Abstract The complexity and heterogeneity of malignant tumors necessitate a paradigm shift from a disease-centric to a patient-centric model of care. Cancer holistic integrative assessment (CHIA) is a multidimensional evaluation process that forms the cornerstone of personalized oncology. CHIA is characterized by four core principles: integrative philosophy, multidimensionality, dynamic individualization, and multidisciplinary collaboration. Key assessment domains include: 1) General status (performance status, physical function, nutrition); 2) Symptom burden ( pain, fatigue, et al.); 3) Organ function and comorbidities to gauge treatment tolerance; 4) Psychological and cognitive state (distress, anxiety, depression, cognitive function); 5) Family and social support systems, including financial toxicity; 6) Tumor biology (stage, molecular profile) to define therapeutic goals; and 7) Genetic risk 8)fertility preservation needs 9) Traditional Chinese Medicine Tumor Pathogenesis Identification and Evaluation. CHIA is a pivotal, dynamic process essential for tailoring safe, effective, and humanistic anticancer therapy. Its systematic implementation, supported by training, standardized protocols, and digital tools, is fundamental to advancing precision oncology and achieving the strategic goal of "Healthy China."
BACKGROUND:In clinical stage IA lung adenocarcinoma (LUAD), rapid and accurate intraoperative diagnosis is crucial to decide whether to perform segmentectomy and lobectomy. Frozen section analysis is time consuming and not always reliable for LUAD diagnosis and grading. We developed deep learning models using surgical resection images to assist in prompt diagnosis and risk stratification of stage IA LUAD to aid in surgical decision making. METHODS:In this prospective, multicentre cohort, patients with clinical stage IA LUAD were enrolled from June 1, 2020, to Sept 30, 2023, from three hospitals in China. Surgical resection images of LUAD were captured using smartphones under natural lighting conditions in the operating theatre. Deep learning models were established based on these images for three tasks: identification of invasive lung adenocarcinoma from non-invasive lung adenocarcinoma lesions; diagnosis of adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive lung adenocarcinoma; and grading of adenocarcinoma in situ, minimally invasive adenocarcinoma, invasive lung adenocarcinoma grade 1, grade 2, and grade 3 according to the International Association for the Study of Lung Cancer Grading System. The study is registered with the Chinese Clinical Trial Registry, ChiCTR2300075999. FINDINGS:We enrolled 1529 patients with 2344 surgical section images from Guangdong Provincial People's Hospital, 116 patients with 307 images from Affiliated Hospital of Guangdong Medical University, and 82 patients with 259 images from Meizhou People's Hospital. The area under curve for the surgical resection image-based model (SuRImage) was 0·84 (95% CI 0·82-0·86) for invasive lung adenocarcinoma identification, 0·87 (0·86-0·88) for invasive lung adenocarcinoma diagnosis, and 0·85 (0·83-0·86) for invasive lung adenocarcinoma grading in Guangdong Provincial People's Hospital. SuRImage showed better diagnosis performance than frozen section. Assisted with SuRImage, average diagnostic accuracy of thoracic surgeons could be improved from 63·80% (95% CI 60·57-67·03) to 73·44% (67·68-79·19) for invasive lung adenocarcinoma grading. INTERPRETATION:This first-in-field diagnostic study focused on intraoperative diagnosis based on surgical resection images in stage IA LUAD and provides insights into the macroscopic morphological features for pathological invasiveness. By elucidating macroscopic morphological indicators of invasiveness, SuRImage empowers surgeons to make more precise, timely decisions, optimise intervention strategies, and streamline the surgical workflow. FUNDING:National Key R&D Program of China; National Natural Science Foundation of China; International Science and Technology Cooperation Program of Guangdong; Natural Science Foundation of Guangdong; Beijing Xisike Clinical Oncology Research Foundation; Meizhou Medical and Health Scientific Research Projects.
Background:Cervical anastomotic leakage is a serious complication following esophagectomy. The selection of the reconstruction route [posterior mediastinal (PM) vs. retrosternal (RS)] is often subjective, and the role of a narrow thoracic inlet as an independent risk factor remains underexplored. This study aimed to investigate the impact of thoracic inlet anatomy and reconstruction route selection based on computed tomography three‑dimensional reconstruction on cervical anastomotic leakage after esophagectomy. Methods:We conducted a retrospective analysis of 100 patients who underwent McKeown esophagectomy between October 2019 and October 2025. After propensity score matching, 33 patients were matched in both the PM and RS groups. Preoperative computed tomography (CT) images were used for three-dimensional reconstruction to measure reconstruction route length and thoracic inlet parameters, including thickness of the clavicle (TC), thickness of the sternum (TS), interclavicular distance (ICD), sternum-trachea distance (STD), sternum-vertebra distance (SVD), and thoracic diameters. Results:The RS route was significantly shorter than the PM route (336±39.3 vs. 356±32.1 mm, P<0.05). Multivariate regression analysis identified STD and thoracic horizontal diameter (HD) as independent risk factors for cervical anastomotic leakage. Conclusions:The RS route is shorter than the PM route. A narrow thoracic inlet, characterized by a smaller STD and a larger HD, is a key risk factor for anastomotic leakage. Preoperative CT assessment of the thoracic inlet provides significant predictive value for surgical planning.
Metabolic reprogramming is a hallmark of cancer that promotes tumor progression and immune evasion. Here, we identify a NIPAL1-driven metabolic-epigenetic circuit in esophageal squamous cell carcinoma (ESCC) that facilitates tumor growth and suppresses antitumor immunity. Mechanistically, NIPAL1 recruits the tyrosine kinase HCK to phosphorylate LDHA at Y10, enhancing glycolysis and lactate production. Lactate accumulation promotes p300-mediated histone H3K18 lactylation (H3K18la), which transcriptionally activates NIPAL1 expression, establishing a self-sustaining NIPAL1-HCK-p-LDHA-lactate-p300-H3K18la loop. This axis functions independently of NIPAL1's canonical magnesium transporter activity and promotes immune escape by impairing CD8+ T cell function. Pharmacological inhibition of HCK or p300 disrupts this loop and restores antitumor immunity, sensitizing tumors to anti-PD-1 therapy. Clinically, expression of NIPAL1, p-LDHA (Y10), and H3K18la correlates with response to immune checkpoint blockade. Our findings reveal a previously unrecognized NIPAL1-HCK-H3K18la signaling loop that integrates tumor metabolism to immune regulation, offering promising targets to improve immunotherapy efficacy in ESCC.
Lung transplantation (LT) is emerging as a critical final treatment for end-stage lung diseases including pneumoconiosis. Outcomes of single lung transplantation (SLT) and double lung transplantation (DLT) in pneumoconiosis remain understudied. This study evaluates clinical differences between the two procedures in pneumoconiosis patients to guide therapeutic decision-making for this occupational population. This retrospective cohort study included 119 pneumoconiosis patients undergoing LT at The Affiliated Wuxi People’s Hospital of Nanjing Medical University between Jan 2018 and Dec 2022. The choice of SLT versus DLT was primarily driven by clinical judgment of high surgical risk, primarily due to severe pleural adhesions or calcification deemed too risky for bilateral pneumonectomy. Data on demographics, intraoperative and postoperative characteristics and patient survival were collected to compare SLT and DLT outcomes using Mann-Whitney U test and Pearson’s chi-square test. The primary outcome was 1-year posttransplant survival. Posttransplant survival was assessed by Kaplan-Meier analysis and Cox proportional hazards models. Of all the transplant recipients, 61 (51.3
Esophageal squamous cell carcinoma (ESCC) is a highly lethal cancer with limited therapeutic options and frequent relapse. RNA acetylation has emerged as a crucial regulator of tumor biology. In this study, we identify circTHBS1 as an oncogenic circRNA that promotes autophagy and drives ESCC progression. Mechanistically, circTHBS1 interacts with the N-acetyltransferase 10 (NAT10), preventing its ubiquitin-mediated proteasomal degradation and thereby increasing global N4-acetylcytidine (ac4C) modification. Rab8a is identified as a key ac4C target, where ac4C modification at a conserved CGCCAG motif within the coding sequence facilitates NAT10 binding and enhances translation. Disruption of this modification impairs Rab8a-driven autophagy and suppresses tumor progression. Collectively, our findings reveal a circTHBS1/NAT10-ac4C/Rab8a axis that reprograms translational control and autophagy, providing new mechanistic insights and potential therapeutic targets for ESCC.
The resection of pulmonary segmental tissue involving isolation and transection of only the target segmental artery without individual dissection of the segmental bronchus is defined as an incomplete anatomic segmentectomy (IAS). Few studies have compared postoperative symptoms between complete anatomical segmentectomy (CAS) and IAS. This study aims to evaluate symptom burden after these two surgical approaches. We analyzed prospective data from patients with stage IA1–IA2 NSCLC (predominantly ground-glass opacity) undergoing segmentectomy (2021–2023). Patients were grouped into CAS or IAS. Symptoms were assessed using the Perioperative Symptom Assessment for Lung Surgery (PSA-Lung) questionnaire via electronic patient reported outcomes system during and after hospitalization. After propensity score matching, postoperative symptom burden was compared between groups. Among 184 patients, 97 patients (52.7
Background Optimizing elective surgical scheduling is a core component of modern hospital management. While weekend–weekday differences have been reported in selected high-risk settings, evidence regarding intra-week variation in elective thoracic surgery remains limited and inconsistent. This study aims to explore the postoperative outcomes of patients with early-stage lung cancer who underwent video-assisted thoracoscopic surgery early or late in the week. Methods From August 2022 to April 2023, we enrolled patients with early-stage lung cancer who underwent video-assisted thoracoscopic surgery from three hospitals. Patients treated surgically between Monday and Wednesday and between Thursday and Saturday were classified into early and late groups based on institutional scheduling practices, respectively. Propensity score matching(PSM) was performed to minimize confounding bias. Traditional clinical outcomes includuing complications, postoperative length of stay, as well as patient-reported outcomes (PROs) assessing postoperative symptoms and functional recovery, were compared between groups. Results 203 patients were included in finally analysis. PSM resulted in 148 patients (74 in each) in the subsequent analysis, and there were no significant differences in the demographic and tumor characteristics. No significant differences were observed between early-week and late-week groups in intraoperative complications, in-hospital complications, 30-day postoperative complications, or patient-reported outcomes. Apparent differences in postoperative length of stay were attenuated after stratification by institutional discharge policies.The uniformly low and comparable patient-reported outcome scores observed in both groups suggest that patient-perceived recovery trajectories after VATS are stable across the surgical week Conclusion These findings suggest that contemporary VATS-based perioperative care for early-stage lung cancer delivers consistent clinical and patient-centered outcomes throughout the surgical week, supporting the stability and reliability of current surgical scheduling practices
Background:The detection of pulmonary nodules (PNs) has increased with the use of low-dose computed tomography screening. Effective management requires timely longitudinal surveillance and reliable comparison with prior examinations, yet access to previous imaging across institutions is often fragmented, leading to delays and potentially unnecessary repeat scans and costs. Cloud-based medical imaging (CMI) solutions offer a potential means of improving access and facilitating cross-institutional data exchange. However, the adoption and utility of CMI in PN care, especially in China, remain underexplored. Objective:This study aims to evaluate the possession, use, and impact of CMI on health care utilization, patient knowledge, and financial burden, as well as to identify usability and interoperability barriers through qualitative investigation. Methods:A mixed methods cross-sectional study was conducted from October 2022 to May 2024. The study involved 701 patients with PNs who completed structured surveys, and 20 participants (10 patients and 10 physicians) were interviewed. CMI use was defined as self-reported ability to view radiological images on a mobile device. We compared CMI users and nonusers and estimated adjusted odds ratios using multivariable logistic regression, then applied 1:1 propensity score matching to examine associations between CMI use and health care utilization, costs, and patient perceptions, and qualitative interviews were analyzed for usability themes. Results:The study found that 611 (87.2%) out of 701 patients had obtained CMI, with 404 (57.6%) out of 701 patients actively using it. In multivariable analysis, older age was independently associated with lower CMI use (odds ratios 0.985, 95% CI 0.972-0.999). After 1:1 propensity score matching, CMI users accessed more internet hospitals, consulted more physicians, and reported lower health care costs compared to nonusers. Users also demonstrated higher disease knowledge. Qualitative data identified key barriers, including poor system usability, limited retention time for images, and weak interoperability. CMI was perceived as beneficial for patient convenience and clinical efficiency, though concerns over image quality and system fragmentation were prevalent. Conclusions:While CMI is widely available, its usage remains suboptimal. Increased use is associated with enhanced health care engagement and reduced costs, suggesting that improving system usability and ensuring consistent access to imaging may help realize potential benefits of CMI. Future improvements should focus on ensuring long-term access, better retention protocols, and overcoming interoperability issues.
ABSTRACT Even ‘low‐risk’ intraductal papillary carcinoma can progress rapidly to invasive disease following unplanned discontinuation of adjuvant endocrine therapy, as illustrated by this case where hepatotoxicity led to treatment cessation and early recurrence. This underscores the critical need for proactive toxicity management, patient education, and consideration of enhanced surveillance for high‐risk patients who interrupt therapy.
Background:Neoadjuvant chemoradiotherapy (NCRT) has long been considered the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC), but its long-term survival benefits remain limited and associated with potential safety concerns. The emergence of neoadjuvant immunochemotherapy (NICT) has shown encouraging short-term efficacy; however, evidence regarding its long-term outcomes and survival-related risk factors is still underexplored. This study aimed to evaluate survival outcomes of patients with resectable ESCC treated with NICT followed by surgery and to develop a nomogram for individualized survival risk prediction. Methods:Clinical data and follow-up information were retrospectively collected for 88 patients with ESCC who underwent NICT followed by McKeown esophagectomy. This study was conducted from January 2019 to December 2022 at Department of Thoracic Surgery, Guangdong Provincial People's Hospital. The median follow-up was 31.5 (range, 12-47) months. Statistical analysis was performed to evaluate clinical data and survival outcomes. Results:The study included 88 patients, equally divided by gender, with 44 males and 44 females. Multivariate regression analysis identified age, number of neoadjuvant treatment cycles, clinical primary tumor stage (cT), clinical lymph node stage (cN), and pathological lymph node stage (pN) as independent risk factors for survival in patients receiving NICT (P<0.05). A nomogram predictive model was constructed, demonstrating a high predictive value with an area under the receiver operating characteristic (ROC) curve of 0.927 [95% confidence interval (CI): 0.873-0.982]. Conclusions:NICT offers significant survival benefits for patients with resectable ESCC. The study identified age, neoadjuvant treatment cycles, cT, cN, and pN as independent risk factors impacting survival. The predictive model developed in this study can aid in selecting suitable postoperative adjuvant therapies, potentially enhancing treatment outcomes.
Accurately predicting the pathological response of lymph nodes to neoadjuvant chemoimmunotherapy in non-small cell lung cancer (NSCLC) remains a challenge. This study aimed to evaluate the effectiveness of [18F]FDG PET/CT imaging in predicting lymph node response to neoadjuvant chemoimmunotherapy in resectable NSCLC. We investigated the predictive value of dynamic changes in imaging features of both primary tumors and lymph nodes. A total of 86 patients with stage IIB–IIIB NSCLC were enrolled. [18F]FDG PET/CT scans were conducted at baseline and after neoadjuvant chemoimmunotherapy, but before surgery. SUVmax and size of primary tumors and lymph nodes were measured, and their dynamic changes were analyzed to correlate with nodal response. The predictive accuracy was assessed using the area under the receiver operating characteristic curve. Event-free survival (EFS) was evaluated using Kaplan–Meier analysis. The metabolism composite index, which combines changes in SUVmax of the primary tumor and post-treatment SUVmax of lymph nodes, significantly improved lymph node response prediction, with an AUC of 0.852 (95
BACKGROUND:Postoperative fatigue is widely recognized as one of the most prevalent adverse effects of surgery, representing a critical determinant of functional recovery and quality of life. However, fatigue is commonly measured at a single time point, failing to capture its dynamic nature. This study aimed to characterize the longitudinal trajectories of postoperative fatigue and identify the potential factors. METHODS:This retrospective study included patients with lung cancer who underwent thoracoscopic surgery between March 2021 and October 2023. Patients completed the Perioperative Symptom Assessment for Lung Surgery Scale (PSA-Lung) daily for 7 days after surgery. Latent class mixed modeling was used to analyze the longitudinal patient-reported data and identify subgroups based on trajectory features. RESULTS:A total of 1,096 patients were included. Three-cluster trajectory model provided the best fit, consisting of deterioration-fatigue group (17.7%), recovery-fatigue group (31.4%) and mild-fatigue group (50.9%). Compared with the mild-fatigue group, patients with comorbidities had a higher risk of being categorized into the recovery-fatigue group (odds ratio 1.44, 95% confidence interval 1.02-2.04; p = 0.040). The presence of recovery-fatigue was associated with lower preoperative hemoglobin level (p = 0.025). Moreover, lower preoperative body mass index and albumin level increased the likelihood of being classified as the deterioration-fatigue group (p = 0.022 and p = 0.026, respectively). CONCLUSIONS:This study elucidated the heterogeneity of fatigue trajectories, with half of the patients experiencing either recovery-fatigue or deterioration-fatigue. The severity of postoperative fatigue was found to be worse in patients with comorbidities or poor nutritional status.
Chronic inflammation is a crucial factor in the development and progression of lung cancer. External factors, such as indoor and outdoor air pollution and occupational hazards, along with imbalances in the lung microbiome, create a pro-inflammatory environment conducive to tumorigenesis. This review explores how various mechanisms drive the production of pro-inflammatory cytokines and immune modulators, leading to a tumor-promoting microenvironment. It also examines the roles of key cells in these processes and highlights the importance of epigenetic modifications in inflammation-driven lung cancer. Understanding these interactions provides insights into targeted therapeutic strategies and underscores the significance of addressing inflammation to reduce lung cancer risk.
Background Video-assisted lobectomy (VAL) and robot-assisted lobectomy (RAL) are recommended standard treatments for early-stage non-small cell lung cancer (NSCLC). Nevertheless, comparisons of long-term survival between VAL and RAL are controversial because of the lack of robust evidence from prospective multicentre randomised controlled trials (RCTs). Method We are conducting a prospective multicentre RCT to evaluate whether RAL is non-inferior to VAL in terms of long-term survival in patients with clinical stage T1-2N0-1M0 (stage I-II) NSCLC who underwent lobectomies (RAVAR study). A total of 1,124 patients will be enrolled from multiple institutions. The primary endpoint is the five-year disease-free survival rate. The secondary endpoints include five-year overall survival and short-term outcomes, such as perioperative complications, length of postoperative hospital stay, operation time, number of dissected lymph nodes, chest tube duration, pain score, and total cost of hospitalisation. The Ethics Committee of the Sun Yat-sen University Cancer Center approved the study protocol in May 2020, and patient enrolment began in August 2020. Approval was obtained from each institutional ethics committee before initiating patient enrolment. Discussion This multicentre RCT compares the long-term outcomes of RAL and VAL in resectable early-stage NSCLC. The expected results of this study will determine whether RAL can achieve satisfactory long-term outcomes that are not inferior to those of VAL in patients with early-stage NSCLC, thereby providing high-level evidence for a minimally invasive approach for these patients. Trial registration The protocol of RAVAR trial was registered in the China Clinical Trials Registry as ChiCTR2000034737 (registration date: July 17, 2020) and ClinicalTrials.gov as NCT06524427 (registration date: July 29, 2024). Date of First Participant Enrollment: August 26, 2020.
Background:Persistent cough after pulmonary resection (CAP) is one of the most common postoperative complications in patients with non-small cell lung cancer (NSCLC) and can impair postoperative recovery and quality of life. While several clinical and surgical risk factors have been identified, the genetic basis of CAP remains unclear. Whole-exome sequencing (WES) allows comprehensive detection of coding-region mutations and may help uncover molecular markers associated with CAP. This retrospective cohort study investigated the association between gene mutations identified by WES and CAP in patients with NSCLC. Methods:Twenty NSCLC patients who underwent surgery were enrolled and categorized into a cough group (n=9) and a non-cough group (n=11) using the Leicester Cough Questionnaire-Mandarin Chinese version (LCQ-MC). Postoperative tissue samples were collected for WES. Clinical data were analyzed to assess the incidence of CAP and related clinical characteristics. Genetic mutations were identified through WES, and a logistic regression model was applied to determine potential risk factors for CAP. Results:Chi-squared tests identified significant associations between CAP and preoperative cough, as well as mutations in the TBC1D2 and SEPT12 genes. No significant associations were observed for gender, comorbidities, family history of cancer, postoperative diagnosis, pleural invasion, pathological stage, pleural effusion, or pneumothorax. These findings may aid in identifying potential diagnostic markers and therapeutic targets for the management of postoperative cough. Conclusions:The TBC1D2 and SEPT12 genes were found to harbor both insertion/deletion (INDEL) and single nucleotide polymorphism (SNP) mutations in NSCLC patients who developed CAP after surgery. These genetic alterations may serve as potential predictive markers for postoperative CAP; however, given the small sample size, the findings should be regarded as hypothesis-generating and require validation in larger cohorts. Patients carrying multiple mutations appeared to have a higher likelihood of developing postoperative CAP.
Objective: The present study aims to explore the roles of infusion time, administration sequence, and interval of immunochemotherapy (IO) in predicting overall survival (OS) in patients with locally advanced ESCC. Methods: This multicenter retrospective study enrolled advanced ESCC who received IO between November 2019 and November 2021. Patients were divided into groups according to the three classifiers (IO infusion time, administration sequence, and infusion interval), and were further analyzed for the roles of these classifiers in predicting the prognosis of the ESCC patients. Results: A total of 183 eligible patients with locally advanced ESCC were included in this study. Patients who received >= 75% of immunotherapy drug infusions after 12:00 h had better OS compared to those who received <75% of immunotherapy drug infusions after 12:00 h in the 1:1 propensity score matching analysis (HRadjusted: 0.38, 95% CI: 0.17-0.82; P=0.013). Cox proportional hazards regression revealed that ESCC patients with shorter infusion intervals (<3.3 h) had better OS (HRadjusted: 0.34, 95% CI: 0.15-0.76; P=0.008). Conclusion: For patients with ESCC, the OS is significantly better when immunotherapy is administered after 12:00 h. A shorter infusion interval (<3.3 h) on the same-day immunochemotherapy could lead to a better prognosis.