Patients with cancer are presumed to be at increased risk from COVID-19 infection–related fatality due to underlying malignancy, treatment-related immunosuppression, or increased comorbidities. A total of 218 COVID-19–positive patients from March 18, 2020, to April 8, 2020, with a malignant diagnosis were identified. A total of 61 (28%) patients with cancer died from COVID-19 with a case fatality rate (CFR) of 37% (20/54) for hematologic malignancies and 25% (41/164) for solid malignancies. Six of 11 (55%) patients with lung cancer died from COVID-19 disease. Increased mortality was significantly associated with older age, multiple comorbidities, need for ICU support, and elevated levels of D-dimer, lactate dehydrogenase, and lactate in multivariate analysis. Age-adjusted CFRs in patients with cancer compared with noncancer patients at our institution and New York City reported a significant increase in case fatality for patients with cancer. These data suggest the need for proactive strategies to reduce likelihood of infection and improve early identification in this vulnerable patient population. Significance: COVID-19 in patients with cancer is associated with a significantly increased risk of case fatality, suggesting the need for proactive strategies to reduce likelihood of infection and improve early identification in this vulnerable patient population. This article is highlighted in the In This Issue feature, p. 890

Head and neck squamous cell carcinoma (HNSCC) can progress and upstage during prolonged time to treatment initiation (TTI), which may increase mortality¹ and the likelihood of recurrence.² Delayed treatment initiation can also result in increased costs due to the need for more aggressive treatment and evoke patient anxiety.³ Quiz Ref ID Despite the apparent benefits of avoiding treatment delay, analysis of the National Cancer Database between 1998 and 2011 found that the median TTI in head and neck cancer had increased from 19 to 30 days.⁴ Murphy et al⁴ ascribed this trend to the progression toward greater complexity of multimodality therapy, increased pretreatment radiologic/pathological workup, and more transitions in care.

PURPOSE: Delays in oncologic time to treatment initiation (TTI) independently and adversely affect disease-specific mortality. Social Determinants of Health (SDoH) are increasingly recognized as significant contributors to patients' disease management and health outcomes. Our academic center has validated a 10-item SDoH screener, and we elucidated which specific needs may be predictive of delayed TTI. METHODS: This is a retrospective cohort study at an urban academic center of patients with a SDoH screening and diagnosis of breast, colorectal, endocrine/neuroendocrine, GI, genitourinary, gynecologic, head and neck, hematologic, hepatobiliary, lung, or pancreatic cancer from 2018 to 2022. Variables of interest included household income, tumor stage, and emergency department (ED) or inpatient admission 30 days before diagnosis. Factors associated with delayed TTI ≥45 days were assessed using multivariable logistic regression. RESULTS: Among 2,328 patients (mean [standard deviation] age, 64.0 (12.8) years; 66.6% female), having >1 unmet social need was associated with delayed TTI (odds ratio [OR], 1.68; 95% CI, 1.54 to 1.82). The disparities most associated with delay were legal help, transportation, housing stability, and needing to provide care for others. Those with ED (OR, 0.49; 95% CI, 0.44 to 0.54) or inpatient (OR, 0.54; 95% CI, 0.50 to 0.58) admission 30 days before diagnosis were less likely to experience delay. CONCLUSION: Delays in oncologic TTI ≥45 days are independently associated with unmet social needs. ED or inpatient admissions before diagnosis increase care coordination, leading to improved TTI. Although limitations included the retrospective nature of the study and self-reporting bias, these findings more precisely identify targets for intervention that may more effectively decrease delay. Patients with SDoH barriers are at higher risk of treatment delay and could especially benefit from legal, transportation, caregiver, and housing assistance.

Purpose: HPV(−) OCSCC resists radiation treatment. The CDKN2A gene, encoding p16INK4A, is commonly disrupted in OCSCC. p16 inhibits CDK4/CDK6, leading to cell cycle arrest, but the biological sequelae of CDK4/6 inhibition in OCSCC remains understudied. This study examines whether inhibition of CDK4/6 enhances radiation response in OCSCC. Methods: MTT assays were performed in OCSCC cell lines HN5 and CAL27 following treatment with palbociclib. Clonogenic survival and synergy were analyzed after radiation (RT-2 or 4Gy), palbociclib (P) (0.5 µM or 1 µM), or concurrent combination treatment (P+RT). DNA damage/repair and senescence were examined. CDK4/6 were targeted via siRNA to corroborate P+RT effects. Three-dimensional immortalized spheroids and organoids derived from patient tumors (conditionally reprogrammed OCSCC CR-06 and CR-18) were established to further examine and validate responses to P+RT. Results: P+RT demonstrated reduced viability and synergy, increased β-gal expression (~95%), and ~two-fold higher γH2AX. Rad51 and Ku80 were reduced after P+RT, indicating impairment of both HR and NHEJ. siCDK4/6 increased senescence with radiation. Spheroids showed reduced proliferation and size with P+RT. CR-06 and CR-18 further demonstrated three-fold reduced proliferation and organoids size with P+RT. Conclusion: Targeting CDK4/6 can lead to improved efficacy when combined with radiation in OCSCC by inducing senescence and inhibiting DNA damage repair.