Liquid Biopsy of Lung Cancer Before Pathological Diagnosis Is Associated With Shorter Time to Treatment.

PURPOSE: Studies have investigated the early use of liquid biopsy (LBx) during the diagnostic workup of patients presenting with clinical evidence of advanced lung cancer, but real-world adoption and impact has not been characterized. The aim of this study was to determine whether the use of LBx before diagnosis (Dx; LBx-Dx) enables timely comprehensive genomic profiling (CGP) and shortens time until treatment initiation for advanced non-small-cell lung cancer (aNSCLC). MATERIALS AND METHODS: This study used the Flatiron Health-Foundation Medicine electronic health record-derived deidentified clinicogenomic database of patients with aNSCLC from approximately 280 US cancer clinics. RESULTS: Of 1,076 patients with LBx CGP ordered within 30 days prediagnosis/postdiagnosis, we focused on 56 (5.2%) patients who ordered LBx before diagnosis date (median 8 days between order and diagnosis, range, 1-28). Compared with 1,020 patients who ordered LBx after diagnosis (Dx-LBx), LBx-Dx patients had similar stage and ctDNA tumor fraction (TF). LBx-Dx patients received CGP results a median of 1 day after Dx versus 25 days for Dx-LBx patients. Forty-three percent of LBx-Dx were positive for an National Comprehensive Cancer Network driver, and 32% had ctDNA TF >1% but were driver negative (presumed true negatives). In 748 patients with previously untreated aNSCLC, median time from Dx to therapy was shorter in the LBx-Dx versus Dx-LBx group (21 v 35 days; P < .001). CONCLUSION: Early LBx in anticipation of pathologic diagnosis of aNSCLC was uncommon in this real-world cohort, yet this emerging paradigm was associated with an abbreviated time to CGP results and faster therapy initiation. Forthcoming prospective studies will clarify the utility of LBx in parallel with biopsy for diagnostic confirmation for patients presenting with suspected advanced lung cancer.

Institutional Scientific Review of Cancer Clinical Research Protocols: A Unique Requirement That Affects Activation Timelines.

PURPOSE: The National Cancer Institute (NCI) requirement that clinical trials at NCI-designated cancer centers undergo institutional scientific review in addition to institutional review board evaluation is unique among medical specialties. We sought to evaluate the effect of this process on protocol activation timelines. METHODS: We analyzed oncology clinical trials that underwent full board review by the Harold C. Simmons Comprehensive Cancer Center Protocol Review and Monitoring Committee (PRMC) from January 1, 2009, through June 30, 2013. We analyzed associations between trial characteristics, PRMC decisions, protocol modifications, and process timelines using the χ2 test, Fisher's exact test, Wilcoxon rank sum test, Kruskal-Wallis test, and logistic regression. RESULTS: A total of 226 trials were analyzed. Of these, 77% were industry sponsored and 23% were investigator initiated. The median time from submission to PRMC approval was 55 days. The length of review was associated with trial phase, timing of approval, and number of committee changes/clarifications requested. The median process time was 35 days for those approved at first decision, 68 days for second decision, and 116 days for third decision ( P < .001). The median process time was 39 days if no changes/clarifications were requested, 64 days for one to three changes/clarifications, and 73 days for four or more changes/clarifications ( P < .001). Requested changes/clarifications had a greater effect on industry-sponsored trials than on investigator-initiated trials. CONCLUSION: NCI-mandated institutional scientific review of oncology clinical trials contributes substantially to protocol activation timelines. Further evaluation of this process and the value added to research quality is warranted.