Early Non-small Cell Lung Cancer Research Articles

Advancing Nonsmall Cell Lung Cancer Diagnosis Accuracy via Dual Detection Fluorescent Nanoprobes.

Among the primary threats to human health worldwide, nonsmall cell lung cancer (NSCLC) remains a significant factor and is a leading cause of cancer-related deaths. Due to subtle early symptoms, NSCLC patients are diagnosed at advanced stages, resulting in low survival rates. Herein, novel Au-Se bond nanoprobes (NPs) designed for the specific detection of Calpain-2 (CAPN2) and Human Neutrophil Elastase (HNE), pivotal biomarkers in NSCLC, were developed. The NPs demonstrated exceptional specificity and sensitivity toward CAPN2 and HNE, enabling dual-color fluorescence imaging to distinguish between NSCLC cells and normal lung cells effectively. The NPs' performance was consistent across a wide pH range (6.2 to 8.0), and it exhibited remarkable resistance to biological thiol interference, indicating its robustness in complex physiological environments. These findings suggest the nanoprobe is a promising tool for early NSCLC diagnosis, offering a novel approach for enhancing the accuracy of cancer detection.

Clinical and economic outcomes associated with lymph node examination status in early-stage non-small cell lung cancer: a real-world US study using the SEER-Medicare linked database.

Clinical practice guidelines recommend adjuvant therapy for patients with early non-small cell lung cancer (eNSCLC), especially those with lymph node metastasis. This study evaluated the prevalence of lymph node examination and its association with adjuvant treatment rates, overall survival (OS), and healthcare costs among United States (US) Medicare patients with resected eNSCLC. This retrospective observational cohort study used Surveillance, Epidemiology, and End Results cancer registry data linked with Medicare claims data. Eligible patients were aged ≥65 years with newly diagnosed non-small cell lung cancer (NSCLC) stages IA to IIIB [the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 7th edition] between January 2010 and December 2017 with surgery ≤1 month prior to or ≤12 months after diagnosis. Patients were grouped by lymph node examination status: no examination (pNX), examination and no metastasis (pN0), or metastasis staging in N1 (pN1) or N2 (pN2). OS and costs were evaluated by examination status and number of lymph node examined. OS was analyzed using extended Cox proportional hazards models for specific time periods and time interaction with examination status, and adjusted for patient characteristics. Adjusted post-surgical healthcare costs per patient per month (PPPM) were analyzed using gamma-log regression models. Among the 14,648 patients included in the study, approximately 11% were pNX, whereas most were pN0 (68%), followed by pN1 (11%) and pN2 (10%). Adjuvant treatment rates were higher for pNX (35%) than pN0 (18%), but lower than pN1 (68%) and pN2 (74%) patients (P<0.001). Unadjusted OS for pNX patients was nearly identical to pN2, and significantly worse compared to pN0 and pN1 (P<0.0001). After adjusting for patient characteristics, pNX patients had higher risk of death relative to pN0 patients (P<0.001). Marginal mean adjusted total costs were comparable across pNX ($15,827 PPPM), pN0 ($12,712 PPPM) and pN1 ($17,089 PPPM), but significantly less for pN0 compared to pN2 ($23,566 PPPM) (P=0.002). Inadequate lymph node examination is associated with underutilization of adjuvant treatment and poor OS in resected NSCLC. In the current era of targeted and immunotherapies, lymph node examination is more important than ever, implicating the need for Quality Improvement practices and multidisciplinary coordination.

Evaluation of the efficacy and safety of robot-assisted and video assisted thoracic surgery for early non-small cell lung cancer: A meta-analysis.

Radical resection of lung cancer and chemotherapy are the main methods for the treatment of early lung cancer, but surgical treatment is still the key and preferred method. To evaluate the efficacy and safety of robotic-assisted thoracic surgery (RATS) and video assisted thoracic surgery (VATS) for non-small cell lung cancer (NSCLC). The clinical cohort studies on the comparison of the effects of RATS and VATS in the treatment of NSCLC published in Web of Science, PubMed, The National Library of Medicine (NLM), China National Knowledge Infrastructure (CNKI) and Wanfang database from January 1, 2015 to December 31, 2022 were searched. Two researchers independently screened the literature, extracted the data, such as operation time, intraoperative conversion rate, intraoperative blood loss, number of lymph nodes dissected, and evaluated the quality of the included literature based on the Newcastle-Ottawa Scale (NOS). RevMan 5.3 software was used for Meat analysis. A total of 18 articles and 21,802 subjects were included. The results of the meta-analysis showed that the intraoperative blood loss of RATS was significantly less than that of VAS, and the difference was statistically significant [MD =-38.43 (95% CI: -57.71, -19.15, P< 0.001)]. Compared with VATS, the number of lymph nodes dissected in RATS was significantly higher [MD = 2.61 (95% CI: 0.47, 4.76, P= 0.02)]. The rate of conversion to thoracotomy in RATS was lower, and the difference was statistically significant [OR = 0.59 (95% CI: 0.50, 0.70, P< 0.001)]. There was no significant difference between RATS and VATS in operation time [MD =-9.34 (95% CI: -28.72, 10.04, P= 0.34)], postoperative thoracic drainage time [MD =-0.08 (95% CI: -0.42, 0.26, P= 0.64)], postoperative hospital stay [MD =-0.05 (95% CI: -0.19, 0.08, P= 0.42)], postoperative mortality [OR = 0.88 (95% CI: 0.56, 1.36, P= 0.56)] and postoperative complications [OR = 1.03 (95% CI: 0.93, 1.13, P= 0.57)]. Compared with VATS, the number of lymph nodes dissected in RATS was significantly more, and the removal of lesions and lymph nodes was more thorough and accurate. More flexible and precise operation avoids the injury of important blood vessels during operation, effectively reduces the amount of blood loss during operation, shortens the indwelling time of thoracic drainage tube, and is conducive to postoperative rehabilitation of patients.

Recent progress in radioactive seed implantation brachytherapy of non-small cell lung cancer: a narrative review.

Brachytherapy, a new form of radiation therapy, has been used to treat lung cancer and consists of two main forms of treatment: endobronchial brachytherapy and radioactive seed implantation brachytherapy (RSI-BT), the latter of which is used to treat non-small cell lung cancer (NSCLC). The use of RSI-BT in the treatment of NSCLC at our centre has yielded some positive results. To more fully consider the context of this application, we conducted a search of PubMed from 2018 to March 5, 2023. The search included a combination of the MeSH terms: "brachytherapy" and "lung neoplasm". The majority of NSCLC patients who received RSI-BT achieved positive benefits. Most patients had a progression-free survival (PFS) of between 12 and 18 months. Additionally, radioactive particle stent implantation as a specific RSI-BT has shown therapeutic potential in the treatment of malignant airway obstruction. With the application of new technologies, RSI-BT will become more precise, efficient and inexpensive. This review demonstrates that RSI-BT can be therapeutic in the treatment of both early and advanced NSCLC with manageable complications. There have also been reports on the combination of RSI-BT with other therapies, but more research is needed on the combination of RSI-BT with them.

Perioperative immunotherapy: the main clinical treatment for resectable non-small cell lung cancer.

Phase 3 clinical trials of perioperative immunotherapy for resectable non-small cell lung cancer (NSCLC): In recent years, immunotherapy for NSCLC is not only limited to advanced disease, but also has shown gratifying efficacy for early resectable NSCLC. With the publication of the results of several phase 3 clinical trials, perioperative immunotherapy will become one of the main treatment modalities for resectable NSCLC.

Radiomics in stereotactic body radiotherapy for non-small cell lung cancer: a systematic review and radiomic quality score study.

Stereotactic body radiotherapy (SBRT) has been widely utilized for curative treatment of early-stage non-small cell lung cancer (NSCLC). It has achieved good local control rate comparable to surgery. Currently, no standard risk model exists for SBRT outcome or complication prediction. Radiomics has the potential to improve clinical outcome prognostication. Here, we reviewed the current literature on the radiomic analyses of thoracic SBRT through the use of radiomic quality score (RQS). Literature search was conducted on PubMed and Embase to retrieve radiomics studies on SBRT for early NSCLC. The literature search included studies up to June 2021. Only full papers published in peer reviewed journals were included. Studies that included metastatic lung cancers or non-lung cancers were excluded. Two independent investigators evaluated each study using the RQS and resolved discrepancies through discussion. A total number of 25 studies were analysed. The mean RQS was 7.76 of a maximum score of 36. This corresponds to 21.56% of the maximum score. Lack of feature reduction strategies, external validation and open data sharing were identified as key limitations of the reviewed studies. Meanwhile, various common radiomic signatures across different studies such as gray level co-occurrence matrix Homogeneity and energy have been identified. Multiple robust radiomic models have also been reviewed that may improve outcome or complication prediction. Radiomics in thoracic SBRT has a very promising future as a prognostication tool. However, larger multicenter prospective studies are required to confirm radiomic signatures. Improvement in future study methodologies can also facilitate its wider application.

Prognostic Analysis of Stage I Non-Small Cell Lung Cancer Abutting Adjacent Structures on Preoperative Computed Tomography.

Early non-small cell lung cancer (NSCLC) that abuts adjacent structures requires careful evaluation due to its potential impact on postoperative outcomes and prognosis. We examined stage I NSCLC with invasion into adjacent structures, focusing on the prognostic implications after curative surgical resection. We retrospectively analyzed the records of 796 patients who underwent curative surgical resection for pathologic stage IA/IB NSCLC (i.e., visceral pleural invasion only) at a single center from 2008 to 2017. Patients were classified based on tumor abutment and then reclassified by the presence of visceral pleural invasion. Clinical characteristics, pathological features, and survival rates were compared. The study included 181 patients with abutting NSCLC (22.7% of all participants) and 615 with non-abutting tumors (77.3%). Those with tumor abutment exhibited higher rates of non-adenocarcinoma (26.5% vs. 9.9%, p<0.01) and visceral/lymphatic/vascular invasion (30.4%/33.1%/12.7% vs. 8.5%/22.4%/5.7%, respectively; p<0.01) compared to those without abutment. Multivariable analysis identified lymphatic invasion and male sex as risk factors for overall survival (OS) and disease-free survival (DFS) in stage I NSCLC measuring 3 cm or smaller. Age, smoking history, vascular invasion, and recurrence emerged as risk factors for OS, whereas the presence of non-pure ground-glass opacity was a risk factor for DFS. NSCLC lesions 3 cm or smaller that abut adjacent structures present higher rates of various risk factors than non-abutting lesions, necessitating evaluation of tumor invasion into adjacent structures and lymph node metastasis. In isolation, however, the presence of tumor abutment without visceral pleural invasion does not constitute a risk factor.

Sublobar Resection in Early Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor Mutant

BackgroundLobectomy is a standard surgical procedure for peripherally located early-stage non-small cell lung cancers (NSCLCs) measuring 2 to 4 cm. However, it is unclear whether sublobar resections, such as wedge resection and segmentectomy, are effective in treating tumors with driver mutations in the epidermal growth factor receptor (EGFR). MethodsWe analyzed the clinicopathologic findings and surgical outcomes of 1395 patients with radiologically solid-dominant NSCLC measuring 2 to 4 cm, without clinical lymph node involvement, who underwent complete resection between 2010 and 2020. The patients, who underwent sublobar resections (n = 231) or lobectomy (n = 1164), were categorized by their EGFR mutation status and the surgical procedures performed. The follow-up was conducted for a median of 45.3 months. ResultsThe 5-year overall survival (OS) rates after sublobar resections (n = 39) were comparable to those after lobectomy (n = 359) in patients with EGFR mutation-positive tumors (80.5% [95% CI, 51.3%-93.2%] vs 88.8% [95% CI, 84.1%-92.1%], respectively; P = .16). Multivariable Cox regression analysis of OS revealed that the surgical procedure was an independent prognostic predictor in the entire cohort (hazard ratio, 0.6; 95% CI, 0.4-1.0; P = .028), but it was not an independent prognostic predictor in patients with EGFR-mutated tumors (hazard ratio, 0.6; 95% CI, 0.2-1.7; P = .32). ConclusionsSublobar resection with a secure surgical margin could be a viable option for appropriately selected patients with peripheral early-stage NSCLC tumors measuring 2 to 4 cm and harboring EGFR mutations, because it provides comparable OS to that of lobectomy.

Outcomes of carbon ion radiotherapy compared with segmentectomy for ground glass opacity-dominant early-stage lung cancer

PurposeThis study aimed to compare the outcomes of patients with ground-grass opacity (GGO)-dominant non-small cell lung cancer (NSCLC) who were treated with carbon ion radiotherapy (CIRT) versus segmentectomy.MethodsA retrospective review of medical records was conducted. The study included 123 cases of clinical stage 0/IA peripheral NSCLC treated with single-fraction CIRT from 2003 to 2012, 14 of which were determined to be GGO-dominant and were assigned to CIRT group. As a control, 48 consecutive patients who underwent segmentectomy for peripheral GGO-dominant clinical stage IA NSCLC were assigned to segmentectomy group.ResultsThe patients in CIRT group, compared with segmentectomy group, were significantly older (75 ± 7.2 vs. 65 ± 8.2 years, P = 0.000660), more likely to be male (13/14 vs. 22/48, P = 0.00179), and had a lower forced vital capacity (91 ± 19% vs. 110 ± 13%, P = 0.0173). There was a significant difference in the 5-years overall survival rate (86% vs. 96%, P = 0.000860), but not in the 5-years disease-specific survival rate (93% vs. 98%, P = 0.368).DiscussionCompared with segmentectomy, CIRT may be an alternative option for patients with early GGO-dominant NSCLC who are poor candidates for, or who refuse, surgery.

EE508 Cost Estimation Model of Prevented Recurrences with Atezolizumab in Early Non-Small Cell Lung Cancer in Italy

EE508 Cost Estimation Model of Prevented Recurrences with Atezolizumab in Early Non-Small Cell Lung Cancer in Italy

Biologically effective dose (BED) value lower than 120Gy improve outcomes in lung SBRT.

Lung SBRT has a well-defined role in the treatment of patients with early stage non-small cell lung cancer who are not surgical candidates or refuse surgery. Biologically effective dose (BED) of greater than or equal to 100Gy has been recommended. However, optimal fractionationremains unclear. Our objective was analyze patients treated with lung SBRT in our institution and evaluate outcomes according prescribed dose. One hundred nine patients with early non-small cell lung cancer and treated with lung SBRT were retrospectively analyzed. Differences between dose received, local control, and survival were evaluated. For comparison of BEDs, the prescribed dose for SBRT was stratified according to two groups: high (BED > 120Gy) and low (BED < 120Gy). A relationship between mortality and total dose (54.7Gy ± 4.8) was observed. Significantly worse survival was observed for patients with higher total doses (p < 0.003). It was found that patients receiving BED > 120 had increased mortality compared to patients receiving BED < 120 (p = 0.021). It was observed mean dose/fraction 12.6Gy/f was a protective factor and decreased the probability of death. Our data suggest that mean total dose lower 54 and a calculated BED < 120Gy is the optimal. Further prospective data are needed to confirm these results and determine the optimal dose fractionation scheme as a function of tumor size and location of volume.

Evaluation of the application value of seven tumor-associated autoantibodies in non-small cell lung cancer based on machine learning algorithms

Objective: Based on the diagnostic model established and validated by the machine learning algorithm, to investigate the value of seven tumor-associated autoantibodies (TAABs), namely anti-p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1 and CAGE antibodies in the diagnosis of non-small cell lung cancer (NSCLC) and to differentiate between NSCLC and benign lung nodules. Methods: This was a retrospective study of clinical cases. Model building queue: a total of 227 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from November 2018 to June 2021 were collected as the NSCLC group, and 120 cases of benign lung nodules, 122 cases of pneumonia and 120 healthy individuals were selected as the control groups. External validation queue: a total of 100 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from May 2022 to December 2022 were collected as the NSCLC group, and 36 cases of benign lung nodules, 32 cases of pneumonia and 44 healthy individuals were selected as the control groups. In addition, NSCLC was divided into early (stage 0-ⅠB) and mid-to-late (stage ⅡA-ⅢB) subgroups. The levels of 7-TAABs were detected by enzyme immunoassay, and serum concentrations of CEA and CYFRA21-1 were detected by electrochemiluminescence. Four machine learning algorithms, XGBoost, Lasso logistic regression, Naïve Bayes, and Support Vector Machine are used to establish classification models. And the best performance model was chosen based on evaluation metrics and a multi-indicator combination model was established. In addition, an online risk evaluation tool was generated to assist clinical applications. Results: Except for p53, the levels of rest six TAABs, CEA and CYFRA21-1 were significantly higher in the NSCLC group (P<0.05). Serum levels of anti-SOX2 [1.50 (0.60, 10.85) U/ml vs. 0.8 (0.20, 2.10) U/ml, Z=2.630, P<0.05] and MAGEA1 antibodies [0.20 (0.10, 0.43) U/ml vs. 0.10 (0.10, 0.20) U/ml, Z=2.289, P<0.05], CEA [3.13 (2.12, 5.64) ng/ml vs. 2.11 (1.25, 3.09) ng/ml, Z=3.970, P<0.05] and CYFRA21-1 [4.31(2.37, 7.14) ng/ml vs. 2.53(1.92, 3.48) ng/ml, Z=3.959, P<0.05] were significantly higher in patients with mid-to late-stage NSCLC than in early stages. XGBoost model was used to establish a multi-indicator combined detection model (after removing p53). 6-TAABs combined with CYFRA21-1 was the best combination model for the diagnosis of NSCLC and early NSCLC. The optimal diagnostic thresholds were 0.410, 0.701 and 0.744, and the AUC was 0.828, 0.757 and 0.741, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in model building queue, and the AUC was 0.760, 0.710 and 0.660, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in external validation queue. Conclusion: In the diagnosis of NSCLC, 6-TAABs is superior to that of traditional tumor markers CEA and CYFRA21-1, and can compensate for the shortcomings of traditional tumor markers. For the differential diagnosis of NSCLC and benign lung nodule, "6-TAABs+CYFRA21-1" is the most cost-effective combination, and plays an important role in prevention and screening for early lung cancer.

Early Non-Small Cell Lung Cancer Heterogeneity and Recurrence Assessed by Tissue Next-Generation Sequencing Genotyping and Circulating Tumor Cell EZH2 Characterization

Early Non-Small Cell Lung Cancer Heterogeneity and Recurrence Assessed by Tissue Next-Generation Sequencing Genotyping and Circulating Tumor Cell EZH2 Characterization

EP07.04-26 Real-World Biomarker Testing and Treatment Patterns Identified Using Machine Learning in Early Non-small Cell Lung Cancer

EP07.04-26 Real-World Biomarker Testing and Treatment Patterns Identified Using Machine Learning in Early Non-small Cell Lung Cancer

Intelligent prognosis evaluation system for stage I-III resected non-small-cell lung cancer patients on CT images: a multi-center study

Prognosis is crucial for personalized treatment and surveillance suggestion of the resected non-small-cell lung cancer (NSCLC) patients in stage I-III. Although the tumor-node-metastasis (TNM) staging system is a powerful predictor, it is not perfect enough to accurately distinguish all the patients, especially within the same TNM stage. In this study, we developed an intelligent prognosis evaluation system (IPES) using pre-therapy CT images to assist the traditional TNM staging system for more accurate prognosis prediction of resected NSCLC patients. 20,333 CT images of 6371 patients from June 12, 2009 to March 24, 2022 in West China Hospital of Sichuan University, Mianzhu People's Hospital, Peking University People's Hospital, Chengdu Shangjin Nanfu Hospital and Guangan Peoples' Hospital were included in this retrospective study. We developed the IPES based on self-supervised pre-training and multi-task learning, which aimed to predict an overall survival (OS) risk for each patient. We further evaluated the prognostic accuracy of the IPES and its ability to stratify NSCLC patients with the same TNM stage and with the same EGFR genotype. The IPES was able to predict OS risk for stage I-III resected NSCLC patients in the training set (C-index 0.806; 95% CI: 0.744-0.846), internal validation set (0.783; 95% CI: 0.744-0.825) and external validation set (0.817; 95% CI: 0.786-0.849). In addition, IPES performed well in early-stage (stage I) and EGFR genotype prediction. Furthermore, by adopting IPES-based survival score (IPES-score), resected NSCLC patients in the same stage or with the same EGFR genotype could be divided into low- and high-risk subgroups with good and poor prognosis, respectively (p<0.05 for all). The IPES provided a non-invasive way to obtain prognosis-related information from patients. The identification of IPES for resected NSCLC patients with low and high prognostic risk in the same TNM stage or with the same EGFR genotype suggests that IPES have potential to offer more personalized treatment and surveillance suggestion for NSCLC patients. This study was funded by the National Natural Science Foundation of China (grant 62272055, 92259303, 92059203), New Cornerstone Science Foundation through the XPLORER PRIZE, Young Elite Scientists Sponsorship Program by CAST (2021QNRC001), Clinical Medicine Plus X - Young Scholars Project, Peking University, the Fundamental Research Funds for the Central Universities (K.C.), Research Unit of Intelligence Diagnosis and Treatment in Early Non-small Cell Lung Cancer, Chinese Academy of Medical Sciences (2021RU002), BUPT Excellent Ph.D. Students Foundation (CX2022104).

Assessment of Precision Irradiation in Early Non-Small Cell Lung Cancer and Interstitial Lung Disease (ASPIRE-ILD): Primary Analysis of a Phase II Trial

The use of stereotactic ablative radiotherapy (SABR) in patients with fibrotic interstitial lung disease (ILD) has been associated with an increased risk of toxicity, but patients with ILD and lung cancer may have no other options for curative-intent treatment. The goal of the ASPIRE-ILD trial was to assess the benefits and toxicities of SABR in patients with fibrotic ILD. We enrolled patients with fibrotic ILD and a diagnosis of T1-2N0 NSCLC who were not candidates for surgery. All patients were centrally reviewed prior to enrollment to confirm the presence and subtype of ILD. After stratification by the ILD-GAP score (a measure of ILD severity and prognosis), patients were treated with SABR to a dose of 50 Gy in 5 fractions EOD (BED = 100 Gy10), with a built-in de-escalation protocol in case of unacceptable toxicity. The primary endpoint was overall survival (OS), powered to distinguish 1-year OS >70% vs. an unacceptable rate of ≤50%. Secondary endpoints included toxicity (CTC-AE version 4.0), progression-free survival (PFS), local control (LC), patient-reported outcomes (FACT-L quality of life and cough severity), and changes in pulmonary function tests (PFTs). The study pre-specified that SABR would be considered worthwhile if median OS was >1 year, with a grade 3-4 toxicity risk <35% and a grade 5 toxicity risk <15%. Target accrual was 39 treated patients. Thirty-nine patients were enrolled and treated with SABR between March 2019 and January 2022, all to a dose of 50 Gy in 5 fractions, at 5 institutions in Canada and 1 in Scotland. Median age was 78 years (interquartile range: 67-83), 59% were male, and 92% had a history of smoking (median 43 pack-years). At baseline, 70% reported dyspnea, median FEV1 was 80% predicted and median DLCO was 49% predicted. ILD-GAP scores were as follows: ≤2 (i.e., best ILD status): n = 14; 3-5: n = 23; ≥6 (i.e., worst ILD status): n = 2. Median follow-up was 19 months. OS at 1-year was 78.9% (p<0.001 by binomial test vs. the unacceptable rate). Median OS was 25 months, median PFS was 19 months, and 2-year LC was 92%. AE rates (possibly, probably or definitely related) were as follows (highest grade per patient): grade 1-2: n = 12 (31%); grade 3: n = 4 (10%); grade 4; n = 0; grade 5 n = 3 (7.7%, all due to respiratory deterioration). AE rates did not differ by ILD-GAP category or ILD subtype. FACT-L scores trended downward over time (p = 0.07), and cough severity scale scores worsened over time (p = 0.02). Comparing last-available PFTs with baseline, DLCO declined (median: -4%; p = 0.046), FVC trended downward (median: -2.5%; p = 0.11), and FEV1 remained stable (median change: 0%). The use of SABR in patients with ILD met the pre-specified acceptability thresholds for both toxicity and efficacy, supporting the use of SABR for curative-intent treatment after a careful discussion of risks and benefits. Further studies exploring pharmacologic options to reduce toxicity may be beneficial in this population. ().

Incidence and Risk Factors for Brain Metastases in Patients with Lung Cancer: A Systematic Review and Meta-Analysis

Brain metastases (BM) are a very common metastatic site in lung cancer, but the exact rate of metastasis is still controversial. Risk factors for BM development are also largely lacking, hampering personalized treatment strategies. This study aimed to identify the incidence and possible risk factors for BM in lung cancer. A systematic review, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guide-lines, was conducted using PubMed, Medline databases and Cochrane Library databases from inception until February 2023. Two investigators independently searched and selected literature, included in randomized controlled trials and cohort studies. Heterogeneity was assessed using the χ2 test and the I2 statistic. Significant heterogeneity was indicated by P <0.05 in Cochrane Q tests and a ratio greater than 40% in I2 statistics. The review is registered on PROSPERO, number: CRD42022370173. Forty-nine studies were included in the meta-analysis. The results showed that the incidence rate of BM in non-small cell lung cancer (NSCLC) was 0.24 (95% confidence interval [CI]: 0.23-0.25; I2 = 97.1%). The incidence rate in early NSCLC was 0.11 (95% CI: 0.10-0.13), locally advanced NSCLC was 0.32 (95% CI: 0.29-0.34), and advanced NSCLC was 0.37 (95% CI: 0.35-0.38). Lung adenocarcinoma was more prone to BM in NSCLC (risk ratio [RR] = 3.59, 95% CI: 1.97-6.54; P<0.001). The BM rate of NSCLC with EGFR mutation was also higher (hazard ratio [HR] = 1.49, 95% CI: 1.14-1.94; P = 0.004). Sex and smoking had no significant effect on the incidence of BM in NSCLC. Prophylactic Cranial Irradiation (PCI) could significantly reduce BM in NSCLC (HR = 0.36, 95% CI: 0.23-0.56; P<0.001), but chemotherapy had no obvious effect on decreasing the rate of BM (HR = 0.91, 95% CI: 0.54-1.54; P = 0.73). The incidence rate of BM in small cell lung cancer (SCLC) was 0.28 (95% CI: 0.27-0.30; I2 = 95.9%), and 0.23 (95% CI: 0.20-0.25) in the limited-stage SCLC. Older age (≥65) (HR = 0.70, 95% CI: 0.54-0.92; P = 0.01) were associated with less BM in SCLC. A higher T stage (≥T3) (HR = 1.72, 95% CI: 1.16-2.56; P = 0.007) was a significant risk factor for BM, while sex, smoking dose were not. PCI could also significantly decreased BM in SCLC (HR = 0.47, 95% CI: 0.38-0.58; P<0.001). This study is the first meta-analysis of BM incidence rate in lung cancer, and further explores the factors affecting BM, providing some suggestions for clinical decision-making of BM prevention in patients with lung cancer.

Befotertinib: First Approval.

Befotertinib (Surmana®) is an orally administered, highly selective, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) being developed by Betta Pharmaceuticals and InventisBio for the treatment of non-small cell lung cancer (NSCLC). In May 2023, befotertinib was approved in China for the second-line treatment of patients with locally advanced or metastatic NSCLC who have received EGFR TKI therapy and have disease progression with positive EGFR T790M mutation. Befotertinib is under regulatory review for the first-line treatment of NSCLC in China. Clinical studies assessing befotertinib as an adjuvant therapy after surgery for early EGFR-mutant NSCLC (phaseIII) and in combination with icotinib for advanced or metastatic EGFR-mutant NSCLC (phaseII) are currently underway in China. This article summarizes the milestones in the development of befotertinib leading to this first approval for the second-line treatment of EGFR T790M-mutated locally advanced or metastatic NSCLC.

129 Assessment of Precision Irradiation in Early Non-Small Cell Lung Cancer and Interstitial Lung Disease (ASPIRE-ILD): Primary Analysis of a Phase II Trial

129 Assessment of Precision Irradiation in Early Non-Small Cell Lung Cancer and Interstitial Lung Disease (ASPIRE-ILD): Primary Analysis of a Phase II Trial

Preoperative small airway dysfunction is associated with skeletal muscle loss in early-stage non-small cell lung cancer

Postoperative skeletal muscle loss (SM loss) was reported to be associated with a poor prognosis in early-stage non-small cell lung cancer (NSCLC). Small airway dysfunction (SAD) is a common but neglected respiratory abnormality. Little information is known about the association between preoperative SAD and postoperative SM loss in early-stage NSCLC. Therefore, this study aimed to investigate the correlation between preoperative SAD and SM loss after surgery in early-stage NSCLC patients. There were 348 NSCLC patients with stages I-IIIA in this study from January 2017 to December 2020. All CT images were contrast-enhanced scans, and the skeletal muscle index (SMI) was measured using CT images. A 10.0% decrease in SMI over 12 months was determined as the cut-off value to define excessive SM loss. Logistic regression analyses were used to examine the relationship between SAD and SM loss. This study included 348 subjects who underwent pulmonary operation (159 males and 189 females; mean age: 57.5±8.8 years). 152 (43.7%) patients were identified as having SAD before surgery, and 179 patients (51.4%) were identified as having SM loss after 1 year. Moreover, a higher incidence of SAD was found in the SM loss group compared with that in the non-SM loss group (52.0% vs. 34.9%, p=0.001). The patients with SAD were older, had larger tumor size, and had lower albumin levels. Furthermore, there were significant correlations between the lung function parameters manifesting SAD and the percentage change in SMI (for the forced expiratory flow when 75% of forced vital capacity has been exhaled (FEF75%), Pearson r=-0.107, p=0.046; for FEF50%, r=-0.142, p=0.008; and for FEF25-75%, r=-0.124, p=0.021; respectively). However, no significant correlations were found between SMI and the lung function parameters reflecting proximal airway obstruction (p>0.05). Logistic regression analysis revealed that preoperative SAD (HR, 2.465; 95% CI, 1.256-4.838; p=0.009) was independent risk factor for postoperative SM loss in early-stage NSCLC. In addition, multivariable analysis revealed that SAD (HR, 1.816; 95% CI, 1.025-3.216, P=0.041) were associated with postoperative complications. Preoperative SAD is significantly associated with postoperative complications and SM loss in early NSCLC patients. Our results suggest that preoperative assessment of SAD may be useful for risk stratification of surgical candidates with potential for targeted interventions.