The impact of cancer metastases on COVID-19 outcomes: A COVID-19 and Cancer Consortium registry-based retrospective cohort study.

BACKGROUND: COVID-19 can have a particularly detrimental effect on patients with cancer, but no studies to date have examined if the presence, or site, of metastatic cancer is related to COVID-19 outcomes. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, the authors identified 10,065 patients with COVID-19 and cancer (2325 with and 7740 without metastasis at the time of COVID-19 diagnosis). The primary ordinal outcome was COVID-19 severity: not hospitalized, hospitalized but did not receive supplemental O2 , hospitalized and received supplemental O2 , admitted to an intensive care unit, received mechanical ventilation, or died from any cause. The authors used ordinal logistic regression models to compare COVID-19 severity by presence and specific site of metastatic cancer. They used logistic regression models to assess 30-day all-cause mortality. RESULTS: Compared to patients without metastasis, patients with metastases have increased hospitalization rates (59% vs. 49%) and higher 30 day mortality (18% vs. 9%). Patients with metastasis to bone, lung, liver, lymph nodes, and brain have significantly higher COVID-19 severity (adjusted odds ratios [ORs], 1.38, 1.59, 1.38, 1.00, and 2.21) compared to patients without metastases at those sites. Patients with metastasis to the lung have significantly higher odds of 30-day mortality (adjusted OR, 1.53; 95% confidence interval, 1.17-2.00) when adjusting for COVID-19 severity. CONCLUSIONS: Patients with metastatic cancer, especially with metastasis to the brain, are more likely to have severe outcomes after COVID-19 whereas patients with metastasis to the lung, compared to patients with cancer metastasis to other sites, have the highest 30-day mortality after COVID-19.

Parent Penalty: Parental Leave Experiences of Trainees and Early-Career Faculty in Oncology Subspecialties.

PURPOSE: Prime childbearing years occur during medical training and early career, leaving physicians with tough choices between family planning and career growth. Restrictive workplace parental leave (PL) policies may negatively affect physician well-being. We evaluate existing PL and lactation policies, as well as return-to-work experiences, among oncology trainees and early-career faculty. METHODS: An anonymous 43-question cross-sectional survey was distributed via e-mail and social media channels between May and June 2021 to oncology trainees and physicians within 5 years of terminal training in the United States. The survey was administered through SurveyMonkey. Descriptive statistics were used to analyze data. Two hundred seventy-five participants were recruited via social media and outreach to program directors and coordinators in adult hematology/oncology and radiation oncology program directors. RESULTS: The average duration of PL was <6 weeks for most participants. Among those who used PL, 50% felt pressured to work while on PL, 60% felt guilty asking coworkers for help, and 79% were overwhelmed with demands of work and home, whereas only 27% had resources available at workplace to assist with transition back to work. Among those who breastfed at return to work, 31% did not have access to a lactation room, 56% did not have adequate pumping breaks, and 66% did not have pumping breaks mandated in contract. CONCLUSION: Our findings underline the immense magnitude of problems surrounding inadequate PL and support for lactating mothers among trainees and early-career physicians in oncology subspecialities. Policies and practices around PL and lactation should be restructured to meet the needs of the evolving oncology workforce.

Systemic Anticancer Therapy and Thromboembolic Outcomes in Hospitalized Patients With Cancer and COVID-19.

Importance: Systematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking. Objective: To assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer. Design, Setting, and Participants: This registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022. Exposure: Treatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19. Main Outcomes and Measures: Main outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up. Results: Of 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13). Conclusions and Relevance: In this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19-related thromboembolism in patients with cancer.

Impact of COVID-19 in patients on active melanoma therapy and with history of melanoma.

INTRODUCTION: COVID-19 particularly impacted patients with co-morbid conditions, including cancer. Patients with melanoma have not been specifically studied in large numbers. Here, we sought to identify factors that associated with COVID-19 severity among patients with melanoma, particularly assessing outcomes of patients on active targeted or immune therapy. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, we identified 307 patients with melanoma diagnosed with COVID-19. We used multivariable models to assess demographic, cancer-related, and treatment-related factors associated with COVID-19 severity on a 6-level ordinal severity scale. We assessed whether treatment was associated with increased cardiac or pulmonary dysfunction among hospitalized patients and assessed mortality among patients with a history of melanoma compared with other cancer survivors. RESULTS: Of 307 patients, 52 received immunotherapy (17%), and 32 targeted therapy (10%) in the previous 3 months. Using multivariable analyses, these treatments were not associated with COVID-19 severity (immunotherapy OR 0.51, 95% CI 0.19 - 1.39; targeted therapy OR 1.89, 95% CI 0.64 - 5.55). Among hospitalized patients, no signals of increased cardiac or pulmonary organ dysfunction, as measured by troponin, brain natriuretic peptide, and oxygenation were noted. Patients with a history of melanoma had similar 90-day mortality compared with other cancer survivors (OR 1.21, 95% CI 0.62 - 2.35). CONCLUSIONS: Melanoma therapies did not appear to be associated with increased severity of COVID-19 or worsening organ dysfunction. Patients with history of melanoma had similar 90-day survival following COVID-19 compared with other cancer survivors.

Breakthrough SARS-CoV-2 infections among patients with cancer following two and three doses of COVID-19 mRNA vaccines: a retrospective observational study from the COVID-19 and Cancer Consortium.

Background: Breakthrough SARS-CoV-2 infections following vaccination against COVID-19 are of international concern. Patients with cancer have been observed to have worse outcomes associated with COVID-19 during the pandemic. We sought to evaluate the clinical characteristics and outcomes of patients with cancer who developed breakthrough SARS-CoV-2 infections after 2 or 3 doses of mRNA vaccines. Methods: We evaluated the clinical characteristics of patients with cancer who developed breakthrough infections using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19; NCT04354701). Analysis was restricted to patients with laboratory-confirmed SARS-CoV-2 diagnosed in 2021 or 2022, to allow for a contemporary unvaccinated control population; potential differences were evaluated using a multivariable logistic regression model after inverse probability of treatment weighting to adjust for potential baseline confounding variables. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) are reported. The primary endpoint was 30-day mortality, with key secondary endpoints of hospitalization and ICU and/or mechanical ventilation (ICU/MV). Findings: The analysis included 2486 patients, of which 564 and 385 had received 2 or 3 doses of an mRNA vaccine prior to infection, respectively. Hematologic malignancies and recent receipt of systemic anti-neoplastic therapy were more frequent among vaccinated patients. Vaccination was associated with improved outcomes: in the primary analysis, 2 doses (aOR: 0.62, 95% CI: 0.44-0.88) and 3 doses (aOR: 0.20, 95% CI: 0.11-0.36) were associated with decreased 30-day mortality. There were similar findings for the key secondary endpoints of ICU/MV (aOR: 0.60, 95% CI: 0.45-0.82 and 0.37, 95% CI: 0.24-0.58) and hospitalization (aOR: 0.60, 95% CI: 0.48-0.75 and 0.35, 95% CI: 0.26-0.46) for 2 and 3 doses, respectively. Importantly, Black patients had higher rates of hospitalization (aOR: 1.47, 95% CI: 1.12-1.92), and Hispanic patients presented with higher rates of ICU/MV (aOR: 1.61, 95% CI: 1.06-2.44). Interpretation: Vaccination against COVID-19, especially with additional doses, is a fundamental strategy in the prevention of adverse outcomes including death, among patients with cancer. Funding: This study was partly supported by grants from the National Cancer Institute grant number P30 CA068485 to C-YH, YS, SM, JLW; T32-CA236621 and P30-CA046592 to C.R.F; CTSA 2UL1TR001425-05A1 to TMW-D; ACS/FHI Real-World Data Impact Award, P50 MD017341-01, R21 CA242044-01A1, Susan G. Komen Leadership Grant Hunt to MKA. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH).

Racial Disparities in COVID-19 Outcomes Among Black and White Patients With Cancer.

Importance: Non-Hispanic Black individuals experience a higher burden of COVID-19 than the general population; hence, there is an urgent need to characterize the unique clinical course and outcomes of COVID-19 in Black patients with cancer. Objective: To investigate racial disparities in severity of COVID-19 presentation, clinical complications, and outcomes between Black patients and non-Hispanic White patients with cancer and COVID-19. Design, Setting, and Participants: This retrospective cohort study used data from the COVID-19 and Cancer Consortium registry from March 17, 2020, to November 18, 2020, to examine the clinical characteristics and outcomes of COVID-19 in Black patients with cancer. Data analysis was performed from December 2020 to February 2021. Exposures: Black and White race recorded in patient's electronic health record. Main Outcomes and Measures: An a priori 5-level ordinal scale including hospitalization intensive care unit admission, mechanical ventilation, and all-cause death. Results: Among 3506 included patients (1768 women [50%]; median [IQR] age, 67 [58-77] years), 1068 (30%) were Black and 2438 (70%) were White. Black patients had higher rates of preexisting comorbidities compared with White patients, including obesity (480 Black patients [45%] vs 925 White patients [38%]), diabetes (411 Black patients [38%] vs 574 White patients [24%]), and kidney disease (248 Black patients [23%] vs 392 White patients [16%]). Despite the similar distribution of cancer type, cancer status, and anticancer therapy at the time of COVID-19 diagnosis, Black patients presented with worse illness and had significantly worse COVID-19 severity (unweighted odds ratio, 1.34 [95% CI, 1.15-1.58]; weighted odds ratio, 1.21 [95% CI, 1.11-1.33]). Conclusions and Relevance: These findings suggest that Black patients with cancer experience worse COVID-19 outcomes compared with White patients. Understanding and addressing racial inequities within the causal framework of structural racism is essential to reduce the disproportionate burden of diseases, such as COVID-19 and cancer, in Black patients.

Assessment of Regional Variability in COVID-19 Outcomes Among Patients With Cancer in the United States.

Importance: The COVID-19 pandemic has had a distinct spatiotemporal pattern in the United States. Patients with cancer are at higher risk of severe complications from COVID-19, but it is not well known whether COVID-19 outcomes in this patient population were associated with geography. Objective: To quantify spatiotemporal variation in COVID-19 outcomes among patients with cancer. Design, Setting, and Participants: This registry-based retrospective cohort study included patients with a historical diagnosis of invasive malignant neoplasm and laboratory-confirmed SARS-CoV-2 infection between March and November 2020. Data were collected from cancer care delivery centers in the United States. Exposures: Patient residence was categorized into 9 US census divisions. Cancer center characteristics included academic or community classification, rural-urban continuum code (RUCC), and social vulnerability index. Main Outcomes and Measures: The primary outcome was 30-day all-cause mortality. The secondary composite outcome consisted of receipt of mechanical ventilation, intensive care unit admission, and all-cause death. Multilevel mixed-effects models estimated associations of center-level and census division-level exposures with outcomes after adjustment for patient-level risk factors and quantified variation in adjusted outcomes across centers, census divisions, and calendar time. Results: Data for 4749 patients (median [IQR] age, 66 [56-76] years; 2439 [51.4%] female individuals, 1079 [22.7%] non-Hispanic Black individuals, and 690 [14.5%] Hispanic individuals) were reported from 83 centers in the Northeast (1564 patients [32.9%]), Midwest (1638 [34.5%]), South (894 [18.8%]), and West (653 [13.8%]). After adjustment for patient characteristics, including month of COVID-19 diagnosis, estimated 30-day mortality rates ranged from 5.2% to 26.6% across centers. Patients from centers located in metropolitan areas with population less than 250 000 (RUCC 3) had lower odds of 30-day mortality compared with patients from centers in metropolitan areas with population at least 1 million (RUCC 1) (adjusted odds ratio [aOR], 0.31; 95% CI, 0.11-0.84). The type of center was not significantly associated with primary or secondary outcomes. There were no statistically significant differences in outcome rates across the 9 census divisions, but adjusted mortality rates significantly improved over time (eg, September to November vs March to May: aOR, 0.32; 95% CI, 0.17-0.58). Conclusions and Relevance: In this registry-based cohort study, significant differences in COVID-19 outcomes across US census divisions were not observed. However, substantial heterogeneity in COVID-19 outcomes across cancer care delivery centers was found. Attention to implementing standardized guidelines for the care of patients with cancer and COVID-19 could improve outcomes for these vulnerable patients.

NCDB Analysis of Melanoma 2004-2015: Epidemiology and Outcomes by Subtype, Sociodemographic Factors Impacting Clinical Presentation, and Real-World Survival Benefit of Immunotherapy Approval.

Background: The incidence of invasive melanoma is rising, and approval for the first immune checkpoint inhibitor (ICI) to treat metastatic melanoma occurred in 2011. We aim to describe the epidemiology and outcomes in recent years, sociodemographic factors associated with the presence of metastasis at diagnosis, and the real-world impact of ICI approval on survival based on melanoma subtype and race. Methods: This is a retrospective analysis of the National Cancer Database (NCDB) from the years 2004-2015. The primary outcome was the overall survival of metastatic melanoma by subtype. Secondary outcomes included sociodemographic factors associated with the presence of metastasis at diagnosis and the impact of treatment facility type and ICI approval on the survival of metastatic melanoma. Results: Of the 419,773 invasive melanoma cases, 93.80% were cutaneous, and 4.92% were metastatic at presentation. The odds of presenting with metastatic disease were higher in African Americans (AA) compared to Caucasians (OR 2.37; 95% CI 2.11-2.66, p < 0.001). Treatment of metastatic melanoma at an academic/research facility was associated with lower mortality versus community cancer programs (OR 0.75, 95 % CI 0.69-0.81, p-value < 0.001). Improvement in survival of metastatic melanoma was noted for Caucasians after the introduction of ICI (adjusted HR 0.80, 95% CI 0.78-0.83, p < 0.001); however, this was not statistically significant for AA (adjusted HR 0.80, 95% CI 0.62-1.02, p-value = 0.073) or ocular cases (HR 1.03, 95% CI 0.81-1.31, p-value = 0.797). Conclusion: Real-world data suggest a 20% improvement in survival of metastatic melanoma since the introduction of ICI. The disproportionately high odds of metastatic disease at presentation in AA patients with melanoma suggest the need for a better understanding of the disease and improvement in care delivery.

Outcomes of in-hospital cardiopulmonary resuscitation for cardiac arrest in adult patients with metastatic solid cancers: A Nationwide Inpatient Sample database analysis from 2012 to 2014.

BACKGROUND: Cardiopulmonary arrest is known to have a poor prognosis, further worsened by preexisting comorbidities. With improved treatment, the prevalence of metastatic cancers is rapidly increasing; however, the outcomes of in-hospital cardiopulmonary resuscitation (ICPR) remain to be well described. This study examines the epidemiology, associations, and outcomes of ICPR in these patients. METHODS: This is a retrospective cohort analysis of the Nationwide Inpatient Sample database (2012-2014) including patients aged ≥18 years with metastatic cancers. Primary outcome was inpatient mortality following ICPR. Factors associated with the primary outcome were analyzed using univariate/multivariate logistic regression analysis. RESULTS: Among all admissions with metastatic cancers (n = 5,500,684), 0.47% (n = 26,070) received ICPR. Inpatient mortality was 81.77% (n = 8905) versus 68.90% among those without metastatic solid cancers and receiving ICPR. Inpatient palliative care encounter was documented in 18.95% of patients with metastatic cancer who received ICPR. On multivariate logistic regression, some of the notable factors associated with higher mortality included being of African American or Hispanic race and hospital admission over the weekend. Factors associated with lower mortality included female sex, elective admission, and head and neck as the primary site. Admissions with ICPR were associated with higher mean total charge of hospitalization (by $48,670) compared with admissions without ICPR. Of those who survived ICPR, 43.82% were transferred to another facility after discharge. CONCLUSIONS: Among adult patients with metastatic solid cancers having ICPR, 81.8% died within the same hospital admission. Race and admission type predicted mortality. Despite known poor prognosis, only a minority had palliative care. LAY SUMMARY: Cardiopulmonary resuscitation during hospitalization for patients who have metastatic cancer has a very poor outcome with a mortality rate of 81.77%. Inpatient cardiopulmonary resuscitation in these patients is also associated with a significantly higher cost of care, longer length of stay, and high rate of transfer to a different health care facility upon discharge. Knowledge of these outcomes is helpful in discussing the pros and cons of pursuing aggressive resuscitative interventions with patients and families.

COVID-19 and Cancer: Lessons Learnt from a Michigan Hotspot.

(1) Background: Outcomes with coronavirus disease 2019 (COVID-19) have been worse in those with comorbidities and amongst minorities. In our study, we describe outcomes amongst cancer patients in Detroit, a major COVID-19 hotspot with a predominant inner-city population. (2) Methods: We retrospectively analyzed 85 patients with active invasive cancers who were infected with COVID-19. The primary outcome was death or transition to hospice. (3) Results: The majority were males (55.3%, n = 47), ≤70 years old (58.5%, n = 50), and African Americans (65.5%, n = 55). The most common primary site was prostate (18.8%, n = 16). Inpatient admission was documented in 85.5% (n = 73), ICU admission in 35.3% (n = 30), and primary outcome in 43.8% (n = 32) of hospitalized patients. On a multivariate analysis, factors associated with increased odds of a primary outcome included an age of >70 years versus ≤70 years (OR 4.7, p = 0.012) and of male gender (OR 4.8, p = 0.008). Recent cancer-directed therapy was administered in 66.7% (n = 20) of ICU admissions versus 39.5% (n = 17) of general floor admissions (Chi-square p-value of 0.023). (4) Conclusions: High rates of mortality/transition to hospice and ICU utilization were noted amongst our patients with active invasive cancer, following a COVID-19 infection. Men and those of >70 years of age had a greater than four-fold increase in odds of death or transition to hospice.

Knowledge, Attitudes, and Practices Pertaining to Lung Cancer Screening Among Primary Care Physicians in a Public Urban Health Network.

INTRODUCTION: Lung cancer screening (LCS) with annual low-dose computed tomography in high-risk groups decreases the mortality related to lung cancer. Its implementation rate has been low, and knowledge relating to LCS has not been assessed in providers treating underserved populations. MATERIALS AND METHODS: An institutional review board-approved anonymous survey was sent to primary care physicians of the Cook County Health system, a safety-net healthcare system. The survey assessed the knowledge pertaining to LCS guidelines, providers' experience with LCS, and their recommendations for quality improvement using 24 questions. The predictors of LCS within the previous 6 months were identified using logistic regression analysis. RESULTS: Of the 152 survey responses, 43% were from nontrainees with diverse training backgrounds. Adequate knowledge of LCS was demonstrated by 72% of the respondents, and pretest counseling was the domain most often answered incorrectly in the questionnaire. LCS had been ordered in the previous 6 months by 57% of the respondents. However, 88% estimated that they had screened < 50% of eligible patients. Higher patient volume, more experience, and family medicine training predicted for ordering LCS in the previous 6 months. In addition, 82.2% indicated that prompts in the electronic medical records would increase LCS, and 78.3% reported that receiving statistics about their LCS practice would increase LCS performance. CONCLUSIONS: Primary care physicians in the hospital healthcare system had reasonable knowledge of LCS, but the implementation rate was low. We have identified areas for improvement relating to LCS implementation.

Incidence and outcomes of heparin-induced thrombocytopenia in solid malignancy: an analysis of the National Inpatient Sample Database.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction to heparin products characterized by thrombocytopenia with or without thrombosis. This study aimed to determine the incidence, morbidity, mortality and economic burden of HIT in solid-malignancy-related hospitalizations. We analyzed the National Inpatient Sample Database (NIS), the largest public database of hospital admissions in the United States, from January 2012 to September 2015. The primary outcome of the study was the incidence of HIT. Secondary outcomes included incidence of venous thrombosis (acute deep venous thrombosis and pulmonary embolism), arterial thrombosis (thrombotic stroke, myocardial infarctions and other arterial thromboembolism), mortality associated with HIT, length of stay, total hospital charges and disposition. During the study period, 7 437 049 hospitalizations had an associated diagnosis of solid malignancy. Approximately 0·08% (n = 6225) hospitalizations had a secondary diagnosis of HIT in this population. The standardized incidence of total thrombotic events was higher in the solid malignancy with HIT compared to the solid malignancy without HIT group (24·7% vs. 6·8%, P < 0·001). The standardized mortality rate was 4·8% in solid malignancy with HIT compared to 3·4% in the without HIT group (OR, 1·53; 95% CI, 1·25-1·89; P < 0·001). HIT in solid malignancy is a rare condition but associated with increased morbidity and mortality.

Epidermal Growth Factor Receptor-mutated Lung Cancer as the Initial Manifestation of Germline TP53 Mutation Associated Cancer.

Epidermal growth factor receptor (EGFR) mutation-driven lung cancer is a rare occurrence in patients with Li-Fraumeni syndrome (LFS) characterized by germline mutations in the tumor protein 53 (TP53) gene. Here we describe a case of primary EGFR mutation-driven lung adenocarcinoma in a young woman with LFS. There is only one other reported case with such presentation. We review the interactions between the TP53 gene and EGFR pathways facilitating lung carcinogenesis. We also review other cases with similar presentations described in the literature and the response to tyrosine kinase inhibitors (TKI) in this rare patient population.