BACKGROUND: This is the largest and only multivariate study evaluating the difference in mortality from coronavirus disease 2019 (COVID-19) between patients with cancer and patients without cancer in the United States. The objective was to assess COVID-19 mortality rates in patients with cancer versus patients without cancer and uncover possible statistically significant characteristics contributing to mortality. METHODS: This retrospective study analyzed patients with cancer and patients without cancer who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March 1 through April 30, 2020. This was a multicenter study in the state of Louisiana throughout the Ochsner Health System in both tertiary and nontertiary centers. Patients older than 18 years were eligible. Three hundred twelve patients with cancer were compared with 4833 patients without cancer. RESULTS: Mortality was found to be higher in the cancer group. Patients of advanced age with cancer had a significant increase in mortality (odds ratio [OR], 5.96; P < .001). Other significant risk factors for increased mortality were male sex (OR, 2.15), a history of chronic kidney disease (OR, 3.84), and obesity (OR, 1.30). In hospitalized patients with cancer, adverse vital signs on admission, decreased absolute lymphocyte counts, thrombocytopenia, elevated creatinine, lactic acidosis, and elevated procalcitonin all seemed to increase the risk of death. Among patients with cancer, active or progressive disease (P < .001) and recent therapy (OR, 2.34; 95% confidence interval, 1.08-5.08) were shown to increase mortality. CONCLUSIONS: Patients with cancer have increased mortality in the setting of infection with SARS-CoV-2 in comparison with patients without cancer. Patients with cancer who are 65 years of age or older and those with certain comorbidities have the greatest risk of death. Recent cancer-directed therapy and disease status also seem to play roles in mortality.
Glioblastoma (GBM) is a highly malignant and lethal cancer of the central nervous system for which there has been limited progress in improving patient outcomes despite intensive research efforts. The current multimodal therapy for newly diagnosed GBM patients includes surgical resection, radiotherapy and cytotoxic chemotherapy with temozolomide (TMZ), conferring a median survival time of just 14.6 months. Failure to generate more effective treatment strategies is due to 1) the infiltrative nature of GBM tumor cells preventing complete surgical resection, and 2) the cellular heterogeneity within GBM tumors, which often comprise a sub-population of GBM cancer stem cells (GSCs) characterized by self-renewal characteristics and resistance to chemotherapeutic alkylating agents including TMZ. Multiple signaling pathways, including Notch, participate to the formation and maintenance of GSCs. Recent studies, including our research, have shown that increased levels of gap junction protein Connexin43 (Cx43) correlate with TMZ resistance in GBM cells and inversely correlated with GBM patient survival. Importantly, Cx43 has also been associated with anti-proliferative effects in glioma, and reduced levels of Cx43 protein occur in high-grade gliomas. Therefore, we hypothesized that altering Cx43 localization and/or activity rather than Cx43 expression represents a potent strategy for GBM treatment. Regulating Cx43 function is primarily associated with the multiple sites for post-translational modifications and protein-protein interactions within the Cx43 carboxy-terminus. Our research identifies crosstalk between Cx43 and Notch signaling in GSCs. Using a Cx43 carboxy-terminus mimetic peptide that modulates non-junctional functions of Cx43, we observe a decrease in Notch1 protein expression and reduced transcription of its downstream targets Hes1 and Hey1 in GSCs derived from patient tumors. Most importantly, our Cx43 mimetic peptide decreases cell survival in TMZ-resistant GSCs, limits GSC neurosphere formation in vitro, and inhibits GSC-derived tumor growth in vivo. Our current research aims at dissecting the molecular mechanisms of Cx43 functions on Notch signaling in GSCs using this Cx43 mimetic peptide. In conclusion, we have identified a novel therapeutic opportunity to decrease the tumorigenic potential of GSCs through altering Cx43 activity and Notch signaling to target chemoresistant GSCs in GBM treatment. Citation Format: Michael Lunski, James Smyth, Jennifer Vaughn, Zhi Sheng, Robert Gourdie, Benjamin Purow, Samy Lamouille. Targeting notch signaling in glioblastoma cancer stem cells through modulation of Connexin43 function [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4284.
Background: Early reports on cancer patients infected with COVID-19 have suggested a high risk of hospitalization and death compared to the general population. Limited data are available on outcomes in specific cancer types. We aim to identify whether hormonal treatment impacts severe outcomes (rate of hospitalization, ICU admission, intubation, and death) in prostate cancer patients. Methods: We conducted a multicenter study in the state of Louisiana, throughout the Ochsner Health System, in both tertiary and nontertiary centers. Patients must carry a diagnosis of prostate cancer and have a completed SARS-CoV-2 test between March 1st and April 30th, 2020. Chi-squared and Fisher’s exact tests were performed to compare the proportion of patients experiencing severe outcomes between treatment groups. Results: As of April 30, 2020, a total of 56 patients with prostate cancer who had a positive SARS-COV-2 test were identified. Median age 69, median BMI 28.8, 78.6% (n=44) black, 58.9% (n=33) current/former smokers, HTN, DM2, and CKD were the most common comorbidities, and 12.5% (n=7) of patients had stage IV disease. Of these patients, 26.8% (n=15) were on hormonal treatment (received within 90 days of COVID+ test). In terms of severe outcomes, 58.9% (n=33) of patients required hospitalization, 17.9% (n=10) required ICU admission with 14.3% (n=8) patients requiring intubation, and 23.2% (n=13) of patients died. There was no statistical difference in rate of severe outcomes (rate of hospitalization, ICU admission, intubation, and death) among prostate cancer patients receiving hormonal therapy vs. those receiving no hormonal therapy. Conclusion: With an ongoing global pandemic of COVID-19, it is important to identify characteristics leading to increased risk of severe events in cohorts of cancer patients. This small cohort does not identify hormonal therapy as a risk factor for increased rate of severe outcomes in patients with prostate cancer. Further analyses describing impact of specific hormonal regimens on risk of hospitalization and death will be completed by time of presentation. Citation Format: Karine Tawagi, Jeff Burton, Diana Maslov, Michael Lunski, Marc Matrana, Daniel Johnson. Prostate cancer and COVID-19: Impact of hormonal therapy on severe outcomes [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-083.
Introduction: While many data have been emerging regarding the outcomes of cancer patients infected with SARS-CoV-2 and their increased risk of mortality, emphasis on patients with hematologic malignancies and how they have been affected during this pandemic is lacking. Louisiana, particularly New Orleans, one of the pandemic epicenters, has a higher-than-average cancer diagnosis rate of multiple myeloma as well as cancer-related deaths. Ochsner Cancer Institute was fortunately prepared for the crisis, which allowed our center to continue taking care of both inpatients and outpatients as needed during the pandemic. Hence, we accumulated ample data among cancer patients and the effects of COVID-19. Here we provide novel initial mortality data on multiple myeloma patients infected with SARS-CoV-2. Methods: Our retrospective, electronic medical record review included 15 patients with a history of multiple myeloma who tested positive for SARS-CoV-2 PCR from March 1st to April 30th, 2020. Medical records were reviewed for inpatient/outpatient status of infection, outcome of infection, multiple myeloma disease and treatment history, and history of autologous stem cell transplant. Results: Out of the 15 patients infected, there were 6 deaths (40%). A total of 11 patients were on active treatment, including all 6 patients who died (54.5%), though active treatment did not appear to be a significant risk factor when compared to off-therapy patients (p=.103). Patients older than 65 years seem to be at increased risk of death when compared to patients less than 65 years of age (p=.011). Hospitalized patients were more likely to succumb to infection compared to non-hospitalized patients (p=.044). Of the 15 patients, 4 had a history of autologous stem cell transplant and this was not found to affect mortality (p=.103). Chronic kidney disease was present in 7 patients and did not appear to impact mortality (p=.315). Of these (n=9), 7 patients had hypogammaglobulinemia and 5 of these patients died (71.4%). Overall, 5 of the 6 patients who died were found to have hypogammaglobulinemia (the 6th death did not have immunoglobulins eligible for review). However, the presence of hypogammaglobulinemia did not appear to increase mortality overall (p=.167). Conclusion: Patients older than 65 years of age with a history of multiple myeloma seem to be at risk of death from COVID-19. Interestingly, a history of autologous stem cell transplant did not appear to affect mortality. While the presence of hypogammaglobulinemia did not affect mortality, its overwhelming finding in the patients who died warrants further discussion in the future. Larger studies are needed to expand on these findings and uncover further characteristics to help stratify at-risk patients in the future. Citation Format: Michael John Lunski, Karine Tawagi, Diana Maslov, Laura Finn. Outcomes of patients with multiple myeloma with COVID-19 infection [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-081.
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