ABSTRACT
Background: Oral mucositis (OM) is a debilitating side effect of concomitant chemoradiotherapy (CRT) for head and neck cancer (HNC). EC-18 may effectively mitigate OM by minimizing the CRT-induced innate immune response. This Phase II, 2-stage trial evaluated safety, tolerability, and efficacy of EC- 18 in reducing the duration, incidence, and trajectory of severe OM (SOM) in HNC patients. Methods: Patients (n = 105) with pathologically confirmed oral cavity, oropharynx, hypopharynx, or nasopharynx squamous cell cancers who received intensity-modulated radiation therapy (IMRT;with ≥ 55 Gy on ≥ 2 oral sites) and weekly or tri-weekly cisplatin were studied. In Stage 1, 24 patients were randomized (n = 6 per arm) to receive 500, 1000, or 2000 mg of EC-18, or placebo. Following independent Data Safety Monitoring Board review, 81 patients in Stage 2 received EC-18 2000 mg (n = 41) or placebo (n = 40) throughout CRT. WHO OM grade was assessed twice weekly during IMRT and then once weekly for up to 6 weeks post-IMRT. The primary efficacy endpoint was duration of SOM during the active and short-term follow-up (STFU) periods in the compliant per-protocol population (PP). Much of Stage 2 was conducted during peak periods of the COVID-19 pandemic which measurably impacted patient compliance relative to test medication dosing and planned radiation. Consequently, to assess efficacy most accurately, the PP population was analyzed (with at least 4 weeks of study drug dosing, minimum cumulative radiation of 55 Gy, 80% study drug compliance in the first 28 days of dosing, and without using not-allowed-therapy). Results: Patient demographics and baseline characteristics were balanced between groups. Adverse events (AEs) were comparable amongst cohorts without drug-related severe AEs. In the PP, the median duration of SOM from baseline through STFU was 0 day in the EC-18 group (n = 22) v 13.5 days in the placebo group (n = 20). SOM incidence through STFU (45.5% v 70%) and opioid use (time to onset: 32.3 v 26.0 days;and duration: 32.8 v 37.5 days) favored EC-18 v placebo. Results of the covariates analyses suggested that EC-18 favorably impacted SOM incidence in patients who experienced SOM treated with weekly low-dose cisplatin (n = 26;37.5% v placebo 70.0%) and HPV+ tumors (n = 29;35.3% v placebo 66.7%;Table). One-year long-term follow-up for tumor outcomes is ongoing. Conclusions: EC-18 safely mitigated the development and the time course of SOM in CRT-treated HNC patients. In addition, EC-18 may provide substantial benefits to subpopulations of HPV+ HNC patients treated with low dose cisplatin.
ABSTRACT
The Abbott ID NOW COVID-19 assay is a rapid point-of-care molecular test for SARS-CoV-2 detection. In theory, it has the potential to decrease turnaround times (TATs) and rapidly facilitate patient flow and triage. Reports for its performance have been mixed, likely due to variations in patient cohorts, preanalytical considerations, and study design. We prospectively evaluated the ID NOW performance against reference reverse transcriptase PCR (RT-PCR) tests, using dual swabs. Patients presented at a large multisite academic hospital with the highest volumes of COVID-19 admissions in Canada. From 1,968 valid swabs, 186 were true positive, 1,760 were true negative, 21 were false negatives, and 1 was false positive. At 10.5% positivity rate, the positive and negative predictive values were 99.5% and 98.8%, respectively. This led to a modest increase in the pretest probability in this cohort of individuals presenting <7 days of symptom onset. The mean times from collection to laboratory receipt and receipt to reporting were 31 and 23 min, respectively. This reduced TAT observed in our study may assist with triage of admitted patients and breaking the chain of transmission through immediate notification of status. We also observed how test performance changed with prevalence, and thus, how the test is used to "rule in" or "rule out" disease must be considered. Although the ID NOW is regarded as a rapid test, it is not high throughput and requires rapid transportation times (<1 h) that may not be plausible in large centers. The utility of this test should be considered with the observed TAT and interpreted in the context of limitations discussed. IMPORTANCE Rapid testing for COVID-19 has been recognized as one potentially important measure in managing the pandemic. However, these rapid tests vary grossly in their performance and their applicability. There have been many studies evaluating the performance of rapid tests for SARS-CoV-2 detection. However, they are frequently not prospective, and patients are not simultaneously swabbed to compare the reference standard RT-PCR. Previous ID NOW study findings are mixed, which may be due to various factors, including patient, epidemiological, and preanalytical considerations. It is critical to consider how the pretest and posttest probabilities and epidemiological factors may affect the performance as the community prevalence of disease fluctuates during this highly dynamic pandemic. We consider how the ID NOW may be utilized in different settings, with considerations of public health and infection control and prevention risk tolerance.