Metastatic Non-Small Cell Lung Cancer

1. Disease Information

Overview / definition

mNSCLC refers to non-small cell lung cancers that have spread beyond the lung/hemithorax to distant organs (clinically aligned with stage IV/M1 disease in many registries and studies). Contemporary studies use “metastatic NSCLC,” “advanced NSCLC,” and “stage IV NSCLC” as overlapping operational terms depending on inclusion criteria and data source. (apter2024realworldtreatmentpatterns pages 1-2, uprety2024racialandsocioeconomic pages 3-4, yang2024disparitiesinutilization pages 1-2)

Key identifiers (as available in retrieved sources)

• Open Targets / EFO: non-small cell lung carcinoma EFO_0003060. (OpenTargets Search: Non-small cell lung carcinoma,Lung adenocarcinoma,Lung squamous cell carcinoma)
• MONDO: non-small cell squamous lung carcinoma MONDO_0056806 (related histology entity). (OpenTargets Search: Non-small cell lung carcinoma,Lung adenocarcinoma,Lung squamous cell carcinoma)
• MeSH / ICD-10 / ICD-11 / OMIM / Orphanet: Not found in the retrieved evidence for mNSCLC or stage IV NSCLC; these would typically be obtained from ontology resources (e.g., MeSH browser, ICD-10/11, MONDO) outside the currently retrieved corpus.

Common synonyms

• Metastatic NSCLC, advanced NSCLC (when metastatic), stage IV NSCLC, M1 NSCLC. (apter2024realworldtreatmentpatterns pages 1-2, uprety2024racialandsocioeconomic pages 3-4, yang2024disparitiesinutilization pages 1-2)

Evidence source types

• Aggregated disease-level resources: SEER/SEER-Medicare population datasets and national registries (Norway). (hektoen2024realworldevidencefor pages 1-2, uprety2024racialandsocioeconomic pages 3-4)
• Real-world evidence (RWE): health system cohorts and EMR datasets. (apter2024realworldtreatmentpatterns pages 1-2, hektoen2024realworldevidencefor pages 5-6)
• Clinical trials: phase 3 biomarker-selected trials (e.g., EGFR-mutant MARIPOSA). (cho2024amivantamabpluslazertinib pages 8-9)

2. Etiology

Primary causal factors (multifactorial)

NSCLC (and thus mNSCLC) arises through a combination of carcinogen exposures and acquired somatic genomic alterations (driver mutations/fusions), with strong contributions from tobacco smoke and additional environmental/occupational carcinogens.

Tobacco smoking

Tobacco is the dominant risk factor in Western settings; a 2024 review of geographic differences states tobacco accounts for “up to 80–90% of cases” in Western societies. (laguna2024geographicdifferencesin pages 1-3)

Ambient air pollution (particulate matter)

Air pollution is classified as carcinogenic to humans, and long-term PM2.5 exposure shows dose–response associations with lung cancer risk and mortality. A 2024 review reports, for example, AHSMOG-2: a 10 μg/m³ PM2.5 increase associated with HR 1.43 (95% CI 1.03–2.00) for lung cancer. (yoo2024updateinassociation pages 2-3)

Mechanistic plausibility described in the same review includes oxidative stress, inflammation, and DNA damage/mutagenesis pathways induced by PM components (e.g., PAHs, metals) and ROS signaling. (yoo2024updateinassociation pages 2-3)

Occupational carcinogens: cadmium (example with quantitative meta-analysis)

A 2024 systematic review/meta-analysis reported higher cadmium exposure associated with increased lung cancer risk: OR 1.31 (95% CI 1.06–1.62; p=0.024), interpreted as a 31% increase. (farahmandian2024investigatingtherelationship pages 1-2)

Radon

Radon is commonly described as a leading non-tobacco cause (particularly in the US) and has no known safe level; the EPA remediation threshold 4 pCi/L (148 Bq/m³) is cited in a 2024 review. (laguna2024geographicdifferencesin pages 1-3)

Protective factors

Direct protective-factor estimates were not retrieved in the current evidence set. In practice, major protective factors include tobacco cessation and reduction of carcinogen exposures; smoking cessation is emphasized as a key preventive action within screening guidelines. (wolf2024screeningforlung pages 7-7)

Gene–environment interactions

A 2024 review notes associations between exposure patterns and driver distributions: EGFR mutations are more common in never-smokers and some populations, while KRAS G12C is associated with smoking history. (laguna2024geographicdifferencesin pages 1-3)

3. Phenotypes

Clinical presentation (metastatic disease)

mNSCLC can present with pulmonary symptoms (cough, dyspnea), systemic symptoms (weight loss), and/or organ-specific symptoms from metastases. In a SEER-M1 analysis, common metastatic organs vary by histology (see “Anatomical structures affected”). (xie2024distantmetastasispatterns pages 1-2, xie2024distantmetastasispatterns pages 2-3)

Metastasis-associated phenotypes & HPO term suggestions

Below are common metastasis-related phenotype groupings relevant to mNSCLC knowledge-base annotation. Frequencies are not uniformly available across all studies in the retrieved evidence; where available, they are provided.

1. Bone metastasis / skeletal complications
2. Evidence of frequency/pattern: In SEER M1 lung cancer, bone metastasis was most common in lung adenocarcinoma (ADC), squamous (SCC), adenosquamous (ASC), and large cell carcinoma (LCC) (e.g., ADC bone metastasis 35.15%). (xie2024distantmetastasispatterns pages 2-3)
3. EGFR-mutant cohort: vertebrae (76.3%) and pelvis (60.9%) were frequent bone sites. (tanaka2024femoralbonemetastasis pages 1-3)

4. Suggested HPO: HP:0002652 (Skeletal metastasis), HP:0002653 (Bone pain), HP:0012655 (Pathologic fracture).

5. Brain metastasis / neurologic manifestations

6. Epidemiology note: brain metastases present in a meaningful subset; a real-world US cohort reported brain metastases present in 22.9% of advanced NSCLC patients at treatment initiation. (hektoen2024realworldevidencefor pages 3-5)

7. Suggested HPO: HP:0002506 (Brain metastasis), HP:0001288 (Gait disturbance), HP:0001250 (Seizures), HP:0002315 (Headache).

8. Liver metastasis / hepatic dysfunction

9. In SEER, liver metastases were particularly common in SCLC rather than NSCLC, but liver involvement in advanced NSCLC is prognostically important (see prognosis section). (xie2024distantmetastasispatterns pages 2-3, brown2024sitespecificresponseand pages 11-12)

10. Suggested HPO: HP:0001410 (Hepatomegaly), HP:0001397 (Hepatic metastasis), HP:0002904 (Elevated hepatic transaminases) (laboratory abnormality).

11. Adrenal metastasis

12. Mentioned as a common extrathoracic site in advanced NSCLC cohorts. (brown2024sitespecificresponseand pages 1-2)
13. Suggested HPO: HP:0031909 (Adrenal metastasis) (if available in HPO; otherwise annotate as adrenal mass + cancer).

Quality of life impact

Direct QoL instrument data (e.g., EQ-5D, SF-36) specific to metastatic NSCLC were not retrieved in the current evidence set; however, the metastatic burden and organ involvement (bone/brain) are consistently associated with poorer survival and often correlate with functional decline. (brown2024sitespecificresponseand pages 11-12, tanaka2024femoralbonemetastasis pages 1-3)

4. Genetic / Molecular Information

Core concept: actionable somatic drivers and biomarkers

Modern mNSCLC management is biomarker-driven: actionable genomic alterations and immune biomarkers (PD-L1, sometimes TMB) are used to select targeted therapy or immunotherapy.

A 2024 review lists actionable first-line targets in unresectable/advanced/metastatic NSCLC including EGFR, ALK, ROS1, RET, NTRK1/2/3 fusions, BRAF V600E, and MET exon 14 skipping; immune selection includes PD-L1 TPS ≥50% for PD-1/PD-L1 monotherapy when no sensitizing EGFR/ALK alterations are present. (li2024evolvingprecisionfirstline pages 1-2)

A separate 2024 review emphasizes broad panels and includes additional emerging targets such as ERBB2 (HER2) and KRAS G12C. (li2024evolvingprecisionfirstline pages 4-6)

Suggested genes (HGNC symbols)

EGFR, KRAS, ALK, ROS1, MET, RET, ERBB2, BRAF, NTRK1, NTRK2, NTRK3, TP53, STK11, KEAP1.

Pathogenic variants (somatic)

• EGFR activating variants: exon 19 deletions, L858R (used as eligibility in EGFR-mutant metastatic trials). (cho2024amivantamabpluslazertinib pages 1-4)
• KRAS G12C: occurs in ~13% of lung adenocarcinomas; KRAS mutations overall ~25–30% of NSCLC; G12C ~40% of KRAS-mutated NSCLC. (chour2024mechanismsofresistance pages 1-2, warnecke2024adagrasibinthe pages 1-2)
• ERBB2 (HER2): HER2 mutations occur in ~4% of NSCLC; common exon 20 insertion A775_G776insYVMA ~34% of HER2 mutations. (ferrari2024her2alterednonsmallcell pages 1-2)

Molecular biomarkers (immune)

• PD-L1 TPS ≥50%: used to select PD-1/PD-L1 monotherapy as standard of care in biomarker-driven algorithms. (li2024evolvingprecisionfirstline pages 1-2)
• A large combined trial + real-world analysis found tumor PD-L1 ≥50% specifically associated with CPI response, and TMB ≥10.44 mut/Mb associated with durable CPI response; combined high TMB + high PD-L1 was the strongest predictor reported (OR 0.04). (hektoen2024realworldevidencefor pages 3-5, cho2024amivantamabpluslazertinib pages 7-8)

Resistance mechanisms (selected examples)

• KRAS G12C inhibitors: resistance frequently acquired; includes on-target KRAS mutations affecting inhibitor binding and off-target bypass via NRAS, BRAF, RET activation, PTEN loss, EMT, and histologic transformation. (chour2024mechanismsofresistance pages 1-2)

Epigenetic / chromosomal abnormalities

Specific epigenetic or chromosomal-abnormality datasets were not retrieved in the current evidence set.

5. Environmental Information

Environmental and lifestyle factors

• Ambient PM2.5 exposure shows increased risk and mortality with mechanistic links to ROS/oxidative stress and DNA damage. (yoo2024updateinassociation pages 2-3)
• Cadmium exposure is associated with increased risk (meta-analysis OR 1.31). (farahmandian2024investigatingtherelationship pages 1-2)
• Radon exposure is emphasized as a major residential risk and policy target (EPA action level 4 pCi/L). (laguna2024geographicdifferencesin pages 1-3)

Infectious agents

No specific infectious causal agents for NSCLC were retrieved in the current evidence set.

6. Mechanism / Pathophysiology

Core oncogenic signaling pathways

• EGFR pathway and downstream MAPK/PI3K signaling drive EGFR-mutant NSCLC; EGFR-directed therapies improve outcomes in biomarker-selected metastatic disease (see Treatments). (cho2024amivantamabpluslazertinib pages 1-4)
• KRAS is a small GTPase cycling between GDP/GTP states; KRAS G12C inhibitors covalently target the inactive GDP-bound state and suppress downstream MAPK and PI3K signaling. (chour2024mechanismsofresistance pages 1-2)

Tumor microenvironment (TME) and immune evasion

Organ-specific microenvironments influence immunotherapy response: bone and liver metastases are associated with lower response and worse outcomes, suggesting site-specific immune resistance. (brown2024sitespecificresponseand pages 11-12, brown2024sitespecificresponseand pages 1-2)

Mechanistic chain (example: KRAS G12C targeted therapy)

1) KRAS G12C mutation → accumulation of KRAS(GDP)-bound fraction amenable to covalent inhibitors → initial MAPK/PI3K suppression → tumor response. (chour2024mechanismsofresistance pages 1-2) 2) Adaptive feedback and bypass signaling (e.g., NRAS/BRAF/RET activation; PTEN loss) and phenotypic shifts (EMT, transformation) → acquired resistance and progression. (chour2024mechanismsofresistance pages 1-2)

Suggested GO biological process terms (illustrative)

• GO:0007169 (transmembrane receptor protein tyrosine kinase signaling pathway)
• GO:0000165 (MAPK cascade)
• GO:0008285 (negative regulation of cell population proliferation) / dysregulation in cancer
• GO:0042110 (T cell activation) (immune context)

Suggested Cell Ontology (CL) terms (illustrative)

• CL:0000182 (T cell)
• CL:0000236 (B cell)
• CL:0000624 (CD4-positive, alpha-beta T cell)
• CL:0000625 (CD8-positive, alpha-beta T cell)
• CL:0000451 (dendritic cell)
• CL:0000235 (macrophage)

(These ontology suggestions are generic to tumor/immune interactions; the retrieved evidence supports immune and microenvironment involvement but does not enumerate CL/GO terms explicitly.) (yoo2024updateinassociation pages 2-3, brown2024sitespecificresponseand pages 11-12)

7. Anatomical Structures Affected

Organ-level sites (metastases)

A SEER-based analysis (2010–2019; 77,827 M1 cases) found histology-specific metastatic patterns: - Bone: most common in ADC, SCC, ASC, LCC (e.g., ADC 35.15%). (xie2024distantmetastasispatterns pages 2-3) - Brain: particularly common in LCNEC. (xie2024distantmetastasispatterns pages 1-2) - Liver: particularly common in SCLC (included here for lung cancer context). (xie2024distantmetastasispatterns pages 2-3) - Lung-to-lung (intrapulmonary): common in carcinoid tumors and SCC. (xie2024distantmetastasispatterns pages 1-2)

UBERON term suggestions (common sites)

• Lung: UBERON:0002048
• Bone tissue: UBERON:0002481
• Brain: UBERON:0000955
• Liver: UBERON:0002107
• Adrenal gland: UBERON:0002369

8. Temporal Development

Onset and progression

Most lung cancer is diagnosed at advanced stages in many populations; a review notes that “most cases are diagnosed in advanced stages,” emphasizing prevention/early diagnosis importance. (laguna2024geographicdifferencesin pages 1-3)

Disease stages

mNSCLC corresponds to metastatic (M1) disease; SEER data indicate substantial proportion present with metastasis at diagnosis (e.g., 41.22% M1 lung cancers with distant metastasis at presentation in one SEER analysis). (xie2024distantmetastasispatterns pages 1-2)

9. Inheritance and Population

Epidemiology (selected, recent population-based data)

• SEER-Medicare metastatic NSCLC (2015–2019; n=17,134): overall median OS 7 months, 1-year OS 34%, 2-year OS 21%. (uprety2024racialandsocioeconomic pages 3-4)
• ICI utilization: ~39% received an immune checkpoint inhibitor; utilization increased from 21.9% (2015) to 55.4% (2019). (uprety2024racialandsocioeconomic pages 3-4)
• Survival disparity: 2-year OS from diagnosis differed by race (White 22%, Asian 23%, Black 15%, Hispanic 17%); among ICI recipients, racial differences in survival were not statistically significant, suggesting access/utilization drives disparity. (uprety2024racialandsocioeconomic pages 1-2)

Genetic etiology and inheritance

mNSCLC is primarily driven by somatic alterations; a 2024 review notes pathogenic germline variants in high/moderate penetrance genes in 4.3% of a cohort (germline susceptibility signal, not typically a Mendelian inheritance pattern for mNSCLC). (laguna2024geographicdifferencesin pages 1-3)

10. Diagnostics

Tissue diagnosis and immunohistochemistry

Histologic classification in small biopsies often uses IHC panels: TTF-1 / napsin A (adenocarcinoma) and p40 / p63 (squamous). (li2024evolvingprecisionfirstline pages 2-4)

Molecular testing (tissue NGS and fusions)

CAP/IASLC/AMP guidance (as summarized in a 2024 review) recommends testing all advanced lung cancers for sensitizing EGFR and ALK, with expansion to ROS1 and BRAF and then RET, MET, ERBB2, KRAS if earlier drivers are negative; NGS is emphasized for SNVs/CNVs/fusions and high yield. (li2024evolvingprecisionfirstline pages 2-4)

RNA-based NGS can improve fusion detection (ALK/ROS1/RET/NTRK). (li2024evolvingprecisionfirstline pages 4-6)

Immune biomarker testing

PD-L1 IHC is used for PD-1/PD-L1 selection; PD-L1 TPS ≥50% is used as a key threshold for monotherapy selection in biomarker algorithms. (li2024evolvingprecisionfirstline pages 1-2)

Liquid biopsy / ctDNA

When tissue is insufficient or re-biopsy may delay care, plasma ctDNA can accelerate profiling and capture alterations from primary and metastatic sites. (li2024evolvingprecisionfirstline pages 4-6)

ctDNA is also used for resistance monitoring (e.g., EGFR T790M) and treatment decision support. (restrepo2024identificationandapplication pages 15-16)

MET amplification testing thresholds (example of concrete numeric definitions)

A 2024 review of MET amplification reports: - Primary METamp prevalence ~4.8%; secondary (post-EGFR-TKI) METamp ~15%. (yang2024nonsmallcelllung pages 1-2) - Definition variability: FISH ratios (MET:CEP7 ≥1.8 to ≥3.0) or gene copy number (GCN ≥5 to ≥10); NGS tissue thresholds (GCN ≥6); liquid biopsy thresholds reported (MET copy number ≥2.1 to >5). (yang2024nonsmallcelllung pages 1-2) - NCCN notes copy number >10 consistent with high-level MET amplification (NGS). (yang2024nonsmallcelllung pages 3-5)

Differential diagnosis

Specific differential-diagnosis algorithms were not retrieved in the current evidence set.

11. Outcome / Prognosis

Survival statistics (recent)

• Population-based metastatic NSCLC (SEER-Medicare 2015–2019): median OS 7 months; 2-year OS 21%. (uprety2024racialandsocioeconomic pages 3-4)
• Real-world first-line immunotherapy era (Norway 2012–2021): median OS improved from 8.0 months (historical chemo) to 13.8 months (pembrolizumab monotherapy) and 12.8 months (pembrolizumab + chemotherapy). (hektoen2024realworldevidencefor pages 1-2)

Prognostic factors (metastatic site)

• Bone metastases are repeatedly associated with worse outcomes.
• In a 2024 cohort, bone metastases were linked to shorter OS (median 10 vs 21 months; HR 1.95) and shorter PFS (HR 1.70). (brown2024sitespecificresponseand pages 11-12)
• A multicenter immunotherapy cohort found presence of bone metastases independently worsened OS (HR 1.26). (xie2024distantmetastasispatterns pages 2-3)

12. Treatment

Current first-line paradigms (conceptual)

For metastatic NSCLC without sensitizing oncogenic drivers, ICIs as monotherapy (PD-L1-high) or chemoimmunotherapy (PD-L1 low/negative) are standard approaches; for biomarker-defined drivers (EGFR/ALK/ROS1/RET/MET/BRAF/etc.) targeted therapies are prioritized. (li2024evolvingprecisionfirstline pages 1-2)

Recent developments / latest research (prioritizing 2023–2024)

EGFR-mutant metastatic NSCLC: MARIPOSA (practice-changing 2024)

MARIPOSA (NEJM, Oct 2024) compared amivantamab + lazertinib vs osimertinib first-line in EGFR exon19del/L858R advanced/metastatic NSCLC. - Efficacy: median PFS 23.7 vs 16.6 months, HR 0.70 (95% CI 0.58–0.85; P<0.001). ORR 86% vs 85%; median DoR 25.8 vs 16.8 months; interim OS HR 0.80 (95% CI 0.61–1.05). (cho2024amivantamabpluslazertinib pages 8-9, cho2024amivantamabpluslazertinib pages 9-11) - Safety: grade ≥3 AEs 75% vs 43%; infusion reactions 63%; venous thromboembolism 37% vs 9%; AE-related discontinuation 35% vs 14%. (cho2024amivantamabpluslazertinib pages 9-11)

Figure evidence: Kaplan–Meier PFS separation and hazard ratio are shown in the extracted figure. (cho2024amivantamabpluslazertinib media ee6afa38)

Abstract quote: “The median progression-free survival was significantly longer in the amivantamab-lazertinib group than in the osimertinib group (23.7 vs. 16.6 months; hazard ratio … 0.70 …; P<0.001).” (cho2024amivantamabpluslazertinib pages 1-4)

Suggested MAXO terms (illustrative): tyrosine kinase inhibitor therapy; monoclonal antibody therapy; combination antineoplastic therapy.

KRAS G12C metastatic NSCLC (targeted therapy; resistance-focused 2024 synthesis)

• Frequency: KRAS G12C is found in ~13% of lung adenocarcinomas. (chour2024mechanismsofresistance pages 1-2)
• Phase 3 evidence: in CodeBreaK 200, sotorasib vs docetaxel improved PFS (5.6 vs 4.5 months, HR 0.66) and ORR (28.1% vs 13.2%) but not OS (10.6 vs 11.3 months). (warnecke2024adagrasibinthe pages 4-5)
• Adagrasib CNS activity (summary): intracranial ORR 42% with intracranial PFS 5.4 months; systemic ORR 30%, PFS 5.3 months. (warnecke2024adagrasibinthe pages 4-5)
• Mechanisms of resistance: bypass activation (NRAS/BRAF/RET), PTEN loss, EMT, histologic transformation; on-target KRAS mutations preventing binding. (chour2024mechanismsofresistance pages 1-2)

Suggested MAXO: targeted small molecule therapy; molecularly targeted therapy; tumor sequencing-guided therapy.

HER2 (ERBB2)-mutant metastatic NSCLC: ADCs (2024 state-of-the-art)

• Frequency: HER2 mutations ~4% of NSCLC; common exon 20 insertion A775_G776insYVMA ~34% of HER2 mutations. (ferrari2024her2alterednonsmallcell pages 1-2)
• Trastuzumab deruxtecan (T-DXd): DESTINY-Lung01 (HER2-mutant; N=91) ORR ~55%, median PFS 8.2 months, median OS 17.8–18.6 months. (lazaratos2024apotentialcentral pages 1-2, wang2024addressingtheunmet pages 3-5)
• DESTINY-Lung02 (dose cohorts): ORR around 53.8% vs 42.9% (5.4 vs 6.4 mg/kg) in one summary. (wang2024addressingtheunmet pages 3-5)
• Intracranial relevance: reviews emphasize CNS activity and report subgroup outcomes in patients with stable brain metastases. (lazaratos2024apotentialcentral pages 2-4, ferrari2024her2alterednonsmallcell pages 1-2)

Suggested MAXO: antibody–drug conjugate therapy; HER2-targeted therapy.

Immunotherapy real-world implementation (effectiveness)

• In a nationwide Norwegian cohort, first-line pembrolizumab OS improved versus historical chemotherapy (median OS 13.8 months for pembrolizumab monotherapy and 12.8 months for pembrolizumab+chemo vs 8.0 months pre-ICI). (hektoen2024realworldevidencefor pages 1-2)
• In an Israeli health-system cohort (mNSCLC), median real-world OS from first-line was 12.5 months for PD-1 monotherapy and 14.8 months for PD-1 + chemotherapy among nonsquamous patients without EGFR/ALK/ROS1; outcomes were better in ECOG 0–1 and PD-L1 ≥50% (e.g., median rwOS 25.1 months for ECOG 0–1 with monotherapy). (apter2024realworldtreatmentpatterns pages 1-2)

Expert analysis in authoritative sources: Real-world cohorts repeatedly observe lower OS than pivotal trials but preservation of the relative benefit compared with chemotherapy, supporting generalizability while highlighting trial-to-practice gaps (age, ECOG, comorbidities). (hektoen2024realworldevidencefor pages 1-2)

13. Prevention

Primary prevention

• Reduce tobacco exposure and implement smoking-cessation interventions; ACS guideline emphasizes cessation counseling and connection to resources for current smokers. (wolf2024screeningforlung pages 7-7)
• Reduce environmental/occupational exposures (PM2.5 reduction, radon mitigation, carcinogen control) supported by risk estimates and mechanistic plausibility. (yoo2024updateinassociation pages 2-3, laguna2024geographicdifferencesin pages 1-3)

Secondary prevention: Screening (ACS 2023 update; published Nov 2024)

ACS recommends annual LDCT lung cancer screening for asymptomatic individuals: - Age: 50–80 years - Smoking: ≥20 pack-years - Smoking status: current or former smokers; years-since-quitting is not used as an eligibility criterion. (wolf2024screeningforlung pages 2-3, wolf2024screeningforlung pages 7-7)

Abstract quote: “The ACS recommends annual LCS with low‐dose computed tomography for asymptomatic individuals aged 50–80 years who currently smoke or formerly smoked and have a ≥20 pack‐year smoking history.” (wolf2024screeningforlung pages 1-2)

14. Other Species / Natural Disease

Direct comparative pathology or naturally occurring non-human mNSCLC content was not retrieved in the current evidence set.

15. Model Organisms / Model Systems

Patient-derived xenografts (PDX)

• A 2024 study established 13 NSCLC-PDXs from 62 patients, reporting preservation of histology/genetics and concordant chemotherapy responses between PDX and matched patients; an osimertinib-resistant PDX implicated DUSP6 M62I and MAPK-ERK overactivation, with trametinib slowing resistant tumor growth. (wang2024utilityofpatientderived pages 1-2)
• TRACERx multi-region analysis generated 48 PDX models from 22 patients, showing multi-region sampling improves engraftment but individual PDXs often represent a single subclone (genomic bottleneck) and do not fully recapitulate intratumor heterogeneity. (hynds2024representationofgenomic pages 1-2)

Patient-derived organoids (PDOs)

• Pleural effusion-derived organoids can be used for rapid therapy-response prediction in advanced EGFR-mutant NSCLC: drug-response evaluation within ~1 week and clinically aligned response classification within 10 days (validated in 14 patients). (lee2024predictionoftki pages 1-2)
• A 2024 Cell Reports Medicine paper describes using LUAD PDOs to model metastases and test resistance mechanisms (e.g., KRASG12C PDOs treated with sotorasib) and notes limitations of PDXs for metastasis biology (rare metastasis in LUAD PDX). (liu2024modelinglungadenocarcinoma pages 1-4)

Evidence tables (for knowledge-base population)

Table: This artifact provides two compact tables: one for disease naming/identifier coverage in the retrieved evidence, and one for pivotal 2024 metastatic NSCLC efficacy and safety figures across major treatment settings. It is useful for quickly mapping terminology and comparing contemporary clinical outcomes across targeted therapy, immunotherapy, and population-level datasets.

Notes on evidence limitations in this run

1) Several requested ontology identifiers (ICD-10/11, MeSH, metastatic-stage MONDO) were not present in the retrieved full-text corpus and should be added from ontology resources. 2) Some sections (QoL instruments, detailed differential diagnosis, epigenetics) require additional targeted retrieval beyond the current evidence set.

References

1. (OpenTargets Search: Non-small cell lung carcinoma,Lung adenocarcinoma,Lung squamous cell carcinoma): Open Targets Query (Non-small cell lung carcinoma,Lung adenocarcinoma,Lung squamous cell carcinoma, 40 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

2. (apter2024realworldtreatmentpatterns pages 1-2): Lior Apter, Sarah Sharman Moser, Ashwini Arunachalam, Sivan Gazit, Moshe Hoshen, Gabriel Chodick, and Nava Siegelmann-Danieli. Real-world treatment patterns, biomarker testing, and clinical outcomes of metastatic non-small cell lung cancer patients in the immunotherapy era. Frontiers in Oncology, Oct 2024. URL: https://doi.org/10.3389/fonc.2024.1442909, doi:10.3389/fonc.2024.1442909. This article has 2 citations.

3. (uprety2024racialandsocioeconomic pages 3-4): Dipesh Uprety, Randell Seaton, Tarik Hadid, Hirva Mamdani, Ammar Sukari, Julie J Ruterbusch, and Ann G Schwartz. Racial and socioeconomic disparities in survival among patients with metastatic non–small cell lung cancer. JNCI Journal of the National Cancer Institute, 116:1697-1704, Jun 2024. URL: https://doi.org/10.1093/jnci/djae118, doi:10.1093/jnci/djae118. This article has 17 citations.

4. (yang2024disparitiesinutilization pages 1-2): Danting Yang, Shama D. Karanth, Hyung-Suk Yoon, Jae Jeong Yang, Xiwei Lou, Jiang Bian, Dongyu Zhang, Yi Guo, Lusine Yaghjyan, Tomi Akinyemiju, Estelamari Rodriguez, Hiren J. Mehta, and Dejana Braithwaite. Disparities in utilization of immune checkpoint inhibitor therapy among older patients with advanced non–small cell lung cancer: a seer-medicare analysis. JCO Oncology Advances, Dec 2024. URL: https://doi.org/10.1200/oa.24.00008, doi:10.1200/oa.24.00008. This article has 6 citations.

5. (hektoen2024realworldevidencefor pages 1-2): Helga H. Hektoen, Kaitlyn M. Tsuruda, Lars Fjellbirkeland, Yngvar Nilssen, Odd Terje Brustugun, and Bettina K. Andreassen. Real-world evidence for pembrolizumab in non-small cell lung cancer: a nationwide cohort study. British Journal of Cancer, 132:93-102, Nov 2024. URL: https://doi.org/10.1038/s41416-024-02895-1, doi:10.1038/s41416-024-02895-1. This article has 27 citations and is from a domain leading peer-reviewed journal.

6. (hektoen2024realworldevidencefor pages 5-6): Helga H. Hektoen, Kaitlyn M. Tsuruda, Lars Fjellbirkeland, Yngvar Nilssen, Odd Terje Brustugun, and Bettina K. Andreassen. Real-world evidence for pembrolizumab in non-small cell lung cancer: a nationwide cohort study. British Journal of Cancer, 132:93-102, Nov 2024. URL: https://doi.org/10.1038/s41416-024-02895-1, doi:10.1038/s41416-024-02895-1. This article has 27 citations and is from a domain leading peer-reviewed journal.

7. (cho2024amivantamabpluslazertinib pages 8-9): Byoung C. Cho, Shun Lu, Enriqueta Felip, Alexander I. Spira, Nicolas Girard, Jong-Seok Lee, Se-Hoon Lee, Yurii Ostapenko, Pongwut Danchaivijitr, Baogang Liu, Adlinda Alip, Ernesto Korbenfeld, Josiane Mourão Dias, Benjamin Besse, Ki-Hyeong Lee, Hailin Xiong, Soon-Hin How, Ying Cheng, Gee-Chen Chang, Hiroshige Yoshioka, James C.-H. Yang, Michael Thomas, Danny Nguyen, Sai-Hong I. Ou, Sanjay Mukhedkar, Kumar Prabhash, Manolo D’Arcangelo, Jorge Alatorre-Alexander, Juan C. Vázquez Limón, Sara Alves, Daniil Stroyakovskiy, Marina Peregudova, Mehmet A.N. Şendur, Ozan Yazici, Raffaele Califano, Vanesa Gutiérrez Calderón, Filippo de Marinis, Antonio Passaro, Sang-We Kim, Shirish M. Gadgeel, John Xie, Tao Sun, Melissa Martinez, Mariah Ennis, Elizabeth Fennema, Mahesh Daksh, Dawn Millington, Isabelle Leconte, Ryota Iwasawa, Patricia Lorenzini, Mahadi Baig, Sujay Shah, Joshua M. Bauml, S. Martin Shreeve, Seema Sethi, Roland E. Knoblauch, and Hidetoshi Hayashi. Amivantamab plus lazertinib in previously untreated egfr -mutated advanced nsclc. New England Journal of Medicine, 391:1486-1498, Oct 2024. URL: https://doi.org/10.1056/nejmoa2403614, doi:10.1056/nejmoa2403614. This article has 450 citations and is from a highest quality peer-reviewed journal.

8. (laguna2024geographicdifferencesin pages 1-3): Juan Carlos Laguna, Miguel García-Pardo, Joao Alessi, Carlos Barrios, Navneet Singh, Humaid O. Al-Shamsi, Herbert Loong, Miquel Ferriol, Gonzalo Recondo, and Laura Mezquita. Geographic differences in lung cancer: focus on carcinogens, genetic predisposition, and molecular epidemiology. Therapeutic Advances in Medical Oncology, Jan 2024. URL: https://doi.org/10.1177/17588359241231260, doi:10.1177/17588359241231260. This article has 64 citations and is from a peer-reviewed journal.

9. (yoo2024updateinassociation pages 2-3): Jiye Yoo, Yongchan Lee, Youngil Park, Jongin Lee, Joon Young Choi, Heekwan Lee, and Jeong Uk Lim. Update in association between lung cancer and air pollution. Tuberculosis and Respiratory Diseases, 88:228-236, Dec 2024. URL: https://doi.org/10.4046/trd.2024.0092, doi:10.4046/trd.2024.0092. This article has 10 citations.

10. (farahmandian2024investigatingtherelationship pages 1-2): Parisa Farahmandian, Abdollah Mohammadian-Hafshejani, Abdolmajid Fadaei, and Ramezan Sadeghi. Investigating the relationship between exposure to cadmium and lung cancer risk: a systematic review and meta-analysis. Journal of Health and Safety at Work, Dec 2024. URL: https://doi.org/10.18502/jhsw.v14i1.17131, doi:10.18502/jhsw.v14i1.17131. This article has 4 citations.

11. (wolf2024screeningforlung pages 7-7): Andrew M. D. Wolf, Kevin C. Oeffinger, Tina Ya‐Chen Shih, Louise C. Walter, Timothy R. Church, Elizabeth T. H. Fontham, Elena B. Elkin, Ruth D. Etzioni, Carmen E. Guerra, Rebecca B. Perkins, Karli K. Kondo, Tyler B. Kratzer, Deana Manassaram‐Baptiste, William L. Dahut, and Robert A. Smith. Screening for lung cancer: 2023 guideline update from the american cancer society. CA: A Cancer Journal for Clinicians, 74:50-81, Nov 2024. URL: https://doi.org/10.3322/caac.21811, doi:10.3322/caac.21811. This article has 425 citations and is from a domain leading peer-reviewed journal.

12. (xie2024distantmetastasispatterns pages 1-2): Tian Xie, Bing-Mei Qiu, Jing Luo, Yi-Fei Diao, Li-Wen Hu, Xiao-Long Liu, and Yi Shen. Distant metastasis patterns among lung cancer subtypes and impact of primary tumor resection on survival in metastatic lung cancer using seer database. Scientific Reports, Sep 2024. URL: https://doi.org/10.1038/s41598-024-73389-6, doi:10.1038/s41598-024-73389-6. This article has 25 citations and is from a peer-reviewed journal.

13. (xie2024distantmetastasispatterns pages 2-3): Tian Xie, Bing-Mei Qiu, Jing Luo, Yi-Fei Diao, Li-Wen Hu, Xiao-Long Liu, and Yi Shen. Distant metastasis patterns among lung cancer subtypes and impact of primary tumor resection on survival in metastatic lung cancer using seer database. Scientific Reports, Sep 2024. URL: https://doi.org/10.1038/s41598-024-73389-6, doi:10.1038/s41598-024-73389-6. This article has 25 citations and is from a peer-reviewed journal.

14. (tanaka2024femoralbonemetastasis pages 1-3): Ichidai Tanaka, Kazumi Hori, Junji Koyama, Soei Gen, Masahiro Morise, Yuta Kodama, Akira Matsui, Ayako Miyazawa, Tetsunari Hase, Yoshitaka Hibino, Toshihiko Yokoyama, Tomoki Kimura, Norio Yoshida, Mitsuo Sato, and Makoto Ishii. Femoral bone metastasis is a poor prognostic factor in egfr-tkis-treated patients with egfr-mutated non-small-cell lung cancer: a retrospective, multicenter cohort study. Therapeutic Advances in Medical Oncology, Jan 2024. URL: https://doi.org/10.1177/17588359241303090, doi:10.1177/17588359241303090. This article has 2 citations and is from a peer-reviewed journal.

15. (hektoen2024realworldevidencefor pages 3-5): Helga H. Hektoen, Kaitlyn M. Tsuruda, Lars Fjellbirkeland, Yngvar Nilssen, Odd Terje Brustugun, and Bettina K. Andreassen. Real-world evidence for pembrolizumab in non-small cell lung cancer: a nationwide cohort study. British Journal of Cancer, 132:93-102, Nov 2024. URL: https://doi.org/10.1038/s41416-024-02895-1, doi:10.1038/s41416-024-02895-1. This article has 27 citations and is from a domain leading peer-reviewed journal.

16. (brown2024sitespecificresponseand pages 11-12): Lauren Julia Brown, Julie Ahn, Bo Gao, Harriet Gee, Adnan Nagrial, Eric Hau, and Inês Pires da Silva. Site-specific response and resistance patterns in patients with advanced non-small-cell lung cancer treated with first-line systemic therapy. Cancers, 16:2136, Jun 2024. URL: https://doi.org/10.3390/cancers16112136, doi:10.3390/cancers16112136. This article has 4 citations.

17. (brown2024sitespecificresponseand pages 1-2): Lauren Julia Brown, Julie Ahn, Bo Gao, Harriet Gee, Adnan Nagrial, Eric Hau, and Inês Pires da Silva. Site-specific response and resistance patterns in patients with advanced non-small-cell lung cancer treated with first-line systemic therapy. Cancers, 16:2136, Jun 2024. URL: https://doi.org/10.3390/cancers16112136, doi:10.3390/cancers16112136. This article has 4 citations.

18. (li2024evolvingprecisionfirstline pages 1-2): Tianhong Li, Weijie Ma, and Ebaa Al-Obeidi. Evolving precision first-line systemic treatment for patients with unresectable non-small cell lung cancer. Cancers, 16:2350, Jun 2024. URL: https://doi.org/10.3390/cancers16132350, doi:10.3390/cancers16132350. This article has 14 citations.

19. (li2024evolvingprecisionfirstline pages 4-6): Tianhong Li, Weijie Ma, and Ebaa Al-Obeidi. Evolving precision first-line systemic treatment for patients with unresectable non-small cell lung cancer. Cancers, 16:2350, Jun 2024. URL: https://doi.org/10.3390/cancers16132350, doi:10.3390/cancers16132350. This article has 14 citations.

20. (cho2024amivantamabpluslazertinib pages 1-4): Byoung C. Cho, Shun Lu, Enriqueta Felip, Alexander I. Spira, Nicolas Girard, Jong-Seok Lee, Se-Hoon Lee, Yurii Ostapenko, Pongwut Danchaivijitr, Baogang Liu, Adlinda Alip, Ernesto Korbenfeld, Josiane Mourão Dias, Benjamin Besse, Ki-Hyeong Lee, Hailin Xiong, Soon-Hin How, Ying Cheng, Gee-Chen Chang, Hiroshige Yoshioka, James C.-H. Yang, Michael Thomas, Danny Nguyen, Sai-Hong I. Ou, Sanjay Mukhedkar, Kumar Prabhash, Manolo D’Arcangelo, Jorge Alatorre-Alexander, Juan C. Vázquez Limón, Sara Alves, Daniil Stroyakovskiy, Marina Peregudova, Mehmet A.N. Şendur, Ozan Yazici, Raffaele Califano, Vanesa Gutiérrez Calderón, Filippo de Marinis, Antonio Passaro, Sang-We Kim, Shirish M. Gadgeel, John Xie, Tao Sun, Melissa Martinez, Mariah Ennis, Elizabeth Fennema, Mahesh Daksh, Dawn Millington, Isabelle Leconte, Ryota Iwasawa, Patricia Lorenzini, Mahadi Baig, Sujay Shah, Joshua M. Bauml, S. Martin Shreeve, Seema Sethi, Roland E. Knoblauch, and Hidetoshi Hayashi. Amivantamab plus lazertinib in previously untreated egfr -mutated advanced nsclc. New England Journal of Medicine, 391:1486-1498, Oct 2024. URL: https://doi.org/10.1056/nejmoa2403614, doi:10.1056/nejmoa2403614. This article has 450 citations and is from a highest quality peer-reviewed journal.

21. (chour2024mechanismsofresistance pages 1-2): Ali Chour, Anne-Claire Toffart, Elodie Berton, and Michael Duruisseaux. Mechanisms of resistance to krasg12c inhibitors in krasg12c-mutated non-small cell lung cancer. Frontiers in Oncology, Sep 2024. URL: https://doi.org/10.3389/fonc.2024.1328728, doi:10.3389/fonc.2024.1328728. This article has 21 citations.

22. (warnecke2024adagrasibinthe pages 1-2): Brian Warnecke and Misako Nagasaka. Adagrasib in the treatment of kras p.g12c positive advanced nsclc: design, development and place in therapy. Drug Design, Development and Therapy, 18:5673-5683, Dec 2024. URL: https://doi.org/10.2147/dddt.s466217, doi:10.2147/dddt.s466217. This article has 5 citations.

23. (ferrari2024her2alterednonsmallcell pages 1-2): Giorgia Ferrari, Benedetta Del Rio, Silvia Novello, and Francesco Passiglia. Her2-altered non-small cell lung cancer: a journey from current approaches to emerging strategies. Cancers, 16:2018, May 2024. URL: https://doi.org/10.3390/cancers16112018, doi:10.3390/cancers16112018. This article has 18 citations.

24. (cho2024amivantamabpluslazertinib pages 7-8): Byoung C. Cho, Shun Lu, Enriqueta Felip, Alexander I. Spira, Nicolas Girard, Jong-Seok Lee, Se-Hoon Lee, Yurii Ostapenko, Pongwut Danchaivijitr, Baogang Liu, Adlinda Alip, Ernesto Korbenfeld, Josiane Mourão Dias, Benjamin Besse, Ki-Hyeong Lee, Hailin Xiong, Soon-Hin How, Ying Cheng, Gee-Chen Chang, Hiroshige Yoshioka, James C.-H. Yang, Michael Thomas, Danny Nguyen, Sai-Hong I. Ou, Sanjay Mukhedkar, Kumar Prabhash, Manolo D’Arcangelo, Jorge Alatorre-Alexander, Juan C. Vázquez Limón, Sara Alves, Daniil Stroyakovskiy, Marina Peregudova, Mehmet A.N. Şendur, Ozan Yazici, Raffaele Califano, Vanesa Gutiérrez Calderón, Filippo de Marinis, Antonio Passaro, Sang-We Kim, Shirish M. Gadgeel, John Xie, Tao Sun, Melissa Martinez, Mariah Ennis, Elizabeth Fennema, Mahesh Daksh, Dawn Millington, Isabelle Leconte, Ryota Iwasawa, Patricia Lorenzini, Mahadi Baig, Sujay Shah, Joshua M. Bauml, S. Martin Shreeve, Seema Sethi, Roland E. Knoblauch, and Hidetoshi Hayashi. Amivantamab plus lazertinib in previously untreated egfr -mutated advanced nsclc. New England Journal of Medicine, 391:1486-1498, Oct 2024. URL: https://doi.org/10.1056/nejmoa2403614, doi:10.1056/nejmoa2403614. This article has 450 citations and is from a highest quality peer-reviewed journal.

25. (uprety2024racialandsocioeconomic pages 1-2): Dipesh Uprety, Randell Seaton, Tarik Hadid, Hirva Mamdani, Ammar Sukari, Julie J Ruterbusch, and Ann G Schwartz. Racial and socioeconomic disparities in survival among patients with metastatic non–small cell lung cancer. JNCI Journal of the National Cancer Institute, 116:1697-1704, Jun 2024. URL: https://doi.org/10.1093/jnci/djae118, doi:10.1093/jnci/djae118. This article has 17 citations.

26. (li2024evolvingprecisionfirstline pages 2-4): Tianhong Li, Weijie Ma, and Ebaa Al-Obeidi. Evolving precision first-line systemic treatment for patients with unresectable non-small cell lung cancer. Cancers, 16:2350, Jun 2024. URL: https://doi.org/10.3390/cancers16132350, doi:10.3390/cancers16132350. This article has 14 citations.

27. (restrepo2024identificationandapplication pages 15-16): Juan Carlos Restrepo, Darly Martínez Guevara, Andrés Pareja López, John Fernando Montenegro Palacios, and Yamil Liscano. Identification and application of emerging biomarkers in treatment of non-small-cell lung cancer: systematic review. Cancers, 16:2338, Jun 2024. URL: https://doi.org/10.3390/cancers16132338, doi:10.3390/cancers16132338. This article has 33 citations.

28. (yang2024nonsmallcelllung pages 1-2): Mo Yang, Erin Mandal, Frank X. Liu, Richard M. O’Hara, Beth Lesher, and Rachel E. Sanborn. Non-small cell lung cancer with met amplification: review of epidemiology, associated disease characteristics, testing procedures, burden, and treatments. Frontiers in Oncology, Jan 2024. URL: https://doi.org/10.3389/fonc.2023.1241402, doi:10.3389/fonc.2023.1241402. This article has 19 citations.

29. (yang2024nonsmallcelllung pages 3-5): Mo Yang, Erin Mandal, Frank X. Liu, Richard M. O’Hara, Beth Lesher, and Rachel E. Sanborn. Non-small cell lung cancer with met amplification: review of epidemiology, associated disease characteristics, testing procedures, burden, and treatments. Frontiers in Oncology, Jan 2024. URL: https://doi.org/10.3389/fonc.2023.1241402, doi:10.3389/fonc.2023.1241402. This article has 19 citations.

30. (cho2024amivantamabpluslazertinib pages 9-11): Byoung C. Cho, Shun Lu, Enriqueta Felip, Alexander I. Spira, Nicolas Girard, Jong-Seok Lee, Se-Hoon Lee, Yurii Ostapenko, Pongwut Danchaivijitr, Baogang Liu, Adlinda Alip, Ernesto Korbenfeld, Josiane Mourão Dias, Benjamin Besse, Ki-Hyeong Lee, Hailin Xiong, Soon-Hin How, Ying Cheng, Gee-Chen Chang, Hiroshige Yoshioka, James C.-H. Yang, Michael Thomas, Danny Nguyen, Sai-Hong I. Ou, Sanjay Mukhedkar, Kumar Prabhash, Manolo D’Arcangelo, Jorge Alatorre-Alexander, Juan C. Vázquez Limón, Sara Alves, Daniil Stroyakovskiy, Marina Peregudova, Mehmet A.N. Şendur, Ozan Yazici, Raffaele Califano, Vanesa Gutiérrez Calderón, Filippo de Marinis, Antonio Passaro, Sang-We Kim, Shirish M. Gadgeel, John Xie, Tao Sun, Melissa Martinez, Mariah Ennis, Elizabeth Fennema, Mahesh Daksh, Dawn Millington, Isabelle Leconte, Ryota Iwasawa, Patricia Lorenzini, Mahadi Baig, Sujay Shah, Joshua M. Bauml, S. Martin Shreeve, Seema Sethi, Roland E. Knoblauch, and Hidetoshi Hayashi. Amivantamab plus lazertinib in previously untreated egfr -mutated advanced nsclc. New England Journal of Medicine, 391:1486-1498, Oct 2024. URL: https://doi.org/10.1056/nejmoa2403614, doi:10.1056/nejmoa2403614. This article has 450 citations and is from a highest quality peer-reviewed journal.

31. (cho2024amivantamabpluslazertinib media ee6afa38): Byoung C. Cho, Shun Lu, Enriqueta Felip, Alexander I. Spira, Nicolas Girard, Jong-Seok Lee, Se-Hoon Lee, Yurii Ostapenko, Pongwut Danchaivijitr, Baogang Liu, Adlinda Alip, Ernesto Korbenfeld, Josiane Mourão Dias, Benjamin Besse, Ki-Hyeong Lee, Hailin Xiong, Soon-Hin How, Ying Cheng, Gee-Chen Chang, Hiroshige Yoshioka, James C.-H. Yang, Michael Thomas, Danny Nguyen, Sai-Hong I. Ou, Sanjay Mukhedkar, Kumar Prabhash, Manolo D’Arcangelo, Jorge Alatorre-Alexander, Juan C. Vázquez Limón, Sara Alves, Daniil Stroyakovskiy, Marina Peregudova, Mehmet A.N. Şendur, Ozan Yazici, Raffaele Califano, Vanesa Gutiérrez Calderón, Filippo de Marinis, Antonio Passaro, Sang-We Kim, Shirish M. Gadgeel, John Xie, Tao Sun, Melissa Martinez, Mariah Ennis, Elizabeth Fennema, Mahesh Daksh, Dawn Millington, Isabelle Leconte, Ryota Iwasawa, Patricia Lorenzini, Mahadi Baig, Sujay Shah, Joshua M. Bauml, S. Martin Shreeve, Seema Sethi, Roland E. Knoblauch, and Hidetoshi Hayashi. Amivantamab plus lazertinib in previously untreated egfr -mutated advanced nsclc. New England Journal of Medicine, 391:1486-1498, Oct 2024. URL: https://doi.org/10.1056/nejmoa2403614, doi:10.1056/nejmoa2403614. This article has 450 citations and is from a highest quality peer-reviewed journal.

32. (warnecke2024adagrasibinthe pages 4-5): Brian Warnecke and Misako Nagasaka. Adagrasib in the treatment of kras p.g12c positive advanced nsclc: design, development and place in therapy. Drug Design, Development and Therapy, 18:5673-5683, Dec 2024. URL: https://doi.org/10.2147/dddt.s466217, doi:10.2147/dddt.s466217. This article has 5 citations.

33. (lazaratos2024apotentialcentral pages 1-2): Anna-Maria Lazaratos, David J. H. Bian, Kevin Petrecca, Marie-Christine Guiot, and Matthew Dankner. A potential central nervous system niche for trastuzumab deruxtecan in patients with her2-expressing non-small cell lung cancer. Translational Lung Cancer Research, 13:3824-3830, Dec 2024. URL: https://doi.org/10.21037/tlcr-24-856, doi:10.21037/tlcr-24-856. This article has 0 citations and is from a peer-reviewed journal.

34. (wang2024addressingtheunmet pages 3-5): Kinsley Wang, Alexis Leyba, and Robert Hsu. Addressing the unmet need in nsclc progression with advances in second-line therapeutics. Exploration of Targeted Anti-tumor Therapy, 5:1297-1320, Nov 2024. URL: https://doi.org/10.37349/etat.2024.00277, doi:10.37349/etat.2024.00277. This article has 4 citations.

35. (lazaratos2024apotentialcentral pages 2-4): Anna-Maria Lazaratos, David J. H. Bian, Kevin Petrecca, Marie-Christine Guiot, and Matthew Dankner. A potential central nervous system niche for trastuzumab deruxtecan in patients with her2-expressing non-small cell lung cancer. Translational Lung Cancer Research, 13:3824-3830, Dec 2024. URL: https://doi.org/10.21037/tlcr-24-856, doi:10.21037/tlcr-24-856. This article has 0 citations and is from a peer-reviewed journal.

36. (wolf2024screeningforlung pages 2-3): Andrew M. D. Wolf, Kevin C. Oeffinger, Tina Ya‐Chen Shih, Louise C. Walter, Timothy R. Church, Elizabeth T. H. Fontham, Elena B. Elkin, Ruth D. Etzioni, Carmen E. Guerra, Rebecca B. Perkins, Karli K. Kondo, Tyler B. Kratzer, Deana Manassaram‐Baptiste, William L. Dahut, and Robert A. Smith. Screening for lung cancer: 2023 guideline update from the american cancer society. CA: A Cancer Journal for Clinicians, 74:50-81, Nov 2024. URL: https://doi.org/10.3322/caac.21811, doi:10.3322/caac.21811. This article has 425 citations and is from a domain leading peer-reviewed journal.

37. (wolf2024screeningforlung pages 1-2): Andrew M. D. Wolf, Kevin C. Oeffinger, Tina Ya‐Chen Shih, Louise C. Walter, Timothy R. Church, Elizabeth T. H. Fontham, Elena B. Elkin, Ruth D. Etzioni, Carmen E. Guerra, Rebecca B. Perkins, Karli K. Kondo, Tyler B. Kratzer, Deana Manassaram‐Baptiste, William L. Dahut, and Robert A. Smith. Screening for lung cancer: 2023 guideline update from the american cancer society. CA: A Cancer Journal for Clinicians, 74:50-81, Nov 2024. URL: https://doi.org/10.3322/caac.21811, doi:10.3322/caac.21811. This article has 425 citations and is from a domain leading peer-reviewed journal.

38. (wang2024utilityofpatientderived pages 1-2): Xiaoqing Wang, Ju Zhu, Lingling Li, Qilin Zhao, Yutang Huang, Chunjie Wen, Dan Chen, and Lanxiang Wu. Utility of patient-derived xenografts to evaluate drug sensitivity and select optimal treatments for individual non-small-cell lung cancer patients. Molecular Medicine, Nov 2024. URL: https://doi.org/10.1186/s10020-024-00934-4, doi:10.1186/s10020-024-00934-4. This article has 6 citations and is from a peer-reviewed journal.

39. (hynds2024representationofgenomic pages 1-2): R. Hynds, A. Huebner, D. Pearce, M. Hill, A. Akarca, David A Moore, S. Ward, K. Gowers, Takahiro Karasaki, M. Al Bakir, G. Wilson, O. Pich, Carlos Martínez-Ruiz, A. M. Hossain, S. Pearce, Monica Sivakumar, Assma Ben Aissa, E. Grönroos, Deepak P Chandrasekharan, K. Kolluri, Rebecca Towns, Kaiwen Wang, Daniel E. Cook, Leticia Bosshard-Carter, C. Naceur-Lombardelli, Andrew Rowan, S. Veeriah, K. Litchfield, Philip A J Crosbie, C. Dive, Sergio A Quezada, S. Janes, M. Jamal-Hanjani, T. Marafioti, Maise Jason F. Amrita Apostolos Azmina Mohamad Molly Reb Al Bakir Lester Bajaj Nakas Sodha-Ramdeen Tufail S, Jason Lester, A. Bajaj, A. Nakas, Azmina Sodha-Ramdeen, M. Tufail, M. Scotland, R. Boyles, S. Rathinam, C. Wilson, Domenic Marrone, S. Dulloo, D. Fennell, Gurdeep Matharu, J. Shaw, E. Boleti, Heather Cheyne, Mohammed Khalil, S. Richardson, Tracey Cruickshank, Gillian Price, K. M. Kerr, Sarah Benafif, Jack French, Kayleigh Gilbert, B. Naidu, Akshay J. Patel, A. Osman, Carol Enstone, G. Langman, Helen Shackleford, M. Djearaman, S. Kadiri, Gary Middleton, Angela E. Leek, Jack Davies Hodgkinson, Nicola Totton, A. Montero, E. Smith, E. Fontaine, F. Granato, A. Paiva-Correia, Juliette Novasio, K. Rammohan, L. Joseph, P. Bishop, Rajesh Shah, Stuart Moss, Vijay Joshi, Katherine D. Brown, M. Carter, A. Chaturvedi, Pedro Oliveira, C. Lindsay, Fiona H. Blackhall, Matthew G. Krebs, Yvonne Summers, A. Clipson, J. Tugwood, Alastair Kerr, D. Rothwell, H. Aerts, R. Schwarz, Tom L. Kaufmann, R. Rosenthal, P. Van Loo, Nicolai J. Birkbak, Zoltan Szallasi, Judit Kisistók, M. Sokač, R. Salgado, M. Dióssy, J. Demeulemeester, Abigail Bunkum, Angela Dwornik, Alastair Magness, A. Frankell, Angeliki Karamani, A. Toncheva, B. Chain, C. Castignani, Chris Bailey, C. Abbosh, C. Puttick, C. Weeden, Claudia Lee, Corentin Richard, C. Hiley, D. Karagianni, D. Biswas, D. Levi, E. L. Cadieux, Emilia L. Lim, Emma C Colliver, E. Nye, F. Gálvez-Cancino, F. Gimeno-Valiente, G. Kassiotis, Georgia Stavrou, Gerasimos Mastrokalos, H. Lowe, Ignacio Matos, I. Noorani, J. Goldman, J. Reading, James R. M. Black, J. Rane, J. Nicod, John A. Hartley, K. Peggs, Katey S. S. Enfield, Kayalvizhi Selvaraju, K. Thol, Kevin Ng, Kezhong Chen, K. Dijkstra, Kristiana Grigoriadis, Krupa Thakkar, L. Ensell, Mansi Shah, Maria Litovchenko, M. W. Sunderland, M. Huska, M. Dietzen, Michelle M Leung, M. Escudero, Mihaela Angelova, M. Tanić, N. Kanu, O. Chervova, Olivia Lucas, Othman Al-Sawaf, Paulina Prymas, Philip S Hobson, Piotr Pawlik, R. Stone, R. Bentham, R. Vendramin, S. Saghafinia, Samuel Gamble, S. Ung, Sharon P. Vanloo, S. Zaccaria, S. Hessey, Sian Harries, S. Boeing, Stephan Beck, S. Bola, Tamara Denner, T. Watkins, Thomas P. Jones, V. Spanswick, Vittorio Barbè, Wei-Ting Lu, William Hill, W. K. Liu, Yin Wu, Yutaka Naito, Zoe Ramsden, C. Veiga, G. Royle, C. Collins-Fekete, Francesco Fraioli, Paul Ashford, Martin D. Forster, Siow-Ming Lee, E. Borg, M. Falzon, D. Papadatos-Pastos, James Wilson, T. Ahmad, A. Procter, Asia Ahmed, Magali N. Taylor, Arjun Nair, David S. Lawrence, D. Patrini, Neal Navani, R. Thakrar, E. Hoogenboom, Fleur Monk, James W. Holding, Junaid Choudhary, Kunal Bhakhri, M. Scarci, Pat Gorman, Reena Khiroya, Robert C. M. Stephens, Y. Wong, Zoltán Káplár, S. Bandula, A. Hackshaw, A. Hacker, A. Sharp, Sean Smith, H. Dhanda, Camilla Pilotti, R. Leslie, Anca-Ioana Grapa, Hanyun Zhang, K. AbdulJabbar, Xiaoxi Pan, Yinyin Yuan, David Chuter, M. Mackenzie, S. Chee, A. Alzetani, Judith Cave, J. Richards, Eric Lim, Paulo De Sousa, S. Jordan, A. Rice, H. Raubenheimer, H. Bhayani, L. Ambrose, A. Devaraj, Hema Chavan, S. Begum, Silviu I. Buderi, Daniel Kaniu, Mpho Malima, S. Booth, Andrew G. Nicholson, Nádia Fernandes, Pratibha Shah, C. Proli, M. Hewish, S. Danson, M. Shackcloth, Lily Robinson, P. Russell, Kevin G. Blyth, A. Kidd, C. Dick, J. Le Quesne, Alan Kirk, Mohd. Asif, Rocco Bilancia, N. Kostoulas, Mathew Thomas, N. Mcgranahan, and C. Swanton. Representation of genomic intratumor heterogeneity in multi-region non-small cell lung cancer patient-derived xenograft models. Nature Communications, May 2024. URL: https://doi.org/10.1038/s41467-024-47547-3, doi:10.1038/s41467-024-47547-3. This article has 24 citations and is from a highest quality peer-reviewed journal.

40. (lee2024predictionoftki pages 1-2): Sang-Hyun Lee, Kyuhwan Kim, Eunyoung Lee, Kyungmin Lee, Kyeong Hwan Ahn, Hansom Park, Yelim Kim, Soeun Shin, Sang Youl Jeon, Yongki Hwang, Dong Hyuck Ahn, Yong-Jun Kwon, Seok Whan Moon, Mi Hyoung Moon, Kyung Soo Kim, Kwanyong Hyun, Tae-Jung Kim, Yeoun Eun Sung, Joon Young Choi, Chan Kwon Park, Sung Won Kim, Chang Dong Yeo, Hyun-Jung Sohn, You-Seok Hyun, Tai-Gyu Kim, Bosung Ku, Jeong Uk Lim, and Seung Joon Kim. Prediction of tki response in egfr-mutant lung cancer patients-derived organoids using malignant pleural effusion. NPJ Precision Oncology, May 2024. URL: https://doi.org/10.1038/s41698-024-00609-7, doi:10.1038/s41698-024-00609-7. This article has 19 citations and is from a peer-reviewed journal.

41. (liu2024modelinglungadenocarcinoma pages 1-4): Yuan Liu, Manendra Lankadasari, Joel Rosiene, Kofi E. Johnson, Juan Zhou, Samhita Bapat, Lai-Fong L. Chow-Tsang, Huasong Tian, Brooke Mastrogiacomo, Di He, James G. Connolly, Harry B. Lengel, Raul Caso, Elizabeth G. Dunne, Cameron N. Fick, Gaetano Rocco, Smita Sihag, James M. Isbell, Mathew J. Bott, Bob T. Li, Piro Lito, Cameron W. Brennan, Mark H. Bilsky, Natasha Rekhtman, Prasad S. Adusumilli, Marty W. Mayo, Marcin Imielinski, and David R. Jones. Modeling lung adenocarcinoma metastases using patient-derived organoids. Cell Reports Medicine, 5:101777, Oct 2024. URL: https://doi.org/10.1016/j.xcrm.2024.101777, doi:10.1016/j.xcrm.2024.101777. This article has 25 citations and is from a peer-reviewed journal.

42. (yang2024disparitiesinutilization pages 2-3): Danting Yang, Shama D. Karanth, Hyung-Suk Yoon, Jae Jeong Yang, Xiwei Lou, Jiang Bian, Dongyu Zhang, Yi Guo, Lusine Yaghjyan, Tomi Akinyemiju, Estelamari Rodriguez, Hiren J. Mehta, and Dejana Braithwaite. Disparities in utilization of immune checkpoint inhibitor therapy among older patients with advanced non–small cell lung cancer: a seer-medicare analysis. JCO Oncology Advances, Dec 2024. URL: https://doi.org/10.1200/oa.24.00008, doi:10.1200/oa.24.00008. This article has 6 citations.

43. (cho2024amivantamabpluslazertinib pages 11-12): Byoung C. Cho, Shun Lu, Enriqueta Felip, Alexander I. Spira, Nicolas Girard, Jong-Seok Lee, Se-Hoon Lee, Yurii Ostapenko, Pongwut Danchaivijitr, Baogang Liu, Adlinda Alip, Ernesto Korbenfeld, Josiane Mourão Dias, Benjamin Besse, Ki-Hyeong Lee, Hailin Xiong, Soon-Hin How, Ying Cheng, Gee-Chen Chang, Hiroshige Yoshioka, James C.-H. Yang, Michael Thomas, Danny Nguyen, Sai-Hong I. Ou, Sanjay Mukhedkar, Kumar Prabhash, Manolo D’Arcangelo, Jorge Alatorre-Alexander, Juan C. Vázquez Limón, Sara Alves, Daniil Stroyakovskiy, Marina Peregudova, Mehmet A.N. Şendur, Ozan Yazici, Raffaele Califano, Vanesa Gutiérrez Calderón, Filippo de Marinis, Antonio Passaro, Sang-We Kim, Shirish M. Gadgeel, John Xie, Tao Sun, Melissa Martinez, Mariah Ennis, Elizabeth Fennema, Mahesh Daksh, Dawn Millington, Isabelle Leconte, Ryota Iwasawa, Patricia Lorenzini, Mahadi Baig, Sujay Shah, Joshua M. Bauml, S. Martin Shreeve, Seema Sethi, Roland E. Knoblauch, and Hidetoshi Hayashi. Amivantamab plus lazertinib in previously untreated egfr -mutated advanced nsclc. New England Journal of Medicine, 391:1486-1498, Oct 2024. URL: https://doi.org/10.1056/nejmoa2403614, doi:10.1056/nejmoa2403614. This article has 450 citations and is from a highest quality peer-reviewed journal.

44. (hektoen2024realworldevidencefor pages 7-8): Helga H. Hektoen, Kaitlyn M. Tsuruda, Lars Fjellbirkeland, Yngvar Nilssen, Odd Terje Brustugun, and Bettina K. Andreassen. Real-world evidence for pembrolizumab in non-small cell lung cancer: a nationwide cohort study. British Journal of Cancer, 132:93-102, Nov 2024. URL: https://doi.org/10.1038/s41416-024-02895-1, doi:10.1038/s41416-024-02895-1. This article has 27 citations and is from a domain leading peer-reviewed journal.

45. (uprety2024racialandsocioeconomic pages 2-3): Dipesh Uprety, Randell Seaton, Tarik Hadid, Hirva Mamdani, Ammar Sukari, Julie J Ruterbusch, and Ann G Schwartz. Racial and socioeconomic disparities in survival among patients with metastatic non–small cell lung cancer. JNCI Journal of the National Cancer Institute, 116:1697-1704, Jun 2024. URL: https://doi.org/10.1093/jnci/djae118, doi:10.1093/jnci/djae118. This article has 17 citations.

46. (dang2024efficacyandtoxicity pages 1-2): Shoutao Dang, Shuyang Zhang, Jingyang Zhao, and Wei Li. Efficacy and toxicity of krasg12c inhibitors in advanced solid tumors: a meta-analysis. World Journal of Surgical Oncology, Jul 2024. URL: https://doi.org/10.1186/s12957-024-03449-8, doi:10.1186/s12957-024-03449-8. This article has 7 citations and is from a peer-reviewed journal.

47. (li2024shra1811(antibodydrugconjugate) pages 1-2): Ziming Li, Zhengbo Song, Wei Hong, N. Yang, Yongsheng Wang, H. Jian, Zibin Liang, Shengxiang Hu, Min Peng, Yan Yu, Yan Wang, Zicong Jiao, Kaijing Zhao, Ke Song, You Li, Wei Shi, and Shun Lu. Shr-a1811 (antibody-drug conjugate) in advanced her2-mutant non-small cell lung cancer: a multicenter, open-label, phase 1/2 study. Signal Transduction and Targeted Therapy, Jul 2024. URL: https://doi.org/10.1038/s41392-024-01897-y, doi:10.1038/s41392-024-01897-y. This article has 38 citations and is from a peer-reviewed journal.