Skull Base Tumors

[Proposal] Here, we retrospectively evaluate risk factors for radiation necrosis and local recurrence after PBT for skull base chordoma or chondrosarcoma. [Patients and Methods] We analyzed 101 patients who received PBT for skull base chordomas and chondrosarcomas from January 1989 to February 2021. Multivariable logistic regression models were applied for local recurrence, temporal lobe radiation necrosis rates, and temporal lobe radiation necrosis. [Results] In multivariate analysis, chordoma and large tumor size were independent significant factors for local recurrence. The 1-, 2-, 3-, 4- and 5-year local recurrence rates were 3.9%, 16.9%, 20.3%, 28.5% and 44.0% for chordoma and 0%, 0%, 0%, 0% and 7.1% for chondrosarcoma, respectively. The local recurrence rates of small tumors (<30 mm) were 4.3%, 14.7%, 17.7%, 17.7% and 25.9%, and those for large tumors were 3.6%, 15.1%, 19.2%, 32.7% and 59.6%, respectively. In multivariate analysis, BED Gy₁₀ and total dose were risk factors for radiation necrosis. [Conclusions] For skull base chordoma and chondrosarcoma, the risk factors of local recurrence were chordoma and large tumor size, and those of radiation necrosis were BED Gy₁₀ and total dose, respectively. DVH analysis is needed to investigate the risk factors for brain necrosis in more detail. Full article

Background: Radiation necrosis (RN) is a possible late complication of stereotactic radiosurgery (SRS), but only a few risk factors are known. The aim of this study was to assess tumor location in correlation to the development of radiation necrosis for skull base (SB) and non-skull base tumors. Methods: All patients treated with radiosurgery for benign neoplasms (2004–2020) were retrospectively evaluated. The clinical, imaging and medication data were obtained and the largest axial tumor diameter was determined using MRI scans in T1-weighted imaging with gadolinium. The diagnosis of RN was established using imaging parameters. Patients with tumors located at the skull base were compared to patients with tumors in non-skull base locations. Results: 205 patients could be included. Overall, 157 tumors (76.6%) were located at the SB and compared to 48 (23.4%) non-SB tumors. Among SB tumors, the most common were vestibular schwannomas (125 cases) and meningiomas (21 cases). In total, 32 (15.6%) patients developed RN after a median of 10 (IqR 5–12) months. Moreover, 62 patients (30.2%) had already undergone at least one surgical resection. In multivariate Cox regression, SB tumors showed a significantly lower risk of radiation necrosis with a Hazard Ratio (HR) of 0.252, p < 0.001, independently of the applied radiation dose. Furthermore, higher radiation doses had a significant impact on the occurrence of RN (HR 1.372, p = 0.002). Conclusions: The risk for the development of RN for SB tumors appears to be low but should not be underestimated. No difference was found between recurrent tumors and newly diagnosed tumors, which may support the value of radiosurgical treatment for patients with recurrent SB tumors. Full article

Clival chordomas are rare but aggressive skull base tumors that pose significant treatment challenges and portend dismal prognosis. The aim of this study was to highlight the advantages and limitations of available treatments, to furnish prognostic indicators, and to shed light on novel therapeutic strategies. We conducted a retrospective study of clival chordomas that were surgically treated at our institution from 2003 to 2022; for comparison purposes, we provided a systematic review of published surgical series and, finally, we reviewed the most recent advancements in molecular research. A total of 42 patients underwent 85 surgeries; median follow-up was 15.8 years, overall survival rate was 49.9% at 10 years; meanwhile, progression-free survival was 26.6% at 10 years. A significantly improved survival was observed in younger patients (<50 years), in tumors with Ki67 ≤ 5% and when adjuvant radiotherapy was performed. To conclude, clival chordomas are aggressive tumors in which surgery and radiotherapy play a fundamental role while molecular targeted drugs still have an ancillary position. Recognizing risk factors for recurrence and performing a molecular characterization of more aggressive lesions may be the key to future effective treatment. Full article

Background: The transorbital approaches (TOAs) have acquired growing notoriety, thanks to their ability to offer alternative corridors to the skull base. However, the limited access and the unfamiliarity with this surgical perspective make recognition of key landmarks difficult, especially for less experienced surgeons. The study wants to offer a detailed description of the anatomy to comprehend the potential and limitations of TOAs. Methods: Measurements of the orbit region and the surrounding areas were performed on two hundred high-resolution CT scans and thirty-nine dry skulls. Five specimens were dissected to illustrate the TOA, and one was used to perform the extradural clinoidectomy. Three clinical cases highlighted the surgical applications. Results: A step-by-step description of the key steps of the TOA was proposed and a comparison with the transcranial anterior clinoidectomy was discussed. The mean work distance was 6.1 ± 0.4 cm, and the lateral working angle increased 20 ± 5.4° after removing the lateral orbital rim. Conclusions: TOAs are indicated in selected cases when tumor involves the lateral portion of the cavernous sinus or the middle skull base, obtaining a direct decompression of the optic nerve and avoiding excessive manipulation of the neurovascular structures. Comprehension of surgical anatomy of the orbit and its surrounding structures is essential to safely perform these approaches. Full article

Background: Skull base chordomas are radio-resistant tumors that require high-dose, high-precision radiotherapy, as can be delivered by particle therapy (protons and carbon ions). We performed a first clinical outcome analysis of particle therapy based on the initial 4-years of operation. Methods: Between August 2017 and October 2021, 44 patients were treated with proton (89%) or carbon ion therapy (11%). Prior gross total resection had been performed in 21% of lesions, subtotal resection in 57%, biopsy in 12% and decompression in 10%. The average prescription dose was 75.2 Gy RBE in 37 fractions for protons and 66 Gy RBE in 22 fractions for carbon ions. Results: At a median follow-up of 34.3 months (range: 1–55), 2-, and 3-year actuarial local control rates were 95.5% and 90.9%, respectively. The 2-, and 3-year overall and progression-free survival rates were 97.7%, 93.2%, 95.5% and 90.9%, respectively. The tumor volume at the time of particle therapy was highly predictive of local failure (p < 0.01), and currently, there is 100% local control in patients with tumors < 49 cc. No grade ≥3 toxicities were observed. There was no significant difference in outcome or side effect profile seen for proton versus carbon ion therapy. Five patients (11.4%) experienced transient grade ≤2 radiation-induced brain changes. Conclusions: The first analysis suggests the safety and efficacy of proton and carbon ion therapy at our center. The excellent control of small to mid-size chordomas underlines the effectiveness of particle therapy and importance of upfront maximum debulking of large lesions. Full article

Introduction: Esthesioneuroblastoma (ENB) is a rare malignant neoplasm arising from the olfactory epithelium of the cribriform plate. Although survival is excellent with a reported 5-year overall survival (OS) of 82%, recurrence is frequent and occurs in 40–50% of cases. This study investigates the characteristics of ENB recurrence and the subsequent prognosis of patients with recurrence. Methods: The clinical records of all patients diagnosed as having ENB with subsequent recurrence at a tertiary hospital from 1 January 1960 to 1 January 2020 were retrospectively reviewed. Overall survival (OS) and progression-free survival (PFS) were reported. Results: A total of 64 out of 143 ENB patients had recurrences. In total, 45 out of 64 recurrences met the inclusion criteria and were included in this study. From these, 10 (22%) had a sinonasal recurrence, 14 (31%) had an intracranial recurrence, 15 (33%) had a regional recurrence, and 6 (13%) had a distal recurrence. The average interval from initial treatment to recurrence was 4.74 years. There were no differences in rates of recurrence with respect to age, sex, or types of surgery (endoscopic, transcranial, lateral rhinotomy, and combined). The time to recurrence was shorter for Hyams grades 3 and 4 compared to Hyams grades 1 and 2 (3.75 years vs. 5.70 years, p < 0.05). Patients with recurrence limited to the sinonasal region had a lower overall primary Kadish stage compared to recurrences beyond the sinonasal region (2.60 vs. 3.03, p < 0.05). A total of 9 (20%) out of 45 patients developed secondary recurrence. Following recurrence, the subsequent 5-year OS and PFS were 63 and 56%, respectively. The mean time to secondary recurrence after treatment of the primary recurrence was 32 months, which was significantly shorter than the time to primary recurrence (32 months vs. 57 months, p = 0.048). The mean age of the secondary recurrence group is significantly older than the primary recurrence group (59.78 years vs. 50.31 years, p = 0.02). No statistically significant differences were observed between the secondary recurrence group and the recurrence group in terms of their overall Kadish stages or Hyams grades. Conclusions: Following an ENB recurrence, salvage therapy appears to be an effective therapeutic option with a subsequent 5-year OS of 63%. However, subsequent recurrences are not infrequent and may require additional therapy. Full article

(1) Background: Transient increase in volume of vestibular schwannomas (VS) after stereotactic radiosurgery (SRS) is common and complicates differentiation between treatment-related changes (pseudoprogression, PP) and tumor recurrence (progressive disease, PD). (2) Methods: Patients with unilateral VS (n = 63) underwent single fraction robotic-guided SRS. Volume changes were classified according to existing RANO criteria. A new response type, PP, with a >20% transient increase in volume was defined and divided into early (within the first 12 months) and late (>12 months) occurrence. (3) Results: The median age was 56 (range: 20–82) years, the median initial tumor volume was 1.5 (range: 0.1–8.6) cm³. The median radiological and clinical follow-up time was 66 (range: 24–103) months. Partial response was observed in 36% (n = 23), stable disease in 35% (n = 22) and PP in 29% (n = 18) of patients. The latter occurred early (16%, n = 10) or late (13%, n = 8). Using these criteria, no case of PD was observed. (4) Conclusion: Any volume increase after SRS for vs. assumed to be PD turned out to be early or late PP. Therefore, we propose modifying RANO criteria for SRS of VS, which may affect the management of vs. during follow-up in favor of further observation. Full article

We characterized the clinical and sociodemographic factors predictive of surgery refusal in pituitary adenoma (PA) patients. We queried the National Cancer Database (NCDB) to identify adult PA patients treated from 2004–2015 receiving or refusing surgery. Multivariate logistic regression and Cox proportional-hazards analysis identified clinical and/or sociodemographic factors predictive of surgery refusal or mortality, respectively. Of the 34,226 patients identified, 280 (0.8%) refused surgery. On multivariate logistic regression, age > 65 (OR: 2.64; p < 0.001), African American race (OR: 1.70; p < 0.001), Charlson-Deyo Comorbidity (C/D) Index > 2 (OR: 1.52; p = 0.047), and government insurance (OR: 2.03; p < 0.001) or being uninsured (OR: 2.16; p = 0.03) were all significantly associated with surgery refusal. On multivariate cox-proportional hazard analysis, age > 65 (HR: 2.66; p < 0.001), tumor size > 2 cm (HR: 1.30; p < 0.001), C/D index > 1 (HR: 1.53; p < 0.001), having government insurance (HR: 1.66; p < 0.001) or being uninsured (HR: 1.67; p < 0.001), and surgery refusal (HR: 2.28; p < 0.001) were all significant predictors of increased mortality. Macroadenoma patients receiving surgery had a significant increase in overall survival (OS) compared to those who refused surgery (p < 0.001). There are significant sociodemographic factors that influence surgery refusal in PA patients. An individualized approach is warranted that considers functional status, clinical presentations, and patient choice. Full article

The management of clival chordoma in our group shifted around 2013 to mostly endoscopic, and proton beam was introduced for our multidisciplinary team. Consecutive patients who had surgical resection from 1987 to 2021 were reviewed. A total of 58 patients (39 patients after 2013) were analyzed. The mean tumor size was 3.7 cm, and the most common location was the upper clivus (43%). Compared to before 2013, after 2013, the endoscopic endonasal approach was more common (90%, p < 0.001), and more gross or near total resections (64%, p = 0.002) were attained. Ten cases (17%) were revision surgeries referred from elsewhere, and three cases (5%) underwent additional surgery elsewhere before adjuvant radiation. The postoperative cerebrospinal fluid leak occurred in 7%. Post-operative new cranial nerve deficits occurred in 32% before 2013, compared to 2.6% after 2013 (p = 0.004). For cases before 2013, 10 patients (53%) recurred during the median follow-up of 144 months (mean, 142 months), whereas for cases after 2013, seven patients (18%) recurred with a median follow-up of 35 months (mean, 42 months). 5-year progression-free survival was 58%, and 5-year overall survival was 87%. A specialized multidisciplinary team improved the resection rate compared to a historical cohort with an excellent morbidity profile. Full article

Sinonasal squamous cell carcinoma (SNSCC) and sinonasal undifferentiated carcinoma (SNUC) are two of the most common, high-grade malignancies of the sinonasal cavity. The standard of care for resectable lesions per the National Comprehensive Cancer Network (NCCN) guidelines includes surgical resection with negative margins plus adjuvant radiation therapy. However, surgery for locally advanced disease with both orbital and intracranial involvement is associated with significant morbidity and poor overall survival. Over the last decade, induction chemotherapy (IC) has emerged as part of a multimodal treatment strategy to optimize locoregional disease control and minimize substantial surgical morbidity such as orbital exenteration without compromising rates of overall survival. The response to IC both guides additional therapy and helps prognosticate a patient’s disease. This narrative review examines the data surrounding the management of patients with SNSCC and SNUC. The pros and cons of upfront surgical management plus adjuvant therapy will be explored, and the case for IC will be presented. The IC-specific regimens and treatment paradigms for SNSCC and SNUC will each be explored in detail. Organ preservation, treatment morbidity, and survival data will be presented, and evidence-based recommendations will be presented for the management of these patients. Full article

The anterior cranial fossa (ACF) is a complex anatomical region that can be affected by a broad spectrum of pathology. For the surgical treatment of these lesions, many approaches have been described, each of them with different scope and potential surgical complications, often associated with significant morbidity. Traditionally, tumors involving the ACF have been operated by transcranial approaches; however, in the last two decades, endoscopic endonasal approaches (EEAs) have been gaining popularity. In this work, the authors review and describe the anatomical aspects of the ACF and the technical nuances of transcranial and endoscopic approaches for tumors located in this region. Four approaches were performed in embalmed cadaveric specimens and the key steps were documented. Four illustrative cases of ACF tumors were selected to demonstrate the clinical application of anatomical and technical knowledge, which are essential in the preoperative decision-making process. Full article

Considering quality of life (QOL) is critical when discussing treatment options for patients undergoing endoscopic endonasal skull base surgery (EESBS) for cancers at the base of the skull. Several questionnaires have been developed and validated in the last 20 years to explore QOL in this patient population, including the Anterior Skull Base Questionnaire, Skull Base Inventory, EESBS Questionnaire, and the Sino-Nasal Outcome Test for Neurosurgery. The Sino-Nasal Outcomes Test-22 and Anterior Skull Base Nasal Inventory-12 are other tools that have been used to measure sinonasal QOL in anterior cranial base surgery. In addition to pathology-related perturbations in QOL endoscopic surgical options (transsellar approaches, anterior cranial base surgery, and various reconstructive techniques) all have unique morbidities and QOL implications that should be considered. Finally, we look ahead to new and emerging techniques and tools aimed to help preserve and improve QOL for patients with anterior cranial base malignancies. Full article

Background: The outcomes of orbital exenteration (OE) in patients with craniofacial lesions (CFLs) remain unclear. The present review summarizes the available literature on the clinical outcomes of OE, including surgical outcomes and overall survival (OS). Methods: Relevant articles were retrieved from Medline, Scopus, and Cochrane according to PRISMA guidelines. A systematic review and meta-analysis were conducted on the clinical characteristics, management, and outcomes. Results: A total of 33 articles containing 957 patients who underwent OE for CFLs were included (weighted mean age: 64.3 years [95% CI: 59.9–68.7]; 58.3% were male). The most common lesion was squamous cell carcinoma (31.8%), and the most common symptom was disturbed vision/reduced visual acuity (22.5%). Of the patients, 302 (31.6%) had total OE, 248 (26.0%) had extended OE, and 87 (9.0%) had subtotal OE. Free flaps (33.3%), endosseous implants (22.8%), and split-thickness skin grafts (17.2%) were the most used reconstructive methods. Sino-orbital or sino-nasal fistula (22.6%), flap or graft failure (16.9%), and hyperostosis (13%) were the most reported complications. Regarding tumor recurrences, 38.6% were local, 32.3% were distant, and 6.7% were regional. The perineural invasion rate was 17.4%, while the lymphovascular invasion rate was 5.0%. Over a weighted mean follow-up period of 23.6 months (95% CI: 13.8–33.4), a weighted overall mortality rate of 39% (95% CI: 28–50%) was observed. The 5-year OS rate was 50% (median: 61 months [95% CI: 46–83]). The OS multivariable analysis did not show any significant findings. Conclusions: Although OE is a disfiguring procedure with devastating outcomes, it is a viable option for carefully selected patients with advanced CFLs. A patient-tailored approach based on tumor pathology, extension, and overall patient condition is warranted. Full article

Background: Infratemporal fossa (ITF) tumors represent various pathologies and are seldom described in the literature, reflecting their rarity. Here we review the literature on tumors invading ITF and describe patient characteristics, treatment strategies, and clinical outcomes. Methods: Relevant articles were retrieved from PubMed, Scopus, and Cochrane. A systematic review and meta-analysis were conducted on the clinical presentation, treatment protocols, and clinical outcomes. Result: A total of 27 articles containing 106 patients with ITF tumors (median tumor size: 24.3 cm³ [interquartile range, 15.2–42 cm³]) were included (median age: 46 years [interquartile range, 32–55 years]; 59.4% were males]). Of the confirmed tumor pathology data, schwannomas (n = 24; 26.1%) and meningiomas (n = 13; 14.1%) were the most common tumors. Facial hypoesthesia (n = 22; 18.5%), auricular/preauricular pain (n = 20; 16.8%), and headaches (n = 11; 9.2%) were the most common presenting symptoms. Of patients who had surgical resection (n = 97; 95.1%), 70 (73.7%) had transcranial surgery (TCS) and 25 (26.3%) had endoscopic endonasal surgery (EES). Among available details on the extent of resection (n = 84), gross-total resection (GTR) was achieved in 62 (73.8%), and 5 (6.0%) had biopsy only. Thirty-five (33.0%) patients had postoperative complications. Among cases with available data on reconstruction techniques (n = 8), four (50%) had adipofascial antero-lateral thigh flap, three (37.5%) had latissimus dorsi free flap, and one (12.5%) had antero-lateral thigh flap. Fourteen (13.2%) patients had adjuvant chemotherapy, and sixteen (15.1%) had adjuvant radiotherapy. During a median follow-up time of 28 months (IQR, 12.25–45.75 months), 15 (14.2%) patients had recurrences, and 18 (17.0%) patients died. The median overall survival (OS) time was 36 months (95% confidence interval: 29–41 months), and the 5-year progression-free survival (PFS) rate was 61%. Conclusion: Various tumor types with different biological characteristics invade the ITF. The present study describes patient demographics, clinical presentation, management, and outcomes. Depending on the tumor type and patient condition, patient-tailored management is recommended to optimize treatment outcomes. Full article