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• The more infectious Omicron sublineage BA.2 replaced sublineage BA.1.1. • Sublineage BA.2 infection produced a higher viral load compared with BA.1.1 infection • High viral loads were observed for both BA.1.1 and BA.2 across all age groups. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has circulated worldwide and causes coronavirus disease 2019 (COVID-19). At the onset of the COVID-19 pandemic, infection control measures were taken, such as hand washing, mask wearing, and behavioral restrictions. However, it is not fully clear how the effects of these non-pharmaceutical interventions changed the prevalence of other pathogens associated with respiratory infections. In this study, we collected 3,508 nasopharyngeal swab samples from 3,249 patients who visited the Yamanashi Central Hospital in Japan from March 1, 2020 to February 28, 2021. We performed multiplex polymerase chain reaction (PCR) using the FilmArray Respiratory Panel and singleplex quantitative reverse transcription PCR targeting SARS-CoV-2 to detect respiratory disease-associated pathogens. At least one pathogen was detected in 246 (7.0%) of the 3,508 samples. Eleven types of pathogens were detected in the samples collected from March–May 2020, during which non-pharmaceutical interventions were not well implemented. In contrast, after non-pharmaceutical interventions were thoroughly implemented, only five types of pathogens were detected, and the majority were SARS-CoV-2, adenoviruses, or human rhinoviruses / enteroviruses. The 0–9 year age group had a higher prevalence of infection with adenoviruses and human rhinoviruses / enteroviruses compared with those 10 years and older, while those 10 years and older had a higher prevalence of infection with SARS-CoV-2 and other pathogens. These results indicated that non-pharmaceutical interventions likely reduced the diversity of circulating pathogens. Moreover, differences in the prevalence of pathogens were observed among the different age groups. [ABSTRACT FROM AUTHOR]

BACKGROUND: Molecular testing is critical for identifying actionable variants in lung cancer for precision medicine. When tumor tissue samples are unavailable, archived cytological specimens (ACSs) can be used. The authors examined whether oncogenic variants could be accurately detected in ACSs versus paired formalin‐fixed, paraffin‐embedded (FFPE) tumor tissues with in vitro diagnostic tests. METHODS: The authors collected 18 ACSs and 15 FFPE tissues from 15 patients with lung cancer and investigated genomic profiles with the Oncomine Dx Target Test Multi‐CDx system, which is an integrated next‐generation sequencing platform that comprehensively examines 4 companion diagnostic target genes (epidermal growth factor receptor [EGFR]; B‐Raf proto‐oncogene, serine/threonine kinase [BRAF]; anaplastic lymphoma kinase [ALK]; and ROS proto‐oncogene 1, receptor tyrosine kinase [ROS1]). They compared the quantity and quality of extracted nucleic acids, the sequencing quality control (QC), and the detected variants between ACSs and FFPE tissues. RESULTS: The total amount of DNA and RNA obtained from 1 slide was higher in FFPE tissues than ACSs. The RNA integrity number was higher in ACSs. There were no differences in sequencing QC between ACSs and FFPE tissues. A total of 21 variants, including EGFR mutations and ALK and ROS1 fusion genes, were detected in both ACSs and FFPE tissues with 100% concordance. CONCLUSIONS: ACSs can be a feasible alternative with which to identify actionable mutations and fusion genes via the Oncomine Dx Target Test Multi‐CDx system. All detected variants are found in both archived cytological specimens (ACSs) and formalin‐fixed, paraffin‐embedded tissues. ACSs may provide new alternative materials for DNA‐ and RNA‐based molecular testing using next‐generation sequencing. [ABSTRACT FROM AUTHOR]

Extensive disease small cell lung cancer (ED‐SCLC) is a systemic disease characterized by diffuse metastases and a poor prognosis. Oligometastatic cases in ED‐SCLC are rare. This study reports the case of a 72‐year‐old Japanese male. A mass lesion was identified on chest computed tomography (CT). Fluorodeoxyglucose‐positron emission tomography/computed tomography (FDG‐PET/CT) revealed a solitary thyroid gland lesion with high FDG uptake as an extrapulmonary finding, suggesting thyroid cancer or a goiter. Upon confirmation of diagnosis, treatment of SCLC was prioritized, and chemoradiotherapy for limited disease SCLC was initiated without further examination of the thyroid gland. The thyroid nodule disappeared after treatment. Two years later, the disease recurred, and a thyroid nodule was found to have reappeared. Upon fine needle aspiration cytology of the thyroid, small cell carcinoma was detected. Therefore, in cases of SCLC, it is necessary to carefully investigate the thyroid for solitary lesions to consider the possibility of oligometastasis. Key points: Significant findings of the study: Manifesting as a solitary lesion, oligometastasis, particularly in the thyroid, is rare in cases of ED‐SCLC. What this study adds: In SCLC cases, it is necessary to carefully investigate the thyroid for solitary lesions to consider the possibility of oligometastasis. [ABSTRACT FROM AUTHOR]

Introductions: When tumor tissue samples are unavailable to search for actionable driver mutations, archival cytology samples can be useful. We investigate whether archival cytology samples can yield reliable genomic information compared to corresponding formalin‐fixed paraffin‐embedded (FFPE) tumor samples. Patients and Methods: Pretreatment class V archival cytology samples with adequate tumor cells were selected from 172 lung cancer patients. The genomic profiles of the primary lung tumors have been analyzed through whole‐exome regions of 53 genes. We compared the genomic profiles based on the oncogenicity and variant allele frequency (VAF) between the archival cytology and the corresponding primary tumors. We also analyzed the genomic profiles of serial cytological samples during the treatment of EGFR‐TKI. Results: A total of 43 patients were analyzed with the paired samples for DNA mutations and other three patients were analyzed for their fusion genes. A total of 672 mutations were detected. Of those, 106 mutations (15.8%) were shared with both samples. Sixty of seventy‐seven (77.9%) shared mutations were oncogenic or likely oncogenic mutations with VAF ≧10%. As high as 90% (9/10) actionable driver mutations and ALK and ROS1 fusion genes were successfully detected from archival cytology samples. Sequential analysis revealed the dynamic changes in EGFR‐TKI‐resistant mutation (EGFR p.T790M) during the course of treatment. Conclusion: Archival cytology sample with adequate tumor cells can yield genetic information compared to the primary tumors. If tumor tissue samples are unavailable, we can use archival cytology samples to search for actionable driver mutations. [ABSTRACT FROM AUTHOR]

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC) and contributed to the development of precision medicine. Osimertinib is a standard first-line (1L) treatment for EGFR -mutated NSCLC and has demonstrated superior survival benefits over previous-generation TKIs. However, resistance to osimertinib is nearly inevitable, and subsequent treatment strategies remain unmet medical needs in this setting. Afatinib, a second-generation EGFR-TKI, exhibits activity against certain uncommon EGFR mutation types in the 1L setting. There are a few case reports on the efficacy of afatinib against EGFR -dependent resistance after osimertinib treatment, although these have not been prospectively investigated., Methods: The present phase II, single-arm multicenter trial aims to verify the efficacy and safety of afatinib rechallenge after 1L osimertinib resistance. Patients (aged ≥20 years) with advanced or recurrent non-squamous NSCLC harboring drug-sensitive EGFR mutations (deletion of exon 19 or L858R) who were previously treated with 1L osimertinib and second-line chemotherapy other than TKIs are considered eligible. Undergoing next-generation sequence-based comprehensive genomic profiling is one of the key inclusion criteria. The primary endpoint is the objective response rate; the secondary endpoints are progression-free survival, overall survival, and tolerability. Thirty patients will be recruited in December 2023., Discussion: The results of this study may promote incorporating afatinib rechallenge into the treatment sequence after 1L osimertinib resistance, a setting in which concrete evidence has not been yet established., Registration: UMIN Clinical Trial Registry: UMIN000049225., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-23-12/coif). The authors have no conflicts of interest to declare., (2023 Translational Lung Cancer Research. All rights reserved.)

The diagnostic accuracy of bronchoscopy for detecting lung cancer, especially peripheral lung cancer with lesions outside the endoscopically visible range, remains unsatisfactory. The aim of this study was to perform next-generation sequencing on bronchoscopic specimens to determine whether this improves the accuracy of bronchoscopy for diagnosing lung cancer and to identify factors influencing sensitivity. The bronchoscopic sensitivity for diagnosing lung cancer was initially evaluated in 191 patients who underwent lobectomy after bronchoscopy at our hospital. Sputum, bronchial wash fluid, and resected lung cancer specimens were subsequently collected from 18 patients with peripheral small cell lung cancer for genomic analysis. DNA was extracted from formalin-fixed, paraffin-embedded surgical tissue specimens and the supernatant and cell fractions of sputum and bronchial wash fluid. Deep sequencing was performed using a lung cancer panel covering all exons of 53 lung cancer-related genes. The bronchoscopic sensitivity for diagnosing lung cancer at our hospital was 60.7%. Multivariate analysis revealed that this was influenced by tumor size and location, but not histological type or lymph node metastasis. The sensitivity was the highest for biopsy followed by curettage and bronchial wash specimens. DNA mutations homologous to those identified in the primary lesions were detected in the bronchial wash fluid of 10 patients (55.6%), while only 2 patients (11.1%) were diagnosed with lung cancer based on conventional cytological examinations. In conclusion, the addition of genomic analysis to routine pathological examinations improves the diagnostic accuracy of bronchoscopy., Competing Interests: CONFLICTS OF INTEREST The authors declare that there are no conflicts of interest.