Perioperative immune checkpoint blockades improve prognosis of resectable non-small cell lung cancer.

OBJECTIVES: Immune checkpoint blockades (ICB) have been proven to improve prognosis of non-small cell lung cancer in the neoadjuvant setting, while whether its perioperative use could bring extra benefit remained unidentified. We aimed to demonstrate the prognostic benefit of perioperative ICB over preoperative-only use and investigate who could benefit from this 'sandwich ICB therapy'. METHODS: Patients undergoing neoadjuvant therapy followed by surgery from 2018 to 2022 were retrospectively reviewed, and were divided into 4 groups based on the perioperative regimens: pre-ICB + post-computed tomography (CT), pre-ICB-only, pre-CT + post-ICB and pre-CT-only. Treatment-related adverse events, surgical outcomes, therapeutic response, recurrence-free survival and overall survival were compared. RESULTS: Of 214 enrolled patients with preoperative therapy, 108 underwent immunochemotherapy and 106 underwent platinum-based chemotherapy. Compared with preoperative chemotherapy, preoperative immunochemotherapy was demonstrated with significantly higher major pathologic response (57/108 vs 12/106) and pathologic complete response (35/108 vs 4/106) rates with comparable adverse events. Regarding survival, perioperative ICB significantly improved the recurrence-free survival [versus pre-CT-only hazard ratio (HR) 0.15; 95% CI 0.09-0.27; versus pre-ICB-only HR 0.36; 95% CI 0.15-0.88] and overall survival (versus pre-CT-only HR 0.24; 95% CI 0.08-0.68). In patients without major pathologic response, perioperative ICB was observed to decrease the risk of recurrence (HR 0.31; 95% CI 0.11-0.83) compared with preoperative ICB, and was an independent prognostic factor (P < 0.05) for recurrence-free survival. CONCLUSIONS: Perioperative ICB showed promising efficacy in improving pathological response and survival outcomes of resectable non-small cell lung cancer. For patients without major pathologic response after resection followed by preoperative ICB, sequential ICB treatment could be considered.

DNA-PK-Mediated Cytoplasmic DNA Sensing Stimulates Glycolysis to Promote Lung Squamous Cell Carcinoma Malignancy and Chemoresistance.

Detection of cytoplasmic DNA is an essential biological mechanism that elicits IFN-dependent and immune-related responses. A better understanding of the mechanisms regulating cytoplasmic DNA sensing in tumor cells could help identify immunotherapeutic strategies to improve cancer treatment. Here we identified abundant cytoplasmic DNA accumulated in lung squamous cell carcinoma (LUSC) cells. DNA-PK, but not cGAS, functioned as a specific cytoplasmic DNA sensor to activate downstream ZAK/AKT/mTOR signaling, thereby enhancing the viability, motility, and chemoresistance of LUSC cells. DNA-PK-mediated cytoplasmic DNA sensing boosted glycolysis in LUSC cells, and blocking glycolysis abolished the tumor-promoting activity of cytoplasmic DNA. Elevated DNA-PK-mediated cytoplasmic DNA sensing was positively correlated with poor prognosis of human patients with LUSC. Targeting signaling activated by cytoplasmic DNA sensing with the ZAK inhibitor iZAK2 alone or in combination with STING agonist or anti-PD-1 antibody suppressed the tumor growth and improved the survival of mouse lung cancer models and human LUSC patient-derived xenografts model. Overall, these findings established DNA-PK-mediated cytoplasmic DNA sensing as a mechanism that supports LUSC malignancy and highlight the potential of targeting this pathway for treating LUSC. SIGNIFICANCE: DNA-PK is a cytoplasmic DNA sensor that activates ZAK/AKT/mTOR signaling and boosts glycolysis to enhance malignancy and chemoresistance of lung squamous cell carcinoma.

Robotic Versus Thoracoscopic Sub-lobar Resection for Octogenarians with Clinical Stage IA Non-small Cell Lung Cancer: A Propensity Score-Matched Real-World Study.

BACKGROUND: Minimally invasive sub-lobectomy is sufficient in treating small early-stage non-small cell lung cancer (NSCLC). However, comparison of the feasibility and oncologic efficacy between robot-assisted thoracoscopic surgery (RATS) and video-assisted thoracoscopic surgery (VATS) in performing sub-lobectomy for early-stage NSCLC patients age 80 years or older is scarce. METHODS: Octogenarians with clinical stage IA NSCLC (tumor size, ≤ 2 cm) undergoing minimally invasive wedge resection or segmentectomy at Shanghai Chest Hospital from 2011 to 2020 were retrospectively reviewed from a prospectively maintained database. Propensity score-matching (PSM) with a RATS versus VATS ratio of 1:4 was performed. Perioperative and long-term outcomes were analyzed. RESULTS: The study identified 594 patients (48 RATS and 546 VATS patients), and PSM resulted in 45 cases in the RATS group and 180 cases in the VATS group. The RATS patients experienced less intraoperative bleeding (60 mL [interquartile range (IQR), 50-100 mL] vs. 80 mL [IQR, 50-100 mL]; P = 0.027) and a shorter postoperative hospital stay (4 days [IQR, 3-5 days] vs. 5 days [IQR, 4-6 days]; P = 0.041) than the VATS patients. The two surgical approaches were comparable concerning other perioperative outcomes and postoperative complications (20.00% vs. 26.11%; P = 0.396). Additionally, during a median follow-up period of 66 months, RATS and VATS achieved comparable 5-year overall survival (90.48% vs. 87.93%; P = 0.891), recurrence-free survival (83.37% vs. 83.18%; P = 0.782), and cumulative incidence of death. Further subgroup comparison also demonstrated comparable long-term outcomes between the two approaches. Finally, multivariate Cox analysis indicated that the surgical approach was not independently correlated with long-term outcomes. CONCLUSIONS: The RATS approach shortened the postoperative hospital stay, reduced intraoperative bleeding by a statistically notable but clinically insignificant amount, and achieved long-term outcomes comparable with VATS in performing sub-lobectomy for octogenarians with early-stage small NSCLC.

Perioperative outcomes of bi-pigtail catheter drainage strategy versus conventional chest tube after uniportal video-assisted thoracic lung surgery.

OBJECTIVES: Chest tube (CT) drainage is a main cause of postoperative pain in lung surgery. Here, we introduced a novel drainage strategy with bi-pigtail catheters (PCs) and conducted a randomized controlled trial to compare with conventional CT drainage after uniportal video-assisted thoracic surgery lung surgery. METHODS: A single-centre, prospective, open-labelled, randomized controlled trial (ChiCTR2000035337) was conducted with a preplanned sample size of 396. The primary outcome was the numerical pain rating scale (NPRS) on the first postoperative day. Secondary outcomes included other indicators of postoperative pain, drainage volume, duration of drainage, postoperative hospital stay, incidence of postoperative complications, CT reinsertion and medical costs. RESULTS: A total number of 396 patients were randomized between August 2020 and January 2021, 387 of whom were included in the final analysis. The baseline and clinical characteristics of the patients were well balanced between 2 groups. The NPRS on the first postoperative day was significantly lower in the PC group than in the CT group (2.40 ± 1.27 vs 3.02 ± 1.39, p < 0.001), as well as the second/third-day NPRS, the incidence of sudden severe pain (9/192, 4.7% vs 34/195, 17.4%, P < 0.001) and pain requiring intervention (19/192, 9.9% vs 46/195, 23.6%, P < 0.001). In addition, the medical cost in the PC group was lower (US$7809 ± 1646 vs US$8205 ± 1815, P = 0.025). Univariable and multivariable analyses revealed that the drainage strategy was the only factor influencing the incidence of pain requiring intervention. CONCLUSIONS: The drainage strategy with bi-PCs in patients undergoing uniportal video-assisted thoracic surgery lung surgery alleviates postoperative pain with adequate safety and efficacy.

Comparison of lobectomy performed through Toumai® surgical robot and da Vinci surgical robot in early-stage non-small cell lung cancer: a retrospective study of early perioperative results.

Background: Robotic-assisted thoracic surgery (RATS) is a safe and efficient minimally invasive thoracic approach compared to thoracotomy. Today, almost all thoracic procedures can be performed by RATS. In recent years, the Chinese government has issued some policies to support the development of domestic surgical robots, leading to the development of the Toumai® surgical robot system. This study aimed to explore the application of the Toumai® surgical robot in performing lobectomy for early-stage non-small cell lung cancer (NSCLC), and to compare its safety, surgical effect, and advantages or disadvantages compared with the mature da Vinci robotic surgical system. Methods: Patients with early-stage NSCLC undergoing robotic-assisted lobectomy in our center between November 2021 and December 2021 were enrolled in the study; Surgeries were performed through the Toumai® surgical robot and the da Vinci robotic system. Anatomical lobectomy and systematic lymph node (LN) dissection were conducted in all patients. Baseline and perioperative outcomes were analyzed to compare the two methods. Results: The combined 19 patients from the Toumai® group (n=9) and the da Vinci group (n=10) were enrolled and eligible for analyses. They had similar baseline characteristics, tumor characteristics, clinical stage, and pathological stage. Conversion to thoracotomy was not observed, and the operation time {95 minutes [interquartile range (IQR), 86.5-136.5 minutes] vs. 86 minutes (IQR, 81-102 minutes), P=0.178} and other perioperative outcomes were comparable in the two groups. There was no significant difference in the number of dissected LNs and lymphatic stations between both groups. Conclusions: The application of Toumai® surgical robot in lobectomy was preliminarily shown to be safe and effective. Compared with the mature da Vinci robotic surgery system, Toumai® surgical robot had similar technical and surgical advantages, highlighting its suitability as an optional method for the new generation of robotic-assisted thoracoscopic surgery.

Improving the prediction of Spreading Through Air Spaces (STAS) in primary lung cancer with a dynamic dual-delta hybrid machine learning model: a multicenter cohort study.

BACKGROUND: Reliable pre-surgical prediction of spreading through air spaces (STAS) in primary lung cancer is essential for precision treatment and surgical decision-making. We aimed to develop and validate a dual-delta deep-learning and radiomics model based on pretreatment computed tomography (CT) image series to predict the STAS in patients with lung cancer. METHOD: Six hundred seventy-four patients with pre-surgery CT follow-up scans (with a minimum interval of two weeks) and primary lung cancer diagnosed by surgery were retrospectively recruited from three Chinese hospitals. The training cohort and internal validation cohort, comprising 509 and 76 patients respectively, were selected from Shanghai Chest Hospital; the external validation cohorts comprised 36 and 53 patients from two other centers, respectively. Four imaging signatures (classic radiomics features and deep learning [DL] features, delta-radiomics and delta-DL features) reflecting the STAS status were constructed from the pretreatment CT images by comprehensive methods including handcrafting, 3D views extraction, image registration and subtraction. A stepwise optimized three-step procedure, including feature extraction (by DL and time-base radiomics slope), feature selection (by reproducibility check and 45 selection algorithms), and classification (32 classifiers considered), was applied for signature building and methodology optimization. The interpretability of the proposed model was further assessed with Grad-CAM for DL-features and feature ranking for radiomics features. RESULTS: The dual-delta model showed satisfactory discrimination between STAS and non-STAS and yielded the areas under the receiver operating curve (AUCs) of 0.94 (95% CI, 0.92-0.96), 0.84 (95% CI, 0.82-0.86), and 0.84 (95% CI, 0.83-0.85) in the internal and two external validation cohorts, respectively, with interpretable core feature sets and feature maps. CONCLUSION: The coupling of delta-DL model with delta-radiomics features enriches information such as anisotropy of tumor growth and heterogeneous changes within the tumor during the radiological follow-up, which could provide valuable information for STAS prediction in primary lung cancer.

Non-linear modifications enhance prediction of pathological response to pre-operative PD-1 blockade in lung cancer: A longitudinal hybrid radiological model.

Major pathologic remission (MPR, residual tumor <10%) is a promising clinical endpoint for prognosis analysis in patients with lung cancer receiving pre-operative PD-1 blockade therapy. Most of the current biomarkers for predicting MPR such as PD-L1 and tumor mutation burden (TMB) need to be obtained invasively. They cannot overcome the spatiotemporal heterogeneity or provide dynamic monitoring solutions. Radiomics and artificial intelligence (AI) models provide a practical tool enabling non-invasive follow-up observation of tumor structural information through high-throughput data analysis. Currently, AI-based models mainly focus on the single baseline scan or pipeline, namely sole radiomics or deep learning (DL). This work merged the delta-radiomics based on the slope of classic radiomics indexes within a time interval and the features extracted by deep networks from the subtraction between the baseline and follow-up images. The subtracted images describing the tumor changes were based on the transformation generated by registration. Stepwise optimization of components was performed by repeating experiments among various combinations of DL networks, registration methods, feature selection algorithms, and classifiers. The optimized model could predict MPR with a cross-validation AUC of 0.91 and an external validation AUC of 0.85. A core set of 27 features (eight classic radiomics, 15 delta-radiomics, one classic DL features, and three delta-DL features) was identified. The changes in delta-radiomics indexes during the treatment were fitted with mathematic models. The fitting results revealed that over half of the features were of non-linear dynamics. Therefore, non-linear modifications were made on eight features by replacing the original features with non-linear fitting parameters, and the modified model achieved an improved power. The dynamic hybrid model serves as a novel and promising tool to predict the response of lesions to PD-1 blockade, which implies the importance of introducing the non-linear dynamic effects and DL approaches to the original delta-radiomics in the future.

Cancer Burden Variations and Convergences in Globalization: A Comparative Study on the Tracheal, Bronchus, and Lung (TBL) and Liver Cancer Burdens Among WHO Regions from 1990 to 2019.

Lung cancer and liver cancer are the leading and third causes of cancer death, respectively. Both lung and liver cancer are with clear major risk factors. A thorough understanding of their burdens in the context of globalization, especially the convergences and variations among WHO regions, is useful in precision cancer prevention worldwide and understanding the changing epidemiological trends with the expanding globalization. The Global Burden of Disease (GBD) and WHO Global Health Observatory (GHO) database were analyzed to evaluate the burden metrics and risk factors of trachea, bronchus, and lung (TBL) cancer and liver cancer. Western Pacific Region (WPR) had the highest age-standardized incidence rate (ASIR) for both liver cancer (11.02 [9.62-12.61] per 100,000 population) and TBL cancer (38.82 [33.63-44.04] per 100,000 population) in 2019. Disability-adjusted life years (DALYs) for liver and TBL cancer elevated with the increasing sociodemographic index (SDI) level, except for liver cancer in WPR and TBL cancer in European Region (EUR). Region of the Americas (AMR) showed the biggest upward trends of liver cancer age-standardized rates (ASRs), as well as the biggest downward trends of TBL cancer ASRs, followed by Eastern Mediterranean Region (EMR). Alcohol use and smoking were the leading cause of liver and TBL cancer death in most WHO regions. Variances of ASRs for liver and TBL cancer among WHO memberships have been decreasing during the past decade. The homogenization and convergence of cancer burdens were also demonstrated in different agegroups and sexes and in the evolution of associated risk factors and etiology. In conclusion, our study reflects the variations and convergences in the liver and lung cancer burdens among the WHO regions with the developing globalization, which suggests that we need to be acutely aware of the global homogeneity of the disease burden that accompanies increasing globalization, including the global convergences in various populations, risk factors, and burden metrics.

Clinical utility of [18F]FDG PET/CT in the assessment of mediastinal lymph node disease after neoadjuvant chemoimmunotherapy for non-small cell lung cancer.

OBJECTIVES: The performance of positron emission tomography/computed tomography (PET/CT) for the prediction of ypN2 disease in non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy has not been reported. This multicenter study investigated the utility of PET/CT to assess ypN2 disease in these patients. METHODS: A total of 181 consecutive patients (chemoimmunotherapy = 86, chemotherapy = 95) at four institutions were enrolled in this study. Every patient received a PET/CT scan prior to surgery and complete resection with systematic nodal dissection. The diagnostic performance was evaluated through area under the curve (AUC). Kaplan-Meier method and Cox analysis were performed to identify the risk factors affecting recurrences. RESULTS: The sensitivity, specificity, and accuracy of PET/CT for ypN2 diseases were 0.667, 0.835, and 0.779, respectively. Therefore, the AUC was 0.751. Compared with the false positive cases, the mean value of max standardized uptake value (SUVmax) (6.024 vs. 2.672, p < 0.001) of N2 nodes was significantly higher in true positive patients. Moreover, the SUVmax of true positive (7.671 vs. 5.976, p = 0.365) and false (2.433 vs. 2.339, p = 0.990) positive cases were similar between chemoimmunotherapy and chemotherapy, respectively. Survival analysis proved that pathologic N (ypN) 2 patients could be stratified by PET/CT-N2(+ vs. -) for both chemoimmunotherapy (p = 0.023) and chemotherapy (p = 0.010). CONCLUSIONS: PET/CT is an accurate and non-invasive test for mediastinal restaging of NSCLC patients who receive neoadjuvant chemoimmunotherapy. The ypN2 patients with PET/CT-N2( +) are identified as an independent prognostic factor compared with PET/CT-N2(-). CLINICAL RELEVANCE STATEMENT: Imaging with 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) plays an integral role during disease diagnosis, staging, and therapeutic response assessments in patients with NSCLC. PET/CT could be an effective non-invasive tool for predicting ypN2 diseases after neoadjuvant chemoimmunotherapy. KEY POINTS: • PET/CT could serve as an effective non-invasive tool for predicting ypN2 diseases. • The ypN2 patients with PET/CT-N2( +) were a strong and independent prognostic factor. • The application of PET/CT for restaging should be encouraged in clinical practice.

Short-term outcomes of robot-assisted versus video-assisted thoracoscopic surgery for non-small cell lung cancer patients with neoadjuvant immunochemotherapy: a single-center retrospective study.

Background: Neoadjuvant immunochemotherapy has been increasingly applied to treat non-small cell lung cancer (NSCLC). However, the comparison between robotic-assisted thoracoscopic surgery (RATS) and video-assisted thoracoscopic surgery (VATS) in the feasibility and oncological efficacy following neoadjuvant immunochemotherapy is scarce. This study aims to assess the superiorities of RATS over (VATS) concerning short-term outcomes in treating NSCLC patients with neoadjuvant immunochemotherapy. Methods: NSCLC patients receiving RATS or VATS lobectomy following neoadjuvant immunochemotherapy at Shanghai Chest Hospital from 2019 to 2022 were retrospectively identified. Baseline clinical characteristics, perioperative outcomes, and survival profiles were analyzed. Results: Forty-six NSCLC patients with neoadjuvant immunochemotherapy were included and divided into the RATS (n=15) and VATS (n=31) groups. The baseline clinical characteristics and induction-related adverse events were comparable between the two groups (all p>0.050). The 30-day mortality in the RATS and VATS groups were 0% and 3.23%, respectively (p=1.000). Patients undergoing RATS were associated with reduced surgical-related intensive unit care (ICU) stay than those receiving VATS (0.0 [0.0-0.0] vs. 0.0 [0.0-1.0] days, p=0.026). Moreover, RATS assessed more N1 LNs (6.27 ± 1.94 vs 4.90 ± 1.92, p=0.042) and LN stations (3.07 ± 1.03 vs 2.52 ± 0.57, p=0.038) compared with VATS. By comparison, no difference was found in surgical outcomes, pathological results, and postoperative complications between the RATS and VATS groups (all p>0.050). Finally, RATS and VATS achieved comparable one-year recurrence-free survival (82.96% vs. 85.23%, p=0.821) and the timing of central nervous system, LN, and bone recurrences (all p>0.050). Conclusion: RATS is safe and feasible for NSCLC patients with neoadjuvant immunochemotherapy, reducing surgical-related ICU stay, assessing increased N1 LNs and stations, and achieving similar survival profiles to VATS.

Short- and medium-term outcomes of video-assisted thoracoscopic surgery versus thoracotomy for carinal lung resection combined with carina reconstruction in locally advanced non-small cell lung cancer patients.

BACKGROUND: The application of video-assisted thoracoscopic surgery (VATS) for complex carina surgeries in treating non-small cell lung cancer (NSCLC) patients with involved carina is controversial. This study compared short- and medium-term outcomes of VATS versus thoracotomy for carinal lung resection with carina reconstruction in treating locally advanced NSCLC, aiming to assess the potential benefit of VATS over thoracotomy for these patients. METHODS: A total of 37 consecutive NSCLC cases receiving VATS (n = 14) or thoracotomy (n = 23) for carinal lung resection with carina reconstruction from 2016 to 2021 were retrospectively identified. Baseline clinicopathological characteristics, perioperative outcomes, and survival profiles were investigated. RESULTS: Patients in the VATS and thoracotomy groups had comparable baseline clinicopathological characteristics (all p > 0.050). VATS decreased postoperative drainage volume compared with thoracotomy (1280 [1170-1510] vs. 1795 [1510-1905] mL, p = 0.012). Regarding surgical-related pains, VATS reduced numeric rating scale scores on the postoperative day 1 (4 [3, 4] vs. 5 [4, 5], p = 0.021) and day 2 (3 [3, 4] vs. 5 [3-5], p = 0.023) than thoracotomy. No difference was found between the VATS and thoracotomy groups in other perioperative outcomes, postoperative complications, and assessment of lymph nodes (LNs) and LN stations (all p > 0.050). Moreover, patients in the two groups had comparable 3-year disease-free survival (DFS), overall survival (OS), and recurrence and mortality patterns. Further subgroup and Cox hazards regression analyses also observed no difference in DFS or OS between the two groups. CONCLUSIONS: VATS reduced postoperative drainage volume and ameliorated surgical-related pain, and achieved comparable medium-term survival compared to thoracotomy for carinal lung resection with carina reconstruction in treating locally advanced NSCLC.

The learning curve on uniportal video-assisted thoracoscopic lobectomy with the help of postoperative review of videos.

Objectives: Video-assisted thoracoscopic lobectomy has become the preferred surgical approach in experienced centers, and uniportal approaches are becoming increasingly used. But the uniportal approach is still not widely applied presumably due to the learning difficulties of this complex procedure. The use of surgical videos may be helpful to accelerate the learning of this new techniques as in other fields. In this study, we aimed to analyze the learning curve of uniportal video-assisted thoracoscopic lobectomy with the help of postoperative review of videos. Methods: 114 patients with early-stage lung cancer who underwent uniportal video-assisted thoracoscopic lobectomy performed from 2020 to 2021 were reviewed in this study. We recorded the operation video for each patient and reviewed all the videos after surgery. The learning curves were assessed using cumulative sum analysis and the collected data of perioperative outcomes were assessed. Results: The CUMSUM curve showed its inflection points were around case 38 and 53. It was less compared with previous studies, which about 57-140 cases are needed to attain the proficient phase. The perioperative outcomes were similar in each phase, which included intraoperative blood loss (79.00 ± 26.70 vs 70.67 ± 26.64 vs 70.56 ± 27.23, p=0.0119), the length of hospital stay (3.60 ± 1.52 days vs. 3.23 ± 0.90 days vs. 3.06 ± 0.88 days, p=0.053), the rate of prolonged air leak and conversion to open thoracotomy. There was also no significant difference in the numbers and station of lymph node dissection among the three phases. Conclusions: Uniportal video-assisted thoracoscopic lobectomy is a safe and reliable approach. Recording and reviewing the operation video could help the surgeon to improve deficiencies and refine the procedure.

Short- and long-term outcomes of robotic-assisted versus video-assisted thoracoscopic lobectomy in non-small cell lung cancer patients aged 35 years or younger: a real-world study with propensity score-matched analysis.

PURPOSE: This study compared short- and long-term outcomes of robotic-assisted thoracoscopic surgery (RATS) versus video-assisted thoracoscopic surgery (VATS) for lobectomy in young adults aged ≤ 35 years with non-small cell lung cancer (NSCLC), aiming to assess the superiority of RATS over VATS for this special group of patients. METHODS: A total of 1355 consecutive NSCLC cases aged 18-35 years undergoing RATS (n = 105) or VATS (n = 1250) between 2014 and 2021 were retrospectively identified from a prospectively maintained database. Propensity score matching (PSM) was applied to establish a 1:3 RATS versus VATS ratio. Baseline clinicopathological characteristics, perioperative outcomes, lymph node (LN) assessment, and long-term survival were investigated. RESULTS: Following PSM, 105 and 315 cases were in the RATS and VATS groups, respectively. RATS led to a shorter postoperative hospital stay than VATS (4.0 ± 1.5 vs 4.3 ± 1.7 days, p = 0.02). The two groups were comparable in other perioperative outcomes and postoperative complications (all p > 0.05). Moreover, RATS assessed more LNs (9.4 ± 4.4 vs 8.3 ± 3.6, p = 0.03), especially N1 LNs (4.2 ± 3.1 vs 3.5 ± 2.2, p = 0.02), than VATS. By comparison, no difference in 5-year recurrence-free survival (RFS), overall survival (OS), or recurrence or mortality patterns was found between the two groups (all p > 0.05). Further subgroup analyses also observed similar long-term outcomes between the two groups regarding age, gender, and smoking history. Finally, Cox's analyses found that the surgical approach was not independently correlated with RFS or OS. CONCLUSION: RATS shortened postoperative hospital stay, assessed more N1 and total LNs, and achieved comparable long-term outcomes to VATS for very young NSCLC patients.

Invasiveness assessment by artificial intelligence against intraoperative frozen section for pulmonary nodules ≤ 3 cm.

PURPOSE: To investigate the performance of an artificial intelligence (AI) algorithm for assessing the malignancy and invasiveness of pulmonary nodules in a multicenter cohort. METHODS: A previously developed deep learning system based on a 3D convolutional neural network was used to predict tumor malignancy and invasiveness. Dataset of pulmonary nodules no more than 3 cm was integrated with CT images and pathologic information. Receiver operating characteristic curve analysis was used to evaluate the performance of the system. RESULTS: A total of 466 resected pulmonary nodules were included in this study. The areas under the curves (AUCs) of the deep learning system in the prediction of malignancy as compared with pathological reports were 0.80, 0.80, and 0.75 for all, subcentimeter, and solid nodules, respectively. Additionally, the AUC in the AI-assisted prediction of invasive adenocarcinoma (IA) among subsolid lesions (n = 184) was 0.88. Most malignancies that were misdiagnosed by the AI system as benign diseases with a diameter measuring greater than 1 cm (26/250, 10.4%) presented as solid nodules (19/26, 73.1%) on CT. In an exploratory analysis involving nodules underwent intraoperative pathologic examination, the concordance rate in identifying IA between the AI model and frozen section examination was 0.69, with a sensitivity of 0.50 and specificity of 0.97. CONCLUSION: The deep learning system can discriminate malignant diseases for pulmonary nodules measuring no more than 3 cm. The AI model has a high positive predictive value for invasive adenocarcinoma with respect to intraoperative frozen section examination, which might help determine the individualized surgical strategy.

Sleeve Lobectomy After Neoadjuvant Chemoimmunotherapy Versus Chemotherapy for Squamous Cell Lung Cancer: A Multicenter, Retrospective Study.

Introduction: To analyze the feasibility and efficacy of sleeve lobectomy after neoadjuvant immunotherapy in multicenter patients with squamous cell lung cancer. Methods: We retrospectively identified patients who received neoadjuvant immunotherapy (n = 14) or chemotherapy alone (n = 33) at five thoracic surgery centers between 2018 and 2020. The primary end point was 30-day major complications. The secondary end point was major pathologic response. Multivariate analysis was performed with a log-binomial regression model adjusting potential risk factors. Results: All patients received induction therapy and underwent sleeve lobectomy without 90-day postoperative deaths. The distribution of age, sex, nutrition status, pulmonary and cardiac function, tumor stage, surgical approach, and location of the pulmonary lobe was well balanced between the two cohorts. In the immunotherapy cohort, two patients (14.3%) experienced a pulmonary major complication, whereas nine pulmonary major complications and one cardiac major complication (30.3%) occurred in the chemotherapy cohort (p = 0.302). Conclusions: Neoadjuvant immunotherapy in addition to chemotherapy did not increase 30-day risk of postoperative complications, and immunotherapy is a favorable factor affecting pathologic downstage and response. Therefore, sleeve lobectomy after induction chemoimmunotherapy appears safe and feasible.

Biocompatible and Long-Term Monitoring Strategies of Wearable, Ingestible and Implantable Biosensors: Reform the Next Generation Healthcare.

Sensors enable the detection of physiological indicators and pathological markers to assist in the diagnosis, treatment, and long-term monitoring of diseases, in addition to playing an essential role in the observation and evaluation of physiological activities. The development of modern medical activities cannot be separated from the precise detection, reliable acquisition, and intelligent analysis of human body information. Therefore, sensors have become the core of new-generation health technologies along with the Internet of Things (IoTs) and artificial intelligence (AI). Previous research on the sensing of human information has conferred many superior properties on sensors, of which biocompatibility is one of the most important. Recently, biocompatible biosensors have developed rapidly to provide the possibility for the long-term and in-situ monitoring of physiological information. In this review, we summarize the ideal features and engineering realization strategies of three different types of biocompatible biosensors, including wearable, ingestible, and implantable sensors from the level of sensor designing and application. Additionally, the detection targets of the biosensors are further divided into vital life parameters (e.g., body temperature, heart rate, blood pressure, and respiratory rate), biochemical indicators, as well as physical and physiological parameters based on the clinical needs. In this review, starting from the emerging concept of next-generation diagnostics and healthcare technologies, we discuss how biocompatible sensors revolutionize the state-of-art healthcare system unprecedentedly, as well as the challenges and opportunities faced in the future development of biocompatible health sensors.

Utility of 18F-FDG PET/CT uptake values in predicting response to neoadjuvant chemoimmunotherapy in resectable non-small cell lung cancer.

INTRODUCTION: Reliable predictive markers are lacking for resectable non-small cell lung cancer (NSCLC) patients treated with neoadjuvant chemoimmunotherapy. The present study investigated the utility of SUVmax values acquired from PET/CT to predict the response to neoadjuvant chemoimmunotherapy for resectable NSCLC. MATERAL AND METHODS: SUVmax, clinical and pathological outcomes, were collected from patients in 5 hospitals. Patients who received dynamic PET/CT surveillance were divided into cohorts A (chemoimmunotherapy) and B (chemotherapy), respectively, while cohort C (chemoimmunotherapy) comprised patients undergoing post-therapy PET/CT. Associations between SUVmax and major pathologic response (MPR) were evaluated through receiver operating characteristic (ROC) curves. RESULTS: A total of 129 cases with an MPR rate of 46.5 % was identified. In neoadjuvant chemoimmunotherapy, ΔSUVmax% (AUC: 0.890, 95 % CI: 0.761-0.949) and post-therapy SUVmax (AUC: 0.933, 95 % CI: 0.802-0.959) could accurately predict MPR. On the contrary, the baseline SUVmax was not associated with MPR (p = 0.184). Furthermore, an independent cohort C proved that post-therapy SUVmax could serve as an independent predictor (AUC: 0.928, 95 % CI: 0.823-0.958). In addition, robust predictive performance could be observed when we use the optimal cut-off point of both ΔSUVmax% (54.4 %, AUC: 0.912, 95 % CI: 0.824-0.994) and post-therapy SUVmax (3.565, AUC: 0.912, 95 % CI: 0.824-0.994) in neoadjuvant chemoimmunotherapy. The RNA data revealed that the expression of PFKFB4, a key enzyme in glycolysis, was positively correlated with SUVmax value and tumor cell proliferation after neoadjuvant chemoimmunotherapy. CONCLUSION: These findings highlighted that the ΔSUVmax% and remained SUVmax were accurate and non-invasive tests for the prediction of MPR after neoadjuvant chemoimmunotherapy.