Analytical validation of NeXT Personal®, an ultra-sensitive personalized circulating tumor DNA assay.

We describe the analytical validation of NeXT Personal®, an ultra-sensitive, tumor-informed circulating tumor DNA (ctDNA) assay for detecting residual disease, monitoring therapy response, and detecting recurrence in patients diagnosed with solid tumor cancers. NeXT Personal uses whole genome sequencing of tumor and matched normal samples combined with advanced analytics to accurately identify up to ~1,800 somatic variants specific to the patient's tumor. A personalized panel is created, targeting these variants and then used to sequence cell-free DNA extracted from patient plasma samples for ultra-sensitive detection of ctDNA. The NeXT Personal analytical validation is based on panels designed from tumor and matched normal samples from two cell lines, and from 123 patients across nine cancer types. Analytical measurements demonstrated a detection threshold of 1.67 parts per million (PPM) with a limit of detection at 95% (LOD95) of 3.45 PPM. NeXT Personal showed linearity over a range of 0.8 to 300,000 PPM (Pearson correlation coefficient = 0.9998). Precision varied from a coefficient of variation of 12.8% to 3.6% over a range of 25 to 25,000 PPM. The assay targets 99.9% specificity, with this validation study measuring 100% specificity and in silico methods giving us a confidence interval of 99.92 to 100%. In summary, this study demonstrates NeXT Personal as an ultra-sensitive, highly quantitative and robust ctDNA assay that can be used to detect residual disease, monitor treatment response, and detect recurrence in patients.

A Learning Health System Approach to Increasing Human Papillomavirus Immunizations Among Young Adults.

INTRODUCTION Immunization rates against the human papillomavirus (HPV) remain suboptimal in the young adult population. Little is known about the most effective means for encouraging vaccination in this population. METHODS The authors conducted a clinical trial of 3 methods to encourage HPV vaccination in a large Northern California integrated Health Plan. Young adults aged 18-26 with evidence of insufficient HPV vaccination were sent a bulk secure message from the Health Plan (standard outreach); those who did not respond were randomized to no further outreach, a second, personalized secure message from a specific practitioner, or a letter mailed to their home. The primary outcome was receipt of at least 1 HPV vaccine within 3 months following the initial bulk secure message. RESULTS In total, 7718 young adults were randomized. After 3 months, 86 patients (3.5%) who received no additional outreach obtained an immunization, compared with 114 (4.6%) who received the second secure message (p = 0.05) and 126 (5.1%) who received the mailed letter (p = 0.006). DISCUSSION Supplemental mailed or personalized electronic messages increased vaccination beyond no additional intervention, although gains were not clinically meaningful. These findings highlight the need for more successful alternatives to encourage uptake of such preventive health interventions among young adults. The successful conduct of this rapid-cycle, randomized trial showed that such evaluations are feasible, providing actionable data to inform implementation strategies. CONCLUSIONS Further study is needed to identify effective strategies for improving preventive health uptake in this important and underserved population. Rapid-cycle randomized evaluation strategies can provide critical information to focus efforts for achieving this goal.