Immunogenicity of high-dose influenza vaccination in patients with primary central nervous system malignancy.

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.

Influenza vaccine immunogenicity in patients with primary central nervous system malignancy.

BACKGROUND: Patients with central nervous system (CNS) malignancies represent an "at-risk" population for contracting influenza, particularly if they are receiving ongoing chemotherapy, radiation, and/or glucocorticoid treatment. The Centers for Disease Control endorses vaccination for these patients, although data are not available to indicate whether they mount an immunologic response adequate to achieve clinical protection. METHODS: A pilot prospective cohort study was designed to evaluate the immunogenicity of the standard-dose trivalent inactivated influenza vaccine in patients with malignant CNS tumors. Baseline data collection included diagnosis, chemotherapy, timing of chemotherapy or radiation relative to vaccination, and glucocorticoid dose. Serum samples were collected at baseline, day 14, day 28, and month 3 following vaccination. Samples were tested using hemagglutinin inhibition to determine seroconversion (4-fold rise in titer) and seroprotection (titer >1:40). RESULTS: A total of 38 patients were enrolled (mean age, 54 years ±13.5 years, 60.5% male, 94.7% Caucasian, and 5.3% African American). CNS tumor diagnoses included glioblastoma multiforme (55.2%), other high-grade glioma (13.2%), low-grade glioma (15.8%), and primary CNS lymphoma (15.8%). At enrollment, 20 patients (52.6%) were taking glucocorticoids, 25 (65.8%) were on active chemotherapy, and 3 (7.9%) were undergoing radiation. Seroconversion rates at day 28 for the A/H1N1, A/H3N2, and B strains were 37%, 23% and 23%, respectively. Seroprotection was 80%, 69%, and 74%, respectively. All rates were significantly lower than published rates in healthy adults (P < .001). CONCLUSION: Influenza vaccine immunogenicity is significantly reduced in patients with CNS malignancies. Future studies are needed to determine the causative etiologies and appropriate vaccination strategies.

Taste and smell disturbances after brain irradiation: a dose-volume histogram analysis of a prospective observational study.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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). CONCLUSIONS: Radiation-induced taste toxicity appears to be more common in temporal lobe tumors, and may be related to the dose received by the nasopharynx.

An automated system for detecting nonadherence in laboratory testing and monitoring for myelosuppression in patients receiving self-administered oral chemotherapy.

INTRODUCTION: 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. PATIENTS AND METHODS: 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). RESULTS: 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). CONCLUSION: 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.