Search Results (59)

Background/Objectives: Perioperative chemo-immunotherapy (CHT-IO) has emerged as a standard treatment strategy for resectable stage II–IIIB NSCLC. However, data regarding surgical feasibility, mini-invasive surgery rates, perioperative outcomes, and postoperative complications in real-world single-center experiences remain limited. Methods: A retrospective single-center analysis was performed including consecutive patients with locally advanced NSCLC treated with perioperative chemo-immunotherapy between March 2024 and March 2026. Patients received platinum-based chemotherapy combined with pembrolizumab or durvalumab, followed by surgical resection with curative intent. Surgical, pathological, and postoperative outcomes were analyzed. Results: Thirty patients received neoadjuvant CHT-IO, of which 25 (83.3%) underwent surgical resection. Reasons for failure to proceed to surgery included treatment-related toxicity or deterioration in performance status (n = 3), disease progression (n = 1), and patient refusal (n = 1). Lobectomy was the most performed procedure (64%), while a minimally invasive approach (uniportal VATS) was adopted in 44% of cases. Moderate-to-severe pleural adhesions (64%) and hilar fibrosis (60%) were observed intraoperatively. Despite these technical challenges, conversion to thoracotomy was required in only one case (4%), no intraoperative complications occurred, and complete (R0) resection was achieved in 96% of patients. Pathological complete response and major pathological response were observed in 36% and 52% of cases, respectively. Postoperative complications occurred in 56% of patients, although most were Clavien–Dindo grade I–II. The presence of comorbidities was the only factor associated with an increased risk of postoperative complications (OR 10.00, 95% CI 0.99–100.46; p = 0.05). Median length of hospital stay was 5.65 ± 2.04 days. One postoperative death due to septic complications was recorded. Conclusions: In this real-world monocentric experience, the combination of perioperative CH-ICIs and surgical resection (including mini-invasive approach) was safe and feasible in patients with locally advanced NSCLC. High rates of complete (R0) resection and encouraging pathological responses were observed, consistent with outcomes reported in randomized trials. Although surgery was overall frequently technically demanding, these changes did not appear to compromise perioperative safety or oncological radicality, even when minimally invasive approaches were adopted. Larger studies with longer follow-up are needed to better define long-term oncological outcomes. Full article

The adoption of neoadjuvant immune checkpoint inhibitor (ICI)-based chemoimmunotherapy has fundamentally transformed the operative landscape of resectable non-small cell lung cancer (NSCLC). Surgeons are now routinely confronted with ICI-altered tissue planes characterized by hilar fibrosis, vascular friability, and disrupted lymph node architecture. Simultaneously, robotic-assisted thoracic surgery (RATS) has consolidated its position as the dominant minimally invasive platform for pulmonary resection, accounting for the majority of lobectomies and segmentectomies performed at high-volume centers in 2023. Whether RATS confers specific technical advantages in this increasingly complex operative context remains incompletely characterized. We conducted a structured narrative review of published evidence, synthesizing data from randomized controlled trials, prospective cohorts, national registry analyses, and emerging technology reports addressing RATS in the setting of neoadjuvant ICI-based therapy for NSCLC. A systematic literature search was conducted across PubMed and EMBASE using predefined search terms. Available evidence, though largely retrospective and limited by small sample sizes, consistently demonstrates that RATS after neoadjuvant chemoimmunotherapy is technically feasible and oncologically sound, with R0 resection achievable in virtually all cases. The enhanced three-dimensional visualization, tremor filtration, and instrument degrees of freedom afforded by robotic platforms appear particularly advantageous in the setting of dense hilar adhesions and fragile pulmonary vasculature. Lymph node yield, a recognized robotic advantage, is preserved or enhanced despite post-ICI fibrosis. Pooled conversion rates to thoracotomy, derived from post hoc surgical analyses of ICI trial populations rather than trials designed to measure conversion, are higher than for upfront resection; available retrospective single-center data, including one direct RATS-versus-VATS comparison, suggest lower conversion rates with RATS in experienced hands, though this conclusion requires prospective validation. Emerging platform integrations, including combined robotic bronchoscopy and thoracoscopic surgery, single-port systems, and artificial intelligence-assisted anatomical navigation, are poised to further extend the reach of minimally invasive surgery in this challenging clinical scenario. In experienced centers, RATS appears to offer a technically favorable minimally invasive platform for pulmonary resection after neoadjuvant ICI-based therapy, with potential advantages over VATS in managing immunotherapy-altered anatomy; however, this conclusion is derived from retrospective series and should be interpreted cautiously pending prospective comparative data. Prospective multicenter trials with standardized surgical endpoints are urgently needed. Full article

Background: Muscle-invasive bladder cancer (MIBC) is an aggressive disease with heterogeneous responses to neoadjuvant chemotherapy and emerging chemo-immunotherapy combinations. Reliable biomarkers to predict treatment responsiveness before therapy initiation are needed to guide patient selection. Objective: The objective of this study was to identify genomic and immune-related features associated with immune-active tumor phenotypes in MIBC using The Cancer Genome Atlas bladder cancer cohort (TCGA-BLCA). Methods: A retrospective bioinformatics analysis of TCGA-BLCA data was performed, evaluating gene expression, somatic mutations, tumor mutational burden (TMB), DNA damage response (DDR) gene status, and immune infiltration signatures. Immune enrichment metrics were derived from transcriptomic data. In the absence of direct treatment response data, a surrogate immune response classification was applied. Associations were analyzed using descriptive statistics and Firth’s penalized logistic regression. Results: Tumors classified as immune-high phenotype group based on immune-related features exhibited significantly higher global immune infiltration, including increased ImmuneScore and enrichment of cytotoxic and innate immune cells. In multivariable analysis, ImmuneScore was the only independent predictor of inferred responsiveness (p = 0.003). Conclusions: Global immune infiltration showed the strongest association with immune-active tumor phenotypes among the features examined in this TCGA-based analysis. These exploratory findings suggest that immune profiling may warrant further investigation as a component of tumor characterization in MIBC, pending validation in cohorts with clinical treatment and outcome data. Full article

Accurate regional lymph node staging is essential for guiding treatment and predicting outcomes in non-small cell lung cancer. While the 9th edition of the TNM classification introduced prognostic subdivisions for N2 disease, the N1 category remains a single, unified descriptor. However, N1 disease is highly heterogeneous. Evidence shows significant survival differences between single-station (N1a) and multi-station (N1b) involvement, as well as between peripheral (N1p) and hilar (N1h) metastases. Standard medical imaging evaluation and conventional bronchoscopy often fail to detect “occult N1 disease,” leading to postoperative stage migration and suboptimal treatment sequencing. This diagnostic gap affects critical clinical decisions, including the selection of patients for sublobar resection, the administration of neoadjuvant chemoimmunotherapy, and the precision of radiation target volumes. The main obstacle to refining N1 staging has been the limited ability of existing clinical staging modalities to access and accurately assess N1p nodes. However, recent technological advances, particularly in thin convex probe endobronchial ultrasound examination, have renewed interest in bronchoscopic evaluation of N1p and in improving preoperative clinical N1 staging. The purpose of this review is to summarize the biological and immunological basis for N1 subclassification and evaluate how emerging technologies can bridge the gap between clinical and pathological staging. Refining the N1 compartment is vital for a personalized staging system that reflects the true biological spectrum of lung cancer. Full article

Background/Objectives: Management of cervical esophageal cancer after induction therapy remains unsettled. Definitive chemoradiotherapy is the guideline default, but a subset of patients with residual but resectable disease may still benefit from surgery. No validated multidisciplinary selection framework exists for this subsite. Methods: We conducted a systematic review registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420261369102) and guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement, using searches of PubMed/MEDLINE, Web of Science, Scopus, and the Cochrane Library from inception through 14 April 2026. We identified 1779 records, removed 873 duplicates, and screened 906 records; 87 full-text reports were assessed, of which 67 were excluded at the full-text stage (66 on population grounds—disease not cervical esophageal; and 1 because cervical-direct outcomes were not separable within a mixed cervical/thoracic cohort), leaving 20 cervical-direct studies included in the primary synthesis. Thoracic and meta-analytic sources are cited for indirect comparison and biological rationale but are not counted in the included set. Included studies were evaluated using the Newcastle–Ottawa Scale (NOS) and Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I); certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. Formal meta-analysis was not performed because study design, treatment approach, and outcome reporting were too heterogeneous. Results: Cervical-specific evidence is predominantly retrospective but consistent in direction. Available cervical-specific observational data suggest benefit mainly in patients with biopsy-confirmed incomplete response, resectable residual disease, preserved performance status, and access to experienced centers. Larynx-preserving resection is feasible in 90% of T1–2 tumors and 54% of T3–4 responders. In thoracic esophageal squamous cell carcinoma, neoadjuvant chemoimmunotherapy yields pathologic complete response rates of approximately 29–48%; in cervical disease, the SCENIC trial has reported interim clinical response of approximately 50% in 28 patients, but pathology-confirmed response is not yet available. We present a proposed multidisciplinary selection framework integrating response depth, post-induction stage, laryngeal preservation feasibility, sarcopenia, circulating tumor DNA dynamics, and programmed death-ligand 1 (PD-L1) expression. The framework has not been prospectively validated and is presented as a hypothesis-generating, conceptual tool for multidisciplinary discussion rather than a clinically validated instrument. Adjuvant nivolumab is recommended for residual pathologic disease after margin-negative (R0) resection when surgery follows preoperative chemoradiotherapy; after PD-1-based induction, adjuvant checkpoint inhibition remains investigational. Conclusions: The available cervical-direct evidence is predominantly retrospective and selection-prone, and several inputs supporting the framework are extrapolated from thoracic ESCC cohorts; conclusions about the survival benefit of surgery should therefore be read as associations rather than causal claims. Surgery has a role after induction therapy in carefully selected incomplete responders. The proposed framework is designed for multidisciplinary use and requires prospective validation before routine clinical application. Full article

Lung cancer is one of the most common cancers worldwide, with non-small-cell lung cancer (NSCLC) being the most prevalent type. While surgical resection followed by adjuvant platinum-based chemotherapy has been the standard for curative-intent therapy for clinical stage II NSCLC since 2005, disappointing 5-year survival prompted the exploration of newer systemic therapies. In recent years, several landmark trials increasingly support the use of immunotherapy and molecular targeted treatments. The evidence for neoadjuvant chemoimmunotherapy is exciting, but the transition from a surgery-first approach to a new standard of care carries important challenges, including increased surgical attrition, intraoperative technical difficulty, and delays in care. This article provides a comprehensive review of the optimal treatments and emerging therapies for resectable stage II NSCLC. By systematically analyzing recent advances and challenges in NSCLC treatment strategies, we aim to highlight a paradigm shift toward a more molecularly guided, individualized treatment sequence in stage II NSCLC care, with the goal of maximizing each patient’s curative potential. Full article

Background/Objectives: Stage III non-small cell lung cancer (NSCLC) is a heterogeneous and clinically challenging disease. Despite therapeutic advances, decisions regarding resectability and treatment sequencing remain complex. Multidisciplinary discussion (MDD) is increasingly recognized as key to personalized, evidence-based care. Methods: The “Integrate 6.0” conference gathered approximately 90 lung cancer specialists, including oncologists, thoracic surgeons, and radiation oncologists, divided into mixed groups simulating multidisciplinary team (MDT) meetings. Groups reviewed complex clinical cases, supported by facilitators providing concise, evidence-based updates. A pre-event survey explored MDT structure and dynamics across institutions. Results: The survey highlighted considerable variability in MDT composition and practices. Most participants had significant involvement in thoracic oncology. Discussions revealed higher consensus in straightforward cases, while complex stage III scenarios—especially with driver mutations or bulky nodal disease—required more nuanced, collaborative decision making. Key topics included neoadjuvant chemoimmunotherapy, surgery in borderline resectable cases, and managing immune-related toxicities. Conclusions: “Integrate 6.0” effectively connected theoretical knowledge with real-world practice through interactive, multidisciplinary dialogue. It underscored the vital role of MDD in managing complex stage III NSCLC and the need for adaptable treatment strategies. Future conferences should assess MDD’s impact on outcomes and expand participation to include molecular pathologists and geriatricians. Full article

Triple-negative breast cancer (TNBC) represents a biologically aggressive subtype with limited therapeutic targets; however, tumor-infiltrating lymphocytes (TILs) have emerged as the most robust immune biomarker with compelling prognostic and predictive significance. This comprehensive review synthesizes current evidence on TIL assessment methodology; the immunobiological landscape of TNBC, including regulatory T cell populations and PD-L1 correlations; gene expression underpinnings of the tumor immune microenvironment; and systematic evidence from meta-analyses and clinical trials. Meta-analytic estimates demonstrate that high TIL levels are associated with improved overall survival (HR 0.58, 95% CI 0.48–0.71) and disease-free survival (HR 0.66, 95% CI 0.57–0.76), with each 10% TIL increment conferring incremental benefit. High TILs predict superior pathologic complete response to neoadjuvant chemotherapy (OR 2.14, 95% CI 1.43–3.19), with lymphocyte-predominant breast cancer achieving pCR rates exceeding 80% with pembrolizumab-based chemoimmunotherapy. Future directions include prospective TIL-guided treatment trials, artificial intelligence-enabled standardization, and emerging adoptive TIL cellular therapies for metastatic disease. Full article

Preoperative sarcopenia has emerged as an important determinant of adverse postoperative and long-term outcomes in patients with resectable non-small cell lung cancer (NSCLC). Its frequent coexistence with systemic inflammation may further worsen survival outcomes. At the same time, neoadjuvant chemotherapy and chemoimmunotherapy have substantially improved pathological response and survival in resectable NSCLC. However, their interaction with host-related factors such as sarcopenia and systemic inflammatory status remains insufficiently characterized. This narrative review aims to synthesize current evidence regarding the interplay between preoperative sarcopenia, systemic inflammation, and neoadjuvant therapy in resectable NSCLC and evaluates their potential combined impact on surgical and oncological outcomes. A narrative synthesis of 20 studies involving patients undergoing lung cancer resection was performed. Sarcopenia was primarily assessed using computed tomography or PET-CT-derived skeletal muscle indices, most commonly the skeletal muscle index, whereas systemic inflammation was evaluated using biochemical inflammatory markers. The available evidence consistently indicates that preoperative sarcopenia is associated with poorer long-term survival, and this adverse effect appears to be amplified in the presence of systemic inflammation. Although neoadjuvant chemoimmunotherapy has improved tumor response and survival outcomes, it may also act as a systemic stressor capable of aggravating muscle loss. Importantly, no study to date has simultaneously evaluated sarcopenia, systemic inflammation, and neoadjuvant therapy within a unified analytical framework. Most available studies focus primarily on sarcopenia, while inflammatory or treatment-related parameters are typically analyzed separately. Overall, while sarcopenia and systemic inflammation are recognized predictors of adverse outcomes in resectable NSCLC, robust evidence integrating them with neoadjuvant therapy is lacking. Clarifying their potential interaction may improve risk stratification and help to optimize perioperative management strategies in the era of neoadjuvant therapy. Full article

Background: Neoadjuvant immunochemotherapy improves pathological response in resectable non-small cell lung cancer (NSCLC), but the need and intensity of postoperative adjuvant therapy across different pathological response rate (PRR) strata remain uncertain. Methods: In this single-center retrospective cohort, 105 patients with resectable NSCLC received neoadjuvant platinum-based chemotherapy with or without PD-1/PD-L1 inhibitors followed by R0 resection. PRR was defined as 1—residual viable tumor fraction and categorized as 0–60%, 60–90%, and ≥90% (major pathological response, MPR). Postoperative strategies included no further therapy, chemotherapy alone, or immunotherapy ± chemotherapy. Event-free survival (EFS) was analyzed using Kaplan–Meier estimates, multivariable Cox models, and restricted cubic spline-based treatment × PRR interaction. Results: Deeper PRR was associated with lower ypT/ypN stage and improved EFS. In the PRR 0–60% subgroup, immunotherapy-containing adjuvant regimens were associated with better EFS, whereas chemotherapy alone did not outperform observation. In the PRR 60–90% and MPR strata, EFS curves for different postoperative strategies largely overlapped, and in MPR patients, hazard ratios were close to 1. Interaction modeling suggested that the absolute 3-year EFS benefit of immunochemotherapy peaked at intermediate PRR (≈60–80%) and diminished as PRR approached ≥90%. Conclusions: The robustness of these findings was further confirmed through a sensitivity analysis focusing on a homogeneous cohort of clinical stage II-III patients receiving adjuvant therapy. Among NSCLC patients treated with neoadjuvant systemic therapy, PRR is a strong prognostic marker and modulates the benefit of postoperative immunotherapy. These data support a response-adapted strategy, with adjuvant immunotherapy intensification in low-PRR patients and potential de-escalation or surveillance alone in MPR patients, warranting validation in prospective PRR-stratified trials. Full article

Background: Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer, with poor outcomes following neoadjuvant chemoradiotherapy (NCRT). Neoadjuvant chemoimmunotherapy (NCIT) has emerged as a promising strategy, but reliable predictive biomarkers remain lacking. This study aimed to develop an AI-driven pathomic model for NCIT response prediction and explore its biological mechanisms. Methods: We analyzed 269 H&E-stained whole-slide images (WSIs) from 198 ESCC patients (104 from Tongji Hospital, 94 from TCGA). Using ResNet152, we segmented WSIs into four tissue categories (tumor cells, stroma, lymphocytes, and necrosis), extracted spatially weighted pathomic features, and constructed the ECiT score via logistic regression. An integrated model combining the ECiT score with clinical variables (T stage, P53 status) was developed. Mechanistic analyses were performed using TCGA-ESCA and GSE160269 datasets. Results: The integrated model achieved AUCs of 0.897 (training) and 0.809 (temporal validation), outperforming clinical (AUC = 0.624) and pathomic-only (AUC = 0.751) models. Mechanistically, a high ECiT score correlated with enhanced immune activation (elevated CD4⁺ memory T cell infiltration), while low scores were linked to endoplasmic reticulum (ER) stress-unfolded protein response (UPR) activation. EIF2S3 was identified as a key molecular mediator, correlating with three pathomic features, UPR activation, and poor prognosis. Conclusions: This study may offer a preliminary indicator that could assist in personalized clinical decision-making. Correlative evidence suggests that the EIF2S3-mediated ER stress–UPR axis represents a potential candidate therapeutic target to overcome NCIT resistance, generating testable hypotheses to advance precision oncology for resectable locally advanced ESCC. Full article

ER-low breast cancer (1–9% ER expression) represents a biologically and clinically distinct entity at the interface between ER-positive and ER-negative disease. Although traditionally managed as hormone receptor-positive, mounting evidence indicates that ER-low tumors share molecular signatures, aggressive behavior, and chemotherapeutic responsiveness with triple-negative breast cancer. Accurate ER assessment is hindered by methodological variability and interpretative challenges, leading to potential misclassification and suboptimal treatment choices. While the benefit of endocrine therapy remains uncertain, ER-low tumors consistently show sensitivity to chemotherapy and promising responses to neoadjuvant chemo-immunotherapy, paralleling outcomes observed in triple-negative breast cancer cohorts. Emerging artificial intelligence tools, including digital pathology and multimodal deep learning, may enhance ER quantification, reduce observer variability, and enable more precise patient stratification. This review synthesizes current pathological and clinical insights into ER-low breast cancer and highlights evolving therapeutic strategies, with a forward-looking perspective on AI-driven approaches to optimize personalized treatment for this challenging subtype. Full article

Triple-negative breast cancer (TNBC) is an aggressive malignancy that disproportionately affects young women. The integration of immune checkpoint inhibitors (ICIs) has significantly improved outcomes in both early-stage and metastatic TNBC, shifting attention toward long-term survivorship issues, particularly endocrine function and fertility. However, the reproductive safety profile of ICIs remains insufficiently characterized. This narrative review synthesizes current preclinical and clinical evidence on ICI-associated reproductive toxicity, focusing on both direct immune-mediated gonadal injury and indirect disruption of the hypothalamic–pituitary–gonadal axis. Experimental models consistently demonstrate immune cell infiltration of ovarian and testicular tissue, cytokine-driven inflammatory cascades, follicular atresia, impaired spermatogenesis, and altered steroidogenesis following PD-1/PD-L1 and CTLA-4 blockade. Emerging clinical data report cases of immune-related orchitis, azoospermia, testosterone deficiency, diminished ovarian reserve, and premature ovarian insufficiency. Secondary hypogonadism due to immune-mediated hypophysitis represents an additional and frequently underdiagnosed mechanism. We further discuss the oncofertility challenges faced by young patients with TNBC treated with chemoimmunotherapy, emphasizing the uncertainty of fertility risk stratification and the importance of early fertility counseling and individualized fertility preservation strategies. To illustrate the potential clinical impact, we present the case of a 34-year-old nulliparous woman who developed premature ovarian insufficiency two years after neoadjuvant chemoimmunotherapy including atezolizumab, despite ovarian suppression. In conclusion, while ICIs have transformed the therapeutic landscape of TNBC, their potential long-term impact on reproductive and endocrine health represents a clinically significant concern. A precautionary, multidisciplinary oncofertility approach and prospective clinical registries are essential to define the true incidence and mechanisms of ICI-associated reproductive toxicity. Full article

Neoadjuvant chemoimmunotherapy has emerged as a promising treatment strategy for head and neck squamous cell carcinoma (HNSCC). There is an urgent need to improve patient responses to this approach. In this study, we aim to elucidate the mechanisms underlying poor response to neoadjuvant chemoimmunotherapy and to identify strategies to enhance therapeutic efficacy in HNSCC. We identified a cancer stem-like cell (CSC) population enriched in patients with partial response (PR) to neoadjuvant chemoimmunotherapy, characterized by high CD80 expression. CD80 was likewise highly expressed in ALDH^highCD44⁺ and BMI1⁺ populations. Functionally, CD80 knockdown attenuated tumor-sphere-forming capacity and reduced the migration and invasion of tumor cells, whereas CD80 overexpression potentiated these pro-tumorigenic activities. Moreover, CD80 inhibition activated signaling pathways of Th1 immune responses and IL-2 production. CD80 blockade enhanced T cell cytotoxicity. In preclinical HNSCC models, inhibition of CD80 significantly decreased tumor burden, accumulated CD8⁺ T cells, and increased the production of cytotoxic effector molecules. Our data demonstrated that CD80 modulated tumor-cell stemness and malignant phenotype while restraining antitumor T cell immunity. Targeting CD80 augments antitumor immunity and provides a compelling strategy to enhance treatment responses to neoadjuvant chemoimmunotherapy in HNSCC. Full article

Background: Patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC) have poor prognosis after surgery. Neoadjuvant chemoimmunotherapy (nCIT) and neoadjuvant chemoradiotherapy (nCRT) may improve outcomes, but their long-term efficacy remains unclear. Methods: This multicenter study analyzed LA-ESCC patients from three Chinese hospitals (2015–2024) who received nCIT or nCRT followed by surgery. Primary endpoint was 3-year overall survival (OS); secondary endpoints included objective response rate (ORR), pathologic complete response (pCR), disease-free survival (DFS), and adverse events. Propensity score matching balanced baseline characteristics. Results: Among 225 patients (87 nCRT, 138 nCIT), matched cohorts (87 per group) showed that nCRT had higher ORR (85.06% vs. 45.98%), T/N downstaging rates (78.16% vs. 58.62%; 85.06% vs. 45.98%), and pCR (37.90% vs. 14.90%) (all p < 0.01). After median follow-up (nCIT: 44.5 months; nCRT: 35.1 months), nCIT improved 3-year OS (75.90% vs. 55.60%) and DFS (66.40% vs. 47.30%) (p < 0.05). Subgroup analysis favored nCRT in N+ or non-cT4 disease. Clinical N stage independently predicted survival. Conclusion: nCIT demonstrates superior survival benefits in LA-ESCC, while nCRT may be more effective for N+ or non-cT4 patients. Further randomized trials are warranted. Full article