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OBJECTIVE Infratemporal fossa (ITF) tumors are unique in histological characteristics and difficult to treat. Predictors of patient outcomes in this context are not known. The objective of this study was to identify independent predictors of outcome and to characterize patterns of failure in patients with ITF carcinoma. METHODS All patients who had been surgically treated for anterolateral skull base malignancy between 1999 and 2017 at the authors’ institution were retrospectively reviewed. Patient demographics, preoperative performance status, tumor stage, tumor characteristics, treatment modalities, and pathological data were collected. Primary outcomes were disease-specific survival (DSS) and local progression-free survival (LPFS) rates. Overall survival (OS) and patterns of progression were secondary outcomes. RESULTS Forty ITF malignancies with skull base involvement were classified as carcinoma. Negative margins were achieved in 23 patients (58%). Median DSS and LPFS were 32 and 12 months, respectively. Five-year DSS and OS rates were 55% and 36%, respectively. The 5-year LPFS rate was 69%. The 5-year overall PFS rate was 53%. Disease recurrence was noted in 28% of patients. Age, preoperative performance status, and margin status were statistically significant prognostic factors for DSS. Lower preoperative performance status and positive surgical margins increased the probability of local recurrence. CONCLUSIONS The ability to achieve negative margins was significantly associated with improved tumor control rates and DSS. Cranial base surgical approaches must be considered in multimodal treatment regimens for anterolateral skull base carcinomas.

BACKGROUND Orbital exenteration (OE) is an ablative procedure used in the management of malignancies of the orbit of either primary or secondary origin. Publications evaluating this procedure have suffered from small patient numbers, heterogeneity of pathologies, and poor patient follow-up. The purpose of this study was to assess patient outcomes in a large cohort of patients undergoing OE at a tertiary cancer center. METHODS A retrospective review was conducted of 180 consecutive patients who underwent OE at the authors' institution. Overall survival (OS) was the primary end point measured in the study. Time to locoregional recurrence (progression-free survival [PFS]) and disease-free survival were secondary end points. RESULTS Between the years 1993 and 2011, 180 consecutive patients received OE for craniofacial malignancy at the authors' institution. The median follow-up for the cohort was 9.7 years (116 months). The median OS was 73 months, and the median PFS was 96 months. The presence of perineural invasion was associated with shorter OS (P = .01) and PFS (P < .01). Magnetic resonance imaging was predictive of perineural invasion (P < .01). Positive margins were associated with shorter PFS than negative margins (P < .01) but with no change in OS (P = .15). The overall complication rate was 15%. The major complication rate (Clavien-Dindo 3b or greater) was 2.8% (n = 5), and there was 1 death observed (0.6%). CONCLUSIONS Used judiciously in the setting of a multidisciplinary management plan, OE for tumor control is a safe therapy. LAY SUMMARY Between the years 1993 and 2011, 180 consecutive patients received orbital exenteration for craniofacial malignancy at the MD Anderson Cancer Center. The median follow-up for the cohort was 9.7 years. The presence of perineural invasion was associated with shorter overall survival (P = .01) and progression-free survival (P < .01). Magnetic resonance imaging was predictive of perineural invasion (P < .01). Positive margins were associated with shorter progression-free survival than negative margins (P < .01). The overall complication rate was 15%. The major complication rate (Clavien-Dindo 3b or greater) was 2.8% (n = 5).

Objective To evaluate the rate of incidental detection of central nervous system (CNS) meningioma in patients undergoing 18F-fluciclovine PET/computed tomography (CT) imaging for the evaluation of prostate cancer. Methods The reports of 850 18F-fluciclovine PET/CT scans in 566 patients with pathologically proven prostate cancer performed from April 2017 to July 2019, were retrospectively reviewed for the presence of CNS meningioma. Results A total of 14 patients (2.8%) (age range: 54-82 years old) had abnormal focal intracranial 18F-fluciclovine uptake, all extra-axial in location (SUVmax range: 3.2-19.3). Two cases out of 14 (0.35%) were diagnosed as metastatic lesions. Twelve out of the 14 patients, had 18F-fluciclovine PET/CT imaging findings suspicious for CNS meningioma, 2 of them received another diagnosis on further imaging, and only 10 cases (2%) had the diagnosis of meningioma according to follow-up MRI and 18F-fluciclovine PET/CT. Conclusion Focal 18F-fluciclovine avid intracranial lesions incidentally detected in patients undergoing PET/CT imaging for prostate cancer are most often CNS meningiomas.

Background Squamous cell carcinoma is the most common type of sinonasal malignancy. Despite improvements in surgical resection and adjuvant therapy, which are considered the standard of care, the outcome for patients with locoregionally advanced disease remains poor. The objective of this study was to investigate the role of induction chemotherapy in patients with locoregionally advanced sinonasal squamous cell carcinoma and to determine the oncologic outcomes in those patients. Methods The study included 123 consecutive patients with previously untreated, locoregionally advanced (stage III and IV) sinonasal squamous cell carcinoma who were treated with curative intent at The University of Texas MD Anderson Cancer Center between 1988 and 2017 with induction chemotherapy followed by definitive local therapy. Patient demographics, tumor staging, treatment details, and oncologic outcomes were reviewed. The outcomes of this study included response to induction chemotherapy, recurrence, organ preservation, and survival. Results The median follow-up was 32.6 months (range, 12.4-240 months). Of the 123 patients, 110 (89%) had T4 disease, and 13 (11%) had T3 disease. Lymph node metastasis at the time of presentation was observed in 36 patients (29.3%). The overall stage was stage IV in 111 patients (90.2%) and stage III in 12 patients (9.8%). The chemotherapy regimen consisted of the combination of a platinum and taxanes in most cases (109 patients; 88.6%), either as a doublet (41 patients) or in combination with a third agent, such as 5-fluorouracil (34 patients), ifosfamide (26 patients), or cetuximab (8 patients). After induction chemotherapy, 71 patients (57.8%) achieved at least a partial response, and 6 patients had a complete response. Subsequent treatment after induction chemotherapy was either: 1) definitive chemoradiation or radiation followed by surgical salvage for any residual disease, or 2) surgery followed by adjuvant radiation or chemoradiation. Overall, 54 patients (49.5%) underwent surgical resection. The 2-year overall and disease-free survival rates for the whole cohort were 61.4% and 67.9%, respectively. The rate of orbital preservation was 81.5%. The recurrence rate was 26.8% (33 patients), and distant metastases occurred in 8 patients (6.5%). Patients who had at least a partial response or stable disease had significantly better overall and disease-free survival than those who had progressive disease (P = .028 and P = .021, respectively). Conclusions The current results indicate that a high proportion of patients with sinonasal squamous cell carcinoma achieved a favorable response to induction chemotherapy. The data suggest that response to induction chemotherapy is associated with an improved outcome and a good chance of organ preservation. The oncologic outcomes in this cohort with locally advanced (mostly T4) disease are better than those historically reported in the literature. Further study of induction chemotherapy in patients with advanced sinonasal squamous carcinoma is warranted.

Background Chordomas are aggressive bone tumors that often recur despite maximal resection and adjuvant radiation. To date there are no Food and Drug Administration (FDA)-approved chemotherapies. Computational drug repositioning is an expanding approach to identify pharmacotherapies for clinical trials. Objective To identify FDA-approved compounds for repurposing in chordoma. Methods Previously identified highly differentially expressed genes from chordoma tissue samples at our institution were compared with pharmacogenomic interactions in the Comparative Toxicogenomics Database (CTD) using ksRepo, a drug-repositioning platform. Compounds selected by ksRepo were then validated in CH22 and UM-Chor1 human chordoma cells in Vitro. Results A total of 13 chemical compounds were identified in silico from the CTD, and 6 were selected for preclinical validation in human chordoma cell lines based on their clinical relevance. Of these, 3 identified drugs are FDA-approved chemotherapies for other malignancies (cisplatin, cytarabine, and lucanthone). Cytarabine, a deoxyribonucleic acid polymerase inhibitor approved for the treatment of various leukemias, exhibited a significant concentration-dependent effect against CH22 and UM-Chor1 cells when compared to positive (THZ1) and negative (venetoclax) controls. Tretinoin exhibited a significant concentration-dependent cytotoxic effect in CH22, sacral chordoma-derived cell lines but to a much lesser extent in UM-Chor1, a cell line derived from skull base chordoma. Conclusion Cytarabine administration reduces the viability of human chordoma cells. The equally effective reduction in viability seen with tretinoin seems to be cell line dependent. Based on our findings, we recommend the evaluation of cytarabine and tretinoin in an expanded set of human chordoma cell lines and animal models.

Sinonasal tumors that harbor neuroendocrine histologic features include olfactory neuroblastoma (previously known as esthesioneuroblastoma), sinonasal neuroendocrine carcinoma, and sinonasal undifferentiated carcinoma. These tumors represent a diverse spectrum of clinical behavior and as such require histology-specific management. Herein, we review the management of these sinonasal tumors with neuroendocrine features and discuss fundamentals of multi-modality care for each histology. An emphasis is placed on olfactory neuroblastomas, given their relative frequency and skullbase origin. A comprehensive literature review on contemporary management of olfactory neuroblastoma, sinonasal neuroendocrine carcinoma, and sinonasal undifferentiated carcinoma was performed. Management of sinonasal tumors with neuroendocrine features can include surgical resection, radiation therapy, and/or chemotherapy. Due to their site of origin, these tumors can frequently involve the skullbase, which can require site-specific care. The optimal treatment modalities and the sequence in which they are performed are largely dependent on histology. In most cases, olfactory neuroblastoma is best managed with surgical resection followed by radiation therapy. Sinonasal neuroendocrine carcinomas represent a variety of histologic phenotypes (carcinoid, atypical carcinoid, small cell, and large cell), which determine the optimal treatment modality. Finally, sinonasal undifferentiated carcinoma is likely best managed by induction chemotherapy with subsequent therapy dictated by the initial response. A team approach to multi-modality care is essential in the treatment of olfactory neuroblastoma, sinonasal neuroendocrine carcinoma, and sinonasal undifferentiated carcinoma. Early biopsy, histologic diagnosis, and comprehensive imaging are critical to determining the appropriate management paradigm.

Skull base primary malignancies represent a heterogeneous group of histologic diagnoses and sarcomas of the skull base are specific malignant tumors that arise from mesenchymal cells and can be classified by site of origin into bony and soft tissue sarcomas. The most common bony sarcomas include: chondrosarcoma, osteosarcoma, chordoma, Ewing's sarcoma. Given the relative rarity of each histologic diagnosis, especially in the skull base, there is limited published data to guide the management of patients with skull base sarcomas. An electronic search of the literature was performed to obtain key publications in the management of bony sarcomas of the skull base published within the last decade. This article is thus a review of the multi-disciplinary management principles of primary bony sarcomas of the skull base. Of note, there have been several recent advancements in the realm of skull base sarcoma management that have resulted in improved survival. These include advances in: imaging and diagnostic techniques, surgical techniques that incorporate oncologic surgical principles, conformal radiation paradigms and targeted systemic therapies. Early access to coordinated multi-disciplinary subspecialty care immediately at suspicion of diagnosis has further improved outcomes. There are several ongoing trials in the realms of radiation therapy and systemic therapy that will hopefully provide further insight about the optimal management of bony sarcomas of the skull base.

Chondrosarcomas of the skull base are malignant tumors for which surgery is the primary therapeutic option. Gross-total resection has been demonstrated to improve survival in patients with these tumors. Chondrosarcomas arising from the petroclival synchondrosis harbor particularly unique anatomical considerations that have long been a barrier to achieving such a resection. Endoscopic endonasal transpterygoid approaches have been recently used to gain improved access to such lesions; however, these approaches have classically relied on a medial to lateral transclival trajectory, which provides limited exposure for complete resection of lateral disease. In this paper the authors describe an endoscopic endonasal transpterygoid transnasopharyngeal approach that provides comprehensive access to the petroclival region through dissection of the eustachian tube with resection of the cartilaginous torus tubarius. Of note, the authors have previously demonstrated the superior outcomes and validity of this approach relative to other cranial base techniques for petroclival chondrosarcomas. Surgical outcomes in 5 cases of chondrosarcoma without medial extension are detailed. Gross-total resection was achieved in 4 of 5 patients. Postoperative complications included transient palatal numbness in all patients and eustachian tube dysfunction due to the approach. With tympanostomy tube placement, no patient had persistent hearing loss. Overall, this approach appears to be a safe and effective technique for resection of petroclival chondrosarcomas.

OBJECTIVEThe objective of this study was to assess outcomes after Gamma Knife radiosurgery (GKRS) re-irradiation for palliation of patients with trigeminal pain secondary to recurrent malignant skull base tumors.METHODSFrom 2009 to 2016, 26 patients who had previously undergone radiation treatment to the head and neck received GKRS for palliation of trigeminal neuropathic pain secondary to recurrence of malignant skull base tumors. Twenty-two patients received single-fraction GKRS to a median dose of 17 Gy (range 15–20 Gy) prescribed to the 50% isodose line (range 43%–55%). Four patients received fractionated Gamma Knife Extend therapy to a median dose of 24 Gy in 3 fractions (range 21–27 Gy) prescribed to the 50% isodose line (range 45%–50%). Those with at least a 3-month follow-up were assessed for symptom palliation. Self-reported pain was evaluated by the numeric rating scale (NRS) and MD Anderson Symptom Inventory–Head and Neck (MDASI-HN) pain score. Frequency of as-needed (PRN) analgesic use and opioid requirement were also assessed. Baseline opioid dose was reported as a fentanyl-equivalent dose (FED) and PRN for breakthrough pain use as oral morphine-equivalent dose (OMED). The chi-square and Student t-tests were used to determine differences before and after GKRS.RESULTSSeven patients (29%) were excluded due to local disease progression. Two experienced progression at the first follow-up, and 5 had local recurrence from disease outside the GKRS volume. Nineteen patients were assessed for symptom palliation with a median follow-up duration of 10.4 months (range 3.0–34.4 months). At 3 months after GKRS, the NRS scores (n = 19) decreased from 4.65 ± 3.45 to 1.47 ± 2.11 (p < 0.001); MDASI-HN pain scores (n = 13) decreased from 5.02 ± 1.68 to 2.02 ± 1.54 (p < 0.01); scheduled FED (n = 19) decreased from 62.4 ± 102.1 to 27.9 ± 45.5 mcg/hr (p < 0.01); PRN OMED (n = 19) decreased from 43.9 ± 77.5 to 10.9 ± 20.8 mg/day (p = 0.02); and frequency of any PRN analgesic use (n = 19) decreased from 0.49 ± 0.55 to 1.33 ± 0.90 per day (p = 0.08). At 6 months after GKRS, 9 (56%) of 16 patients reported being pain free (NRS score 0), with 6 (67%) of the 9 being both pain free and not requiring analgesic medications. One patient treated early in our experience developed a temporary increase in trigeminal pain 3–4 days after GKRS requiring hospitalization. All subsequently treated patients were given a single dose of intravenous steroids immediately after GKRS followed by a 2–3-week oral steroid taper. No further cases of increased or new pain after treatment were observed after this intervention.CONCLUSIONSGKRS for palliation of trigeminal pain secondary to recurrent malignant skull base tumors demonstrated a significant decrease in patient-reported pain and opioid requirement. Additional patients and a longer follow-up duration are needed to assess durability of symptom relief and local control.

Objective The objective of this study was to identify factors associated with improved tumor control at individual sites of recurrence and to define the role of stereotactic radiosurgery (SRS) in the management of local or distant progression following prior radiotherapy. Study Design Clinical data of patients with recurrent skull base chordoma following prior radiotherapy were retrospectively reviewed. Setting and Participants This is a single-center retrospective study including 16 patients from the University of Texas MD Anderson Cancer Center Houston, Texas, United States. Main Outcome Measures Each site of recurrence was considered independently, and the primary outcome was freedom from treatment site progression (FFTSP). Results There were 40 episodes of either local or distant progression treated in 16 patients with skull base chordoma. Tumor recurrence was classified as either local, distant, or both local and distant involving the skull base, spinal column, or leptomeninges. Patients were treated with repeat surgical resection (n = 16), SRS (n = 21), or chemotherapy (n = 25). In multivariate analysis, SRS was the only treatment modality associated with improved FFTSP (p = 0.006). For tumors treated with SRS, there was no evidence of tumor progression or adverse radiation events. Other factors associated with worse FFTSP included the number of progressive episodes (>3), tumor histology, and leptomeningeal disease. Conclusions For local recurrence following prior radiotherapy, SRS was associated with improved FFTSP. SRS may represent an effective palliative treatment offering durable tumor control at the treated site without significant treatment-related morbidity.

PURPOSE Multimodal therapy is a well-established approach for the treatment of sinonasal undifferentiated carcinoma (SNUC); however, the optimal sequence of the various treatments modalities is yet to be determined. This study aimed to assess the role of induction chemotherapy (IC) in guiding definitive therapy in patients with SNUC. METHODS Ninety-five previously untreated patients diagnosed with SNUC and treated between 2001 and 2018 at The University of Texas MD Anderson Cancer Center were included in the analysis. Patients were treated with curative intent and received IC before definitive locoregional therapy. The primary end point was disease-specific survival (DSS). Secondary end points included overall and disease-free survival, disease recurrence, and organ preservation. RESULTS A total of 95 treatment-naïve patients were included in the analysis. For the entire cohort, the 5-years DSS probability was 59% (95% CI, 53% to 66%). In patients who had partial or complete response to IC, the 5-year DSS probabilities were 81% (95% CI, 69% to 88%) after treatment with definitive concurrent chemoradiotherapy (CRT) after IC and 54% (95% CI, 44% to 61%) after definitive surgery and postoperative radiotherapy or CRT after IC (log-rank P = .001). In patients who did not experience at least a partial response to IC, the 5-year DSS probabilities were 0% (95% CI, 0% to 4%) in patients who were treated with concurrent CRT after IC and 39% (95% CI, 30% to 46%) in patients who were treated with surgery plus radiotherapy or CRT (adjusted hazard ratio of 5.68 [95% CI, 2.89 to 9.36]). CONCLUSION In patients who achieve a favorable response to IC, definitive CRT results in improved survival compared with those who undergo definitive surgery. In patients who do not achieve a favorable response to IC, surgery when feasible seems to provide a better chance of disease control and improved survival.

Objectives/hypothesis Olfactory neuroblastoma (ONB) is a rare sinonasal malignant neoplasm that is known to develop late recurrence. The aim of this study is to evaluate the long-term outcomes of patients with ONB and to determine the factors associated with prognosis. Study design Retrospective study. Methods A retrospective review of the medical records of 139 patients diagnosed with ONB at MD Anderson Cancer Center was performed between 1991 and 2016. Descriptive statistics were calculated, and Kaplan-Meier curves were utilized to assess survival. Results Median follow-up time was 75 months. Overall, 129 patients (92.8%) had surgery as part of their treatment and 82 (58.9%) patients received postoperative radiation therapy (PORT) or concurrent chemoradiotherapy. Endoscopic approaches were utilized for 72 patients, 69.4% of whom had pure endoscopic endonasal approaches. Five-year overall survival and disease-specific survival were 85.6% and 93.4%, respectively. Recurrence rate was 39.6% with a median time to recurrence of 42 months. Among the 31 patients who received elective nodal irradiation (ENI), two patients developed neck recurrence (6.4%) compared with 20 who developed neck recurrence when ENI was omitted (34.4%) (P = .003). Advanced Kadish stage, orbital invasion, intracranial invasion, and presence of cervical lymphadenopathy at the time of presentation were significantly associated with poor survival. Conclusion ONB has an excellent survival. Surgical resection with PORT when indicated is the mainstay of treatment. Endoscopic approaches can be used as a good tool. Elective neck irradiation reduces the risk of nodal recurrence among patients with clinically N0 neck. Despite the excellent survival, recurrence rate remains high and delayed, highlighting the need for long-term surveillance. Level of evidence Level 4 Laryngoscope, 2021.

OBJECTIVE Sinonasal malignancies that extend to the anterior skull base frequently require neurosurgical intervention. The development of techniques for craniofacial resection revolutionized the management of these neoplasms, but modern and long-term data are lacking, particularly those related to the incorporation of endoscopic techniques and novel adjuvant chemotherapeutics into management schema. The present study was performed to better define the utility of surgical management and to determine factors related to outcome. METHODS Patients who underwent surgery between 1993 and 2020 were included in this retrospective cohort study. Only patients with greater than 6 months of clinical and radiological follow-up were included. Outcome measures included progression, survival, and treatment-related complications. RESULTS Two hundred twenty-five patients were included. The mean clinical follow-up was 6.5 years. The most common histological diagnosis was olfactory neuroblastoma (33%). Overall, metastatic disease and brain invasion were present in 8% and 19% of patients, respectively, at the time of surgery. A lumbar drain was used in 54% of patients. When stratified by decade, higher-stage disease at surgery became more frequent over time (15% of patients had metastatic disease in the 3rd decade of the study period vs 4% in the 1st decade). Despite the inclusion of patients with progressively higher-stage disease, median overall survival (OS) remained stable in each decade at approximately 10 years (p = 0.16). OS was significantly worse in patients with brain invasion (p = 0.006) or metastasis at the time of surgery (p = 0.014). Complications occurred after 28% of operations, but typically resulted in no long-term negative sequelae. Use of a lumbar drain was a significant predictor of complications (p = 0.02). Permanent ophthalmological disabilities were observed after 4% of surgical procedures. One patient died during the perioperative period. Finally, major complications (Clavien-Dindo grade ≥ IIIb) decreased from 27% of patients in the 1st decade to 10% in the 3rd decade (p = 0.007). CONCLUSIONS The surgical management of sinonasal malignancies with anterior skull base involvement is effective and generally safe. Surgical management, however, is only one facet of the overall multimodal management paradigms created to optimize patient outcomes. Survival outcomes have remained stable despite more extensive disease at surgery in patients who have presented in recent decades. The safety of such surgery has improved over time owing to the incorporation of endoscopic surgical techniques and the avoidance of lumbar spinal drainage with open resection.

Pituitary carcinoma is an aggressive tumor characterized by metastatic spread beyond the sellar region that leads to debilitating symptoms and poor survival. Pituitary carcinomas recur despite conventional multimodality treatments. Given the recent advances in the use of immune checkpoint inhibitors (CPIs) to treat various solid cancers, there is interest in exploring the role of immunotherapy for treating aggressive, refractory pituitary tumors. We treated four pituitary carcinoma patients with pembrolizumab as part of a phase II clinical trial (NCT02721732). Here, we present their clinical course and outcomes and correlate responses with available molecular data: hypermutation status, PD-L1 staining, tumor-infiltrating lymphocyte score, microsatellite status and tumor mutational burden. Patients 1 and 2, with heavily pretreated, refractory corticotroph pituitary carcinoma, had partial radiographic (60% and 32% per irRECIST, respectively) and hormonal responses. Patient 1’s response continues 42 months after initiation of pembrolizumab and his baseline tumor tissue obtained after treatment with temozolomide demonstrated a hypermutator phenotype with MSH2 and MSH6 gene mutations. Patient 2’s tumor was not sampled after exposure to temozolomide, but prior somatic mutational testing was negative. Patient 3 (non-functioning corticotroph tumor) had a best response of stable disease for four months. Patient 4 (prolactin-secreting carcinoma) had progressive disease. The latter two patients’ tumors did not demonstrate a hypermutator phenotype after treatment with temozolomide. PD-L1 staining was negative in all tumors. TIL score was 2 in Patients 1 and 4, negative in Patient 3 and not available in Patient 2. All patients tolerated the treatment well with mild adverse events. Our study generates the hypothesis that an alkylating agent-induced hypermutator phenotype may be an indicator of response to CPIs in pituitary carcinomas. The role of CPI in treating patients with pituitary carcinoma and mechanisms of hypermutation in this population require further study.

Autopsy studies suggest that skull base metastases are likely underrecognized in patients with cancer. Patients frequently present with one or a combination of skull base clinical syndromes that manifest as pain or cranial neuropathy. Once a skull base metastasis is suspected, establishing a histologic diagnosis, dedicated imaging, and restaging (if appropriate) are the first steps in management. A multidisciplinary approach should then be used to identify the optimal histology-based treatment strategy, taking into account the burden of systemic disease. Finally, definitive treatment may include one or a combination of surgical management, radiation therapy, or chemotherapy."

OBJECTIVES To evaluate the incidence of histopathologic diagnostic discrepancy for patients referred to our institution, identify pathologies susceptible to diagnostic error, and assess the impact on survival of histopathologic diagnostic discrepancies. METHODS Three hundred ninety-seven patients with sinonasal cancers were identified, and discordance between the outside pathologic report and MD Anderson Cancer Center pathologic report was assessed. Overall survival and disease-specific survival were analyzed using Kaplan-Meier and log rank methods. RESULTS Discordance of major histopathologic diagnoses was present in 24% (97 of 397) of reports, with sinonasal undifferentiated carcinoma, sarcoma, neuroendocrine carcinoma, and poorly differentiated carcinoma pathologies having the highest change in diagnosis (P

Background Skull base osteoradionecrosis (ORN) is a challenging treatment-related complication sometimes seen in patients with cancer. Although ORN management strategies for other anatomic sites have been reported, there is a paucity of data guiding the management of skull base ORN. Objective To report a single-center tertiary care series of skull base ORN and to better understand the factors affecting ORN recurrence after surgical management. Methods We conducted a retrospective cohort study of patients with skull base ORN treated at our center between 2003 and 2017. Univariate and multivariate binary logistic regressions were performed to identify predictors of recurrence. Results A total of 31 patients were included in this study. The median age at ORN diagnosis was 61.1 yr (range, 32.8-84.9 yr). Of these 31 patients, 15 (48.4%) patients were initially treated medically. All 31 patients underwent surgery. Three (14.3%) of 21 patients treated with a free flap and 4 (50.0%) of 8 patients who underwent primary closure experienced recurrence. Cox regression analysis revealed that reconstruction with local tissue closure (P = .044) and ongoing treatment for active primary cancer (P = .022) were significant predictors of recurrence. The median overall survival from index surgery for ORN treatment was 83.9 mo. At 12-mo follow-up, 78.5% of patients were alive. Conclusion In this study, we assess the outcomes of our treatment approach, surgical debridement with vascularized reconstruction, on recurrence-free survival in patients with skull base ORN. Further studies with larger cohorts are needed to assess current treatment paradigms.

Background Skull base chondrosarcomas (CSA) are difficult tumors to cure and there is little data regarding salvage therapy. Objective This study aims to identify presentation and treatment-related factors which impact the progression free survival (PFS) and disease specific survival (DSS) for recurrent CSA, and to identify salvage treatment factors associated with successful restoration to the natural history following primary treatment. Methods This single-institution retrospective review included patients with recurrent/progressive CSA over a 25-year period. Survival analysis for factors impacting PFS and DSS was performed. Salvage treatment factors associated with achieving PFS ≥newly diagnosed median PFS were identified using univariate statistics. Analysis was performed on first recurrences and all recurrences combined. Results A total of 47 recurrence/progression events were analyzed from 17 patients (median two events/patient, range = 1–8). The overall PFS and DSS for the initial recurrence was 32 (range = 3–267) and 79 (range = 3–285) months, respectively. Conventional grade III or mesenchymal histology significantly predicted shorter PFS and DSS (p Conclusion In this series, high grade histology and prior radiation treatment negatively impacted salvage treatment outcomes, while GTR was associated with restoration to natural history following primary treatment. Careful consideration of histology, systemic disease status, previous treatments, and the anatomic extent of the skull base disease can optimize the outcomes of salvage intervention.

Meningiomas of the olfactory groove and planum sphenoidale are relatively common skullbase meningiomas. They are typically of low grade but may grow to large size due to the insidious nature of their growth. Surgical resection remains the mainstay of treatment.

Surgery and radiation therapy are the standard treatment options for meningiomas, but these treatments are not always feasible. Expression profiling was performed to determine the presence of therapeutic actionable biomarkers for prioritization and selection of agents. Meningiomas (n = 115) were profiled using a variety of strategies including next-generation sequencing (592-gene panel: n = 14; 47-gene panel: n = 94), immunohistochemistry (n = 8–110), and fluorescent and chromogenic in situ hybridization (n = 5–70) to determine mutational and expression status. The median age of patients in the cohort was 60 years, with a range spanning 6–90 years; 52% were female. The most frequently expressed protein markers were EGFR (93%; n = 44), followed by PTEN (77%; n = 110), BCRP (75%; n = 8), MRP1 (65%, n = 23), PGP (62%; n = 84), and MGMT (55%; n = 97). The most frequent mutation among all meningioma grades occurred in the NF2 gene at 85% (11/13). Recurring mutations in SMO and AKT1 were also occasionally detected. PD-L1 was expressed in 25% of grade III cases (2/8) but not in grade I or II tumors. PD-1 + T cells were present in 46% (24/52) of meningiomas. TOP2A and thymidylate synthase expression increased with grade (I = 5%, II = 22%, III = 62% and I = 5%, II = 23%, III = 47%, respectively), whereas progesterone receptor expression decreased with grade (I = 79%, II = 41%, III = 29%). If predicated on tumor expression, our data suggest that therapeutics directed toward NF2 and TOP2A could be considered for most meningioma patients.

Head and neck mucosal melanoma is a locally aggressive tumor with a high recurrence rate. The paranasal sinuses and nasal cavity are the most common primary tumor sites. The purpose of this retrospective study was to identify independent predictors of outcome in sinonasal mucosal melanoma (SNMM) and characterize the patterns of treatment failure. This study included 198 patients with SNMM who had been treated at The University of Texas MD Anderson Cancer Center from 1 January 1991 through 31 December 2016. The survival outcomes included overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), local recurrence-free survival, and distant metastasis-free survival. A stepwise regression analysis was used to assess associations in the multivariate models. The 5-year OS, DSS, and DFS rates were 38, 58, and 27%, respectively. Independent predictors of poor OS and DSS were the paranasal sinuses as the primary tumor site [hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.11–2.66; and HR 2.12, 95% CI 1.21–3.74, respectively] and the presence of distant metastases at presentation (HR 4.53, 95% CI 2.24–7.83; and HR 3.6, 95% CI 1.12–7.1). Recurrence occurred in 96 patients (48%). The most common cause of treatment failure was distant metastasis in 69 of 198 patients (35%), followed by local [36 (18%)] and regional [22 (11%)] recurrence. The most common cause of treatment failure in SNMM is distant metastasis. The tumor site and the presence of metastatic disease at presentation were the only independent predictors of survival. These data can be used to inform quality improvement efforts and the counseling of high-risk SNMM patients.

To determine if early access to multidisciplinary surgical care affects outcomes in patients with skull base chordoma. A retrospective chart review of prospectively collected data was performed on 51 patients treated from 1993 to 2014. The cohort was divided into those presenting (1) for initial management (ID, n = 21) or (2) with persistent/progressive disease after prior biopsy/surgery (PD, n = 30) outside of a multidisciplinary setting. The impact of initial surgical management in a multidisciplinary center on progression-free survival (PFS) was assessed with Kaplan-Meier and log-rank analyses. Mean follow-up, median PFS, median overall survival (OS), and 10-year OS for the entire cohort was 70 months, 47 months, 159 months, and 19%, respectively. Initial management in a multidisciplinary center resulted in a significant improvement in PFS versus initial surgery with or without radiotherapy (XRT) outside of this setting (64 vs 25 months, p = 0.035). Initial surgical resection outside of a multidisciplinary setting increased the risk of recurrence/progression on univariate (HR, 2.276; p = 0.022) and multivariate analysis (HR, 2.831; p = 0.006), respectively. The results from this study emphasize the impact that coordinated multidisciplinary surgical care has on patient outcomes for chordomas of the clivus. Biopsy followed by attempted radical resection at a dedicated center does not affect PFS and, therefore, represents a reasonable first step in management for patients presenting outside of multidisciplinary setting.

Background Mucosal melanomas in the head and neck region are most often located in the nasal cavity and paranasal sinuses. To the authors' knowledge, the prognostic effects of lymph node metastasis in patients with sinonasal mucosal melanoma (SNMM) have not been established. Therefore, the objective of the current study was to determine the effects of lymph node metastasis on survival. Methods The current study included 198 patients with SNMM who had been treated between 1985 and 2016 at The University of Texas MD Anderson Cancer Center in Houston. Patients' clinical and pathologic lymph node statuses were evaluated and characterized. A multivariate analysis was used to assess the associations between regional spread and survival outcomes. Results Therapeutic neck dissection was performed in 23 patients with SNMM (11.6%). Regional disease recurrence occurred in 7 of the patients who had lymph node metastasis at the time of presentation (30.4%) and in 30 of those who had N0 disease at the time of presentation (17.1%) (P = .15). Metastasis to the contralateral lymph nodes was present in 7 patients (3.5%). The 5-year disease-specific survival rate was 66% in patients with lymph node spread compared with 45% in patients with N0 status (P = .04, log-rank test). A multivariate analysis demonstrated that distant metastasis was the only variable found to be independently associated with both overall survival (hazard ratio, 2.96; 95% confidence interval, 1.54-6.95 [P = .01]) and disease-specific survival (hazard ratio, 3.32; 95% confidence interval, 1.79-7.14 [P = 0.01]). Conclusions The results of the current study demonstrated that lymph node status in patients with SNMM was not a significant predictor of outcome. This finding, together with the low incidence of lymph node metastases in patients with SNMM, suggests that elective treatment of the neck should be highly selective in this patient population. Cancer 2018;124:514-20. © 2017 American Cancer Society.

Limited data exist to guide the management of recurrent chordomas arising in the skull base.To determine factors affecting tumor control rates and disease-specific survival (DSS) in recurrent disease.A retrospective review was performed of 29 patients with 55 recurrences treated at our institution. Tumor and treatment factors were assessed for impact on freedom from progression (FFP; primary outcome) and DSS (secondary outcome).Postradiotherapy disease failure was much more difficult to manage vs progression after surgery alone (15.9 vs 41.4 mo, P = .094). Distant metastases and, specifically, leptomeningeal disease at presentation were associated with poorer DSS and FFP (P.05). For local progression after surgery alone, repeat resection (P.05) improved median FFP. With postradiotherapy local failure, repeat resection did not confer any benefit (13.5 vs 17.6 mo, P.05), while a trend towards improved FFP was seen with stereotactic radiosurgery (28.3 vs 16.2 mo, P = .233). For distant metastases, site-directed therapy (surgery or radiation) allowed for site control (P.05) but did not affect FFP or DSS. Presentation with early progression6 mo from previous treatment portended significantly worse DSS (19.3 vs 77.6 mo, P.05).There is a need for treatment of recurrent disease to be tailored to the pattern of tumor recurrence and previously received treatments. Postradiotherapy progression poses particular challenges given the apparent limited role of repeat resection alone. Stereotactic radiosurgery may have a role in this setting. While patients with systemic metastases appear to respond well to site-directed therapy, those with leptomeningeal disease have a dismal prognosis.

Nasopharyngeal carcinoma (NPC) is a head and neck cancer arising out of the epithelium of the nasopharynx. There is an annual incidence of 0.5–2.0 cases per 100,000 in the US and Europe, although numbers as high as 25 per 100,000 may be seen in endemic countries such as China 1. Males are at an increased risk and while there has been evidence of a link to dietary practices in endemic areas, the vast majority of data suggest Epstein–Barr virus (EBV) as the predominant pathogenic factor in NPC 2, 3. Given the association with EBV, the histology and natural history of NPC differ from most other cancers of the head and neck. Treatment of early and locally advanced disease is typically nonsurgical because of the proximity of nearby vital structures. Thus, there is a strong role for noninvasive therapy in the form of radiation ± chemotherapy, which is considered standard of care for this disease 4. Detection of nodal metastasis in the neck or spread to adjacent structures including the skull base, nasal cavity, sphenoid bones, pterygoids, prevertebral muscles, and oropharynx with occult or frank primary disease is relatively common in NPC 5, 6. In contrast, intracranial extension of NPC is not as common especially in the absence of an obvious primary lesion 7. In this case report, we discuss a patient with a diagnosis of NPC that presented with extensive skull base disease and metastasis to the right temporal lobe with subtle findings in the nasopharynx.

Chordomas are rare, slowly growing, locally aggressive bone neoplasms that arise from embryonic remnants of the notochord, showing dual epithelial-mesenchymal differentiation. The high plasticity probably is the main reason for the high variety in phenotypes of chordoma, from its high heterogeneity on a cellular level to its subtype variations depending on tissue location, with its potential to develop from an inactive quiescent form to an aggressive cancer with extreme adaptability and resistance to drugs and other treatments. Gene expression profiles of formalin-fixed, paraffin-embedded skull chordoma, spine chordoma, and normal tissue specimens were generated and compared. Using strict criteria, we identified 222 differentially expressed transcripts unique to skull base chordoma, 261 unique to spine chordoma, and 192 common to both chordoma subtypes. Further analysis of these three groups of transcripts allowed the selection of three subsets of highly differentially expressed genes as potential biomarkers, disease drivers, and therapeutic targets in both chordoma subtypes. Immunohistochemistry revealed LMX1A to be dominant in skull base chordoma, SALL3 to be unique to spine chordoma, and T to be common to both chordoma subtypes. In both chordoma subtypes, the genes with the highest expression were predominantly development-related genes, mostly transcription factors. Our findings indicate that these developmental genes play important oncogenic roles in chordoma, mainly causing high plasticity and resistance to therapy in both these cancer subtypes but also determining their differentiation status and proliferation activity, pointing to features expected of heterogeneous stem cell-like tissues with similarities to their notochord origins.

Purpose Sinonasal mucosal melanoma (SNMM) is a locally aggressive tumor. This study aimed to define the role of adjuvant treatment and its association with survival outcomes of SNMM. Methods This retrospective study investigated 152 patients with SNMM treated between 1991 and 2016 in MD Anderson Cancer Center. Patients were divided into the following treatment groups: surgery alone, surgery with postoperative radiotherapy (PORT), surgery with postoperative chemoradiation (POCRT), and induction chemotherapy followed by surgery and PORT. Overall survival (OS), disease-specific survival, and relapse-free survival were compared. Survival between the groups was compared using univariate and multivariate analyses. Results The median follow-up was 28 months (range: 2–220 months). Five-year OS rates were 39, 42, 47, and 27% for the surgery only, PORT, POCRT, and neoadjuvant chemotherapy groups, respectively (log rank p = 0.73). Distant metastasis was the most common form of treatment failure and occurred in 59 (39%) patients. Five-year distant metastasis rates were 51, 45, and 58% for patients treated with surgery alone, PORT, and POCRT, respectively (log rank p = 0.21) but unable to be estimated in the neoadjuvant chemotherapy group due to low OS rates. Multivariate analysis demonstrated tumor site (hazard ratio [HR] = 2.32, 95% confidence interval [CI] = 1.24–4.15) and smoking status (HR = 1.77, 95% CI = 1.02–3.1) to be significant prognostic factors for survival. Conclusion Tumor site and smoking status were significant prognosticators in SNMM. A high rate of distant metastatic disease suggests that further investigation into novel, systemic therapies is required to improve outcomes in this disease entity.

Summary Background After brain metastasis resection, whole brain radiotherapy decreases local recurrence, but might cause cognitive decline. We did this study to determine if stereotactic radiosurgery (SRS) to the surgical cavity improved time to local recurrence compared with that for surgical resection alone. Methods In this randomised, controlled, phase 3 trial, we recruited patients at a single tertiary cancer centre in the USA. Eligible patients were older than 3 years, had a Karnofsky Performance Score of 70 or higher, were able to have an MRI scan, and had a complete resection of one to three brain metastases (with a maximum diameter of the resection cavity ≤4 cm). Patients were randomly assigned (1:1) with a block size of four to either SRS of the resection cavity (within 30 days of surgery) or observation. Patients were stratified by histology of the primary tumour, metastatic tumour size, and number of metastases. The primary endpoint was time to local recurrence in the resection cavity, assessed by blinded central review of brain MRI scans by the study neuroradiologist in the modified intention-to-treat population that analysed patients by randomised allocation but excluded patients found ineligible after randomisation. Participants and other members of the treatment team (excluding the neuroradiologist) were not masked to treatment allocation. The trial is registered with ClinicalTrials.gov, number NCT00950001, and is closed to new participants. Findings Between Aug 13, 2009, and Feb 16, 2016, 132 patients were randomly assigned to the observation group (n=68) or SRS group (n=64), with 128 patients available for analysis; four patients were ineligible (three from the SRS group and one from the observation group). Median follow-up was 11·1 months (IQR 4·8–20·4). 12-month freedom from local recurrence was 43% (95% CI 31–59) in the observation group and 72% (60–87) in the SRS group (hazard ratio 0·46 [95% CI 0·24–0·88]; p=0·015). There were no adverse events or treatment-related deaths in either group. Interpretation SRS of the surgical cavity in patients who have had complete resection of one, two, or three brain metastases significantly lowers local recurrence compared with that noted for observation alone. Thus, the use of SRS after brain metastasis resection could be an alternative to whole-brain radiotherapy. Funding National Institutes of Health.

Background: Sinonasal mucosal melanoma (SNMM) comprises

Optic nerve sheath meningiomas (ONSMs) account for less than 2% of meningiomas and 1.7% of orbital tumors. Although rare, the management of these tumors is important as unilateral blindness often results in untreated cases. Radiotherapy has emerged as the preferred treatment. However, therapies for ONSMs are controversial due to the variable natural history of the disease and limitations of surgical and radiotherapy options. A 60-year-old woman presented with monocular left diminished color perception and blurred vision. Magnetic resonance imaging demonstrated a homogenously enhancing 5-mm left optic nerve mass with evidence of nerve compression. Conservative management was advised. However, 1 month after diagnosis her visual acuity deteriorated further. Because of the small focal location of the tumor within the optic canal, surgery was considered. Given the tumor's location inferomedial to the optic nerve, an endoscopic endonasal approach to the optic canal was performed. This patient recovered fully with resolution of visual symptoms immediately following surgery. Postoperative imaging 24 hours after surgery demonstrated gross total resection of the tumor; 1 year postoperatively the patient has a normal ophthalmologic examination. This report highlights the value of endoscopic endonasal approaches in the management of select optic canal pathology, otherwise inaccessible via transcranial approaches.

BACKGROUND Craniopharyngiomas (CP) are frequently associated with a malignant clinical trajectory despite their benign histology. This population frequently has endocrinopathies and autonomic dysfunction due to tumour location, which may influence cardiac function and long term health outcome. In this study, we evaluated for clinical and paraclinical cardiac abnormalities in adult and pediatric patients with craniopharyngioma. METHODS We retrospectively identified patients in our neurosurgery database with a diagnosis of craniopharyngioma that received neurosurgery at MD Anderson Cancer Center. We queried the medical record for demographic and disease-related information, as well as clinical information regarding cardiac risk factors. Perioperative electrocardiograms (EKGs) were analyzed where available. RESULTS We identified 56 patients with craniopharyngioma, 27 (48.2%) of which were female. Average age was 39 years, and all patients had undergone subtotal (49.1%), gross total (32.7%), or near gross total (18.2%) resection. Over half (53.6%) had undergone radiation, none had received systemic therapy, and 1 (1.8%) intra-cystic chemotherapy. The majority had adamantanomatous-type histology (83%) and the remainder papillary (17%). At diagnosis, average BMI was elevated at 30.98. Hypertension (30.4%), diabetes mellitus (32.1%), and thyroid dysfunction (80%), were found in this cohort. Nearly a quarter (23.2%) were on statin therapy for dyslipidemia. Stimulant (14.3%) and neuropleptic (3.6%) use were also identified. Of patients with perioperative EKG performed (N= 39), 30 were available for review. Of these, patients were identified with abnormal rate (N=9, 30.0%), PR interval (N=2, 6.7%), QRS interval (N=4, 13.3%), and QTc interval (N=1, 3.3%). Some patients presented with a history of heart palpitations (1.8%) and syncopal episodes (3.6%), but not chest pain. CONCLUSION This analysis demonstrates frequent vascular and cardiac risk factors in patients with craniopharyngioma. We advocate for increased awareness of cardiac health in this young population. Further prospective evaluation is warranted to better understand cardiac health in this patient group.

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-naive patients, R0 resections also had improved impact on PFS (P = .04) and DSS (P = .027). For radiation-naive 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-naive 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.

Pituitary carcinoma is an aggressive tumor characterized by metastatic spread beyond the sellar region. Symptoms can be debilitating due to hormonal excess and survival is poor. Pituitary carcinomas recur despite conventional multimodality treatments. Given the recent advances in the use of immune checkpoint inhibitors (CPIs) to treat various solid cancers, there has been interest in exploring the role of immunotherapy for treating aggressive, refractory pituitary tumors. We treated 4 patients with pituitary carcinoma with pembrolizumab as part of a phase II clinical trial. Two patients (patients 1 and 2) with functioning corticotroph pituitary carcinomas (refractory to surgery, radiotherapy and chemotherapy) had partial radiographic (60% and 32% per Immune-Related Response Evaluation Criteria In Solid Tumors, respectively) and hormonal responses. Patient 1’s response continues 42 months after initiation of pembrolizumab and his tumor tissue obtained after treatment with temozolomide demonstrated a hypermutator phenotype with MSH2 and MSH6 gene mutations. Patient 2’s tumor after exposure to temozolomide was not sampled, but prior somatic mutational testing was negative. One patient with a non-functioning corticotroph tumor (patient 3) had a best response of stable disease for 4 months. One patient with a prolactin-secreting carcinoma (patient 4) had progressive disease. The latter 2 patients’ tumors did not demonstrate a hypermutator phenotype after treatment with temozolomide. Programmed death-ligand 1 staining was negative in all tumors. We report 2 cases of corticotroph pituitary carcinoma responsive to pembrolizumab after prior exposure to alkylating agents. The role of CPIs in treating patients with pituitary carcinoma, the relationship between tumor subtype and response to immunotherapy and mechanisms of hypermutation in this orphan disease require further study.Trial registration number: NCT02721732.

BACKGROUND Midline ventral skull base meningiomas may be amenable to an endonasal endoscopic approach, which has theoretical advantages and may help preserve quality of life (QOL) when compared with transcranial approaches. OBJECTIVE To investigate the effect of age on QOL following endonasal endoscopic surgery, given the documented impact of age on QOL outcomes following transcranial resection of midline ventral skull base meningiomas. METHODS We reviewed a prospectively acquired database of endonasal endoscopic surgery for meningiomas. Inclusion criteria included patients who had completed long-term postoperative (≥6 months follow-up) QOL questionnaires (Anterior Skull Base Questionnaire [ASBQ] and Sino-Nasal Outcome Test [SNOT-22]). Postoperative QOL scores were also compared with preoperative QOL in a patient subset. RESULTS Long-term QOL data were available in 34 patients. Average postoperative ASBQ and SNOT-22 scores were 3.39 and 23.0, respectively. Better QOL was statistically associated with age

Cancer-associated facial pain can be caused by a variety of pathologic conditions. Here the authors describe the symptoms and incidence of facial pain secondary to three separate anatomic subcategories of cancer. The authors subsequently discuss the effectiveness and drawbacks of the most common methods of treatment.

BACKGROUND Selection of systemic therapy for recurrent meningiomas with progression after resection and/or radiation therapy represents a challenge. The combination of everolimus, an mTOR inhibitor, plus octreotide long-acting repeatable (LAR), a somatostatin agonist, suggests synergistic activity in preclinical studies. Its long-term clinical impact in recurrent meningiomas warrants further study. METHODS We reviewed the records of adult patients with recurrent intracranial or spinal meningioma (WHO grade I, II, or III), not candidates for further surgery or radiation therapy, who were treated with everolimus and octreotide, between 1/1/2015 and 06/1/2020 at MD Anderson Cancer Center. Patients received everolimus (10 mg PO daily) each 28-day cycle and octreotide 30 mg SC once monthly. Molecular features were determined by next generation sequencing (T-200–1, Oncomine). RESULTS A total of 18 patients were identified, including WHO grade I tumors (n=4), grade II (n=10), and grade III (n=4); furthermore, 8 patients harbored NF2 mutation, followed by mutations in CREBBP (n=2), NOTCH2 (n=1), MHL1 (n=1), PTEN (n=1), SETD2 (n=1), and TP53 genes (n=1). One patient had spinal meningioma. The 6- and 12-month PFS were 77.8% and 61.1%, 6- and 12-month OS were 94.4% and 83.3% respectively. Seven (38.9%) patients had tolerated treatment for more than 12 cycles, 3 (16.7%) remain on treatment for more than 24 cycles and 1 patient is still on treatment for 31 cycles. Only 1 patient required dose reduction to 7.5 mg daily due to pneumonitis, otherwise there is an acceptable toxicity profile. Four patients had resolution of trigeminal neuralgia. CONCLUSIONS In our patient population, combination treatment with everolimus and octreotide seems to have antitumor activity and proved to be safe without major side effects from long-term exposure. It also contributed to control of neuralgia. Further tissue analysis of the role of mTOR pathway and SSTR2A expression is ongoing.

Sinonasal malignancies are rare, pathologically diverse, and biologically unpredictable tumors. They tend to have minimal or nonspecific symptoms that mimic benign (inflammatory) disease until there is invasion of adjacent structures. Most patients present with advanced disease. Computed tomography and magnetic resonance imaging are complimentary studies but magnetic resonance imaging optimally defines the tumor’s extent and dictates the need for neurosurgical attention. Advanced endoscopic techniques allow for the resection of some well-selected tumors as part of a multimodal treatment plan. The intimate relationships with the orbit and brain make surgical management challenging. Optimal patient outcomes can only be achieved with carefully constructed, multidisciplinary, multimodal management paradigms.

Background The anterior skull base is an uncommon site for brain metastases. A limited number of cases have been reported where a region of the skull base is accessed through an expanded/extended transsphenoidal route. In addition, reports of overall and progression-free survival rates are lacking. Objective To report progression-free and overall survival rates for skull base metastases treated with aggressive endoscopic endonasal surgery and radiation therapy. Methods We retrospectively review a prospective database of patients at New York Presbyterian Hospital undergoing expanded endoscopic endonasal surgery from 2004 to 2014. From this database, we identified all patients whose final pathology revealed a metastatic lesion in the midline skull base. Results Seven hundred forty-nine patients underwent endonasal endoscopic surgery. Final pathology in 12 patients (1.6%) revealed metastasis to the sellar or parasellar region. Tumors were located in the sella, suprasellar cistern, clivus, ethmoid sinuses, sphenoid sinus, cavernous sinus, and craniovertebral junction. Breast and lung cancers were the most common primary diagnoses. Gross total resection was achieved in 41.6% of patients. There were no postoperative cerebrospinal fluid leaks. Adjuvant radiation therapy was used in 92% of cases. Median follow-up was 14 months (range, 1–55). Median progression-free and overall survival were 18 and 16 months, respectively. Conclusions The range of anterior skull base metastatic lesions that can be managed endonasally has increased with the advent of extended endonasal endoscopic surgical approaches. Favorable results can be obtained with this surgical approach as part of the overall management paradigm for patients with skull base metastases.

OBJECT Craniopharyngiomas are benign parasellar tumors for which surgical removal, although potentially curative, often leads to morbidity with resulting decreases in quality of life (QOL). The endonasal endoscopic approach is a minimal-access technique for removing these tumors and may reduce postoperative morbidity. The QOL following this method for resection of craniopharyngiomas has not been documented. METHODS The authors reviewed a database of consecutive endonasal endoscopic surgeries done at Weill Cornell Medical College. Adult patients with histologically proven craniopharyngiomas were included who had completed either only postoperative (> 9 months) or both pre- and postoperative QOL forms, the Anterior Skull Base Quality of Life (ASBQ) questionnaire, and the 22-Item Sinonasal Outcome Test (SNOT-22). Rates of gross-total resection (GTR), complications, and visual and endocrine function were collected. Retrospective independence (Wen score) was also assigned. A contemporaneous group of patients undergoing endonasal endoscopic pituitary macroadenoma resection was used as a control. RESULTS This study included 33 procedures performed in 31 patients. The average postoperative ASBQ score was 3.35 and the SNOT-22 score was 19.6. Better QOL was associated with GTR and postoperative radiation. Worse QOL was associated with persistent visual defects, hypopituitarism, tumor recurrence, increase in body mass index, and worsening Wen score. In a subset of 10 patients, both pre- and postoperative (> 9 months) QOL scores were obtained. Both ASBQ and SNOT-22 scores showed stability and a trend toward improvement, from 2.93 ± 0.51 to 2.96 ± 0.47 (ASBQ) and 23.7 ± 10.8 to 18.4 ± 11.6 (SNOT-22). Compared with 62 patients undergoing endoscopic pituitary macroadenoma resection, patients with craniopharyngiomas had worse postoperative QOL on the ASBQ (3.35 vs 3.80; p = 0.023) and SNOT-22 (19.6 vs 13.4; p = 0.12). CONCLUSIONS This report of validated site-specific QOL following endoscopic surgery for craniopharyngiomas shows an overall maintenance of postoperative compared with preoperative QOL. Better QOL could be seen in patients with GTR and radiation therapy, and worse QOL was found in patients with visual or endocrine deficits. Nevertheless, patients with craniopharyngiomas still had worse QOL than those undergoing similar surgery for pituitary macroadenomas, confirming the worse prognosis of craniopharyngiomas even when removed via a minimally invasive approach. These measures should serve as benchmarks for comparison with open transcranial approaches to similar tumors.

Background There are no guidelines regarding post-treatment surveillance specific to skull base chordomas. Objective To determine an optimal imaging surveillance schedule to detect both local and distant metastatic skull base chordoma recurrences. Methods A retrospective review of 91 patients who underwent treatment for skull base chordoma between 1993 and 2017 was conducted. Time to and location of local and distant recurrence(s) were cataloged. Existing chordoma surveillance recommendations (National Comprehensive Cancer Network [NCCN], London and South East Sarcoma Network [LSESN], European Society for Medical Oncology [ESMO], Chordoma Global Consensus Group [CGCG]) were applied to our cohort to compare the number of recurrent patients and months of undiagnosed tumor growth between surveillances. These findings were used to inform the creation of a revised imaging surveillance protocol (MD Anderson Cancer Center Chordoma Imaging Protocol [MDACC-CIP]), presented here. Results Thirty-four patients with 79 local/systemic recurrences met inclusion criteria. Mean age at diagnosis and follow-up time were 45 yr and 79 mo, respectively. The MDACC-CIP imaging protocol significantly reduced the time to diagnosis of recurrence compared with the LSESN and CGCG/ESMO imaging protocols for surveillance of local disease with a cumulative/average of 576/16.9 (LSESN), 336/9.8 (CGCG), and 170/5.0 (MDACC-CIP) months of undetected growth, respectively. The NCCN and MDACC-CIP guidelines for distant metastatic surveillance identified a cumulative/average of 65/6.5 and 51/5.1 mo of undetected growth, respectively, and were not significantly different. Conclusion The MDACC-CIP for skull base chordoma accounts for recurrence trends unique to this disease, including a higher rate of leptomeningeal spread than sacrococcygeal primaries, resulting in improved sensitivity and prompt diagnosis.

Objective Compare outcomes of patients with olfactory neuroblastoma (ONB) without skull base involvement treated with and without resection of the dura and olfactory bulb. Methods Retrospective review of ONB patients treated from 1992 to 2013 at the MD Anderson Cancer Center (The University of Texas, Houston, Texas, U.S.A.). Primary outcomes were overall and disease-free survival. Results Thirty-five patients were identified. Most patients had Kadish A/B. tumors (97%), Hyams grade 2 (70%), with unilateral involvement (91%), and arising from the nasal cavity (68%). Tumor involved the mucosa abutting the skull base in 42% of patients. Twenty-five patients (71%) received surgery and radiation, whereas the remainder had surgery alone. Five patients (14%) had bony skull base resection, and eight patients (23%) had resection of bony skull base, dura, and olfactory bulb. Surgical margins were grossly positive in one patient (3%) and microscopically positive in four patients (12%). The 5- and 10-year overall survival were 93% and 81%, respectively. The 5- and 10-year disease-free survival (DFS) were 89% and 78%, respectively. Bony cribriform plate resection was associated with better DFS (P = 0.05), but dura and olfactory bulb resection was not (P = 0.11). There was a trend toward improved DFS in patients with negative resection margins (P = 0.19). Surgical modality (open vs. endoscopic) and postoperative radiotherapy did not impact DFS. Conclusion Most Kadish A/B ONB tumors have low Hyams grade, unilateral involvement, and favorable survival outcomes. Resection of the dura and olfactory bulb is not oncologically advantageous in patients without skull base involvement who are surgically treated with negative resection margins and cribriform resection. Level of evidence 4. Laryngoscope, 128:1274-1280, 2018.

Background Optimal treatment and prognostic factors affecting long-term survival in patients with sinonasal adenoid cystic carcinoma (ACC) have yet to be clearly defined. Methods We conducted a retrospective review of patients treated with curative intent from 1980-2015 at MD Anderson Cancer Center. Results One hundred sixty patients met inclusion criteria, including 8 who were treated with radiotherapy alone. Median follow-up time was 55 months. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 67.0% and 49.0%, respectively. The 10-year OS and DFS rates were 44.8% and 25.4%, respectively. Factors that portended for poor survival on multivariate analysis were recurrent disease, any solid type histology, epicenter in the sinus cavity, the presence of facial symptoms, or the original disease not treated with surgery. There was no association between surgical margin status or nodal status and survival. Conclusion In this large cohort of patients with sinonasal ACC with extended follow-up, long-term survival is better than reported in prior literature. Future research should target patients with adverse risk factors.

Numerous approaches have been reported in the management of skull base chondrosarcomas. Data are lacking for surgical outcomes by the tumor site of origin.To provide insight into outcomes by site of origin and factors affecting resection in order to aid in surgical approach selection.A retrospective review was conducted of 49 patients with chondrosarcoma treated at our institution. Charts were reviewed for tumor- and treatment-related factors. Extent of resection was the primary outcome, while neurological function and surgical complications were secondary outcomes. Statistical analyses were performed assessing variables for their impact on the primary outcome.The gross total resection rate for the overall cohort was 67.3%, and 97.8% of patients were either neurologically stable or improved postoperatively. A petroclival site of origin had lower rates of resection vs all other sites (P .05). Histology and previous surgery did not predict outcome (P .05), while previous radiotherapy and cavernous sinus invasion correlated with a subtotal resection (P .05). In the petroclival cohort, clival, jugular tubercle, and soft tissue involvement correlated with a subtotal resection (P .05). An endoscopic endonasal transpterygoid approach alone or combined with a transcranial approach yielded the highest resection rates for petroclival tumors (P .05).Chondrosarcomas pose unique challenges based on the site of origin and pattern of extension. While current surgical strategies appear to yield adequate results at a majority of skull base sites, petroclival tumors represent a particular cohort in which improvement is needed. Based on our analysis, strategies incorporating both endoscopic and transcranial skull base approaches are likely necessary to achieve optimal outcomes.

Meningiomas are typically benign, slow-growing lesions that present after an insidious onset of symptoms related to mass effect. The acute presentation of a patient who has suffered a transtentorial herniation event due to a meningioma is rare. There are only few publications describing such a presentation in the absence of hemorrhage [1]. In this case report, a patient with an olfactory groove meningioma presenting with signs and symptoms of transtentorial herniation in the absence of tumor-associated hemorrhage is discussed. This is a unique presentation of such a lesion. The patient developed Anton’s syndrome—binocular visual loss with blindness denial. Management considerations for patients with meningiomas that present with acute deterioration are discussed.

Objective To report an initial experience with a medial transorbital approach to the midline skull base performed via a transconjunctival incision. Methods The authors retrospectively reviewed their clinical experience with this approach in the management of benign cranial base pathology. Preoperative imaging, intraoperative records, hospitalization charts, and postoperative records were reviewed for relevant data. Results During the period 2009–2011, six patients underwent a transconjunctival craniotomy performed by a neurosurgeon and otolaryngologist–head and neck surgeon working together. The indications for surgery were esthesioneuroblastoma in one patient, juvenile angiofibroma in one patient, Paget disease in one patient, and recalcitrant cerebrospinal fluid leaks in three patients. Three patients had prior cranial base surgery (either open craniotomy or an endonasal approach) done at another institution. The mean length of stay was 3.8 days; mean follow-up was 6 months. Surgery was considered successful in all cases (negative margins or no leak recurrence); diplopia was noted in one patient postoperatively. Conclusions The transconjunctival medial orbital craniectomy provides a minimally invasive keyhole approach to lesions located anteriorly along the anterior cranial fossa that are in the midline with lateral extension over the orbital roof. Based on our initial experience with this technique, the working space afforded limits complex surgical dissection; this approach is primarily well suited for less extensive pathology.

Glioblastoma (GB) is rarely found in the cerebellum. Because of its rarity, it is poorly understood if cerebellar GB (CGB) behaves similarly to supratentorial GB. Studies have been limited to case reports and small case series. A better understanding of CGB may help guide treatment strategies.Surveillance, Epidemiology and End Results database was analyzed from 1973 to 2009 for all adult patients with GB located in the cerebellum. Stepwise multivariate proportional hazards regression analyses were used to identify factors independently associated with survival.Two hundred eight (0.9%) patients with CGB were identified from 23,329 GB patients with known locality. The mean age was 58 years. Median survival was 8 months, with 1-, 2- and 5-year survival rates of 21%, 13%, and 2%. When compared to supratentorial GB, CGB occurred in younger patients (58 ± 16 vs. 61 ± 13 years, P = 0.001), less commonly in Whites (85.6% vs. 91.3%, P = 0.005), and were smaller (3.7 ± 1.1 vs. 4.5 ± 1.7 cm, P = 0.001). A cerebellar location independently predicted poorer survival when compared to other GB locations (P = 0.048). In multivariate analysis for patients with CGB, younger age (P0.001), Asian or Pacific Islander race (P = 0.046), and radiation therapy (P0.001) were independently associated with prolonged survival.CGBs are difficult to analyze using institutional series because of their rarity. This study shows they are clinically different from supratentorial GB. Among patients with CGB, radiation therapy may prolong survival. This may help guide treatment strategies aimed at prolonging survival for patients with these extremely rare lesions.