Accurate diagnosis and staging of lung cancer are critical for optimal clinical management. Fibroblast activation protein inhibitor (FAPI) imaging has emerged as a promising modality with superior detection capabilities for lung cancer. We hypothesized that [1⁸F]FAPI-42 PET/CT would enhance diagnosis, TNM staging, and influence oncologic management in patients with suspected or confirmed lung cancer.

In this retrospective study, 155 patients with clinically suspected or confirmed lung cancer underwent both conventional imaging and [1⁸F]FAPI-42 PET/CT scans within a one-week interval, without any intervening treatment. Lesions were visually assessed and categorized to evaluate the diagnostic capability of [18F]FAPI-42 PET/CT. Tracer activity was quantified using maximum standardized uptake values (SUVmax) and tumor-to-background ratios. TNM staging was independently determined by a board-certified radiologist or nuclear medicine physician using both imaging modalities, and discrepancies were assessed. Changes in TNM staging were documented and evaluated for their impact on clinical management.

Of the 155 patients, 99 were evaluated for primary lesion diagnosis and staging. Pathological examination confirmed malignant tumors in 87 patients and benign tumors in 12. The diagnostic sensitivity and positive predictive value of [18F]FAPI-42 PET/CT for detecting primary lung tumors were 96.77% and 92.78%, respectively. Malignant lesions exhibited significantly higher SUVmax compared to benign lesions (5.2 vs. 1.5, P = 0.0002), with an area under the ROC curve of 0.87. In total, 1,556 malignant lesions were identified among patients with lung cancer, and [18F]FAPI-42 PET/CT demonstrated a diagnostic accuracy of 95.50%. However, its sensitivity for detecting adrenal metastases was lower at 33.33%, with a specificity of 100% and an accuracy of 53.85%. The use of [18F]FAPI-42 PET/CT resulted in changes in TNM staging for 46% of patients, leading to upstaging in 58 patients and downstaging in 5. These staging adjustments directly impacted clinical management in 34 patients, prompting modifications in treatment plans.

[18F]FAPI-42 PET/CT is a promising modality for lung cancer diagnosis and staging, demonstrating high sensitivity and specificity. Its use significantly altered TNM staging in nearly half of the patients, directly impacting oncologic management and treatment planning. However, its limited sensitivity for detecting adrenal metastases underscores the need for additional imaging techniques.

Despite curative surgery for lung cancer, 30% to 55% of patients experience recurrence or death, which highlights the importance of adjuvant treatment. Adjuvant osimertinib therapy effectively prolongs disease-free and overall survival in patients with lung cancer harboring common epidermal growth factor receptor (EGFR) mutations. To identify potential candidates for adjuvant osimertinib, it is crucial to understand the rates and identify risk factors of recurrence.

This multicenter, retrospective cohort study was conducted in the Republic of Korea and enrolled patients who, between 2010 and 2017, underwent resection of stages I-III adenocarcinomas, with common EGFR mutations. The primary outcomes comprised the rate and risk factors of postoperative recurrence.

Among the 759 participants, the overall recurrence rate and median recurrence-free survival were 39.1% and 59.8 (interquartile range [IQR], 26.3-84.2) months, respectively, during a median follow-up of 73.0 (IQR, 55.4-95.0) months. The recurrence rates for stages IA, IB, IIA, IIB, IIIA, and IIIB were 14.7%, 45.5%, 53.8%, 72.5%, 80.3%, and 93.3%, respectively. Multivariate analysis revealed that age ≥ 65 years, body mass index < 18.5 kg/m², the Del19 subtype of EGFR mutation, tumor size ≥ 2.3 cm, N1 involvement, N2 involvement, predominantly micropapillary or solid pattern, and the presence of visceral pleural invasion were independently associated with recurrence.

This multicenter cohort study demonstrated that stages I-III EGFR-mutated adenocarcinoma has a postoperative recurrence rate of 39.1%, and identified 7 independent risk factors for recurrence.

Preoperative invasive nodal staging is standard of care for early-stage non-small cell lung cancer (NSCLC). Complications and delays in care are not negligible and diagnostic accuracy varies. In our system, invasive nodal staging is performed for clear radiographic indications (node > 1.0 cm short axis or standardized uptake value > 3.0, tumor > 4.0 cm). This study assessed whether unexpected mediastinal upstaging was less common in patients receiving preoperative invasive nodal staging.

This retrospective study evaluated nodal upstaging, defined as pathological N2 or IIIA+ disease, based on receipt or non-receipt of invasive nodal staging. Clinical stage I-II NSCLC patients who underwent resection (2009-2019) were identified from our cancer registry. Stage and preoperative nodal staging information were confirmed through chart review. Associations between patient characteristics, invasive nodal staging receipt, and clinical to pathological stage changes were analyzed.

Among 2576 patients, 18.7% (n = 481) underwent invasive nodal staging. After resection, 6.2% of all patients had nodal upstaging and 24.9% had TNM upstaging. Only 0.3% (n = 9) were upstaged to N2 and 0.5% (n = 13) were upstaged to IIIA+. Lack of preoperative nodal sampling was not associated with N2 or IIIA+ upstaging. Findings were consistent in subanalyses of patients with surgical specimens meeting Commission on Cancer nodal sampling criteria and with clinical IB+ disease.

Although most patients did not undergo invasive nodal staging, <1% had unexpected N2 on surgical pathology. There was no association between lack of preoperative invasive nodal sampling and N2 nodal upstaging. Preoperative invasive nodal staging did not increase pathologic N2 nodal upstaging in early-stage NSCLC patients in our integrated health system.

Stereotactic body radiotherapy is pivotal in the treatment of lung tumors, demonstrating effective local control. However, challenges persist with intra-fractional anatomical changes and organs at risk during delivery. Magnetic resonance-guided online adaptive stereotactic body radiotherapy (MRgSBRT) represents a novel technique promising to achieve safe delivery of ablative doses with improved outcomes for primary lung tumors or lung oligometastases.

In this single-institution retrospective analysis, we evaluated 64 patients (92 lesions) with primary lung cancer or lung oligometastases treated with MRgSBRT. Using Kaplan-Meier method and log-rank test; we estimated local control (LC), local progression-free survival (LPFS), distant progression-free survival (DPFS), and overall survival (OS).

A total of 64 patients (92 lesions) treated with MRgSBRT were included comprising 14.1% primary lung cancer lesions and 85.9% lung oligometastases. Median total dose, fraction number, fraction dose and BED10 were 50 Gy (range, 21-70 Gy), 5 (range, 1-10), 10 Gy (range, 6-34 Gy), 100 Gy (range, 48-180.0 Gy) respectively. Of the 420 fractions administered, 88.6% (n = 372) involved on-table adapted plans. Median LPFS was not reached and the 1‑ and 3‑year LPFS rates were 96.3% (95% CI 92.4-100.0%) and 86.4% (95% CI 76.9-95.9%), respectively. No local recurrences were observed post-treatment with a total dose of > 50 Gy, BED10 > 100 Gy, fractional dose of > 10 Gy or a CCI > 0.96.

Our study of MRgSBRT in 92 lung lesions revealed a 1-year and 3‑year LPFS rates of 96.3 and 86.4%, respectively without ≥ grade 3 toxicity. Future prospective studies evaluating lung MRgSBRT are awaited.

Recent therapeutic advancements for non-metastatic non-small cell lung cancer (NSCLC) have increased the need for real-world baselines against which future changes in patient management and clinical outcomes can be compared.

Data on patient characteristics, initial treatment, and overall survival (OS) were derived from adult patients diagnosed with stage I-IIIC NSCLC (2010-2020) in a regional Canadian database (Oncology Outcomes [O2]), an English national registry (Cancer Analysis System [CAS]), and four regional German registries (VONKOdb) and retrospectively analyzed separately using analogous methodology.

Data from 85,433 patients were analyzed. Stage at diagnosis varied, with proportions with stage I NSCLC ranging from 30.9% (VONKOdb) to 44.2% (O2) and with stage III disease from 36.9% (O2) to 48.5% (VONKOdb). Across the data sources, proportions receiving surgery ± other treatments were similar for stages I and II, but decreased through stages IIIA, IIIB, and IIIC (range, 24.7-42.7%, 4.6-21.8%, and 0.9-7.5%, respectively). Overall, 70.3-85.2% of patients received active treatment for NSCLC, with a trend toward lower proportions among those with stage III disease. Reached median OS tended to be longest in patients with resected stage I/II NSCLC (range, 28.8-128.0 months) and shortest in patients with stage IIIB/IIIC disease treated with systemic anticancer therapy (SACT) alone, radiotherapy alone, or SACT + palliative radiotherapy (range, 4.8-21.2 months).

These data provide insights into treatment pathways and survival outcomes before the widespread use of immunotherapy-based and targeted therapies and will serve as an important baseline for future evaluations of emerging treatments for patients with non-metastatic NSCLC.

Postoperative adjuvant epidermal growth factor receptor (EGFR) inhibitor osimertinib is the standard care for stage IB-IIIB non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutation, following complete tumour resection, with or without prior platinum-based adjuvant chemotherapy. However, the role of EGFR tyrosine kinase inhibitors (TKIs) in this setting is debated, particularly concerning long-term curative effects versus recurrence delay. Uncertainties persist around treatment duration, harms, and effectiveness across disease stages, prior chemotherapy, or EGFR-sensitising mutation types.

To assess the effectiveness and harms of adjuvant EGFR tyrosine kinase inhibitors (TKIs) in people with resected stage I to III non-small-cell lung cancer (NSCLC) harbouring an activating EGFR mutation.

We searched major databases (CENTRAL, MEDLINE, Embase) to 9 December 2024, along with conference proceedings (from 2019) and clinical trial registries.

We included randomised controlled trials (RCTs) reporting benefits or harms of adjuvant EGFR TKIs in adults with resected stage I-III NSCLC. Trials compared EGFR TKIs with platinum-based chemotherapy, placebo/best supportive care (BSC), or second-and/or third-generation EGFR TKIs versus first- and/or second-generation EGFR TKIs. Participants were adults with histologically confirmed stage I-III NSCLC.

Three review authors independently assessed search results, resolving disagreements with a fourth author. Primary outcomes were overall survival (OS), disease-free survival (DFS), and adverse events (AEs); secondary outcomes included health-related quality of life (HRQoL), relapse risk during drug-off time, and brain relapse risk. We conducted meta-analyses using random-effects and fixed-effect models with hazard ratios (HRs) or risk ratios (RRs) and 95% confidence intervals (CIs). We assessed heterogeneity with the I² statistic.

We included nine RCTs involving 2603 participants, and identified six ongoing trials. Five trials compared EGFR TKIs with placebo/BSC, and four compared them with chemotherapy. We found no trials comparing second-and/or third-generation to first- and/or second-generation EGFR TKIs. Six trials had low selection bias risk; most had unclear or high risk for detection or performance bias; and four were high risk for other biases. The certainty of the evidence (GRADE) ranged from moderate to very low, depending on the outcome. First-, second-, and/or third-generation EGFR TKIs versus placebo/BSC EGFR TKIs probably improve overall survival compared to placebo/BSC (HR 0.54, 95% CI 0.40 to 0.73; 3 studies, 864 participants; moderate-certainty evidence). TKIs may improve disease-free survival compared to placebo/BSC, but the evidence is very uncertain (HR 0.34, 95% CI 0.28 to 0.41; 5 studies, 1153 participants). We are uncertain if there is a difference between groups in serious adverse events (≥ grade 3) as the evidence is very uncertain, with wide confidence intervals spanning both potential harm and no effect (RR 2.52, 95% CI 0.44 to 14.37; 4 studies, 1134 participants). Mild-to-moderate adverse events (grades 1 and 2) may be more frequent with EGFR TKIs compared to placebo/BSC, but the evidence is very uncertain (RR 1.57, 95% CI 1.08 to 2.29; 4 studies, 1134 participants). One study assessed HRQoL, with no clinically meaningful decline compared to placebo/BSC (592 participants; moderate-certainty evidence). First-, second-, and/or third-generation EGFR TKIs versus chemotherapy Overall survival was similar between EGFR TKIs and chemotherapy (HR 0.79, 95% CI 0.52 to 1.18; 4 studies, 878 participants; moderate-certainty evidence). TKIs may have improved disease-free survival compared to chemotherapy (HR 0.54, 95% CI 0.35 to 0.83; 4 studies, 878 participants; low-certainty evidence). TKIs may have reduced serious adverse events (≥ grade 3) compared to chemotherapy (RR 0.31, 95% CI 0.18 to 0.52; 4 studies, 811 participants; low-certainty evidence). TKIs may have increased mild-to-moderate adverse events (grades 1 and 2) (RR 2.13, 95% CI 1.20 to 3.78; 4 studies, 811 participants; low-certainty evidence). Two studies assessed HRQoL, showing no clear difference compared to chemotherapy, as assessed with the Functional Assessment of Cancer Therapy-Lung instrument (2 studies, 399 participants) and the Lung Cancer Symptom Scale (2 studies, 400 participants), both with moderate-certainty evidence.

Adjuvant EGFR TKIs may improve disease-free survival compared to both placebo/BSC and chemotherapy. There is moderate-certainty evidence that EGFR TKIs increase overall survival compared to placebo/BSC. However, they likely result in little to no difference in overall survival compared to chemotherapy. We could not rule out a potential survival benefit of adjuvant chemotherapy in people with EGFR-mutant NSCLC. Approximately 50% of participants experienced relapse or death within one year of stopping TKI therapy, indicating that the disease-free survival benefit may wane after withdrawal. This raises the possibility that prolonged adjuvant TKI therapy could be associated with improved long-term outcomes, although further research is needed to clarify this.

The evolving TNM classification has emphasized the tumor size's role in NSCLC prognosis, reclassifying stage IIIA patients from the previous edition as stage IIIB (T3-4N2M0, 8th edition). However, the prognostic implications of tumor size and survival in stage III NSCLC patients undergoing neoadjuvant therapy remain unexplored. Therefore, we investigated the association between tumor size and mortality in N2 non-small cell lung cancer (NSCLC) patients undergoing neoadjuvant concurrent chemoradiotherapy followed by surgery (trimodality therapy), considering the number of metastatic N2 stations and histology. We analyzed 756 patients with stage III (T1-3N2) NSCLC who underwent trimodality therapy, excluding those with T3 tumors with invasion components or additional nodules (2003-2019). Overall survival was compared using the Cox-proportional hazards model, while the tumor size-survival relationship was estimated using restricted cubic splines. Using 8th TNM edition, 32.1%, 48.5%, and 19.3% were clinical T1, T2, and T3. During a median follow-up of 53.5 months, 398 patients died. The adjusted hazard ratios for overall survival comparing T2 and T3 to T1 were 1.46 (95% confidence interval, 1.14-1.85) and 1.48 (1.10-1.99). For the extent of clinical N2, large tumor size increased the mortality risk in patients with N2b but not in N2a. Tumor size did not increase mortality risk in squamous cell carcinoma patients; however, the mortality risk was increased with larger tumors in adenocarcinoma. These findings raise the importance of considering tumor size in treatment planning and suggesting tailored strategies.

Imaging markers for lung-brain interaction and brain metastasis of non-small cell lung cancer (NSCLC) are lacking. This study aimed to explore the effect of NSCLC on brain glucose metabolism using total-body positron emission tomography (PET) imaging.

Fifty-six healthy controls (HCs) and 42 NSCLC patients underwent total-body PET imaging. Concentrations of serum tumor markers were obtained for NSCLC patients. Pseudo-time series data of NSCLC were generated based on the tumor, node, metastasis (TNM) staging system. A novel causal metabolic covariance network (CaMCN) between NSCLC and brain glucose metabolism was conducted with maximum and mean of standardized uptake value (SULmax and SULmean), serum tumor markers as the seed series, respectively. Reliability was evaluated by reverse CaMCN analysis. Finally, post-hoc analysis was performed on brain regions that exhibited causality from NSCLC.

CaMCN analysis demonstrated significant causality from NSCLC to glucose uptake of the posterior fossa regions, the anatomic "watershed areas" and the gray-white matter junction in the frontal, temporal and occipital lobes. Reverse CaMCN analysis demonstrated significant distinctions from the original CaMCN results. Post-hoc analysis revealed that glucose uptake in the inferior temporal gyrus, thalamus, superior frontal gyrus, precentral gyrus and postcentral gyrus exhibited significant differences among HCs and different stages of NSCLC.

The proposed method can capture causal relationships from NSCLC to brain metabolism, providing pathophysiological insights into the lung-brain interaction in NSCLC. Moreover, the identified brain regions were the areas where NSCLC brain metastases frequently occur, holding the promise as biomarkers for brain metastases of NSCLC.

Proteins are fundamental biomolecules composed of one or more chains of amino acids. They are essential for all living organisms, contributing to various biological functions and regulatory processes. Alterations in protein structures and functions are closely linked to diseases, emphasizing the need for in-depth study. A thorough understanding of these associations is crucial for developing targeted and more effective therapeutic strategies.Computational analyses of biomedical data facilitate the identification of specific patterns in proteins associated with diseases, providing novel insights into their biological roles. This study introduces a computational approach designed to detect relevant sequence patterns within proteins. These patterns, characterized by specific amino acid arrangements, can be critical for protein functionality. The proposed methodology was applied to proteins targeted by drugs used in lung cancer treatment, a disease that remains the leading cause of cancer-related mortality worldwide. Given that non-small cell lung cancer represents 85-90% of all lung cancer cases, it was selected as the primary focus of this study.Significant sequence patterns were identified, establishing connections between drug-target proteins and proteins associated with lung cancer. Based on these findings, a novel computational framework was developed to extend this pattern-based analysis to proteins linked to other diseases. By employing this approach, relationships between lung cancer drug-target proteins and proteins associated with four additional cancer types were uncovered. These associations, characterized by shared amino acid sequence features, suggest potential opportunities for drug repurposing. Furthermore, validation through an extensive literature review confirmed biological links between lung cancer drug-target proteins and proteins related to other malignancies, reinforcing the potential of this methodology for identifying new therapeutic applications.

Timely initiation of treatment is a core principle of oncologic care, especially for aggressive cancers such as lung cancer. However, the real-world impact of short-term delays in treatment initiation on survival outcomes in lung cancer remains unclear. This meta-analysis evaluates the association between treatment delays of 4, 8, and 12 weeks and all-cause mortality in lung cancer patients. A systematic search was conducted in PubMed, Scopus, and Web of Science for studies published between 2000 and 2025. Of 5360 screened records, 15 studies were included, comprising 16 cohorts for overall survival of lung cancer patients. Hazard ratios (HRs) for 4-, 8-, and 12-week treatment delays were estimated using random-effects meta-analyses. Heterogeneity was measured with the I2 statistic, and publication bias was assessed using funnel plots and Egger's test. No significant association was found between treatment delay and survival at any of the time points. Pooled HRs were 1.00 (95% CI, 0.99-1.02) for a 4-week delay, 1.01 (95% CI, 0.99-1.03) for an 8-week delay, and 1.01 (95% CI, 0.98-1.05) for a 12-week delay. Despite high heterogeneity (I2 = 97%), no evidence of publication bias was detected. This meta-analysis found no significant impact of short-term treatment delays (up to 12 weeks) on mortality in lung cancer patients. These findings challenge the assumption that brief delays universally worsen outcomes and underscore the importance of individualized treatment planning and prioritization.

Immunotherapy has altered the treatment landscape for resectable non-small cell lung cancer, increasing the complexity of treatment planning. Understanding treatment patterns and outcomes prior to the advent of immunotherapy can provide context for assessing the benefit of immunotherapies and other novel agents.

We aimed to characterize real-world demographics, clinical characteristics, treatment patterns, and clinical outcomes of patients with early-stage non-small cell lung cancer before widespread immunotherapy use.

Analyses included patients from the US CancerLinQ Discovery® database diagnosed with stage I-III non-small cell lung cancer between 2014 and 2020 without known EGFR mutations who underwent surgical resection within 140 days of diagnosis. The primary outcome was treatment patterns by disease stage.

Analyses included 3077 patients with stage I (n = 1673), II (n = 853), and III (n = 551) disease. Most (92.8%, 52.3%, and 36.5% of stage I, II, and III patients) received surgery without systemic therapy. Among stage I, II, and III patients, 7.2%, 44.8%, and 46.6% received adjuvant therapy only. Of stage II and III patients, 2.0% and 10.2% received neoadjuvant therapy only, and 0.9% and 6.7% received both (stage I patients who received neoadjuvant only or perioperative therapy were excluded because of low numbers [n = 4]). Five-year overall survival rates were 73.4%, 61.9%, and 50.5% in stage I, II, and III patients; 5-year real-world relapse-free survival rates were 35.4%, 23.1%, and 14.0%. In an exploratory multivariate analysis, neoadjuvant treatment was associated with improved overall survival and real-world relapse-free survival in stage II-III patients (stage I patients not evaluable). Adjuvant treatment was associated with improved real-world relapse-free survival, but not overall survival, in stage II-III patients.

Most patients received surgery alone, though the proportion receiving systemic treatment increased with disease stage. Modest 5-year, real-world relapse-free survival rates indicate a need for more effective neoadjuvant or adjuvant treatments in this setting.

Background/Objectives: Lung cancer is the leading cause of cancer-related deaths worldwide. Non-Small-Cell Lung Cancer (NSCLC) accounts for 80-90% of all lung cancers. Antibody-Drug Conjugates (ADCs) represent an expanding targeted therapy option for the treatment of NSCLC. The aim is to perform a systematic literature review to evaluate the efficacy and safety profiles of ADCs currently undergoing clinical trials for the treatment of NSCLC. Methods: The study adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Literature searches were conducted in PubMed, ClinicalTrial.gov and Web of Science databases, covering the period from 2014 to 2024. Only randomized and non-randomized phase II-IV clinical trials focusing on ADC-based therapies for adult patients affected by NSCLC were selected. The Revised Cochrane Risk-of-Bias Tool for Randomized Trials (RoB 2.0) and the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) were used to evaluate the overall risk of bias in the included randomized and non-randomized studies, respectively. While GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology was used to assess the certainty of the evidence. Efficacy endpoints were categorized based on primary outcomes while safety was assessed through the frequency and severity of Treatment-Emergent Adverse Events (TEAEs), and a qualitative summary of the findings was conducted. Results: A total of seven studies, including three randomized, three non-randomized, and one without specific allocation, were included, comprising 1287 patients, with 693 (54%) men, and an average age of 63 years old. Two studies were deemed to have a low risk of bias, while six had a moderate risk or some concerns. Five ADCs were evaluated: trastuzumab deruxtecan (T-DXd), trastuzumab emtansine (T-DM1), telisotuzumab vedotin, patritumab deruxtecan, and datopotamab deruxtecan (Dato-DXd). T-DXd demonstrated superior efficacy in HER2-overexpressing and HER2-mutant NSCLC, with an ORR of 52.9% and 49.0%, respectively. However, HER2-mutant patients exhibited a longer median DOR (16.8 vs. 6.2 months) but a higher incidence of grade ≥ 3 TEAEs (38.6% vs. 22%). T-DM1 showed modest efficacy, with an ORR of 20% in HER2-overexpressing NSCLC and 6.7% in HER2-mutant patients. Dato-DXd demonstrated improved ORR (26.4% vs. 12.8%) and PFS (4.4 vs. 3.7 months) compared to docetaxel. Patritumab deruxtecan achieved an ORR of 39% in EGFR-mutant NSCLC, while telisotuzumab vedotin exhibited limited activity in c-MET-positive NSCLC (ORR 9%, median DOR 7.5 months). Frequency and severity of TEAEs varied across ADCs, with ILD being a major concern, highlighting the need for strict patient monitoring and early intervention to mitigate severe adverse events. Conclusions: ADCs represent a promising advancement in NSCLC treatment, offering targeted therapeutic options beyond conventional chemotherapy and immunotherapy. T-DXd has emerged as the most effective ADC for HER2-mutant NSCLC with manageable safety profile, whereas Dato-DXd provides a viable alternative for TROP2-expressing tumors. While ADCs offer significant clinical benefits, careful patient selection and proactive management of adverse events remain crucial. Ongoing and future trials will further refine the role of ADCs in personalized NSCLC treatment, potentially expanding their tumor-agnostic use to broader patient populations.

The PACIFIC trial established chemoradiation followed by 1-year durvalumab consolidation as standard of care for unresectable locally advanced non-small cell lung cancer (LA-NSCLC). This study aims to investigate therapeutic strategies and clinical outcomes after durvalumab failure in the real-world.

Patients with stage III LA-NSCLC from 23 Italian centres were retrospectively enrolled at durvalumab progression. Subsequent treatments (Sub-Tx) were prospectively collected and classified as follows:chemo-immunotherapy (subgroup-1), platinum-based chemotherapy (subgroup-2), non-platinum-based chemotherapy (subgroup-3), and targeted therapy (subgroup-4). Durvalumab progression free survival (Dur-PFS) and overall survival (Dur-OS), as well as outcomes of Sub-Tx (Sub-PFS and Sub-OS) were estimated by using the Kaplan-Meier approach.

A total of 122 patients were enrolled. Median Dur-PFS was 9.3 months (95 % CI: 7.1 - 11.4) and median Dur-OS 24.2 months (95 % CI: 18.7 - 29.7). Out of 93 patients receiving a Sub-Tx, 21.5 %, 43.0 %, 28.0 %, and 7.5 % were in the subgroup 1, 2, 3, and 4, respectively. Median Sub-PFS were 12.0, 4.1, 2.7, and 6.0 months, respectively. Patients who completed 12 months of durvalumab were 65.0 %, 27.5 %, 19.2 %, and 42.9 % across the four subgroups. In univariate analysis, the duration of durvalumab therapy was an independent factor for selecting Sub-Tx (p < 0.007). Median time to next treatment (TTNT) was 6.7 months with chemo-immunotherapy and 2.1 with chemotherapy (p = 0.009). Out of 15 patients with a TTNT > 1 year, 40 % were rechallenged with immunotherapy.

Platinum-based chemotherapy was the predominant treatment after durvalumab consolidation. Immunotherapy rechallenge was associated with the best survival outcome in selected cases, warranting further investigation.

Radiomics is a health technology that has the potential to extract clinically meaningful biomarkers from standard of care imaging. Despite a wealth of exploratory analysis performed on scans acquired from patients with lung cancer and existing guidelines describing some of the key steps, no radiomic-based biomarker has been widely accepted. This is primarily due to limitations with methodology, data analysis, and interpretation of the available studies. There is currently a lack of guidance relating to the entire radiomic workflow from study design to critical appraisal. This guide, written with early career lung cancer researchers, describes a more complete radiomic workflow. Lung cancer image analysis is the focus due to some of the unique challenges encountered such as patient movement from breathing. The guide will focus on CT imaging as these are the most common scans performed on patients with lung cancer. The aim of this article is to support the production of high-quality research that has the potential to positively impact outcome of patients with lung cancer.

Evaluate safety and efficacy of lung cancer cryoablation in patients with stereotactic body radiation therapy (SBRT) recurrence.

Between 9/2018 and 11/2023, all patients with non-small cell lung cancer (NSCLC) treated with lung cryoablation after SBRT recurrence were retrospectively identified. Histories of smoking, COPD, post-procedural pneumothorax, adverse events requiring immediate post-procedural hospitalization, and initiation/worsening of home oxygen requirements 3-6 months later were obtained. Technical success was defined as ability to envelope the targeted tumor with an ice-ball without premature cessation of the cryoablation protocol. Outcome measures included local control, local progression-free survival, and overall survival at 6 months, 1 year, 2 years, and 3 years.

29 patients with NSCLC recurrence after SBRT underwent percutaneous cryoablation with 35 treatment sessions. Mean lesion size and standard deviation was 2.8 ± 1.5 cm (Range, 1.0-7.4 cm). Pneumothorax and hospitalization rates were 44.4% (16/36) and 36.1% (14/36). The mean number of ablation probes was 2.5 ± 1.5 (Range, 1-6). Twenty-six patients had COPD (92.9%), of which 3.8% (1/26) had new or worsened home oxygen requirements. All (36/36) cryoablations achieved technical success. Local control, local progression-free survival, and overall survival were 100%/92.9%/92.9% at 6 months, 76.2%/70.8%/92.9% at 1 year, 64.9%/60.3%/62.3% at 2 years, and 31.5%/22.6%/35.4% at 3 years.

Percutaneous cryoablation of non-small cell lung cancer may be a safe and effective treatment alternative for recurrence after SBRT without worsening pulmonary function.

This document reviews the evidence supporting different imaging modalities and techniques used to evaluate patients with a history of lung cancer. It focuses on the imaging evaluation of patients treated for stage I-III non-small-cell lung cancer and small-cell lung cancer, whether using individual modalities or combinations. Guidelines for both routine surveillance of stage I-III lung cancer and for the evaluation of suspected recurrence or disease progression are provided. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Circulating tumor DNA (ctDNA) has the potential to become a reliable biomarker for identifying minimal residual disease (MRD) and predicting recurrence in patients with non-small cell lung cancer (NSCLC) following curative treatment. However, there is a lack of studies that investigate the clinical validity of ctDNA using a tumor-agnostic approach, which can provide significant clinical benefits.

We analyzed samples from 45 NSCLC patients recruited in a prospective national multicenter study, all of whom had undergone curative treatment. A total of 38 pre-treatment plasma samples and 76 post-treatment plasma samples were examined using a commercially available cancer personalized profiling by deep sequencing (CAPP-seq) strategy, and a tumor-agnostic approach. Post-treatment samples were collected at two distinct landmark time points: Follow-up 1 (0.5-4.5 months post-treatment) and Follow-up 2 (4.5-7.5 months post-treatment).

Detectable ctDNA post-treatment was significantly associated with increased risk of tumor recurrence and shorter recurrence-free survival (RFS). Using only a single blood sample taken from Follow-up 2, we correctly identified MRD in 50% of the patients who later experienced recurrence. However, subgroup analysis further revealed that in patients treated with radiotherapy or chemoradiotherapy (CRT), ctDNA detection was significantly linked to shorter RFS in the MRD analysis from Follow-up 2, but not in the MRD analysis from Follow-up 1.

These findings suggest that post-treatment ctDNA, detected using a tumor-agnostic approach, is a reliable biomarker for predicting recurrence in NSCLC patients following curative treatment. However, the optimal timing for blood sampling to detect MRD appears to depend on the type of curative treatment received.

Precision medicine based on biomarkers, such as genetic abnormalities and PD-L1 expression, has been established for the treatment of nonsmall cell lung cancer. Recently, liquid biopsy has emerged as a valuable and minimally invasive alternative. This method analyzes blood and other bodily fluids to detect cancer-related genetic abnormalities and molecular residual disease (MRD). Liquid biopsy, which includes testing for circulating tumor cells, circulating tumor DNA (ctDNA), and microRNA (miRNA), offers several advantages over conventional methods. It is minimally invasive, can be performed repeatedly, and provides crucial information for early cancer diagnosis, genotyping, and treatment monitoring. Elevated ctDNA levels and miRNA markers show promise for early diagnosis. Liquid biopsy complements traditional tissue biopsy during genotyping, particularly when tumor samples are insufficient. Tests such as Cobas® EGFR Mutation Test v2 and Guardant360® CDx have been shown to be effective in detecting genetic mutations and guiding treatment decisions. Although the accuracy of liquid biopsy is still lower than that of tissue biopsy, its clinical utility continues to improve. For cancer prediction recurrence and treatment monitoring, ctDNA analysis can detect MRD earlier than conventional imaging, offering potential benefits for treatment adjustment and early relapse detection. The continuous development and validation of liquid biopsy methods are essential for improving personalized lung cancer treatment strategies.

Data-driven gating (DDG) is an emerging technology that can reduce the respiratory motion artifacts in positron emission tomography (PET) images.

The aim of this study is to use phantom and patient data to validate the performance of DDG with a motion correction algorithm based on the reconstruct, register, and average (RRA) method.

A customized motion platform drove the phantom (five spheres with diameters of 10-28 mm) using a periodic motion that had a duration of 3-5 s and amplitudes of 2-4 cm. Normalized ratio of ungated and RRA PET relative to the ground-truth static PET was calculated for RSUVmax, RSUVmean, RSUVpeak, RVolume, and relative contrast-to-noise ratio (RCNR). Additionally, 30 lung cancer patients with 76 lung lesions less than 3 cm in diameter were prospectively studied. The overall image quality of patient examination was scored using a 5-point scale by two radiologists. SUVmax, SUVmean, SUVpeak, volume, and CNR of lesions measured in ungated and RRA PET were compared, and subgroup analysis was conducted.

In RRA PET images, motion artifacts of the spheres in the phantom were effectively mitigated, regardless of changes in movement amplitudes or duration. For all spheres with different ranges of motion and cycles, RSUVmax, RSUVmean, RSUVpeak, and RCNR increased significantly (p ≤ 0.001) and RVolume decreased significantly (p < 0.001) in RRA PET images. The average radiologist scores of image quality were 3.90 ± 0.86 with RRA PET, and 3.03 ± 1.19 with ungated PET. In RRA PET images, the SUVmax (p < 0.001), SUVmean (p < 0.001), SUVpeak (p < 0.001), and CNR (p < 0.001) of the lesions increased, while the volume (p < 0.001) of the lesions decreased. Δ%SUVmax, Δ%SUVmean, Δ%SUVpeak, and Δ%CNR of the lesions increased by 3.9%, 6.5%, 5.6%, and 4.3%, respectively, while Δ%Volume of the lesions decreased by 18.4%. Subgroup analysis showed that in lesions in the upper and middle lobes, only SUVpeak (p < 0.001) significantly increased by 5.6% in RRA PET, while their volume (p < 0.001) notably decreased by 12.4% (p < 0.001).

DDG integrated with RRA motion correction algorithm can effectively mitigate motion artifacts, thus enhancing the quantification accuracy and visual quality of images in lung cancer PET/CT.

Post-treatment surveillance is recommended for NSCLC owing to a high risk of recurrence, but evidence on the optimal surveillance method is lacking. This trial evaluates fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) versus contrast-enhanced CT (ceCT) for surveillance in patients with NSCLC.

In this multicenter, randomized controlled trial (SUPE_R, ClinicalTrials.gov NCT03740126), patients with stage IA-to-IIIC NSCLC were randomized one-to-one to standard surveillance (ceCT) or surveillance with [18F]FDG PET/CT after completion of curative treatment. The primary outcome was the proportion of recurrences treated with curative intent. Secondary outcomes included time to recurrence (TTR) and overall survival (OS).

Between February 2019 and February 2022, 750 patients were randomized to PET/CT (n = 373) or CT (n = 377). Recurrences occurred in 164 patients (22%). The proportion of recurrences treated with curative intent was identical in the PET group (42/87) and CT group (37/77), both 48% (p = 0.98). More recurrences were detected through scheduled follow-up in the PET group (90%) than in the CT group (77%; p = 0.02). There were no significant differences in TTR (hazard ratio 1.12, 95% confidence interval 0.82-1.52, p = 0.48) or OS (hazard ratio 0.97, 95% confidence interval 0.66-1.43, p = 0.89) between groups.

Surveillance with [18F]FDG PET/CT did not improve rates of curatively treated recurrences, TTR, or OS compared with ceCT in patients with NSCLC after curative treatment. These findings do not support the routine use of [18F]FDG PET/CT for post-treatment surveillance in this patient population.

The introduction of screening programs and the increase in life expectancy in developed countries have significantly raised the incidence of early-stage non-small cell lung cancer (ES-NSCLC). Surgery remains the standard of care for ES-NSCLC; however, stereotactic body radiotherapy (SBRT) has become the treatment of choice for patients with inoperable ES-NSCLC. Despite its growing use, there is a lack of robust data from randomized phase III trials comparing SBRT to surgery, mostly due to challenges in recruitment. This gap is particularly pronounced in the elderly, who are often excluded from clinical studies. With the rising incidence of ES-NSCLC and an aging population, non-invasive therapies like SBRT may offer significant advantages by minimizing treatment-related morbidity while effectively controlling the disease. This review critically evaluates the current literature on managing ES-NSCLC in elderly patients and assesses the potential benefits and limitations of SBRT as a standard of care in this complex population.

Molecular subtyping is an essential complementarity after pathological analyses for targeted therapy. This study aimed to investigate the consistency of next-generation sequencing (NGS) results between circulating tumor DNA (ctDNA)-based and tissue-based in non-small cell lung cancer (NSCLC) and identify the patient characteristics that favor ctDNA testing.

Patients who diagnosed with NSCLC and received both ctDNA- and cancer tissue-based NGS before surgery or systemic treatment in Lung Cancer Center, Sichuan University West China Hospital between December 2017 and August 2022 were enrolled. A 425-cancer panel with a HiSeq 4000 NGS platform was used for NGS. The unweighted Cohen's kappa coefficient was employed to discriminate the high-concordance group from the low-concordance group with a cutoff value of 0.6. Six machine learning models were used to identify patient characteristics that relate to high concordance between ctDNA-based and tissue-based NGS.

A total of 85 patients were enrolled, of which 22.4% (19/85) had stage III disease and 56.5% (48/85) had stage IV disease. Forty-four patients (51.8%) showed consistent gene mutation types between ctDNA-based and tissue-based NGS, while one patient (1.2%) tested negative in both approaches. Patients with advanced diseases and metastases to other organs would be suitable for the ctDNA-based NGS, and the generalized linear model showed that T stage, M stage, and tumor mutation burden were the critical discriminators to predict the consistency of results between ctDNA-based and tissue-based NGS.

ctDNA-based NGS showed comparable detection performance in the targeted gene mutations compared with tissue-based NGS, and it could be considered in advanced or metastatic NSCLC.

Minimally invasive thermal therapies show great prospect in non-small cell lung cancer (NSCLC) treatment. However, changes in immune cell populations following microwave ablation (MWA) in NSCLC microenvironment are not fully revealed.

The present study was conducted to identify changes in immune cell populations and analyse dysregulated genes in immune cells after MWA in NSCLC microenvironment.

The patients received fractionated MWA in two treatments separated by 3 weeks. Tumor biopsy samples were obtained through core-needle biopsy before each fractionated MWA procedure at the same site and used for single-cell RNA sequencing with the 10x Genomics pipeline.

A total of 9 major cell types were identified after MWA, which include neutrophils, T cells, B cells, monocytes, epithelial cells, chondrocytes, macrophages, tissue stem cells, and endothelial cells. After MWA, the tumor tissue exhibited an increased proportion of T cells. MWA altered gene expression in each cell cluster at the single-cell level. Cell trajectory analysis revealed that the cells at the starting point were most like T helper cells, naïve T cells, and regulatory T cells; they then developed into anergic T cells, T follicular cells, natural killer T cells, T memory cells, and exhausted T cells, and finally ended as γδ T cells and cytotoxic T cells. Moreover, after MWA, more interaction between monocytes and T cells (or B cells) were identified.

MWA increases local T-cell abundance and alters monocyte interactions, thereby reshaping the tumor microenvironment. This study lays a foundation for investigating dysregulated genes that may contribute to the MWA-induced immune response in NSCLC.

Thermal ablation may change the immune profiles of patients by activating various steps in the cancer immunity cycle. However, changes in immune cell populations following MWA of NSCLC have not been fully reported.

After MWA, an increase in interactions between monocytes and T cells intratumorally was observed, which promoted antitumor immunity.

The current study illuminates the MWA-caused systemic immune response in NSCLC, which may help to identify the dysregulated genes involved in the MWA-caused immune response.

Despite PACIFIC set a new milestone in the clinical management of unresectable stage III non-small cell lung cancer (NSCLC), it left some critical questions pending for clinical research: the efficacy of durvalumab in the real-world setting; the activity of less intensive regimens for frail populations; the role of targeted therapies in oncogene-addicted tumors; the selection of subsequent strategies at immunotherapy failure; the efficacy of novel and intensified treatments; the role of molecular biomarkers for patients' selection. This review aims to describe the evolving landscape of unresectable stage III NSCLC and provides an updated overview of the available evidence, analyzing lights and shadows emerging from recent clinical trials and discussing the most relevant challenges of post-PACIFIC era.

Despite treatment with curative intent, many patients with localized non-small cell lung cancer (NSCLC) develop recurrence. The current challenge is to identify high-risk patients to guide adjuvant treatment. Identification of residual disease by detection of circulating tumor DNA (ctDNA) may allow more accurate clinical decision-making, but its reliability in NSCLC is not established. We aimed to build on previous data to validate a tissue-informed personalized ctDNA assay, to predict recurrence in patients with early-stage disease.

Tumor tissue and plasma was collected from patients with stage 0-III NSCLC enrolled to LEMA (Lung cancer Early Molecular Assessment trial, NCT02894853). Serial plasma was collected before and after definitive treatment, with the latter including key timeframes of interest (1-3 days post-treatment, between 14 and 122 days after treatment end, and ≥14 days after treatment end). Somatic mutations identified by tumor exome sequencing were used to design patient-specific assays, to analyze ctDNA. Results were compared and combined with an independent dataset (LUCID; LUng Cancer CIrculating Tumour Dna study, NCT04153526). In LEMA, 130 patients (57% male; median age 66 years (range 44-82); 69% adenocarcinoma, 22% squamous cell carcinoma (SCC); 3%/49%/19%/29% with stage 0/I/II/III) were treated with curative intent. Tumor tissue originated from surgical resection or diagnostic biopsy in 118 and 12 patients respectively. LUCID included 88 patients (51% male; median age 72 years (range 44-88); 63% adenocarcinoma, 31% SCC; 49%/28%/23% with stage I/II/III). Before treatment, ctDNA was detected in 48% LEMA and 51% LUCID patients. Sensitivity, specificity, positive and negative predictive value of ctDNA detection post-treatment (≥1 positive sample ≥14 days after treatment end) to predict recurrence were 61%, 97%, 92% and 84% for LEMA and 64%, 96%, 90% and 83% for LUCID. In the combined cohort, ctDNA detection after treatment was associated with shorter recurrence-free survival (hazard ratio (HR) 11.4 (95% confidence interval (CI) [7.0,18.7]; p < 0.001)) and overall survival (HR 8.1 (95% CI [4.6,14.2]; p < 0.001)), accounting for guarantee-time bias. Of note, a key limitation of this work was the irregular sample collection schedules, during routine follow-up visits, of both studies.

ctDNA detection predicted recurrence in independent retrospective cohorts with notable reproducibility, including near-identical detection rates and predictive values, confirming its ability to differentiate patients at high- versus low risk of recurrence. Our results support the potential of tissue-informed ctDNA analysis as a decision-support tool for adjuvant therapy in NSCLC.

Lung cancer is a prevalent malignant disease with the highest mortality rate among oncological conditions. The assessment of its clinical TNM staging primarily relies on contrast-enhanced computed tomography (CT) of the thorax and proximal abdomen, sometimes with the addition of positron emission tomography/CT scans, mainly for better evaluation of mediastinal lymph node involvement and detection of distant metastases. The purpose of TNM staging is to establish a universal nomenclature for the anatomical extent of lung cancer, facilitating interdisciplinary communication for treatment decisions and research advancements. Recent studies utilizing a large international database and multidisciplinary insights indicate a need to update the TNM classification to enhance the anatomical categorization of lung cancer, ultimately optimizing treatment strategies. The eighth edition of the TNM classification, issued by the International Association for the Study of Lung Cancer (IASLC), transitioned to the ninth edition on 1 January 2025. Key changes include a more detailed classification of the N and M descriptor categories, whereas the T descriptor remains unchanged. Notably, the N2 category will be split into N2a and N2b based on the single-station or multi-station involvement of ipsilateral mediastinal and/or subcarinal lymph nodes, respectively. The M1c category will differentiate between single (M1c1) and multiple (M1c2) organ system involvement for extrathoracic metastases. This review article emphasizes the role of radiologists in implementing the updated TNM classification through CT imaging for correct clinical lung cancer staging and optimal patient management.

Lung cancer is responsible for premature cancer deaths in women and is the first cause of cancer deaths in women in many countries. The problem of lung cancer in women seems to be underestimated in many aspects, including low participation in clinical trials and screening tests.

Current research progress has contributed to a better understanding of the issue and makes it possible to describe the problem in a new light. In our paper, the problem of lung cancer in women was discussed in a broad aspect, taking into account women's health, the harmful effects of smoking and the current diagnostic and treatment process. The results of treatment also differ in relation to sex. All these aspects of the diversity of women's lung cancer were presented on the basis of newest and most comprehensive literature.

Lung cancer in women is and will remain an important health problem worldwide, which is justified by epidemiological data, basic research and treatment results.

Neoadjuvant immunochemotherapy (NICT) is a new treatment method for resectable non-small-cell lung cancer (NSCLC). Network meta-analysis assessed efficacy, safety, and optimal treatment.

We searched for randomized controlled trials (RCTs) comparing NICT with neoadjuvant chemotherapy (NCT) in PubMed, Embase, Web of Science, Cochrane Library, and international conferences. Outcomes were surgical resection rate, pathological complete response(pCR),event-free survival (EFS), and Grade 3-5 treatment-related adverse events (TRAEs).

RCTs of 3,387 patients, six treatment combinations, and two modalities were included. Meta-analysis showed that NICT yielded higher pCR and EFS rates than NCT. The toripalimab-chemotherapy combination had the highest surgical resection rate (OR = 1.68, 95% CI: 1.05-2.73), pCR (OR = 38.84, 95% CI: 11.05-268.19) and EFS (HR = 0.40, 95% CI: 0.28-0.58).This regimen worked well for patients with low programmed death-ligand 1 (PD-L1) expression or squamous cell pathology. For high PD-L1 expression and patients with NSCLC, neoadjuvant nivolumab with chemotherapy had the most efficacy. The incidence of treatment-related adverse events increased with longer treatment cycles, with perioperative nivolumab combined with chemotherapy showing the worst safety profile (RR = 1.32, 95% CI: 1.00-1.76), while neoadjuvant nivolumab combined with chemotherapy alone had the best safety profile (RR = 0.91, 95% CI: 0.68-1.21). Indirect comparison showed no survival benefit for neoadjuvant-adjuvant immunotherapy (HR = 0.93, 95% CI: 0.65-1.35). In the indirect comparison between the two immune checkpoint inhibitors(ICIs), although there was no significant difference in EFS (HR = 0.81, 95% CI: 0.61-1.08), PD-1 inhibitors may still be the most effective treatment option.

NICT effectively and safely treats resectable NSCLC. The optimal treatment combination is typically toripalimab and chemotherapy. Treatment based on PD-L1 expression and pathological type is recommended.

THASSOS-INTL (NCT04808050), a multinational, retrospective study, evaluated treatment patterns and associated outcomes in patients with early-stage non-small cell lung cancer (NSCLC) from seven countries in the Asia-Pacific and the Middle-East and Africa.

Eligible adult patients (≥ 18 years) with resectable clinical stage (CS) IA-IIIB NSCLC (7th AJCC) diagnosed from 01/01/2013 to 31/12/2017 were followed until death, last recorded clinical visit, or 31/12/2020 (data cut-off).

Of 755 patients (CS I: 30.6%, CS II: 35.0%, CS III: 34.2%) with a median age of 62 [range: 56-69] years enrolled, 69.3% were male, and 75.0% were current/ex-smokers. Of 24.2% of patients tested for EGFR, 28.4% (52/183) were positive, while 23/44 patients tested (52.3%) had PD-L1 expression (≥ 1%: 16; unknown: 7). Overall, 82.9% had surgery, of whom 39.1% (245/626) had surgery alone; 21.1% received neoadjuvant therapy, 51.1% received adjuvant therapy, and 5.8% received both; 11.2% (58/519) patients received targeted therapy (adjuvant: 47 patients; neoadjuvant: 11 patients), and 4.6% (24/519) received immunotherapy (adjuvant: 22 patients; neoadjuvant: 2 patients). The 3-year survival was 77.4% with a median overall survival (mOS) of 7.5 (95% confidence interval [CI]: 6.7-NE) years, with the highest mOS recorded with adjuvant therapy (7.5 [95% CI: 7.0-NE] years).

This real-world study showed > 50% use of adjuvant therapy per guideline recommendations but poor use of neoadjuvant therapy. Biomarker testing at diagnosis was low, reflecting the study period being before targeted and immunotherapies. With recent approvals of newer (neo)adjuvant agents, a multidisciplinary approach is needed for better treatment decisions to improve the prognosis of early-stage NSCLC.

Maternal embryonic leucine zipper kinase (MELK) is an oncogene in many tumors, although its contribution to lung adenocarcinoma (LUAD) is unclear. We examined MELK expression in patient LUAD tissue and matched healthy lung tissues. We investigated the connection between MELK expression and tumor differentiation, lymph node metastasis, and patient survival. We downregulated MELK expression using small-hairpin RNA to assess its impact on LUAD cell proliferation, clonogenicity, and invasion. We also investigated the molecular mechanism underlying these effects. MELK expression was significantly heightened in LUAD tissue as opposed to the matching healthy lung tissues. LUAD patients who had MELK overexpression had a worse prognosis. Suppression of MELK hinders proliferation, clonogenicity, and invasion of LUAD cells. The MELK suppression led to the arrest of the cell cycle's G1/S phase by reducing the cyclin E1 and cyclin D expression. Our outcomes manifest that MELK can function as a beneficial prognostic indication and a new therapy target for LUAD. MELK has an essential function in progressing LUAD, manifesting potential as a viable target for therapeutic intervention in this disease management.

To develop and validate a machine learning (ML) model based on positron emission tomography/computed tomography (PET/CT) multi-modality fusion radiomics to improve the prediction efficiency of mediastinal-hilar lymph node metastasis (LNM).

Eighty-eight non-small cell lung cancer (NSCLC) patients with 559 LNs from centre 1 were divided into training and internal validation cohorts (7:3 ratio), and 75 patients with 543 LNs from centre 2 were assigned as external validation cohorts. PET and CT images were fused by wavelet transform. Multi-modality fusion radiomics features from six images of lymph nodes were extracted. The multi-modality fusion radiomics (MFR), multi-modality fusion radiomics + metabolic parameters (MFRM), CT, PET and PET + CT models were developed based on the best one among the 11 ML algorithms. The receiver operating characteristic (ROC) curve and the Delong test were used to assess and compare the performance of the models.

The CatBoost algorithm was chosen, and the MFR, MFRM, CT, PET and PET + CT models were constructed. The MFR and MFRM models showed a high AUC for predicting LNM in centre 1 (AUC = 0.950 and 0.952) and centre 2 (AUC = 0.923 and 0.927), and there were significant differences in centre 2 (P=0.036). The diagnostic efficacy of MFR and MFRM models was significantly higher than CT, PET, PET + CT models and SUVmax≥3.5 (P<0.001). The MFRM prediction was statistically different from the MFR prediction in the hilar/interlobar zone.

Both the MFR and MFRM models based on multi-modality fusion radiomics showed great potential for non-invasively predicting mediastinal-hilar LNM in NSCLC.

(1) Background: Exploring real-world data (RWD) regarding immune-related adverse events (irAEs) is crucial to better understand the efficacy and safety of immunotherapy in cancer patient populations excluded from clinical trials. An analysis was conducted to evaluate the presumptive predictive causality between endocrine irAEs and the efficacy of immune check-point inhibitors (ICIs) in metastatic non-small-cell lung cancer (mNSCLC) patients treated in daily practice in Romania. (2) Methods: This was a retrospective cohort study of mNSCLC patients treated with ICIs in a tertiary level hospital in Romania for a period of almost seven years, from November 2017 till July 2024. Endocrine irAEs were well defined as any occurring autoimmune endocrinopathy during ICIs and related to immunotherapy. The hospital endocrinologist (M.C.C.O) diagnosed, treated, and followed these endocrine irAEs in a multidisciplinary approach. We investigated multiple medical variables to assess their impact on ICI effectiveness. Descriptive and statistical analyses were performed. (3) Results: Of 487 cancer patients treated with ICIs, we identified 215 mNSCLC patients who were evaluated for endocrine irAEs and co-medications during ICI therapy. Forty-seven (21.8%) patients experienced endocrine irAEs, thyroiditis being the most frequent and prevalent autoimmune endocrinopathy in 60% of cases. Endocrine irAEs were statistically significant, correlated with ICI efficacy (p = 0.002) for survival analysis. Steroids and proton-pump inhibitors used as co-medication during ICIs had a negative impact on response to therapy. (4) Conclusions: Endocrine irAEs might be considered predictive biomarkers for successful immunotherapy in mNSCLC patients. Co-medication during ICIs had a major influence on the effectiveness of these cutting-edge therapies. RWD plays an important role for oncology daily practice whenever clinical trial evidence is not available to guide decision.