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Abstract
The management of lung cancer has evolved very rapidly in the past decade. The introduction
of targeted and immunotherapies have significantly improved outcomes especially in
advanced stage disease (1), endobronchial technology to improve early diagnostic yields
(2), robotic surgery to perform challenging surgery in more precise manner (3), and
liquid biopsies to diagnose and guide treatments. However, these past great leaps
in lung cancer management, as Sir Winston Churchill once said, “… is not the end.
It is not even the beginning of the end. But it is perhaps, the end of the beginning.”
In this special series of “Lung Cancer Management—The Next Decade”, we have invited
some of the top clinician scientists in the field, many of them pioneers and trailblazers
in their topics, to provide us with their unique perspectives. The articles cover
the latest developments in: (I) the use of circulating tumour DNA and the potentials
it holds [Lam et al. (4)]; (II) the current and future technologies of using robotic
bronchoscopy [Ho et al. (5)] and cone beam computed tomography (CT) scan for accurate
tissue biopsy acquisition [Verhoeven et al. (6)]; (III) the state of the art in non-invasive
and minimally invasive surgical approaches to treat lung cancer by transbronchial
ablation therapies [Chan et al. (7)] and uniportal robotic surgery [Gonzalez-Rivas
et al. (8)]; (IV) the current use of targeted therapy with preview to how it might
change in the next decade [Li et al. (9)]; and (V) other technologies such as artificial
intelligence [Bardoni et al. (10)] and 3D printing [Aravena et al. (11)] that could
revolutionize how lung cancer is managed. We hope you will enjoy reading this special
series, where leading clinician scientists dare to push the boundaries and dream of
what might become standard care in their own sub-specialty or area of research interest
in the next golden decade.
Calvin S. H. Ng
Supplementary
The article’s supplementary files as
10.21037/atm-2024-01
The uniportal access for robotic thoracic surgery presents itself as a natural evolution of minimally invasive thoracic surgery (MITS). It was developed by surgeons who pioneered the uniportal video-assisted thoracic surgery (U-VATS) in all its aspects following the same principles of a single incision by using robotic technology. The robotic surgery was initially started as a hybrid procedure with the use of thoracoscopic staplers by the assistant. However, due to the evolution of robotic modern platforms, the staplers can be nowadays controlled by the main surgeon from the console. The pure uniportal robotic-assisted thoracic surgery (U-RATS) is defined as the robotic thoracic surgery performed through a single intercostal (ic) incision, without rib spreading, using the robotic camera, robotic dissecting instruments and robotic staplers. There are presented the advantages, difficulties, the general aspects and specific considerations for U-RATS. For safety reasons, the authors recommend the transition from multiportal-RATS through biportal-RATS to U-RATS. The use of robotic dissection and staplers through a single incision and the rapid undocking with easy emergent conversion when needed (either to U-VATS or to thoracotomy) are safety advantages over multi-port RATS that cannot be overlooked, offering great comfort to the surgeon and quick and smooth recovery to the patient.
Background and Objective The adoption of targeted therapy and immunotherapy has revolutionised the treatment landscape of non-small cell lung cancer. For early staged disease, incorporation of targeted therapy and immunotherapy has recently been demonstrated to reduce recurrence. Development of targeted therapies in advanced lung cancer is driven by advanced genomic sequencing techniques, better understanding of drug resistance mechanisms, and improved drug designs. The list of targetable molecular alteration is continuously expanding, and next generation molecular therapies have shown promise in circumventing drug resistance. Lung cancer patients may achieve durable disease control with immune checkpoint inhibitors however most patients develop immunotherapy resistance. A wide spectrum of resistance mechanisms, ranging from impaired T-cell activation, presence of coinhibitory immune checkpoints, to immunosuppressive tumour microenvironment, have been proposed. A multitude of novel immunotherapy strategies are under development to target such resistance mechanisms. This review aims to provide a succinct overview in the latest development in targeted therapy and immunotherapy for NSCLC management. Methods We searched all original papers and reviews on targeted therapy and immunotherapy in non-small cell lung cancer (NSCLC) using PubMed in June 2022. Search terms included “non-small cell lung cancer”, “targeted therapy”, “immunotherapy”, “EGFR”, “ALK”, “ROS1”, “BRAF V600E”, “MET”, “RET”, “KRAS”, “HER2”, “ERBB2”, “NRG1”, “immune checkpoint”, “PD-1”, “PD-L1”, “CTLA4”, “TIGIT”, “VEGF”, “cancer vaccine”, “cellular therapy”, “tumour microenvironment”, “cytokine”, and “gut microbiota”. Key Content and Findings We first discuss the incorporation of targeted therapy and immunotherapy in early staged NSCLC. This includes the latest clinical data that led to the approval of neoadjuvant immunotherapy, adjuvant immunotherapy and adjuvant targeted therapy for early staged NSCLC. The second section focuses on targeted therapy in metastatic NSCLC. The list of targetable alteration now includes but is not limited to EGFR, ALK, ROS1, BRAF V600E, MET exon 14 skipping, RET, KRAS G12C, HER2 and NRG1. Potential drug resistance mechanisms and novel therapeutics under development are also discussed. The third section on immunotherapy in metastatic NSCLC, covers immunotherapy that are currently approved [anti-PD-(L)1 and anti-CTLA4], and agents that are under active research (e.g., anti-TIGIT, cancer vaccine, cellular therapy, cytokine and other TME modulating agents). Conclusions This review encompasses the latest updates in targeted therapy and immunotherapy in lung cancer management and discusses the future direction in the field.
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