surgery. Results. Twenty-five procedures were performed in 18 consecutive patients. In 24% of all surgeries, resection was stopped because a functional area or cortical tract was identified in the resection area or because motor evoked potential amplitudes were reduced in an area where fluorescent tumor cells were still seen intraoperatively. Grosstotal resection could be achieved in 16 (64%) of the surgeries with preservation of all functional areas and fiber tracts. In 2 patients presurgical hemiparesis became accentuated postoperatively, and 1 of these patients also suffered from a new homonymous hemianopia following a second resection. Conclusions. The authors’ first results show that tumor resections with 5-ALA in combination with intraoperative cortical stimulation have the advantages of both methods and, thus, provide additional safety for the neurosurgeon during resections of primary malignant brain tumors in eloquent areas. Nonetheless, more cases and additional studies are necessary to further prove the advantages of this multimodal strategy.

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Patterns of Care and Survival in a Retrospective Analysis of 1059 Patients With Glioblastoma Multiforme Treated Between 2002 and 2007: A Multicenter Study by the Central Nervous System Study Group of Airo (Italian Association of Radiation Oncology)

Neurosurgery 67:446-458, 2010 DOI: 10.1227/01.NEU.0000371990.86656.E8

OBJECTIVE: To investigate the pattern of care and outcomes for newly diagnosed glioblastoma in Italy and compare our results with the previous Italian Patterns of Care study to determine whether significant changes occurred in clinical practice during the past 10 years.

METHODS: Clinical, pathological, therapeutic, and survival data regarding 1059 patients treated in 18 radiotherapy centers between 2002 and 2007 were collected and retrospectively reviewed.

RESULTS:Most patients underwent both computed tomography and magnetic resonance imaging either preoperatively (62.7%) or postoperatively (35.5%). Only 123 patients (11.6%) underwent a biopsy. Radiochemotherapy with temozolomide was the most frequent adjuvant treatment (70.7%). Most patients (88.2%) received 3-dimensional conformal radiotherapy. Median survival was 9.5 months. Two- and 5-year survival rates were 24.8% and 3.9%, respectively. Multivariate analysis showed the statistical significance of age, postoperative Karnofsky Performance Status scale score, surgical extent, use of 3-dimensional conformal radiotherapy, and use of chemotherapy. Use of a more aggressive approach was associated with longer survival in elderly patients. Comparing our results with those of the subgroup of patients included in our previous study who were treated between 1997 and 2001, relevant differences were found: more frequent use of magnetic resonance imaging, surgical removal more common than biopsy, and widespread use of 3-dimensional conformal radiotherapy + temozolomide. Furthermore, a significant improvement in terms of survival was noted (P < .001).

CONCLUSION: Changes in the care of glioblastoma over the past few years are documented. Prognosis of glioblastoma patients has slightly but significantly improved with a small but noteworthy number of relatively long-term survivors.

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Clinical Characteristics and Surgical Outcomes of Patients Presenting With Meningiomas Arising Predominantly From the Floor of the Middle Fossa

Neurosurgery 67:80-86, 2010. DOI: 10.1227/01.NEU.0000370938.46353.77

Little is known regarding meningiomas that primarily arise from the floor of the middle fossa as opposed to the sphenoid wing, the cavernous sinus, the anterior petrous ridge, or the lateral convexity dura.

OBJECTIVE: Given the relative paucity of literature addressing this disease entity, we review the University of California at San Francisco (UCSF) experience with these tumors.

METHODS: Between 1991 and 2006, 1228 patients were seen by neurosurgeons at UCSF for meningiomas of which 17 (1.1%) patients met our criteria for a “middle fossa floor” meningioma, of which 15 underwent first-time surgery and were included in this series. The most common presenting symptoms were headache (9 patients), seizures (6 patients), trigeminal nerve dysfunction (5 patients), hearing loss (5 patients), gait disturbance (5 patients), and cognitive decline (3 patients). All patients underwent surgical resection via frontotemporal craniotomy, with or without orbitozygomatic osteotomy.

RESULTS:We were able to achieve a Simpson grade 1 or 2 resection in 10 of 15 patients (67%). The operative morbidity was clustered in 5 patients, as 10 of 15 patients (67%) experienced no operative morbidity. There were 4 known clinical recurrences in this group at 5 years median follow-up. All patients had either higher grade tumors, or received a Simpson grade 3 or higher resection.

CONCLUSION:We present the clinical characteristics and surgical outcome of a series of patients presenting with meningiomas primarily arising from the concave floor of the middle cranial fossa. Given the relatively uncommon nature of these lesions, more investigation into the clinical behavior of this entity is warranted.

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Clinical management of petroclival meningiomas and the eternal quest for preservation of quality of life. Personal experiences over a period of 20 years

Acta Neurochir (2010) 152:1099–1116.DOI 10.1007/s00701-010-0633-6

Within the realm of neurosurgery, petroclival meningiomas are regarded as probably the most difficult tumour to be treated by microsurgery. This is due to the not infrequently large size of the tumours which, although predominantly located in the posterior fossa, may occupy more than one cranial compartment, with often significant space-occupying effect and brain stem compression. Frequent tight brain stem adherence as well as encasement of the basilar artery, its perforators and cranial nerves adds to the sometimes extreme difficulties of surgical tumour removal. Counselling patients as well as pre- and intraoperative decision making in petroclival meningiomas is even more difficult because upon clinical and radiological tumour detection, despite sometimes surprisingly large tumours, clinical symptoms are often only mild. Summarising the complicated development of petroclival meningioma surgery over the last 60 years, this paper represents the conceptual thinking of the author in regard to the treatment of petroclival meningiomas which has evolved over more than two decades, based on a special interest in these treacherous tumours, and accumulated experiences in the treatment of over 150 patients. Surgical concepts and the operative decision-making process are demonstrated in four illustrative cases.

Methods Over a period of slightly over 20 years, between January 1988 and December 2008, 161 patients with petroclival meningiomas were managed clinically by the author or under his direct surveillance in four academic neurosurgical institutions. The observation period ranged from 4 to 242 months. Thirteen patients were lost to followup so, all together, complete data were available for 148 patients. In 119 patients (80%), the tumour was large. Giant tumours accounted for 7% and 11 patients, medium-sized tumours were found in 12 patients (8%) and small tumours in only six patients (4%). Sixty-two percent of the patients had invasion of Meckel’s cave or some part of the cavernous sinus, mainly the posterior region to different degrees. All giant tumours and one third of the large tumours extended into more than one cranial fossa.

Results The treatment modalities in the 148 patients were as follows: microsurgery alone was performed in 71 patients (48%), microsurgery and adjuvant radiosurgery in 22 patients (15%) so in 93 patients (63%), altogether, microsurgery was the primary treatment. Twenty-nine patients (20%) underwent radiosurgery as their only treatment, and two patients (1%), during the very early phase of the study period, received radiotherapy. Twentyfour patients (16%) were only observed without any additional therapy. Gross total resection was achieved in 34 patients (37%), and subtotal resection, defined as removal of more than 90% of the tumour volume, was performed in another 36 patients (39%). Radical tumour removal was possible in 76% of the patients. There was no procedure-related death within 3 months post-surgery; the early post-op surgical complication rate was 31% with new neurological deficits or worsening of pre-existing deficits. During the observation period, almost all patients recovered significantly bringing the percentage of permanent neurological deficits, again mainly cranial nerve deficits, down to 22%.

Conclusions Based on the experiences of the author, the following treatment principles in petroclival meningiomas are proposed: small tumours in asymptomatic patients should be observed. If tumour growth is detected on serial magnetic resonance imaging or treatment is desired by the patient, surgery should be the first choice. Radiosurgery in growing small tumours should be reserved to patients with advanced age or significant co-morbidities. In medium-sized tumours and symptomatic patients, radical surgery should be attempted, if possible by judicious intraoperative judgement. In large and giant petroclival meningiomas, tumour resection as radical as possible judged intraoperatively with decompression of neural structures should be performed, followed by observation and, in the case of growing tumour remnants, radiosurgery. Thus, by a combined application of advanced microsurgical techniques, thoughtful, intraoperative decision making with limited surgical aggressively and, in selected patients, with small tumours or small tumour remnants simple observation or alternative or adjunct radiosurgery, excellent results as measured by tumour control and preservation of quality of life can be achieved.

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Different microsurgical approaches to meningiomas of the anterior cranial base

Acta Neurochir (2010) 152:931–939. DOI 10.1007/s00701-010-0646-1

Meningiomas of the anterior skull base show specific characteristics, which render them difficult to handle. These tumors include olfactory groove, supra- and parasellar, anterior sphenoid ridge, cavernous sinus, and spheno-orbital meningiomas. Tumor localization and size, encasement of important structures as well as the extent of dural attachment may influence the decision for an adequate approach.

Discussion Various approaches to the anterior cranial fossa exist, each with corresponding advantages and disadvantages. Recently, endoscopic approaches have increasingly been used. In this review, the different approaches to meningiomas of the anterior cranial fossa in respect of anatomical issues, indications, and associated risks are discussed.

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Cavernous sinus meningiomas: a large LINAC radiosurgery series

J Neurooncol (2010) 98:195–202. DOI 10.1007/s11060-010-0173-1

One hundred and seventeen patients with cavernous sinus meningiomas had LINAC radiosurgery at our institution in the period 1993–2007. Six cases were lost and 9 had less than 1 year follow up. The remaining 102 patients were prospectively followed up at 1 y intervals with clinical, neuro-ophthalmological and MRI examinations. Patients’ age ranged between 31 and 86 years (mean 57). Seventy percent were females. The mean tumor volume was 7 cc. Thirty-three patients had previous microsurgery. Tumors were defined with high resolution MRI obtained 1–2 days before treatment and fused to stereotactic CT. Treatment was mostly delivered through a minimultileaf collimator and multiple dynamic arcs. The minimal dose to the tumor margin was 12–17.5 Gy (mean 13.5) encompassed by the 80% isodose shell. Radiation dose to the optic apparatus was kept below 10 Gy. Follow up ranged from 12 to 180 months (mean 67 months). Tumor control (lack of growth) was 98% (58% of the tumors reduced their volumes). Sixty-four patients presented with cranial nerve deficit. Thirty-nine percent improved or resolved following radiosurgery. Cranial neuropathy had significantly higher resolution rates when radiosurgery was performed early (\1 year) after its appearance (53% as opposed to 26%) even in patients with deficits post surgery. Complications were seen in five patients (1 with deafferentation pain, 1 with facial hypesthesia, 1 with visual loss and 2 with partial VI neuropathy). Radiosurgery had a high control rate for meningiomas of the cavernous sinus with few and mild complications. Cranial neuropathy can be solved by treatment, particularly those of recent onset.

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Awake Mapping Optimizes the Extent of Resection for Low-Grade Gliomas in Eloquent Areas

Neurosurgery 66:1074-1084, 2010 DOI: 10.1227/01.NEU.0000369514.74284.78

Awake craniotomy with intraoperative electrical mapping is a reliable method to minimize the risk of permanent deficit during surgery for low-grade glioma located within eloquent areas classically considered inoperable. However, it could be argued that preservation of functional sites might lead to a lesser degree of tumor removal. To the best of our knowledge, the extent of resection has never been directly compared between traditional and awake procedures.

OBJECTIVE: We report for the first time a series of patients who underwent 2 consecutive surgeries without and with awake mapping.

METHODS: Nine patients underwent surgery for a low-grade glioma in functional sites under general anesthesia in other institutions. The resection was subtotal in 3 cases and partial in 6 cases. There was a postoperative worsening in 3 cases. We performed a second surgery in the awake condition with intraoperative electrostimulation. The resection was performed according to functional boundaries at both the cortical and subcortical levels.

RESULTS: Postoperative magnetic resonance imaging showed that the resection was complete in 5 cases and subtotal in 4 cases (no partial removal) and that it was improved in all cases compared with the first surgery (P = .04). There was no permanent neurological worsening. Three patients improved compared with the presurgical status. All patients returned to normal professional and social lives.

CONCLUSION: Our results demonstrate that awake surgery, known to preserve the quality of life in patients with low-grade glioma, is also able to significantly improve the extent of resection for lesions located in functional regions.


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