Stage Non-small Cell Lung Cancer Research Articles

Immunotherapy Improves Clinical Outcome in Kirsten Rat Sarcoma Virus-Mutated Patients with Unresectable Non-Small Cell Lung Cancer Stage III: A Subcohort Analysis of the Austrian Radio-Oncological Lung Cancer Study Association Registry (ALLSTAR)

Background/Objectives: Current evidence suggests that patients with unresectable non-small cell lung cancer (NSCLC) whose tumours harbour driver mutations do not benefit from immune checkpoint inhibition. Kirsten rat sarcoma virus mutations (KRASmts), however, seem to be the exceptions to the rule. To this end, we compared KRASmt patients who were treated with immunotherapy to those without. Methods: ALLSTAR is a nationwide registry for patients with histologically verified non-operable NSCLC aged 18 or older having a curative treatment option. This report presents a subcohort of KRASmt patients who were recruited between 2020/03 and 2023/04. The diagnostic work-up included 18F-FDG-PET-CT scan and contrast-enhanced cranial CT or—preferably—MRI. Patients were treated with chemoradiotherapy (CRT) either followed by immune checkpoint inhibition (ICI) or not. Results: Thirty-two KRASmt patients with a median follow-up of 25.9 months were included in this analysis. After CRT, 27/32 (84%) patients received ICI. The 2-year overall survival rate in KRASmt patients who received immunotherapy was significantly better compared to those without ICI (N = 32; 84% versus 20%; p < 0.001). Likewise, the 2-year progression-free-survival with immunotherapy was also significantly better than in those without ICI (N = 32; 75% versus 20%; p < 0.001). Of the 12/32 patients (38%) who had received radiation doses > 66 Gy, none had a locoregional relapse, whereas in the other 20 patients, 5 (25%) events occurred (p-value = 0.116). Conclusions: Since KRASmt patients could benefit from ICI treatment, immunotherapy should be offered to these patients, similar to those without actionable genetic drivers. Additionally, radiation dose escalation > 66 Gy may also improve locoregional control in this subset of patients.

Brain Imaging in Patients with Non-Small Cell Lung Cancer—A Systematic Review

Background: Lung cancer frequently metastasizes to the brain, liver, and adrenal glands with a significant negative prognostic impact on overall survival and quality of life (QoL). To optimize treatment and prognosis, adequate staging with the detection of distant metastases is crucial. The incidence of brain metastases in potentially resectable early-stage non-small cell lung cancer (NSCLC) is as low as 3%; hence, the need for preoperative brain imaging has been a constant matter of debate, especially in stage II. In stages III and IV NSCLC, neuroimaging is an essential part of staging. Methods: A systematic literature search was performed. Publications from 1999 to 2024, focusing on preoperative brain imaging (BI) in the staging of stages I–IV NSCLC, were included. Data extraction included study population characteristics, the modality of BI, the incidence of brain metastases (BMs), and the main outcomes of the studies. The final included studies were selected according to the PRISMA criteria. In the second step, guidelines on BI in NSCLC staging of major importance were identified and compared. Results: A total of 530 articles were identified, of which 25 articles were selected. Four prospective studies and 21 retrospective investigations were included. Most of the investigations focused on BI in the early stages. The main imaging modality for BI was magnetic resonance imaging (MRI), followed by computed tomography (CT). Besides the identified 25 studies, the most important internationally applied guidelines on brain imaging in the staging of NSCLC were reviewed. While some guidelines agree on preoperative BI in NSCLC stage III (Union for International Cancer Control—UICC eighth edition) patients, other guidelines recommend earlier BI starting from clinical stage II. All mentioned guidelines homogenously recommend BI in patients with symptoms suggestive of brain pathologies. Conclusions: BI in NSCLC staging is recommended in neurologically symptomatic patients suggestive of brain metastases as well as NSCLC patients with stage III disease. Neuroimaging in stage IA patients, as well as in pure GGO (Ground-Glass Opacity) lesions, was considered unnecessary. The predominantly applied imaging modality was ce-MRI (contrast-enhanced magnetic resonance imaging). Inconsistency exists concerning BI in stage II. The identification of prognostic factors for developing BM in patients with early-stage NSCLC could help to clarify which subgroup might benefit from preoperative BI.

Age Is Just a Number? A Retrospective Review of Cause of Death in Patients 85 Years and Over Receiving Lung Stereotactic Ablative Radiotherapy.

Patients aged > 85 years are under-represented in research that has established stereotactic body radiotherapy (SBRT) as the standard of care in early stage non-small cell lung cancer (NSCLC) not suitable for or refusing surgery. With an ageing population in Australia, it is important to assess SBRT and cause of death (COD) in elderly patients receiving curative intent lung SBRT. This is a multi-centre retrospective review of eligible patients treated across Australia from 2016 to 2022 with curative intent lung SBRT for early stage primary NSCLC, and aged 85 years or over. The primary outcomes were estimated 2-year overall survival (OS) and COD. Secondary outcomes include cancer-specific survival (CSS), progression-free survival (PFS) and local PFS following SBRT. Univariate Cox regression was used to determine factors associated with survival outcomes or progression. In the study, 103 patients were identified, treated with 109 courses of SBRT. Median age was 87.6 years (range 85-97.1) with 52.4% male (n = 54). Median follow-up was 19.6 months (range 0.2-55.6). The estimated 2-year survival was 78.7% (95% CI 67.8-86.3). Of the 27.2% (n = 28) of patients deceased, COD was established in 89.3% (n = 25) of cases. In addition, 39.2% (n = 11) of deaths were related to lung cancer. Univariate analysis demonstrated that survival varied significantly with poorer performance status. This study increases knowledge of efficacy of lung SBRT in the very elderly, suggests similar outcomes to the general patient population and supports the use of lung SBRT in those aged 85 years or over. Prospective data including outcomes, comorbidities, pulmonary function and toxicity are required to help inform clinicians and patients about decisions regarding treatment.

Advances in adjuvant therapy for operable N2 non-small cell lung cancer: a narrative review.

Non-small cell lung cancer (NSCLC) is still the disease with the highest incidence rate among malignant tumors, in which NSCLC under N2 stage has obvious survival differences among different patients due to its high heterogeneity. For NSCLC under this stage, the current treatment options are: preoperative neoadjuvant therapy, surgical treatment, postoperative adjuvant chemotherapy, postoperative adjuvant radiotherapy (PORT), Postoperative adjuvant targeted therapy and postoperative adjuvant immunotherapy. Whether postoperative adjuvant radiotherapy is routinely administered to patients with pN2 remains controversial in clinical application. Meanwhile, the booming development of adjuvant targeted therapy and adjuvant immunotherapy also provides newer therapeutic options for the prognosis of postoperative pN2 stage NSCLC, and some new markers will guide the adaptive application of immune drugs in the future. This article analyzes the current stage of therapeutic advances in operable stage N2 non-small cell lung cancer, and discusses in detail in this article the therapeutic controversy of postoperative adjuvant radiotherapy in pN2 stage non-small cell lung cancer, so as to explore a more reasonable treatment mode for future patients with stage N2 non-small cell lung cancer.

Study Protocol of the Korean EGFR Registry: A Multicenter Prospective and Retrospective Cohort Study in Nonsmall Cell Lung Cancer Patients With EGFR Mutation.

The provision of treatment for epidermal growth factor receptor (EGFR)-mutated nonsmall cell lung cancer (NSCLC) patients has increased in Korea. However, multicenter studies on the clinicopathologic dataset and treatment outcomes, using a large-scale dataset, have not been conducted. The current study is a prospective and retrospective multicenter observational cohort study that registers all stages of EGFR-mutated NSCLC patients. The Korean EGFR Registry was designed to enroll 2000 patients with all stages of EGFR-mutated NSCLC from 40 university hospitals across Korea. This study, encompassing both retrospective and prospective cohorts, aims to analyze clinical characteristics, treatment modalities, and outcomes in these patients. Data collection will include patient demographics, smoking history, quality of life assessments, pathological data, and treatment outcomes, with follow-up until December 2026. The primary endpoint is disease-free survival in patients who have undergone radical therapy (surgery and radiotherapy) or progression-free survival in those receiving targeted therapy (first, second, and subsequent lines), chemotherapy (first and subsequent lines), combination therapy, and palliative/maintenance therapy according to stages of EGFR-mutated NSCLC. The study will explore the diagnostic methods for EGFR mutations, clinical outcomes based on treatment modalities, and metastatic patterns in EGFR-mutated NSCLC patients. Moreover, it will investigate various aspects, including the safety and efficacy of a new third-generation EGFR tyrosine kinase inhibitor (TKI), lazertinib, approved for both first- and second-line treatments. This study is expected to provide valuable insights into the epidemiology, risk factors, progression, and treatment outcomes of EGFR-mutated NSCLC in Korea. The Korean EGFR Registry will contribute significantly to the understanding of the complex dynamics of EGFR-mutated NSCLC, aiding in the development of more effective and personalized treatment strategies.

Quality of Life Outcomes Between Robotic-Assisted and Video-Assisted Thoracoscopic Surgery for Early Stage Non-Small Cell Lung Cancer

Quality of Life Outcomes Between Robotic-Assisted and Video-Assisted Thoracoscopic Surgery for Early Stage Non-Small Cell Lung Cancer

Gut Microbiome and Metabolite Characteristics Associated With Different Clinical Stages in Non-Small Cell Lung Cancer Patients.

Our research has pinpointed the gut microbiome's role in the progression of various pathological types of non-small cell lung cancer (NSCLC). Nonetheless, the characteristics of the gut microbiome and its metabolites across different clinical stages of NSCLC are yet to be fully understood. The current study seeks to explore the distinctive gut flora and metabolite profiles of NSCLC patients across varying TNM stages. The research team gathered stool samples from 52 patients diagnosed with non-small cell lung cancer (NSCLC) and 29healthy individuals. Subsequently, they performed 16S rRNA gene amplification sequencing and untargeted gas/liquid chromatography-mass spectrometry metabolomics analysis. The study revealed that the alpha-diversity of the gut microbiome in NSCLC patients at different stages did not exhibit statistically significant differences. Notably, Lachnospira and Blautia were more abundant in healthy controls. The distribution of gut microbial species in patients with varying stages of NSCLC was uneven, with Bacteroides and Bacteroidaceae being most prevalent in stage T2, and Prevotella dominating in stage T4. Levels of Ruminococcus gnavus were notably elevated in stages N3 and M. The genus levels of Klebsiella, Parabacteroides, and Tannerellaceae were higher in stage II patients. Rodentibacter was the bacterium with increased levels in stage III NSCLC patients. Further metabolomics studies revealed significantly elevated levels of quinic acid and 3-hydroxybenzoic acid in the healthy control group. In contrast, Stage I+II non-small cell lung cancer (NSCLC) patients exhibited reduced levels of L-cystathionine. Notably, quinic acid, phthalic acid, and L-lactic acid were observed to be increased in Stage III+IV NSCLC patients. Compared to the analysis of a single microbial dataset, this study provides deeper functional insights by incorporating comprehensive metabolomic profiling. This approach demonstrates that both the gut microbiome and associated metabolites are altered in NSCLC patients across different clinical stages. Our findings may offer novel perspectives on the pathogenesis of NSCLC at various TNM stages. Further research is warranted to validate and clinically apply these potential biomarkers.

Quality of life and aspects related nutrition in advance stages non-small cell lung cancer patients.

Background: The quality of life (QoL) associated nutritional symptoms among advanced non-small cell lung cancer (NSCLC) patients remains uncertain. This study aimed to assess the impact of nutrition-related symptoms (indicated by Patient Generated Subjective Global Assessment-PG-SGA) to QoL among individuals diagnosed with advanced NSCLC, utilizing the EORTC QLQ-LC13 tool. Methods: A cross-sectional study included 170 patients diagnosed with NSCLC (TxNxM1) with periodically chemotherapy treatment at Hanoi Oncology hospital were invited to the study. The PG-SGA and EORTC QLQ-LC13 were assessed by a dietitian. Results: Poor nutritional status related with decrease in QoL (p < 0.05). Cough and short of breath moderate-positively correlated with PG-SGA score, while pain, take medicine for pain and trouble swallowing were fairly correlated. The symptoms of cough up blood, sore mouth or tongue, tingling and hair lost had poor correlation with PG-SGA score. Loss of appetite and anorexia had poor negative correlation with short of breath and pain in arm or shoulder. Conclusions: QoL declined in advance stage NSCLC malnutrition patients. Nutrition-related symptoms had poor to fair correlation with QoL categories, which suggests the insufficiency on solely addressing nutritional symptoms to enhance QoL in this group.

Neoadjuvant therapy for resectable non-small cell lung cancer

Treatment perspectives for non-small cell lung cancer (NSCLC) have been significantly expanded by the integration of immune checkpoint inhibitors into multimodal therapy concepts. Currently, combined, immune checkpoint-inhibitor-based therapy concepts are also advancing into early, resectable stages of NSCLC. Neoadjuvant and perioperative chemoimmunotherapy opened up a promising new preoperative treatment approach, but also raises some new questions and challenges. With the expanded perioperative treatment options and the perspective on a further improvement in the absence of recurrence after tumor resection, there is push towards comprehensively collecting therapy-relevant findings for imaging, molecular and histopathological diagnostics at an early stage. All patients with lung carcinoma, regardless of the therapy intention, should be presented to an interdisciplinary tumor board with thoracic oncological expertise. This is regularly given in certified lung cancer centers.A standardized procedure contributes to optimized pre-therapeutic diagnostics and facilitates coordination for the best possible multimodal approach in the interdisciplinary tumor board. In the case of centrally located resectable tumors, for example, neoadjuvant treatment increases the chances of a procedure that is as parenchymal sparing as possible. Some questions cannot yet be answered conclusively. Perioperative systemic therapy with molecular-targeted and immune checkpoint inhibitors is the subject of numerous ongoing studies. The considerable dynamics in newly approved therapies and the development of perioperative therapy concepts require continuous adaptation of diagnostic algorithms and standards. Integration into standard pre-surgical routine makes rapid classification of the relevant findings as well as close coordination between the diagnostic and interventional disciplines essential.

Self-supervised learning improves robustness of deep learning lung tumor segmentation models to CT imaging differences.

Self-supervised learning (SSL) is an approach to extract useful feature representations from unlabeled data, and enable fine-tuning on downstream tasks with limited labeled examples. Self-pretraining is a SSL approach that uses curated downstream task dataset for both pretraining and fine-tuning. Availability of large, diverse, and uncurated public medical image sets presents the opportunity to potentially create foundation models by applying SSL in the "wild" that are robust to imaging variations. However, the benefit of wild- versus self-pretraining has not been studied for medical imageanalysis. Compare robustness of wild versus self-pretrained models created using convolutional neural network (CNN) and transformer (vision transformer [ViT] and hierarchical shifted window [Swin]) models for non-small cell lung cancer (NSCLC) segmentation from 3D computed tomography (CT) scans. CNN, ViT, and Swin models were wild-pretrained using unlabeled 10,412 3D CTs sourced from the cancer imaging archive and internal datasets. Self-pretraining was applied to same networks using a curated public downstream task dataset (n = 377) of patients with NSCLC. Pretext tasks introduced in self-distilled masked image transformer were used for both pretraining approaches. All models were fine-tuned to segment NSCLC (n = 377 training dataset) and tested on two separate datasets containing early (public n = 156) and advanced stage (internal n = 196) NSCLC. Models were evaluated in terms of: (a) accuracy, (b) robustness to image differences from contrast, slice thickness, and reconstruction kernels, and (c) impact of pretext tasks for pretraining. Feature reuse was evaluated using centered kernel alignment. Wild-pretrained Swin models resulted in higher feature reuse at earlier level layers and increased feature differentiation close to output. Wild-pretrained Swin outperformed self-pretrained models for analyzed imaging acquisitions. Neither ViT nor CNN showed a clear benefit of wild-pretraining compared to self-pretraining. Masked image prediction pretext task that forces networks to learn the local structure resulted in higher accuracy compared to contrastive task that models global image information. Wild-pretrained Swin networks were more robust to analyzed CT imaging differences for lung tumor segmentation than self-pretrained methods. ViT and CNN models did not show a clear benefit for wild-pretraining overself-pretraining.

Comparison between lymph and non-lymph node resection in patients with stage IA non-small-cell lung cancer: A retrospective study.

This retrospective study aimed to determine the need for lymph node resection during surgical treatment in patients with stage IA non-small-cell lung cancer (NSCLC). A total of 1428 patients diagnosed with cT1N0M0 1 A stage NSCLC who underwent surgery were divided into two groups: lymphadenectomy (n = 1324) and nonlymphadenectomy (n = 104). The effects of lymph node resection on overall survival (OS) and recurrence-free survival (RFS) and on clinicopathological factors that affected the prognosis of the patients were investigated. The group that underwent lymph node resection had a better 5-year OS (89.2% vs 81.1%) and 3-year RFS (87.6% vs 79.2%) than the one that did not. Multivariate Cox regression analysis revealed that the risk of OS in the nonlymphadenectomy group increased by 72% compared to that in the lymphadenectomy group [hazard ratio (HR), 1.72; 95% confidence interval (CI), 1.08-2.74; P < 0.05]. The risk of RFS in the group without lymphadenectomy increased by 45% compared to that in the group with lymphadenectomy (HR, 1.45; 95% CI, 0.98-2.14;P = 0.06). Significant reductions in the OS (HR, 5.90; 95% CI, 1.80-20.00; P < 0.005) and RFS (HR, 4.00; 95% CI, 1.50-11.00;P < 0.005) can be seen in the absence of lymph node resection in NSCLC patients with emphysema. A thorough evaluation and removal of the hilar and mediastinal lymph nodes may prove useful in determining the cancer stage and assessing the need for further treatment, thus enhancing the prognosis of patients with stage IA NSCLC.

Phase Ib/II study of imprime PGG and pembrolizumab in patients with previously treated advanced non-small cell lung cancer (NSCLC): BTCRC LUN 15-017.

Therapeutic strategies to engage anti-tumor innate immunity are still underdeveloped. Imprime PGG (imprime), a pathogen-associated molecular pattern (PAMP), through pattern recognition receptors, successfully illicit a broad-based innate immune response in preclinical models against various cancers. We aimed to study safety and efficacy of imprime in combination with pembrolizumab in advanced stage non-small cell lung cancer (NSCLC). We conducted an investigator-initiated, multi-institutional, single-arm, phase Ib/II trial in previously treated, advanced stage NSCLC patients. Primary endpoints were maximum-tolerated dose (MTD) of imprime for the phase Ib, and progression-free survival (PFS) for the phase II study (NCT03003468). All 33 eligible patients were included in the safety analysis. No dose-limiting toxicity was observed and the imprime dose of 4 mg/kg was determined as the MTD. Thirty patients treated at the MTD (phase Ib, 6; phase II, 24) were included in the efficacy analysis. Median length of follow-up was 10.8 months. Confirmed objective response rate was 10% [95% confidence interval (CI): 2-27%], with one complete and two partial responses. Median PFS was 2.6 months (95% CI: 1.4-7.0), and 6- and 12-month PFS rates were 37% and 17%, respectively. Median overall survival (OS) was 11.1 months, and 6- and 12-month OS rates were 75% and 46%. Univariate analysis was performed to assess the impact of age, sex, race, disease-stage, programmed death-ligand 1 (PD-L1) expression levels, and prior immunotherapy on PFS and OS. Of these, prior immunotherapy negatively influenced OS [hazard ratio (HR): 2.95, 95% CI: 1.21-7.24]. Overall, the combination was safe and tolerable. The combination of imprime and pembrolizumab is tolerable but did not improve the outcome of advanced stage NSCLC patients who previously progressed on anti-programmed death 1 (PD-1)/PD-L1 immunotherapies. Further investigation is needed to understand the effects of therapeutic PAMPs to mount a strong innate immune response against cancer.

Sex-based differences in CEACAM5 expression in lung cancer.

Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is expressed in 20-25% of non-small cell lung cancer (NSCLC) and there is interest in CEACAM5 as a biomarker given its potential for blood-based detection and investigational study as a drug target. Increased expression of CEACAM5 has been observed in semi-solid lung adenocarcinoma lesions, which have an increased prevalence in women and never smokers. Given this association, sex-based differences in CEACAM5 were evaluated. The Cancer Genome Atlas (TCGA) data on CEACAM5 expression in NSCLC tumors (n=994) in women (n=398) and men (n=596) were analyzed for differences in expression of CEACAM5 based on sex and histologic subtypes of adenocarcinoma and for correlations with overall survival (OS). Among all stages of NSCLC, mean expression of CEACAM5 was 143.3 fragments per kilobase of transcript per million (FPKM) with differences observed between female and male patients (194.5 vs. 109.2 FPKM, P<0.0001) and between adenocarcinoma and squamous cell carcinoma (239.3 vs. 46.2 FPKM, P<0.0001). Differences persisted among combined sex and histology subgroups. High CEACAM5 was not predictive of survival in NSCLC or adenocarcinoma overall, but was associated with worse survival among stage I female patients with adenocarcinoma (5-year OS CEACAM5 high =33% vs. low =64%, log-rank P=0.008). Higher levels of CEACAM5 expression are observed in NSCLC tumors in female patients and adenocarcinoma histology. High CEACAM5 expression in lung adenocarcinoma is associated with worse survival among female patients. The biologic impact of sex on CEACAM5 as a biomarker warrants further study.

Neoadjuvant immune checkpoint inhibitor reduced recurrence in operable NSCLC patients with pathological complete response: a retrospective analysis

BackgroundThis study aimed to evaluate if neoadjuvant immune checkpoint inhibitor (ICI) plus chemotherapy (CT) reduced tumor recurrence after surgery than neoadjuvant CT alone in non–small cell lung cancer (NSCLC) patients with pathologic complete response (pCR).MethodsFrom January 1st 2019 to April 30th 2022, 16 NSCLC patients with pCR who received both neoadjuvant ICI and CT were designated as ICI/CT group. Another 8 patients, who received neoadjuvant CT alone, were designated as CT group. The tumor recurrence and patients’ survival status were analyzed.ResultsSquamous cell carcinoma was the predominant histology type in both groups. The CT group had higher percentage of patients who received adjuvant CT than the ICI/CT group (100% vs. 75%, p = 0.046). All patients had been followed up for at least 20 months. At 20 months after surgery, the ICI/CT group had a tumor recurrence rate of 6.25%, which was significantly lower than 37.5% recurrence rate of the CT group. One patient of the CT group died of gastrointestinal hemorrhage and severe anemia at 11 months after surgery, and no patient in the ICI/CT group died. During adjuvant therapy, the ICI/CT group had significantly lower risk of anemia (12.5% vs. 50%) than the CT group (p = 0.046).ConclusionThe study found that in NSCLC patients with pCR, neoadjuvant ICI reduced tumor recurrence rate. This indicated that like in advanced stage NSCLC, the ICI might bring similar long-term anti-tumor effect in operable NSCLC patients.

Changes in Staging and Management of Non-Small Cell Lung Cancer (NSCLC) Patients Following the Implementation of Low-Dose Chest Computed Tomography (LDCT) Screening at Kaohsiung Medical University Hospital.

Low-dose computed tomography (LDCT) has been widely adopted for lung cancer screening due to its proven ability to reduce lung cancer mortality, especially among high-risk populations. This retrospective study aims to evaluate the impact of LDCT screening on non-small cell lung cancer (NSCLC) staging at Kaohsiung Medical University Hospital (KMUH) from 2011 to 2020, following the introduction of LDCT in 2013. The study examines the correlation between LDCT screening volume and changes in the distribution of NSCLC stages, particularly early-stage (stages 0 and I) and late-stage (stage IV) diagnoses. Additionally, it explores the differences in histopathological subtypes, focusing on adenocarcinoma and squamous cell carcinoma, and assesses the impact of early detection on five-year survival rates. The results show a significant increase in early-stage NSCLC diagnoses, particularly in adenocarcinoma cases, where early-stage diagnoses rose from 10.4% in 2010 to 38.7% in 2019. However, the number of stage IV cases remained stable, indicating that LDCT may not substantially reduce late-stage diagnoses. Pearson's correlation analysis demonstrated a strong positive correlation between LDCT screening and early-stage NSCLC detection, particularly for adenocarcinoma (p < 0.001), though the early detection of squamous cell carcinoma and small cell carcinoma remained limited. The study concludes that LDCT screening plays a crucial role in improving early NSCLC detection and five-year survival rates. Future research should focus on optimizing screening strategies to capture more at-risk populations and enhance the detection of harder-to-diagnose subtypes like squamous cell carcinoma.

Clinical stage IA non-small cell lung cancer with occult pathologic N1 and N2 disease after segmentectomy: does a completion lobectomy justify?

When final pathology shows pathologic N1 or N2 disease after a pulmonary segmentectomy for early stage non-small cell lung cancer (NSCLC), completion of lobectomy could be considered and recommended as an option for treatment. We explored outcomes after segmentectomy for clinical stage IA NSCLC with occult pN1 or pN2 disease. We identified clinical stage IA NSCLC undergoing segmentectomy or lobectomy from the National Cancer Database (NCDB) between 2010 and 2020. We categorized patients by pathologic N diseases (pN0/pN1/pN2). We compared segmentectomy to lobectomy adjusting for patient and clinical characteristics. We explored survival using time-varied Cox regression, 30-day, 90-day mortality and unplanned 30-day readmission using logistic regression, and length of stay using Poisson regression. Of 123 085 clinical IA NSCLC, 7.9% underwent segmentectomy. Pathology showed 2.8% pN1 and 1.9% pN2 after segmentectomy, and 6.5% pN1 and 3.7% pN2 after lobectomy. For pN1, segmentectomy conferred 33% better survival within 2 years (aHR = 0.67, P = 0.03), but similar survival after 2 years (aHR = 1.06, P = 0.7). For pN2, segmentectomy had similar survival with lobectomy (aHR = 0.96, P = 0.7). For all clinical IA NSCLC, segmentectomy was associated with lower 30-day mortality (aOR = 0.55, P < 0.001), 90-day mortality (aOR = 0.57, P < 0.001), readmission (aOR = 0.86, P = 0.01) and shorter length of stay (aRR = 0.76, P < 0.001) than lobectomy. Outcomes after segmentectomy for clinical stage IA NSCLC may be associated with better short-term mortality, readmission rate and length of stay. Survival with occult pN1 and pN2 after segmentectomy is at least equivalent to lobectomy in completely resected clinical stage IA patients. A completion lobectomy may not be needed after pN1 and N2 findings after the permanent pathology was released.

Real-world evidence for pembrolizumab in non-small cell lung cancer: a nationwide cohort study

BackgroundBased on favourable results from clinical trials, immune checkpoint inhibitors (ICI) have become the standard first line (1 L) systemic anticancer treatment (SACT) for advanced stage non-small cell lung cancer (NSCLC) without targetable mutations. We evaluate whether these results are generalizable to everyday clinical practice and compare overall survival (OS) of patients treated with ICI to a historical cohort of patients treated with chemotherapy and results from clinical trials.MethodsOur study comprised all advanced NSCLC patients initiating SACT in 2012–21 in Norway. Clinical characteristics and treatment information was retrieved from Norwegian Health Registries.ResultsSurvival for all 8416 advanced NSCLC patients treated with SACT increased concurrently with the gradual implementation of ICIs. Median OS of patients treated with 1 L pembrolizumab after 2017 was better (mono-/combination therapy: 13.8/12.8 months) than for patients treated with chemotherapy before 2017 (8.0 months). Although median OS for patients treated with pembrolizumab was lower in clinical practice than clinical trials (Keynote-024/189: 26.3/22.0 months), the survival benefit relative to chemotherapy was similar.ConclusionOur nationwide study demonstrated a survival benefit over conventional chemotherapy of a similar magnitude as observed in clinical trials and confirms the effectiveness of pembrolizumab in routine clinical practice.

A Nomogram for Predicting Recurrence in Stage I Non-Small Cell Lung Cancer.

Early-stage non-small cell lung cancer (NSCLC) is being diagnosed increasingly, and in 30% of diagnosed patients, recurrence will develop within 5 years. Thus, it is urgent to identify recurrence-related markers to optimize the management of patient-tailored therapeutics. The eligible datasets were downloaded from TCGA and GEO. In the discovery phase, two algorithms, least absolute shrinkage and selector operation and support vector machine-recursive feature elimination, were used to identify candidate genes. The recurrence-associated signature was developed by penalized Cox regression. The nomogram was constructed and further tested via other independent cohorts. In this retrospective study, 14 eligible datasets and 7 published signatures were included. A 13-gene based signature was generated by penalized Cox regression categorized training cohort into high-risk and low-risk subgroups (HR = 8.873, 95% CI: 4.228-18.480 p < 0.001). Furthermore, a nomogram integrating the recurrence-related signature, age, and histology was developed to predict the recurrence-free survival in the training cohort, which performed well in the two external validation cohorts (concordance index: 0.737, 95% CI: 0.732-0.742, p < 0.001; 0.666, 95% CI: 0.650-0.682, p < 0.001; 0.651, 95% CI: 0.637-0.665, p < 0.001, respectively). The nomogram was further performed well in the Jiangsu cohort enrolled 163 patients (HR = 2.723, 95% CI: 1.526-4.859, p = 0.001). Post-operative adjuvant therapy achieved evaluated disease-free survival in high and intermediate risk groups (HR = 4.791, 95% CI: 1.081-21.231, p = 0.039). The proposed nomogram is a promising tool for estimating recurrence-free survival in stage I NSCLC, which might have tremendous value in management of early stage NSCLC and guiding adjuvant therapy strategies.

Impact of GAP score on surgical prognosis of non-small-cell lung cancer with usual interstitial pneumonia.

Post-surgical survival outcomes in patients with non-small-cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis (IPF) are expected to be worse than those in patients with other idiopathic interstitial pneumonias (IIPs). However, these remain unclear regarding patients with NSCLC and IPF histologically diagnosed as usual interstitial pneumonia [IPF(UIP)]. We aimed to assess the surgical and survival outcomes and identify prognostic factors in patients with NSCLC and IPF(UIP). This retrospective cohort study included patients with pathological stage I-III NSCLC and UIP. Prognostic factors and their association with lung cancer deaths (LCDs) and non-LCDs (NLCDs) were investigated. The overall survival of patients with UIP was significantly poorer than that of others with IIPs. The main causes of death were lung cancer (36%) and respiratory disease (44%). Multivariate analyses revealed the pathological stage of NSCLC ≥ II (hazard ratio [HR], 2.196; p = 0.009) and GAP stage ≥ II (HR, 2.821; p = 0.016) to be significant prognostic factors. NLCD incidence was significantly high in patients with GAP stage ≥ II. Recurrence occurred in 26 patients (36.1%); the period from recurrence to death was shorter in patients with IPF(UIP) than in patients without IPF(UIP). Patients with NSCLC and IPF(UIP) had poor prognosis after surgery. However, the prognosis varied greatly depending on the GAP stage. Considering the difficulty in managing post-surgical recurrence and high incidence of LCDs in patients with IPF(UIP), pursuing a radical resection is recommended in patients with GAP stage I. For patients with GAP stage ≥ II, comprehensive management of UIP is also necessary.

Optimal first-line treatment for EGFR-mutated NSCLC: a comparative analysis of osimertinib and second-generation EGFR-TKIs

BackgroundOsimertinib is an irreversible third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). It is the preferred first-line treatment for EGFR-mutated non-small cell lung cancer (NSCLC) compared to first-generation EGFR-TKIs. However, limited research has compared its clinical effectiveness with second-generation (2nd G) EGFR-TKIs.Materials and methodsThis study recruited patients diagnosed with stage IIIb-IV EGFR-mutated NSCLC who received first-line treatment with either 2nd G EGFR-TKIs (afatinib and dacomitinib) or osimertinib between April 2020 and April 2023.ResultsThe final analysis included 168 patients, of whom 113 received 2nd G EGFR-TKIs (afatinib or dacomitinib) and 55 received osimertinib. The median progression-free survival (PFS) did not differ significantly between 2nd G EGFR-TKIs and osimertinib (del 19: 17.6 months; L858R: 20.0 months vs. 28.3 months, p = 0.081). In patients with the EGFR exon 19 deletion, osimertinib conferred a longer median PFS (28.3 vs. 17.6 months, p = 0.118) and time to treatment failure (30.2 vs. 22.7 months, p = 0.722) than 2nd G EGFR-TKIs. However, the differences were not statistically significant. In patients with with the EGFR exon 19 deletion and central nervous system metastasis, the median PFS did not differ significantly between those treated with osimertinib (14.3 months) and those treated with 2nd G EGFR-TKIs (17.6 months; p = 0.881). Multivariate regression analysis revealed that the NSCLC stage was the only independent negative predictor of PFS. The treatment patterns in the second line also differed significantly between groups (p = 0.008).ConclusionsThis study found comparable effectiveness between osimertinib and 2nd G EGFR-TKIs as first-line treatment for advanced EGFR-mutated NSCLC, with only the NSCLC stage identified as a negative predictor of PFS. However, whether the different second-line treatments affect overall survival should be examined.