ABSTRACT
Background: Patients with cancer have worse outcomes from COVID-19 infection. However, the specific impact of COVID-19 on patients with (HNC) is largely unknown. The COVID-19 and Cancer Consortium (CCC19) maintains an international registry (NCT04354701) aimed to investigate the clinical course and complications of COVID-19 in patients with cancer. Here, we report severity of COVID-19 and its complications among HNC patients. Methods: The CCC19 registry was queried for patients with HNC and laboratory confirmed SARS-CoV-2 infection. The co-primary outcomes were severity of COVID-19 illness on an ordinal scale (0: no complications;1: hospitalized, no oxygen (O2);2: hospitalized, required O2;3: ICU admission;4: mechanical ventilation (MV);5: death), and severity of complications (mild, moderate, serious). The outcomes were further stratified by demographics, recent treatment (systemic vs local;surgery, radiation (RT) vs systemic), treatment intent (palliative vs curative), and cancer status (remission, responding, stable, progressing). Results: From March 2020 to December 2021, 356 HNC patients were identified. Median age was 65 (interquartile range 58-74), 29% were female, 56% were white, 67% were former or current smokers, 20% had a BMI >30, 15% had an ECOG performance status >2, and 57% had >2 comorbidities. 154 (43%) had no complications, 61 (17%) were hospitalized without O2, 135 (38%) were hospitalized with O2, 50 (14%) required ICU, 32 (9%) required MV, and 74 (21%) died. 88 (25%) had mild, 59 (17%) had moderate, and 132 (37%) had serious complications. 33% of patients who received systemic therapy and 30% who received RT within 3 mo prior to COVID-19 diagnosis died. Mortality was higher in patients receiving palliative when compared to curative intent treatment (44% vs 16%). In addition, 50% of patients with actively progressing cancer, and 45% who had serious complications died. Importantly, 37 (n=12 palliative systemic therapy and n=25 local therapy) patients had a treatment delay due to COVID-19 diagnosis. Conclusions: Our study is the largest cohort to date describing COVID-19 outcomes in HNC patients and suggest a high rate of mortality even in those receiving local and curative intent treatment. Variables stratified by COVID-19 severity. Note: Ordinal levels 3 and 4 not shown due to small case numbers.
ABSTRACT
Background: Trial recruitment that requires specific actionable mutations based on next-generation sequencing (NGS) is challenging. Barriers can include competing studies, physician study awareness, site proximity, mutation incidence, among other concerns. Methods: This study (NCT04432454) opened clinical sites using two methods during the COVID-19 pandemic. The “Traditional” approach included site selection, IRB and contract approval, and trial activation prior to a patient being identified for enrollment. The second approach used the Tempus “TIME” Trials network that would only open a site after identifying a patient with a mutation of interest and eligible for the trial. Results: The first patient enrolled was on 10/12/20 and the last patient was on 6/24/21. A total of 16 sites (6 Traditional and 10 TIME) participated. All Traditional sites, and none of the TIME sites, were affiliated with major academic institutions. Duration for full CTA execution for Traditional sites averaged 200.5 days (range 142 to 257) and for TIME sites averaged 7.6 days (range 2 to 14). IRB approval time average for Traditional sites was 27.5 days (range 12 to 71) and TIME sites was 3.0 days (range 1 to 12 days). Days from site selection to activation letter for Traditional sites was on average 250.0 days (range 187 to 281) and for TIME sites was 131.6 days (range 22 to 248). Time from study activation to first consent was 33.3 days (range 18 to 58) for Traditional sites and 8.8 days (range 1 to 35) for TIME sites. The first patient on-study was at a TIME site 115 days prior to a Traditional site and the first 7 patients enrolled were at TIME sites. Traditional sites consented 23 and enrolled 16 patients while the TIME sites consented 16 and enrolled 13. The trial enrolled all 29 patients in 8 months with the anticipated enrollment duration being 12 to 18 months. Conclusions: Although the Traditional and TIME programs had different operational models, they both contributed a significant number of patients and reduced the projected enrollment timeline. TIME sites enrolled the initial patients. These results demonstrate that the “Just-in-Time model,” in conjunction with a Traditional model, can reduce projected overall time to enrollment in biomarker-driven studies.
ABSTRACT
BACKGROUND: Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of antineoplastic systemic therapies can result in less robust antibody titers following vaccination and possible risk of breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history of cancer and those on active immunosuppression (including chemotherapy), limited evidence is available to inform the clinical efficacy of COVID-19 vaccination across the spectrum of patients with cancer. PATIENTS AND METHODS: We describe the clinical features of patients with cancer who developed symptomatic COVID-19 following vaccination and compare weighted outcomes with those of contemporary unvaccinated patients, after adjustment for confounders, using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19). RESULTS: Patients with cancer who develop COVID-19 following vaccination have substantial comorbidities and can present with severe and even lethal infection. Patients harboring hematologic malignancies are over-represented among vaccinated patients with cancer who develop symptomatic COVID-19. CONCLUSIONS: Vaccination against COVID-19 remains an essential strategy in protecting vulnerable populations, including patients with cancer. Patients with cancer who develop breakthrough infection despite full vaccination, however, remain at risk of severe outcomes. A multilayered public health mitigation approach that includes vaccination of close contacts, boosters, social distancing, and mask-wearing should be continued for the foreseeable future.