Diagnosis and Treatment of Advanced ALK Rearrangement-Positive Non-Small-Cell Lung Cancer in Portugal: Results of a National Questionnaire.

BACKGROUND: Rearrangements in the anaplastic lymphoma kinase (ALK) gene define a molecular subgroup of non-small-cell lung carcinoma (NSCLC) that should be treated with ALK-targeting tyrosine kinase inhibitors (TKIs). OBJECTIVE: This study aimed to portray the Portuguese reality about the diagnosis and treatment of stage IV ALK-positive NSCLC. METHODS: Institutions that treat lung cancer in Portugal were invited to participate in an anonymous electronic questionnaire. A total of 22/35 geographically dispersed institutions responded. A descriptive statistical analysis of the results was performed. RESULTS: Reflex molecular testing was done in 54.6% of the institutions. Next-generation sequencing (NGS) was the preferred diagnostic method (90.9%). Typically, physicians obtained molecular study results within 14-21 days. Alectinib was the most commonly used first-line treatment. For patients with brain metastases, 86.4% of the physicians preferred alectinib and 13.6% preferred first-line brigatinib. In the case of asymptomatic oligoprogression in the central nervous system, 85.7% of physicians performed local treatment and kept the patient on a TKI; if symptomatic, 66.7% gave local treatment and stayed with the TKI, while 28.6% gave local treatment and altered the TKI. For patients with symptomatic systemic progression, 47.6% and 38.1% of physicians prescribed lorlatinib after initial treatment with alectinib or brigatinib, respectively. After progression on lorlatinib, 42.9% of respondents chose chemotherapy and 57.1% requested detection of resistance mutations. CONCLUSIONS: NGS is widely used for the molecular characterization of ALK-positive NSCLC in Portugal. The country has access to up-to-date therapy. Overall, national clinical practice follows international recommendations for the diagnosis and treatment of ALK-positive NSCLC.

Liquid biopsy in the management of advanced lung cancer: Implementation and practical aspects.

Non-small-cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide. In recent years, the discovery of actionable molecular alterations has changed the treatment paradigm of the disease. Tissue biopsies have been the gold standard for the identification of targetable alterations but present several limitations, calling for alternatives to detect driver and acquired resistance alterations. Liquid biopsies reveal great potential in this setting and also in the evaluation and monitoring of treatment response. However, several challenges currently hamper its widespread adoption in clinical practice. This perspective article evaluates the potential and challenges associated with liquid biopsy testing, considering a Portuguese expert panel dedicated to thoracic oncology point of view, and providing practical insights for its implementation based on the experience and applicability in the Portuguese context.

Detection and quantification of EGFR T790M mutation in liquid biopsies by droplet digital PCR.

BACKGROUND: Liquid biopsy allows the identification of targetable cancer mutations in a minimally invasive manner. In patients with advanced non-small cell lung cancer (NSCLC), droplet digital PCR (ddPCR) is increasingly used to genotype the epidermal growth factor receptor (EGFR) gene in circulating cell-free DNA (cfDNA). However, the sensitivity of this method is still under debate. The aim of this study was to implement and assess the performance of a ddPCR assay for detecting the EGFR T790M mutation in liquid biopsies. METHODS: A ddPCR assay was optimized to detect the EGFR T790M mutation in plasma samples from 77 patients with NSCLC in progression. RESULTS: Our ddPCR assay enabled the detection and quantification of the EGFR T790M mutation at cfDNA allele frequency as low as 0.5%. The mutation was detected in 40 plasma samples, corresponding to a positivity rate of 52%. The number of mutant molecules per mL of plasma ranged from 1 to 6,000. A re-biopsy was analyzed for 12 patients that had a negative plasma test and the mutation was detected in 2 cases. A second liquid biopsy was performed for 6 patients and the mutation was detected in 3 cases. CONCLUSIONS: This study highlights the value of ddPCR to detect and quantify the EGFR T790M mutation in liquid biopsies in a real-world clinical setting. Our results suggest that repeated ddPCR tests in cfDNA may obviate tissue re-biopsy in patients unable to provide a tumor tissue sample suitable for molecular analysis.