Number of involved nodal stations predicts survival in small cell lung cancer.

BACKGROUND: In small cell lung cancer (SCLC), the pathological N category is identical to it in non-small cell lung cancer (NSCLC) and remains unchanged over a decade. Here we verified the discriminability of number of involved nodal stations (nS) in SCLC and compared its efficacy in predicting survival with currently used pathological nodal (pN) staging. METHODS: We retrospectively analyzed the patients who received operations and were pathologically diagnosed as SCLC at Shanghai Pulmonary Hospital between 2009 and 2019. X-tile software was adopted to determine optimal cut-off values for nS groups. Kaplan-Meier method and Cox regression analysis were used to compare survival between different groups. Decision curve analysis (DCA) was employed to evaluate the standardized net benefit. RESULTS: A total of 369 patients were included. The median number of sampled stations was 6 (range 3-11), and the median number of positive stations was 1 (range 0-7). The optimal cutoff for nS groups was: nS0 (no station involved), nS1-2 (one or two stations involved), and nS ≥ 3 (three or more stations involved). Overall survival (OS) and relapse-free survival (RFS) were statistically different among all adjacent categories within the nS classification (p < 0.001, for both OS and RFS between each two subgroups), but survival curves for subgroups in pN overlapped (OS, p = 0.067; RFS, p = 0.068, pN2 vs. pN1). After adjusting for other confounders, nS was a prognostic indicator for OS and RFS. The DCA revealed that nS had improved predictive capability than pN. CONCLUSIONS: Our cohort study demonstrated that the nS might serve as a superior indicator to predict survival than pN in SCLC and was worth considering in the future definition of the N category.

Optimal surgical timing for lung cancer following SARS-CoV-2 infection: a prospective multicenter cohort study.

BACKGROUND: With the ongoing prevalence of the emerging variant and global vaccination efforts, the optimal surgical timing for patients with resectable lung cancer in the Omicron-dominant period requires further investigation. METHODS: This prospective multicenter study involved patients who underwent radical surgery for lung cancer between January 29, 2023 and March 31, 2023. Patients were categorized into four groups based on the interval between SARS-CoV-2 infection and surgery. The main outcomes evaluated were 30-day mortality and 30-day morbidity. RESULTS: A total of 2081 patients were enrolled in the study, of which 1837 patients (88.3%) had a confirmed SARS-CoV-2 diagnosis before surgery. Notably, no instances of 30-day mortality were observed in any patient. Patients without prior infection had a 30-day morbidity rate of 15.2%, with postoperative pneumonia occurring in 7.0% of cases. In contrast, patients diagnosed with SARS-CoV-2 before surgery had significantly higher rates of 30-day morbidity and postoperative pneumonia when surgery was performed within 4-5 weeks (adjusted odds ratio (aOR) (95% CI):2.18 (1.29-3.71) and 2.39 (1.21-4.79), respectively) or within 6-7 weeks (aOR (95% CI):2.07 (1.36-3.20) and 2.10 (1.20-3.85), respectively). Conversely, surgeries performed ≥ 8 weeks after SARS-CoV-2 diagnosis exhibited similar risks of 30-day morbidity and pneumonia compared to those in the no prior infection group (aOR (95% CI):1.13 (0.77-1.70) and 1.12 (0.67-1.99), respectively). CONCLUSIONS: Thoracic surgery for lung cancer conducted 4-7 weeks after SARS-CoV-2 infection is still associated with an increased risk of 30-day morbidity in the Omicron-dominant period. Therefore, surgeons should carefully assess the individual risks and benefits to formulate an optimal surgical strategy for patients with lung cancer with a history of SARS-CoV-2 infection.

Predicting complication risks after sleeve lobectomy for non-small cell lung cancer.

Background: Sleeve lobectomy is a challenging procedure with a high risk of postoperative complications. To facilitate surgical decision-making and optimize perioperative treatment, we developed risk stratification models to quantify the probability of postoperative complications after sleeve lobectomy. Methods: We retrospectively analyzed the clinical features of 691 non-small cell lung cancer (NSCLC) patients who underwent sleeve lobectomy between July 2016 and December 2019. Logistic regression models were trained and validated in the cohort to predict overall complications, major complications, and specific minor complications. The impact of specific complications in prognostic stratification was explored via the Kaplan-Meier method. Results: Of 691 included patients, 232 (33.5%) developed complications, including 35 (5.1%) and 197 (28.5%) patients with major and minor complications, respectively. The models showed robust discrimination, yielding an area under the receiver operating characteristic (ROC) curve (AUC) of 0.853 [95% confidence interval (CI): 0.705-0.885] for predicting overall postoperative complication risk and 0.751 (95% CI: 0.727-0.762) specifically for major complication risks. Models predicting minor complications also achieved good performance, with AUCs ranging from 0.78 to 0.89. Survival analyses revealed a significant association between postoperative complications and poor prognosis. Conclusions: Risk stratification models could accurately predict the probability and severity of complications in NSCLC patients following sleeve lobectomy, which may inform clinical decision-making for future patients.

Neoadjuvant camrelizumab (an anti-PD-1 antibody) plus chemotherapy or apatinib (a VEGFR-2 inhibitor) for initially unresectable stage II-III non-small-cell lung cancer: a multicentre, two-arm, phase 2 exploratory study.

This multicentre, two-arm, phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II-III non-small-cell lung cancer (NSCLC). Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks (arm A) or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily (arm B), for 2-4 cycles, followed by surgery. The primary endpoint was major pathological response (MPR) rate. Thirty patients in arm A and 21 in arm B were enrolled. Surgery rates were 50.0% (15/30) in arm A and 42.9% (9/21) in arm B, with all patients achieving R0 resections. Of these patients, the MPR and pathological complete response rates were both 20.0% (95% CI 4.3-48.1) in arm A and were 55.6% (95% CI 21.2-86.3) and 11.1% (95% CI 0.3-48.2) in arm B, respectively. The corresponding objective response rates were 33.3% (95% CI 11.8-61.6) and 55.6% (95% CI 21.2-86.3). With a median follow-up of 22.4 months (95% CI 19.0-26.0), the median event-free survival was not reached (NR; 95% CI 13.6-NR) in arm A and 16.8 months (95% CI 8.6-NR) in arm B. Grade 3 or above treatment-related adverse events occurred in eight (26.7%) patients in arm A and three (14.3%) in arm B. Biomarker analysis showed baseline TYROBP expression was predictive of treatment response in arm B. Neoadjuvant camrelizumab plus chemotherapy or apatinib exhibits preliminary efficacy and manageable toxicity in patients with initially unresectable stage II-III NSCLC.

Insights into the heterogeneity of the tumor microenvironment in lung adenocarcinoma and squamous carcinoma through single-cell transcriptomic analysis: Implications for distinct immunotherapy outcomes.

BACKGROUND: Immune checkpoint blockade has emerged as a key strategy to the therapy landscape of non-small cell lung cancer (NSCLC). However, notable differences in immunotherapeutic outcomes exist between the two primary NSCLC subtypes: lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). This disparity may stem from the tumor immune microenvironment's heterogeneity at the transcriptome level. METHODS: By integrative analysis of transcriptomic characterization of 38 NSCLC patients by single-cell RNA sequencing, the present study revealed a distinct tumor microenvironment (TME) between LUAD and LUSC, with relevant results further confirmed in bulk transcriptomic and multiplex immunofluorescence (mIF) validation cohort of neoadjuvant immunotherapy patients. RESULTS: LUAD exhibited a more active immune microenvironment compared to LUSC. This included highly expression of HLA I/II in cancer cells, reinforced antigen presentation potential of dendritic cells and enhanced cytotoxic activity observed in T/NK cells. In LUSC, cancer cells highly expressed genes belonging to the aldo-keto reductases, glutathione S-transferases and aldehyde dehydrogenase family, negatively correlating with immunotherapy outcomes in the validation cohort of our center. Further analysis revealed elevated infiltrated cancer-associated fibroblasts (CAFs) in LUSC, which was corroborated in The Cancer Genome Atlas cohort. Corresponding increased infiltration of ADH1B+ CAFs in major pathologic response (MPR) patients and the higher presence of FAP+ CAFs in non-MPR patients were demonstrated by multiplex mIF. Moreover, upregulating immunosuppressive extracellular matrix remodeling was identified in LUSC. CONCLUSIONS: These comprehensive analyses advance the understanding of the differences in TME between LUAD and LUSC, offering insights for patient selection and developing subtype-specific treatment strategies.

The supraclavicular approach in the management of cervicothoracic-junction benign neurogenic tumors: A real-world analysis.

Objectives: The study objectives were to evaluate the safety, feasibility, and risk of neurologic complications with the supraclavicular approach in the operative management of cervicothoracic-junction benign neurogenic tumors. Methods: Between January 2012 and April 2023, 115 patients who underwent surgical resection for cervicothoracic-junction benign neurogenic tumors were retrospectively enrolled. Patients were divided into 3 groups based on the surgical approach: supraclavicular alone (Supraclav-Alone), n = 16; Transthoracic-Alone (video-assisted thoracoscopic surgery/Open), n = 87; and supraclavicular combined with transthoracic (Supraclav + video-assisted thoracoscopic surgery/open), n = 12. Clinicopathologic variables and postoperative morbidity including neurologic complications were summarized among the groups. Logistic regression analysis was performed to identify predictors for long-term (>6 months) brachial plexus injuries. Results: The cohort comprised 28 patients (24.3%) who underwent surgical resection using a supraclavicular approach. The Supraclav-Alone group portended the most cephalad location of tumor, the smallest pathologic tumor size, the shortest operative time, the least blood loss, and the least postoperative pain. The incidence of surgical complications, phrenic nerve neuropraxia, recurrent laryngeal nerve neuropraxia, or Horner's syndrome was similar among the groups postoperatively. However, use of the supraclavicular-alone approach (adjusted odds ratio, 0.165; 95% CI, 0.017-0.775) was a predictor for long-term brachial plexus injury complications. Among patients who experienced brachial plexus injury complications, the proportion of patients achieving complete resolution was higher among those undergoing a supraclavicular approach group (Supraclav-Alone: 80.0% vs Supraclav + video-assisted thoracoscopic surgery/Open: 60.0% vs video-assisted thoracoscopic surgery/Open: 25.8%). Conclusions: The supraclavicular approach may be a safe and feasible strategy in the management of cervicothoracic-junction benign neurogenic tumors that does not increase surgical complications and minimizes the severity of brachial plexus injury.

Safety and efficacy of delayed completion lobectomy following wedge resection vs. segmentectomy-a retrospective cohort study.

Background: Data regarding the safety and efficacy of delayed completion lobectomy (CL) following sublobar resections remain scant. We evaluated the technical difficulty and short-term outcomes of CL occurring at least 3 months following the anatomical segmentectomy or wedge resection. Methods: Consecutive non-small cell lung cancer (NSCLC) patients who underwent a second resection within the same lobe at least 3 months after their initial resection from January 2013 to December 2019 at the Shanghai Pulmonary Hospital were retrospectively included. The patients were divided into a segmentectomy group (SG group) and a wedge resection group (WR group) based on their initial resection strategy. Baseline characteristics and short-term outcomes after CL between the two groups were compared. Results: Twenty-five patients undergoing CL were included, nine in the SG group and 16 in the WR group. No deaths occurred within 30 days postoperatively, and the rate of overall postoperative complications was 28.0% (7/25). Statistically significant differences were found in rates of postoperative complications between the two groups (SG: 55.6% vs. WR: 12.5%, P=0.03) and in the use of bronchoplasty or angioplasty during the CL (SG: 33.3% vs. WR: 0.0%, P=0.04). After CL, no significant differences were found in 5-year recurrence-free survival (RFS) (WR: 66.7% vs. SG: 61.0%, P=0.31) or overall survival (OS) (WR: 93.8% vs. SG: 66.7%, P=0.06) between two groups. Conclusions: Delayed CL occurring over 3 months after sublobar resection is a safe and effective procedure, with no deaths occurring within 30 days postoperatively. As compared to a segmentectomy at the time of the index operation, a wedge resection may portend less morbidity, with a decreased risk of needing adjunctive bronchoplasty or angioplasty procedures during CL. After CL, 5-year RFS and OS were comparable between WR and SG groups.

Limited resection is comparable to lobectomy for tumor size ≤ 2 cm pulmonary invasive mucinous adenocarcinoma.

OBJECTIVES: Invasive mucinous adenocarcinoma (IMA) has a rare incidence with better prognosis than nonmucinous adenocarcinoma. We aimed to investigate the prognosis between limited resection and lobectomy for patients with clinical stage IA IMA ≤ 2 cm. METHODS: Data were taken from two cohorts: In Shanghai Pulmonary Hospital (SPH) corhort, we identified 403 patients with clinical stage IA IMA who underwent surgery. In the SEER corhort, 480 patients with stage T1 IMA who after surgery were included. Recurrence-free survival (RFS) for SPH corhort, lung cancer-specific survival (LCSS) for the SEER corhort and overall survival (OS) for both corhort were compared between patients undergoing lobectomy and limited resection by Log-rank and Cox proportional hazard regression model. RESULTS: In SPH corhort, patients who underwent limited resection had equivalent prognosis than those underwent lobectomy (5-year RFS: 79.3% versus. 82.6%, p = 0.116; 5-year OS: 86.2% versus. 88.3%, p = 0.235). However, patients with IMA > 2 to 3 cm had worse prognosis than those with IMA ≤ 2 cm (5-year RFS: 73.7% versus. 86.1%, p = 0.007). In the analysis of IMA > 2 to 3 cm subgroup, multivariate analysis showed that limited resection was an independent risk factor of RFS (hazard ratio, 2.417; 95% confidence interval, 1.157-5.049; p = 0.019), while OS (p = 0.122) was not significantly different between two groups. For IMA ≤ 2 cm, limited resection was not a risk factor of RFS (p = 0. 953) and OS (p = 0.552). In the SEER corhort, IMA ≤ 2 cm subgroup, limited resection was equivalent prognosis in LCSS (p = 0.703) and OS (p = 0.830). CONCLUSIONS: Limited resection could be a potential surgical option which comparable to lobectomy in patients with clinical stage IA IMA ≤ 2 cm.

Effect of NLRP3 Inflammasome on Lung Cancer Immune Microenvironment Activation and Its Mechanism.

Objective: The NLRP3 inflammasome plays a dual role in the occurrence and development of tumors, and its role in lung cancer remains unclear. This study aims to investigate the impact of NLRP3 inflammasome activation on the proliferation and migration of lung cancer cells. Methods: Data from the GEPIA, TCGA, and HPA databases were utilized to analyze the expression of NLRP3 in lung adenocarcinoma and its microenvironment. GO/KEGG enrichment analysis and GSEA analysis were employed to annotate the functions of differentially expressed genes related to NLRP3. The impact of NLRP3 inflammasome activation on the proliferation and migration of lung cancer cells was further investigated by CCK-8 assay and scratch assay. The effects of blocking NLRP3 inflammasome activation with IL-1RA and IL-18BP on the proliferation and migration of lung cancer cells were further assessed. Survival analysis was conducted to analyze the impact of NLRP3 expression on the prognosis of patients with lung adenocarcinoma. Results: The expression of NLRP3 in lung cancer was lower than in normal tissues, with notably higher expression observed in macrophages compared to other cells. Patients with higher NLRP3 expression exhibit increased infiltration of M2 macrophages. Activation of the NLRP3 inflammasome using LPS+ATP promotes the proliferation and migration of A549 cells. Simultaneous use of IL-1RA and IL-18BP reverses the promoting effect of NLRP3 inflammasome activation on cell proliferation and migration. Survival analysis results indicate that patients with high NLRP3 expression have a poorer prognosis compared to those with low NLRP3 expression (Hazzard Ratio =1.44; 95% Confidence Interval: 1.21-1.71). Conclusions: The activation of the NLRP3 inflammasome promotes the proliferation and migration of A549 cells through secretion of IL-1ß and IL-18, potentially influencing patient prognosis. Simultaneously blocking IL-1ß and IL-18 can reverse the pro-proliferative and migration-promoting effects.

MAIT cells are associated with responsiveness to neoadjuvant immunotherapy in COPD-associated NSCLC.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) experience worse clinical outcomes but respond better to immunotherapy than patients with NSCLC without COPD. Mucosal-associated invariant T (MAIT) cells, a versatile population of innate immune T lymphocytes, have a crucial function in the response to infection and tumors. This study investigated the distribution of MAIT cells in COPD-associated NSCLC and their involvement in the immune response. METHODS: Flow cytometry, immunohistochemistry, and immunofluorescence were performed on tissue samples of patients with NSCLC, with or without COPD, treated with or without anti-programmed death 1 (PD1) immunotherapy. MAIT cells were stimulated with 5-OP-RU using a mouse subcutaneous tumor model. RESULTS: Tumors contained significantly more MAIT cells than paraneoplastic tissues, and CD8+ MAIT cells accounted for more than 90% of these cells. Patients with NSCLC and COPD had higher CD8+ MAIT cell counts than those with NSCLC without COPD. Additionally, patients with NSCLC and COPD displayed reduced expression of the activation marker, CD69, and functional markers, granzyme B (GZMB) and interferon γ (IFNγ), and higher expression of the immune exhaustion marker, PD1. Among patients who received immunotherapy, the proportion with a complete or partial response was higher in those with COPD than in those without COPD. In patients with NSCLC and COPD, the major pathologic response (MPR) group had higher MAIT levels than those in the no major pathologic response (NPR) group. In the mouse subcutaneous tumor model stimulation of MAIT cells using 5-OP-RU enhanced the antitumor effects of anti-PD1. CONCLUSIONS: In patients with NSCLC and COPD, response to immunotherapy is associated with accumulation of CD8+ MAIT cells showing immune exhaustion. These findings may contribute to innovative approaches for immunotherapy targeting CD8+ MAIT cells.

Pulmonary Function Recovery and Displacement Patterns After Anatomic Segmentectomy vs Lobectomy.

BACKGROUND: The functional benefit of segmentectomy compared with lobectomy remains controversial. This ambispective study characterizes the changes in pulmonary function as correlated to displacement patterns of residual lung after segmentectomies vs lobectomies. METHODS: Patients with normal preoperative pulmonary function and undergoing segmentectomy or lobectomy between 2017 and 2021 were considered. Pulmonary function testing was scheduled preoperatively and at least 3 months postoperatively. Differences in the proportions of the median forced expiratory volume in 1 second (FEV1) reduction between segmentectomy and lobectomy were calculated. Covariance analysis was used to estimate the adjusted postoperative FEV1 (apoFEV1) and compare the difference value (DV) in apoFEV1 between segmentectomy and lobectomy. RESULTS: The study enrolled 634 patients (334 lobectomies and 300 segmentectomies). Median difference in the proportions of the FEV1 reduction between segmentectomy and lobectomy was 4.58%, with maximal difference observed in right S6 (9.08%) and minimal difference in left S1+2+3 (2.80%). For resections involving the upper lobe, apoFEV1 was significantly higher after segmentectomy than after lobectomy (DV, 0.15-0.22 L), except for left S3 and S1+2+3 segmentectomies (DV, 0.08 L and 0.06 L, respectively). Compared with a lower lobe lobectomy, S6 segmentectomy conferred a higher apoFEV1, whereas S7+8 and S9+10 had a similar apoFEV1 (DV, 0.16-0.18 L, 0.07 L, and 0.00-0.06 L, respectively). Functional recovery after segmentectomy was associated with the number of intersegment planes (P < .01) and the presence of an adjacent nonoperated on lobe (P = .03). CONCLUSIONS: Basilar and left S3 segmentectomies did not preserve more pulmonary function compared with their corresponding lobectomies, possibly due to the presence of multiple intersegmental resection planes.

Surgical strategies for benign acquired tracheoesophageal fistula.

OBJECTIVES: Tracheoesophageal fistula (TEF) is characterized by abnormal connectivity between the posterior wall of the trachea or bronchus and the adjacent anterior wall of the oesophagus. Benign TEF can result in serious complications; however, there is currently no uniform standard to determine the appropriate surgical approach for repairing TEF. METHODS: The PubMed database was used to search English literature associated with TEF from 1975 to October 2023. We employed Boolean operators and relevant keywords: 'tracheoesophageal fistula', 'tracheal resection', 'fistula suture', 'fistula repair', 'fistula closure', 'flap', 'patch', 'bioabsorbable material', 'bioprosthetic material', 'acellular dermal matrix', 'AlloDerm', 'double patch', 'oesophageal exclusion', 'oesophageal diversion' to search literature. The evidence level of the literature was assessed based on the GRADE classification. RESULTS: Nutritional support, no severe pulmonary infection and weaning from mechanical ventilation were the 3 determinants for timing of operation. TEFs were classified into 3 levels: small TEF (<1 cm), moderate TEF (≥1 but <5 cm) and large TEF (≥5 cm). Fistula repair or tracheal segmental resection was used for the small TEF with normal tracheal status. If the anastomosis cannot be finished directly after tracheal segmental resection, special types of tracheal resection, such as slide tracheoplasty, oblique resection and reconstruction, and autologous tissue flaps were preferred depending upon the site and size of the fistula. Oesophageal exclusion was applicable to refractory TEF or patients with poor conditions. CONCLUSIONS: The review primarily summarizes the main surgical techniques employed to repair various acquired TEF, to provide references that may contribute to the treatment of TEF.

Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies.

We performed comprehensive proteogenomic characterization of small cell lung cancer (SCLC) using paired tumors and adjacent lung tissues from 112 treatment-naive patients who underwent surgical resection. Integrated multi-omics analysis illustrated cancer biology downstream of genetic aberrations and highlighted oncogenic roles of FAT1 mutation, RB1 deletion, and chromosome 5q loss. Two prognostic biomarkers, HMGB3 and CASP10, were identified. Overexpression of HMGB3 promoted SCLC cell migration via transcriptional regulation of cell junction-related genes. Immune landscape characterization revealed an association between ZFHX3 mutation and high immune infiltration and underscored a potential immunosuppressive role of elevated DNA damage response activity via inhibition of the cGAS-STING pathway. Multi-omics clustering identified four subtypes with subtype-specific therapeutic vulnerabilities. Cell line and patient-derived xenograft-based drug tests validated the specific therapeutic responses predicted by multi-omics subtyping. This study provides a valuable resource as well as insights to better understand SCLC biology and improve clinical practice.

Surgery for bronchiectasis-destroyed lung: feasibility of video-assisted thoracoscopic surgery, and surgical outcomes.

OBJECTIVES: To provide the experience of surgical treatment for bronchiectasis-destroyed lung (BDL) and evaluate the feasibility of video-assisted thoracoscopic surgery (VATS). METHODS: BDL patients underwent surgical treatment between January 2013 and June 2018 were included. Logistic regression was performed to assess factors for major complications, and Cox's regression was performed to assess factors affected symptomatic outcome. RESULTS: Totally, 143 patients were treated by VATS (n = 64) and thoracotomy (n = 79). Nine (14.1%) cases scheduled for VATS were converted to thoracotomy for dense adhesions (n = 6) and frozen hilum (n = 3). The VATS group had a median chest tube duration, hospitalization and a time of returning to full activity of 4 days, 5 days and 1.5 months, respectively. Major complications occurred in 28 (19.6%) of all patients, 50.0% after pneumonectomy and 13.4% after lobectomy/extensive lobectomy. Multivariable analysis identified pneumonectomy [odds ratio, 3.64; 95% confidence interval (CI), 1.18-11.21] as a significant predictor for major complications. Overall, 141 (98.6%) patients benefitted from surgery (completely asymptomatic, n = 109; acceptable alleviation, n = 32). Thirty-four patients experienced relapse of the disease, including 13 with productive cough, 11 with haemoptysis and 10 with recurrent infections. Pseudomonas aeruginosa infection [hazard ratio (HR), 3.07; 95% CI, 1.38-6.83] and extent of remanent bronchiectatic areas (HR, 1.03; 95% CI, 1.00-1.05) were independent risk factors for shorter relapse free interval. CONCLUSIONS: VATS for BDL is feasible in well-selected patients. Pneumonectomy increased the risk of postoperative major complications. Removing all BDL lesions contributed to satisfactory prognosis.

Recurrence prediction of lung adenocarcinoma using an immune gene expression and clinical data trained and validated support vector machine classifier.

Background: Immune microenvironment plays a critical role in cancer from onset to relapse. Machine learning (ML) algorithm can facilitate the analysis of lab and clinical data to predict lung cancer recurrence. Prompt detection and intervention are crucial for long-term survival in lung cancer relapse. Our study aimed to evaluate the clinical and genomic prognosticators for lung cancer recurrence by comparing the predictive accuracy of four ML models. Methods: A total of 41 early-stage lung cancer patients who underwent surgery between June 2007 and October 2014 at New York University Langone Medical Center were included (with recurrence, n=16; without recurrence, n=25). All patients had tumor tissue and buffy coat collected at the time of resection. The CIBERSORT algorithm quantified tumor-infiltrating immune cells (TIICs). Protein-protein interaction (PPI) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to unearth potential molecular drivers of tumor progression. The data was split into training (75%) and validation sets (25%). Ensemble linear kernel support vector machine (SVM) ML models were developed using optimized clinical and genomic features to predict tumor recurrence. Results: Activated natural killer (NK) cells, M0 macrophages, and M1 macrophages showed a positive correlation with progression. Conversely, T CD4+ memory resting cells were negatively correlated. In the PPI network, TNF and IL6 emerged as prominent hub genes. Prediction models integrating clinicopathological prognostic factors, tumor gene expression (45 genes), and buffy coat gene expression (47 genes) yielded varying receiver operating characteristic (ROC)-area under the curves (AUCs): 62.7%, 65.4%, and 59.7% in the training set, 58.3%, 83.3%, and 75.0% in the validation set, respectively. Notably, merging gene expression with clinical data in a linear SVM model led to a significant accuracy boost, with an AUC of 92.0% in training and 91.7% in validation. Conclusions: Using ML algorithm, immune gene expression data from tumor tissue and buffy coat may enhance the precision of lung cancer recurrence prediction.

Use of an autologous dermal flap and rib cartilage graft in the repair of a large tracheoesophageal fistula with tracheal stenosis.

Management of large tracheoesophageal fistulas complicated by tracheal stenosis remains challenging as it requires an ideal replacement for the membranous defect as well as a permanent buttress to reconstruct the stenotic segment. We present the successful use of an autologous free dermal flap reinforced with a pedicled pectoralis major muscle to repair the tracheal membranous wall and a rib cartilage graft to enlarge the tracheal lumen.

Neoadjuvant Afatinib for stage III EGFR-mutant non-small cell lung cancer: a phase II study.

Afatinib, an irreversible ErbB-family blocker, could improve the survival of advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer patients (NSCLCm+). This phase II trial (NCT04201756) aimed to assess the feasibility of neoadjuvant Afatinib treatment for stage III NSCLCm+. Forty-seven patients received neoadjuvant Afatinib treatment (40 mg daily). The primary endpoint was objective response rate (ORR). Secondary endpoints included pathological complete response (pCR) rate, pathological downstaging rate, margin-free resection (R0) rate, event-free survival, disease-free survival, progression-free survival, overall survival, treatment-related adverse events (TRAEs). The ORR was 70.2% (95% CI: 56.5% to 84.0%), meeting the pre-specified endpoint. The major pathological response (MPR), pCR, pathological downstaging, and R0 rates were 9.1%, 3.0%, 57.6%, and 87.9%, respectively. The median survivals were not reached. The most common TRAEs were diarrhea (78.7%) and rash (78.7%). Only three patients experienced grade 3/4 TRAEs. Biomarker analysis and tumor microenvironment dynamics by bulk RNA sequencing were included as predefined exploratory endpoints. CISH expression was a promising marker for Afatinib response (AUC = 0.918). In responders, compared to baseline samples, increasing T-cell- and B-cell-related features were observed in post-treatment tumor and lymph-node samples, respectively. Neoadjuvant Afatinib is feasible for stage III NSCLC+ patients and leads to dynamic changes in the tumor microenvironment.

Prognostic factors and role of postoperative radiotherapy in surgically resected thymomas.

Objective: To investigate the prognostic factors in and role of postoperative radiotherapy (PORT) for surgically resected thymomas. Methods: A total of 1540 patients with pathologically confirmed thymomas undergoing resection between 2000 and 2018 were identified retrospectively from the SEER (Surveillance, Epidemiology, and End Results) database. Tumors were restaged as local (limited to thymus), regional (invasion to mediastinal fat and other neighboring structures), or distant stage. Disease-specific survival (DSS) and overall survival (OS) were estimated by the Kaplan-Meier method and the log-rank test. Adjusted hazard ratios (HRs) with 95% CIs were calculated by Cox proportional hazards modeling. Results: Tumor stage and histology were independent predictors of both DSS (regional: HR, 3.711; 95% CI, 2.006-6.864; distant: HR, 7.920; 95% CI, 4.061-15.446; type B2/B3: HR, 1.435; 95% CI, 1.008-2.044) and OS (regional: HR, 1.461; 95% CI, 1.139-1.875; distant: HR, 2.551; 95% CI, 1.855-3.509; type B2/B3: HR, 1.409; 95% CI, 1.153-1.723). For patients with regional stage and type B2/B3 thymomas, PORT was associated with better DSS after thymectomy/thymomectomy (HR, 0.268; 95% CI, 0.099-0.727), but the association was not significant after extended thymectomy (HR, 1.514; 95% CI, 0.516-4.44). Among patients with lymph node metastases, those who received PORT (HR, 0.372; 95% CI, 0.146-0.949), chemotherapy (HR, 0.843; 95% CI, 0.303-2.346), or both (HR, 0.296, 95% CI, 0.071-1.236) had a better OS. Conclusions: The extent of invasion and tumor histology were independent predictors of worse survival following surgical resection of thymoma. Patients with regional invasion and type B2/B3 thymoma who undergo thymectomy/thymomectomy may benefit from PORT, while patients with nodal metastases may benefit from multimodal therapy, including PORT and chemotherapy.

Multiparametric MRI for evaluation of pathological response to the neoadjuvant chemo-immunotherapy in resectable non-small-cell lung cancer.

OBJECTIVES: This study aimed to explore the predictive value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and diffusion kurtosis imaging (DKI) quantitative parameters for the response to neoadjuvant chemo-immunotherapy (NCIT) in resectable non-small-cell lung cancer (NSCLC) patients, so as to provide a basis for clinical individualized precision treatment. METHODS: Treatment naive locally advanced NSCLC patients who enrolled in 3 prospective, open-label, and single-arm clinical trials and received NCIT were retrospectively analyzed in this study. Functional MRI imaging was performed at baseline and following 3 weeks of treatment as an exploratory endpoint to evaluate treatment efficacy. Univariate and multivariate logistic regressions were used to identify independent predictive parameters for NCIT response. Prediction models were built with statistically significant quantitative parameters and their combinations. RESULTS: In total of 32 patients, 13 were classified as complete pathological response (pCR) and 19 were non-pCR. Post-NCIT ADC, ΔADC, and ΔD values in the pCR group were significantly higher than those in the non-pCR group, while the pre-NCIT D, post-NCIT Kapp, and ΔKapp were significantly lower than those in non-pCR group. Multivariate logistic regression analysis demonstrated that pre-NCIT D and post-NCIT Kapp values were independent predictors for NCIT response. The combined predictive model, which consisted of IVIM-DWI and DKI, showed the best prediction performance with AUC of 0.889. CONCLUSIONS: The pre-NCIT D, post-NCIT parameters (ADC and Kapp) and Δ parameters (ΔADC, ΔD, and ΔKapp) were effective biomarkers for predicting pathologic response, and pre-NCIT D and post-NCIT Kapp values were independent predictors of NCIT response for NSCLC patients. CLINICAL RELEVANCE STATEMENT: This exploratory study indicated that IVIM-DWI and DKI MRI imaging would predict pathologic response of neoadjuvant chemo-immunotherapy in locally advanced NSCLC patients at initial state and early treatment, which could help make clinical individualized treatment strategies. KEY POINTS: • Effective NCIT treatment resulted in increased ADC and D values for NSCLC patients. • The residual tumors in non-pCR group tend to have higher microstructural complexity and heterogeneity, as measured by Kapp. • Pre-NCIT D and post-NCIT Kapp values were independent predictors of NCIT response.

The Prognostic Impact of Epidermal Growth Factor Receptor Mutation in Clinical Stage I Lung Adenocarcinoma.

BACKGROUND: This study investigated the prognostic impact of epidermal growth factor receptor (EGFR) mutation in clinical stage I lung adenocarcinoma patients. METHODS: Data for 952 patients who received surgical resection and underwent detection of oncogenic driver mutations were retrospectively collected. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared using the log-rank test. The adjusted hazard ratio (aHR) with 95% CI of the prognosticator was calculated by Cox proportional hazards model, and cumulative incidence function was measured by competing risk regression model. RESULTS: EGFR mutation was detected in 581 patients (61.0%) and was more frequent in women (63.9%), nonsmokers (85.5%), and those with ground-glass nodules (GGNs; 56.6%). EGFR mutation was not associated with recurrence and death in the entire cohort or GGN cohort. However, for patients with radiologic pure-solid appearance, EGFR mutation was an independent risk factor for RFS (aHR, 1.623; 95% CI, 1.192-2.210) and distant recurrence (aHR, 1.863; 95% CI, 1.311-2.650), but not OS. Subsequently, subgroup analysis based on EGFR mutation subtypes, including exon 19 deletions (19-Del), exon 21 L858R substitution (L858R), and rare mutations in patients with radiologic pure-solid appearance, revealed that all 3 subtypes have poorer RFS (19-Del: aHR, 1.424; 95% CI, 0.991-2.047; L858R: aHR, 1.708; 95% CI, 1.172-2.490; rare mutations: aHR, 2.500; 95% CI, 1.400-4.465) and higher prevalent distant recurrence (19-Del: aHR, 1.595; 95% CI, 1.061-2.400; L858R: aHR, 2.073; 95% CI, 1.371-3.140; rare mutations: aHR, 2.657; 95% CI, 1.397-5.050) compared with wild-type. CONCLUSIONS: In clinical stage I lung adenocarcinoma, EGFR mutation was associated with worse RFS and higher prevalent distant recurrence in patients with radiologic pure-solid appearance but not in patients with GGN.