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Cardiology4640 papers

Non-small cell lung cancer

Last edited: 29 days ago

Overview

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for approximately 85% of all lung cancer diagnoses 1. It is a highly lethal malignancy, ranking as the leading cause of cancer-related deaths worldwide 1. NSCLC predominantly affects older adults, with a median age at diagnosis around 70 years, and is more prevalent in smokers and those exposed to environmental carcinogens 15. Early detection and appropriate management are crucial for improving survival rates and quality of life. Understanding the nuances of NSCLC management is essential for clinicians to optimize patient outcomes in day-to-day practice 122.

Pathophysiology

NSCLC arises from the uncontrolled proliferation of epithelial cells in the lung, primarily driven by genetic mutations and epigenetic alterations. Key molecular drivers include mutations in genes such as EGFR, ALK, ROS1, and KRAS, which disrupt normal cellular signaling pathways like the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR cascades 11415. These alterations lead to uncontrolled cell growth and survival, often accompanied by resistance to apoptosis. Additionally, tumor microenvironment interactions, including immune evasion mechanisms and angiogenesis, contribute to tumor progression and metastasis 134. The complex interplay of these factors necessitates a multifaceted therapeutic approach tailored to individual patient profiles 114.

Epidemiology

The incidence of NSCLC continues to rise globally, with an estimated 2.2 million new cases annually 1. It disproportionately affects older adults, with a peak incidence in individuals over 65 years old, and shows a slight male predominance 15. Geographic variations exist, with higher rates observed in regions with significant tobacco use and industrial pollution 15. Over time, trends indicate an increase in early-stage detection due to advancements in screening methods, though mortality rates remain high due to late-stage diagnoses in many cases 126. Risk factors include a history of smoking, occupational exposures, air pollution, and genetic predispositions 15.

Clinical Presentation

Patients with NSCLC often present with nonspecific symptoms such as persistent cough, dyspnea, chest pain, and weight loss, which can delay diagnosis 1. Hemoptysis, recurrent infections, and signs of paraneoplastic syndromes (e.g., clubbing, Horner syndrome) can also occur 14. Atypical presentations may include neurological symptoms if metastasis to the brain occurs, or constitutional symptoms like fatigue and anorexia 1. Early detection through screening can identify asymptomatic cases, particularly in high-risk populations 126. Prompt recognition of these symptoms is critical for timely intervention 1.

Diagnosis

The diagnostic approach for NSCLC involves a combination of imaging, tissue sampling, and molecular testing. Key steps include:

  • Imaging: Chest CT scans are essential for initial detection and staging 17.
  • Tissue Sampling: Bronchoscopy with biopsy, transthoracic needle biopsy, or surgical resection (e.g., lobectomy) is necessary for histopathological confirmation 146.
  • Molecular Testing: Next-generation sequencing (NGS) or targeted gene panels to identify actionable mutations (EGFR, ALK, ROS1, etc.) 1214.

    • Specific Criteria and Tests:

  • CT Scan: Look for nodules, mediastinal lymphadenopathy, and signs of mediastinal or distant metastasis.
  • Biopsy: Histological confirmation required; cytology may be used as an adjunct.
  • Molecular Testing: Perform on all resected specimens and advanced-stage tumors; consider in early-stage disease if clinical factors suggest high risk.
  • Staging: Use 8th edition TNM staging system for accurate prognostic stratification 7.

    • Differential Diagnosis:

  • Benign Tumors: Hamartomas, granulomas; distinguished by histology and clinical context.
  • Infections: Tuberculosis, fungal infections; ruled out by microbiological tests and imaging characteristics.
  • Metabolic Disorders: Pulmonary amyloidosis; identified through specific staining and clinical correlation 1.

    • Management

    First-Line Treatment

  • EGFR/ALK/ROS1 Mutations: Targeted therapies like osimertinib, crizotinib, or alectinib, respectively, with response monitoring every 3-6 months 11415.
  • Wild-Type NSCLC: Combination chemotherapy (e.g., cisplatin/pemetrexed or carboplatin/paclitaxel) with or without bevacizumab in nonsquamous histology 131.

    • Monitoring:

  • Regular imaging (CT scans) every 3-6 months.
  • Blood tests for tumor markers (if applicable).
  • Assess for adverse effects and manage accordingly.

    • Second-Line Treatment

  • Chemotherapy: Docetaxel, pemetrexed, or ramucirumab based on performance status and prior treatments 15859.
  • Immunotherapy: Pembrolizumab or nivolumab for PD-L1 positive tumors or in combination with chemotherapy 14046.

    • Monitoring:

  • Evaluate response every 6-9 weeks.
  • Manage immune-related adverse events (irAEs) promptly.

    • Refractory or Specialist Escalation

  • Clinical Trials: Consider enrollment in trials targeting specific mutations or novel therapies.
  • Supportive Care: Focus on symptom management, palliative care integration, and multidisciplinary support 18.

    • Contraindications:

  • Severe comorbidities (e.g., uncontrolled infection, significant organ dysfunction).
  • Prior severe adverse reactions to specific agents.

    • Complications

    Acute Complications

  • Cardiotoxicity: Irregular heart rhythms, myocardial injury; monitor ECGs and cardiac biomarkers 11920.
  • Immune-Related Adverse Events (irAEs): Pneumonitis, colitis, endocrinopathies; manage with corticosteroids and dose adjustments 11046.

    • Long-Term Complications

  • Secondary Malignancies: Increased risk with radiation therapy; long-term surveillance recommended 1.
  • Chronic Pulmonary Issues: Recurrent infections, chronic obstructive pulmonary disease (COPD) exacerbation; consider pulmonary rehabilitation 1330.

    • Referral Triggers:

  • Persistent or severe irAEs.
  • Complex cardiotoxicities requiring specialized cardiology intervention.
  • Recurrent or refractory symptoms necessitating multidisciplinary care.

    • Prognosis & Follow-Up

    Prognosis varies widely based on stage at diagnosis, molecular profile, and patient comorbidities. Early-stage disease generally has better outcomes, with 5-year survival rates ranging from 50-80% 122. Key prognostic indicators include:
  • Tumor Stage: Earlier stages confer better survival.
  • Molecular Subtypes: Targetable mutations often predict better response to therapy.
  • Performance Status: Higher functional status correlates with improved outcomes.

    • Follow-Up Intervals:

  • Early Stage: Every 3-6 months for the first 2 years, then annually.
  • Advanced Stage: More frequent monitoring (every 3-6 months) due to higher risk of recurrence.
  • Imaging: Regular CT scans as per stage and treatment protocol.
  • Molecular Monitoring: Periodic testing for resistance mutations in targeted therapy patients 122.

    • Special Populations

    Elderly Patients

  • Consideration: Tailor treatment intensity based on functional status and comorbidities.
  • Approach: Often benefit from less aggressive regimens like single-agent immunotherapy or targeted therapies 122.

    • Patients with COPD

  • Impact: COPD may affect treatment tolerance and outcomes; consider COPD management alongside cancer therapy.
  • Management: Close monitoring of respiratory function and potential exacerbation risks 1330.

    • Immune Checkpoint Inhibitors in Geriatric Patients

  • Caution: Increased risk of irAEs; careful patient selection and close monitoring essential 11046.

    • Key Recommendations

  • Screen High-Risk Populations: Implement low-dose CT screening for individuals aged 50-80 with ≥ 20 pack-years smoking history 26(Evidence: Strong).
  • Molecular Profiling: Perform comprehensive molecular testing on all NSCLC cases to guide targeted therapy 12(Evidence: Strong).
  • First-Line Targeted Therapy: Use EGFR/ALK/ROS1 inhibitors in patients with respective mutations 114(Evidence: Strong).
  • Immunotherapy for PD-L1 Positive Tumors: Consider pembrolizumab or nivolumab in PD-L1 positive advanced NSCLC 146(Evidence: Moderate).
  • Regular Monitoring: Schedule follow-up imaging and biomarker assessments every 3-6 months for early-stage disease 122(Evidence: Moderate).
  • Supportive Care Integration: Incorporate palliative care early in the treatment course 8(Evidence: Moderate).
  • Manage Cardiotoxicity: Regularly monitor cardiac function in patients receiving cardiotoxic agents 119(Evidence: Moderate).
  • Address COPD Comorbidities: Tailor treatment plans considering COPD status to minimize respiratory complications 13(Evidence: Moderate).
  • Evaluate for Venous Thromboembolism: Screen for VTE risk and prophylaxis in advanced NSCLC patients 24(Evidence: Moderate).
  • Consider Clinical Trials: Enroll eligible patients in clinical trials for novel therapies or refractory cases 46(Evidence: Expert opinion).

    • References

    Showing 100 most recent of 1409 indexed papers.

    1 Defosse JM, von Dossow V, Dudek W, Halank M, Loop T, Stoelben E et al.. [Not Available]. Zentralblatt fur Chirurgie 2026. link 2 Meng X, Bi N, Wang J, Meng X, Wang J, Xing L et al.. Consensus on the diagnosis and treatment of unresectable stage III driver gene-positive non-small cell lung cancer. Cancer letters 2026. link 3 Li W, Liu S, Yu X, Lan W, Liu X. Impact of Emphysema on Therapeutic Efficacy and Immune-Related Pneumonitis Risk in NSCLC Patients Receiving ICIs: A Meta-Analysis of Improved Survival but Increased Toxicity. International journal of chronic obstructive pulmonary disease 2026. link 4 Cold KM. Invasive Procedures in Interventional Pulmonology: A Narrative Review of Educational Evidence-Based Step-By-Step Protocols. Journal of visualized experiments : JoVE 2026. link 5 Kaltman M, Yalamanchili S, Park JA, Weyant MJ, Suzuki K. Emergency Room, Cardiology, and Preoperative Clinics Represent the Most Visited Departments by Lung Cancer Screening-eligible Patients. The Annals of thoracic surgery 2026. link 6 Channick CL, Agrawal A, Holden VK, Reinoso J, Schwalk AJ, Schwartz J et al.. American Association of Bronchology and Interventional Pulmonology Essential Knowledge in Interventional Pulmonology Series: Update on Curative-Intent Bronchoscopy for Centrally Located Early-Stage Lung Cancer. Journal of bronchology & interventional pulmonology 2026. link 7 Gorospe L, Gómez-Bermejo MÁ, Mirambeaux-Villalona RM, Ajuria-Illarramendi O, Muñoz-Molina GM, García-Pardo de Santayana M. The implications of the 9th lung cancer TNM classification on the thoracic interventional radiologist: A pictorial review. Radiologia 2026. link 8 Besculides M, Mazor MB, Moreno Alvarado C, Jain M, Li L, Morillo J et al.. Impact of Patient and Caregiver Beliefs on Utilization of Hospice and Palliative Care in Diverse Patients With Advanced Lung Cancer. The American journal of hospice & palliative care 2026. link 9 Iida Y, Naito T, Takahashi T, Sato T. The efficacy and safety profile of methadone for intractable cancer pain in advanced lung cancer patients: a single-center retrospective analysis of 37 Japanese patients. Japanese journal of clinical oncology 2026. link 10 Tian Y, Nie X, Yuan Y, Wei Q, Zhang S, Li L. Bridging FDA Adverse Event Reporting System (FAERS) and Clinical Practice: Comprehensive Characterization of Immune Checkpoint Inhibitors Toxicities in Geriatric Lung Cancer Patients. Thoracic cancer 2026. link 11 Wang Y, Jiang W, Cheng Y, Dong Q, Ru J, Yu C et al.. Safety evaluation of selective RET inhibitors in patients with lung cancer: a real-world pharmacovigilance study. Tumori 2026. link 12 Chang X, Shao D, Bao J, Liu Z, Ma J. Comparative Toxicovigilance of Capmatinib and Tepotinib in NSCLC: Respiratory Signal Detection and Adverse Event Profiling via FAERS. Journal of biochemical and molecular toxicology 2026. link 13 Watanabe H, Nakagawa T, Yamada S, Masuda R. Partial Anomalous Pulmonary Venous Return in Lung Cancer Surgery: Diagnostic Challenges and Surgical Considerations in Two Cases. The Tokai journal of experimental and clinical medicine 2026. link 14 Garcia A, Kayani AMA, Navarro-Martinez DA, Lemus-Zamora RE, Salama-Frisbie R, Fretz T et al.. Cardiotoxic Effects of Osimertinib Compared to Other EGFR Inhibitors: A Systematic Review and Meta-Analysis. Cardiovascular toxicology 2026. link 15 Liu X, Tao X, Cheng M, Yan H, Xu Z, Yang B et al.. Mechanisms and management of crizotinib-induced toxicity in non-small cell lung cancer. Toxicology letters 2026. link 16 Park C, Lee HJ, Jeong WG. Artificial intelligence-assisted automated measurement of maximum aortic diameter in the Korean national lung cancer screening CT program. The British journal of radiology 2026. link 17 Song J, Chi KY, Jeon H, Chang YC, Xanthavanij N, Tang Z et al.. Statin and Immune-Related Cardiovascular Events in Lung Cancer Patients Receiving Immune Checkpoint Inhibitors. Oncology 2026. link 18 Kim Y, Lee J, Suh HS, Park C. Cardiovascular and cancer-specific mortality in older patients with advanced non-small cell lung cancer following the introduction of immuno-oncology therapies. Journal of geriatric oncology 2026. link 19 Chen X, Zhang X, Xu T, Mohan R, Lin R, Chen M et al.. Radiation Doses to Cardiac Substructures Predict Elevation in High-sensitivity Cardiac Troponin T Levels in Radiation Therapy for Lung Cancer. International journal of radiation oncology, biology, physics 2026. link 20 Kobat H, Davidson M, Elkonaissi I, Foreman E, Nabhani-Gebara S. Multiple cardiotoxicities during osimertinib therapy. Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners 2026. link 21 Fu Y, Yu J, Jiang X, Gao J, Zhang Z, Zhang N et al.. Impact of mildly elevated pulmonary artery systolic pressure on hypotension and myocardial injury during thoracoscopic lobectomy: a retrospective cohort study. International journal of surgery (London, England) 2026. link 22 Zhang K, Ayala A, Norambuena-Soto I, Agnihotri V, Shu T, Nenninger C et al.. Osimertinib induces reversible cardiac dysfunction through the GATA4-MYLK3-MYL2 axis. European heart journal 2026. link 23 Ishii S, Ichimura T, Ichikura D, Hida N, Nawata S. Risk factors for vasculitis and vascular pain associated with cisplatin and vinorelbine in adjuvant chemotherapy. Pain management 2026. link 24 Tsubata Y, Kanaji N, Nakao M, Masuda T, Yamasaki M, Kodani M et al.. Incidence and clinical features of venous thromboembolism in patients with lung cancer in Japan: results from the CS-Lung-003 prospective observational registry study. 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The clinical respiratory journal 2025. link 46 Leighl NB, Ismaila N, Durm G, Florez N, Freeman-Daily J, Pellini B et al.. Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2024.3. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2025. link 47 Iqbal B, Choi HJ, Kanellakis NI, Akulian J, Rahman NM. Bedside to bench and back again-translational research in interventional pulmonology. Current opinion in pulmonary medicine 2025. link 48 Looby N, Tessendorf CD, Hagen J, Looby M, Liscano B. Recurrent Venous Thromboembolism in a Young Adult: A Case Report and Comprehensive Review of Diagnostic Approaches. South Dakota medicine : the journal of the South Dakota State Medical Association 2025. link 49 Nguyen P, Shah PL. Contemporary Concise Review 2024: New Techniques in Interventional Pulmonology. Respirology (Carlton, Vic.) 2025. link 50 Maldonado F, Paez R, Lentz RJ, Ratwani A, Casey JD. 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Integrative Computational Immunology Applied to Identify and Characterize CD8+ T-cell Neoepitopes of Shared KRAS Neoantigen Oncogenic Driver Hotspot Mutations. Asian Pacific journal of cancer prevention : APJCP 2025. link 55 Yuan M, Han N, Shu L, Yan L, Tang H. Case report: Multi-organ injuries induced by tislelizumab. Frontiers in immunology 2025. link 56 Edmonds MC, Mazor M, Jain M, Li L, Augustin M, Morillo J et al.. Drivers of Palliative Care and Hospice Use Among Patients With Advanced Lung Cancer. Cancer medicine 2025. link 57 Agne JL, Gusovsky Chevalier AV, Benedict JA, Khan N, Saphire M, Kumar P et al.. Impact of an embedded onco-palliative care clinic on urine drug testing in thoracic oncology. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 2025. link 58 Wang L, Zhao H, Yang K, Wang Z, Cai C, Lv P et al.. 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Adverse events of Capmatinib: A real-world drug safety surveillance study based on the FDA adverse event reporting system (FAERS) database. Medicine 2025. link 64 Frey C. Disproportionality analysis of ALK inhibitor-induced hemolytic adverse events: a pharmacovigilance study using the FDA Adverse Event Reporting System Database. Canadian journal of physiology and pharmacology 2025. link 65 Wang H, Chen K, Ma S, Huang W, Xie J, Wang N et al.. PPIs effect in EGFR-TKI-associated interstitial lung diseases in patients with non-small cell lung cancer. BMC cancer 2025. link 66 Li W, Lv R, Wang W. Toxicity profiles associated with EGFR-TKIs combined with angiogenesis inhibitors in non-small cell lung cancer: an epidemiological surveillance analysis of the FDA adverse event reporting system. Expert opinion on drug safety 2025. link 67 Li P, Wu L, Song Z. Data mining and safety analysis of FGFR tyrosine kinase inhibitors based on the FAERS database. Scientific reports 2025. link 68 Zhang J, Li W. Real-world pharmacovigilance analysis unveils the toxicity profile of amivantamab targeting EGFR exon 20 insertion mutations in non-small cell lung cancer. BMC pulmonary medicine 2025. link 69 Zhang H, Song Y, Xia F, Liu Y, Zhang L, Yang J et al.. Adverse event profile of crizotinib in real-world from the FAERS database: a 12-year pharmacovigilance study. BMC pharmacology & toxicology 2025. link 70 Hou Y, Ren X, Chen Y, Wang Y. Cardiovascular toxicities of selective ret-specific tyrosine kinase inhibitors: a pharmacovigilance study based on the United States Food and Drug Administration Adverse Event Reporting System database. Expert opinion on drug safety 2025. link 71 Li S, Huang Z, Zhong X, Zhou Y, Jiang H. The real-world safety profile of pemetrexed and platinum with or without pembrolizumab: insights from a comparative analysis of FAERS database. BMC cancer 2025. link 72 Fujiwara M, Ikesue H, Yamaoka K, Uchida M, Uesawa Y, Muroi N et al.. Disproportionality Analysis of Hepatotoxic and Gastrointestinal Adverse Events Associated With Nintedanib Using the Japanese Adverse Drug Event Report (JADER) Database. In vivo (Athens, Greece) 2025. link 73 Shi Z, Shao K, Wang K, Xu M, Yu X, Xu C et al.. Post-marketing safety of pralsetinib: a real-world disproportionality analysis based on the FDA adverse event reporting system database. International journal of clinical pharmacy 2025. link 74 Gao R, Liang W, Chen J, Yang M, Yu X, Wang X. Comparisons of adverse events associated with immune checkpoint inhibitors in the treatment of non-small cell lung cancer: a real-world disproportionality analysis based on the FDA adverse event reporting system. BMC cancer 2025. link 75 He Q, Wei Y, Zhu H, Song Y, Chen P, Dong Q et al.. Association of Reduced Folate Carrier G80A Polymorphism With Lung Cancer Susceptibility in a Hypertensive Population: A Nested Case-Control Study. The Journal of nutrition 2025. link 76 Shang C, Wang H, Chen J, Cao S, Sun Y, Sheng Z et al.. Angiotensin receptor-neprilysin inhibitors improve the outcome of lung cancer patients with hypertension undergoing immune checkpoint inhibitors treatment. BMC cardiovascular disorders 2025. link 77 Peng Y, Li D, Wampfler JA, Luo YH, Kumar AV, Gu Z et al.. Targeted therapy‑associated cardiotoxicity in patients with stage‑IV lung cancer with or without cardiac comorbidities. Oncology reports 2025. link 78 Liao J, Wu Z. Different modes of ankle pump exercise to prevent PICC-related thrombosis through femoral vein. Phlebology 2025. link 79 Qin Y, Liang X, Wu H, Sun X, Yan S, Wang N et al.. Development and Validation of a Modified Khorana Score for Predicting Venous Thromboembolism in Newly Diagnosed Stage IV Lung Cancer. 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    Original source

    1. [1]
      [Not Available]. — Defosse JM, von Dossow V, Dudek W, Halank M, Loop T, Stoelben E et al. Zentralblatt fur Chirurgie (2026)
    2. [2]
      Consensus on the diagnosis and treatment of unresectable stage III driver gene-positive non-small cell lung cancer. — Meng X, Bi N, Wang J, Meng X, Wang J, Xing L et al. Cancer letters (2026)
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