Clinical Features and Surgical Treatment of Synchronous Multiple Primary Lung Adenocarcinomas With Different EGFR Mutations

BackgroundWith the popularity of lung cancer screening and advances in imaging technology, more and more synchronous multiple primary lung adenocarcinomas (SMPLA) are being diagnosed clinically, however, the clinical characteristics and prognosis of SMPLA with different EGFR mutations remains unclear. We aimed to explore clinical features and surgical outcomes of these patients to aid in the diagnosis and treatment of SMPLA.MethodsMedical records of patients with different EGFR mutations who have been diagnosed as SMPLA and underwent surgical resection from March 2015 to December 2019 were retrospectively analyzed. Clinical characteristics, surgical outcomes, recurrence-free survival (RFS) and overall survival (OS) were investigated.ResultsA total of 70 patients (68.6% female and 77.1% non-somkers) were included. Total of 161 lesions in all patients, 84.4% were ground-glass opacity (GGO) lesions. EGFR mutations were detected in 108 lesions, most of which were L858R (35.4%) and 19Del (20.5%). The mutation rate of mixed GGO is significantly higher than that of pure GGO and solid nodules (SN); the mutation rate of invasive adenocarcinoma is significantly higher than that of other histology subtypes; the mutation rate of lesions >20 mm was significantly higher than that of ≤20 mm. However, there is no significant difference in the mutation rate of specific driver gene between different radiological features, pathological characteristics and sizes. After a median follow-up time of 29 months, the 3-year OS and RFS were 94.4% and 86.0%, respectively.ConclusionsA high discordance of EGFR mutations were identified between tumors in patients with SMPLA. Synchronous multiple lung adenocarcinomas with predominantly multiple GGO should be considered as SMPLA, and surgery may be aggressively performed for these patients due to a good prognosis.

EGFR Exon 20 Insertion Mutations in Sinonasal Squamous Cell Carcinoma

Recurrent epidermal growth factor receptor (EGFR)-activating mutations have been identified in a rare form of head and neck cancer known as sinonasal squamous cell carcinoma (SNSCC), a malignant disease with a 5-year mortality rate of ~40%. Interestingly, the majority of EGFR mutations identified in patients with primary SNSCC are exon 20 insertions (Ex20ins), which is in contrast to non-small-cell lung cancer (NSCLC), where the EGFR exon 19 deletion and L858R mutations predominate. These studies demonstrate that EGFR Ex20ins mutations are not exclusive to lung cancer as previously believed, but are also involved in driving SNSCC pathogenesis. Here we review the landscape of EGFR mutations in SNSCC, with a particular focus on SNSCC associated with inverted sinonasal papilloma (ISP), a benign epithelial neoplasm. Taking lessons from NSCLC, we also discuss potential new treatment options for ISP-associated SNSCC harbouring EGFR Ex20ins in the context of targeted therapies, drug resistance and precision cancer medicine. Moving forward, further basic and translational work is needed to delineate the biology of EGFR Ex20ins in SNSCC in order to develop more effective treatments for patients with this rare disease.

Uncommon EGFR Compound Mutations in Non-Small Cell Lung Cancer (NSCLC): A Systematic Review of Available Evidence

Compound epidermal growth factor receptor (EGFR) mutations represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations. We conducted a systematic review to investigate the available data on this patients’ subgroup. Overall, we found a high heterogeneity in the incidence of compound mutations (4–26% of total EGFR mutant cases), which is dependent on the different testing methods adopted and the specific mutations considered. In addition, the relative incidence of distinct compound subclasses identified is reported with extreme variability in different studies. Preclinical and clinical data, excluding de novoEGFR exon 20 p.T790M compound mutations, show good responses with EGFR tyrosine kinase inhibitors (TKIs) (combined common mutations: response rate (RR) ≥ 75% with either first- or second-generation TKIs; combined common plus uncommon: RR 40–80% and 100% with first-generation TKIs and afatinib, respectively; combined uncommon: RR 20–70%, ~80% and ~75% with first-generation TKIs, afatinib and osimertinib, respectively). Overall, data are consistent in supporting the use of EGFR TKIs in treating compound EGFR mutations, taking into account different sensitivity profile of accompanying EGFR mutations for selecting the most adequate EGFR TKI for individual patients.

p53 and EGFR gene mutations in malignant tumors of the lung

Relevance: Increased incidence of lung cancer globally and in Kazakhstan, lack of screening in hereditary cases, high mortality, and low survival of patients necessitate the study of the molecular genetic causes of the disease. At present, gene mutation studies for lung cancer diagnostics are expanding. However, many gene mutations revealed remain undercovered in the scientific literature, and there is not enough data on their prognostic and diagnostic value. The purpose of the study was to discover the specifics of the р53 gene mutations and reveal the EGFR exon 19 deletions and exon 21 L858R mutations in malignant tumors of the lung of various histogenesis. Methods: The mutations were studied in tumors (200 samples) and adjacent tissue (200 samples) of patients with lung cancer (squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of the lung) by polymerase chain reaction (PCR), electrophoresis, and EcoR1- and Pst1-restriction of samples after p53 gene fragments and cDNA amplification and mRNA revertase treatment. Another 263 lung cancer samples were evaluated by real-time PCR for EGFR exon 19 deletions and EGFR exon 21 L858R mutations. Results: The p53 gene was not expressed in 50% of SCC and adenocarcinoma of the lung samples. Restriction revealed p53 mRNA mutations in 100% of SCC and 75% of ADC samples. p53 exon-intron 5-6 was mutated in 50% of ADC and 70% of SCC samples, exon-intron 7-9 – in 60% of SCC cases. EGFR exons 19 and 21 mutations found in 65 of 263 lung tumor samples were associated with increased sensitivity to EGFR tyrosine kinase inhibitors. Conclusion: The p53 gene mutations revealed in most samples of SCC and ADC of the lung could be used to diagnose lung cancer and predict its severity. The identified EGFR mutations allow predicting the effectiveness of targeted therapy