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Relevant Articles About Research and Clinical Trials in Lung Cancer

RELATED :SCLC (Small Cell Lung Cancer):NSCLC (Non-Small Cell Lung Cancer)

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OncWeekly Featured Trials

NSCLC (Non-Small Cell Lung Cancer)Datopotamab deruxtecanPembrolizumabRilvegostomigActiveAustraliaAustriaBelgiumBrazilCanadaGermanyHungaryIndiaItalyJapanKorea, Republic ofPolandSpainTaiwanTurkeyUnited KingdomUnited States 9NCT06357533Phase 3TROPION-Lung10
Phase III, Open-label, Study of First-line Dato-DXd in Combination With Rilvegostomig for Advanced Non-squamous NSCLC With High PD-L1 Expression (TC ≥ 50%) and Without Actionable Genomic Alterations

Phase III, Open-label, Study of First-line Dato-DXd in Combination With Rilvegostomig for Advanced Non-squamous NSCLC With High PD-L1 Expression (TC ≥ 50%) and Without Actionable Genomic Alterations

NSCLC (Non-Small Cell Lung Cancer)Datopotamab deruxtecanOsimertinibActiveAustraliaBrazilCanadaChinaGermanyItalyKorea, Republic ofPolandSpainTaiwanThailand 9NCT06350097Phase 3TROPION-Lung14
Phase III, Open-label Study of First-line Osimertinib With or Without Datopotamab Deruxtecan for EGFRm Locally Advanced or Metastatic Non-small Cell Lung Cancer

Phase III, Open-label Study of First-line Osimertinib With or Without Datopotamab Deruxtecan for EGFRm Locally Advanced or Metastatic Non-small Cell Lung Cancer

MelanomaNSCLC (Non-Small Cell Lung Cancer)Other CancersSCC (Squamous Cell Carcinoma)Biological: T3011Combination Product: T3011 + pembrolizumabRecruitingAustraliaUnited States 0NCT04370587Phase 1Phase 2
A Clinical Study of Intratumoral MVR-T3011 (T3011) Given as a Single Agent and in Combination With Intravenous Pembrolizumab in Participants With Advanced or Metastatic Solid Tumors

A Clinical Study of Intratumoral MVR-T3011 (T3011) Given as a Single Agent and in Combination With Intravenous Pembrolizumab in Participants With Advanced or Metastatic Solid Tumors

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En Bloc Resection in NSCLC Feasibility and Outcomes

KEY TAKEAWAYS

  • The study aimed to evaluate the safety and efficacy of en bloc surgery vs. conventional surgery for resectable NSCLC.
  • Researchers revealed that en bloc surgery is feasible for patients with potentially N-positive NSCLC.

Non-small-cell lung cancer (NSCLC) is a common type of lung cancer often treated with surgical resection. While conventional surgery involves separating the affected lobe and lymph nodes, en bloc surgery is a novel technique that removes them as a single unit.

Toshiyuki Nagata and the team aimed to compare en bloc surgery with conventional surgery in terms of surgical outcomes and survival rates in patients with NSCLC.

The study retrospectively reviewed patients who underwent lobectomy and lymph node dissection for stages I-III NSCLC. Using propensity score-matching to minimize bias, researchers compared 317 pairs of patients who underwent either en bloc or conventional surgery. The primary outcomes were surgical parameters (operation time, blood loss, postoperative complications) and survival rates.

The results demonstrated that en bloc surgery was not associated with increased operative time, blood loss, or postoperative complications compared to conventional surgery. While the number of resected lymph nodes and the rate of N upstaging were comparable between groups, en bloc surgery was linked to a statistically significant improvement in overall survival (OS) (P= 0.012). This survival advantage was particularly notable in patients with pathologically confirmed N-positive disease (P= 0.005), but not in those with N-negative disease.

The study suggested that en bloc surgery is a safe and feasible technique for patients with resectable NSCLC, potentially offering a survival benefit, especially in cases of N-positive disease. Further research is warranted to confirm these findings and determine the optimal patient population for this surgical approach.

No funding information was given.

Source: https://pubmed.ncbi.nlm.nih.gov/39231734/

Nagata T, Aoki M, Maeda K, et al. (2024). ‘En Bloc Resection of a Primary Tumor and Lymph Nodes in Non-Small-Cell Lung Cancer.” Ann Thorac Cardiovasc Surg. 2024;30(1):10.5761/atcs.oa.24-00108. doi:10.5761/atcs.oa.24-00108

Real-World Benefits of Trilaciclib in ES-SCLC Treatment

KEY TAKEAWAYS

  • The study aimed to assess trilaciclib’s real-world impact on SN in ES-SCLC.
  • The primary endpoint was to evaluate SN incidence during treatment.
  • Researchers noticed that trilaciclib improved safety without affecting survival outcomes in ES-SCLC.

Trilaciclib has demonstrated significant reductions in severe neutropenia (SN) incidence compared to placebo plus carboplatin, etoposide, ± atezolizumab (PEA) in patients with extensive-stage small cell lung cancer (ES-SCLC). However, its real-world application remains underutilized. Joseph Elijah and the team aimed to assess the real-world effectiveness and safety of trilaciclib in ES-SCLC treatment to better understand its practical benefits in clinical settings.

Trilaciclib has demonstrated significant reductions in SN incidence compared to PEA in patients with ES-SCLC. However, its real-world application remains underutilized.

Joseph Elijah and the team aimed to assess the real-world effectiveness and safety of trilaciclib in ES-SCLC treatment to better understand its practical benefits in clinical settings.

They conducted a comprehensive analysis comparing trilaciclib + PEA (PEAT) to PEA in patients with ES-SCLC. This single-center study covered April 1, 2021, to July 31, 2022, for PEAT recipients and February 1, 2020, to February 28, 2021, for PEA recipients. The primary endpoint assessed was the incidence of SN after cycle 1 and throughout the treatment period, while secondary endpoints focused on myelopreservation and patient outcomes.

About 34 patients in the PEAT cohort and 44 patients in the PEA cohort were analyzed. Baseline characteristics were comparable, except for a higher median age (69 vs 64 years) and a greater proportion of males (64.7% vs 38.6%) in the PEAT group. The PEAT cohort exhibited a lower SN rate (3%) compared to the PEA cohort (18%), with statistical significance demonstrated on multivariate analysis (P = 0.015). Furthermore, the PEAT cohort showed significant reductions in red blood cell transfusion requirements (3% vs 23%; P = 0.02), grade 3-4 anemia (6% vs 25%; P = 0.03), and grade 3-4 thrombocytopenia (0% vs 11%; P = 0.045).

The study concluded that trilaciclib, in combination with PEA, significantly improved the safety profile by reducing SN and related complications without compromising survival outcomes in patients with ES-SCLC. These findings highlight the potential benefits of incorporating trilaciclib into real-world clinical practice to enhance patient care.

The study received open-access funding provided by Northeastern University Library.

Source: https://pubmed.ncbi.nlm.nih.gov/39215800/

Elijah J, Jain P, Holdsworth A, et al. (2024). “Trilaciclib use in extensive-stage small cell lung cancer (ES-SCLC): are clinical benefits seen in the real-world setting?” Support Care Cancer. 2024;32(9):622. Published 2024 Aug 31. doi:10.1007/s00520-024-08828-1

Impact of TLS Density and Prognosis in NSCLC

KEY TAKEAWAYS

  • The study aimed to investigate TLS density and distribution in different regions of NSCLC.
  • Researchers found that higher E-TLS density in the IM region predicts poorer NSCLC outcomes, likely due to TLS maturation inhibition by suppressive cells.

Tertiary lymphoid structures (TLS), which are organized clusters of tumor-infiltrating immune cells within the tumor immune microenvironment (TIME), are crucial for the development and anti-tumor immunity in various cancers, such as liver, colon, and gastric cancers.

Although previous research has shown TLS presence in intra-tumoral (IT), invasive margin (IM), and peri-tumoral (PT) regions at different maturity stages, the density of TLS in different regions of non-small cell lung cancer (NSCLC) has not been thoroughly explored.

Shuyue Xin and the team sought to evaluate TLS density across these NSCLC regions and examine its association with patient prognosis.

They performed an inclusive analysis of 82 patients with NSCLC, assessing TLS and tumor-infiltrating immune cells using immunohistochemistry (IHC) staining. Tumor samples were divided into 3 subregions: IT, IM, and PT. TLS were classified as early/primary TLS (E-TLS) or secondary/follicular TLS (F-TLS).

The distribution of TLS in different maturity statuses was evaluated, along with their correlation with clinicopathological characteristics and prognostic value. Nomograms were used to predict the probability of 1-, 3-, and 5-year overall survival (OS) in patients with NSCLC.

Regarding the density of TLS and the proportion of F-TLS, the IT region exhibited significantly higher values (90.2%, 0.45/mm², and 61.0%, respectively) compared to the IM region (72.0%, 0.18/mm², and 39.0%, respectively) and the PT region (67.1%, 0.16/mm², and 40.2%, respectively).

A lower density of TLS, particularly E-TLS, in the IM region, was associated with a better prognosis in patients with NSCLC. CD20+ B cells, CD3+ T cells, CD8+cytotoxic T cells, and CD68+ macrophages were significantly overexpressed in the IM region.

There was a significant correlation between CD20+ B cells and CD3+ T cells in the IM region with the density of E-TLS, while no statistically significant correlation was observed with F-TLS. The E-TLS density in the IM region and the TNM stage were identified as independent prognostic factors for patients with NSCLC. Additionally, the nomogram demonstrated good prognostic ability.

The study concluded that a higher density of E-TLS in the IM region correlates with worse prognosis in patients with NSCLC, potentially due to the inhibition of TLS maturation caused by the increased density of suppressive immune cells at the tumor invasion front.

This study was funded by the United Fund of the Second Hospital of Dalian Medical University and Dalian Institute of Chemical Physics, Chinese Academy of Sciences (UF-ZD-202011), and Project of Science and Technology of Liaoning Province (2023-MS-272).

Source: https://pubmed.ncbi.nlm.nih.gov/39192984/

Xin S, Wen S, He P, et al. (2024). “Density of tertiary lymphoid structures and their correlation with prognosis in non-small cell lung cancer.” Front Immunol. 2024;15:1423775. Published 2024 Aug 13. doi:10.3389/fimmu.2024.1423775

Impact of ct-DNA Dynamics on Survival in EGFR-M NSCLC

Impact of ct-DNA Dynamics on Survival in EGFR-M NSCLC

KEY TAKEAWAYS

  • The study aimed to investigate how baseline detection and early clearance of EGFR ct-DNA in plasma affect survival outcomes in advanced EGFR-m NSCLC.
  • Researchers found that ct-DNA persistence at first follow-up predicts worse PFS and OS.

To determine if circulating tumor DNA (ct-DNA) dynamics of epidermal growth factor receptor (EGFR) mutation in plasma can identify a subset of patients with EGFR-mutant (EGFR-m) non-small cell lung cancer (NSCLC) with inferior survival outcomes, we analyzed and compared survival outcomes among patients with and without baseline presence and early clearance of EGFR ct-DNA in plasma.

A Joel and the team conducted a study involving patients with advanced EGFR-m NSCLC, examining the impact of ct-DNA detection at baseline and its clearance at first follow-up on progression-free survival (PFS) and overall survival (OS).

They performed an inclusive analysis involving 66 patients newly diagnosed with EGFR-m NSCLC. Plasma samples were collected at baseline and at the first response assessment, conducted between 12 and 24 weeks, for ct-DNA extraction. The ct-DNA (EGFR exons 18, 19, 20, and 21) was quantified using droplet digital polymerase chain reaction (dd-PCR) on the QX200 ddPCR system (BioRad, USA). Patients with detectable EGFR ct-DNA at baseline and either undetectable or persistent detectable ct-DNA in follow-up samples were classified as clearers and non-clearers, respectively.

About 53 patients received 1st/2nd generation EGFR tyrosine kinase inhibitors (TKIs), while 13 patients were treated with either a 3rd generation TKI (osimertinib) or chemotherapy plus gefitinib. The baseline ct-DNA-positive group exhibited a higher prevalence of extra thoracic disease (60.4% vs. 48.5%). For the entire cohort, there was no significant difference in median PFS between baseline ct-DNA-negative (13.57 months) and ct-DNA-positive patients (12.32 months) (HR 0.74).

However, a significant improvement in PFS was observed among early ct-DNA clearers compared to non-clearers (12.32 months vs. 9.92 months; HR 0.57). For patients treated with 1st/2nd generation EGFR TKIs, the improvement in median PFS among early ct-DNA clearers versus non-clearers was even more pronounced (11.76 months vs. 6.8 months; HR 0.34).

The study concluded that baseline detection of ct-DNA for EGFR mutations in plasma was not predictive of first-line (1L) PFS but was associated with extra thoracic disease. Persistence of ct-DNA at the first follow-up correlated with worse PFS and OS compared to those who cleared ct-DNA from plasma, particularly among patients treated with 1st/2nd generation EGFR TKIs.

This study was funded by the Department of Science and Technology and the Government of India.

Source: https://pubmed.ncbi.nlm.nih.gov/39183550/

Joel A, Abarna R, Chacko RT, et al. (2024). “Analysis of the effect of baseline detection and early clearance of ct-DNA, on survival outcomes among patients with advanced EGFR-mutant non-small cell lung cancer.” Analýza efektu detekce časné clearance ct-DNA při baseline na přežití u pacientů s pokročilým EGFR mutovaným nemalobuněčným karcinomem plic. Klin Onkol. 2024;38(1):40-49. doi:10.48095/ccko202440

Segmentectomy vs Lobectomy: Effects on NSCLC Recovery

KEY TAKEAWAYS

  • The study aimed to compare segmentectomy and lobectomy by analyzing postoperative cardiopulmonary function and serum tumor markers.
  • Results showed segmentectomy better preserves lung function and reduces oxidative stress in NSCLC, with minimal impact on tumor markers.

In patients with early non-small cell lung cancer (NSCLC), single-port thoracoscopic anatomical segmentectomy is a common treatment. However, lung function recovery is slow post-surgery. In contrast, anatomical segmental pneumonectomy, which removes less lung tissue, might lead to faster recovery.

Yiting Shi and the team aimed to compare 2 surgical approaches by analyzing postoperative changes in cardiopulmonary function and serum tumor markers.

Researchers conducted a retrospective analysis of 120 patients with NSCLC from October 2020 to October 2023. Patients were divided into 2 groups based on their surgical intervention.The pulmonary segmentectomy group, which underwent uniportal video-assisted thoracoscopic anatomical pulmonary segmentectomy (n=57), and the lobectomy group, which received uniportal video-assisted thoracoscopic anatomical lobectomy (n=63).

Surgical parameters and perioperative stress indicators were recorded for both groups. Additionally, they compared cardiopulmonary function indicators and serum biomarker levels before and three months after surgery.

The segmentectomy group had a longer operation time and higher intraoperative blood loss compared to the lobectomy group. However, the segmentectomy group had shorter postoperative hospital stays, less chest drainage volume, and shorter drainage tube indwelling times (P< 0.001).

Post-treatment, the segmentectomy group showed higher forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and maximal voluntary ventilation (MVV) compared to the lobectomy group (P< 0.001).

Additionally, stroke volume (SV) and left ventricular ejection fraction (LVEF) were higher in the segmentectomy group (P< 0.001). There were no significant differences in carbohydrate antigen 50 (CA50), carcinoembryonic antigen (CEA), or cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) levels between the groups after treatment (P> 0.05). After 1 day surgery, levels of epinephrine (E), norepinephrine (NE), and cortisol (Cor) were lower in the segmentectomy group (P< 0.001).

The study concluded that anatomical pulmonary segmentectomy for NSCLC better reduces surgery-induced damage to cardiopulmonary function and lowers perioperative oxidative stress compared to uniportal video-assisted thoracoscopic lobectomy. Both surgical approaches, however, have minimal effects on serum tumor marker levels.

No funding information was provided.

Source: https://pubmed.ncbi.nlm.nih.gov/39186341/

Shi Y, Xiao S. (2024). “Effect of Anatomical Pulmonary Segmentectomy and Lobectomy under Uniportal Video-Assisted Thoracoscopic Surgery on Cardiopulmonary Function and Serum Tumor Markers in Patients with Early-Stage Non-Small Cell Lung Cancer.” Ann Ital Chir. 2024;95(4):593-602. doi:10.62713/aic.3462

ERAS Boosts Recovery and Lowers Costs for VATS Lobectomy

KEY TAKEAWAYS

  • The study aimed to evaluate the clinical effects of ERAS in patients with NSCLC undergoing VATS lobectomy.
  • Researchers provided strong evidence for the effectiveness of ERAS guidelines in improving outcomes for patients undergoing VATS lobectomy.

Enhanced Recovery After Surgery (ERAS) guidelines are a set of evidence-based interventions and care measures aimed at optimizing recovery after surgery and reducing postoperative complications, including those in patients with non-small cell lung cancer (NSCLC).

Yinhui Xu and the team aimed to assess how ERAS measures and care bundles can reduce post-operative complications and enhance recovery for patients undergoing video-assisted thoracic surgery (VATS) lobectomy.

The study included 120 patients, divided into 2 groups including a control group receiving routine care and an observation group following ERAS guidelines. The ERAS group received a bundle of care, incorporating various evidence-based treatments and care measures.

Researchers collected data on baseline characteristics, clinical parameters, and postoperative outcomes for both groups.

There were no significant differences in gender, age, TNM stages, smoking, or drinking between the ERAS and non-ERAS groups (P> 0.05). Likewise, no significant differences were found in cardiac ejection fraction (≥50%), FEV1%, forced vital capacity (FVC), lymphocytes, neutrophils (%), or tumor diameter (P> 0.05).

However, significant differences were observed in FVC, FEV1%, DLCO SB, albumin, C-reactive protein, leukocytes, monocytes, lymphocytes (%), hemoglobin, and neutrophils between the 2 groups (P< 0.05). ROC analysis identified leukocytes, DLCO, CRP, FEV1%, monocytes, lymphocytes (%), neutrophils (%), and BMI as key predictors for ERAS effectiveness.

Cutoff values for leukocytes >12.5, FEV1% >112.9, monocytes >16.8 (109/L), and neutrophils >11.6 indicated a higher likelihood of rapid recovery in patients undergoing VATS lobectomy. Integrating ERAS measures with care bundles reduced extubation time to less than 5.5 days, VAS score to below 3.5, and post-operative hospital stay to under 10.5 days.

The study concluded that ERAS management measures based on care bundles can significantly enhance the prognosis for patients undergoing VATS lobectomy, reduce post-operative complications, and expedite safe rehabilitation.

Additionally, these measures can shorten hospital stays, lower overall healthcare costs, and ease social and family burdens. Notable differences may be linked to factors such as leukocytes, FEV1%, monocytes, and neutrophils.

No funding information was provided.

Source: https://pubmed.ncbi.nlm.nih.gov/39186349/

Xu Y, Liang G, Wang W, et al. (2024). “Clinical Effects of Enhanced Recovery after Surgery in Perioperative Period Patients with Video-Assisted Thoracoscopic Lobectomy.” Ann Ital Chir. 2024;95(4):583-592. doi:10.62713/aic.3386

Curcumin Targets ATOX1 to Reduce Copper in NSCLC Cells

KEY TAKEAWAYS

  • The study aimed to explore curcumin’s effects on the AToX1-mediated copper pathway in NSCLC.
  • Curcumin suppresses copper accumulation in NSCLC cells by binding to ATOX1, revealing a potential therapeutic mechanism.

Non-small cell lung cancer (NSCLC) is linked to the accumulation of copper within cells. Antioxidant 1 (ATOX1) acts as a copper chaperone, playing a role in copper transport and regulation within the cell. Understanding the mechanisms involving copper metabolism in NSCLC is crucial for developing targeted therapies.

Xiao Qin and the team investigated the anti-cancer effects of curcumin on the ATOX1-mediated copper pathway in NSCLC, exploring its potential as a therapeutic strategy.

Researchers assessed the binding activity between curcumin and ATOX1 through molecular docking. The NSCLC cell lines, A549 and H1299, were treated with varying doses of curcumin (10, 20, 40 µM) or DC-AC50 (5, 10, 20 µM) for 24 hours. They also monitored cell viability and ATOX1, ATP7A, and COX17 protein levels.

Cells overexpressing ATOX1 were created using pcDNA3.1-ATOX1 transfection for 24 hours. These overexpressing cells were then treated with 40 µM curcumin or 20 µM DC-AC50 to explore curcumin’s mechanism in NSCLC treatment. Cell viability was measured using CCK-8, and western blotting determined protein levels. Copper levels in cells were labeled using copper sensor-1.

Additionally, A549 cell injected nude mice were treated with either 20 mg/kg/day DC-AC50 or 40 mg/kg/day curcumin, and tumor growth was assessed by measuring tumor volume and weight. The ATOX1, ATP7A, and COX17 levels in tumors were analyzed using immunohistochemistry and western blotting.

The results showed that curcumin demonstrated a binding affinity to ATOX1 (score =-6.1 kcal/mol), leading to decreased ATOX1, ATP7A, and COX17 protein levels in NSCLC cells. Both curcumin and DC-AC50 treatments reduced cell viability by inhibiting the ATOX1-mediated copper signaling pathway in these cells.

However, cells overexpressing ATOX1 showed a significantly reduced response to curcumin’s effects on copper accumulation and the pathway (P<0.05). In mouse models, treatments with curcumin or DC-AC50 also inhibited tumor growth by targeting the ATOX1-mediated copper pathway.

The study concluded that curcumin binds to ATOX1, effectively suppressing copper accumulation in NSCLC cells. This finding reveals a novel mechanism through which curcumin may serve as a potential therapeutic strategy for treating NSCLC.

The study was funded by the Qilu Traditional Chinese Medicine Advantageous Speciality Cluster Construction Project and the Project of Yantai Science and Technology Plan.

Source: https://pubmed.ncbi.nlm.nih.gov/39169392/

Qin X, Wang P, Liang H, et al. (2024). “Curcumin suppresses copper accumulation in non-small cell lung cancer by binding ATOX1.” BMC Pharmacol Toxicol. 2024;25(1):54. Published 2024 Aug 21. doi:10.1186/s40360-024-00784-0

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