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.

Proton therapy with a fixed beamline for skull-base chordomas and chondrosarcomas: outcomes and toxicity.

AIM: This study presents an analysis (efficacy and toxicity) of outcomes in patients with skull-base chordomas or chondrosarcomas treated with a fixed horizontal pencil proton beam. BACKGROUND: Chordomas (CAs) and chondrosarcomas (CSAs) are rare tumours that are usually located near the base of the skull and very close to the brain's most critical structures. Proton therapy (PT) is often considered the best radiation treatment for these diseases, but it is still a limited resource. Active scanning PT delivered via a fixed pencil beamline might be a promising option. METHODS: This is a single-centre experience describing the results of proton therapy for 31 patients with CA (n = 23) or CSA (n = 8) located near the base of the skull. Proton therapy was utilized by a fixed pencil beamline with a chair to position the patient between May 2016 and November 2020. Ten patients underwent resection (32.2%), 15 patients (48.4%) underwent R2 resection, and 6 patients had unresectable tumours (19.4%). In 4 cases, the tumours had been previously irradiated. The median PT dose was 70 GyRBE (relative biological efficacy, 1.1) [range, 60 to 74] with 2.0 GyRBE per fraction. The mean GTV volume was 25.6 cm3 [range, 4.2-115.6]. Patient demographics, pathology, treatment parameters, and toxicity were collected and analysed. Radiation-induced reactions were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. RESULTS: The median follow-up time was 21 months [range, 4 to 52]. The median overall survival (OS) was 40 months. The 1- and 2-year OS was 100%, and the 3-year OS was 66.3%. Four patients died due to non-cancer-related reasons, 1 patient died due to tumour progression, and 1 patient died due to treatment-related injuries. The 1-year local control (LC) rate was 100%, the 2-year LC rate was 93.7%, and the 3-year LC rate was 85.3%. Two patients with CSA exhibited progression in the neck lymph nodes and lungs. All patients tolerated PT well without any treatment interruptions. We observed 2 cases of ≥ grade 3 toxicity, with 1 case of grade 3 myelitis and 1 case of grade 5 brainstem injury. CONCLUSION: Treatment with a fixed proton beam shows promising disease control and an acceptable toxicity rate, even the difficult-to-treat subpopulation of patients with skull-base chordomas or chondrosarcomas requiring dose escalation.

Determinants of Survival in Skull Base Osteosarcoma: A National Cancer Database Study.

OBJECTIVE: Skull base osteosarcoma is a rare and aggressive tumor that is most commonly treated with primary surgical resection and adjuvant chemoradiation. Using the National Cancer Database, we analyzed demographic and clinical prognosticators for overall survival (OS). METHODS: The National Cancer Database was queried for cases of histologically confirmed skull base osteosarcoma treated between 2004 and 2015, excluding patients receiving palliation or having <1 month of follow-up. A total of 314 patients treated with surgery alone (n = 82), surgery with adjuvant radiotherapy (n = 35), surgery with chemotherapy (n = 114), or trimodality therapy (n = 56) were identified. The χ2 test for categorical variables, Cox proportional hazards models, and Kaplan-Meier log-rank analysis were used to test associations with treatment, OS, and survival time. RESULTS: None of the studied demographic characteristics (age, sex, race, overall health) and socioeconomic factors (income and average regional education) were associated with OS (none P < 0.05). Treatment modalities also did not show a significant association with OS (none P < 0.05). Certain tumor characteristics showed an association with OS, with fibroblastic and Paget histologic subtypes (each P = 0.003), poorly differentiated tumor grade (P = 0.03), and tumor size >5 cm (P = 0.045) associated with poorer OS. CONCLUSIONS: Tumor histologic subtype, advanced tumor grade, and greater tumor size are predictors of worse OS in skull base osteosarcoma. No significant differences in OS were identified based on treatment modality, which warrants further investigation.

The importance of flaps in reconstruction of locoregionally advanced lateral skull-base cancer defects: a tertiary otorhinolaryngology referral centre experience.

BACKGROUND: The aim of the study was to identify the value of extensive resection and reconstruction with flaps in the treatment of locoregionally advanced lateral skull-base cancer. PATIENTS AND METHODS: The retrospective case review of patients with lateral skull-base cancer treated surgically with curative intent between 2011 and 2019 at a tertiary otorhinolaryngology referral centre was made. RESULTS: Twelve patients with locoregionally advanced cancer were analysed. Lateral temporal bone resection was performed in nine (75.0%), partial parotidectomy in six (50.0%), total parotidectomy in one (8.3%), ipsilateral selective neck dissection in eight (66.7%) and ipsilateral modified radical neck dissection in one patient (8.3%). The defect was reconstructed with anterolateral thigh free flap, radial forearm free flap or pectoralis major myocutaneous flap in two patients (17.0%) each. Mean overall survival was 3.1 years (SD = 2.5) and cancer-free survival rate 100%. At the data collection cut-off, 83% of analysed patients and 100% of patients with flap reconstruction were alive. CONCLUSIONS: Favourable local control in lateral skull-base cancer, which mainly involves temporal bone is achieved with an extensive locoregional resection followed by free or regional flap reconstruction. Universal cancer registry should be considered in centres treating this rare disease to alleviate analysis and multicentric research.

Local Control After Proton Therapy for Pediatric Chordoma.

PURPOSE: Due to the location and high dose required for disease control, pediatric chordomas are theoretically well-suited for treatment with proton therapy, but their low incidence limits the clinical outcome data available in the literature. We sought to report the efficacy and toxicity of proton therapy among a single-institution cohort. METHODS AND MATERIALS: Between 2008 and 2019, 29 patients with a median age of 14.8 years (range, 3.8-21.8) received passive-scattered proton therapy for nonmetastatic chordoma. No patient received prior irradiation. Twenty-four tumors arose in the clivus/cervical spine region and 5 in the lumbosacral spine. Twenty-six tumors demonstrated classic well-differentiated histology and 3 were dedifferentiated or not otherwise specified. Approximately half of the tumors underwent specialized testing: 14 were brachyury-positive and 10 retained INI-1. Three patients had locally recurrent tumors after surgery alone (n = 2) or surgery + chemotherapy (n = 1), and 17 patients had gross disease at the time of radiation. The median radiation dose was 73.8 Gy relative biological effectivness (range, 69-75.6). RESULTS: With a median follow-up of 4.3 years (range, 1.0-10.7), the 5-year estimates of local control, progression-free survival, and overall survival rates were 85%, 82%, and 86%, respectively. No disease progression was observed beyond 3 years. Excluding 3 patients with dedifferentiated/not-otherwise-specified chordoma, the 5-year local control, progression-free survival, and overall survival rates were 92%, 92%, and 91%, respectively. Serious toxicities included 3 patients with hardware failure or related infection requiring revision surgery, 2 patients with hormone deficiency, and 2 patients with Eustachian tube dysfunction causing chronic otitis media. No patient experienced brain stem injury, myelopathy, vision loss, or hearing loss after radiation. CONCLUSIONS: In pediatric patients with chordoma, proton therapy is associated with a low risk of serious toxicity and high efficacy, particularly in well-differentiated tumors. Complete resection may be unnecessary for local control, and destabilizing operations requiring instrumentation may result in additional complications after therapy.

Dosimetric analysis of local failures in skull-base chordoma and chondrosarcoma following pencil beam scanning proton therapy.

BACKGROUND: Despite combined modality treatment involving surgery and radiotherapy, a relevant proportion of skull-base chordoma and chondrosarcoma patients develop a local recurrence (LR). This study aims to analyze patterns of recurrence and correlate LR with a detailed dosimetric analysis. METHODS: 222 patients were treated with proton radiotherapy for chordoma (n = 151) and chondrosarcoma (n = 71) at the PSI between 1998 and 2012. All patients underwent surgery, followed by pencil-beam scanning proton therapy to a mean dose of 72.5 ± 2.2GyRBE. A retrospective patterns of recurrence analysis was performed: LR were contoured on follow-up MRI, registered with planning-imaging and the overlap with initial target structures (GTV, PTVhigh-dose, PTVlow-dose) was calculated. DVH parameters of planning structures and recurrences were calculated and correlated with LR using univariate and multivariate cox regression. RESULTS: After a median follow-up of 50 months, 35 (16%) LR were observed. Follow-up MRI imaging was available for 27 (77%) of these recurring patients. Only one (3.7%) recurrence was located completely outside the initial PTV (surgical pathway recurrence). The mean proportions of LR covered by the initial target structures were 48% (range 0-86%) for the GTV, 70% (range 0-100%) for PTVhigh and 83% (range 0-100%) for PTVlow. In the univariate analysis, the following DVH parameters were significantly associated with LR: GTV(V < 66GyRBE, p = 0.01), GTV(volume, p = 0.02), PTVhigh(max, p = 0.02), PTVhigh(V < 66GyRBE, p = 0.03), PTVhigh(V < 59GyRBE, p = 0.02), PTVhigh(volume, p = 0.01) and GTV(D95, p = 0.05). In the multivariate analysis, only histology (chordoma vs. chondrosarcoma, p = 0.01), PTVhigh(volume, p = 0.05) and GTV(V < 66GyRBE, p = 0.02) were independent prognostic factors for LR. CONCLUSION: This study identified DVH parameters, which are associated with the risk of local recurrence after proton therapy using pencil-beam scanning for patients with skull-base chordoma and chondrosarcoma.

Long-term outcomes in the treatment of pediatric skull base chordomas in the endoscopic endonasal era.

OBJECTIVE: Pediatric skull base chordoma is a rare entity that is traditionally considered to display aggressive behavior with an increased risk of recurrence. There is an absence of literature examining outcomes in the pediatric population in general and using the endoscopic endonasal approach (EEA). METHODS: The authors retrospectively reviewed all patients with skull base chordomas presenting by the age of 18 years to the Children's Hospital of Pittsburgh or the University of Pittsburgh Medical Center from 2004 to 2019. Clinical outcomes, the number and location of recurrences, and progression-free survival time were determined. RESULTS: Twenty patients met the study criteria. The most common presenting complaints were diplopia (n = 7), headache (n = 6), and swallowing difficulty (n = 4). Three cases were incidentally discovered. Twelve patients underwent single-stage EEA alone, 2 patients had two-stage EEA, and 6 patients had combined EEA with open far-lateral or extreme-lateral approaches. Fourteen patients underwent gross-total resection (GTR), and 6 patients had near-total resection. Larger tumors were more likely to require staging or a combined approach (86% vs 7%) and were less likely to receive GTR (33% vs 86%) but had comparable recurrence and mortality rates. Five patients developed CSF leaks requiring reoperation, 2 patients developed a permanent abducens nerve palsy, 1 patient suffered an internal carotid artery injury, 1 patient developed an epidural hematoma, and 1 patient developed a subdural empyema. Four (20%) patients had recurrence during follow-up (mean radiographic follow-up 59 months and mean time to local recurrence 19 months). Two patients with recurrence underwent further resection, and 1 patient elected to stop treatment. Both patients who underwent repeat resection experienced a second recurrence, one of whom elected to stop treatment. Both patients who died had an elevated Ki-67 (p = 0.039), one of whom developed de-differentiated histology. A third patient died of progressive spinal metastases without local recurrence and is one of 2 patients who developed postoperative spinal metastases. Both patients whose tumors became de-differentiated progressed from tumors with an initial Ki-67 of 15 or greater (p = 0.035) and received prior radiotherapy to the bulk tumor (p = 0.03). CONCLUSIONS: The majority of pediatric skull base chordomas, when managed at a specialized center with a goal of GTR, may have a better outcome than traditionally believed. Elevated Ki-67 rates may predict poor outcome and progression to de-differentiation.

Endoscopic endonasal resection and radiotherapy as treatment for skull base chordomas.

BACKGROUND: The role of endonasal endoscopic surgery and radiotherapy in the treatment of skull base chordomas remains unclear. OBJECTIVE: We investigated the effect of endonasal endoscopic surgery and radiotherapy as treatment for skull base chordomas. METHOD: We investigated 46 patients (2006-2018) treated at the Affiliated Eye Ear Nose and Throat Hospital, Fudan University. We documented demographics, clinical presentation, operative resection, complications, postoperative radiotherapy, follow-up time, and survival in all patients. RESULT: Complete tumour resection was performed in 18 (39.1%), subtotal tumour resection in 16 (34.8%), and partial tumour resection in 12 (26.1%) patients. Most common clinical manifestations included nasal obstruction (41%), headaches (30%), and visual impairment (20%). The median duration of progression-free survival (PFS) and overall survival (OS) was 21.5 and 33.5 months, respectively. Primary vs. recurrent disease (p = .043), partial resection (PR) vs. subtotal resection (STR) (p = .006), STR vs. gross total resection (GTR) (p = .020), GTR vs. PR (p = .001), and complicated vs. uncomplicated status (p = .002) were significantly associated with PFS. Primary vs. recurrent disease (p = .002), PR vs. STR (p = .001), GTR vs. PR (p = .001), surgery alone vs. surgery concomitant with radiotherapy (p = .048), and complicated vs. uncomplicated status (p = .017) were significantly associated with OS. CONCLUSION: Surgery is the primary treatment for chordoma; higher tumour resection rates are associated with higher OS and PFS. Surgeons should aim to resect as much tumour as is safely possible. Postoperative radiotherapy is useful adjuvant treatment to improve OS, and IMRT serves as an effective alternative to PBRT.The optimal radiotherapeutic technique is determined by cost, accessibility, availability of the modality, and tumour volume.

The endoscopic endonasal approach for sinonasal and nasopharyngeal adenoid cystic carcinoma.

OBJECTIVE: To determine factors affecting outcomes for patients with sinonasal and nasopharyngeal adenoid cystic carcinoma (SNACC) treated using the endoscopic endonasal approach (EEA) with preservation of key structures followed by adjuvant radiotherapy (RT). METHOD: Retrospective case series of 30 patients treated at the University of Pittsburgh between 2000 and 2014. Hospital records were reviewed for clinical and pathologic data. Outcome measures included overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) rates. RESULTS: The majority of patients had T4a and T4b disease (23.3%, and 63.3%). Microscopically positive margins were present in 21 patients (63.6%). Positive margins were present in nine patients (30.0%). The mean and median follow-up were 3.97 and 3.29 years. Five-year OS, DFS, LRFS, and DMFS were 62.66%, 58.45%, 87.54%, and 65.26%. High-/intermediate-grade tumors had worse DFS (P = .023), and LRFS (P = .026) (HR = 4.837, 95% CI, 1.181-19.812). No factors were associated with significantly worse DMFS. No patient suffered CSF leak, optic nerve, or internal carotid injury. The mean and median length of hospital stay was 4.1 days and 2.0 days (range: 0-32 days). CONCLUSION: Organ-preserving EEA with adjuvant RT for low-grade SNACC offers 5-year survival similar to that reported by other studies, which include radical, open skull base surgery. Patients with high-grade disease do poorly and may benefit from novel treatment strategies. For low-grade disease, organ-preserving EEA with RT may be the best option, offering a balance of survival, quality of life, and decreased morbidity for patients with this difficult-to-cure disease. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1414-1421, 2020.

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.

Surgical Management of Primary Skull Base Osteosarcomas: Impact of Margin Status and Patterns of Relapse.

BACKGROUND: Skull base osteosarcomas are aggressive neoplasms characterized by bony invasion and extracompartmental/extra-osseous soft tissue extension that pose obstacles to achieving complete resection. Management is further complicated by the paucity of data regarding the efficacy of surgery within the treatment paradigm. OBJECTIVE: To identify the impact of margin status on local progression free survival (PFS) and disease specific survival (DSS). METHODS: A retrospective review was performed of 36 patients with osteosarcoma who underwent gross total resection with negative margins (R0), or positive margins (R1). Patient demographics, prior treatments, relapse patterns, and survival were collected. Univariate analysis was performed to determine the impact of margin status on the PFS (primary outcome) and DSS (secondary outcome). RESULTS: R0 resection was achieved in 67%, 25% patients had local recurrence, and 19.4% patients had distant metastasis. In assessing the entire cohort, R0 resections had improved DSS (P = .002) and PFS (P = .04). In chemotherapy-naïve patients, R0 resections also had improved impact on PFS (P = .04) and DSS (P = .027). For radiation-naïve patients, improvements in PFS (P = .026) and DSS (P = .031) were also noted. CONCLUSION: Skull base osteosarcomas present management challenges in which both local and systemic disease progression is the cause of mortality. Achieving R0 resections significantly improves PFS and DSS in treatment-naïve patients within multimodality treatment paradigms. Salvage surgery may benefit in patients after failing previous radiation and chemotherapy treatments. Further work is needed to determine optimal treatment strategies. These data represent the largest series reported to date.

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.

Radiomic signature: A novel magnetic resonance imaging-based prognostic biomarker in patients with skull base chordoma.

BACKGROUND AND PURPOSE: We used radiomic analysis to establish a radiomic signature based on anatomical magnetic resonance imaging (MRI) sequences and explore its effectiveness as a novel prognostic biomarker for skull base chordoma (SBC). MATERIALS AND METHODS: In this retrospective study, radiomic analysis was performed using preoperative axial T1 FLAIR, T2-weighted, and enhanced T1 FLAIR from a single hospital. The primary clinical endpoint was progression-free survival. A total of 1860 3-D radiomic features were extracted from manually segmented region of interest. Pearson correlation coefficient was used for feature dimensional reduction and a ridge regression-based Cox proportional hazards model was used to determine a radiomic signature. Afterwards, radiomic signature and nine other potential prognostic factors, including age, gender, histological subtype, dural invasion, blood supply, adjuvant radiotherapy, extent of resection, preoperative KPS, and postoperative KPS were analyzed to build a radiomic nomogram and a clinical model. Finally, we compared the nomogram with each prognostic factor/model by DeLong's test. RESULTS: A total of 148 SBC patients were enrolled, including 64 with disease progression. The median follow-up time was 52 months (range 4-122 months). The Harrell's concordance index of the radiomic signature was 0.745 (95% CI, 0.709-0.781) for the validation cohort, and its discrimination accuracy in predicting progression risk at 5 years in the same cohort was 82.4% (95% CI, 72.6-89.7%). CONCLUSIONS: The radiomics is a low-cost, non-invasive method to predict SBC prognosis preoperatively. Radiomic signature is a potential prognostic biomarker that may allow the individualized evaluation of patients with SBC.

Surgical approaches for infratemporal fossa tumor resection: Fifteen years' experience of a single center.

BACKGROUND: The aims of this study were to report our center's experience with infratemporal fossa (ITF) tumors, to review the treatment modalities and outcomes. METHODS: Data of patients that underwent resection of ITF tumors in a single tertiary referral medical center were collected and analyzed. RESULTS: Sixty-three patients were included. Sarcoma was the most common pathology (18; 29%). The most common surgical approach was the preauricular-orbitozygomatic approach (24; 38%), followed by endoscopic, craniofacial resection, and combined approaches. Forty-seven patients (75%) required reconstruction, 23 (49%) involving free tissue transfer. Thirty-five patients (76%) with malignant lesions required adjuvant therapy consisting of radiotherapy, chemotherapy, or both. Thirty-three patients suffered from complications related to surgery or adjuvant therapy. The three- and five-years survival rates for malignancy were 82% and 66%, respectively. CONCLUSION: Complete surgical resection of ITF involving tumors is feasible, providing good long-term survival. Multidisciplinary approach is the key for success.

Temporal myofascial segmentation for multilayer reconstruction of middle cranial fossa floor after extradural subtemporal approach to the clival and paraclival region.

BACKGROUND: Skull-base reconstruction represents a concern after resection of middle fossa (MF) tumors by the extradural subtemporal transzygomatic approach (ESTZ). Regional pedicled flaps appear to be the best option. This study describes a technique for temporal myofascial segmentation to harvest a multilayered vascularized flap for MF reconstruction, which might preserve temporal muscle (TM) function and its blood supply. METHODS: The technique to harvest a combined segmented temporal myofascial flap (CSTMF) is described. The flap consists in a temporal fascial (TFF) and a muscle flap (TMF), composed by TM anterior-medial bundle (AMB). RESULTS: CSTMF provides wide coverage of dural lining, through the TFF, and of dead-space, through the TMF. The possibility to tailor TMF according to the need, anatomically preserving the blood supply, enables to significantly increase its volume. CONCLUSION: CSTMF represents an effective option as regional multilayered pedicled flap for MF reconstruction, potentially preserving TM function and minimizing the cosmetic impact.

The clinical outcomes for chordomas in the cranial base and spine: A single center experience.

Owing to the special growth pattern of chordomas and the limited treatment options currently available, the treatment of chordoma still remains difficult. In this study, we hope to further clarify the relationship between surgical treatment and radiotherapy of chordoma and disease progression.All patients with a primary histopathological diagnosis of clival or spinal chordomas recorded in our institution between 1976 and 2017 were examined.A total of 60 patients (location: skull base/clival, n = 24; vertebral column, n = 5; sacrum, n = 31) had a mean follow-up time of 7.7 years (range 12 months-35 years). Compared with patients who received subtotal resection (n = 5, 5-year and 10-year survival = 61% and 39%, respectively), the annual survival rate of patients who received total resection (n = 55, 5-year and 10-year survival = 67%, respectively) was significantly higher. The overall 10-year survival rate (58%) of patients treated with surgery alone was significantly different from those treated with a combination of surgery and radiation (73%). The long-term prognosis of sacral chordoma was the worst (10-year survival rate = 48%).The best treatment strategy for improved long-term survival in chordoma was a combination of surgical resection and radiation therapy. Adjuvant radiotherapy for chordoma significantly improves disease-free survival, although the long-term survival benefit remains to be determined. A worse prognosis and poor long-term survival are seen in sacral chordomas.

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.

Predictive Value of Transforming Growth Factor-α and Ki-67 for the Prognosis of Skull Base Chordoma.

OBJECTIVE: We aimed to characterize the expression of transforming growth factor-α (TGF-α) and Ki-67 and to assess the relationship between TGF-α and Ki-67 expression and prognostic factors in skull base chordoma. METHODS: We retrospectively analyzed the data from 46 patients with skull base chordoma. The follow-up duration ranged from 1 to 168 months (mean, 74.1). The survival data were statistically analyzed using the Kaplan-Meier method and multivariate Cox regression analysis. The expression of TGF-α and Ki-67 were detected by immunohistochemical staining of paraffin-embedded patient tissue specimens. RESULTS: The total resection (TR) group had longer overall survival compared with the non-TR group (P = 0.042). The TR group also had longer progression-free survival (PFS) than did the non-TR group (P = 0.046). The group with a high Ki-67 labeling index (Ki-67LI) had shorter overall survival than did the group with a low Ki-67LI (P = 0.039). Also, the group with a high Ki-67LI had significantly shorter PFS than did the group with a low Ki-67LI (P = 0.016). Moreover, the group with high TGF-α expression had significantly shorter PFS compared with the group with low TGF-α expression (P = 0.005). CONCLUSIONS: Our results have shown that high levels of TGF-α and Ki-67 are associated with shorter PFS in patients with chordoma. We have confirmed the role of Ki-67 as a functional molecular marker of poor prognosis. We also identified TGF-α as a potential novel biomarker for predicting prognosis for patients with skull base chordoma.

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.