ABSTRACT
Purpose: Determine the role of social determinants of health (SDOH), including socioeconomic status (SES) (education, income in predicting intent to vaccinate for COVID-19 among a diverse community-based population, over sampled for cancer survivors in Connecticut (CT). Background: Race, ethnicity, and the SDOH (e.g., food insecurity, housing instability, trouble paying utilities bills) have a known impact on COVID-19 incidence, morbidity, and mortality. Although the impact on cancer survivors is not as well understood, this population may also face disproportionately severe outcomes. To our knowledge, there are no published studies that address intention to vaccinate in community based populations that are predominantly African American/Black (AA) or Hispanic/Latinx (H/L), nor in the cancer survivors who live in these communities. Prior studies have suggested that some vulnerable populations have lowered willingness to vaccinate (e.g., for influenza) than other groups. This study will explore the role of the high burden of SDOH barriers and selected socio-cultural factors such as perceived risk, medical mistrust, and source of health information. Methods: Data for this study are from 252 CT residents, collected from August - December, 2020 using Qualtrics, an online survey platform. Using an extensive network of community partners, we recruited through list serves and social media, targeting communities known to be most impacted by the pandemic. The intent was to enroll a population that was similar to the racial/ethnic sociodemographic profile of the city of New Haven, while oversampling cancer survivors. Using SAS 9.4, we conducted descriptive and multivariate analyses to identify the role of SDOH in willingness to vaccinate. Results: The study population was disproportionately African American/Black (23.5%) and Hispanic/Latinx (17.5%) and included 83 (32.9%) cancer survivors. In this high-risk population, 38.9% of the sample were unwilling or uncertain whether they would vaccinate against Covid-19 in the future. In multivariate adjusted model, individuals reporting at least one SDOH barrier (food insecurity, trouble paying utilities bills, or housing instability) were significantly less likely to vaccinate (odds ratio=2.26;95% Confidence Interval 1.17-4.36). Other significant predicators included low perceived risk and lacking confidence in information provided through the health care system. Conclusion: Social determinants of health play a critical role in predicting intent to vaccinate for COVID-19. Special efforts are needed to ensure that vulnerable populations understand their individual risk, the benefits and risks of getting the COVID-19 vaccine, with interventions aimed at enlisting trusted entities that may not be recognized as traditional sources of health information.
ABSTRACT
Cancer patients display immunomodulation related to malignancy and anti-cancer therapies, but how these factors impact COVID-19 remains unknown. To investigate immune responses in cancer patients with COVID-19, we undertook a prospective case-control study, enrolling hospitalized solid tumor patients with acute COVID-19, as well as age-, gender-, and comorbidity-matched COVID-19 patients without cancer as controls. Using biospecimens collected during hospitalization, we performed virologic measurements as well as in-depth immunophenotyping of cellular, antibody and cytokine responses. We enrolled 17 cancer patients (cases) admitted to Yale-New Haven Hospital between March 15 and June 30, 2020 with COVID-19, as well as 17 matched non-cancer patients (controls) admitted with COVID-19. No significant differences were observed between cases and controls based on patient characteristics (age, gender, race, co-morbidities, smoking history, days from symptom onset to COVID-19 diagnosis) or outcomes (COVID-19 severity, length of hospital stay, rate of intubation or mortality). The most common primary tumor sites were lung (4/17) and gastrointestinal (4/17);all cases had received cancer-directed therapy within 6 months of COVID-19 diagnosis, with 13/17 receiving treatment less than 1 month prior to hospitalization. Three of 17 cases had received immune checkpoint inhibitor therapies. Despite having similar SARS-CoV-2 viral RNA loads at the time of COVID-19 diagnosis when compared with controls, cancer cases had increased viral RNA abundance during hospitalization, suggesting slower clearance. Antibody responses against SARS-CoV-2 were preserved in cancer cases, with cases displaying similar levels of IgM and IgG antibodies directed against SARS-CoV-2 epitopes compared to controls. Cytokine profiling revealed higher plasma levels of CCL3, IL1A and CXCL12 in cancer cases compared to controls. Using flow cytometric immunophenotyping, we found that innate immune and non-T cell adaptive immune parameters were similar between cases and controls hospitalized with COVID-19. However, among cancer cases on conventional therapies, T cell lymphopenia was more profound, and these cases demonstrated higher levels of CD8+ exhausted (CD8+CD45RA-PD1+TIM3+ ), CD8+GranzymeB+ and CD4+CD38+HLA-DR+ and CD8+CD38+HLA-DR+ activated T cells when compared with controls;interestingly, these differences were not observed in patients who had received immune checkpoint inhibition. Thus, we found reduced viral RNA clearance and specific alterations in T cell and cytokine responses in cancer patients hospitalized with COVID-19 compared with matched controls with COVID-19. This dysregulated T cell response in cancer patients, which may reflect immune modulation due to chronic antigen stimulation as well as cancer therapies, may lead to altered virologic and clinical outcomes in this population.
ABSTRACT
Objective: Assess consumer experience and health impact among under-resourced individuals who were enrolled into longitudinal navigation to address social determinants of health (SDOH) needs and health goals related to cancer primary and secondary prevention. Background: The Yale Cancer Disparities Firewall Project is a multi-tiered initiative to address the social determinants of health (SDOH) and other challenges that prevent at-risk communities from receiving the full benefit of the many available cancer prevention and cancer screening options. A communityfacing health navigation program, staffed by community members who have received extensive multidisciplinary training is a central component of this program. Methods: Of the 61 currently enrolled individuals (all of whom are either African American/Black or Hispanic/Latinx), we collected questionnaire data from 24 individuals (39% response rate). In general, participants are enrolled for a minimum of 1 year, but most have been followed for 2 years. Respondents were similar to non-respondents with respect to race (60% were Black/African American vs 61.2%, respectively) and age (mean = 44.8 vs 47.2 years, respectively). Respondents were more likely to be female (85% vs 71.4%, p =.009), Hispanic/Latinx (35% vs 42%), but significantly less likely to be foreign-born (15% vs 26.5 %, p = .021). We assessed satisfaction with assigned navigator(s), uptake of referred services, knowledge gained, health behavior change, and self-rated health (SRH). Results: Per self-report, 79.2% of participants agreed and a further 12.5% somewhat agreed that they were overall satisfied with their experience with the health navigation program. Importantly, two-thirds (66.7%) agreed and a further 20.8% somewhat agreed that they changed their behavior to improve their health and well-being because of the program. Of the 5 health focused services offered, the most commonly reported uptake was physical activity (87.5%), followed by learning how to eat healthier and losing weight. Additionally, one third (33.3%) of participants received assistance with reducing or stopping smoking. In terms of secondary prevention, 62.5% of clients received assistance with cancer screening. Of the 5 SDOH focused services offered, the most common was assistance with finding food to eat (66.7%) followed by assistance with paying utilities (45.8%), a shift from the priority needs at baseline (40% needing food assistance, and 35% with housing concerns), presumably reflecting the additional strains associated with the COVID-19 pandemic. Conclusions: Against the backdrop of COVID-19, these findings suggest that addressing SDOH barriers through individual navigation is an important add-on service when facilitating access to services to maintain healthy lifestyle and adhere to cancer screening guidelines. Although this was a pilot program, we foresee the opportunity to utilize trained non-clinical navigators and/or community health workers and to promote cancer prevention in at risk communities.
ABSTRACT
Background: The therapeutic landscape in metastatic NSCLC has dramatically changed with approvals of immunotherapy agents in both treatment-naïve and previously treated cancer patients (pts) and irrespective of histology. Pts with tumors that develop resistance is a significant area of unmet need. Vascular endothelial growth factor (VEGF) has been shown to modulate the tumor immune microenvironment and combination immune checkpoint and VEGF/VEGF receptor inhibition have shown benefit in multiple tumor types. Lung-MAP is a master protocol for pts with stage IV, previously treated NSCLC. Pts who were not eligible for a biomarker-matched substudy enrolled in S1800A. The adverse event profile will be presented. Methods: S1800A is a phase II randomized trial for pts who previously received PD-1 or PD-L1 inhibitor therapy for at least 84 days and platinum-based doublet therapy with ECOG 0-1 stratified by PD-L1 expression, histology and intent to receive ramucirumab in the standard of care (SOC) arm. Pts were randomized 1:1 to pembrolizumab and ramucirumab P+R or SOC (docetaxel +R [SOC w R];docetaxel, pemetrexed or gemcitabine [SOC wo R]). The primary endpoint was overall survival. Secondary endpoints included response, duration of response, investigator assessed-progression free survival and evaluation of toxicity. Results: From May 17, 2019 to November 16, 2020, 166 pts enrolled and 140 determined eligible [69 (49%) P+R;46 (33%) SOC w R;25 (18%) SOC wo R]. Treatments for those who received SOC wo R included 3 on docetaxel (19%);12 on gemcitabine (75%);and on 1 on pemetrexed (6%). 131 were eligible for adverse event (AE) assessment. The most common AE were fatigue (38%), proteinuria (28%), hypertension (23%), diarrhea (22%) and hypothyroidism (22%) on P+R;fatigue (61%), anemia (48%), diarrhea (41%) and neutropenia (39%) on SOC w R and anemia (56%), leukopenia (56%), fatigue (44%) and neutropenia (44%) on SOC wo R. Grade ≥ 3 treatment-related AEs occurred in 32% of pts on P+R, 54% of pts on SOC w R and 56% of pts on SOC wo R. Cardiac and thromboembolic events occurred in 12% of pts on P+R, 11% of pts on SOC w R and 0% of pts on SOC wo R. Grade 5 AE occurred in 2 pts on P+R (respiratory failure and cardiac arrest), 3 pts on SOC w R (2 respiratory failure and sepsis) and 1 pt on SOC wo R (sepsis). Four patients were diagnosed with COVID-19 (1 on P+R and 3 on SOC) and 3 died (1 on P+R and 2 on SOC). Conclusions: Grade 3 toxicities were lower in P+R compared to SOC arms with or without R. Cardiac and thromboembolic events were similar in arms that included R. P+R was generally well-tolerated. Efficacy outcomes will be presented when data matures.