PubMed：

(tuberculosis[Title/Abstract]) OR (lung cancer [Title/ Abstract])

Filters applied: from 2026/03/01 - 2026/03/31.

1.Nature. 2026 Mar;651(8104):231-241. doi: 10.1038/s41586-025-09985-x. Epub 2026 Jan 21.

Critical role for a high-plasticity cell state in lung cancer.

Plasticity-the ability of cells to undergo phenotypic transitions-drives cancer progression and therapy resistance1-3. Recent studies have suggested that plasticity in solid tumours is concentrated in a minority subset of cancer cells4-6, yet functional studies examining this high-plasticity cell state (HPCS) in situ are lacking. Here we develop mouse models enabling the detection, longitudinal lineage tracing and ablation of the HPCS in autochthonous lung tumours in vivo. Lineage tracing reveals that the HPCS cells possess a high capacity for cell state transitions, giving rise to both early neoplastic (differentiated) and progressed lung cancer cell states in situ. Longitudinal lineage tracing using secreted luciferases reveals that HPCS-derived cells have a high capacity for growth compared with bulk cancer cells or another cancer cell state with features of differentiated lung epithelium. Ablation of HPCS cells in early neoplasias abrogates benign-to-malignant transition, whereas ablation in established tumours by suicide gene or chimeric antigen receptor (CAR) T cells robustly reduces tumour burden. We further demonstrate that the HPCS gives rise to therapy-resistant cell states, whereas HPCS ablation suppresses resistance to chemotherapy and oncoprotein-targeted therapy. Notably, an HPCS-like state is ubiquitous in regenerating epithelia and in carcinomas of multiple other tissues, revealing a convergence of plasticity programs. Our work establishes the HPCS as a critical hub enabling reciprocal transitions between cancer cell states. Targeting the HPCS in lung cancer and in other carcinomas may suppress cancer progression and eradicate treatment resistance.

PMID: 41565826 [Indexed for MEDLINE]

2. Lancet. 2026 Mar 21;407(10534):1182-1190. doi: 10.1016/S0140-6736(26)00031-0.

Survival outcome of VATS compared with open lobectomy for lung cancer: an individual patient data meta-analysis of randomised trials.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) is currently the most common approach for pulmonary lobectomy in early-stage lung cancer. Reported advantages include less pain, fewer complications, faster recovery, and improved postoperative quality of life. The widespread adoption of VATS lobectomy is principally based on non-oncological benefits. Its oncological equivalence to open surgery remains assumed as no single trial has been powered for survival. To address this important question, we sought to conduct an individual patient data meta-analysis of eligible randomised trials.

METHODS: We systematically reviewed PubMed, MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, limiting the searches to papers published between Jan 1, 2000, and June 13, 2025. We included completed randomised controlled trials comparing VATS versus open lobectomy performed after the year 2000 conducted for clinical early-stage non-small-cell lung cancer in adults aged 18 years or older that collected information on mortality and disease recurrence. Individual patient data were extracted from the included studies, and authors were contacted where data were unavailable. The primary outcome was overall survival, and the secondary outcome was disease-free survival. Risk of bias was assessed using the Cochrane risk of bias tool for randomised trials. The primary analytical strategy was a one-stage random effects Cox proportional hazards model. A two-stage approach was performed to assess consistency.

FINDINGS: We screened 554 articles and three studies were eligible for inclusion. Data were provided for 1185 patients (586 randomised to VATS and 599 randomised to open lobectomy). Overall survival favoured VATS lobectomy, reflecting a 21% mortality risk reduction (pooled hazard ratio [HR] 0·79 [95% CI 0·65-0·96]). Disease-free survival was similar in both groups (pooled HR 0·91 [0·75-1·12]). There was no evidence of statistical heterogeneity across trials for either outcome.

INTERPRETATION: This meta-analysis provides evidence that surgical access by VATS lobectomy improved overall survival compared with open surgery without any compromise to disease-free survival. These results underscore the importance of prioritising VATS when technically feasible as the access of choice for surgical resection of early-stage non-small-cell lung cancer.

PMID: 41864749 [Indexed for MEDLINE]

3.CA Cancer J Clin. 2026 Mar-Apr;76(2):e70071. doi: 10.3322/caac.70071.

Aumolertinib with carboplatin-pemetrexed versus aumolertinib for nonsmall cell lung cancer with EGFR and concomitant tumor suppressor genes (ACROSS2): An open-label, multicenter, randomized phase 3 study.

Third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard first-line therapy for advanced, EGFR-mutated nonsmall cell lung cancer (NSCLC). However, their benefit is limited in patients who have co-existing tumor suppressor gene (TSG) mutations, highlighting a need for intensified strategies to improve outcomes. ACROSS2 (ClinicalTrials.gov identifier NCT04500717) is the first prospective, multicenter, randomized phase 3 study to compare the third-generation EGFR-TKI aumolertinib in combination with carboplatin-pemetrexed versus aumolertinib monotherapy in patients who had NSCLC with EGFR mutations and concomitant TSG mutations. In total, 126 patients were enrolled and randomly assigned to either combination therapy (n = 62) or monotherapy (n = 64). The primary end point was median progression-free survival (PFS). At a median follow-up of 25.3 months, combination therapy significantly prolonged median PFS compared with monotherapy (19.78 vs 16.53 months; hazard ratio, 0.58; 95% confidence interval, 0.34-0.97). Landmark PFS rates at 12, 18, and 24 months were 78.7% versus 65.3%, 67.2% versus 40.8%, and 41.0% versus 29.9%, respectively. Subgroup analyses demonstrated a clear PFS benefit in patients who had co-existing tumor protein p53 (TP53) mutations. Grade 3 or greater adverse events occurred in 25.9% of patients who received combination therapy versus 17.2% of those who received monotherapy; no drug-related deaths were observed. Overall survival data were immature (data maturity, 4%). The ACROSS2 trial provides the first prospective evidence supporting a genotype-directed, chemotherapy-targeted intensification approach favoring aumolertinib plus carboplatin-pemetrexed for this molecularly defined population.

PMID: 41818162 [Indexed for MEDLINE]

4. Nat Med. 2026 Mar 19. doi: 10.1038/s41591-026-04294-w. Online ahead of print.

Long-term risk of death after tuberculosis diagnosis and treatment.

Tuberculosis (TB) remains a major societal burden, yet data on long-term mortality following TB diagnosis and treatment are limited. We conducted a nationwide Brazilian cohort study using linked data (2004-2018) to quantify long-term mortality (up to 14 years) following TB. We matched: (i) individuals diagnosed with TB or (ii) individuals who had completed TB treatment to TB-free individuals. We used competing risk methods to analyze natural causes (that is, defined as deaths excluding TB, HIV and external causes) and cause-specific mortality. In the diagnosed cohort (185,921 pairs), the risk of 14-year natural cause mortality was significantly higher (risk ratio (RR) = 2.16, 95% confidence interval = 1.96-2.37); RRs were significantly elevated for deaths due to cancer, cardiovascular, endocrine, respiratory and external causes. The treated cohort (111,871 pairs) presented elevated natural cause mortality risk(RR = 1.77,1.55-2.03), with similarly increased RRs across specific causes. We showed that TB survivors, even after treatment, faced a significantly elevated, prolonged risk of death from various causes up to 14 years later. This finding highlights the need for long-term monitoring to reduce the burden of TB.

PMID: 41857197

5.Clin Microbiol Rev. 2026 Mar 12;39(1):e0019425. doi: 10.1128/cmr.00194-25. Epub 2026 Jan 7.

The power of resistance: mechanisms of antimicrobial resistance in Mycobacterium tuberculosis and its impact on tuberculosis management.

The global resurgence of drug-resistant tuberculosis (DR-TB) presents a formidable challenge to public health, driven by a complex interplay of mycobacterial evolution, dynamics and outcomes of host-pathogen interactions and systemic gaps in diagnosis and treatment strategies. This comprehensive review delineates the multifactorial basis of antimicrobial resistance (AMR) in Mycobacterium tuberculosis (Mtb), integrating molecular, immunological, and pharmacological perspectives to inform next-generation strategies for effective TB control. We reconceptualize TB as a dynamic clinical spectrum-ranging from asymptomatic infection to overt disease-shaped by granuloma biology and bacterial adaptation. This spectrum underpins both diagnostic ambiguity and therapeutic failure, particularly in the context of phenotypic drug tolerance/resistance to current anti-TB drugs. We discuss Mtb's intrinsic and extrinsic resistance mechanisms, including the lipid-rich cell envelope, efflux systems, and enzymatic drug modification, which are compounded by acquired mutations that disrupt drug activation, alter targets, and confer cross-resistance. These adaptations are further potentiated by granuloma-induced pharmacokinetic heterogeneity and host-induced metabolic quiescence. We highlight the emerging role of therapeutic drug monitoring and pharmacokinetic/pharmacodynamic modeling in optimizing individualized therapy, particularly for novel regimens incorporating bedaquiline, pretomanid, and linezolid. Moreover, we underscore the diagnostic limitations in detecting heteroresistance and early-stage disease, advocating for expanded deployment of advanced and targeted molecular diagnostic modalities. Finally, we propose a paradigm shift toward integrated, precision-based TB management, leveraging host-directed therapies, biofilm-disrupting agents, and real-time pharmacokinetics-guided dosing to preempt resistance emergence and improve clinical outcomes. This review provides a translational framework for addressing the biological and operational complexities of DR-TB in the era of AMR.

PMID: 41498549 [Indexed for MEDLINE]

6. Lancet Glob Health. 2026 Mar;14(3):e444-e454.doi: 10.1016/S2214-109X(25000 478-4.

The tuberculogenic environment.

Tuberculosis persists as the world's deadliest infectious disease, despite improved diagnostics and effective treatment. The tuberculogenic environment describes the sum of influences, vulnerabilities, policies, life conditions, and health factors that sustain the tuberculosis pandemic in vulnerable communities. The persistence of these environments is attributable to challenges upstream of the health system, involving sectors such as trade, taxation, finance, agriculture, employment, social services, and education. The availability, affordability, access, and acceptability of safe infrastructure (including housing), nutritious foods, protection against harmful consumption (tobacco,alcohol, sugar, etc), and adequately resourced health services are all linked to tuberculosis risk. Yet people affected by tuberculosis and national tuberculosiscontrol programmes continue to bear almost the sole responsibility for a problemthat is largely beyond their control. Reframing tuberculosis through the lens ofcomplex systems science highlights the array of decision makers who, by actionor inaction, have a shared responsibility to end tuberculosis as a globalpandemic.

PMID: 41713446 [Indexed for MEDLINE]

7. Cancer Cell. 2026 Mar 5:S1535-6108(26)00106-6. doi:10.1016/j.ccell.2026.02.008. Online ahead of print.

Vascular STING activation facilitates NK cell anti-tumor immunity in small cell lung cancer.

Small cell lung cancer (SCLC) typically displays a "cold" tumor microenvironment with a paucity of immune infiltrate. Neuroendocrine SCLC cells also profoundly repress MHC-I expression, rendering them vulnerable to NK cell-mediated cytotoxicity. Here, we confirm that neuroendocrine SCLC cells are sensitive to NK cell-mediated attack, yet the quantitative spatial profiling of the SCLC immune microenvironment in patient samples reveals that effector immune cells, including NK cells, are excluded from MHC-Ilow/neg SCLC regions. To study this biology, we develop dynamic single-cell RNA sequencing of microphysiological immune tumor environments (DynaMITE-seq) and integrate findings with spatial transcriptomics in patient tissue, unveiling the microvasculature as a major checkpoint restricting NK cell extravasation/recruitment. We demonstrate that the activation of vascular Stimulator of Interferon Genes (STING) signaling restores NK cell infiltration and killing of neuroendocrine SCLC, suggesting a strategy to overcome this key SCLC immunologic barrier and prime therapeutic response to DLL3-targeted CAR-NK cell therapy.

PMID: 41791380

8. J Clin Oncol. 2026 Mar 26:JCO2501489. doi: 10.1200/JCO-25-01489. Online ahead of print.

Final Efficacy and Safety Data From the Phase I/II ARROW Study of Pralsetinib in Patients With Advanced RET Fusion-Positive Non-Small Cell Lung Cancer.

RET fusions appear in 1%-2% of non-small cell lung cancers (NSCLCs). The results from the ARROW study (ClinicalTrials.gov identifier: NCT03037385) supported US Food and Drug Administration approval of pralsetinib, an oral selective RET inhibitor, for metastatic RET-altered NSCLC and RET fusion-positive thyroid cancers. ARROW was a phase I/II open-label study of pralsetinib 400 mg once daily in RET fusion-positive NSCLCs. Coprimary end points were overall response rate (ORR) and safety. Key secondary end points included duration of response, progression-free survival, and overall survival (OS). At data lock (May 20, 2024), 281 patients initiated pralsetinib (median treatment duration, 15.0 months). ORR (measurable disease patients; n = 259) was 78% (95% CI, 69 to 86) for treatment-naïve patients and 63% (95% CI, 54 to 71) for prior platinum-based chemotherapy patients. Median OS was 44.3 months (95% CI, 30.9 to 53.1), 50.1 months (95% CI, 28.3 to not reached) in treatment-naïve patients, and 39.7 months (95% CI, 27.8 to 53.2) in prior platinum patients. Common grade ≥3 treatment-related adverse events were anemia (21%), hypertension (15%), and decreased neutrophils (13%). Three treatment-related deaths occurred (pneumonia, n = 2; interstitial lung disease and rhabdomyolysis, n = 1 each). Safety was consistent with previous ARROW reports; no hypersensitivity was reported in patients receiving prior immunotherapies. Pralsetinib produced robust, durable responses with manageable safety in treatment-naïve and previously treated patients with RET fusion-positive NSCLCs, confirming previous findings with longer follow-up.

PMID: 41886723

9. J Clin Oncol. 2026 Mar;44(7):e56-e88. doi: 10.1200/JCO-25-02825. Epub 2026 Feb 3.

Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO

PURPOSE: To provide evidence-based recommendations for patients with stage IV non-small cell lung cancer (NSCLC) without driver alterations.METHODS: This ASCO living guideline offers continually updated recommendations based on an ongoing systematic review of randomized controlled trials (RCTs), with the latest time frame spanning March-October 2025. An Expert Panel of medical oncology, pulmonary, community oncology, research methodology, and advocacy experts was convened. The literature search included systematic reviews, meta-analyses, and RCTs. Outcomes of interest include efficacy and safety. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations.

RESULTS: This guideline consolidates all previous updates and reflects the body of evidence informing this guideline topic. Six new RCTs were identified in the latest search of the literature to date.

RECOMMENDATIONS: Evidence-based recommendations were updated to address first, second, and subsequent treatment options for patients without driver alteration. Additional information is available at www.asco.org/thoracic-cancer-guidelines.

PMID: 41632927

10. Nat Med. 2026 Mar 27. doi: 10.1038/s41591-026-04323-8. Online ahead of print.

Gotistobart or docetaxel in metastatic squamous non-small cell lung cancer: stage 1 of the randomized phase 3 PRESERVE-003 trial.

PRESERVE-003 is a two-stage phase 3 trial evaluating gotistobart (BNT316/ONC-392), a novel pH-sensitive anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) antibody that selectively depletes regulatory T cells within the tumor microenvironment, in patients with metastatic squamous non-small cell lung cancer (sqNSCLC) without actionable genomic alterations who progressed on programmed cell death protein/programmed death ligand 1 inhibitor/platinum-based chemotherapy-a population with a poor prognosis. Here we report on stage 1, which aimed to confirm the dose and assess the preliminary efficacy (primary outcome: overall survival; secondary outcomes: progression‑free survival, objective response rate and duration of response) and safety of gotistobart compared to docetaxel. Patients with sqNSCLC were randomized (1:1) to gotistobart (6 mg kg-1 with two 10 mg kg-1 loading doses every 3 weeks (N = 45)) or docetaxel (75 mg m-2 every 3 weeks (N = 42)). After a median follow-up of 14.5 months, median overall survival was not reached with gotistobart (95% confidence interval (CI) 9.3 to not evaluable) versus 10.0 months (95% CI 6.2 to 11.9 months) with docetaxel (hazard ratio 0.46, 95% CI 0.25 to 0.84, nominal two-sided P = 0.0102). Safety was manageable, with grade ≥3 treatment-related adverse events in 42% and 49% of patients receiving gotistobart and docetaxel, respectively. Stage 1 results suggest that gotistobart monotherapy can provide clinically meaningful benefit for patients with programmed cell death protein/programmed death ligand 1-resistant and chemotherapy-resistant metastatic sqNSCLC. ClinicalTrials.gov identifier: NCT05671510 .

PMID: 41896648

11. Cancer Discov. 2026 Mar 6. doi: 10.1158/2159-8290.CD-25-0960. Online ahead of print.

ELIOS: A Multicenter, Molecular Profiling Study of Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer Treated with First-Line Osimertinib.

ELIOS (NCT03239340) prospectively compared tumor biopsies obtained pretreatment and post-progression to characterize acquired resistance mechanisms to first-line osimertinib in EGFR-mutant advanced non-small cell lung cancer (NSCLC). Of 154 patients enrolled, 52 patients had next-generation sequencing (NGS) results from paired tissue biopsies. The most common acquired alterations at progression were MET amplification (17%), deletion of CDKN2A/CDKN2B (15%) and MTAP (13%), and EGFR C797S (13%). Proteogenomic analysis (n = 32 at baseline and n = 18 post-progression) showed TROP2 was highly expressed at baseline and post-progression, irrespective of genetic alterations observed. In a separate analysis of patients with matched tissue and plasma samples post-progression (n = 51), 82% had potential resistance alterations by NGS, demonstrating the complementary roles of tissue and plasma NGS. These results highlight the challenges of obtaining tissue biopsies in patients with NSCLC progressing on targeted therapy, the potential for heterogeneous resistance and the need for broad-acting treatment strategies.

PMID: 41790042

12. J Clin Oncol. 2026 Mar;44(7):e15-e55. doi: 10.1200/JCO-25-02822. Epub 2026 Feb 3.

Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, 2026.3.0.

PURPOSE: To provide evidence-based recommendations for patients with stage IV non-small cell lung cancer with driver alterations.

METHODS: This ASCO living guideline offers continually updated recommendations based on an ongoing systematic review of randomized controlled trials (RCTs), with the latest time frame spanning March-October 2025. An Expert Panel of medical oncology, pulmonary, community oncology, research methodology, and advocacy experts was convened. The literature search included systematic reviews, meta-analyses, and RCTs. Outcomes of interest include efficacy and safety. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations.

RESULTS: This guideline consolidates all previous updates and reflects the body of evidence informing this guideline topic. Thirteen studies were identified in the latest search of literature to date.

RECOMMENDATIONS: Evidence-based recommendations were updated to address first, second, and subsequent treatment options for patients with driver alterations. Additional information is available at www.asco.org/thoracic-cancer-guidelines.

PMID: 41632926

13. Cell. 2026 Mar 11:S0092-8674(26)00220-5. doi: 10.1016/j.cell.2026.02.013. Online ahead of print.

Respiratory viral infections prime accelerated lung cancer growth.

The COVID-19 pandemic has highlighted the long-term consequences of viral pneumonia, yet its impact on cancer development remains unclear. Here, we show that patients previously hospitalized with severe COVID-19 have an increased risk of subsequent lung cancer. Across multiple murine models, severe respiratory viral infections accelerated lung cancer growth, whereas vaccination mitigated infection-enhanced tumor progression. Mechanistically, prior viral pneumonia reprogrammed the lung into a pro-tumor microenvironment marked by the sustained accumulation of tumor-associated neutrophils and heightened immunosuppression. We observed persistent chromatin remodeling at key cytokine loci in immune and structural cells, linking inflammatory memory to tumor-promoting signals. Therapeutically, combined blockade of neutrophil recruitment and programmed death-ligand 1 (PD-L1) restored CD8+ T cell function and suppressed tumor growth. Together, these findings establish a causal link between prior viral pneumonia and lung tumorigenesis, underscoring the need for enhanced surveillance and targeted interventions to reduce post-COVID cancer risk.

PMID: 41819102

14. Nat Med. 2026 Mar 23. doi: 10.1038/s41591-026-04292-y. Online ahead of print.

Implementation of the NHS England Lung Cancer Screening Programme over 5 years.

Lung cancer screening with low-dose computed tomography has been proven to reduce lung-cancer-specific and all-cause mortality. The UK launched the NHS England Targeted Lung Health Check Programme in 2019, which has now become the national Lung Cancer Screening Programme, with full coverage expected by 2030. Here we present the progress and outcomes of the program. People aged 55-74 were offered low-dose computed tomography of the thorax if they had ever smoked and if risk thresholds, as determined by multivariable models, were met. Delivery of the program is through regionally federated clinical infrastructure and leadership, with national strategic, clinical and economic frameworks. The program has invited over two million people, with 7,193 lung cancers diagnosed-63.1% at tumor, node, metastasis stage 1 and 12.6% stage 2-to March 2025. This has increased the early-stage proportion of lung cancer in England over 5 years, particularly in socioeconomically deprived regions. The NHS England Programme exemplifies how large-scale implementation can be achieved at speed through centralized protocols and effective project management. The program has demonstrated feasibility and scalability in reaching high-risk and underserved populations, but needs to further address inequalities in participation. These findings support adoption of lung cancer screening across the UK and globally, and offer practical tools for international adaptation.

PMID: 41872602

15. Laeknabladid. 2026 Mar;112(3):120-123. doi: 10.17992/lbl.2026.03.883.

Perianal tuberculosis

Perianal tuberculosis is a rare manifestation of tuberculosis. This reportdescribes a healthy 41-year-old man diagnosed with a perianal abscess that required examination and surgical drainage under general anesthesia. The wound healed poorly over the following months, prompting repeat cultures and tissue sampling. Histological diagnosis revealed necrotizing granulomatous inflammation and acid-fast bacilli, indicating mycobacterial infection. Further investigation revealed pulmonary tuberculosis. The patient received a six-month course of anti-tuberculosis medications and recovered fully. The perianal wound healed well following treatment. Tuberculosis is an important differential diagnosis in individuals with a wound or a lesion near the anus or elsewhere that heals slowly or recurs.

PMID: 41733318 [Indexed for MEDLINE]

16. Gastroenterol Hepatol. 2026 Mar;49(3):502587. doi:10.1016/j.gastrohep.2025.502 587. Epub 2025 Oct 14.

Tuberculosis and inflammatory bowel disease.

Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, carries an increased risk of tuberculosis (TB), particularly in patients treated with immunosuppressive therapies such as anti-TNF agents. The risk is further elevated when combined with immunomodulators. Other drugs, including anti-integrins, IL-12/23 inhibitors, and JAK inhibitors (JAK-i), present a variable risk of TB reactivation. Given this risk, screening for latent tuberculosis infection (LTBI) is essential in IBD patients before initiating immunosuppressive therapy. Guidelines recommend performing this screening ideally at the time of IBD diagnosis or, alternatively, before advanced therapy. Diagnostic tests include the tuberculin skin test (TST) and interferon-gamma release assays (IGRA). In immunocompromised patients, false negatives may occur; therefore, dual testing is advised. Chest X-rays are reserved for cases with positive tests or clinical suspicion. In the presence of LTBI, chemoprophylaxis with isoniazid or rifampicin is recommended prior to initiating immunosuppression. If active TB is diagnosed, immunosuppressive therapy must be discontinued and standard antituberculous treatment initiated. The reintroduction of immunosuppressive therapy should be assessed on a case-by-case basis, prioritizing agents with lower reactivation risk. Finally, BCG vaccination is not recommended in IBD patients undergoing immunosuppressive treatment due to its nature as a live vaccine.

PMID: 41101460 [Indexed for MEDLINE]

17. Nat Immunol. 2026 Mar;27(4):867-880. doi: 10.1038/s41590-026-02431-8. Epub 2026 Feb 23.

The immunometabolic topography of cellular organization and bacterial control in tuberculosis granulomas.

Despite being heavily infiltrated by immune cells, tuberculosis (TB) granulomas often subvert the host response to Mycobacterium tuberculosis (Mtb) infection and support bacterial persistence. Human TB granulomas are enriched for immunosuppressive factors typically associated with tumor-immune evasion, raising the possibility that they promote tolerance to infection. Here we identify candidate drivers for establishing this tolerogenic niche and show that the magnitude of this response correlates with bacterial persistence. We conducted a multimodal spatial analysis of 52 granulomas from 16 nonhuman primates infected with low-dose Mtb for 9-12 weeks. Each granuloma's bacterial burden was quantified individually, enabling us to assess how granuloma spatial structure and function relate to infection control. We found that a universal feature of TB granulomas is partitioning of the myeloid core into two distinct metabolic environments, one of which is hypoxic. This hypoxic environment is associated with pathological immune cell states, dysfunctional cellular organization of the granuloma, and a near-complete blockade of lymphocyte infiltration that would be required for a successful host response. The extent of these hypoxia-associated features correlates with higher bacterial burden. We conclude that hypoxia correlates with immune cell state and organization within granulomas and might subvert immunity to TB.

PMID: 41731147 [Indexed for MEDLINE]

18. Lancet Respir Med. 2026 Mar;14(3):267-280. doi: 10.1016/S2213-2600(25)00329 7. Epub 2025 Oct 30.

Climate change and tuberculosis: an analytical framework.

Climate change is likely to exacerbate a range of determinants that drive tuberculosis, the world's leading cause of death from a single infectious agent. However, tuberculosis is often neglected in wider climate health discussions.Commissioned by WHO, we developed an analytical framework outlining potentialcausal relationships between climate change and tuberculosis. We drew onexisting knowledge of tuberculosis determinants, identified determinants likely to be sensitive to the effects of climate change, and conceptualised the mechanistic pathways through which these effects might occur. We collated evidence for these pathways, but found no studies directly linking climate change and tuberculosis, warranting research to build evidence for action. Nevertheless, the available indirect evidence supports the existence of plausible causal links between climate change and tuberculosis. This evidence highlights the need to consider tuberculosis as a climate-sensitive disease, and include tuberculosis in climate risk adaptation and mitigation programmes, and climate-resilient funding and response mechanisms. Only through urgent research and comprehensive action can we address this overlooked intersection and ensure that climate change does not become a barrier to ending the global tuberculosis epidemic.

PMID: 41177169 [Indexed for MEDLINE]

19. Lancet Glob Health. 2026 Mar;14(3):e337-e346. doi: 10.1016/S2214109X(25)004 31-0. Epub 2026 Jan 7.

Global estimates of tuberculosis incidence during pregnancy and postpartum: a

rapid review and modelling analysis.

BACKGROUND: Despite known maternal, perinatal, and infant health risks of tuberculosis during pregnancy, global estimates of incidence remain scarce. Existing estimates are outdated, and do not include the postpartum period, HIV co-infection, age, or specific changes in risk, limiting our understanding of the true scale of disease in this understudied population.

METHODS: In this rapid review and modelling analysis, we estimated the global tuberculosis incidence in pregnant and postpartum women using a population-based modelling approach. We searched MEDLINE and EMBASE, with no date or language limits, and included studies reporting tuberculosis incidence in pregnancy or postpartum with suitable comparison groups; we also used Feb 6, 2025, interim data from the ongoing ORCHID cohort. We combined WHO age and sex-stratified tuberculosis incidence data with country-specific population and fertility data to estimate baseline tuberculosis incidence, and applied systematic review-based risk ratios to account for elevated increased risk during pregnancy and postpartum. Uncertainty in all inputs was propagated using standard error propagation formulae and summarised as mean tuberculosis incidence rates and mean incidence rate ratios (IRRs), each reported with 95% quantile-based uncertainty intervals (UIs).

FINDINGS: We identified 37 studies published between 1996 and 2020, of which three were of sufficient quality to provide data for HIV-negative women. One additional study (ORCHID; Odayar et al, unpublished) provided data for women living with HIV. Compared with non-pregnant women without HIV, tuberculosis IRRs were 1·34 (95% CI 1·17-1·54) during pregnancy and 1·91 (1·53-2·39) during postpartum among HIV-negative women. For women living with HIV, IRRs were 5·73(95% CI 2·64-10·94) during pregnancy and 3·58 (0·85-9·63) postpartum. We estimated 239500 pregnant women (95% UI 216 300-262 800) and 97 600postpartum women (90 100-105 200) developed tuberculosis disease globally in 2023, with HIV contributing to 21·3% (19·8-22·8) and 10·6% (9·9-11·3) of cases, respectively. The WHO African region had the highest incidence (110 600 [95% UI96 700-124 500] in pregnant women and 40 900 [36 300-45 400] in postpartum women), followed by the South-East Asia region (79 900 [64 100-95 700] in pregnant women and 35 900 [30 800-41 100] in postpartum women).

INTERPRETATION: Pregnant and postpartum women face substantial tuberculosis risk, yet remain under-represented in global estimates. Our findings underscore the need for improved surveillance and targeted interventions to reduce tuberculosis incidence in this group.

PMID: 41519136 [Indexed for MEDLINE]

20. Clin Microbiol Rev. 2026 Mar 12;39(1):e0023225. doi: 10.1128/cmr.00232-25. Epub 2025 Dec 15.

Comprehensive review and reflective evaluation of cell therapies for tuberculosis.

SUMMARY Tuberculosis (TB) remains a major infectious disease threatening global health. An estimated 2 billion people worldwide are infected with Mycobacterium tuberculosis (Mtb), and 5-10% of those with latent infection will develop active TB. Despite the success of existing anti-TB drugs in controlling transmission, significant challenges remain, including long treatment durations, severe side effects, suboptimal treatment adherence, and inevitable drug resistance. Even newly developed drugs may fail to keep pace with the rising number of drug-resistant cases. Moreover, these treatments do not adequately address persistent lung dysfunction after cure. A primary reason for these therapeutic challenges in TB management may be that all current anti-TB drugs are solely aimed at achieving antibacterial, bacteriostatic, or bactericidal efficacy, which neglects the critical role of host cellular responses during disease progression. Future strategies should explore the potential of cell-based therapies, an area that has received limited attention in previous reviews. From the perspective of cell therapy, this article comprehensively reviews key clinical studies, animal models, and in vitro experiments from recent decades that utilized cells or cytokines for TB treatment, providing clinicians and researchers with a unique perspective and support for developing more integrated therapeutic strategies toward ending TB.

PMID: 41395933 [Indexed for MEDLINE]

21. Lancet Infect Dis. 2026 Mar 18:S1473-3099(26)00019-8. doi:10.1016/S1473-3099(26)00019-8. Online ahead of print.

Accelerating research and development of new vaccines against tuberculosis: 5-year progress on the global roadmap.

In 2021, a global tuberculosis vaccine research and development roadmap proposed a series of actions to accelerate the development of new, effective, and affordable vaccines that are urgently needed to eliminate tuberculosis globally. Since then, the pipeline has diversified, several candidates are currently in phase 3 clinical trials, and many low-income and middle-income countries have made important steps in anticipating regulatory approval. However, the number of candidates in active clinical trials is small and product development challenges persist. Engagement with vaccine manufacturers has increased but is hampered by unclear demand and insufficient committed procurement. Investment in tuberculosis vaccine research and development therefore remains risky and inadequate. In parallel, more work is needed to identify and plan for cost-effective implementation while mitigating potential hesitancy and stigma to ensure uptake of new tuberculosis vaccines once licensed. Increased diversification of funders and strategic coordination of multiple stakeholders is needed more than ever.

PMID: 41864213

22. Lancet Glob Health. 2026 Mar;14(3):e347-e355. doi:10.1016/S2214109X(25)004 541.

Characterising progression and regression patterns across the spectrum of tuberculosis: a multistate modelling approach.

BACKGROUND: The conceptualisation of tuberculosis has undergone a paradigm shift from binary states to a spectrum, resulting in the International Consensus for Early TB (ICE-TB) framework. This study aimed to use data from a prospective, observational cohort study and multistate modelling to address the lack of contemporary data to quantify movement between ICE-TB states.

METHODS: ERASE-TB was a prospective, observational cohort study evaluating novel diagnostic tests for earlier detection of tuberculosis. Household contacts aged at least 10 years in Zimbabwe, Tanzania, and Mozambique were followed up 6-monthly for 12-24 months with comprehensive tuberculosis investigations at each visit. Those not diagnosed with prevalent tuberculosis, with state classification from at least two timepoints were included. ICE-TB states were defined by use of symptomatology, interferon gamma release assays, chest radiographs, and sputum microbiology. A Markov multistate model based on ICE-TB was applied with one initial state (Mycobacterium tuberculosis non-infection), two intermediate states (M tuberculosis infection and non-infectious disease [asymptomatic-symptomatic]), and one absorbing state (infectious disease [asymptomatic-symptomatic]). Transition probabilities were predicted.

FINDINGS: 1789 (84·8%) of 2109 recruited household contacts were included. At enrolment, most (1000 [55·9%]) did not have M tuberculosis infection; 674 (37·7%) had M tuberculosis infection, and 115 (6·5%) had non-infectious disease.34 people developed infectious disease (23 asymptomatic, 11 symptomatic). In the multistate model, the transition probabilities of progressing from M tuberculosis non-infection to M tuberculosis infection and M tuberculosis infection to non-infectious disease were 13% and 3% by month 12. For those in non-infectious disease, the probabilities of regression and progression by month 12 were 85% and 13%, respectively.

INTERPRETATION: This study applied the ICE-TB framework to describe movement between states by use of contemporary, granular, longitudinal data. Although most people remained static over time, the non-infectious state was more dynamic, with most people regressing over time.

PMID: 41713438 [Indexed for MEDLINE]

23. Lancet Respir Med. 2026 Mar 23:S2213-2600(26)00056-1. doi:10.1016/S2213-2600(26)00056-1. Online ahead of print.

PET-CT benchmarked detection and 5-year progression of asymptomatic tuberculosis: a longitudinal, prospective cohort study.

BACKGROUND: To understand how lung pathology relates to symptoms, microbiology, and progression risk in tuberculosis and to advance diagnostic development, we determined the frequency at screening of tuberculosis-consistent lesions in asymptomatic individuals within 5 years of tuberculosis diagnosis using highly sensitive imaging ([18F]-fluorodeoxyglucose PET-CT) and compared with chest x-ray computer-aided detection (CAD).

METHODS: We enrolled a prospective longitudinal cohort in Khayelitsha, Cape Town, South Africa, of asymptomatic, HIV-uninfected contacts aged 18-65 years of patients with rifampicin-resistant tuberculosis, a tuberculosis high-risk group not eligible for chemoprophylaxis. Participants underwent baseline PET-CT, chest x-ray, phlebotomy, and intensive sputum collection, and were classified into four PET-CT lung categories: consistent with tuberculosis, inactive tuberculosis, other lesions, and normal. Chest x-ray was processed by three types of CAD software (CAD4TB [version 7.0], qXR [version 3.0.0], and Lunit [version 3.1.4.111]). Follow-up included symptom-agnostic tuberculosis screening (23-38 months) and provincial register review (≤74 months), and a subgroup had repeat PET-CT (5-15 months). Tuberculosis was defined as bacteriologically confirmed or clinically diagnosed. The primary outcome measures were hazard ratio (HR) for tuberculosis diagnosis and treatment by baseline PET-CT lung abnormality category with normal as the reference group, and diagnostic performance of chest x-ray CAD software using area under the receiver operator characteristic curve (AUC).

FINDINGS: 250 asymptomatic adults were enrolled between March 3, 2015, and Oct 11, 2017, irrespective of tuberculosis history or previous infection, and followed up for 1107 person-years (median 4·7 years [IQR 4·0-5·1]). 18 (7%) participants were treated for tuberculosis (16 [89%] of 18 bacteriologically confirmed). Six of 18 participants were diagnosed at baseline (four requiring induced sputum culture) and 12 of 18 after a median of 32 months (IQR 12-35). By baseline PET-CT category, tuberculosis was diagnosed and treated in 12 (41%) of 29 participants with scans consistent with tuberculosis, two (7%) of 30 with scans consistent with inactive tuberculosis, two (2%) of 83 with scans showing other lesions, and two (2%) of 108 with scans showing normal lungs. Participants with baseline PET-CT scans consistent with tuberculosis had the highest risk of 5-year tuberculosis diagnosis (HR 28·54 [95% CI 6·37-127·81] compared with those with scans showing normal lungs, p<0·0001), with no significant risk for scans consistent with inactive tuberculosis (3·55 [0·50-25·21], p=0·21) or other lung lesions (1·30 [0·18-9·23], p=0·79). 11 (69%) of the 16 participants with bacteriologically confirmed tuberculosis were asymptomatic at bacteriological confirmation, and ten (91%) of 11 had baseline PET-CT scans consistent with tuberculosis. Using baseline PET-CT classification as reference, the AUC for chest x-ray CAD software ranged from 0·86 (95% CI 0·72-0·99) to 0·89 (0·75-1·00) for bacteriologically confirmed tuberculosis.

INTERPRETATION: Most adult asymptomatic contacts diagnosed with tuberculosis over 5 years had baseline radiographically evident disease, not radiographically negative incipient tuberculosis. Although PET-CT is not feasible for routine screening, it provides a highly sensitive reference benchmark for diagnostic development, with chest x-ray CAD performing comparatively well.

PMID: 41887246

24. Clin Microbiol Rev. 2026 Mar 30:e0025825. doi: 10.1128/cmr.00258-25. Online ahead of print.

From T-cell sensitization to molecular-intelligent stratification: a roadmap for precision diagnosis of latent tuberculosis infection.

One quarter of the world's population carries latent tuberculosis infection (LTBI), an invisible reservoir that must be drained to end the global tuberculosis (TB) epidemic. This review charts the evolution of LTBI diagnosis from the tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) to a new molecular-intelligent paradigm. At the clinical level, we propose a CD4/age-stratified, resource-matched decision framework that delivers actionable screening and sequencing strategies for people living with HIV, children, the immunosuppressed, and pregnant women. At the biomarker level, we integrate host-derived analytes (CXCL1, CCL8, IP-10, CD38+CD27⁻ T cells, and Fc-glycosylated antibodies) with pathogen-derived antigens (dormancy survival regulator [DosR], resuscitation-promoting factor [Rpf], heparin-binding hemagglutinin [HBHA], and PE/PPE) to create a three-tier index: single-analyte triage, multi-analyte confirmation, and dynamic treatment monitoring. At the technology level, we benchmark multi-omics-plus-AI models, single-molecule Simoa arrays, and microfluidic point-of-care testing (POCT) platforms for sensitivity, accessibility, and cost. High-quality cross-population validation, standardized thresholds, and resource-tiered deployment remain the principal translational bottlenecks. We call for integrated programs that combine key-population multicenter cohorts, explainable AI, and ASSURED criteria to propel LTBI management from the T-cell-sensitization era into the molecular-intelligent age. Achieving this vision within 5 years is technically feasible and will accelerate global elimination targets by enabling precision preventive therapy at an unprecedented scale.

PMID: 41910258

25. Lancet Glob Health. 2026 Apr;14(4):e579-e588. doi:10.1016/S2214109X(25)00 489-9.

Association of linezolid interruption and rechallenge with clinical outcomes in patients with rifampicin-resistant tuberculosis in South Africa, 2018-22: an observational cohort study.

BACKGROUND: Linezolid is a key component of treatment regimens for rifampicin-resistant or multidrug-resistant tuberculosis. Toxicity-related linezolid interruption is not uncommon, but little is known about its effect on treatment-related outcomes. Furthermore, there are no data on the frequency of successful rechallenge and its associated predictors. This study aimed to ascertain the relationship between linezolid discontinuation and treatment outcome, and the likelihood of successful rechallenge in patients who discontinued linezolid.

METHODS: We conducted an observational cohort study to review programmatic data from a South African national database on which all patients with drug-resistant tuberculosis are required to be registered. Data were extracted between Jan 1, 2018, and March 16, 2022. Data capture occurs at primary, secondary, and tertiary centres. We included adults 18 years or older with rifampicin-resistant or multidrug-resistant tuberculosis who had received linezolid and had recorded treatment outcomes. We excluded patients with extrapulmonary tuberculosis, those who were not exposed to a bedaquiline-containing regimen, and patients who died before completing their course of linezolid. The frequency of linezolid interruption and subsequent linezolid rechallenge was evaluated from clinical data for patients in the database. The primary outcome measure was the proportion of patients with an unfavourable outcome (death, treatment failure, or loss to follow-up) in those in whom linezolid was interrupted compared with those who continued treatment. Outcomes were ascertained using logistic regression to estimate adjusted odds ratios (aORs).

FINDINGS: 10 102 (83·7%) of 12 064 patients registered on the database between Jan 1, 2018, and Dec 31, 2020, met the study inclusion criteria and were included in the analysis. 6142 (60·8%) patients were male and 3960 (39·2%) were female. Treatment with linezolid was interrupted in 1974 (19·5%) patients, and the median time to interruption was 4·6 weeks (IQR 2·0-8·6). After adjusting for potentially confounding variables, linezolid interruption was associated with greater odds of an unfavourable outcome compared with completion of treatment (aOR 4·24 [95% CI 3·79-4·75], p<0·0001). Of the 1974 patients who interrupted their course of linezolid, only 65 (3·3%) were rechallenged and, of these, 47 (72·3%) successfully completed their linezolid course. Those successfully rechallenged were more likely to have a favourable outcome than were those in whom rechallenge failed (OR 4·03 [1·08-15·0], p=0·038). A shorter time to initial linezolid interruption was associated with reduced rechallenge success (OR 0·26 [0·08-0·85], p=0·022) and a higher likelihood of unfavourable outcome (OR 1·59 [1·33-1·93]; p<0·0001).

INTERPRETATION: Linezolid interruption was common and associated with unfavourable clinical outcomes. Linezolid rechallenge was frequently successful and associated with better clinical outcomes. These findings inform clinical practice and have implications for the management of patients receiving oral, short-course regimens for multidrug-resistant tuberculosis.

PMID: 41856141 [Indexed for MEDLINE]

26.Nature. 2026 Mar 11. doi: 10.1038/s41586-026-10216-0. Online ahead of print.

Ageing promotes metastasis via activation of the integrated stress response.

Lung cancer predominantly affects older individuals, yet how physiological ageing influences tumour evolution remains poorly understood1. Here we show that ageing reprograms the evolutionary trajectory of KRAS-driven lung adenocarcinoma, limiting primary tumour growth while promoting metastatic dissemination through epigenetic activation of the integrated stress response (ISR). The ISR effector ATF4 drives epithelial and metabolic plasticity, conferring metastatic competence. Mechanistically, aged tumour cells show increased sensitivity to the PERK-eIF2α arm of the unfolded protein response, sustaining persistent ATF4 signalling. Targeting ISR-ATF4 genetically or pharmacologically abolishes these adaptations and limits dissemination, whereas ATF4 overexpression alone is sufficient to induce metastasis. The ageing-ATF4 axis imposes a dependency on glutamine metabolism, revealing a therapeutically actionable vulnerability. Clinical analyses confirm that ATF4 is enriched in aged tumours and correlates with poor survival and advanced-stage disease. Collectively, these results define epigenetic ISR-ATF4 activation as a causal driver of lineage plasticity and metastasis in aged tumours, revealing a therapeutic opportunity in older patients with lung adenocarcinoma, the most common yet understudied subset of lung cancer.

PMID: 41813904

27. Cancer Discov. 2026 Mar 24. doi: 10.1158/2159-8290.CD-25-1936. Online ahead of print.

The oncogenic EGFR-SHC1 fusion confers insensitivity to EGFR-TKI via dual activation of N-EGFR kinase domain and C-SHC1 phosphorylation sites in lung cancer.

While epidermal growth factor receptor (EGFR) fusions in non-small cell lung cancer (NSCLC) typically show sensitivity to tyrosine kinase inhibitors (TKIs), we identified an EGFR-SHC1 fusion subtype that exhibits intrinsic resistance to EGFR-TKI monotherapy through a dual activation mechanism in the preclinical and clinical setting. EGFR-SHC1 fusion protein comprises of N-terminal EGFR and C-terminal SHC1. We demonstrated that EGFR-SHC1 simultaneously activates the EGFR kinase domain (KD) and SRC-mediated phosphorylation of the SHC1 fusion partner, thereby driving ERK/AKT pathway activation and tumorigenesis independent of KD inhibition. Structural modeling coupled with domain-specific mutagenesis revealed that SHC1 phosphorylation establishes a kinase-independent bypass mechanism. Notably, dual-targeted inhibition using afatinib (EGFR-TKI) in combination with dasatinib (SRC-TKI) induced marked tumor regression in a TKI-refractory NSCLC patient with EGFR-SHC1. This study illustrates a cooperative oncogenesis between kinase and scaffold protein in fusions, providing a clinically actionable strategy for overcoming TKI resistance in patients with these oncogenic fusions.

PMID: 41874451

28. Lancet Respir Med. 2026 Mar 24:S2213-2600(26)00051-2. doi: 10.1016/S2213-2600(26)00051-2. Online ahead of print.

Consensus definition of stage III non-small-cell lung cancer technical resectability to standardise inclusion criteria for clinical trials: a multisocietal EORTC-Lung Cancer Group collaboration.

The decision regarding resectability in stage III non-small-cell lung cancer (NSCLC) is complex. To improve consistency in eligibility criteria in clinical trials, the European Organisation for Research and Treatment of Cancer (EORTC) initiated a Delphi study to establish a standardised definition of technical resectability for stage III NSCLC. 36 experts from the EORTC, European Respiratory Society, International Association for the Study of Lung Cancer, European Society for Radiotherapy and Oncology, European Thoracic Oncology Platform and International Breast Cancer Study Group, European Society of Thoracic Surgeons, and European Society of Pathology formulated 34 consensus statements on the definition of resectability. Consensus was defined as 75% agreement. After three Delphi rounds there was unanimous consensus that the decision on resectability should be made by experienced thoracic surgeons within the context of a multidisciplinary team. Initial assessments should include PET-CT, brain MRI, and invasive mediastinal staging. Stage IIIA was generally classified as resectable. Tumours with N2 involvement might be resectable depending on the nature of lymph node involvement (ie, single or multi-station, bulky or non-bulky, and invasive or non-invasive). Stage IIIB might be considered resectable, depending on lymph node characteristics: N2single mostly resectable; N2multi mostly unresectable; N2bulky mostly unresectable; and N2invasive or N3 unresectable. Stage IIIC was classified as unresectable. The proposed definitions aim to standardise inclusion criteria for clinical trials facilitating a more consistent evaluation of multimodal treatments for stage III NSCLC. Further data collection, especially on the nature of N2 disease, is needed to refine the definition.

PMID: 41895314

29.Cancer Cell. 2026 Mar 5:S1535-6108(26)00104-2.doi:10.1016/j.ccell.2026.02.006. Online ahead of print.

HS-20093, a B7-H3-targeted antibody-drug conjugate in lung cancer: Results from the ARTEMIS-001 phase 1a/b trial.

This phase 1a/b study (NCT05276609) evaluated the safety, pharmacokinetics, and efficacy of B7-H3-targeted antibody-drug conjugate HS-20093 (GSK5764227) in 306 patients with previously treated advanced solid tumors. In phase 1a, 12.0 mg/kg was established as the maximum tolerated dose. Among 236 lung cancer patients who received 8.0 or 10.0 mg/kg HS-20093, the most frequent grade ≥3 treatment-related adverse events (AEs) included decreased neutrophil (25.5% vs. 50.5%) and white blood cell counts (19.7% vs. 42.4%), and anemia (16.8% vs. 34.3%), respectively. Treatment-related interstitial lung disease and AEs leading to death occurred in 3.4% and 3.8% of patients, respectively. Among response-evaluable patients, the confirmed objective response rate was 52.3% (95% CI: 39.5, 64.9) for extensive-stage SCLC (ES-SCLC, N = 65) and 22.4% (95% CI: 16.0, 29.8) for non-small cell lung cancer (NSCLC, N = 152) patients, with comparable rates between 8.0 mg/kg and 10.0 mg/kg dose cohorts across both groups. These results support further development of HS-20093, with 8.0 mg/kg selected for phase 3 trials.

PMID: 41791381

30. Lancet Oncol. 2026 Mar 10:S1470-2045(26)00049-5. doi: 10.1016/S1470-2045(26)00049-5. Online ahead of print.

Benmelstobart plus anlotinib versus pembrolizumab as first-line treatment for PD-L1-positive, advanced non-small-cell lung cancer (CAMPASS): a blinded, randomised, controlled, phase 3 trial.

BACKGROUND: PD-1 and PD-L1 inhibitors have been shown to synergise with anti-angiogenic agents in non-small-cell lung cancer (NSCLC). We aimed to compare benmelstobart plus anlotinib with pembrolizumab in patients with previously untreated, driver gene-negative, PD-L1-positive, advanced NSCLC.

METHODS: The blinded, randomised, controlled, phase 3 CAMPASS trial was conducted in 79 centres across China. Patients aged 18-75 years with stage IIIB-IV squamous or non-squamous NSCLC, no previous systemic treatment for advanced, recurrent or metastatic diseases, a PD-L1 tumour proportion score of 1% or greater, a life expectancy of 3 months or longer, at least one measurable lesion, and an Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (2:1) to receive intravenous benmelstobart (1200 mg once on day 1) plus oral anlotinib (12 mg daily on days 1-14) or intravenous pembrolizumab (200 mg once on day 1) plus placebo every 3 weeks. Randomisation was done centrally and stratified by tumour histology, PD-L1 tumour proportion score, and brain metastases. Treatment allocation was open label for investigators and masked to patients and statisticians. The primary endpoint was progression-free survival as assessed by a blinded independent review committee per Response Evalutation Criteria in Solid Tumours version 1.1 in the intention-to-treat population (all randomly assigned patients). Safety was assessed in all randomly assigned patients who received at least dose of study drug. Results reported here are from a preplanned final analysis for progression-free survival. This ongoing study is closed to recruitment and is registered with ClinicalTrials.gov, NCT04964479.

FINDINGS: Between Aug 6, 2021, and Dec 14, 2022, 531 patients were randomly assigned (354 to the benmelstobart plus anlotinib group and 177 to the pembrolizumab plus placebo group). 449 (85%) patients were male, 82 (15%) were female, and 493 (93%) were of Han ethnicity. Two patients in the benmelstobart plus anlotinib group and one patients in the pembrolizumab plus placebo group were untreated and therefore excluded from the safety population. After a median follow-up of 11·4 months (95% CI 9·4-13·1) for the benmelstobart plus anlotinib group and 10·6 months (9·0-13·0) for the pembrolizumab plus placebo group, median progression-free survival was 11·0 months (9·2-12·6) and 7·1 months (5·8-9·5), respectively (hazard ratio [HR] 0·70 [95% CI 0·54-0·90]; log-rank p=0·0057). Grade 3 or worse treatment-related adverse events occurred in 206 (59%) of 352 patients in the benmelstobart plus anlotinib group and 51 (29%) of 176 patients in the pembrolizumab plus placebo group, and the most frequent one was hypertension (90 [26%] vs five [3%]). Serious treatment-related adverse events occurred in 89 (25%) patients in the benmelstobart plus anlotinib group and 37 (21%) patients in the pembrolizumab plus placebo group, the most common of which were haemoptysis (nine [3%] vs none) and immune-mediated pulmonary diseases (eight [2%] vs five [3%]). Five (1%) treatment-related deaths occurred in the benmelstobart plus anlotinib group (two due to haemoptysis and one each due to immune-mediated pulmonary disease, disease progression, and infection pneumonia) and four (2%) occurred in the pembrolizumab plus placebo group (one each due to respiratory failure, pulmonary inflammation, disease progression, and myocardial injury).

INTERPRETATION: Benmelstobart plus anlotinib showed longer progression-free survival than pembrolizumab plus placebo and no unexpected safety signals were reported, suggesting benmelstobart plus anlotinib as a potential first-line option in driver gene-negative, PD-L1-positive, advanced NSCLC. Longer term follow-up is needed to establish effects on overall survival.

PMID: 41825453

31. JAMA Oncol. 2026 Mar 26:e260392. doi: 10.1001/jamaoncol.2026.0392. Online ahead of print.

Combination of Radiotherapy and Immunotherapy in Advanced Non-Small Cell Lung Cancer.

IMPORTANCE: The optimal sequencing of radiotherapy (RT) combined with immunotherapy (iRT) and the value of chemotherapy remain undefined for advanced non-small cell lung cancer (NSCLC), where randomized data are limited.

OBJECTIVE: To compare real-world overall survival (OS) between sequential and concurrent iRT in newly diagnosed advanced NSCLC, assess the effect of immune checkpoint inhibitor (ICI) maintenance after RT in refractory disease, and evaluate the association of chemotherapy with survival.

DESIGN, SETTING, AND PARTICIPANTS: This is a territory-wide study (OCEANUS) based on the Hong Kong Hospital Authority Clinical Data Analysis and Reporting System (more than 90% population coverage). Patients with NSCLC diagnosed from January 1, 2010, to December 31, 2021, who subsequently received iRT for advanced or refractory disease were included. Overlap weighting was the primary propensity score-weighted method, with inverse probability of treatment weighting used for sensitivity analysis. Data were analyzed from December 2024 to April 2025.

EXPOSURES: Sequential vs concurrent iRT for newly diagnosed advanced NSCLC; RT with vs without ICI maintenance for refractory NSCLC; receipt of chemotherapy. MAIN OUTCOMES AND MEASURES: The primary outcome was real-world OS after landmark, estimated with weighted Kaplan-Meier and Cox models. When proportional hazards were violated (per Schoenfeld residuals), treatment effects were summarized using restricted mean survival time.

RESULTS: Of 3522 patients who received ICIs, 335 received RT, including 155 with newly diagnosed advanced and 180 with refractory NSCLC. Of these, 247 (73.7%) were male, and the median (range) age was 64 (34-90) years. In newly diagnosed NSCLC, patients treated with sequential iRT had significant longer real-world OS than those treated with concurrent iRT (median, 20.3 months [95% CI, 13.3 to not reached] vs 16.0 months [95% CI, 8.3-30.0]; adjusted hazard ratio, 0.68; 95% CI, 0.47-0.99; P = .045). Chemotherapy was also associated with longer survival in patients with newly diagnosed advanced NSCLC. In refractory NSCLC, RT with ICI maintenance was associated with a numerically longer median real-world OS (11.2 months [95% CI, 7.9-20.6] vs 6.7 months [95% CI, 4.4-17.4]; P = .20). Addition of chemotherapy was not significant for real-world OS. Inverse probability of treatment weighting analyses produced similar estimates.

CONCLUSIONS AND RELEVANCE: In this cohort study, sequential iRT was associated with longer survival than concurrent iRT in patients with newly diagnosed advanced NSCLC, and chemotherapy was associated with longer survival. In patients with refractory NSCLC who survived at least 90 days, RT with ICI maintenance resulted in nonsignificantly longer survival and an unclear association with chemotherapy. These findings are hypothesis generating and support prospective randomized studies to define optimal sequencing of iRT and use of systemic treatment partners.

PMID: 41885834

32. J Clin Oncol. 2026 Apr;44(10):893-902. doi: 10.1200/JCO-25-01929. Epub 2026 Mar 4.

Izalontamab Brengitecan in Locally Advanced or Metastatic Non-Small Cell Lung Cancer With Actionable Genomic Alterations Outside of Classical EGFR Mutations: A Phase Ib Study.

PURPOSE: To evaluate the safety and efficacy of izalontamab brengitecan (iza-bren) in patients with non-small cell lung cancer (NSCLC) harboring actionable genomic alterations (GAs) outside of classical epidermal growth factor receptor (EGFR) mutations.

METHODS: Eligible patients had locally advanced or metastatic NSCLC with prespecific actionable GAs, had progressed after standard treatment and received no more than one previous line of chemotherapy. iza-bren was administered at the dose of 2.5 mg/kg once per day on days 1 and 8 of each 3-week cycle. The primary end point was safety. The secondary end points included objective response rate (ORR), disease control rate (DCR), and duration of response. The exploratory end points included progression-free survival (PFS) and overall survival (OS).

RESULTS: A total of 83 patients with NSCLC were enrolled in four cohorts: EGFR exon20ins/nonclassical mutations (n = 14), human epidermal growth factor receptor 2 (HER2) mutation (n = 19), KRAS/BRAF/MET mutation (n = 26), and ALK/ROS1/RET/NTRK fusion (n = 24). The most common grade ≥3 treatment-related adverse events (TRAEs) were thrombocytopenia (51.8%), anemia (44.6%), and neutropenia (43.4%). The most frequent nonhematologic TRAEs of all grades were nausea (49.4%), asthenia (45.8%), stomatitis (44.6%), and diarrhea (38.6%). One case of grade 2 interstitial lung disease was observed. The confirmed ORR was 39.7%, and the DCR was 85.9%. The median PFS was 7.0 months (95% CIs, 5.4 to 10.5), while OS data were immature. Patients with EGFR exon20ins or other nonclassical mutations achieved an ORR of 69.2% with a median PFS of 10.5 months (95% CI, 6.9 to not reached); the HER2-mutant cohort had an ORR of 52.9% and a median PFS of 7.5 months (95% CI, 5.4 to not reached).

CONCLUSION: iza-bren demonstrated encouraging antitumor activity and a manageable safety profile in pretreated NSCLC patients with diverse GAs outside of classical EGFR mutations, especially in EGFR exon20ins/nonclassical and HER2 mutations.

PMID: 41779981 [Indexed for MEDLINE]

33. J Clin Oncol. 2026 Mar 10;44(8):630-640. doi: 10.1200/JCO-25-01569. Epub 2026 Jan 13.

Chemoradiation ± Atezolizumab in Limited-Stage Small Cell Lung Cancer: Results of NRG Oncology/Alliance LU005.

PURPOSE: NRG Oncology/Alliance LU005 (ClinicalTrials.gov identifier: NCT03811002) tested the addition of atezolizumab to concurrent chemoradiation (CRT) in this open-label, phase III international trial.

METHODS: Patients with limited-stage small cell lung cancer (LS-SCLC), stage Tx-IV, N0-3, and M0 with Eastern Cooperative Group performance status (PS) 0-2 received one cycle of chemotherapy (platinum/etoposide) before study registration and were randomly assigned to CRT alone versus CRT plus concurrent and adjuvant atezolizumab, 1,200 mg once daily, every 3 weeks until investigator-assessed progression or intolerable side effects for a maximum of 17 cycles. Patients were stratified by choice of chemotherapy (cisplatin v carboplatin), radiation fractionation schedule (66 Gy once daily v 45 Gy twice daily), sex, and PS (0/1 v 2). The primary end point was overall survival (OS). Secondary end points included investigator-assessed progression-free survival (PFS), objective response rate, local control, and distant-metastasis-free survival (DMFS).

RESULTS: patients were randomly assigned from May 2019 to December 2023. The median OS was 36.1 months (95% CI, 28.1 to 42.5) for the CRT-alone arm and 31.1 months (95% CI, 28.5 to 44.7) for the CRT + atezolizumab arm, respectively (hazard ratio [HR], 1.03 [95% CI, 0.80 to 1.32]). The median PFS was 11.4 months (95% CI, 10.3 to 13.2) for the CRT-alone arm and 12.1 months (95% CI, 10.9 to 15.2) for the CRT + atezolizumab arm, respectively (HR, 0.98 [95% CI, 0.79 to 1.22]). The median DMFS was 13.0 months (95% CI, 11.3 to 18.2) for the CRT-alone arm and 16.8 months (95% CI, 12.1 to 21.6) for the CRT + atezolizumab arm (HR, 0.96 [95% CI, 0.76 to 1.21]). No unexpected safety signals with concurrent atezolizumab were observed.

CONCLUSION: Concurrent and adjuvant atezolizumab with chemoradiation did not improve survival in patients with LS-SCLC.

PMID: 41529214 [Indexed for MEDLINE]

34. Nat Med. 2026 Mar 24. doi: 10.1038/s41591-026-04253-5. Online ahead of print.

AI-based chest X-ray prioritization in the lung cancer diagnostic pathway: the Lung IMPACT randomized controlled trial.

Prioritizing artificial intelligence (AI)-detected imaging findings may reduce the time to diagnosis of lung cancer. This prospective, multicentre, randomized controlled trial tested whether immediate AI prioritization of primary care-requested chest X-rays (CXR) influenced time to computed tomography (CT) and lung cancer diagnosis, the primary outcomes. Secondary outcomes included the number of urgent suspected lung cancer referrals, incidence and stage of lung cancer, times to urgent referral and treatment, concordance between AI and radiology reports, and algorithm accuracy. AI was available in both study arms, with AI prioritization randomized by day. Of 97,731 participant CXRs, 4,405 were excluded due to data compliance issues or failure of randomization, resulting in 93,326 CXRs analyzed (45,987 and 47,339 in the prioritization 'on' or 'off' arms, respectively). A total of 13,347 CTs were identified, with 2,766 performed within 14 days of CXR. Median (interquartile range) times to CT were 53 days (17-145) and 53 days (19-141), with and without AI prioritization, corresponding to a ratio of geometric means of 0.97 (95% confidence interval (CI) = 0.93-1.02; P = 0.31). When restricted to CTs performed within 14 days of CXR, the median time to CT was 8 days (5-11) in both groups. Lung cancer was diagnosed in 558 people (0.6% of CXRs). Median times to diagnosis were 44 days (26-90) and 46 days (24-105) respectively, with a ratio of geometric means of 0.98 (95% CI = 0.83-1.16; P = 0.84). No significant differences were observed in time to lung cancer referral (14 versus 15 days; P = 0.13), time to treatment (76 versus 72.5 days; P = 0.99) or stage at diagnosis (P = 0.34). Discordance between AI and radiology reports occurred in 28,261 CXRs (30.3%) and expert radiology review identified actionable findings in 6,750 cases (23.9%). AI prioritization of CXR requested by UK primary care has no significant impact on the lung cancer pathway. Therefore, CXR AI deployments should not include worklist prioritization in this context. Future research should differentiate between primary pathway changes and the direct impact of AI. ISRCTN registration: 78987039.

PMID: 41876649

35. J Clin Oncol. 2026 Mar;44(7):553-564. doi: 10.1200/JCO-25-01828. Epub 2026 Jan 13.

Adjuvant Durvalumab in Completely Resected Early-Stage Non-Small Cell Lung Cancer.

PURPOSE: Adjuvant immunotherapy improved patient outcomes in two trials in completely resected non-small cell lung cancer (NSCLC), but with conflicting primary end point results. The Canadian Cancer Trials Group BR.31 trial evaluated adjuvant durvalumab in completely resected early-stage NSCLC.

METHODS: Following resection of stage IB (≥4 cm) to IIIA NSCLC (American Joint Committee on Cancer 7th Edition) and optional adjuvant chemotherapy, patients were randomly assigned 2:1 to durvalumab 20 mg/kg or placebo 20 mg/kg once every 4 weeks for 12 cycles. Random assignment was stratified by stage, extent of nodal dissection, tumor cell (TC) PD-L1 expression, adjuvant chemotherapy use, and center. The primary end point was investigator-assessed disease-free survival (DFS). Secondary outcomes included overall survival (OS), adverse events, and quality of life. The primary analysis was in the subgroup with cancers that had a PD-L1 TC expression ≥25%, no common activating EGFR mutations (EGFR-), and no ALK gene rearrangements (ALK-). Secondary analyses in hierarchical order included DFS in the subgroup whose tumors were EGFR-/ALK- with PD-L1 TC ≥1%, followed by all patients whose tumors were EGFR-/ALK-, followed by OS in the same primary and secondary subgroups in the same hierarchical order.

RESULTS: Of 1,415 patients randomly assigned, 1,219 (86%) had EGFR-/ALK-tumors: 815 randomly assigned to durvalumab and 404 to placebo. With a median follow-up of 60 months, there were no differences in DFS between patients assigned durvalumab (316) versus placebo (161) in the primary population (stratified hazard ratio [HR], 0.93 [95% CI, 0.71 to 1.25]; P = .64) or in the secondary populations. Grade 3 to 4 adverse events were higher in durvalumab-treated patients (D = 26% v P = 20%).

CONCLUSION: Adjuvant durvalumab following complete resection was not associated with improvement in DFS compared with placebo in EGFR-/ALK- NSCLC, regardless of PD-L1 status.

PMID: 41529222