Clinical outcomes of solitary fibrous tumors and hemangiopericytomas and risk factors related to recurrence and survival based on the 2021 WHO classification of central nervous system tumors

J Neurosurg 140:69–79, 2024

OBJECTIVE The authors aimed to explore the clinical outcomes and risk factors related to recurrence of and survival from solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) that were reclassified according to the 2021 WHO classification of central nervous system (CNS) tumors.

METHODS The authors retrospectively collected and analyzed the clinical and pathological data of SFTs and HPCs recorded from January 2007 to December 2021. Two neuropathologists reassessed pathological slides and regraded specimens on the basis of the 2021 WHO classification. The prognostic factors related to progression-free survival (PFS) and overall survival (OS) were statistically assessed with univariate and multivariate Cox regression analyses.

RESULTS A total of 146 patients (74 men and 72 women, mean ± SD [range] age 46.1 ± 14.3 [3–78] years) were reviewed, and 86, 35, and 25 patients were reclassified as having grade 1, 2, and 3 SFTs on the basis of the 2021 WHO classification, respectively. The median PFS and OS of the patients with WHO grade 1 SFT were 105 months and 199 months after initial diagnosis; for patients with WHO grade 2 SFT, 77 months and 145 months; and for patients with WHO grade 3 SFT, 44 months and 112 months, respectively. Of the entire cohort, 61 patients experienced local recurrence and 31 died, of whom 27 (87.1%) died of SFT and relevant complications. Ten patients had extracranial metastasis. In multivariate Cox regression analysis, subtotal resection (STR) (HR 4.648, 95% CI 2.601–8.304, p < 0.001), tumor located in the parasagittal or parafalx region (HR 2.105, 95% CI 1.099–4.033, p = 0.025), tumor in the vertebrae (HR 3.352, 95% CI 1.228–9.148, p = 0.018), WHO grade 2 SFT (HR 2.579, 95% CI 1.343–4.953, p = 0.004), and WHO grade 3 SFT (HR 5.814, 95% CI 2.887–11.712, p < 0.001) were significantly associated with shortened PFS, whereas STR (HR 3.217, 95% CI 1.435–7.210, p = 0.005) and WHO grade 3 SFT (HR 3.433, 95% CI 1.324–8.901, p = 0.011) were significantly associated with shortened OS. In univariate analyses, patients who received adjuvant radiotherapy (RT) after STR had longer PFS than patients who did not receive RT.

CONCLUSIONS The 2021 WHO classification of CNS tumors better predicted malignancy with different pathological grades, and in particular WHO grade 3 SFT had worse prognosis. Gross-total resection (GTR) can significantly prolong PFS and OS and should serve as the most important treatment method. Adjuvant RT was helpful for patients who underwent STR but not for patients who underwent GTR.

Management of cavernous sinus meningiomas: Consensus statement on behalf of the EANS skull base section

Brain and Spine 2 (2022) 100864

The evolution of cavernous sinus meningiomas (CSMs) might be unpredictable and the efficacy of their treatments is challenging due to their indolent evolution, variations and fluctuations of symptoms, heterogeneity of classifications and lack of randomized controlled trials. Here, a dedicated task force provides a consensus statement on the overall management of CSMs. Research question: To determine the best overall management of CSMs, depending on their clinical presentation, size, and evolution as well as patient characteristics.

Material and methods: Using the PRISMA 2020 guidelines, we included literature from January 2000 to December 2020. A total of 400 abstracts and 77 titles were kept for full-paper screening.

Results: The task force formulated 8 recommendations (Level C evidence). CSMs should be managed by a highly specialized multidisciplinary team. The initial evaluation of patients includes clinical, ophthalmological, endocrinological and radiological assessment. Treatment of CSM should involve experienced skull-base neurosurgeons or neuro-radiosurgeons, radiation oncologists, radiologists, ophthalmologists, and endocrinologists.

Discussion and conclusion: Radiosurgery is preferred as first-line treatment in small, enclosed, pauci-symptomatic lesions/in elderly patients, while large CSMs not amenable to resection or WHO grade II-III are candidates for radiotherapy. Microsurgery is an option in aggressive/rapidly progressing lesions in young patients presenting with oculomotor/visual/endocrinological impairment. Whenever surgery is offered, open cranial approaches are the current standard. There is limited experience reported about endoscopic endonasal approach for CSMs and the main indication is decompression of the cavernous sinus to improve symptoms. Whenever surgery is indicated, the current trend is to offer decompression followed by radiosurgery.

Aggressive pituitary neuroendocrine tumors: current practices, controversies, and perspectives, on behalf of the EANS skull base section

Acta Neurochirurgica (2021) 163:3131–3142

Aggressive pituitary neuroendocrine tumors (APT) account for 10% of pituitary tumors. Their management is a rapidly evolving field of clinical research and has led pituitary teams to shift toward a neuro-oncological-like approach.

The new terminology “Pituitary neuroendocrine tumors” (PitNet) that was recently proposed to replace “pituitary adenomas” reflects this change of paradigm. In this narrative review, we aim to provide a state of the art of actual knowledge, controversies, and recommendations in the management of APT.

We propose an overview of current prognostic markers, including the recent five-tiered clinicopathological classification. We further establish and discuss the following recommendations from a neurosurgical perspective: (i) surgery and multi-staged surgeries (without or with parasellar resection in symptomatic patients) should be discussed at each stage of the disease, because it may potentialize adjuvant medical therapies; (ii) temozolomide is effective in most patients, although 30% of patients are non-responders and the optimal timeline to initiate and interrupt this treatment remains questionable; (iii) some patients with selected clinicopathological profiles may benefit from an earlier local radiotherapy and/or chemotherapy; (iv) novel therapies such as VEGF-targeted therapies and anti-CTLA-4/anti-PD1 immunotherapies are promising and should be discussed as 2nd or 3rd line of treatment.

Finally, whether neurosurgeons have to operate on “pituitary adenomas” or “PitNets,” their role and expertise remain crucial at each stage of the disease, prompting our community to deal with evolving concepts and therapeutic resources.

Adjuvant Radiotherapy Versus Watchful Waiting for World Health Organization Grade II Atypical Meningioma

Neurosurgery 88:E435–E442, 2021

Atypical meningiomas (AMs) are meningiomas that have a higher rate of recurrence than grade Imeningioma. Due to the higher risk of recurrence, adjuvant radiotherapy (RT) after resection of AM has been employed. At our institution, some neurosurgeons employ adjuvant RT on all primarily resected AMs, while others employ watchful waiting with serial imaging.

OBJECTIVE: To study the effect of adjuvant RT on newly resected AMs.

METHODS: A retrospective review of all AMs primarily resected at our institution from 1996 to 2018 was completed. Data on patient demographics, radiographic findings, use of adjuvant RT, time of follow-up, and recurrences were collected. Adjuvant RT was defined as RT that occurred within 6 mo of initial resection.

RESULTS: A total of 162 patients met the inclusion criteria. Gross total resection was achieved in 73% of cases. Average time until recurrence in the cohort was 37mo. A total of 108 patients had adjuvant RT, while 54 patients did not. On multivariate survival analysis, sex, Simpson grade resection, and use of adjuvant RT were independent predictors of recurrence. Mean time to recurrence in patients who received adjuvant RT was 43.7 mo versus 34.7 mo for those who did not receive adjuvant RT.

CONCLUSION: This study includes the largest retrospective cohort of patients who have received adjuvant RT after primary resection of AM. Our results suggest that the use of adjuvant RT is independently associated with a lower chance of recurrence. These data suggest that practitioners can consider the use of adjuvant RT for newly resected AMs, regardless of Simpson grade resection.

Frameless Stereotactic Radiosurgery on the Gamma Knife Icon: Early Experience From 100 Patients

Neurosurgery 86:509–516, 2020

The Gamma Knife (GK) Icon (Elekta AB) uses a cone-beam computed tomography (CBCT) scanner and an infrared camera system to support the delivery of frameless stereotactic radiosurgery (SRS). There are limited data on patients treated with frameless GK radiosurgery (GKRS).

OBJECTIVE: To describe the early experience, process, technical details, and short-term outcomes with frameless GKRS at our institution.

METHODS: We reviewed our patient selection and described the workflow in detail, including image acquisition, treatment planning, mask-based immobilization, stereotactic CBCT localization, registration, treatment, and intrafraction monitoring. Because of the short interval of follow-up, we provide crude rates of local control.

RESULTS: Data from 100 patients are reported. Median age is 67 yr old. 56 patients were treated definitively, 21 postoperatively, and 23 had salvage GKRS for recurrence after surgery. Forty-two patients had brain metastases, 26 meningiomas, 16 vestibular schwannomas, 9 high-grade gliomas, and 7 other histologies. Median doses to metastases were 20 Gy in 1 fraction (range: 14-21), 24 Gy in 3 fractions (range: 19.5-27), and 25 Gy in 5 fractions (range: 25-30 Gy). Thirteen patients underwent repeat SRS to the same area. Median treatment time was 17.7 min (range: 5.8-61.7). We found an improvement in our workflow and a greater number of patients eligible for GKRS because of the ability to fractionate treatments.

CONCLUSION: We report a large cohort of consecutive patients treated with frameless GKRS. We look forward to studies with longer follow-up to provide valuable data on clinical outcomes and to further our understanding of the radiobiology of hypofractionation in the brain.

Radiosurgery and fractionated radiotherapy for cavernous sinus meningioma: a systematic review and meta-analysis

Acta Neurochirurgica (2018) 160:2367–2378

Radiosurgery (RS) and fractionated radiotherapy (FRT) are part of the therapeutic armamentarium for the management of cavernous sinus meningiomas. We propose a systematic review of the local tumor control and clinical outcomes after monofractionated radiosurgical treatment, including gamma knife radiosurgery (GKRS) and linear accelerator (Linac RS), or fractionated radiotherapy.

Materials and Methods: The current review and meta-analysis adhered to the PRISMA guidelines. We performed a search in PubMed, Embase, and Medline based on the following mesh terms, used alone or in diverse combinations, in both title and abstract: “cavernous sinus”, “meningioma”, “radiosurgery”, “gamma knife”,”linac”, “cyberknife” and “radiotherapy”. We screened 425 studies. We selected 36 studies, matching all selection criteria: 24 for GK, 5 for Linac, and 7 for FRT.

Results: Were included 2817 patients (GKRS, n = 2047, LinacRS, n = 350, FRT, n = 420). Half of patients benefited from upfront RS or FRT; the other half benefited from adjuvant RS or FRT (combined approach or tumor recurrence). The mean gross target volume (GTV) was smaller for RS as compared to FRT (p = 0.07). The median marginal doses were 13.9 Gy (range, 11 to 28) for GKRS and 14 Gy (range, 12.8 to 17.7) for LinacRS. For FRT, patients received a mean dose of 51.2 Gy (25.5 fractions, 1.85 Gy each). The mean overall follow-up values were 48 months (range, 15 to 89) for GKRS, 69 months (range, 46 to 87) for Linac, and 59.5 months (range, 33 to 83) for FRT. PFS at 5 years for GKRS, LinacRS, and FRT were respectively 93.6%, 95.6%, and 97.4% (p = 0.32, the Kruskal-Wallis). Monofractionated treatments (GKRS and LinacRS) induced more tumor volume regression than FRT (p = 0.001). Tumor recurrence or progression ranged between 3 and 5.8%, without statistically significant differences between modalities (p > 0.05). Trigeminal symptoms improved in approximately 54%, and III-IV-VI cranial nerves (CN) palsies improved in approximately 45%. After GKRS, visual acuity improved in 21% (not enough data available for other modalities). De novo deficits occurred in 5 to 7.5%. Adverse radiation effects appeared in 4.6 to 9.3% (all techniques pooled).

Conclusion: RS achieved a twice-higher rate of tumor volume regression than FRT. GKRS series reported an improvement in visual acuity in 21% of the cases. GKRS, Linac, and FRT provided similar clinical post therapeutic outcomes for the trigeminal and oculomotor CN.

Esthesioneuroblastoma: A Patterns-of-Care and Outcomes Analysis of the National Cancer Database

Neurosurgery 83:940–947, 2018

BACKGROUND: The available literature to guide treatment decision making in esthesioneuroblastoma (ENB) is limited.

OBJECTIVE: To define treatment patterns and outcomes in ENB according to treatment modality using a large national cancer registry.

METHODS: This study is a retrospective cohort analysis of 931 patients with a diagnosis of ENB who were treated with surgery, radiation therapy, and/or chemotherapy in the United States between the years of 2004 and 2012. Log-rank statisticswere used to compare overall survival by primary treatment modality. Logistic regression modeling was used to identify predictors of receipt of postoperative radiotherapy (PORT). Cox proportional hazardsmodeling was used to determine the survival benefit of PORT. Subgroup analyses identified subgroups that derived the greatest benefit of PORT.

RESULTS: Primary surgery was the most common treatment modality (90%) and resulted in superior survival compared to radiation (P < .01) or chemotherapy (P < .01). On multivariate analysis, PORT was associated with decreased risk of death (hazard ratio [HR] 0.53, P<.01). PORT showed a survival benefit in Kadish stage C (HR 0.42, P<.01) and D (HR 0.09, P = .01), but not Kadish A (HR 1.17, P = .74) and B (HR 1.37, P = .80). Patients who received chemotherapy derived greater benefit from PORT (HR 0.22, P < .01) compared with those who did not (HR 0.68, P=.13). Predictors of PORT included stage, grade, extent of resection, and chemotherapy use.

CONCLUSION: Best outcomes were obtained in patients undergoing primary surgery. The benefit of PORT was driven by patients with stages C and D disease, and by those also receiving chemotherapy.

 

Anaplastic meningioma: an analysis of the National Cancer Database from 2004 to 2012

J Neurosurg 128:1684–1689, 2018

Anaplastic meningiomas represent 1%–2% of meningioma diagnoses and portend a poor prognosis. Limited information is available on practice patterns and optimal management. The purpose of this study was to define treatment patterns and outcomes by treatment modality using a large national cancer registry.

METHODS The National Cancer Database was used to identify patients diagnosed with anaplastic meningioma from 2004 to 2012. Log-rank statistics were used to compare survival outcomes by extent of resection, use of adjuvant radiotherapy (RT), and use of adjuvant chemotherapy. Least-squares linear regression was used to evaluate the utilization of RT over time. Logistic regression modeling was used to identify predictors of receipt of RT. Cox proportional hazards modeling was used to evaluate the effect of RT, gross-total resection (GTR), and chemotherapy on survival.

RESULTS A total of 755 adults with anaplastic meningioma were identified. The 5-year overall survival rate was 41.4%. Fifty-two percent of patients received RT, 7% received chemotherapy, and 58% underwent GTR. Older patients were less likely to receive RT (OR 0.98, p < 0.01). Older age (HR 1.04, p < 0.01), high comorbidity score (HR 1.33, p = 0.02), and subtotal resection (HR 1.57, p = 0.02) were associated with increased risk of death on multivariate modeling, while RT receipt was associated with decreased risk of death (HR 0.79, p = 0.04). Chemotherapy did not have a demonstrable effect on survival (HR 1.33, p = 0.18).

CONCLUSIONS Anaplastic meningioma portends a poor prognosis. Gross-total resection and RT are associated with improved survival, but utilization of RT is low. Unless medically contraindicated, patients with anaplastic meningioma should be offered RT.

Management of Atypical Cranial Meningiomas, Part 2: Predictors of Progression and the Role of Adjuvant Radiation After Subtotal Resection

Meningioma_-_brain_invasion_-_high_mag

Neurosurgery 75:356–363, 2014

The efficacies of adjuvant stereotactic radiosurgery (SRS) and external beam radiation therapy (EBRT) for atypical meningiomas (AMs) after subtotal resection (STR) remain unclear.

OBJECTIVE: To analyze the clinical, histopathological, and radiographic features associated with progression in AM patients after STR.

METHODS: Fifty-nine primary AMs after STR were examined for predictors of progression, including the impact of SRS and EBRT, in a retrospective cohort study.

RESULTS: Twenty-seven patients (46%) progressed after STR (median, 30 months). On univariate analysis, spontaneous necrosis positively (hazard ratio = 5.2; P = .006) and adjuvant radiation negatively (hazard ratio = 0.3; P = .009) correlated with progression; on multivariate analysis, only adjuvant radiation remained independently significant (hazard ratio = 0.3; P = .006). SRS and EBRT were associated with greater local control (LC; P = .02) and progression-free survival (P = .007). The 2-, 5-, and 10-year actuarial LC rates after STR vs STR/EBRT were 60%, 34%, and 34% vs 96%, 65%, and 45%. The 2-, 5-, and 10-year actuarial progression-free survival rates after STR vs STR/EBRT were 60%, 30%, and 26% vs 96%, 65%, and 45%. Compared with STR alone, adjuvant radiation therapy significantly improved LC in AMs that lack spontaneous necrosis (P = .003) but did not improve LC in AMs with spontaneous necrosis (P = .6).

CONCLUSION: Adjuvant SRS or EBRT improved LC of AMs after STR but only for tumors without spontaneous necrosis. Spontaneous necrosis may aid in decisions to administer adjuvant SRS or EBRT after STR of AMs.

Management of Atypical Cranial Meningiomas, Part 1: Predictors of Recurrence and the Role of Adjuvant Radiation After Gross Total Resection

Meningioma_-_brain_invasion_-_high_mag

Neurosurgery 75:347–355, 2014

Indications for external beam radiation therapy (EBRT) for atypical meningiomas (AMs) remain unclear.

OBJECTIVE: To analyze features associated with recurrence in AM patients after gross total resection (GTR) and to assess the relative benefit of EBRT in a retrospective cohort study.

METHODS: One hundred fifty-one primary AMs after GTR (88 female patients; median follow-up, 45.0 months) were examined for possible predictors of recurrence (age, sex, location, volume, bone involvement, brain invasion). The Fisher exact and Wilcoxon rank-sum tests were used to analyze the association between these predictors and use of EBRT. The impact on recurrence for these predictors and EBRT was analyzed with Kaplan-Meier and Cox regression.

RESULTS: Of 151 patients, 13 (8.6%) experienced recurrence after GTR (median, 47.0 months). Multivariate analysis identified elevated mitotic index (P = .007) and brain invasion (P = .002) as predictors of recurrence. Larger volume (P = .96) was not associated with recurrence but was more likely to prompt EBRT (P = .001). Recurrences occurred in 11 of 112 with GTR (9.8%; median, 44 months) and 2 of 39 with GTR/EBRT (5.1%; median, 133 months). The 2-, 5-, and 10-year progression-free survival rates after GTR vs GTR/ EBRT were 97%, 86%, and 68% vs 100%, 100%, and 78%. Kaplan-Meier analysis demonstrated no difference in progression-free survival or overall survival after GTR vs GTR/ EBRT (P = .8, P . .99).

CONCLUSION: Brain invasion and high mitotic rates may predict recurrence. After GTR of AMs, EBRT appears not to affect progression-free survival and overall survival, suggesting that observation rather than EBRT may be indicated after GTR.

Endoscopic endonasal approach in the management of skull base chordomas

Endoscopic approach skull base chordomas

Neurosurg Rev (2014) 37:217–225

Skull base chordomas represent very interesting neoplasms, due to their rarity, biological behavior, and resistance to treatment. Their management is very challenging. Recently, the use of a natural corridor, through the nose and the sphenoid sinus, improved morbidity and mortality allowing also for excellent removal rates.

Prospective analysis of 54 patients harboring a skull base chordoma that were managed by extended endonasal endoscopic approach (EEA). Among the 54 patients treated (during a 72 months period), 21 were women and 33 men, undergoing 58 procedures. Twenty-two cases (40 %) were recurrent and 32 (60 %) newly diagnosed chordomas. Among the 32 newly diagnosed chordomas, a gross total resection was achieved in 28 cases (88%), a near total (>95%of tumor) in 2 cases (6%), a partial (>50 % of tumor) in 2 cases (6 %). Among the 22 recurrent chordomas, resection was complete in 7 cases (30 %), near total in 7 (30%), and partial in 8 (40 %). The global gross total resection rate was 65 % (35/54 cases). Four patients (11 %) recurred and 4 (11 %) progressed within a mean follow-up of 34 months (range 12–84 months). Four patients (11 %) were re-operated; one patient (1.8 %) died due to disease progression, one patient (1.8 %) died 2 weeks after surgery due to a massive bleeding from an ICA pseudo aneurysm. CSF leakage occurred in four patients (8 %), and meningitis in eight cases (14 %). No new permanent neurological deficit occurred.

The EEA management of skull base chordomas requires a long and gradual learning curve that once acquired offers the possibility of either similar or better resection rates as compared to traditional approaches while morbidity is improved.

Solitary clival plasmocytomas

Solitary clival plasmocytomas

Acta Neurochir (2013) 155:1849–1856

Tumours of the clivus are exceptionally rare, representing a diagnostic and a therapeutic challenge. Clival solitary plasmocytomas have been described only as single case reports or included in small clinical series with other intracranial location.

Methods Authors report clinical, radiological, and survival data of four patients, who underwent surgery for clival plasmocytomas between 1989 and 2012 in a single centre. Current knowledge about solitary plasmocytomas of the clivus are reviewed.

Results Follow-up time was 54 months (range: 9–165). Mean age of patient was 57 years, no gender predilection was observed. Main symptoms were headache (75 %) and double vision (75 %), due to third or sixth cranial nerve palsy. Mean time to diagnosis was 8.2 months. All patients underwent surgery as primary treatment, through either a transsphenoidal (75 %) or a transmaxillary approach (25 %). In all cases adjuvant conventional radiotherapy was performed with a median delivered dose of 45 Gy. Only one case of progression into multiple myeloma was observed 13 months after surgery, and the patient died 9 months later. No other recurrences or progression were observed. Mean overall survival and progression free survival time were, respectively, 54 and 51.7 months.

Conclusions Although extremely rare, clival plasmocytomas have to be considered in the differential diagnosis of a solitary clival lesion. Biological and clinical features of these tumours strongly differ from those of similar lesions in other part of the body. Early diagnosis, extensive tumour removal, opportune indication of adjuvant treatment with radiotherapy and chemotherapy are the keys to manage these cases.

Separation surgery and postoperative SRS for spinal metastases

Local disease control for spinal metastases following “separation surgery” and adjuvant hypofractionated or high-dose single-fraction stereotactic radiosurgery

J Neurosurg Spine 18:207–214, 2013

Decompression surgery followed by adjuvant radiotherapy is an effective therapy for preservation or recovery of neurological function and achieving durable local disease control in patients suffering from metastatic epidural spinal cord compression (ESCC). The authors examine the outcomes of postoperative image-guided intensity-modulated radiation therapy delivered as single-fraction or hypofractionated stereotactic radiosurgery (SRS) for achieving long-term local tumor control.

Methods. A retrospective chart review identified 186 patients with ESCC from spinal metastases who were treated with surgical decompression, instrumentation, and postoperative radiation delivered as either single-fraction SRS (24 Gy) in 40 patients (21.5%), high-dose hypofractionated SRS (24–30 Gy in 3 fractions) in 37 patients (19.9%), or low-dose hypofractionated SRS (18–36 Gy in 5 or 6 fractions) in 109 patients (58.6%). The relationships between postoperative adjuvant SRS dosing and fractionation, patient characteristics, tumor histology–specific radiosensitivity, grade of ESCC, extent of surgical decompression, response to preoperative radiotherapy, and local tumor control were evaluated by competing risks analysis.

Results. The total cumulative incidence of local progression was 16.4% 1 year after SRS. Multivariate Gray competing risks analysis revealed a significant improvement in local control with high-dose hypofractionated SRS (4.1% cumulative incidence of local progression at 1 year, HR 0.12, p = 0.04) as compared with low-dose hypofractionated SRS (22.6% local progression at 1 year, HR 1). Although univariate analysis demonstrated a trend toward greater risk of local progression for patients in whom preoperative conventional external beam radiation therapy failed (22.2% local progression at 1 year, HR 1.96, p = 0.07) compared with patients who did not receive any preoperative radiotherapy (11.2% local progression at 1 year, HR 1), this association was not confirmed with multivariate analysis. No other variable significantly correlated with progression-free survival, including radiation sensitivity of tumor histology, grade of ESCC, extent of surgical decompression, or patient sex.

Conclusions. Postoperative adjuvant SRS following epidural spinal cord decompression and instrumentation is a safe and effective strategy for establishing durable local tumor control regardless of tumor histology–specific radiosensitivity. Patients who received high-dose hypofractionated SRS demonstrated 1-year local progression rates of less than 5% (95% CI 0%–12.2%), which were superior to the results of low-dose hypofractionated SRS. The local progression rate after singlefraction SRS was less than 10% (95% CI 0%–19.0%).

Multisession Radiosurgery for Optic Nerve Sheath Meningiomas

Neurosurgery 69:1116–1123, 2011 DOI: 10.1227/NEU.0b013e31822932fe
Traditional treatment options for optic nerve sheath meningiomas (ONSMs) include observation, surgery, and radiotherapy, but to date none of these has become the clear treatment of choice.
OBJECTIVE: To evaluate the effectiveness and safety of multisession radiosurgery for ONSMs.
METHODS: From May 2004 to June 2008, 21 patients with ONSMs were treated by radiosurgery using the frameless CyberKnife system. Patient age ranged from 36 to 73 years (mean, 54 years). All patients were treated using multisession radiosurgery, with 5 fractions of 5 Gy each to a total dose of 25 Gy prescribed to the 75% to 85% isodose line. Patients were evaluated for tumor growth control and visual function.
RESULTS: The median pretreatment tumor volume was 2.8 mL (range, 0.3-23 mL). The mean follow-up was 30 months (range, 11-68 months). All patients tolerated treatment well, with only 1 patient in whom a mild optic neuropathy developed (which remitted after systemic steroid therapy). No other acute or late radiation-induced toxicities were observed. No patients showed ONSM progression on follow-up magnetic resonance imaging. Two patients (10%) had a partial response. No patients had worsening of visual function; visual function was stable in 65% and improved in 35% of patients.
CONCLUSION: Multisession radiosurgery for ONSMs was found to be safe and effective. The preliminary results from this study, in terms of growth control, visual function improvement, and toxicity, are quite promising. Further investigations are warranted.

Endocrinologic, neurologic, and visual morbidity after treatment for craniopharyngioma

J Neurooncol (2011) 101:463–476. DOI 10.1007/s11060-010-0265-y

Craniopharyngiomas are locally aggressive tumors which typically are focused in the sellar and suprasellar region near a number of critical neural and vascular structures mediating endocrinologic, behavioral, and visual functions. The present study aims to summarize and compare the published literature regarding morbidity resulting from treatment of craniopharyngioma.

We performed a comprehensive search of the published English language literature to identify studies publishing outcome data of patients undergoing surgery for craniopharyngioma. Comparisons of the rates of endocrine, vascular, neurological, and visual complications were performed using Pearson’s chi-squared test, and covariates of interest were fitted into a multivariate logistic regression model.

In our data set, 540 patients underwent surgical resection of their tumor. 138 patients received biopsy alone followed by some form of radiotherapy. Mean overall follow-up for all patients in these studies was 54 ± 1.8 months. The overall rate of new endocrinopathy for all patients undergoing surgical resection of their mass was 37% (95% CI = 33– 41). Patients receiving GTR had over 2.5 times the rate of developing at least one endocrinopathy compared to patients receiving STR alone or STR + XRT (52 vs. 19 vs. 20%, v2 P<0.00001). On multivariate analysis, GTR conferred a significant increase in the risk of endocrinopathy compared to STR + XRT (OR = 3.45, 95% CI = 2.05–5.81, P<0.00001), after controlling for study size and the presence of significant hypothalamic involvement. There was a statistical trend towards worse visual outcomes in patients receiving XRT after STR compared to GTR or STR alone (GTR = 3.5% vs. STR 2.1% vs. STR + XRT 6.4%, P = 0.11). Given the difficulty in obtaining class 1 data regarding the treatment of this tumor, this study can serve as an estimate of expected outcomes for these patients, and guide decision making until these data are available.

Factors affecting outcome following treatment of patients with cavernous sinus meningiomas

J Neurosurg 113:1087–1092, 2010. (DOI: 10.3171/2010.3.JNS091807)

Although there is a considerable volume of literature available on the treatment of patients with cavernous sinus meningiomas (CSMs), most of the data regarding tumor control and survival come from case studies or single-institution series. The authors performed a meta-analysis of reported tumor control and survival rates of patients described in the published literature, with an emphasis on specific prognostic factors.

Methods. The authors systematically analyzed the published literature and found more than 3000 patients treated for CSMs. Separate meta-analyses were performed to calculate pooled rates of recurrence and cranial neuropathy after 1) gross-total resection, 2) subtotal resection without adjuvant postoperative radiotherapy or radiosurgery, and 3) stereotactic radiosurgery (SRS) alone. Results were expressed as pooled proportions, and random-effects models were used to incorporate any heterogeneity present to generate a pooled proportion. Individual studies were weighted using the inverse variance method, and 95% CIs for each group were calculated from the pooled proportions.

Results. A total of 2065 nonduplicated patients treated for CSM met inclusion criteria for the analysis. Comparisons of the 95% CIs for recurrence of these 3 cohorts revealed that SRS-treated patients experienced improved rates of recurrence (3.2% [95% CI 1.9–4.5%]) compared with either gross-total resection (11.8% [95% CI 7.4–16.1%]) or subtotal resection alone (11.1% [95% CI 6.6–15.7%]) (p < 0.01). The authors found that the pooled mixed-effects rate of cranial neuropathy was markedly higher in patients undergoing resection (59.6% [95% CI 50.3–67.5%]) than for those undergoing SRS alone (25.7% [95% CI 11.5–38.9%]) (p < 0.05).

Conclusions. Radiosurgery provided improved rates of tumor control compared with surgery alone, regardless of the subjective extent of resection.

Treatment of Giant Cerebral Arteriovenous Malformation: Hypofractionated Stereotactic Radiation as the First Stage

Neurosurgery 67:1253–1259, 2010 DOI: 10.1227/NEU.0b013e3181efbaef

Treatment of giant cerebral arteriovenous malformations (AVMs) remains a challenge.

OBJECTIVE: To propose hypofractionated stereotactic radiotherapy (HSRT) as a part of staged treatment, and evaluate its effect by analyzing AVM volume changes.

METHODS: From 2001 to 2007, 20 AVMs larger than 5 cm were treated by HSRT and followed up using magnetic resonance imaging. Patients’ median age was 34 years (8–61 years). Eleven patients presented with hemorrhage and 9 with seizure. Ten patients had previous embolization and radiosurgery had failed in 4. Thirteen AVMs (65%) were classified as Spetzler-Martin grade V and 7 as grade IV. Median pretreatment volume was 46.84 cm3 (12.51-155.38 cm3). Dose was 25 to 30 Gy in 5 to 6 daily fractions. Median follow-up was 32 months.

RESULTS: Median AVM volume decreased to 13.51 cm3 (range, 0.55-147.14 cm3). Residual volume varied from 1.5% to 98%. Volume decreased 44% every year on average. We noted that 6-Gy fractions were more effective (P = .040); embolized AVM tended to respond less (P = .085). After HSRT, we reirradiated 4 AVMs, with 3 amenable to single dose and one with fractions. After HSRT, one patient had an ischemic stroke and one had increased seizure frequency. One AVM bled during follow-up (2.06%/year). No complete obliteration was confirmed.

CONCLUSION: HSRT can turn some giant AVMs manageable for single-dose radiosurgery. Six-Gray fractions were better than 5-Gy and routine embolization seemed unhelpful. There was no increase in bleeding risk with this approach. Future studies with longer follow-up are necessary to confirm our observation.

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.

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.

High-grade intramedullary astrocytomas: 30 years’ experience at the Neurosurgery Department of the University of Rome “Sapienza”

J Neurosurg Spine 12:144–153, 2010. (DOI: 10.3171/2009.6.SPINE08910)

The goal in this study was to review a series of patients who underwent surgical removal of intramedul- lary high-grade gliomas, focusing on the functional outcome, recurrence rates, and technical problems continually debated in neurosurgical practice.

Methods. Between December 1976 and December 2006, 22 patients underwent removal of intramedullary high- grade gliomas. Lesions were located in the cervical spinal cord in 12 patients, and in the thoracic cord in 10.

Results. Histological examinations showed 10 Grade III astrocytomas and 12 glioblastomas. Only 2 of the 22 high-grade astrocytomas could be completely removed. The clinical postoperative status worsened in 14 patients (63.6%), was unchanged in 7 patients (31.8%), and there was 1 case of intraoperative death (4.5%). None of the 22 patients showed improvement in their neurological status postoperatively. In this series, excluding the 1 intraopera- tive death, all patients died of progression of the malignancy.

Conclusions. Surgical treatment did not ameliorate the postoperative neurological status; instead, in the majority of cases, it prompted a worsening of the deficit. Radiotherapy and chemotherapy have a little influence on the length of survival. In this series, multimodality treatment of intramedullary high-grade astrocytomas has been shown to increase length of survival without improving the neurological status.