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This retrospective chart review identified six patients with recurrent MG andFour patients were assessed for response. One patient had a partial response, two patients achieved stable disease and one was refractory. One patient with anOsimertinib had a tolerable safety profile in this heavily pretreated brain tumor population. Osimertinib may benefit select patients with recurrent MG containing

Background: EGFR alterations are commonly observed in malignant gliomas (MG). Osimertinib, an irreversible EGFR-tyrosine kinase inhibitor, effectively penetrates the blood brain barrier and achieves therapeutic concentrations in brain tissue. Materials and Methods: This retrospective chart review identified six patients with recurrent MG and EGFR alterations who received osimertinib. Results: Four patients were assessed for response. One patient had a partial response, two patients achieved stable disease and one was refractory. One patient with an EGFR vIII rearrangement remained on treatment for 236 days and a second patient with an EGFR vIII mutation remained on treatment for 294 days and continued on treatment at the time of analysis. Thrombocytopenia occurred in two patients, one patient developed grade 1 diarrhea and pneumonia, and another patient developed grade 1 mucositis. Conclusion: Osimertinib had a tolerable safety profile in this heavily pretreated brain tumor population. Osimertinib may benefit select patients with recurrent MG containing EGFR alterations.

Background For cancer patients, rates of influenza-associated hospitalization and death are 4 times greater than that of the general population. Previously, we reported reduced immunogenicity to the standard-dose influenza vaccine in patients with central nervous system malignancy. In other poorly responding populations (eg, elderly patients), high-dose vaccination has improved efficacy and immunogenicity. Methods A prospective cohort study was designed to evaluate the immunogenicity of the Fluzone® high-dose influenza vaccine in brain tumor patients. Data on diagnosis, active oncologic treatment, and immunologic status (eg, CD4 count, CD8 count, CD4:CD8 ratio) were collected. All patients received the high-dose vaccine (180 µg). Hemagglutination inhibition titers were measured at baseline, day 28, and 3 months following vaccination to determine seroconversion (≥4-fold rise) and seroprotection (titer ≥1:40), which were compared to our prior results. Results Twenty-seven patients enrolled. Diagnoses included high-grade glioma (85%), CNS lymphoma (11%), and meningioma (4%). Treatment at enrollment included glucocorticoids (n = 8, 30%), radiation (n = 2, 7%), and chemotherapy (n = 9, 33%). Posttreatment lymphopenia (PTL, CD4 ≤ 200) was observed in 4 patients (15%). High-dose vaccination was well tolerated with no grade III-IV toxicity. Overall, seroconversion rates for the A/H1N1, A/H3N2, and B vaccine strains were significantly higher than in our prior study: 65% vs 37%, 69% vs 23%, and 50% vs 23%, respectively (all P < .04). Seroconversion was universally poor in patients with PTL. While seroprotection at 3 months declined in our prior study, no drop was observed following high-dose vaccination in this cohort. Conclusions The immunologic response to HD influenza vaccination was higher in this cohort than standard-dose influenza vaccination in our prior report. These findings mirror those in elderly patients where high-dose vaccination is the standard of care and raise the possibility of an immunosenescence phenotype.

EGFR alterations are commonly observed in malignant gliomas (MG), especially glioblastomas, making this pathway an appealing therapeutic target. Unlike other EGFR tyrosine kinase inhibitors (TKIs), osimertinib (osi), a third-generation, irreversible EGFR-TKI commonly used to treat EGFR-mutant lung cancer, is able to effectively penetrate the blood brain barrier (BBB) and achieve therapeutic concentrations in brain tissue. METHODS: A retrospective chart review identified six patients (pts) aged 46–74 years with recurrent MG and known EGFR alterations identified by next generation sequencing who received at least one dose of osi between 1/1/2018 and 5/26/2020. Patients received osi 80 mg by mouth once daily and continued treatment until disease progression, the development of unacceptable side effects, medical complications, or death. RESULTS: All patients had EGFR amplification. Other EGFR alterations identified included EGFRvIII (1 pt), deletion of introns 1–7 (3 pts) and deletion of introns 13–15 (2 pts). Four of the six patients were evaluable for response. Three patients (75.0%) had stable disease (SD) as best response and one patient (25.0%) was refractory to treatment. One patient with an EGFRvIII mutation achieved stable disease on osi and remained on treatment for 236 days. Thrombocytopenia developed in 2 patients (grade 2 (1), grade 3 (1) in patient also on concurrent bevacizumab) and 1 patient developed grade 1 diarrhea and pneumonia. Overall, this heavily pretreated patient population tolerated osi therapy and half of the patients had a best response of SD which lasted from 77 to 236 days. CONCLUSIONS: Osi has a tolerable safety profile in this heavily pretreated brain tumor population, and it may benefit selected patients with recurrent MG containing EGFR alterations. Further clinical investigations are needed, particularly in patients whose tumors express an EGFRvIII mutation, to identify which EGFR alterations may sensitize tumors to this BBB penetrant EGFR-TKI.

BACKGROUND Social determinants of health (SDH) are modifiable factors that contribute to health outcomes. Despite studies linking SDHs with cervical, ovarian, and prostate cancer outcomes, few studies have explored SDHs in glioma patients. We conducted a cross-sectional survey to characterize and contextualize SDHs in glioma patients by community income, rural/urban residence, and treatment status. METHODS Two validated instruments: PRAPARE (Protocol for responding to and assessing patents’ assets risks and experiences) and AHC (accountable health communities instrument) quantified SDHs; along with study-specific supplemental questions. Risk scores were calculated and combined into an overall and domain-specific (economic, education, neighborhood environment, social context, and healthcare) SDH risk, with a higher score being indicative of higher SDH risk. Scores were compared between low-income (LIC) vs high-income (HIC) communities (defined by median household income), urban vs rural (defined by zip code), and active treatment vs surveillance (determined by patient medical record) using Wilcoxon rank-sum test. RESULTS 100 glioma patients were enrolled: mean age 53 years (range: 22–78); 49% male; 18% oligodendroglioma, 34% diffuse astrocytoma, 38% glioblastoma, 10% other glioma; 68% resided in LICs, 27% in rural zip codes, and 51% were on active treatment. Overall, SDH risk scores were low (mean= 4.43-out-of-38). Scores in the healthcare domain were the highest. Compared to patients from LICs, patients from HICs had higher healthcare risk scores (p< 0.05). Surveillance patients had higher overall SDH risk on the AHC than patients in active treatment (p< 0.05), with age being a confounder. In multivariable analysis, younger age, and astrocytoma histology were associated with higher social health risk. CONCLUSION Glioma patients report relatively few SDH risk factors on standardized instruments designed for general clinic populations. The higher health risk observed in patients in HICs and higher AHC risk for those in surveillance will be further explored in planned qualitative analysis.

Radiation-induced taste and smell disturbances are prevalent in patients receiving brain radiation therapy, although the mechanisms underlying these toxicities are poorly understood. We report the results of a single institution prospective clinical trial aimed at correlating self-reported taste and smell disturbances with radiation dose delivered to defined areas within the brain and nasopharynx.Twenty-two patients with gliomas were enrolled on a prospective observational trial in which patients underwent a validated questionnaire assessing taste and smell disturbances at baseline and at 3 and 6 weeks after commencement of brain radiation therapy. Fourteen patients with glioblastoma, 3 patients with grade 3 gliomas, and 5 patients with low grade gliomas participated. Median dose to tumor volume was 60 Gy (range, 45-60 Gy). Dose-volume histogram (DVH) analysis was performed for specific regions of interest that were considered potential targets of radiation damage, including the thalamus, temporal lobes, nasopharynx, olfactory groove, frontal pole, and periventricular stem cell niche. The %v10 (percent of region of interest receiving 10 Gy), %v40, and %v60 were calculated for each structure. Data from questionnaires and DVH were analyzed using stepwise regression.Twenty of 22 patients submitted evaluable questionnaires that encompassed at least the entire radiation therapy course. Ten of 20 patients reported experiencing some degree of smell disturbance during radiation therapy, and 14 of 20 patients experienced taste disturbances. Patients reporting more severe taste toxicity also reported more severe toxicities with sense of smell (r(2) = 0.60, P.006). Tumor location in the temporal lobe predicted for increased severity of taste toxicity (F3, 16 = 1.44, P.06). The nasopharynx was the only structure in which the DVH data predicted the presence of radiation-induced taste changes (r(2) = 0.28, P.02).Radiation-induced taste toxicity appears to be more common in temporal lobe tumors, and may be related to the dose received by the nasopharynx.

Preservation of cognitive functioning is a top priority for brain tumor patients but is often not addressed in a systematic manner. To address this unmet need, we established a virtual neurocognitive clinic within our brain tumor center. The aim was to incorporate standardized neuropsychological examinations into routine care. To make neuropsychological testing achievable for patients with primary brain tumors, we developed a one-hour battery to measure core cognitive functions. We established a process where patients are offered cognitive testing at initial consult by neuro-oncology or radiation oncology. To reduce the burden of an extra appointment, patients are seen by neuropsychology in the Cancer Center (as opposed to the main hospital). Appointments are coordinated on the same day as other essential visits. Results are reviewed in multidisciplinary tumor boards. When possible, patients are seen for serial cognitive assessments at 3, 6 and 12 months after RT treatment. Providers in neuro-oncology, neurosurgery, and radiation oncology were encouraged to refer survivors to neuropsychology. After the clinic launch in 2017, 143 brain tumor patients were referred to neuropsychology. Prior to the clinic launch, 22 referrals were made over a comparable timeframe. Cognitive deficits were identified in most patients. After testing, patients received education on the brain-function relationship pertaining to their deficits. The patients’ referring provider received a full report containing recommendations for interventions based on testing outcomes 11 of the 38 patients who underwent pre-treatment assessments underwent testing 6 months post-RT. With the recent addition of a dedicated clinical coordinator, the rate of successful post-treatment cognitive evaluation is increasing. The cognitive, emotional, behavioral, and psychosocial impact of a brain tumor can be difficult to categorize and treat without formal evaluation. Integrating neuropsychological examination into routine care has resulted in a massive increase in the number of brain tumor patients getting a neuropsychologic assessment.

Patient compliance with routine monitoring for self-administered chemotherapy is problematic. We sought to assess monitoring lapses and incidents of myelosuppression in patients undergoing self-administered chemotherapy for glioblastoma, as well as test software designed to detect and alert clinicians to lapses in monitoring.A retrospective analysis was conducted to identify patients (N=117) who received standard oral temozolomide for glioblastoma at our institution from 2003 to 2010. Gaps in monitoring were classified as minor (10 to 12 days) or major (13 to 28 days), and adverse events were graded using standard criteria. During the prospective portion of the study, we tested a software-based system that alerted clinicians of monitoring lapses and adverse events among patients receiving self-administered temozolomide for glioblastoma (n=37).Our retrospective review found that 34 of 117 patients experienced monitoring gaps during treatment. No association between gaps and risk of myelosuppression were found. Patients with gaps were more likely to be male (P=.04). Patients monitored prospectively with the software experienced no major gaps in monitoring (P=.007 compared with retrospective patients).Our retrospective review demonstrated that monitoring nonadherence was occurring at a substantial rate. Our computerized system eliminated major gaps in monitoring in the prospective portion of our study. Although there is no association between monitoring gaps and the occurrence of adverse events, when they do coincide, continuing oral chemotherapy during an unrecognized adverse event may worsen the patient's condition. Automated systems are justified and serve a function not currently being addressed.

Influenza is a common RNA virus that causes yearly epidemics with an illness typically presenting with fever, myalgias, constitutional symptoms, and upper and/or lower respiratory tract symptoms. Patients with malignancies receiving chemotherapy are at increased risk for influenza-related illness1,2 and have been shown to have higher complication and mortality rates.3–5 The Centers for Disease Control (CDC) recommends annual influenza vaccination for all persons older than 6 months.6 The CDC endorses the practice of influenza vaccination for patients with malignancies, although little concrete evidence exists to suggest that patients with malignancies and/or those undergoing active chemotherapy mount a sufficient immunologic response to achieve clinical protection. In the general population, influenza vaccination results in prevention of infection in ∼70%–90% of healthy young adults.7,8 Serologic response is high, with seroconversion rates of 75%–80% and seroprotection rates of around 95% based on hemagglutinin inhibition (HI) titer assessment.9,10 Studies have demonstrated reduced immunogenicity in elderly populations, with seroconversion rates of 23%–51% and seroprotection rates of 68%–97%,11 as well as other groups including patients with end-stage renal disease,12 renal transplants,13,14 liver transplants,15 and lung transplants,16 HIV populations,17 and others. Investigation of influenza vaccine efficacy in patients with malignancies has been limited. Cancer patients are vaccinated at rates well below 50%. Lack of awareness of the current recommendations, fear of side effects, and concerns about vaccine efficacy have been cited as the primary reasons for not offering vaccination.18 Studies have demonstrated seroconversion and seroprotection rates similar to healthy adults following vaccination of patients with lung cancer19 as well as those with a variety of solid tumors.20 In patients with hematologic malignancies, seroconversion rates have been reported to be lower (21%).21 Some studies have evaluated the efficacy of single vaccination, while others have suggested additional efficacy using a multidose regimen.22 The efficacy of influenza vaccination has not been evaluated in patients with central nervous system (CNS) malignancies. Nevertheless, this is a potentially robust population for study given the immunosuppressive effects of gliomas and its associated treatment,23 variable degrees of therapy-induced lymphopenia and neutropenia, and the inclusion of glucocorticoids into pharmocotherapeutic regimens. The current study pilots an investigation into influenza vaccine immunogenicity in a group of patients with CNS malignancy.

e20669 Background: Cancer patients have a 4-times greater rate of influenza-associated hospitalization and death. Previously, we reported reduced immunogenicity to the standard (SD) influenza vacci...

BACKGROUND: In a previous investigation, we demonstrated reduced immunogenicity to the standard trivalent inactivated influenza vaccine in patients with primary central nervous system (CNS) malignancy (Neuro-Oncol 2014, PMID 24714522). Other populations with similar reduced responses have shown improved immunogenicity to a high-dose vaccine. OBJECTIVE: A pilot prospective cohort study was designed to evaluate the immunogenicity of the Fluzone® High-Dose influenza vaccine in patients with CNS malignancy. METHODS: Baseline data on diagnosis, chemotherapy, radiation, glucocorticoids, and timing of treatment were collected. All patients underwent vaccination with of the Fluzone® High-Dose influenza vaccine. Serum samples are actively being collected at baseline, day 28, and 3 months following vaccine administration. Hemagglutination inhibition (HAI) titers will be measured to determine seroconversion (4-fold rise) and seroprotection (titer 1:40). RESULTS: A total of 27 patients were enrolled. Mean age at baseline was 52.7 years (+/-12.6); 41% male; 93% white and 7% black. Diagnoses included high-grade glioma (85%), CNS lymphoma (11%), and meningioma (4%). At enrollment, 8 patients (30%) were taking glucocorticoids, 4 (15%) were undergoing active radiation, 14 (52%) were on chemotherapy, and 5 (19%) began chemotherapy following vaccine administration. Prior radiation (n = 19, 70%) and chemotherapy (n = 14, 52%) were common. Seven patients (26%) reported post-vaccination symptoms potentially attributable to vaccination; 6 experienced only local soreness or redness at the injection site and 1 suffered headache, nausea, vomiting. All symptoms were transient and resolved completely. At baseline, 8 patients (30%) had absolute CD4 < 300. Serum samples for HAI assay are being collected. Seroconversion and seroprotection rates are forthcoming. CONCLUSION: Studies have shown that populations known to respond poorly to standard yearly influenza vaccination (e.g. the elderly) can mount an effective immunologic response to the high-dose vaccine. This prospective cohort study will provide preliminary data regarding the immunologic response to high-dose vaccination in patients with primary CNS malignancy. Funding: The Fluzone® High Dose vaccine and HAI titer measurements were provided by Sanofi Pasteur. Acknowledgement: This research was supported by the Clinical Research Unit of the Wake Forest Translational Science Institute.

296 Background: Protracted outpatient oral chemotherapy regimens have created new challenges for monitoring patients for toxicity. Unlike IV chemotherapy which guarantees clinician access to the patient before proceeding with therapy, oral agents can continue to be taken despite missed follow-up visits and lab draws. After observing patients return from unrecognized lapses in monitoring with severe myelosuppression, we sought to retrospectively measure risks and to prospectively test a software-based monitoring system designed to flag and notify team members of missed lab monitoring. Methods: We evaluated 117 patients who had received a standard 42-day continuous course of oral temozolomide as therapy for newly diagnosed primary malignant brain tumors to assess monitoring compliance, as well as adverse events. Standard practice is to obtain a weekly CBC with differential and platelets during the 6 weeks of concurrent chemoradiation. Grade 3 or higher hematologic events were observed in 9 (7.7%) patients. Gaps in monitoring were defined as no testing for 10 days or more, and were classified as minor (10-12 days) and major (13-27 days). Results: 34 (29.1%) patients had one or more gaps during treatment; 19 (16.2%) had majors and 18 (15.4%) had minors. 2 of the patients with gaps in coverage exhibited grade 3 or 4 myelosuppression upon their return to monitoring. We have currently monitored 36 patients prospectively with prototype software designed to email staff whenever a patient was not monitored for 7 days or had scheduled visits too far in the future. The software uses data downloaded from the electronic medical record (12,889 labs, [908 pertinent], 441 visits) and was effective in finding patients that missed labs or did not get properly scheduled visits. Five such mistakes were detected and 4 were corrected based on the system flag. Problems encountered were mainly false positives associated with entry of chemotherapy stop dates. Conclusions: Monitoring failures pose risks to patients receiving oral chemotherapy and traditional medical information systems make detection of missing data difficult. Systems such as ours are simple to build and could be integrated with most EMR systems.