Background A well-coordinated adaptive immune response is crucial for limiting COVID-19 disease. Some individuals with immunodeficiency are at a high risk of developing severe COVID-19. Therefore, the development of standardized methods for measuring different arms of the vaccine response in the setting of immunodeficiency is of particular interest. In this study, we compared the vaccine response of individuals living with immunodeficiency with healthy controls in terms of interferon gamma (IFN-γ) production and spike protein-specific antibody level post primary COVID-19 vaccination and booster vaccines. Additionally, the disease severity of those individuals who contracted COVID-19 was assessed. Methods Whole blood was stimulated overnight from 71 participants and 99 healthy controls. Commercially available PepTivator® peptide pool and trimeric spike protein stimulation were used. ELISA was used to analyze IFN-γ levels. The total SARS-CoV-2 spike protein antibody titre was measured using a Roche Elecsys® S total antibody assay. Patient characteristics, COVID-19 infection status and IDDA 2.1 ‘Kaleidoscope’ scores were recorded. Vaccine responses were scored from zero to three. Results 99% of healthy controls, 89% of individuals with IEI and 76% with secondary immunodeficiency (SID) had an IFN-γ level above the validated reference range after peptide mix stimulation following primary vaccination. There was an increase in IFN-γ levels in patients with inborn errors of immunity (IEI) following the booster vaccine (p = 0.0156). 100% of healthy controls, 70% of individuals living with IEI and 64% of individuals living with SID had detectable spike protein-specific antibody levels following the primary vaccination. 55% of immunodeficiency patients who had mild COVID-19 and 10% with moderate/severe COVID-19 had detectable antibody and IFN-γ levels post vaccine. The mean pre-infection IDDA 2.1 scores were higher in individuals who developed moderate/severe COVID-19 (25.2 compared to 9.41). Conclusions Covid whole-blood IGRA is a highly accurate, straightforward and robust assay and can be easily adapted to measure cellular response to COVID-19. A complete evaluation of the vaccine response may be particularly important for individuals living with immunodeficiency. A clinical immunodeficiency score and a validated vaccine response score may be valuable tools in estimating COVID-19 disease risk and identifying individuals living with immunodeficiency who may benefit from enhanced vaccination schedules.

The evidence to support any specific cervix high dose rate (HDR) brachytherapy schedule has never been very strong, leading to a wide variety of fractionation schedules. We present survival and toxicity data in a sample of patients treated with 2 fractions of HDR brachytherapy, the schedule routinely used in our institution since 2001. We included all consecutive patients (since August 2001) treated radically in our department with external beam radiotherapy (EBRT) to the pelvis and concomitant weekly cisplatin chemotherapy followed by HDR Brachytherapy. Data prior to January 2005 was collected retrospectively, and prospectively beginning at that date. Only patients with at least 18 months of follow-up were included. 3 and 5 year Kaplan-Meier overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), including local recurrence-free survival (LRFS) and distant recurrence-free survival (DRFS) were analyzed. Long-term genitourinary (GU) and gastrointestinal (GI) toxicity was measured. We performed a univariate analysis, by application of log–rank statistic, to identify potential prognostic factors. Multivariate analyses were performed using Cox proportional hazards modeling in those factors that showed significance on univariate analysis. 82 patients (FIGO Stage IB-IVA) were identified, EBRT median dose was 46 Gy (46–50 Gy). Chemotherapy was prescribed in 68 (14 were not considered to be fit). Prescribed dose, for each HDR Brachytherapy fraction, to point A, was 8.5 Gy. A parametrial EBRT boost was used in 2 cases, with a median dose of 8 Gy. In 3 cases with enlarged para-aortic lymph nodes, they were treated with EBRT as well, with a median dose of 46 Gy (45–60 Gy). Median rectal and bladder doses were 5.54 Gy (3.30–7.73) and 6.14 Gy (2.60–7.57) per fraction. Median treatment time was 44 days (30–72 days). Median follow-up was 35.9 months. 3 and 5-year overall OS was are 70.3% and 54.4%; the 3 and 5-year DSS was 79.8% and 70.9%; the 3 and 5-year LRFS was 87.4% and 85.2% and the 3 and 5-year DRFS was 85.4% and 78.0% (all actuarial values). RTOG Grade 3–4 GI and GU toxicity was identified in 5 patients (6.2%) and 9 patients (11.1%), respectively. Radical treatment for cervix cancer with chemo-radiotherapy and 2 fractions of HDR brachytherapy appears to be an effective approach. The reported toxicity was slightly higher than reported in some other series. Larger HDR fractions could account for this extra toxicity. 3D conformal Brachytherapy planning has been proven to reduce toxicity and it should be explored in this setting. It could enable a safe minimization of overall treatment time and it could lead to a more efficient use of finite oncological resources.

2078 Background: The combination of surgery, radiation and TMZ has become the standard therapy for pts with newly diagnosed MG; however, no standard has emerged for recurrent disease. Continuous dosing of TMZ for periods longer than 7 days has been shown to decrease the intratumoral concentration of the DNA repair enzyme methyl-guanine-methyl transferase and anecdotal evidence suggests that prolonged TMZ dosing has activity in pts whose tumors have progressed on standard adjuvant dosing regimens. Methods: Using an institutional neuro-oncology database, we retrospectively identified all pts with recurrent MG treated with a prolonged TMZ dosing schedule between 4/05 and 11/07. Results: Nineteen pts were identified who received prolonged TMZ dosing at recurrence at a dose of 50-100mg/m2/day for 21 consecutive days followed by 7 days off drug. All pts had received prior TMZ, 14 concurrent with and 17 following radiation. Their median age was 56 years (range 34–69) and 58% of these pts were male. Seventeen pts had glioblastoma multiforme and 2 had anaplastic astrocytomas. Seven pts had received 2 prior regimens and 2 pts had been treated with 3 prior therapies. The median number of prolonged TMZ cycles delivered was 2 (range 1–17+). Three pts were treated with concurrent tamoxifen and one received imatinib along with prolonged TMZ. Median time to progression was 9.5 weeks (range 4–112+). Only 1 brief partial response was seen while 4 pts had stable disease on last imaging. One pt remains on treatment. Hematologic toxicity included grade 3/4 lymphopenia (6 pts) and grade 3 thrombocytopenia (2 pts). No grade 3/4 anemia or neutropenia was seen. No opportunistic infections occurred. One pt had grade 3 thrombosis and transaminitis. No pt discontinued treatment due to toxicity. Conclusions: Prolonged TMZ dosing was well tolerated in pts with recurrent MG and prior TMZ treatment. Few responses were seen, but several pts exhibited prolonged disease stabilization. This data suggests a potential role for prolonged TMZ dosing, alone or in combination, in pts with recurrent MG following initial TMZ therapy. A multi-institution phase II study with correlative endpoints including assessment of MGMT inhibition is planned. No significant financial relationships to disclose.