Profiling Cell-Free DNA from Malignant Pleural Effusion for Oncogenic Driver Mutations in Patients with Treatment-Naive Stage IV Adenocarcinoma: A Multicenter Prospective Study.

INTRODUCTION: Comprehensive next-generation sequencing (NGS) of non-small-cell lung cancer specimens can identify oncogenic driver mutations and their corresponding targeted therapies. Plasma cell-free DNA (cfDNA) genotyping is easy to perform; however, false negatives cannot be overlooked. We explored malignant pleural effusion (MPE), a rich source of cfDNA, as a non-inferior alternative to tumor tissues for genotyping. METHODS: We conducted a prospective trial including 39 patients with newly diagnosed stage IV lung adenocarcinoma who presented with MPE. Tissue tests matching hotspot variants, including EGFR, ALK, and ROS1, were compared with the AlphaLiquid100 of PE-cfDNA. RESULTS: Among the 39 PE-cfDNA samples successfully sequenced, 32 (82.1%) had a PE cell-block tumor content of < 10%. Standard tissue or cell-block testing for EGFR, ALK, and ROS1 identified 20 mutations (51.3%), whereas PE cfDNA identified 25 mutations (64.1%). Five EGFR mutations were observed in PE cfDNA but not in Cobas EGFR owing to coverage or insufficient tumor content issues. The overall rate of oncogenic mutations identified in the PE cfDNA was 92.3%, and the mutation distribution was as follows: even with a very low cfDNA input, high detection rates could be achieved. Otherwise, most patients harbored co-mutations. Comparison of pleural fluid NGS with traditional testing revealed differences in accuracy. We also followed up with patients with EGFR-sensitizing mutations who had a treatment response rate of 97.2% after 3 months. CONCLUSIONS: Genotyping of MPE supernatant cfDNA is feasible in clinical practice, in addition to plasma and tumor testing, to improve diagnostic yield and extend patients' benefit from targeted therapies.

Real world experience on the effectiveness and safety of pirfenidone in patients with idiopathic pulmonary fibrosis in Taiwan.

Introduction: Randomized controlled trials have demonstrated a reduction in the decline of lung function and a reduced risk of acute exacerbation in patients with idiopathic pulmonary fibrosis treated with the antifibrotic prifenidone. The present study aimed to investigate the real-world effectiveness and safety profile of pirfenidone treatment for patients with IPF in Taiwan. Methods: Between January 1, 2019 and December 31, 2020, we enrolled 50 patients who were newly diagnosed with IPF and had at least 12 months follow-up period after pirfenidone administration. Result: The primary outcome of pharmacologic effect showed that the mean differences in the absolute values of forced vital capacity from baseline were 0.2 liter (n = 36), 0.13 liter (n = 32), 0.04 liter (n = 26), and - 0.004 liter (n = 26) after 3, 6, 9, and 12 months of administration, respectively. A slight improvement in quality of life, including scores of chronic obstructive pulmonary disease assessment test and St. George's respiratory questionnaire scores. The most common adverse effects were gastrointestinal upset and dermatological problems. No new safety concerns were observed in the present study. Conclusion: Our real-world study describe for the first time in Taiwan, the use of pirfenidone over a 12 months period. This drug preserves the lung function and improves quality of life with tolerable side effects.

Oral glutamine supplements reduce concurrent chemoradiotherapy-induced esophagitis in patients with advanced non-small cell lung cancer.

BACKGROUND: Complications related to concurrent chemoradiotherapy (CCRT) such as acute radiation-induced esophagitis (ARIE) may cause significant morbidity and unplanned treatment delays in patients with advanced non-small cell lung cancer (NSCLC). We designed a prospective randomized study to assess the impact of glutamine (GLN) supplementation in preventing CCRT-induced toxicities of advanced NSCLC patients. METHODS: From September 2014 to September 2015, 60 patients diagnosed with NSCLC were included to the study. Thirty patients (50%) received prophylactic powdered GLN orally at a dose of 10 g/8 h. The prescribed radiation dose to the planning target volume was 30 Gy in 2-Gy fractions. The endpoints were radiation-induced esophagitis, mucositis, body weight loss, overall survival and progression-free survival. RESULTS: The 60 patients with NSCLC included 42 men and 18 women with a mean age ±â€Šstandard deviation of 60.3 years ±â€Š18.2 (range, 44-78 years).At a median follow-up of 26.4 months (range 10.4-32.2), all patients tolerated GLN well. A administration of GLN was associated with a decrease in the incidence of grade 2 or 3 ARIE (6.7% vs 53.4% for Gln+ vs Gln-; P = .004). GLN supplementation appeared to significantly delay ARIE onset for 5.8 days (18.2 days vs 12.4 days; P = .027) and reduced incidence of weight loss (20% vs 73.3%; P = .01). DISCUSSION: Our study suggests a beneficial effect of oral glutamine supplementation for the prevention from radiation-induced injury and body weight loss in advanced NSCLC patients who receiving CCRT.