Translational lung cancer research最新文献

Background: Tumor markers such as serum carcinoembryonic antigen (CEA) and cytokeratin fragment 19 (CYFRA 21-1) are utilized for assessing the effectiveness of chemotherapy in non-small cell lung cancer (NSCLC) patients. Yet, it remains uncertain whether these markers can reliably forecast responses to combined chemoimmunotherapy. Our study aimed to examine the significance and effectiveness of these markers in predicting responses among NSCLC patients undergoing combined chemoimmunotherapy.

Methods: This two-part observational study involved patients with NSCLC who were treated with combined chemoimmunotherapy in Japanese hospitals. An initial retrospective study of these patients, with serum CEA and CYFRA 21-1 as prognostic factors for combined chemoimmunotherapy outcomes, served as a discovery cohort. Patients in a subsequent prospective study served as a validation cohort, where we assessed the prognostic accuracy of CEA and CYFRA 21-1 cut-off points determined by the discovery cohort.

Results: In total, 121 patients treated with combined chemoimmunotherapy were included, with 44 and 77 patients in the discovery and validation cohorts, respectively. Serum CYFRA 21-1 levels >3.0 ng/mL were significantly associated with progression-free survival (PFS) in both the discovery and validation cohorts (P=0.01, P=0.04, respectively). PFS did not differ significantly by CEA levels (P=0.21).

Conclusions: After combined chemoimmunotherapy treatment, serum CYFRA 21-1 stands out as a potentially valuable biomarker for predicting the prognosis of NSCLC.

Background: With increasing significance of lung cancer screening programs, it is essential to determine the group of participants, who would benefit the most from screening. In our study, we aimed to establish the correlation between lung emphysema and lung cancer risk.

Methods: The study design was cross-sectional. Low-dose computed tomography (LDCT) scans of 896 subjects from MOLTEST-BIS lung cancer screening program, including 100 subjects with detected lung cancer, were visually evaluated for the presence, type and severity of emphysema. Quantitative emphysema evaluation was performed with Siemens syngo.via Pulmo 3D application.

Results: Visually detected presence of centrilobular emphysema (CLE) correlated with male gender (P=0.02), age (P<0.001) and pack-years of smoking (P=0.004), as well as with quantitative assessment of Emphysema Index (EI) (P=0.008), and with emphysema clusters of given size (Clas 1-4) Clas 1, Clas 3 and Clas 4 (P<0.001). Visually assessed severity grade of emphysema correlated with age (P<0.001), pack-years of smoking history (P=0.002) and EI (P<0.001). There was a correlation between lung cancer occurrence and pack-years (P<0.001), age (P<0.001), and presence of CLE (P<0.001) but no correlation with gender (P=0.88) and EI (P=0.32) was found. In the logistic regression model pack-years, age, qualitative severity of CLE and Clas 1 were significant factors correlated with lung cancer occurrence (P<0.001).

Conclusions: Qualitative and quantitative emphysema evaluation correlate with each other. Both, presence and severity of CLE correlate with higher incidence of lung cancer. Severity of visually assessed emphysema, age and pack-years of smoking are significant predictors of lung cancer occurrence.

Background: Family history of cancer (FHC) has been reported to increase mortality of non-small cell lung cancer, mainly comprised of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). However, the impact of FHC on long-term survival remains controversial. This study aims to identify the impact of FHC on postoperative survival in LUAD and LUSC.

Methods: Patients underwent lung resection for LUAD or LUSC in West China Hospital from 2009 to 2021 were enrolled. The 5-year overall survival (OS), lung cancer-specific survival (LCSS) and progression-free survival (PFS) were compared between the patients with and without FHC. Multivariable Cox regression was also performed.

Results: A total of 6,253 patients were enrolled, including 5,685 LUAD and 568 LUSC. Altogether 18.9% (1,077/5,685) patients had FHC in LUAD, and 12.7% (72/568) patients had FHC in LUSC. In LUAD, the patients with FHC showed comparable survival compared with the patients without FHC regarding 5-year OS (87.9% vs. 86.5%, P=0.49), 5-year PFS (84.8% vs. 80.9%, P=0.06), and 5-year LCSS (89.2% vs. 88.0%, P=0.96). In LUSC, the patients with FHC had poorer survival compared with the patients without FHC according to 5-year OS (40.9% vs. 68.2%, P=0.007), 5-year PFS (42.3% vs. 66.2%, P=0.003), and 5-year LCSS (45.8% vs. 72.7%, P=0.003). Multivariate analyses indicated that FHC was an independent prognostic factor of OS, PFS, and LCSS in the patients with LUSC.

Conclusions: FHC was associated with a poor survival after lung resection in LUSC not LUAD patients. More attention should be paid in postoperative monitoring and treatment in LUSC patients with FHC.

Background: Immunotherapy has been recommended for neoadjuvant therapy in patients with locally advanced non-small cell lung cancer (NSCLC). However, its effect on surgical resection has not yet been examined. This study aimed to examine the effect of induction immunotherapy on surgical resection in terms of the surgical approach, resection extent, and perioperative recovery.

Methods: We performed a real-world study comprising consecutive patients with clinical stage IB-IIIB NSCLC who received surgical resection after induction immunotherapy from January 2019 to September 2021. The perioperative outcomes were compared in terms of the surgical approach and resection extent.

Results: Among 68 patients, 37 (54.4%) achieved a clinical objective response. Standard resection was performed in 37 patients (54.4%), while extended resection was necessary in the other 31 patients (45.6%). Minimally invasive surgery (MIS) was attempted in 37 cases (54.4%), with only 1 (2.7%) conversion. MIS was significantly more commonly accomplished in patients with a clinical objective response than those without (67.6% vs. 35.5%, P=0.008). Patients with a clinical objective response were more likely to have their tumors removed via MIS and/or standard resection (75.7% vs. 51.6%, P=0.04), while those without a clinical objective response more often required extended resection using an open approach. Patients receiving standard resection or MIS had significantly better perioperative outcomes than those who underwent extended resection or thoracotomy (all P<0.05).

Conclusions: The results of this large single-center retrospective cohort indicate that in terms of a better clinical response, effective induction immunotherapy could help reduce the resection extent and/or provide more opportunities to perform MIS, resulting in better recovery.

Background: Chemotherapy combined with immunotherapy is currently the standard first-line treatment for advanced small-cell lung cancer (SCLC). Immunotherapy can induce specific adverse events, called immune-related adverse events (irAEs). IrAEs of bones have rarely been reported. However, identifying bone irAEs could be important in avoiding misdiagnosis and ensuring appropriate patient management. This is the first report describing the diagnosis of irAEs of osteoblastic bone changes mimicking bone metastasis in a SCLC patient treated with durvalumab.

Case description: In this report, we describe a unique and challenging case in which a 54-year-old female patient with SCLC treated with durvalumab, an immunotherapy drug, exhibited osteoblastic bone changes that appeared similar to bone metastasis on imaging but were actually a side effect of immunotherapy. Before treatment, imaging revealed no bone metastasis. In the third month after treatment with durvalumab, computed tomography (CT) revealed multiple bone alterations, predominantly osteoblastic lesions with minor osteolytic changes. Various imaging tests suggested bone metastasis, but she had no symptoms related to bone disease. Notably, the lesions in the chest had achieved a partial response. Based on a comprehensive analysis of the CT-guided pathological biopsy results, the patient's symptoms, and the biological characteristics of SCLC, we determined that these bone changes were irAEs occurring in the skeletal system. The patient was followed up for 10 months, during which time the bone lesions remained stable.

Conclusions: IrAEs of bones are rare, and their manifestations vary. Sometimes, the imaging manifestations of bone irAEs are difficult to distinguish from bone metastasis. If patients show variable treatment responses between different lesions, careful evaluation (including a pathological biopsy) is necessary.

Background: Lung cancer is responsible for most cancer-related deaths, and non-small cell lung cancer (NSCLC) accounts for the majority of cases. Targeted therapy has made promising advancements in systemic treatment for NSCLC over the last two decades, but inadequate drug targets with clinically proven survival benefits limit its universal application in clinical practice compared to chemotherapy and immunotherapy. There is an urgent need to explore new drug targets to expand the beneficiary group. This study aims to identify druggable genes and to predict the efficacy and prognostic value of the corresponding targeted drugs in NSCLC.

Methods: Two-sample mendelian randomization (MR) of druggable genes was performed to predict the efficacy of their corresponding targeted therapy for NSCLC. Subsequent sensitivity analyses were performed to assess potential confounders. Accessible RNA sequencing data were incorporated for subsequent verifications, and Kaplan-Meier survival curves of different gene expressions were used to explore the prognostic value of candidate druggable genes.

Results: MR screening encompassing 4,863 expression quantitative trait loci (eQTL) and 1,072 protein quantitative trait loci (pQTL, with 453 proteins overlapping) were performed. Seven candidate druggable genes were identified, including CD33, ENG, ICOSLG and IL18R1 for lung adenocarcinoma, and VSIR, FSTL1 and TIMP2 for lung squamous cell carcinoma. The results were validated by further transcriptomic investigations.

Conclusions: Drugs targeting genetically supported genomes are considerably more likely to yield promising efficacy and succeed in clinical trials. We provide compelling genetic evidence to prioritize drug development for NSCLC.

Background: Despite its efficacy in reducing lung cancer (LC)-specific mortality by 20%, screening with low-dose computed tomography (LDCT) in eligible groups remains low (5-16%). Black individuals are more commonly affected by LC than other racial/ethnic groups in the United States (U.S.) but less likely to undergo LC screening (LCS). Our study aimed to explore the knowledge and beliefs of Black individuals at high risk regarding LCS.

Methods: Black individuals (n=17) who met the 2021 United States Preventive Services Task Force (USPSTF) LCS eligibility criteria were recruited in upstate New York. In-depth semi-structured interviews were conducted, audio recorded, and transcribed to explore knowledge and beliefs that could influence the uptake of LCS. A qualitative thematic analysis method was used to identify and analyze themes within the data.

Results: We identified principal themes about LC and LCS. Although most participants reported that smoking was the major risk factor for LC, some participants placed more emphasis on other factors as the major risk factors for LC and de-emphasized the role of smoking. Most participants were not aware that screening for LC existed. Several barriers and facilitators for LCS were identified.

Conclusions: Awareness about LCS among Black individuals is low. Addressing barriers may help increase LCS rates among Black individuals, ultimately reducing their LC mortality. The findings from our study have important implications in designing more effective interventions involving community health workers and healthcare clinicians to increase LCS uptake among Black individuals at high risk.

Background: Research has demonstrated that radiomics models are capable of forecasting the characteristics of lung cancer. Nevertheless, due to radiomics' poor interpretability, its applicability in clinical settings remains restricted. This investigation sought to verify the correlation between radiomics features (RFs) and the biological behavior of clinical stage IA adenocarcinomas.

Methods: A retrospective analysis was conducted on patients diagnosed with clinical stage IA lung adenocarcinoma who underwent resection between May 2005 and December 2018. Detailed radiomics examination of the primary tumor was carried out utilizing preoperative computed tomography (CT) images. Subsequently, patients were grouped based on their RFs using consensus clustering, enabling comparison of tumor biological characteristics among the clusters. Survival disparities among the clusters were evaluated through Kaplan-Meier and Cox analyses.

Results: A consensus cluster analysis was performed on 669 patients [median age, 58 years; interquartile range (IQR), 50-64 years, 257 males, 412 females], and three distinct clusters were identified. Cluster 2 was associated with radiological solid adenocarcinoma [119 of 324 (36.7%), P<0.001], larger tumors with median tumor size of 2.1 cm with IQR of 1.7 to 2.5 cm (P<0.001), central tumor [91 of 324 (28.1%), P=0.002], pleural invasion [87 of 324 (26.9%), P<0.001], occult lymph node metastasis (ONM) [106 of 324 (32.7%), P<0.001], and a higher frequency of metastasis or recurrence [62 of 324 (19.1%), P<0.001]. The frequency of histological grade 3 was the highest in Cluster 3 [8 of 34 (23.5%), P<0.001]. Cluster 1 was associated with pure ground glass nodules (pGGNs) [184 of 310 (59.4%), P<0.001], smaller tumors with median tumor size of 1.1 cm with IQR of 0.8 to 1.4 cm (P<0.001), no pleural invasion [276 of 310 (89.0%), P<0.001], histological grade 1 [114 of 248 (46.0%), P<0.001], ONM negative [292 of 310 (94.2%), P<0.001], and a lower rate of metastasis or recurrence [298 of 310 (96.1%), P<0.001].

Conclusions: Differences in tumor biological behavior were detected among consensus clusters based on the RFs of clinical stage IA adenocarcinoma.

Background: The International Association for the Study of Lung Cancer (IASLC) pathology panel has proposed a new grading system for invasive lung adenocarcinoma (LADC). This study aims to validate this novel grading system for invasive LADC using propensity score matching (PSM), with a specific focus on patients exhibiting spread through air space (STAS).

Methods: We retrospectively analyzed the clinicopathologic features of a large cohort of 910 non-mucinous LADCs with STAS from 2017 to 2020 and classified them according to the novel grading system. We applied PSM to adjust for potential confounders between the grading groups. Kaplan-Meier and Cox proportional hazards models were adopted for prognostic evaluation.

Results: The results showed that the IASLC grading system (grades 2 and 3) stratified well in terms of recurrence-free survival (RFS) and overall survival (OS) (P=0.02 and P=0.02, respectively) after matching, with Grade 3 being an independent predictor of RFS [hazard ratio (HR), 1.533; P=0.02] and OS (HR, 2.765; P=0.02) in multivariable models. The concordance index (C-index) and area under the curve (AUC) of the IASLC system were 0.719 and 0.754 for recurrence and 0.844 and 0.891 for death, respectively. In addition, anaplastic lymphoma kinase (ALK) fusion and tumor protein p53 (TP53) mutations were detected more frequently in grade 3 tumors, while epidermal growth factor receptor (EGFR) mutations were more prevalent in grade 2 tumors. The IASLC grade did not predict the benefit of adjuvant chemotherapy (ACT).

Conclusions: This study suggests that the new IASLC grading system is a valuable prognostic tool for patients with STAS-positive LADC.