The utility of inflammatory biomarkers in predicting overall survival and recurrence in skull base chordoma.

OBJECTIVE: Numerous studies have investigated the impact of inflammatory factors in cancer, yet few attempts have been made to investigate these markers in skull base chordoma (SBC). Inflammatory values including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), systemic immune inflammation index (SII), and systemic inflammation response index (SIRI) can serve as prognostic markers in various cancers. This study aimed to determine whether these inflammatory factors influence overall survival (OS) or progression-free survival (PFS) in patients with primary SBC. METHODS: The electronic medical records of patients with primary SBC who underwent resection from 2001 to 2020 were retrospectively reviewed for the associations of sex, age at diagnosis, preoperative steroid use, tumor volume, extent of resection, adjuvant radiation after surgery, tumor metastasis, Ki-67 index, percent homozygous deletion of 9p23 and percent 1p36 loss, and potential prognostic inflammatory markers of NLR, PLR, LMR, SII, and SIRI with the primary outcome measures of OS and PFS. Maximum log-rank statistical tests were used to determine inflammatory marker thresholds for grouping prior to Kaplan-Meier and Cox proportional hazards analysis for OS and PFS of the elucidated groups. RESULTS: The cohort included 115 primary SBC patients. The mean ± SD tumor volume was 23.0 ± 28.0 cm3, 73% of patients received gross-total resection, 40% received postoperative radiation, 25% had local recurrence, and 6% had subsequent metastatic disease (mean follow-up 47.2 months). Univariable Cox analysis revealed that NLR (p < 0.01), PLR (p = 0.04), LMR (p = 0.04), SII (p < 0.01), and SIRI (p < 0.01) were independently associated with PFS. Additionally, NLR (p = 0.05) and SII (p = 0.03) were significant in multivariable Cox analysis of PFS. However, both univariable and multivariable Cox analysis revealed no correlations with OS. CONCLUSIONS: The routine assessment of inflammatory biomarkers such as NLR and SIRI could have prognostic value in postresection SBC patients.

Outcomes following proton therapy for Ewing sarcoma of the cranium and skull base.

PURPOSE: Despite the dosimetric advantages of proton therapy, little data exist on patients who receive proton therapy for Ewing sarcoma of the cranium and skull base. This study reports local disease control and toxicity in such patients. MATERIALS/METHODS: We reviewed 25 patients (≤21 years old) with nonmetastatic Ewing sarcoma of the cranium and skull base treated between 2008 and 2018. Treatment toxicity was graded per the Common Terminology Criteria for Adverse Events v4.0. The Kaplan-Meier product limit method provided estimates of disease control and survival. RESULTS: Median patient age was 5.9 years (range, 1-21.7). Tumor subsites included the skull base (48%), non-skull-base calvarial bones (28%), paranasal sinuses (20%), and nasal cavity (4%). All patients underwent multiagent alkylator- and anthracycline-based chemotherapy; 16% underwent gross total resection (GTR) before radiation. Clinical target volume (CTV) 1 received 45 GyRBE and CTV2 received 50.4 GyRBE following GTR or 54-55.8 GyRBE following biopsy or subtotal resection. Median follow-up was 3.7 years (range, 0.26-8.3); no patients were lost. The 4-year local control, disease-free survival, and overall survival rates were 96%, 86%, and 92%, respectively. Two patients experienced in-field recurrences. One patient experienced bilateral conductive hearing loss requiring aids, two patients developed intracranial vasculopathy, and 6 patients required hormone replacement therapy for neuroendocrine deficits. None developed a secondary malignancy. CONCLUSION: Proton therapy is associated with a favorable therapeutic ratio in children with large Ewing tumors of the cranium and skull base. Despite its high conformality, we observed excellent local control and no marginal recurrences. Treatment dosimetry predicts limited long-term neurocognitive and neuroendocrine side effects.

Lateral sphenoid wing meningiomas without bone invasion-still skull base surgery?

Sphenoid wing meningiomas are generally considered as skull base meningiomas (SBMs). However, given their surgical similarities with non-skull base meningiomas (NSBMs), we hypothesized that lateral sphenoid wing meningiomas (LSWMs) without bone invasion (BI) should be considered as NSBMs. N = 65 LSWMs without BI operated between 1990 to 2010 at a single-center were compared to N = 352 NSBMs, represented by convexity meningiomas (CMs), and to N = 23 SBMs, represented by spheno-orbital meningiomas (SOMs), with respect to baseline demographics, clinical presentations, Simpson grades, complications, adjuvant therapies, as well as overall survival (OS) and progression-free survival (PFS). Only WHO grade I meningiomas were included. No significant differences in baseline demographics, clinical presentation, or pre-operative KPS were found between the three groups. Simpson grade 1-3 was achieved in 90.1% of LSWMs, 97.1% in CMs (p = 0.05), and 82.6% in SOMs (p = 0.23). There were no significant differences in postoperative infection, hematoma, neurological worsening, 30-day mortality, or OS between the three groups. Lower re-treatment rates were observed in LSWMs and CMs compared to SOMs (p = 0.06). With respect to PFS, there was no significant difference between LSWMs and CMs (89.1% and 88.5% at 5 years, respectively), whereas PFS was significantly higher in LSWMs than in SOMs (79% at 5 years) (p = 0.05). LSWMs without BI should be considered as an intermediate entity between NSBMs and SBMs. LSWMs are similar to SOMs with respect to extent of resection, but more similar to CMs with respect to re-treatment rates and PFS.

Clinicopathological implications of TIM3+ tumor-infiltrating lymphocytes and the miR-455-5p/Galectin-9 axis in skull base chordoma patients.

Chordoma is difficult to eradicate due to high local recurrence rates. The immune microenvironment is closely associated with tumor prognosis; however, its role in skull base chordoma is unknown. The expression of Galectin-9 (Gal9) and tumor-infiltrating lymphocyte (TIL) markers was assessed by immunohistochemistry. Kaplan-Meier and multivariate Cox analyses were used to assessing local recurrence-free survival (LRFS) and overall survival (OS) of patients. MiR-455-5p was identified as a regulator of Gal9 expression. Immunopositivity for Gal9 was associated with tumor invasion (p = 0.019), Karnofsky performance status (KPS) score (p = 0.017), and total TIL count (p < 0.001); downregulation of miR-455-5p was correlated with tumor invasion (p = 0.017) and poor prognosis; and the T-cell immunoglobulin and mucin-domain 3 (TIM3)+ TIL count was associated with chordoma invasion (p = 0.010) and KPS score (p = 0.037). Furthermore, multivariate analysis indicated that only TIM3+ TIL density was an independent prognostic factor for LRFS (p = 0.010) and OS (p = 0.016). These results can be used to predict clinical outcome and provide a basis for immune therapy in skull base chordoma patients.

Chordomas: Histopathological Study in View of Anatomical Location.

BACKGROUND: Chordomas are aggressive bone tumors that have a predilection for the axial skeleton including the skull base and spinal/sacral bones. However, the histopathological and clinical differences between skull base chordoma (SBC) and sacral/spinal chordoma (SC) are unclear as previous studies have been focused on patient prognosis and treatment outcome. This study aimed to evaluate the clinicopathologic features and prognosis of chordoma according to its location. METHODS: Patients with chordomas were enrolled, and the histopathologic features were compared according to the tumor location. RESULTS: A total of 52 patients were enrolled. SBCs had more abundant chondroid matrix and diffuse growth pattern, while SCs had non-chondroid, myxoid matrix and a lobulating pattern, typical of chordoma. Old age and residual tumors were risk factors for shorter overall survival in SBCs. The chondroid matrix was an independent risk factor for shorter disease-free survival in the overall population. CONCLUSION: Chordomas have different histopathologic features depending on the anatomical location.

High control rates of proton- and carbon-ion-beam treatment with intensity-modulated active raster scanning in 101 patients with skull base chondrosarcoma at the Heidelberg Ion Beam Therapy Center.

BACKGROUND: The current study compares the results of irradiation with protons and irradiation with carbon ions via a raster scan technique in patients with G1 and G2 skull base chondrosarcomas. METHODS: Between 2009 and 2014, a total of 101 patients (40 men and 61 women) with a median age of 44 years (range, 19-77 years) were irradiated with carbon ions (79 patients) or protons (22 patients) via a raster scan technique at the Heidelberg Ion Beam Therapy Center. The median total dose was 60 Gy (relative biological effectiveness [RBE]) at 3 Gy per fraction for carbon ions and 70 Gy (RBE) at 2 Gy per fraction for protons. The median boost planning target volume was 38 cm3 (range, 8-133 cm3 ). Overall survival (OS) and local control (LC) were evaluated with the Kaplan-Meier method. RESULTS: The median follow-up period was 40 months (range, 0.8-78.1 months). At the start of the irradiation, all patients had residual macroscopic tumors. Five patients (5%) developed a local recurrence during the follow-up. The 1-, 2-, and 4-year LC rates were 100%, 100%, and 100%, respectively, for protons and 98.6%, 97.2%, and 90.5%, respectively, for carbon ions. The OS rates during the same periods of time were 100%, 100%, and 100%, respectively, for protons and 100%, 98.5%, and 92.9%, respectively, for carbon ions. An age ≤ 44 years was associated with a trend for a better outcome. No toxicity worse than Common Toxicity Criteria grade 3 was observed after treatment. CONCLUSIONS: No significant difference between carbon ions and protons in the therapy of skull base chondrosarcoma could be detected in these initial retrospective results. Cancer 2018;124:2036-44. © 2018 American Cancer Society.

Imatinib and everolimus in patients with progressing advanced chordoma: A phase 2 clinical study.

BACKGROUND: We present the results of an academic phase 2 study on imatinib plus everolimus in patients who have progressive advanced chordoma. METHODS: In January 2011, 43 adult chordoma patients were enrolled in the study and received imatinib 400 mg/day and everolimus 2.5 mg/day until progression or limiting toxicity. Eligible patients had progressed in the 6 months before study entry. PDGFRB, S6, and 4EBP1 expression and phosphorylation were evaluated by way of immunohistochemistry and/or western blotting. The primary endpoint was the overall response rate (ORR) according to Choi criteria. Secondary endpoints were RECIST 1.1 response, progression-free survival (PFS), overall survival (OS), correlation between S6/4EBP1 phosphorylation and response. RESULTS: Thirteen of 43 patients were pretreated with imatinib. Among 40 of the 43 patients who were evaluable by Choi criteria, the best responses were 9 with partial response (ORR, 20.9%), 24 with stable disease (SD) (ORR, 55.8%), and 7 with progressive disease (ORR, 16.3%). Forty-two patients were evaluable by RECIST criteria, with 1 partial response (ORR, 2.3%), 37 stable disease (ORR, 86%), and 4 progressive disease (ORR, 9.3%). The median PFS according to Choi criteria was 11.5 months (range, 4.6-17.6 months), and 58.8% and 48.1% of patients were progression-free at 9 and 12 months, respectively. The median PFS by RECIST criteria was 14 months; the median OS was 47.1 months. When assessable, S6/4EBP1 was phosphorylated in a high and moderate/low proportion of tumor cells in responsive and nonresponsive patients, respectively. Toxicity caused a temporary and definitive treatment discontinuation in 60.5% and 30.2% of patients, respectively. CONCLUSIONS: Imatinib plus everolimus showed a limited activity in progressing advanced chordoma. Interestingly, the amount of tumor cells activated for mammalian target of rapamycin effectors correlated with the response. Toxicity was not negligible.

Cranial nerve outcomes after primary stereotactic radiosurgery for symptomatic skull base meningiomas.

OBJECTIVE: To evaluate cranial nerve (CN) outcomes after primary stereotactic radiosurgery (SRS) for petroclival, cavernous sinus, and cerebellopontine angle meningiomas. METHODS: From our prospectively maintained database of 2022 meningioma patients who underwent Leksell stereotactic radiosurgery (SRS) during a 30-year interval, we found 98 patients with petroclival, 242 with cavernous sinus, and 55 patients with cerebellopontine angle meningiomas. Primary radiosurgery was performed in 245 patients. Patients included in this report had at least one CN deficit at the time of initial presentation and a minimum of 12 month follow up. Median age at the time of SRS was 58 years. Median follow up was 58 months (range 12-300 months), Median tumor volume treated with SRS was 5.9 cm3 (range 0.5-37.5 cm3), and median margin dose was 13 Gy (range 9-20Gy). RESULTS: Tumor control was achieved in 229 patients (93.5%) at a median follow up of 58 months. Progression free survival rate (PFS) after SRS was 98.7% at 1 year, 96.4% at 3 years, 93.7% at 5 years, and 86.4% at 10 years Overall, 114 of the 245 patients (46.5%) reported improvement of CN function. Patients with CP angle meningiomas demonstrated lower rates of CN improvement compared to petroclival and cavernous sinus meningioma patients. Deterioration of CN function after SRS developed in 24 patients (10%). The rate of deterioration was 2.8% at 1 year, 5.2% at 3 years, and 8% at 10 years. CONCLUSION: Primary SRS provides effective tumor control and favorable rate of improvement of preexisting CN deficit.

Effect comparisons among treatment measures on progression-free survival in patients with skull base chordomas: a retrospective study of 234 post-surgical cases.

BACKGROUND: Skull base chordoma (SBC) is a rare and refractory tumor with a high rate of relapse. We aimed to investigate the relationships between different treatment measures and progression-free survival (PFS) outcomes. METHODS: Data from 234 SBC patients from one institution were retrieved from a prospectively maintained database. After grouping, the clinicopathological features and mean estimated PFS times were subject to inter-group and intra-group comparisons, and prognostic factors of PFS were estimated by statistical analyses. Two typical primary patients who suffered from repeated tumor relapses are described. RESULTS: In addition to pathological subtype (p = 0.005), the initial treatment measure for the primary cases (n = 180) was identified as an independent factor of tumor progression (p = 0.002). The patients with gross total resection exhibited the best mean estimated PFS time (109.5 months). Patients with intralesional resection exhibited the shortest PFS time (38.3 months), with an almost significant difference (p = 0.058) compared to those with adjuvant radiotherapy following intralesional resection (56.6 months). For the recurrent group (n = 54), marginal resection (p = 0.007) and adjuvant radiotherapy (p = 0.041) were confirmed as independent protective factors for PFS. The longest mean PFS time (60.3 months) was noted in those patients who received marginal resection followed by adjuvant radiotherapy. CONCLUSIONS: Treatment measures were crucial for post-surgical tumor progression in both primary and recurrent cases. For primary cases, gross total resection and adjuvant radiotherapy offered more PFS benefits to all patients and those who underwent intralesional resection. Marginal resection and adjuvant radiotherapy, which are proposed as a general treatment paradigm for primary tumors, were also equally effective when applied to relapsing tumors.

Clival chordoma: a single-centre outcome analysis.

BACKGROUND: The treatment of clival chordomas remains challenging. Total tumour resection is often impossible without hampering adjacent anatomical structures and causing functional sequelae. On the other hand, chordomas show limited response to non-surgical treatment modalities. Up to now, no well-established interdisciplinary treatment algorithms for clival chordomas exist. In this regard, we analysed the data from all patients that underwent interdisciplinary treatment for clival chordoma in our institution over the last 10 years. METHOD: Retrospective report of all patients treated at the authors' institution from 2005 to 2015. RESULTS: Thirteen patients underwent 24 surgeries, of which 2 (8%) were gross total resections and 22 (92%) incomplete resections. Neurological deterioration, endocrinological disturbances and other surgical complications were observed in six (25%), three (13%) and nine (38%) cases, respectively. Three surgeries (13%) led to an improvement of the initial preoperative neurological condition. All patients were discussed on the interdisciplinary tumour board and all underwent one type of radiotherapy following initial surgery: proton beam in 11 cases (85%) and photon beam in two (15%) cases. In the course of their recurrent disease, three patients (23%) received systemic therapy (imatinib, pazopanib and nivolumab). One patient received a personalised cellular immunotherapy. One patient (8%) was lost to follow-up. Of the remaining 12 patients, four patients (33%) died in the period of analysis; all deaths were chordoma-related. The 5-year cumulative survival rate was 83% (52-97%, CI 95%), 5-year progression-free survival rate was 53% (26-79%, CI 95%). The eight patients (66%) still alive had favourable outcome (KPS, 90 ± 10.7%). SF36 analysis among the survivors revealed 43 points for the Physical Component Summary (12% above, 38% at and 50% below the general population norm) and 47 points for the Mental Component Summary (25% above, 38% at and 38% below). CONCLUSIONS: Our patients show a low rate of gross total resection but an outcome well comparable to other published results. This emphasises the importance of interdispiplinary treatment strategies, with surgery supplying maximal safe resection and avoiding severe neurological deficit, allowing patients to undergo adjusted radiotherapy and other treatment options in a good condition.

Endonasal Endoscopic Resection and Radiotherapy in Skull Base Chordomas.

OBJECTIVES: This study evaluates the impact combined endonasal endoscopic resection and radiotherapy for skull base chordomas. METHODS: Thirty-two patients with skull base chordomas between July 2006 and June 2015 were divided into 2 groups: the surgery alone group and the surgery with radiation therapy group. RESULTS: Gross total resection was achieved in 9 (28.1%) patients with skull base chordoma, subtotal resection was achieved in 16 (50.0%) patients, and partial resection was achieved in 7 (21.9%) patients. The progression-free survival (PFS) rate at 3 and 5 years was 44.0% and 16.5%, respectively. The overall survival (OS) rate at 3 and 5 years was 79.4% and 69.5%, respectively. Kadish staging predicted PFS and OS with statistical significance when the extent of resection was categorized into gross total resection, subtotal resection, and partial resection (P = 0.035 and P = 0.003, respectively). There was a significant OS advantage for the surgery plus radiation group compared with the surgery alone group (P = 0.035). CONCLUSION: Gross total resection can achieve very good results for the treatment of skull base chordomas. Postoperative adjuvant radiation therapy is recommended for all skull base chordomas, as it offered a higher OS rate.

[Sinunasal Tumors]. / Sinunasale Tumoren.

Sinunasal tumors represent a rare and very heterogeneous group of lesions of the nose, sinuses and skull base with a broad spectrum of different biological activities and clinical behavior, which require an individual and primarily surgical treatment strategy. Despite of mild improvement in the overall survival of patients with sinunasal malignancies (SNM) over the last decade, treatment outcome remains stable on a moderate to low level. This analysis brings up the necessity of a more effective local as well as systemic treatment. Especially new concepts in surgery, chemo radiation as well as antibody treatment offer multimodal treatment strategies that may improve quality of life and overall survival in patients with sinunasal tumors.

High control rate in patients with chondrosarcoma of the skull base after carbon ion therapy: first report of long-term results.

BACKGROUND: The current study was performed to evaluate the safety and effectiveness of irradiation with carbon ions using raster scanning as well as prognostic factors in patients with skull base chondrosarcomas. METHODS: Between 1998 and 2008, 79 patients with chondrosarcoma of the skull base were treated using carbon ions in raster scanning. The applied median total dose was 60 gray equivalent (GyE) at 3 GyE per fraction. Local control and overall survival (OS) were evaluated using the Kaplan-Meier method. Long-term toxicity was quantitatively assessed using questionnaires. RESULTS: The median follow-up after irradiation was 91 months (range, 3 months-175 months). Within the follow-up, 10 patients developed local disease recurrence. The 3-year, 5-year, and 10-year local control rates were 95.9%, 88%, and 88%, respectively; the corresponding OS rates were 96.1%, 96.1%, and 78.9%, respectively. With a median follow-up of 110 months after first diagnosis, the corresponding 3-year, 5-year, and 10-year OS rates were 97.5%, 97.5%, and 91.5%, respectively. Age ≤ 45 years and boost volume ≤ 55 mL were associated with significantly better local control rates. We observed a clinically relevant improvement in cranial nerve deficits 7 to 10 years after treatment (range, 45.5%-53.3%) compared with the baseline (73.4%). During follow-up, none of the patients in the current study developed a secondary malignancy. CONCLUSIONS: Carbon ion therapy is a safe and effective treatment in patients with chondrosarcoma of the skull base. For further evaluation, a prospective randomized phase 3 trial comparing protons versus carbon ions has been recruiting patients with low-grade and intermediate-grade chondrosarcoma of the skull base since 2009.

MRI-detected skull-base invasion: prognostic value and therapeutic implication in intensity-modulated radiotherapy treatment for nasopharyngeal carcinoma.

PURPOSE: With advances in imaging and radiotherapy, the prognostic value of skull-base invasion in nasopharyngeal carcinoma (NPC) needs to be reassessed. We aimed to define a classification system and evaluate the prognostic value of the classification of magnetic resonance imaging (MRI)-detected skull-base invasion in NPC treated with intensity-modulated radiotherapy (IMRT). PATIENTS AND MATERIALS: We retrospectively reviewed 749 patients who underwent MRI and were subsequently histologically diagnosed with nondisseminated NPC and treated with IMRT. RESULTS: MRI-detected skull-base invasion was not found to be an independent prognostic factor for overall survival (OS), distant metastasis-free survival (DMFS), local relapse-free survival (LRFS), or disease-free survival (DFS; p > 0.05 for all). Skull-base invasion was classified according to the incidence of each site (type I sites inside pharyngobasilar fascia and clivus vs. type II sites outside pharyngobasilar fascia). The 5-year OS, DMFS, LRFS, and DFS rates in the classification of skull-base invasion in NPC were 83 vs. 67 %, 85 vs.75 %, 95 vs. 88 %, and 76 vs. 62 %, respectively (p < 0.05 for all). Multivariate analysis indicated the classification of skull-base invasion was an independent prognostic factor. CONCLUSION: MRI-detected skull-base invasion is not an independent prognostic factor in patients with NPC treated with IMRT. However, classification according to the site of invasion has prognostic value. Therefore, patients with various subclassifications of stage T3 disease may receive treatment with different intensities; however, further studies are warranted to prove this.

Morbidity in survivors of child and adolescent meningioma.

BACKGROUND: The extent of initial surgical resection has been identified as the strongest prognostic indicator for survival in child and adolescent meningioma. Given the paucity of data concerning long-term outcome, the authors undertook a meta-analysis to analyze morbidity in survivors of this disease. METHODS: Individual patient data were obtained from 19 case series published over the last 23 years through direct communication with the authors. Ordinal logistic regression models were used to assess the influence of risk factors on morbidity. RESULTS: Of 261 patients, 48% reported a completely normal life with no morbidity, and 25% had moderate/severe meningioma-associated morbidity at last follow-up. Multivariate analysis identified relapse as the only independent variable associated with an increased risk of morbidity (odds ratio, 4.02; 95% confidence interval, 2.11-7.65; P ≤ .001). Univariate analysis also revealed an increased risk for patients with neurofibromatosis (odds ratio, 1.90; 95% confidence interval, 1.04-3.48; P = .04). Subgroup analysis identified a higher incidence of morbidity among patients who had intracranial tumors with a skull base location compared with a nonskull base location (P ≤ .001). Timing at which morbidity occurred was available for 70 patients, with persistence of preoperative tumor-related symptoms in 67% and as a result of therapy in 20%. CONCLUSIONS: The majority of survivors of child and adolescent meningioma had no or only mild long-term morbidity, whereas 25% had moderate/severe morbidity, with a significantly increased risk in patients with relapsed disease. In the majority, morbidity occurred as a consequence of the tumor itself, justifying aggressive surgery to achieve gross total resection. However, for patients with neurofibromatosis and skull base meningioma, a more cautious surgical approach should be reserved.

Outcomes and complications of endoscopic approaches for malignancies of the paranasal sinuses and anterior skull base.

OBJECTIVES: Malignant tumors of the paranasal sinuses are traditionally approached by a variety of external incisions. Recent advances in endoscopic endonasal surgery have allowed for some of these tumors to be treated endoscopically. The purpose of this study was to assess the outcomes and complications of the endoscopic approach in a series of patients with paranasal sinus malignancies. METHODS: A retrospective chart review was performed of patients with sinonasal or skull base malignancies treated with endoscopic or endoscopic-assisted resections at a tertiary care institution from 2002 to 2010. Patient data were collected on symptoms, tumor type, operative technique, and postoperative course. Baseline risk factors, overall and disease-free survival data, and surgical outcomes were compared between the two groups. RESULTS: Of the total 49 patients, 36 (73%) underwent an endoscopic approach and 13 (27%) underwent endoscopic-assisted approaches. Sarcomas (9 cases) were the most common tumor type, followed by squamous cell carcinoma (8), adenocarcinoma (8), and melanoma (7). The mean follow-up time for all patients was 3.58 years (range, 1.1 to 8.8 years). Surgical complications were more frequent with open approaches than with endoscopic approaches (23.1% versus 5.6%; p = 0.11). Medical complications were significantly more common with open approaches (38.5% versus 8.3%; p = 0.02). The disease-specific mortality rate was 8% (4 of 49). The local tumor recurrence rate was 16% (8 of 49). The 3-year disease-free survival rates were 86.8% in the endoscopic group and 67.7% in the open group (p = 0.047); however, the patients in the endoscopic group had lower T stages (p = 0.0068) and lower ASA scores (p = 0.03). CONCLUSIONS: Endoscopic approaches to the sinuses and skull base have become progressively more sophisticated with advances in skull base reconstruction, advances in surgical technique, and improvements in technology. This study demonstrates the relative safety and utility of the endoscopic approach for sinonasal and skull base malignancies. In carefully selected patients, endoscopic approaches demonstrate survival rates comparable to those of traditional surgery, and fewer perioperative complications. With appropriate planning and careful surgical decision-making, endoscopic surgery shows promise as a minimally invasive alternative in the treatment of sinonasal malignancies.

[Endoscopic endonasal anterior extended transsphenoidal approach in craniopharyngioma surgery].

The paper describes results of treatment of 56 patients with suprasellar craniopharyngioma (stem, intra-extraventricular) who were operated in Burdenko Neurosurgical Institute using endoscopic endonasal anterior extended transsphenoidal approach. Assessed dynamics of major clinical syndromes (neuro-ophthalmological symptoms, neurological and hormonal status), radicality of surgery, incidence and nature of postoperative complications, postoperative mortality. A comparative analysis of the results obtained in previous studies of our Institute, as well as with those of foreign authors is performed. Obtained data show that endoscopic endonasal anterior extended transsphenoidal approach in craniopharyngioma surgery is an efficient and non-traumatic technique, capable of providing a radical removal of the tumor along with a high quality of life after surgery, and relatively low rates of postoperative complications and mortality.

[Primary and metastatic Ewing sarcoma of the skull base - case reports and comparative analysis].

UNLABELLED: The aim of the present study was to evaluate and compare diagnostic/and treatment modalities of primary and metastatic Ewing sarcoma (ES) of the skull base. MATERIAL AND METHODS: We analyzed nine cases of the skull base ES patients operated in Burdenko Neurosurgical Institute from 2003 to 2011. Among them there were five cases of primary ES, the other four were of metastatic origin. Clinical history, neuroimaging and pathology data together with IHC are presented. Treatment options and results are discussed. Seven patients were operated transcranially, in the other two cases endoscopic endonsnasal operations/were performed. Mean follow up was 11-92 months. RESULTS: We did not reveal arW pathological or IHC differences between primary and metastatic tumors. The labeling index Ki-67 was insignificantly higher in the metastatic tumors gro'Vip. In one case the patient developed relapse of the metastatic tumour in the temporal bone; he underwent second surgery and died 7 months after the operation. CONCLUSION: Despite both metastatic and primary ES of the skull base are of maMignant behavior, the long-term relatively good prognosis can be achieved when combined treatment, including surgery, chemotherapy and radiation is applied.

Chordomas of the skull base and cervical spine: clinical outcomes associated with a multimodal surgical resection combined with proton-beam radiation in 40 patients.

Previous studies of chordoma have focused on either surgery, radiotherapy, or particular tumor locations. This paper reviewed the outcomes of surgery and proton radiotherapy with various tumor locations. Between 2001 and 2008, 40 patients with chordomas of the skull base and cervical spine had surgery at our hospital. Most patients received proton therapy. Their clinical course was reviewed. Age, sex, tumor location, timing of surgery, extent of resection, and chondroid appearance were evaluated in regard to the progression-free survival (PFS) and overall survival (OS). The primary surgery (PS) group was analyzed independently. The extensive resection rate was 42.5%. Permanent neurological morbidity was seen in 3.8%. Radiotherapy was performed in 75% and the mean dose was 68.9 cobalt gray equivalents. The median follow-up was 56.5 months. The 5-year PFS and OS rates were 70% and 83.4%, respectively. Metastasis was seen in 12.5%. The tumor location at the cranio-cervical junction (CCJ) was associated with a lower PFS (P = 0.007). In the PS group, a younger age and the CCJ location were related to a lower PFS (P = 0.008 and P < 0.001, respectively). The CCJ location was also related to a lower OS (P = 0.043) and it was more common in young patients (P = 0.002). Among the survivors, the median of the last Karnofsky Performance Scale score was 80 with 25.7% of patients experiencing an increase and 11.4% experiencing a decrease. Multimodal surgery and proton therapy thus improved the chordoma treatment. The CCJ location and a younger age are risks for disease progression.

Curative treatment for central nervous system medulloepithelioma despite residual disease after resection. Report of two cases treated according to the GPHO Protocol HIT 2000 and review of the literature.

Medulloepithelioma of the central nervous system (CNS) is an uncommon primitive neuroectodermal tumor (PNET) usually occurring in early childhood. It is characterized by highly malignant behavior with a propensity for progression, recurrence, and dissemination despite intensive therapy. Due to its rarity, the optimal management is still unknown. However, gross total resection (GTR) has been considered crucial to achieve cure. In this article, the authors report on 2 cases of CNS medulloepithelioma in which long-term survival (more than 6 years) could be achieved despite evidence of, or suspected postoperative residual disease with an otherwise dismal prognosis.The patients were treated according to different strata of the protocol for primitive neuroectodermal tumors (PNET) of the German-Austrian multicenter trial of the German Society for Pediatric Oncology and Hematology (GPOH) for childhood brain tumors (HIT 2000). Treatment included postoperative hyperfractionated radiotherapy of the craniospinal axis followed by a boost to the tumor site in combination with chemotherapy. A review of the 2 reported and 37 previously published cases confirmed GTR and older age as positive prognostic factors.