Social media insights for neurosurgical oncologists: a survey of the American Association of Neurological Surgeons and Congress of Neurological Surgeons Joint Section on Tumors.

PURPOSE: There is a paucity in the literature regarding the characteristics and attitudes of social media (SM) utilization in a professional manner by neurosurgical oncologists. METHODS: A 34-question electronic survey was created using Google Forms and disseminated via email to members of the AANS/CNS Joint Section on Tumors. Demographic data were compared amongst those who utilize social media versus those who do not. Factors associated with positive effects of professional SM use and with having more followers on SM were analyzed. RESULTS: The survey received 94 responses, of which 64.9% reported that they currently use SM in a professional manner. Age < 50 years was found to be associated with SM use (p = 0.038). Facebook (54.1%), Twitter (60.7%), Instagram (41%), and LinkedIn (60.7%) were the most used SM platforms. Having a higher number of followers was associated with practicing in academics (p = 0.005), using Twitter (p = 0.013), posting about their own research publications (p = 0.018), posting interesting cases (p = 0.022), and posting about upcoming events (p = 0.001). Having a higher number of followers on SM was also associated with positive effects, specifically new patient referrals (p = 0.04). CONCLUSION: Neurosurgical oncologists can benefit by using social media professionally for increased patient engagement and networking within the medical community. Practicing in academics, making use of Twitter, and posting about interesting cases, upcoming academic events, and one's own research publications can help gain followers. In addition, having a large following on social media could lead to positive effects such as new patient referrals.

Identification of essential genes for cancer immunotherapy.

Somatic gene mutations can alter the vulnerability of cancer cells to T-cell-based immunotherapies. Here we perturbed genes in human melanoma cells to mimic loss-of-function mutations involved in resistance to these therapies, by using a genome-scale CRISPR-Cas9 library that consisted of around 123,000 single-guide RNAs, and profiled genes whose loss in tumour cells impaired the effector function of CD8+ T cells. The genes that were most enriched in the screen have key roles in antigen presentation and interferon-γ signalling, and correlate with cytolytic activity in patient tumours from The Cancer Genome Atlas. Among the genes validated using different cancer cell lines and antigens, we identified multiple loss-of-function mutations in APLNR, encoding the apelin receptor, in patient tumours that were refractory to immunotherapy. We show that APLNR interacts with JAK1, modulating interferon-γ responses in tumours, and that its functional loss reduces the efficacy of adoptive cell transfer and checkpoint blockade immunotherapies in mouse models. Our results link the loss of essential genes for the effector function of CD8+ T cells with the resistance or non-responsiveness of cancer to immunotherapies.

Predictors of hearing functional outcome following surgery for cerebellopontine angle meningioma.

OBJECTIVE: Cerebellopontine angle (CPA) meningiomas can affect hearing function and require expeditious treatment to prevent permanent hearing loss. The authors sought to determine the factors associated with functional hearing outcome in CPA meningioma patients treated with surgery and/or radiation therapy in the form of either stereotactic radiosurgery or stereotactic radiation therapy. METHODS: Consecutive patients with CPA meningiomas who had presented at our hospital from 2008 to 2018 were identified through retrospective chart review. Hearing function (as defined by pure tone average (PTA) and speech discrimination score (SDS) on Audiogram) was assessed before and after surgery for CPA meningioma. Audiograms with PTA > 50 dB and SDS < 69% were defined as poor hearing functional outcome. Multivariable Cox Proportional Hazards Regression Model was used to assess the associations between pre-operative hearing functional assessment and post-operative hearing functional outcomes. RESULTS: The study cohort included 31 patients (80.6% females, with a mean age of 61.3 ± 15.2 years) with a median clinical follow-up of 5 months (range: 1 week-98 months). The mean pre-operative PTA and SDS were 23.8 ± 11.2 dB and 64.4 ± 22.2% respectively. At the last visit, there was significant hearing recovery, with an improvement of 29.7 ± 18.0 dB (p < 0.001) and 87.6 ± 17.8% (p < 0.001) in PTA and SDS respectively. After adjusting for age, gender, tumor volume, location, and tumor classification, Multivariable Cox Proportional Hazards Regression Model was conducted which revealed that patients undergoing surgery through retro sigmoid approach [Hazards Ratio (HR): 32.1, 95% Confidence Interval (CI): 2.11-491.0, p = 0.01] and gross total resection (GTR) (HR: 2.99, 95% CI: 1.09-9.32, p = 0.05) had significantly higher risk of poor hearing functional outcome compared to petrosal approach and near/subtotal resection. Moreover, patients with poor preoperative hearing had 85% higher chance of poor hearing functional outcome postoperatively (HR: 0.15, 95%CI: 0.03-0.59, p = 0.007). CONCLUSION: Postoperative improvement in hearing is a reasonable expectation following surgery for CPA meningioma. Preoperative hearing, surgical approach and extent of surgical resection are predictive factors of postoperative hearing function outcome and can therefore aid in identification of patients at higher risk of hearing loss.

Time from stereotactic radiosurgery to immunotherapy in patients with melanoma brain metastases and impact on outcome.

BACKGROUND: The role of immunotherapy for metastatic melanoma has expanded over the past decade triggering questions regarding the combination and timing of immunotherapy and radiation for brain metastases. We used the National Cancer Database (NCDB) to see if the time from radiation to immunotherapy in patients with melanoma brain metastases had an impact on survival. METHODS: We queried the NCDB from 2010 to 2015 for patients with melanoma brain metastases treated with immunotherapy and stereotactic radiosurgery (SRS). Receiver operator characteristic (ROC) curve analysis was done to determine a timepoint associated with outcome. Cox regression was used to identify predictors of survival. Propensity matching was done to account for indication bias. RESULTS: We identified 247 patients meeting the above criteria. The median patient age was 62 years (27-90) and the vast majority were Caucasian (99%). The median SRS dose was 22 Gy (18-24 Gy).The median time to SRS was 39 days (0-344) and the median time to immunotherapy was 56 days (6-454). The ROC analysis revealed 8 days from SRS to immunotherapy as associated with outcome. Fifty-six patients had immunotherapy prior to SRS, 30 patients had immunotherapy within 0-7 days of SRS, and the remaining 161 had immunotherapy greater than 7 days from SRS. Three year survival rates were 21%, 55%, and 35% for those timeframes, respectively (p = 0.0153). Propensity matching of the 0-7 day and > 7 day groups yielded 28 pairs and Kaplan Meier analysis showed 3 year overall survival of 55% and 35%, in favor of immunotherapy within 7 days of SRS (p = 0.0357). Multivariable Cox regression identified lack of extracranial disease, more recent year of treatment, and time from SRS to immunotherapy of 0-7 days as predictors of improved survival. CONCLUSIONS: Immunotherapy within 7 days of SRS shows a possible association with improve outcomes in patients with brain metastases from melanoma.

US Food and Drug Administration regulatory updates in neuro-oncology.

OBJECTIVE: Contemporary management of patients with neuro-oncologic disease requires an understanding of approvals by the US Food and Drug Administration (FDA) related to nervous system tumors. To summarize FDA updates applicable to neuro-oncology practitioners, we sought to review oncology product approvals and Guidances that were pertinent to the field in the past year. METHODS: Oncology product approvals between January 1, 2020, and December 31, 2020, were reviewed for clinical trial outcomes involving tumors of the nervous system. FDA Guidances relevant to neuro-oncology were also reviewed. RESULTS: Five oncology product approvals described outcomes for nervous system tumors in the year 2020. These included the first regulatory approval for neurofibromatosis type 1: selumetinib for children with symptomatic, inoperable plexiform neurofibromas. Additionally, there were 4 regulatory approvals for non-central nervous system (CNS) cancers that described clinical outcomes for patients with brain metastases. These included the approval of tucatinib for metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer including patients with brain metastases, brigatinib for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), and pralsetinib and selpercatinib for RET fusion-positive NSCLC. Finally, two FDA Guidances for Industry, "Cancer Clinical Trial Eligibility Criteria: Brain Metastases" and "Evaluating Cancer Drugs in Patients with Central Nervous System Metastases" were published to facilitate drug development for and inclusion of patients with CNS metastases in clinical trials. CONCLUSIONS: Despite the challenges of the past year brought on by the COVID-19 pandemic, progress continues to be made in neuro-oncology. These include first-of-their-kind FDA approvals and Guidances that are relevant to the management of patients with nervous system tumors.

Stereotactic Radiosurgery for Pituitary Carcinoma.

A pituitary carcinoma (PC) is a rare neoplasm, accounting for only 0.2% of pituitary tumors, and is defined by the presence of noncontiguous metastatic disease. Its management requires a multimodal approach including surgery, irradiation, and medical therapy. Stereotactic radiosurgery (SRS) by means of the Gamma Knife or CyberKnife may be considered potentially useful in such cases. It has mainly been applied for localized metastases and symptomatic lesions, but it may also be effective in control of aggressive tumor growth at the primary site after sufficient surgical debulking of the lesion. Given the infrequency of PC and their heterogeneous nature with regard to the histopathological type, local extension, and location of metastases, large clinical series have not been compiled to date. While, in such cases, SRS is certainly not curative and does not prevent disease progression, it is quite reasonable to incorporate this treatment option into a multimodal management strategy and apply it judiciously at the treating clinician's discretion on a case-by-case basis.

Temporal bone resection for lateral skull-base malignancies.

INTRODUCTION: Malignancies involving the temporal bone are increasingly common and require specialized multi-disciplinary care. Given this complex location, involvement of the lateral skull base and local neurovascular structures is common. In this review we discuss general principles for temporal bone resection, as well as alternative and complementary surgical approaches that should be considered in the management of patients with temporal bone cancer. METHODS: A comprehensive review on literature pertaining to temporal bone resection was performed. RESULTS: The primary surgical strategy for malignancies of the temporal bone is temporal bone resection. This may be limited to the ear canal and tympanic membrane (lateral temporal bone resection) or may include the otic capsule and its contents (subtotal temporal bone resection), and/or the petrous apex (total temporal bone resection). Management of adjacent neurovascular structures including the facial nerve, the carotid artery, and the jugular bulb/sigmoid sinus should be considered during surgical planning. Finally, adjunctive procedures such as parotidectomy and neck dissection may be required based on tumor stage. CONCLUSIONS: Temporal bone resection is an important technique in the treatment of lateral skull-base malignancies. This strategy should be incorporated into a multi-disciplinary approach to cancer.

Management of olfactory neuroblastoma, neuroendocrine carcinoma, and sinonasal undifferentiated carcinoma involving the skullbase.

INTRODUCTION: 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. METHODS: A comprehensive literature review on contemporary management of olfactory neuroblastoma, sinonasal neuroendocrine carcinoma, and sinonasal undifferentiated carcinoma was performed. RESULTS: 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. CONCLUSIONS: 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.

Options and strategies for hearing restoration in pediatric neurofibromatosis type 2.

PURPOSE: In this article, we will review the mechanisms and natural history of hearing loss in neurofibromatosis type 2 (NF2) and discuss the hearing outcomes with different rehabilitation options. METHODS: Review of the published literature. RESULTS: NF2 is a rare autosomal dominant syndrome characterized by vestibular schwannomas and other intracranial and spinal tumors. Bilateral vestibular schwannomas are the hallmark of the disease which occur in 90 to 95% of the patients. As a result, hearing loss will eventually occur in almost all NF2 patients. Deafness can occur from tumor progression or from treatment of vestibular schwannomas and is among the most debilitating aspects of NF2. A number of surgical and non-surgical rehabilitation options are available for these patients including cochlear and auditory brainstem implants. The audiologic outcomes with surgical rehabilitation options have been variable but most patients are able to achieve sound awareness and benefit from auditory cues in lip reading. CONCLUSION: Early identification and treatment of NF2 patients can help in achieving better hearing outcomes in the pediatric population. An increasing number of NF2 patients are receiving open set word understanding with refinement in surgical techniques.

Ganglioglioma Arising from the Septum Pellucidum: Case Report and Review of the Literature.

BACKGROUND: Gangliogliomas are low-grade neoplasms that typically affect patients under the age of 30 and present with epilepsy and symptoms of mass effect. Here, we report a case of an intraventricular ganglioglioma involving the septum pellucidum in a pediatric patient with history of optic glioma. Only one other pediatric intraventricular ganglioglioma arising from the septum pellucidum has been reported previously. CASE REPORT: The patient initially presented at 9 months of age with a pilocytic astrocytoma centered on the optic chiasm, treated with chemotherapy and radiation at 3 years of age. Routine follow-up imaging at 13 years of age revealed the development of a mass in the septum pellucidum, which was subtotally resected endoscopically because of its proximity to the fornices. Pathology confirmed a ganglioglioma positive for the BRAF V600E mutation. The tumor residual progressed and was treated with stereotactic radiosurgery. The patient was asymptomatic at her 6-month follow-up visit and the size of the nodule remained stable. LITERATURE REVIEW: Our review of the 25 previously reported intraventricular gangliogliomas found that their pre-surgical diagnoses were often incorrect, reflecting the difficulty of making the diagnosis with signs, symptoms, and imaging alone. Patients can be reassured that the prognosis is generally favorable following uncomplicated neurosurgical resection.

Repeat stereotactic radiosurgery for Cushing's disease: outcomes of an international, multicenter study.

Stereotactic radiosurgery (SRS) is frequently used for Cushing's disease (CD) after failed pituitary surgery. Management of patients with persistent CD after failed SRS is complex, as the alternative therapeutic options harbor significant risks. The outcomes of repeat pituitary radiosurgery, however, have not been described. We sought to determine the outcomes of repeat SRS in patients with CD. We pooled data from five institutions participating in the International Gamma Knife Research Foundation for patients with recurrent or persistent CD ≥ 12 months after initial SRS. Patients were included in the study if they had ≥ 6 months endocrine follow-up after repeat SRS. Twenty patients were included in the study. Repeat single-session SRS was performed 1.3-9.7 years after initial SRS. Median endocrine follow-up was 6.6 years (1.4-19.1 years). Median margin dose was 20 Gy (range 10.8-35 Gy). Endocrine remission after second SRS was noted in 12 patients (60%), with a median time to remission of 6 months (range 2-64 months). Biochemical recurrence occurred in two patients (17%) after initial remission. Overall, the cumulative rates of durable endocrine remission at 5 and 10 years were 47 and 53%, respectively. Two patients (10%) experienced adverse radiation effects, including transient visual loss and permanent diplopia. Repeat SRS achieves lasting biochemical remission in approximately half of patients with CD refractory to both prior microsurgery and SRS. Because of the morbidity of refractory or recurrent CD, repeat SRS should be considered for carefully selected patients with hypercortisolism confirmed one or more years after initial SRS.

Endoscopic endonasal resection of sinonasal/anterior skull base malignancy (Kadish C esthesioneuroblastoma).

BACKGROUND: The surgical management of anterior skull base malignancies requires the full complement of open and endoscopic skull base approaches. Due to the evolution of endoscopic techniques, endoscopic approaches are now being employed for complex skull base tumors. METHODS: We present our technique for endoscopic management for an advanced (T4) anterior skull base malignancy that provides a systematic approach to resection, margin assessment, and reconstruction. CONCLUSION: Our surgical strategy provides a systematic approach by which an oncologic resection can be performed within the context of a spectrum of surgical strategies necessary to manage skull base malignancies.

Tumors displaying hybrid schwannoma and neurofibroma features in patients with neurofibromatosis type 2.

Although schwannoma and neurofibroma tumors are generally reported as distinct pathologic diagnoses, sporadic schwannoma/neurofibroma hybrid nerve sheath tumors have been reported in the general population with components of both entities. We report the clinicopathological features of these hybrid nerve sheath tumors in patients with neurofibromatosis type 2 (NF2). A retrospective review of nerve sheath tumor surgical specimens from patients with NF2 enrolled at the National Institutes of Health was performed. Those specimens reported to have schwannoma-like and neurofibromalike features were selected for further characterization by morphology, immunohistochemical panel (CD34, S100, neurofilament triplet protein (immunostain) (NFTP), epithelial membrane antigen (EMA)), and confirmation as hybrid tumors. Of 43 total NF2 patients undergoing resection of nerve sheath tumors, 11 specimens from 11 (26%) patients were found to be benign nerve sheath tumors exhibiting hybrid features of both neurofibroma and schwannoma. Immunohistochemical studies showed the schwannoma component to be S100+, CD 34- while the neurofibroma component was CD34+, variable S100+. Our experience emphasizes the importance of including this distinct tumor subtype, the schwannoma/neurofibroma hybrid tumor, in the differential diagnosis of nerve sheath tumors in NF2 patients and suggests that the relationship between neurofibroma and schwannoma tumors is closer than previously suspected..

Pituitary insufficiency from large unruptured supraclinoid internal carotid artery aneurysm.

A 59-year-old female presented with headache and fatigue. Angiography revealed a giant superior hypophyseal aneurysm with intrasellar extension. Serum endocrine panel demonstrated pituitary insufficiency. The aneurysm was treated with a pipeline flow-diverting stent and the hypopituitarism was treated with hormone replacement. Pituitary insufficiency from aneurysmal compression is extremely rare.

Facial Nerve Schwannoma Treatment with Stereotactic Radiosurgery (SRS) versus Resection followed by SRS: Outcomes and a Management Protocol.

Background Stereotactic radiosurgery (SRS) and resection are treatment options for patients with facial nerve schwannomas without mass effect. Objective This article evaluates outcomes of patients treated with SRS versus resection + SRS. Method We retrospectively compared 43 patients treated with SRS to 12 patients treated with resection + SRS. The primary study outcome was unfavorable combined endpoint, defined as worsening or new clinical symptoms, and/or tumor radiological progression. SRS (38.81 ± 5.3) and resection + SRS (67.14 ± 11.8) groups had similar clinical follow-ups. Results At the time of SRS, the tumor volumes of SRS (mean ± standard error; 1.83 ± 0.35 mL) and resection + SRS (2.51 ± 0.75 mL) groups were similar. SRS (12.15 ± 0.08 Gy) and resection + SRS (12.16 ± 0.14 Gy) groups received similar radiation doses. SRS group (42/43, 98%) had better local tumor control than the resection + SRS group (10/12, 83%, p = 0.04). Most of SRS (32/43, 74%) and resection + SRS (10/12, 83%) group patients reached a favorable combined endpoint following SRS ( p = 0.52). Considering surgical associated side effects, only 2/10 patients of the resection + SRS group reached a favorable endpoint ( p < 0.001). Patients of SRS group, who are > 34 years old ( p = 0.02), have larger tumors (> 4 mL, 0.04), internal auditory canal (IAC) segment tumor involvement ( p = 0.01) were more likely to reach an unfavorable endpoint. Resection + SRS group patients did not show such a difference. Conclusion While resection is still needed for larger tumors, SRS offers better clinical and radiological outcomes compared to resection followed by SRS for facial schwannomas. Younger age, smaller tumors, and non-IAC situated tumors are factors that portend a favorable outcome.

Use of Single-Arm Trials for US Food and Drug Administration Drug Approval in Oncology, 2002-2021.

Importance: Single-arm trials have allowed for transformative therapies to be made available to patients expeditiously. However, using single-arm trials to support drug approval presents several challenges that must be carefully considered. Observations: Between January 1, 2002, and December 31, 2021, the US Food and Drug Administration granted 176 new malignant hematology and oncology indications based on single-arm trials, including 116 accelerated approvals (AAs) and 60 traditional approvals. Overall, 87 approvals (49%) were for new molecular entities or original biologics and 89 (51%) were supplemental indications. Response rate (RR) was the most common end point used to support approval in these single-arm trials (173 of 176 [98%]). Of the 116 AAs based on single-arm trials, 45 (38%) fulfilled their postmarketing requirement to verify clinical benefit, 61 (52%) are pending verification of benefit, and 10 (9%) were withdrawn from the market as of December 31, 2021. Most (56 of 61 [92%]) AAs based on single-arm trials pending verification of benefit occurred during the previous 5 years and have ongoing confirmatory trials as of December 2021. Conclusions and Relevance: Single-arm trials have been a common development strategy to support regulatory approval as early-stage expansion cohorts with promising durable RRs have become more prevalent. In the appropriate context, single-arm trials using durable RRs can allow patients expedited access to novel therapies and will continue to serve a role in advancing drug development in oncology. However, single-arm trials have a smaller noncomparative safety data set, inability to use time-to-event end points, and other limitations that require careful consideration within the context of the disease and available therapies. The randomized clinical trial remains the preferred approach in clinical investigation.

Project Confirm: Accelerated Drug Approvals for Chronic Myeloid Leukemia.

The FDA has an accelerated approval program for drugs that have been identified as promising treatments for serious conditions when the available data suggest that the benefits outweigh the foreseeable risks. All of the currently available treatment options for chronic myeloid leukemia (CML) initially went through the accelerated approval program. Here, a group of academic CML experts, patient panelists, and members from the FDA convened to discuss the utility of the accelerated approval program as it pertains to CML, and the utility of this program in future drug development in this disease. The results of that discussion are summarized here.