crossing96/oncoscreening huggingface dataset:
Population pharmacokinetic analysis of fluorouracil and oxaliplatin in the absence or presence of zolbetuximab in locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.	PURPOSE: Zolbetuximab, a monoclonal antibody targeting claudin 18.2 (CLDN18.2), is approved in combination with chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative, CLDN18.2-positive, unresectable, advanced or recurrent gastric cancer (in Japan) and in combination with fluoropyrimidine- and platinum-containing chemotherapy for first-line locally advanced unresectable or metastatic HER2-negative, CLDN18.2-positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (in geographies including but not limited to the US, Europe, and China). Noncompartmental analysis (NCA) was previously used to evaluate the effect of zolbetuximab on pharmacokinetics (PK) of 5-fluorouracil (5-FU) and oxaliplatin; however, limitations of NCA confounded the results. This study utilized population pharmacokinetic (PopPK) analysis to address these limitations. METHODS: In Cohort 2 of the phase 2 ILUSTRO study (NCT03505320), patients with locally advanced unresectable or metastatic HER2-negative, CLDN18.2-positive G/GEJ adenocarcinoma received zolbetuximab with modified folinic acid, 5-FU, and oxaliplatin. PopPK models were developed to evaluate the impact of zolbetuximab on PK of 5-FU and oxaliplatin (including simultaneous analysis of free and total platinum). RESULTS: PK of 5-FU was adequately described by a 1-compartment model with zero-order input and first-order elimination. PK of free and total platinum was simultaneously described by a 3-compartment model with zero-order input, first-order elimination, and time-dependent free fraction. No impact of zolbetuximab on 5-FU PK or on systemic clearance or free fraction of oxaliplatin in plasma was observed. The effect of zolbetuximab on oxaliplatin distribution volume (12.3% decrease) was statistically significant but not considered clinically relevant. CONCLUSION: PopPK analysis suggests no effect of zolbetuximab on 5-FU or oxaliplatin PK.	esophagus
Efficacy and safety of HIPEC combined with PD-1 and SOX chemotherapy for gastric or oesophagogastric junctional cancer with peritoneal metastasis (HISTORIA): protocol for a prospective, multicentre, single-arm, phase II study.	INTRODUCTION: Despite advances in diagnostics, many patients with gastric cancer (GC) or oesophagogastric junction cancer present with advanced disease, most commonly peritoneal metastasis (PM), which conveys a poor prognosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) and anti-programmed cell death protein-1 (PD-1) therapy have each shown promise in GC. We describe the protocol for a study evaluating the efficacy and safety of combining HIPEC with the anti-PD-1 antibody tislelizumab and SOX (oxaliplatin+S-1) chemotherapy in patients with GC/oesophagogastric junction cancer and PM. METHODS AND ANALYSIS: This is a multicentre, single-arm, phase II trial conducted at 13 high-volume tertiary referral hospitals across China. We will enrol 50 adults (18-75 years) with histologically confirmed GC/oesophagogastric junction adenocarcinoma and PM diagnosed by laparoscopy. Participants will receive one laparoscopy-guided HIPEC cycle (paclitaxel, total dose: 175 mg/m(2), 3000 mL of physiological saline at 43°C for 60 min, inflow rate 1.5 L/min, 10 min physiological saline preconditioning at 41°C) followed-after a 3-week interval-by up to three 3-week cycles of tislelizumab 200 mg plus SOX (oxaliplatin 130 mg/m² and S-1 dose-escalated by body surface area). HER2-positive patients will also receive trastuzumab. PRIMARY ENDPOINT: 1-year overall survival. Secondary endpoints: 1-year progression-free survival, completeness of Cytoreduction Score and objective response rate. Follow-up includes imaging and toxicity assessments every 3 months for at least 1 year. ETHICS AND DISSEMINATION: The protocol was approved by the Ethics Committee of The First Affiliated Hospital of Nanjing Medical University (ID 2024-SR-198). All participants will provide written informed consent. Results will be disseminated via peer-reviewed publications; de-identified individual participant data will be available from the corresponding author on reasonable request after publication. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT06427252.	esophagus
Approaches for esophagectomy for esophageal cancer: a Network Meta-Analysis.	INTRODUCTION: Esophageal cancer remains a leading cause of cancer-related mortality worldwide. Esophagectomy is the cornerstone of curative treatment, but the optimal surgical approach remains debated. Newer techniques such as hybrid esophagectomy, minimally invasive esophagectomy (MIE), and robot-assisted minimally invasive esophagectomy (RAMIE) have been developed to improve perioperative outcomes while maintaining oncologic efficacy. We aim to compare the effects of open, hybrid, minimally invasive, and robot-assisted approaches to esophagectomy on survival and perioperative outcomes in patients with esophageal cancer. METHODS: A systematic review and network meta-analysis (NMA) were conducted, including 10 reports from 6 randomized controlled trials identified via PubMed, Cochrane Library, Embase, CINAHL, ClinicalTrials.gov, and ICTRP. Comparative analyses between open esophagectomy (OE), hybrid laparoscopy-thoracotomy (HYB LapS-ThoT), MIE, and RAMIE were performed using random-effects NMA models. Hazard ratios (HR), odds ratios (OR), and mean differences (MD) were calculated for outcomes. RESULTS: There were no significant differences in overall survival among OE, HYB LapS-ThoT, MIE, and RAMIE. Pulmonary complications were significantly lower with MIE (OR 0.47, 95 % CI 0.33-0.69, p < 0.0001) and RAMIE (OR 0.39, 95 % CI 0.27-0.57, p < 0.0001) compared to OE. RAMIE yielded a higher lymph node harvest (MD 1.56, 95 % CI 0.58-2.54, p = 0.002) and lower reoperation rates (OR 0.65, 95 % CI 0.45-0.93, p = 0.020) than OE. HYB LapS-ThoT was associated with increased anastomotic leakage compared to OE (OR 1.66, 95 % CI 1.02-2.69, p = 0.041). CONCLUSION: MIE and RAMIE significantly reduce pulmonary complications without compromising survival. Hybrid approaches appear to increase the risk of anastomotic leakage. These findings support minimally invasive techniques, especially RAMIE; however, more evidence and further studies are needed to allow for a clearer and more definitive conclusion.	esophagus
The enhanced pathological response from additional immunotherapy improved recurrence-free survival for esophageal squamous cell carcinoma: a multi-center cohort study.	BACKGROUND: Immunotherapy shows promise in enhancing pathological responses in locally advanced esophageal squamous cell carcinoma (LA-ESCC), but its long-term survival benefits remain uncertain. This study aims to evaluate the impact of adding immunotherapy to neoadjuvant chemotherapy (nCT) on survival in ESCC patients. METHODS: From five medical centers, 273 ESCC patients were studied, receiving either neoadjuvant chemoimmunotherapy (nICT) or nCT. Recurrence-free survival (RFS) was the primary endpoint, with locoregional recurrence-free survival (L-RFS) and distant metastasis-free survival (D-MFS) as secondary endpoints. To address confounding biases, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were utilized. An 18-month landmark analysis and Kaplan-Meier curves assessed survival differences. RESULTS: The pathological response was significantly improved in the nICT group compared to the nCT group. Cox analysis confirmed nICT as an independent factor associated with better prognosis (HR = 3.05, 95% CI 1.81-5.14, p < 0.001). Before matching, the nICT group showed superior RFS (p < 0.001), L-RFS (p = 0.002), and D-MFS (p < 0.001). After PSM, nICT showed its advantage in RFS (p < 0.001) and D-MFS (p = 0.003), with a trend toward improved L-RFS (p = 0.075). Similarly, after IPTW, nICT maintained its survival benefit in RFS (p = 0.001), D-MFS (p = 0.015), with an observed trend toward enhanced L-RFS (p = 0.085). Stratified analyses revealed greater survival benefits of nICT in patients with ypStage III/IV (p < 0.001). The 18-month landmark analysis demonstrated that nICT significantly enhanced RFS (p < 0.001), L-RFS (p = 0.048), and D-MFS (p < 0.001) with the first 18 months after surgery. CONCLUSION: nICT substantially improves prognostic outcomes in LA-ESCC patients, especially in terms of D-MFS and the period of the first 18-month post-surgery, suggesting nICT could be a more effective treatment strategy. Besides, more prospective investigations are required to substantiate these findings.	esophagus
Comparative analysis of immunochemotherapy with versus without radiation therapy for stage IVB esophageal squamous cell carcinoma confined to non-regional nodal metastases: a multicenter propensity score matching study.	BACKGROUND: The survival benefit of adding radiotherapy (RT) to immunochemotherapy (ICT) in patients with stage IVB esophageal squamous cell carcinoma (ESCC) confined to non-regional lymph node metastases remains uncertain. This study evaluated whether RT combined with first-line PD-1 inhibitor-based ICT improves outcomes. METHODS: In this multicenter retrospective cohort study, 343 patients with stage IVB ESCC (non-regional nodal metastases only; AJCC 8th edition) treated with PD-1 inhibitors plus chemotherapy between 2019 and 2021 were analyzed. Patients were stratified into RT (ICT + RT, n = 181) and non-RT (ICT alone, n = 162) groups. Propensity score matching (PSM) balanced baseline characteristics (age, sex, metastatic sites, etc.), yielding 125 matched pairs. RT (> 40 Gy to primary lesions) was delivered via IMRT/VMAT (median dose, 50.4 Gy). Primary endpoints were overall survival (OS) and progression-free survival (PFS). RESULTS: After PSM, the RT group showed significantly longer median OS (22.3 vs 14.9 months; HR 0.51, 95% CI 0.37-0.71; P < 0.001) and PFS (14.0 vs 6.1 months; HR 0.57, 95% CI 0.42-0.77; P < 0.001) versus non-RT. Sequential RT (post-induction ICT) conferred maximal OS benefit (median OS 29.2 vs 12.1 months; HR 0.38, P < 0.001). Exploratory analysis indicated that the most significant survival benefit was observed in patients receiving sequential RT targeting the primary tumor with or without metastatic nodes, rather than metastasis-directed RT alone. Grade 3-5 treatment-related adverse events were comparable between groups; however, RT was associated with significantly higher rates of grade 3-4 lymphopenia (15.2% vs 4.0%, p = 0.004) and esophagitis (11.2% vs 0%, p < 0.001). CONCLUSION: Adding RT to first-line ICT improves survival in stage IVB ESCC with non-regional nodal metastases, particularly when delivered sequentially to the primary tumor.	esophagus
Recent advances in risk stratification of patients with Barrett's esophagus.	Barrett's esophagus (BE) is the only recognized precursor to esophageal adenocarcinoma, but progression risk is highly heterogeneous. While most patients with nondysplastic BE have an annual cancer risk less than 0.5%, a subset with dysplasia or adverse molecular profiles carries markedly higher risk. This variability necessitates precision risk stratification to optimize surveillance and intervention. We review the evolution of BE risk stratification from historical consensus frameworks to contemporary clinical, histologic, and molecular models. Key clinical predictors, validated scoring systems, and recent advances in biomarker-based and imaging-driven surveillance are summarized, with emphasis on their validation and clinical applicability. Established clinical risk factors-age, male sex, smoking, segment length, and dysplasia-remain central to risk prediction. Biomarker assays, including p53 immunohistochemistry, tissue systems pathology and methylation-based assays may provide risk stratification beyond histology. Advances in endoscopic imaging, wide-area transepithelial sampling, and non-endoscopic capsule-based collection platforms could transform surveillance into a risk-adapted paradigm. The management of BE is shifting from a one-size-fits-all surveillance model toward personalized, biomarker-guided care. Integration of clinical, histologic, and molecular data-underpinned by artificial intelligence and real-world validation-promises to refine surveillance, reduce overtreatment, and improve early cancer detection in Barrett's esophagus.	esophagus
Esophageal pericardial fistula following radiation therapy after placement of an esophageal stent: A case report and literature review.	Esophageal pericardial fistula is a rare complication of esophageal cancer. This article reports the first documented case of an esophageal pericardial fistula following radiotherapy in the presence of an esophageal stent. A 62-year-old man with advanced esophageal and cardiac cancer underwent radiotherapy after esophageal stent placement and subsequently developed an esophageal pericardial fistula. He was admitted to the hospital with symptoms of epigastric pain and breathlessness. A computed tomography scan of the chest revealed an esophageal pericardial fistula, massive pericardial effusion, and pneumopericardium. The esophagogram revealed esophageal extravasation and an enlarged pericardium. On the basis of these findings, the patient was diagnosed with an esophageal pericardial fistula. His symptoms improved after pericardiocentesis with drainage, nasogastric tube feeding, and short-term antibiotic therapy. Unfortunately, he died 1 month after discharge from the hospital due to sudden massive upper gastrointestinal bleeding.	esophagus
Locoregional treatment of esophageal oligometastatic disease to the liver: single center experience, a systematic review and meta-analysis.	BACKGROUND: The prognosis of patients with esophageal cancer remains poor, even more when distant metastases are present. Despite the recent advances in definition and diagnosis of oligometastatic disease (OMD), consensus on the treatment of this condition has not been established. The aim of the study is to describe our center experience and to compare it to the existing literature. MATERIALS AND METHODS: Patients with esophageal cancer, treated with locoregional therapies for liver metastases between 2010 and 2023, were retrospectively analyzed. Data on demographics, treatment, overall survival (OS), and disease-free survival (DFS) were collected. A systematic review and two meta-analyses were performed in accordance with the PRISMA 2020 guidelines: a meta-analysis of proportions and a comparative effectiveness meta-analysis to compare 1-year OS between locoregional therapies and systemic therapy alone. RESULTS: Eleven patients were treated with locoregional therapies. The overall median OS and DFS were 27 months and 16 months, respectively. A meta-analysis of proportions estimated a 1-year OS rate of 57 % (95 % CI: 45 %-68 %) with moderate heterogeneity (I(2) = 49 %). A meta-analysis of comparative effectiveness documented a significant survival advantage for locoregional therapies over systemic therapy alone (odds ratio: 0.12 [95 % CI: 0.04-0.37], p < 001), again strongly supporting their role in this setting. CONCLUSION: Our findings show that locoregional treatments may offer a survival benefit for oligometastatic liver disease from esophageal cancer, especially in the context of multimodal therapeutic approach. Results are aligned with current literature. Future studies should be designed as large, multicenter, randomized trials that confirm the efficacy of such treatments.	esophagus
Pharmacological activation of SIRT6 suppresses progression of head and neck and esophageal squamous cell carcinoma by modulation of cellular metabolism and protein translation.	Sirtuin 6 (SIRT6), a NAD+-dependent histone deacetylase, has been shown to function as a tumor suppressor in several cancer types, including squamous cell carcinoma of the head and neck and the esophagus (HNSCC and ESCC). However, the potential of therapies involving the activation of SIRT6 in HNSCC and ESCC remains unexplored. In this work, we investigated the therapeutic potential and mechanisms of action of the allosteric SIRT6 activator MDL-800 in HNSCC and ESCC models. MDL-800 treatment inhibited the proliferation and migration of HNSCC and ESCC cell lines in vitro, and delayed tumor growth in cell-derived xenograft models, in vivo. Mechanistically, global H3K9ac acetylation profiling and protein arrays demonstrated that MDL-800 treatment potently inhibits glucose metabolism and protein translation by inhibiting mTOR signaling, E2F-related G1/S transcription, ribosomal protein S6 (S6) and 4E-BP1 activity. This inhibition of mTOR induces a compensatory feedback loop activating IGF-1R/INSR signaling, limiting the anti-tumor activity of MDL-800. Combination of MDL-800 with the alpha-specific PI3K inhibitor (BYL719/Alpelisib) disrupted this feedback loop activation and resulted in a synergistic anti-proliferative effect. In vivo, the combined treatment of MDL-800 and BYL719 resulted in a prolonged anti-tumor response. Overall, our study identifies the molecular mechanism underlying SIRT6 activation in HNSCC and ESCC and highlights the therapeutic potential of SIRT6 activators, alone or in combination with PI3K inhibitors in cancers where SIRT6 is downregulated or serves as a tumor suppressor.	esophagus
Addition of immunotherapy to perioperative chemotherapy for resectable gastric and gastroesophageal junction cancer: a meta-analysis of phase 2/3 trials.	BACKGROUND: The integration of immune checkpoint inhibitors (ICIs) with perioperative chemotherapy (CT) has become a major focus of clinical research in resectable gastric or gastroesophageal junction (G/GEJ) cancer. Recent phase 2 and 3 trials have reported disparate outcomes, generating considerable debate. To synthesize this evidence, we conducted a meta-analysis to evaluate the efficacy and safety of adding ICIs to CT in this setting. METHODS: A systematic literature search of PubMed and major conference proceedings was conducted up to August 15, 2025. Efficacy outcomes included summary relative risks (RRs) for pathological complete response (pCR) and R0 resection rate, and hazard ratios (HRs) for event-free survival (EFS) and overall survival (OS). Safety was assessed using RRs for treatment-related adverse events (AEs). RESULTS: Four trials (one phase 2 [NEOSUMMIT-01], one phase 2/3 [DANTE], and two phase 3 [KEYNOTE-585, MATTERHORN]), encompassing 2,358 patients, were included. The addition of ICIs to CT significantly improved pCR (RR: 2.80; 95% CI: 1.68-4.67), EFS (HR: 0.76; 95% CI: 0.67-0.87), and OS (HR: 0.78; 95% CI: 0.61-0.99), although it did not increase the R0 resection rate. Regarding safety, the combination did not increase the risk of overall grade 3-5 treatment-related AEs. However, it was associated with a significantly higher risk of grade 3-5 immune-related AEs (RR: 2.88; 95% CI: 1.95-4.24) and treatment-related serious AEs (RR: 1.14; 95% CI: 1.01-1.28). CONCLUSION: The addition of ICIs to perioperative CT confers significant improvements in pCR, EFS, and OS in resectable G/GEJ cancer, with a generally manageable safety profile. However, longer follow-up is required to validate survival benefits, and the increased risk of immune-related toxicity underscores the need for administration in specialized centers. These findings suggest that perioperative chemo-immunotherapy is a promising treatment strategy, though its definitive role awaits confirmation from ongoing phase 3 trials. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD420251131385.	esophagus
Prognostic value of neutrophil to lymphocyte ratio in patients with esophagus cancer receiving neoadjuvant therapy: a systematic review and meta-analysis.	BACKGROUND: Growing research reveals a relation of the neutrophil-to-lymphocyte ratio (NLR) to clinical outcomes of the esophageal cancer (EC) population undergoing neoadjuvant therapy. However, current findings remain inconclusive and somewhat controversial. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were thoroughly retrieved until April 22, 2025 to collect studies on the link of NLR to prognosis among the EC population following neoadjuvant therapy. Eligible studies were selected as per predefined eligibility criteria. The primary outcomes encompassed overall survival (OS), recurrence-free survival (RFS), and pathological complete response (pCR). Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were pooled for prognostic significance assessment along with subgroup analyses. The evidence was graded via the GRADE method. RESULTS: 11 cohort studies involving 2,220 patients were included in the analysis. The results demonstrated a notable link of risen NLR to less favorable OS (HR = 1.99, 95% CI: 1.43-2.76, P < 0.0001; I² = 88%), shorter RFS (HR = 2.69, 95% CI: 1.77-4.08, P < 0.00001; I² = 47%), and lower pCR rates (OR = 0.67, 95% CI: 0.47-0.94, P = 0.02; I² = 62%). Subgroup analyses by sample size, follow-up length, age, treatment modality, and NLR cut-off value consistently demonstrated a strong correlation between elevated NLR and shortened RFS across all subgroups. Notably, in patients receiving neoadjuvant chemoradiotherapy (NCRT), the link of increased NLR to OS and RFS appeared more robust compared to those receiving neoadjuvant chemotherapy (NCT) alone. CONCLUSION: In patients with EC undergoing neoadjuvant therapy, a higher pre-treatment NLR is significantly linked to worse OS and RFS, as well as a lower likelihood of achieving pCR. Therefore, NLR can be a valuable prognostic biomarker in this patient population, potentially aiding clinicians in risk stratification and treatment decision-making. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42024610088.	esophagus
Induction chemotherapy plus camrelizumab followed by concurrent chemoradiotherapy in unresectable locally advanced esophageal squamous cell carcinoma: a single-arm phase II trial.	Concurrent chemoradiotherapy (CCRT) has remained the standard treatment for unresectable locally advanced esophageal squamous cell carcinoma (ESCC), yet survival remains poor. This single-arm, phase II trial aims to evaluate the efficacy and safety of two cycles of induction chemotherapy with camrelizumab followed by CCRT in previously untreated patients with unresectable locally advanced ESCC. The primary endpoint, the 1-year overall survival (OS) rate in the per-protocol population (N = 46), was 87.0% (95% confidence interval [CI]: 77.7%-97.3%), exceeding the pre-specified target. Secondary endpoints included OS in the intention-to-treat (ITT) population, progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), duration of response, safety, and health-related quality of life. In the ITT population (N = 49), the 1-year OS rate was 85.7% (95% CI: 76.5%-96.1%). The 1-year PFS rates in the per-protocol and ITT populations were 71.7% (95% CI: 59.8%-86.0%) and 71.4% (95% CI: 59.8%-85.3%), respectively. The median OS, PFS, and duration of response were not reached. Following CCRT, the ORR was 93.5%, with a DCR of 95.7%. Lymphopenia was the most frequent Grade ≥3 adverse event (100%). One patient died from treatment-related myelosuppression. Health-related quality of life generally improved after induction therapy, with significant improvements in global health status, emotional functioning, and some symptom relief, despite a slight decline in physical functioning. Here, we show that induction chemoimmunotherapy followed by CCRT exhibits promising efficacy and manageable safety in patients with unresectable locally advanced ESCC, thus warranting further randomized controlled trials. Trial number: ChiCTR2000034304.	esophagus