Background Developing liquid biopsy technology with higher sensitivity and specificity especially for low-frequency mutations remains crucial. This study demonstrated superior performance of the newly developed digital PCR (dPCR) kit for ctDNA-based EGFR p.T790M detection in metastatic non-small-cell lung cancer (NSCLC) against ARMS-PCR. Methods This large-scale, multi-centered diagnostic study recruited 1,045 patients including 1,029 patients diagnosed with advanced NSCLC and 16 patients with specific samples between April 1st 2018 and November 30th 2019. EGFR p.T790M in plasma samples from mNSCLC patients were tested using dPCR with ADx-ARMS PCR and Cobas® EGFR Mutation Test V2 as comparator assays to confirm cut-off value for dPCR and evaluate its performance against ARMS-PCR-based assays. Efficacy was evaluated for patients with EGFR p.T790M detected by dPCR or ARMS-PCR, who underwent Osimertinib treatment. Results The sensitivity, specificity, and concordance of dPCR against ADx-ARMS PCR was 98.15%, 88.66% and 90.16%, respectively for 1,026 plasma samples. Additional 9.26% patients were detected positive by dPCR. The majority of those samples had a mutation allele frequency between 0.1% and 1%. In 45 paired tissue and plasma samples, the sensitivity improved from 30.77% to 53.85% by dPCR with the specificity over 90%. The response of Osimertinib in 74 EGFR p.T790M-positive patients detected by dPCR, including 26 determined as negative by ARMS-PCR, were evaluated to have an ORR of 44.59% and a DCR of 90.54%. Conclusions dPCR is a sensitive and accurate tool for ctDNA-based EGFR p.T790M detection due to its significantly improved sensitivity without compromising specificity, and dPCR is equivalent to ARMS-PCR as a companion diagnostic tool while benefiting more patients under Osimertinib treatment. Trial Registration Chinese Clinical Trial Registry identifier: ChiCTR2100043147.

Aims: To assess healthcare resource utilization (HCRU) and costs in patients with non-small cell lung cancer treated with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors afatinib or erlotinib as first-line treatment.Materials and methods: This retrospective analysis used data from three large administrative claims databases in the US: Truven MarketScan, IMS PharMetrics Plus, and Optum Clinformatics Data Mart. Patients with diagnosis codes of lung cancer treated with afatinib or erlotinib were included in the sample. Treatment cohorts were matched on baseline characteristics using propensity scores to account for potential selection bias. HCRU and healthcare costs were compared between the matched afatinib and erlotinib cohorts.Results: In total, 3,152 patients met the study inclusion criteria; propensity score matching of the afatinib and erlotinib patients yielded 525 matched pairs with well-balanced baseline characteristics. The afatinib cohort had significantly fewer patients with ≥1 inpatient visits (40.4% vs 52.2%, p = 0.0001) and outpatient emergency room (ER) visits (45.7% vs 54.1%, p = 0.0066). Per patient per month (PPPM) visits were significantly different between afatinib compared to erlotinib for inpatient visits (0.1 vs 0.2, p = 0.0152), other outpatient visits PPPM (2.6 vs 3.0, p = 0.022) and outpatient office visits (2.0 vs 1.7, p = 0.0059). Although costs of outpatient office ($1,624 vs $1,070; p = 0.0086) and pharmacy ($6,709 vs $5,932; p < 0.0001) visits were higher for afatinib vs erlotinib, total costs did not differ significantly between cohorts ($14,972 vs $14,412; p = 0.4415).Limitations: Retrospective claims data can be subject to coding errors or data omissions; patients were required to have continuous health plan enrolment; EGFR mutation status was not confirmed.Conclusions: Patients treated with afatinib as first-line monotherapy experienced fewer inpatient stays and ER visits compared with erlotinib. Total costs were not significantly different between the two treatment cohorts.

Aim: Evaluate duration of therapy among patients treated with afatinib or erlotinib as first-line therapy for non-small-cell lung cancer (NSCLC). Materials & methods: NSCLC patients initiating afatinib or erlotinib between 2014 and 2017 were identified in three large claims databases in the USA. Propensity score matching was conducted to compare the duration of treatment between patients by treatment. Results: Patients prescribed afatinib had a significantly longer median duration of treatment compared with those prescribed erlotinib (12.1 vs 9.9 months; p = 0.035) and experienced a 14% reduction in risk of discontinuing therapy (adjusted hazard ratio: 0.86; CI: 0.75-0.99). Conclusion: First-line treatment duration in a real-world setting was significantly longer for patients prescribed afatinib compared with erlotinib.

Familial cerebral cavernous malformation (FCCM) is a rare autosomal dominant inherit vascular disorder of the central nerves system. The authors reviewed the literature and presented four members who harbored FCCM within a Chinese family: A 14-year-old male (proband, III-1) was admitted to our hospital for a sudden onset of headache and dizziness; his elder parental cousin(III-3) without any symptoms nor other medical history but multiple brain lesions were detected by magnetic resonance imaging (MRI); his mother(II-2), a 38-year-old female, presented with recurrent headaches for more than 2 years. All of the three patients above were treated upfront with Gamma Knife radiosurgery (GKS). Besides, the proband’s paternal uncle (II-3) had previously undergone surgery and cerebral cavernous malformation (CCM) was confirmed by the pathological examination. All the patients above are now leading a normal life with the condition and follow-up periodically.