Category: Oncology

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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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Tentorial meningiomas with special aspect to the tentorial fold: management, surgical technique, and outcome

Acta Neurochir (2010) 152:827–834. DOI 10.1007/s00701-009-0591-z

From a surgical perspective, tentorial fold (TF) meningiomas (TFM) are a unique entity of tumors. They involve the supra- and infratentorial space and often are in close contact to the cavernous sinus, cranial nerves, and the mesencephalon. Complete resection is challenging and can be hazardous. We present our experience with this rare tumor entity and demonstrate the surgical outcome related to a topographical classification.

Methods A retrospective analysis on 21 consecutive patients (female/male ratio 17/4) with meningiomas originating from the TF, who underwent surgery between 1992 and 2005 in our clinic, was performed. The follow-up period ranged from 6 to 93 months. The cases were classified according to tumor extension in three different types: type I, TF meningiomas with compression of the brain stem; type II, with extension into the anterior portion of middle fossa; and type III, a combination of type I and II. Depending on tumor location, surgical approaches consisted of pterional (nine cases), subtemporal (nine cases), or combined subtemporal–pterional craniotomies (three cases). We defined transient and persistent operative complications in relation to Simpson grade and TF classification.

Results Tumor size ranged from 1 to 6 cm in diameter, with a median at 2.5 cm. The presenting symptoms of the patients were anisocoria (six cases), diplopia (six cases), ptosis (five cases), hemianopia (four cases), and ataxia (two cases). Extent of tumor resection was Simpson grade II in 19 patients, grade III in one patient, and grade IV in one patient. There was no operative mortality (first 30 days after surgery). The rate of postoperative transient new neurological deficits was found at 9.5%, the rate of permanent at 33%. The neurological deficits at admission recovered in two patients.

Conclusion In the majority of patients with TF meningiomas, total resection can be achieved through a pterional, subtemporal, or combined approaches but at a substantial toll in terms of permanent morbidity. Radiotherapy after volume reductive surgery in TFM type II and III and decompression of eloquent anatomical structures with low tolerance of radiation should be considered.

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Radiosurgery for large-volume (> 10 cm3) benign meningiomas

J Neurosurg 112:951–956, 2010. DOI: 10.3171/2009.8.JNS09703

Stereotactic radiosurgery (SRS) has proven to be a safe and effective treatment for many patients with intracranial meningiomas. Nevertheless, the morbidity associated with radiosurgery of larger meningiomas is poorly understood.

Methods. The authors performed a retrospective review of 116 patients who underwent SRS for meningiomas (WHO Grade I) > 10 cm3 between 1990 and 2007, with a minimum follow-up of 12 months. Patients with atypical or malignant meningiomas and those who received prior radiotherapy were excluded. The average tumor volume was 17.5 cm3 (range 10.1–48.6 cm3); the average tumor margin dose was 15.1 Gy (range 12–18 Gy); and the mean follow-up duration was 70.1 months (range 12–199 months).

Results. Tumor control was 99% at 3 years and 92% at 7 years after radiosurgery. Thirty complications after radiosurgery were noted in 27 patients (23%), including 7 cases of seizures, 6 cases of hemiparesis, 5 cases of trigeminal injury, 4 cases of headaches, 3 cases of diplopia, 2 cases each of cerebral infarction and ataxia, and 1 case of hearing loss. Patients with supratentorial tumors experienced a higher complication rate compared with patients with skull base tumors (44% compared with 18%) (hazard ratio 2.9, 95% CI 1.3–6.7, p = 0.01).

Conclusions. The morbidity associated with SRS for patients with benign meningiomas > 10 cm3 is greater for supratentorial tumors compared with skull base tumors. Whereas radiosurgery is relatively safe for patients with large-volume skull base meningiomas, resection should remain the primary disease management for the majority of patients with large-volume supratentorial meningiomas.

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Endoscopic endonasal transclival resection of chordomas: operative technique, clinical outcome, and review of the literature

J Neurosurg 112:1061–1069, 2010. DOI: 10.3171/2009.7.JNS081504

Transcranial approaches to clival chordomas provide a circuitous route to the site of origin of the tumor often involving extensive bone drilling and brain retraction, which places critical neurovascular structures between the surgeon and pathology. For certain chordomas, the endonasal endoscopic transclival approach is a novel minimal access, but it is an equally aggressive alternative providing the most direct route to the tumor epicenter.

Methods. The authors present a consecutive series of patients undergoing endonasal endoscopic resection of clival chordomas. Extent of resection was determined by postoperative volumetric MR imaging and divided into > 95% and < 95%.

Results. Seven patients underwent 10 operations. Preoperative cranial neuropathies were present in 4. The mean patient age was 52.0 years. The mean tumor volume was 34.9 cm3. Intraoperative lumbar drainage was used in 1 patient, and the tumors extended intradurally in 3. One patient underwent 2 intentionally palliative procedures for subtotal debulking. Greater than 95% resection was achieved in 7 of 8 operations in which radical resection was the goal (87%). All tumors with volumes < 50 cm3 had > 95% resection (p = 0.05). The overall mean follow-up was 18.0 months. Cranial neuropathies resolved in all 3 patients with cranial nerve VI palsies. One patient with recurrent nasopharyngeal chordoma died of disease progression; another experienced 2 recurrences before receiving radiation therapy. All surviving patients remain progression free. There were no intraoperative complications; however, 1 patient developed a pulmonary embolus postoperatively. There were no postoperative CSF leaks.

Conclusions. The endonasal endoscopic transclival approach represents a less invasive and more direct approach than a transcranial approach to treat certain moderate-sized midline skull base chordomas. Longer follow-up is necessary to determine comparability to transcranial approaches for long-term control. Large tumors with significant extension lateral to the carotid artery may not be suitable for this approach.

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Biopsy versus resection in the management of malignant gliomas: a systematic review and meta-analysis

J Neurosurg 112:1020–1032, 2010. DOI: 10.3171/2009.7.JNS09758

The aim of this study was to answer the question whether quality of life and progression-free and overall survival are increased in adults with supratentorial malignant glioma who are treated with cytoreductive resection as compared with those who only undergo biopsy.

Methods. A literature search of the electronic databases MEDLINE, EMBASE, and CENTRAL was performed to identify relevant studies published before May 2008. Hand-searching of reference lists of the identified studies and relevant review articles was also performed. A study was considered eligible, regardless of study design (prospective or retrospective), if: 1) quality of life and/or progression-free and/or overall survival was compared among adult patients undergoing biopsy or resection, and 2) patient age and Karnofsky Performance Scale scores were not significantly different among the 2 groups compared.

Results. One randomized controlled trial and 4 retrospective studies (involving a total of 1111 patients) were found eligible for this systematic review. A meta-analysis of the eligible studies demonstrated a significant increase in overall survival in the patients treated with resection instead of biopsy (hazard ratio 0.61, 95% CI 0.52–0.71, p < 0.0001, fixed-effect model). Although statistical pooling was not feasible, the available data suggest that quality of life was increased in patients treated with resection rather than biopsy, while there did not seem to be any significant difference in progression-free survival between the 2 groups.

Conclusions. Based on the best available evidence, it appears that cytoreductive resection in adults with supratentorial malignant glioma is associated with improved overall survival as compared with biopsy. However, well designed prospective studies are needed for more solid conclusions to be drawn.

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A proposed classification system that projects outcomes based on preoperative variables for adult patients with glioblastoma multiforme

J Neurosurg 112:997–1004, 2010. DOI: 10.3171/2009.9.JNS09805

Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor in adults. Although the average survival is ~ 12 months, individual survival is heterogeneous. The ability to predict short- and long-term survivors is limited. Therefore, the aims of this study were to ascertain preoperative risk factors associated with survival, develop a preoperative prognostic grading system, and evaluate the utility of this grading system in predicting survival for patients undergoing resection of a primary intracranial GBM.

Methods. Cases involving adult patients who underwent surgery for an intracranial primary (de novo) GBM between 1997 and 2007 at The Johns Hopkins Hospital, an academic tertiary-care institution, were retrospectively reviewed. Multivariate proportional hazards regression analysis was used to identify preoperative factors associated with survival, after controlling for extent of resection and adjuvant therapies. The identified associations with survival were then used to develop a grading system based on preoperative variables. Survival as a function of time was plotted using the Kaplan-Meier method, and survival rates were compared using Log-rank analysis. Associations with p < 0.05 were considered statistically significant.

Results. Of the 393 patients in this study, 310 (79%) had died as of most recent follow-up (median time from surgery to death 11.9 months). The preoperative factors, independent of extent of resection and adjuvant therapies (carmustine wafers, temozolomide, and radiation), found to be negatively associated with survival were: age > 60 years (p < 0.0001), Karnofsky performance status score ≤ 80 (p < 0.0001), motor deficit (p = 0.02), language deficit (p = 0.001), and periventricular tumor location (p = 0.04). Patients possessing 0–1, 2, 3, and 4–5 of these variables were assigned a preoperative grade of 1, 2, 3, and 4, respectively. Patients with a preoperative grade of 1, 2, 3, and 4 had a median survival of 16.6, 10.2, 6.8, and 6.1 months, respectively.

Conclusions. The present study found that older age, poor performance status, motor deficit, language deficit, and periventricular tumor location independently predicted poorer survival in patients undergoing GBM resection. A grading system based on these factors was able to identify 4 distinct groups of patients with different survival rates. This grading system, based only on preoperative variables, may provide patients and physicians with prognostic information that may guide medical and surgical therapy before any intervention is pursued

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A modified far-lateral approach for large or giant meningiomas of the posterior fossa

J Neurosurg 112:907–912, 2010. DOI: 10.3171/2009.6.JNS09120

Resecting large meningiomas along the posterior fossa convexity or cerebellopontine angle (CPA) through a suboccipital approach can be challenging. Limitations include a restricted angle of view, high venous pressures, and suboptimal brain relaxation. While a far-lateral craniotomy is a viable alternative, the risks associated with condylar resection are undesirable.

Methods. The authors retrospectively evaluated a modified far-lateral approach in a consecutive series of 12 patients with large or giant posterior fossa convexity and CPA meningiomas. This approach incorporates transversesigmoid sinus exposure and C-1 laminectomy, but there is no condylar resection.

Results. Between January 2006 and February 2008, 12 patients (mean age 52 years) presented with large or giant meningiomas of the posterior fossa convexity or CPA. The mean tumor volume was 72.6 cm3 (range 8–131 cm3). Signs and symptoms at presentation included headache (in 8 patients), cranial neuropathy (in 4), and progressive hemiparesis (in 4). There were no operative complications, and the majority of patients (9) had Simpson Grade I or II resections. There were no new permanent neurological deficits following resection, although 2 patients (17%) had transient deficits. The mean modified Rankin score decreased from 2.2 preoperatively to 0.6 postoperatively.

Conclusions. A modified far-lateral approach to the posterior fossa and CPA allows for safe, and often total, resection of large meningiomas with minimal morbidity. While avoiding the risks of condylar resection, this microsurgical strategy allows for greater field of view, minimal venous bleeding, and immediate access to the spinal subarachnoid space.

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Magnetic resonance imaging–graded hypothalamic compression in surgically treated adult craniopharyngiomas determining postoperative obesity

Neurosurg Focus 28 (4):E3, 2010. DOI: 10.3171/2010.1.FOCUS09303

Obesity as a consequence of management of pediatric craniopharyngioma is a well-described phenomenon related to the degree of hypothalamic involvement. However, weight change and obesity have not been analyzed in adult patients. Therefore, the purpose of this study was 1) to evaluate the pattern of postoperative weight gain related to preoperative body mass index (BMI), 2) determine if postoperative weight gain is an issue in adult patients, and 3) develop an objective MR imaging grading system to predict risk of postoperative weight gain and obesity in adults treated for craniopharyngioma.

Methods. The authors retrospectively screened 296 patients with known craniopharyngioma for the following inclusion criteria: pathologically confirmed craniopharyngioma, index surgery at the authors’ institution, and operative weight and height recorded with at least 3 months of follow-up including body weight measurement. Patients aged 18 years or younger were excluded, yielding 28 cases for analysis. Cases of craniopharyngiomas were compared with age- and sex-matched controls (pituitary adenoma patients) to evaluate the pattern and significance of perioperative weight changes.

Results. Mean age was 46 ± 17 years at surgery, and 64% of the patients were male. Complete resection was achieved in 71% of cases. There was no correlation of preoperative BMI and postoperative weight gain testing in a linear model. Sixty-one percent and 46% of patients had postoperative weight gains greater than 4 and 9%, respectively. Comparing craniopharyngioma patients (cases) to age- and sex-matched controls, the preoperative BMIs were similar (p = 0.93) between cases (mean 28.9 [95% CI 30.9–26.9]) and controls (mean 29.3 [95% CI 31.9–26.7]). However, there was a trend to a greater mean postoperative weight change (percentage) in cases (10.1%) than in controls (5.6%) (p = 0.24). Hypothalamic T2 signal change and irregular contrast enhancement correlated and predicted higher-grade hypothalamic involvement. Furthermore, they can be used to objectively grade hypothalamic involvement as the authors propose. Progressive hypothalamic involvement correlated with larger postoperative weight gains (p = 0.022); however, hypothalamic involvement did not correlate with preoperative BMI (p = 0.5).

Conclusions. Postoperative weight gain in adult patients undergoing surgery for craniopharyngioma is a significant problem and correlates with hypothalamic involvement, as it does in pediatric patients. Finally, objective MR imaging criteria can be used to predict risk of postoperative weight gain and aid in grading of hypothalamic involvement.

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Craniopharyngiomas: intratumoral chemotherapy with interferon-α: a multicenter preliminary study with 60 cases

Neurosurg Focus 28 (4):E12, 2010. (DOI: 10.3171/2010.1.FOCUS09310)

The authors assessed the efficacy of intratumoral interferon-α (IFNα)–based chemotherapy in pediatric patients with cystic craniopharyngiomas.

Methods. In a prospective multicenter study of 60 pediatric patients, the authors assessed the efficacy of intratumoral INFα2A-based chemotherapy. The study was conducted between 2000 and 2009 at 3 locations: the Medical School of the Federal University of São Paulo, Catholic University of Rome, and the Neurosurgery Institute of Santiago, Chile. The assessment included clinical and radiological control examinations, side effects observed, and total dose used.

Results. Sixty cases of cystic craniopharyngioma were analyzed. The cohort consisted of 35 male and 25 female children (mean age 11 years). Clinical and radiological improvement was achieved in 76% of the cases. New endocrinological deficits were observed in 13% of the cases. In approximately 30% of the patients, the evolution included some light side effects, the most common being headache (33%) and eyelid edema (28%). The number of cycles varied from 1 to 9 (mean 5 cycles), and the total dose applied per cycle was 36,000,000 IU.

Conclusions. This has been the largest documented series of intratumoral chemotherapy using INFα for the control of cystic craniopharyngiomas. The treatment has proved efficacious; there was no mortality, and morbidity rates were low.


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Tolerance of the Optic Apparatus in Single-Fraction Irradiation Using Stereotactic Radiosurgery: Evaluation in 100 Patients With Craniopharyngioma

Neurosurgery 66:688-695, 2010. DOI: 10.1227/01.NEU.0000367554.96981.26

OBJECTIVE: To determine the limiting dose to the optic apparatus in single-fraction irradiation in patients with craniopharyngioma treated with gamma knife radiosurgery (GKRS).

METHODS: One hundred patients with 109 craniopharyngiomas treated with GKRS were evaluated with a median follow-up period of 68 months. Tumor volume varied from 0.1 to 36.0 (median, 3.3) cm3. Marginal doses varied from 10 to 18 (median, 11.4) Gy. Maximum dose to any part of the optic apparatus varied from 2 to 18 (median, 10) Gy.

RESULTS: The actuarial 5- and 10-year overall rates of survival of tumor progression after GKRS were 93% and 88%, respectively. Similarly, the actuarial 5- and 10-year progressionfree survival rates were 62% and 52%, respectively. Among 94 patients in whom visual function was evaluable after GKRS, only 3 patients developed radiation-induced optic neuropathy, indicating an overall Kaplan-Meier radiation-induced optic neuropathy rate of 5%. Of these patients, 2 received 15 Gy or greater to the optic apparatus. Another patient who received 8 Gy or less had undergone previous fractionated radiation therapy with a biologically effective dose of 60 Gy.

CONCLUSION: The optic apparatus seems to be more tolerant of irradiation than previously thought. Careful dose planning is essential, particularly in patients who underwent prior external beam radiation therapy.

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Functional outcome after complete surgical removal of giant vestibular schwannomas

J Neurosurg 112:860–867, 2010. (DOI: 10.3171/2009.7.JNS0989)
The authors evaluated the outcome of radical surgery in a consecutive series of patients with giant vestibular schwannomas (VSs).
Methods. Fifty patients with VSs > 4.0 cm in maximal extrameatal diameter were included in this retrospective study (Group A). The group was compared with a matched group of 167 patients with VSs < 3.9 cm (Group B). In all cases the retrosigmoid approach was used. Outcome measures included completeness of tumor removal, facial nerve function, hearing, and the surgery-related complication rate.
Results. The mean tumor size in Group A was 4.4 cm and that in Group B was 2.3 cm. Total removal was achieved in all Group A patients and in 97.6% of Group B patients. The anatomical integrity of the facial nerve was preserved in 92% in Group A and in 98.8% in Group B. At last follow-up 75% of the patients with giant VSs had excellent or good facial nerve function, 19% had fair function, and 6% had poor function. In 33% of patients (3 cases) with good preoperative hearing level, it was preserved. Newly developed lower cranial nerve dysfunction occurred in 3 patients but proved to be temporary in 2 of them. A CSF leak developed in 6% of those who not previously undergone surgery. Compared with Group B, a significant difference was found only in the rates of the following parameters: excellent facial nerve function, useful and good hearing, lower cranial nerve dysfunction, and blood collection (p < 0.05). The perioperative mortality rate in both groups was 0%.
Conclusions. In patients with a giant VS, total tumor removal can be achieved via the retrosigmoid approach with a 0% mortality rate and low morbidity rate, especially with regards to facial nerve function. In selected cases even hearing preservation is possible. Tumor size significantly correlates with postoperative outcome.

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The role of radiosurgery in the treatment of craniopharyngiomas

Neurosurg Focus 28 (4):E11, 2010. (DOI: 10.3171/2010.2.FOCUS09311)

The treatment of craniopharyngiomas is composed of an intricate balance of multiple modalities. Resection and radiotherapy have been combined to synergistically control tumor growth while preventing undue harm to crucial neurovascular structures. Although a craniopharyngioma is a benign lesion pathologically, it may induce severe neurological injury due to its location and rate of growth. More recently, the advent of targeted, fractionated radiotherapy has allowed for more aggressive tumor control while reducing the necessity for large resections. Initial studies have demonstrated significant tumor control in patients who are treated with resection combined with radiation therapy, versus surgery alone, with a lower rate of treatment-associated neurological deficits. In this review, a detailed account of the current studies evaluating the role of stereotactic radiosurgery in the management of craniopharyngiomas is presented. The authors also provide a short account of their experience to aid in defining the role of CyberKnife radiosurgery.

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Anterior Interhemispheric Approach for 100 Tumors in and Around the Anterior Third Ventricle

Neurosurgery 66[ONS Suppl 1]:ons65-ons74, 2010 DOI: 10.1227/01.NEU.0000365550.84124.BB

We report our experience with anterior interhemispheric approach for tumors in and around the anterior third ventricle, including surgical technique, instrumentation, pre- and postoperative hormonal disturbances, and resection rate.

METHODS: One hundred patients with 46 craniopharyngiomas, 12 hypothalamic gliomas, 12 meningiomas, 6 hypothalamic hamartomas, and 24 other lesions were operated on using an anterior interhemispheric approach with or without opening of the lamina terminalis. This surgical approach involves no frontal sinus opening; a narrow (approximately 15–20 mm in width) access between the bridging veins, which is sufficient to remove the tumor totally; and sparing of the anterior communicating artery. Specially designed long bipolar forceps and scissors are necessary for this approach, and concomitant use of angled instruments (endoscope, aspirator, and microforceps) is required frequently. The postsurgical follow-up period varied from 4 months to 18 years. RESULTS: Total removal of the neoplasm was accomplished in 37 of 46 patients with craniopharyngiomas (80.4%), whereas subtotal resection was performed in hypothalamic gliomas. No significant differences in pre- and postoperative hormonal disturbances were observed in 37 craniopharyngiomas and 10 hypothalamic gliomas. There was no operative mortality. Visual acuity was preserved or improved in 68 of 75 patients assessed. The Karnofsky Performance Scale score did not deteriorate in 72 of 75 patients tested.

CONCLUSION: The minimally invasive anterior interhemispheric approach, with or without opening of the lamina terminalis, is useful for removal of tumors in and around the anterior third ventricle, such as craniopharyngiomas and hypothalamic gliomas.

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Activation of PI3K/mTOR pathway occurs in most adult low-grade gliomas and predicts patient survival

J Neurooncol (2010) 97:33–40. DOI 10.1007/s11060-009-0004-4

Recent evidence suggests the Akt-mTOR pathway may play a role in development of low-grade gliomas (LGG). We sought to evaluate whether activation of this pathway correlates with survival in LGG by examining expression patterns of proteins within this pathway.

Forty-five LGG tumor specimens from newly diagnosed patients were analyzed for methylation of the putative 50-promoter region of PTEN using methylationspecific PCR as well as phosphorylation of S6 and PRAS40 and expression of PTEN protein using immunohistochemistry. Relationships between molecular markers and overall survival (OS) were assessed using Kaplan-Meier methods and exact log-rank test. Correlation between molecular markers was determined using the Mann-Whitney U and Spearman Rank Correlation tests.

Eight of the 26 patients with methylated PTEN died, as compared to 1 of 19 without methylation. There was a trend towards statistical significance, with PTEN methylated patients having decreased survival (P = 0.128). Eight of 29 patients that expressed phospho-S6 died, whereas all 9 patients lacking p-S6 expression were alive at last follow-up. There was an inverse relationship between expression of phospho-S6 and survival (P = 0.029). There was a trend towards decreased survival in patients expressing phospho-PRAS40 (P = 0.077).

Analyses of relationships between molecular markers demonstrated a statistically significant positive correlation between expression of p-S6(235) and p-PRAS40 (P = 0.04); expression of p-S6(240) correlated positively with PTEN methylation (P = 0.04) and negatively with PTEN expression (P = 0.03). Survival of LGG patients correlates with phosphorylation of S6 protein. This relationship supports the use of selective mTOR inhibitors in the treatment of low grade glioma

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