The presence of anaplastic lymphoma kinase (ALK) rearrangement defines a molecular subtype of non-small cell lung cancer (NSCLC). ALK inhibitors (ALKIs) confer significant clinical benefits in patients with ALK-positive advanced NSCLC; therefore, it is of great clinical significance to select accurate, rapid, and appropriate ALK testing methods to screen for patients who are suitable for anti-ALK treatment. In recent years, great progress has been made in the development and clinical application of ALKIs, as well as in our understanding of acquired drug resistance mechanisms. Meanwhile, new ALK companion diagnostic platforms have been developed and applied in clinical practice. Although many studies have shown that there is a high rate of concordance among these platforms, new problems continue to appear during testing. To maximize the benefit for patients, accurate testing results can be obtained by first selecting the appropriate testing method and then formulating, optimizing, and complying with the standardized testing process in accordance with the testing population and specimen types. With the ongoing accumulation of clinical practice data, experience from quality control of ALK testing, and results from multicenter research, an updated expert consensus is necessary. The experts who participated in the discussion and development of this guideline have a rich background in theoretical and clinical testing experience, which ensures the practical value of the information presented in this guideline.

UNASSIGNED: Lung cancer remains an important cause of cancer-related mortality in Singapore, with a greater proportion of non-smokers diagnosed with non-small cell lung cancer (NSCLC) in the past 2 decades. The higher prevalence of targetable genomic alterations in lung cancer diagnosed in Singapore compared with countries in the West, as well as the expanding therapeutic landscape for NSCLC in the era of precision medicine, are both factors that underscore the importance of efficient and effective molecular profiling.
UNASSIGNED: This article provides consensus recommendations for biomarker testing for early-stage to advanced NSCLC. These recommendations are made from a multidisciplinary group of lung cancer experts in Singapore with the aim of improving patient care and long-term outcomes.
UNASSIGNED: The recommendations address the considerations in both the advanced and early-stage settings, and take into account challenges in the implementation of biomarker testing as well as the limitations of available data. Biomarker testing for both tumour tissue and liquid biopsy are discussed.
UNASSIGNED: This consensus statement discusses the approaches and challenges of integrating molecular testing into clinical practice for patients with early- to late-stage NSCLC, and provides practical recommendations for biomarker testing for NSCLC patients in Singapore.

UNASSIGNED: Osimertinib is recommended by major guidelines for use in the adjuvant setting in patients with EGFR mutation-positive NSCLC following the significant improvement in disease-free survival observed in the Phase III ADAURA trials. Due to limited real-world data in the adjuvant setting, little guidance exists on how to approach potential recurrences either during or after the completion of the treatment. This study aimed to reach a broad consensus on key treatment decision criteria in the events of recurrence.
UNASSIGNED: To reach a broad consensus, a modified Delphi panel study was conducted consisting of two rounds of surveys, followed by two consensus meetings and a final offline review of key statements. An international panel of experts in the field of NSCLC (n=12) was used to provide clinical insights regarding patient management at various stages of NSCLC disease including patient monitoring, diagnostics, and treatment approach for specific recurrence scenarios. This study tested recurrences occurring 1) within or outside the central nervous system (CNS), 2) during or after the adjuvant-osimertinib regimen in NSCLC disease which is 3) amenable or not amenable to local consolidative therapy.
UNASSIGNED: Panellists agreed on various aspects of patient monitoring and diagnostics including the use of standard techniques (e.g., CT, MRI) and tumour biomarker assessment using tissue and liquid biopsies. Consensus was reached on 6 statements describing treatment considerations for the specific NSCLC recurrence scenarios. Panellists agreed on the value of osimertinib as a monotherapy or as part of the overall treatment strategy within the probed recurrence scenarios and acknowledged that more clinical evidence is required before precise recommendations for specific patient populations can be made.
UNASSIGNED: This study provides a qualitative expert opinion framework for clinicians to consider within their treatment decision-making when faced with recurrence during or after adjuvant-osimertinib treatment.

Mesenchymal epithelial transition (MET) factor alteration in non-small cell lung cancer (NSCLC) includes MET exon 14 skipping alteration (METex14 skipping), MET gene amplification, MET gene mutation (mainly kinase domain mutation), MET gene fusion, and MET protein overexpression. The incidence of METex14 skipping in patients with NSCLC is 0.9-4.0%. At present, drugs targeting METex14 skipping have been approved in China and other countries like Japan and USA. Patients with advanced NSCLC should undergo testing, including METex14 skipping, to screen the population with benefit from targeted therapy with MET inhibitors. The incidence of de novo MET gene amplification in NSCLC patients is 1-5%, the incidence of acquired MET gene amplification in epidermal growth factor receptor tyrosine kinase inhibitor (TKI)-resistant patients is 5-50%, and the incidence in anaplastic lymphoma kinase (ALK) TKI-resistant patients is about 13%; the incidence of MET protein overexpression in NSCLC patients is 13.7-63.7%. Several clinical trials on MET gene amplification and MET protein overexpression are ongoing, which have demonstrated their important guiding significance as biomarkers in the clinical treatment with MET inhibitors. Accurate detection of MET alterations is a prerequisite for MET inhibitor therapy. Since there are many types of MET alterations and related testing methods, as well as many problems and challenges during clinical testing, further sorting and standardization are required. Combined with clinical practice experience, literature review, and expert discussion, the writing group developed this consensus on the three main types of MET alterations (METex14 skipping, MET gene amplification, and MET protein overexpression) in order to guide the practical applications of clinical MET testing.

RNA-based next-generation sequencing (NGS) has been recommended as a method for detecting fusion genes in non-small cell lung cancer (NSCLC) according to clinical practice guidelines and expert consensus. The primary targetable alterations in NSCLC consist of gene mutations and fusions, making the detection of gene mutations and fusions indispensable for assessing the feasibility of targeted therapies. Currently, the integration of DNA-based NGS and RNA-based NGS allows for simultaneous detection of gene mutations and fusions and has been partially implemented in clinical practice. However, standardized guidelines and criteria for the significance, application scenarios, and quality control of RNA-based NGS in fusion gene detection are still lacking in China. This consensus aims to provide further clarity on the practical significance, application scenarios, and quality control measures of RNA-based NGS in fusion gene detection. Additionally, it offers guiding recommendations to facilitate the clinical implementation of RNA-based NGS in the diagnosis and treatment of NSCLC, ultimately maximizing the benefits for patients from fusion gene detection.
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【中文题目：基于RNA-based NGS检测非小细胞肺癌
融合基因临床实践中国专家共识】 【中文摘要：基于RNA水平的二代测序（RNA-based next-generation sequencing, RNA-based NGS）技术已被非小细胞肺癌（non‑small cell lung cancer, NSCLC）临床实践指南和专家共识推荐为融合基因的检测方法之一。NSCLC可用药靶点主要包括基因突变和融合，用于评估靶向治疗可行性的基因突变和融合基因检测均不可或缺。目前，基于DNA水平的NGS（DNA-based NGS）结合RNA-based NGS一次性同步检测基因突变和融合的技术已部分应用于临床实践。然而，RNA-based NGS检测融合基因的应用时机、应用场景和质控方面在我国仍缺乏规范和标准。本共识将进一步明确RNA-based NGS在融合基因检测中的应用时机、应用场景和质控，并给予指导性建议，推动RNA-based NGS在NSCLC临床诊疗中的应用，使患者能够最大程度地从融合基因检测中获益。
】 【中文关键词：非小细胞肺癌；融合基因；RNA-based NGS；靶向治疗；专家共识】.

The oligometastatic state in non-small cell lung cancer (NSCLC) has recently become well-established. However, the specific definition of oligometastases remains unclear. Several smaller randomized studies have investigated the safety and efficacy of radiation as metastasis-directed therapy (MDT) in oligometastatic NSCLC, which have led the way to larger studies currently accruing patients globally.
This review covers the definitions of \'oligometastases\' and explains why the oligometastatic state is becoming increasingly relevant in metastatic NSCLC. This includes the rationale for MDT in oligometastatic NSCLC, specifically reviewing stereotactic body radiation therapy (SBRT) as a treatment strategy. This review details many randomized trials that support radiation as MDT and introduces trials that are currently accruing patients. Finally, it explores some of the controversies that warrant further investigation.
Radiation treatment, specifically SBRT, has been shown to be safe, convenient, and cost-effective as MDT. As systemic therapy, including targeted agents and immunotherapy, continues to improve, the precise role(s) and timing of radiation therapy may evolve. However, radiation therapy as MDT will continue to be an integral part of treatment in patients with oligometastatic NSCLC.

The PACIFIC trial showed a survival benefit with durvalumab through five years in stage III unresectable non-small cell lung cancer (NSCLC). However, optimal use of imaging to detect disease progression remains unclearly defined for this population. An expert working group convened to consider available evidence and clinical experience and develop recommendations for follow-up imaging after concurrent chemotherapy and radiation therapy (CRT). Voting on agreement was conducted anonymously via online survey. Follow-up imaging was recommended for all suitable patients after CRT completion regardless of whether durvalumab is received. Imaging should occur every 3 months in Year 1, at least every 6 months in Year 2, and at least every 12 months in Years 3-5. Contrast computed tomography was preferred; routine brain imaging was not recommended for asymptomatic patients. The medical oncologist should follow-up during Year 1 of durvalumab therapy, with radiation oncologist involvement if pneumonitis is suspected; medical and radiation oncologists can subsequently alternate follow-up. Some patients can transition to the family physician/community primary care team at the end of Year 2. In Years 1-5, patients should receive information regarding smoking cessation, comorbidity management, vaccinations, and general follow-up care. These recommendations provide guidance on follow-up imaging for patients with stage III unresectable NSCLC whether or not they receive durvalumab consolidation therapy.

Lung resection remains the gold-standard of treatment for non-small cell lung cancer (NSCLC). British Thoracic Society (BTS) guidelines recommends the pursuit of pre-operative histological diagnosis and staging where possible. In the absence of pre-operative histology, surgical treatment can be offered in conjunction with multidisciplinary team (MDT) and patient consensus. We undertook a single-centre analysis of the accuracy of the lung cancer MDT in recommending surgical resection for those with suspected lung malignancy in the absence of pre-operative histological diagnosis over a six-year period.
A retrospective review was performed of patients undergoing any pulmonary oncological resection with therapeutic intent without pre-operative histological diagnosis at the recommendation of the lung cancer MDT in our unit between May 2016 and July 2022.
270 consecutive patients underwent lung resection for a lung nodule of indeterminate significance. This accounted for 45% of the oncological resections performed over this period. The mean age of the cohort was 67.9 years, and 47.4% were male. Overall, 10% of resected specimens (n = 27) were benign on final histopathology. 93% of those undergoing a lobectomy received a malignant diagnosis. Across the study cohort, surgical resection was well tolerated with a low complication rate.
Lung cancer resection in the absence of pre-operative histological diagnosis is feasible in a select patient cohort. This approach requires an experienced multi-disciplinary team and careful patient counselling. Our study demonstrates this adapted approach to be a pragmatic solution to the management of indeterminate pulmonary nodules in centres where biopsy is not routinely available due to existing constraints on the health system.

Lung cancer is the malignant tumor with the highest incidence and mortality rate in China, among which non-small cell lung cancer (NSCLC) accounts for about 85%. BRAF mutation occurs about 1.5% to 5.5% in NSCLC patients, while BRAF V600 accounts for about 30% to 50% of all BRAF mutations. The overall prognosis of patients with BRAF-mutation is poor. At present, there are many clinical trials on BRAF-mutation NSCLC and new drugs constantly emerging. However, there is no standardized consensus on the diagnosis and treatment of BRAF-mutation NSCLC in China. The expert group of the Lung Cancer Professional Committee of the Chinese Anti-Cancer Association formulated this consensus by integrating foreign and domestic BRAF-mutation-related guidelines, consensus, and existing clinical trials, and combining with Chinese experts\' clinical experience in the diagnosis and treatment of BRAF-mutation NSCLC. This consensus provides systematic recommendations for the clinical diagnosis and treatment process, rational drug choice, and adverse events management of BRAF-mutation NSCLC, aiming to provide reference for the standard of diagnosis and treatment of BRAF-mutation NSCLC.
肺癌是中国发病率和死亡率均排第1位的恶性肿瘤，其中非小细胞肺癌(NSCLC)约占肺癌的85%。BRAF突变在NSCLC患者中的发生率约为1.5%~5.5%，而BRAF V600突变约占所有BRAF突变的30%~50%，BRAF突变患者整体预后较差。目前，关于BRAF突变NSCLC的临床研究探索越来越多，新药研发层出不穷，但国内尚无BRAF突变NSCLC诊疗相关的规范化共识。中国抗癌协会肺癌专业委员会专家组整合国内外BRAF突变相关的指南共识和现有的临床研究结果，结合我国BRAF突变的NSCLC诊疗经验，制定了中国晚期非小细胞肺癌BRAF突变诊疗专家共识，针对BRAF突变NSCLC的临床评估、诊疗流程、合理用药、不良反应管理等给出了详细建议，旨在为BRAF突变NSCLC的规范化管理和诊疗提供参考意见。.

Non-small cell lung cancer (NSCLC) presents the greatest number of identified therapeutic targets, some of which have therapeutic utility. Currently, detecting EGFR, BRAF, KRAS and MET mutations, ALK, ROS1, NTRK and RET translocations, and PD-L1 expression in these patients is considered essential. The use of next-generation sequencing (NGS) facilitates precise molecular diagnosis and allows the detection of other emerging mutations, such as the HER2 mutation and predictive biomarkers for immunotherapy responses. In this consensus, a group of experts in the diagnosis and treatment of NSCLC selected by the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM) have evaluated currently available information and propose a series of recommendations to optimize the detection and use of biomarkers in daily clinical practice.