Hypercoagulability is a recognized feature in SARS-CoV-2 infection. There exists a need for a dedicated risk assessment model (RAM) that can risk-stratify hospitalized COVID-19 patients for venous thromboembolism (VTE) and guide anticoagulation. We aimed to build a simple clinical model to predict VTE in COVID-19 patients. This large-cohort, retrospective study included adult patients admitted to four hospitals with PCR-confirmed SARS-CoV-2 infection. Model training was performed on 3531 patients hospitalized between March and December 2020 and validated on 2508 patients hospitalized between January and September 2021. Diagnosis of VTE was defined as acute deep vein thrombosis (DVT) or pulmonary embolism (PE). The novel RAM was based on commonly available parameters at hospital admission. LASSO regression and logistic regression were performed, risk scores were assigned to the significant variables, and cutoffs were derived. Seven variables with assigned scores were delineated as: DVT History = 2; High D-Dimer (>500–2000 ng/mL) = 2; Very High D-Dimer (>2000 ng/mL) = 5; PE History = 2; Low Albumin (<3.5 g/dL) = 1; Systolic Blood Pressure <120 mmHg = 1, Tachycardia (heart rate >100 bpm) = 1. The model had a sensitivity of 83% and specificity of 53%. This simple, robust clinical tool can help individualize thromboprophylaxis for COVID-19 patients based on their VTE risk category.

Objective: To assess and compare tolerability for standard-of-care treatments and evaluate outcomes in older and younger patients with oropharyngeal cancer (OPC). Methods and Materials: We queried our institutional database for nonmetastatic OPC treated curatively between January 2009 and June 2020, with radiation therapy ± systemic therapy, or surgery ± adjuvant radiation therapy ± systemic therapy. We compared clinicopathological, treatment-related, and therapeutic toxicity features, and survival outcomes between older (≥ 65 y at diagnosis) and younger (< 65 y at diagnosis) patients across human papilloma virus (HPV) subtypes. Multivariate analyses for predictors of survival in all patients were performed. Results: In this retrospective study, we evaluated 340 patients with OPC: 123 (36%) older and 217 (64%) younger. There were 252 patients (74%) with HPV+ve OPC. The HPV+ve older patients showed an increasing trend over the years studied. Definitive radiation therapy ± systemic therapy was utilized in 73.2%, while the remainder had surgery ± adjuvant radiation therapy ± systemic therapy. After a median follow-up of 5.24 (interquartile range: 3.53) years, no significant differences in treatment received, overall, disease-free, locoregional recurrence-free, or distant metastasis-free survival were seen between age groups, regardless of HPV status. Significantly larger proportions of older patients received cetuximab (25.8% vs 11.9%; P < .001), required hospitalization (46.6% vs 26.9%; P < .001), required feeding tubes (63.6% vs 49.5%; P = .02), and were switched to a less-toxic systemic therapy protocol (18.3% vs 7.7%; P = .019). For all patients, factors such as radiation therapy course completion, radiation therapy delays, unplanned hospitalizations, and feeding tubes never removed were independently associated with various survival endpoints. Conclusion: While survival outcomes were equivalent between older and younger patients with OPC, older patients exhibited lower tolerance and higher toxicity from systemic therapy, suggesting a need for enhanced multidisciplinary supportive care including geriatric assessment, for older patients receiving concomittant radiation and systemic therapy.

Epithelial Ovarian Cancer (EOC) is the most lethal gynecologic cancer with no predominant genetic alteration identified that can be therapeutically targeted. Low-cost non-toxic approaches such as dietary modulations alter the responses of host and the cancer cells. Limited scientific investigations have examined the link between nutrition and EOC. Here, we tested the outcome of intermittent fasting (IF) on EOC progression with focus on fasting driven anti-tumor immune responses. Female C57/B6 mice were injected intraperitoneally with 5x10⁶ mouse epithelial ovarian cancer ID8 (p53^-/-, ID8 p53^{-/-, PTEN-/-} and ID8 p53^{-/-, BRCA-/-}) cells and fed either ad libitum (RD) or subjected to IF, where they underwent 16 hour fasting and 8 hour feeding window for 5 days/week. Tumor progression was monitored by ascites formation and abdominal circumference. Immune profiling was performed by flow cytometry using BD FACS Calibur. Untargeted metabolomics was performed in plasma from RD and IF mice using LC-MS/MS. Enhancement of immunotherapy was tested by combining IF with anti-PD 1 (100 µg/mice, every 5^th day, 3 times) in ID8 p53^-/- tumor bearing mice and similar parameters were examined. IF reduced the growth of ID8 (p53^-/-, ID8 p53^{-/-, PTEN-/-} and ID8 p53^{-/-, BRCA-/-}) tumors, increased overall survival when compared to RD mice. IF promoted anti-tumor T cell response as seen by increase in CD4⁺ and CD8⁺ cells with enhanced expression of IFNγ, granzyme B and perforin compared to RD mice bearing ID8 cells in the ascites and blood. A striking observation was that the CD4⁺ T cells from IF mice exhibited a strong Th1 phenotype (CD4⁺IFNγ⁺), while Th2 phenotype (CD4⁺IL4⁺) was significantly decreased. IF when combined with anti-PD-1 treatment significantly improved survival and potentiated the T cell mediated anti-tumor response. Metabolic analysis revealed an enrichment in ketone body biosynthetic pathway as reflected by 5fold increase in serum ketone bodies such as beta hydroxy butyrate (BHB) and acetoacetate, when compared to RD. Receptors that have been reported to response to BHB as a ligand, specifically GPR109A and GPR41, were highly expressed on T cells derived from IF mice. BHB treatment enhanced the CD8+ T cell effector function as reflected by increased levels of IFNγ, granzyme B and perforin compared to untreated CD8+ T cells. Our study shows that IF significantly restricts EOC growth, improve survival, potentiate chemotherapy and immunotherapy anti-tumor response by augmenting T cell mediated anti-tumor immune responses. We also provide evidence that IF generated bioactive metabolite BHB which can be a potential substitute for availing the ant-tumor benefits of IF. Thus, our data provides strong evidence for IF and its metabolic mediator BHB for ameliorating EOC progression and as a viable approach in maintaining and sustaining an effective anti-tumor T cell response alone and in combination with immunotherapy. Citation Format: Mary Priyanka Udumula, Laila Poisson, Lin Chun-Hui, Nivedita Tiwari, Harshit Singh, Giri Shailendra, Ramandeep Rattan. Fasting fueled ketogenesis inhibits ovarian cancer and promotes anti-tumor T cell response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2161.

Click on the article title to read more.