crossing96/oncoscreening huggingface dataset:
A phase II study of trifluridine/tipiracil in combination with ramucirumab in advanced, refractory gastric, or gastroesophageal junction adenocarcinomas.	BACKGROUND: Ramucirumab plus paclitaxel after progression on fluoropyrimidine/platinum in metastatic gastric (GA) and gastroesophageal junction adenocarcinoma (GEJC) has shown improvement in overall survival over paclitaxel alone. However, the incidence of neuropathy was 46%. Therefore, there is an unmet need for novel treatment to minimize the long-term toxicity of neuropathy. We conducted a single arm phase II study of ramucirumab and trifluridine/tipiracil (FTD/TPI) in metastatic GA/GEJC. METHODS: Patients received ramucirumab at 8 mg/kg intravenously on day 1 and 15, and FTD/TPI at 35 mg/m2 orally twice daily on days 1-5 and days 8-12 on every 28-days cycle. The primary endpoint was 6-months overall survival (OS) rate and secondary endpoints were progression free survival (PFS), objective response rate and safety. RESULTS: At data cut-off of August 15, 2021, 23 pts were enrolled. The median age was 62 years. Most common treatment-related toxicities were diarrhea (39%), fatigue (39%), hypertension (39%), and nausea (35%). Most common treatment related Grade 3 or 4 adverse events were neutropenia (17%) and anemia (13%). The median PFS and OS was 4.8 and 6.1 months, respectively. The 6-month OS rate was 57% (95% CI: 36.4%-79.8%). Of the 18 evaluable patients with at least one post-baseline imaging, 2 (11%) patients demonstrated objective partial response, and 15 (83%) had stable disease. CONCLUSION: The combination of ramucirumab and FTD/TPI demonstrated well-manageable safety profile. Our study did not meet primary endpoint. Ongoing clinical trials will help us understand if ramucirumab plus FTD/TPI is noninferior to ramucirumab/paclitaxel. The trial was registered at www.clinicaltrials.gov (NCT03686488).	esophagus
Efficacy of local radiotherapy in first-line treatment of recurrent or metastatic esophageal squamous cell carcinoma based on immunotherapy.	BACKGROUND: The treatment strategy for recurrent or metastatic esophageal squamous cell carcinoma (ESCC) is immunotherapy-based systemic treatment. The effect of local radiotherapy on the survival of recurrent or metastatic ESCC patients is unclear. This work is aimed to investigate the efficacy of local radiotherapy in combination with immunotherapy-based systemic therapy. METHODS: In this retrospective observational study, data were collected from recurrent or metastatic ESCC patients treated at the Radiotherapy Department of Jiangsu Province Hospital between March 2019 and December 2022. This study enrolled a total of 73 patients with recurrent or metastatic ESCC. The overall survival (OS) of all patients and OS stratified by different treatment patterns were analyzed. Prognostic factors influencing OS were examined using uni- and multi-variate Cox tests. RESULTS: The median OS of the study population was 21.4 (95%CI: 13.7-29.1) months. The median OS of patients who received radiotherapy in additional to systemic therapy was 31.5 (13.5-49.5) months, while the patients who received systemic therapy alone had a significantly shorter median OS of 10.7 (95%CI: 8.0-13.4) months. OS was also significantly different among patients receiving different cycles of immunotherapy. The median OS of patients after 1-6 cycles of immunotherapy was 14.6 (95%CI: 11.3-18.0) months, that after 7-12 cycles was 21.1 (95%CI: 0-43.8) months, and that after more than 12 cycle was 52.1 (25.6-78.6) months. CONCLUSIONS: In the first-line therapy of recurrent or metastatic ESCC based on immunotherapy, the addition of local radiotherapy significantly improves patient survival. As the number of immunotherapy cycles increases, the survival benefits become more pronounced.	esophagus
Retrograde gastric decompression and anterograde enteral nutrition feeding in retrosternal esophagectomy for esophageal cancer.	BACKGROUND: Postoperative care after McKeown esophagectomy remains challenging. The aim of this study was to evaluate retrograde gastric decompression and feeding as an alternative to nasogastric decompression and nasogastric-jejunal feeding. METHODS: This retrospective study analyzed 142 esophageal cancer patients undergoing McKeown esophagectomy (between June 2020 and August 2022): retrograde gastric decompression and feeding (n=74) vs. nasogastric-jejunal (n=68). Outcomes included operative parameters, complications, and recovery metrics. RESULTS: Retrograde gastric decompression and feeding required longer operative time (183.0±41.7 vs. 169.4±32.6 min, p=0.031) but showed comparable blood loss, R0 resection rates (95.9 vs. 97.1%), and lymph node yield. Gastric tube retention was shorter with retrograde gastric decompression and feeding (3.2±1.6 vs. 3.6±1.4 days). Complication rates (anastomotic leak: 10.8 vs. 10.3%; respiratory: 16.2 vs. 16.2%) and in-hospital mortality (1.4 vs. 1.5%) were similar. Tube-related complications trended lower with retrograde gastric decompression and feeding (5.4 vs. 10.3%, p=0.276). CONCLUSION: Retrograde gastric decompression and feeding is a safe, effective method for enteral nutrition and decompression post-esophagectomy.	esophagus
Body Weight Loss at Recurrence as an Independent Prognostic Factor in Patients With Recurrent Esophageal Cancer After Esophagectomy Who Receive First-line Treatment After Recurrence.	BACKGROUND/AIM: Body weight loss (BWL) is frequently observed after esophagectomy in patients with esophageal cancer (EC). We conducted a retrospective study to evaluate the clinical impact of BWL at recurrence on oncological outcomes in patients with recurrent EC who underwent esophagectomy and chemotherapy after recurrence. PATIENTS AND METHODS: We retrospectively reviewed the medical records and collected data from consecutive patients with recurrent EC who received systemic chemotherapy after recurrence at Yokohama City University from 2005 to 2022. Patients included in this study met the following criteria: histological diagnosis of esophageal adenocarcinoma, adenosquamous carcinoma, or squamous cell carcinoma based on a histological examination, and an imaging-based diagnosis of stage IV disease. RESULTS: Sixty-eight patients were included in this study. The median BWL was 12% (range=-26% to 41.1%). According to the 1- and 3-year OS rates, we set the cutoff value of BWL at 15% in the present study. Among the 68 patients, 49 were classified into the BWL-low group and 19 were classified into BWL-high group. The median OS was 22.2 months in the BWL-low group, while the median OS was 14.2 months in the BWL-high group (p=0.005). In addition, the 1- and 3-year OS rates were 69.6% and 43.9%, respectively in the BWL-low group and 51.7% and 0.0% in the BWL-high group. In the univariate and multivariate analyses for OS, BWL was selected as an independent prognostic factor (hazard ratio=2.111; 95% confidence interval=1.109-4.018, p=0.023). The best overall response rate was 52.6% in the BWL-low group and 34.7% in the BWL-high group (p=0.178). CONCLUSION: BWL at recurrence was an independent prognostic factor in patients with recurrent EC who underwent esophagectomy. In addition, BWL at recurrence may affect first-line treatment after recurrence. Therefore, patients with EC after esophagectomy require careful attention for BWL, even when curative treatment and nutritional management or care are needed to maintain body weight.	esophagus
Employing cancer driver genes for the identification of immunological features in two esophageal cancer subtypes to facilitate immunotherapy.	BACKGROUND: Esophageal cancer (ESCA) is a pervasive health threat, and cancer driver genes (CDGs) are under investigation as potential biomarkers for its treatment. METHODS: This study applied univariate regression to identify CDGs affecting survival and performed clustering analysis in TCGA-ESCA samples based on CDG expression. It explored differentially expressed genes (DEGs) and immune landscapes between the subtypes, analyzed tumor mutations, and further predicted the potential small-molecule drugs. In addition, we collected ESCA-related cell lines and investigated the expression levels of CDGs that were most significantly differentially expressed and related to survival. RESULTS: Our research pinpointed 18 survival-associated CDGs and split TCGA-ESCA patients into cluster 1 and cluster 2 via consensus clustering. The subtypes exhibited different levels of immune cell infiltration, with lower Tumor Immune Dysfunction and Exclusion scores in cluster 1. Enrichment analysis revealed that DEGs between the two subtypes were primarily linked to the humoral immune response, receptor ligand activity, and neuroactive ligand-receptor interaction. Mutation analysis did not find significant differences in mutation rates between the subtypes. Additionally, potential small-molecule drugs targeting DEGs in ESCA were investigated, such as 3,3'-diindolylmethane, SJ-172550, aminoglutethimide, nitrazepam, actarit, and epigallocatechin. The results of qRT-PCR showed that RUNX1, NONO, and TSC2 were not only significantly associated with the survival of esophageal squamous cell carcinoma (ESCC) but also significantly overexpressed in the ESCC cell lines (KYSE150 and KYSE450). CONCLUSION: This study is valuable for elucidating CDG functions in ESCA and for biomarker identification.	esophagus
Association of waiting time from diagnosis to neoadjuvant chemoradiotherapy on interval distant metastases in esophageal cancer patients: A study based on the Netherlands cancer registry.	INTRODUCTION: In patients with resectable esophageal cancer, interval distant metastases may be detected following neoadjuvant-intent chemoradiotherapy ((n)CRT). The specific association between the waiting time from diagnosis to the initiation of (n)CRT and interval metastases remains unclear. METHODS: Patients with esophageal cancer (cT1-4a N0-3 M0) received CRT with or without surgery were extracted from the Netherlands Cancer Registry. Multivariable logistic and cox regression analyses were used to compare different waiting times (≤4, 4-8 and >8weeks) on the risk of interval metastases, post-(n)CRT short-term metastases (detected preoperatively, intraoperatively, or postoperatively within 120 days after CROSS regimen CRT) and overall survival (OS). Subgroup analysis based on cN stage was performed. RESULTS: Between 2015 and 2021, a total of 4394 patients were included. Compared to the waiting ≤4 weeks, the waiting >8 weeks was associated with higher risk of interval metastases (p-value = 0.045),but the longer waiting times were not associated with higher risk of post-(n)CRT short-term metastases or worse OS. In the cN0 subgroup, compared to the waiting ≤4 weeks, the waiting 4-8weeks (p-value = 0.049; p-value = 0.046) and >8 weeks (p-value = 0.006; p-value = 0.006) was associated with higher risk of interval metastases and post-(n)CRT short-term metastases, but was not associated with worse OS. In the cN + subgroup, the longer waiting times were not associated with interval metastases or post-(n)CRT short-term metastases or OS. CONCLUSION: A longer waiting time from diagnosis to the initiation of (n)CRT was associated with a higher risk of interval metastases, but not with an increased risk of post-(n)CRT short-term metastases or worse OS.	esophagus
Trends in oesophageal cancer surgery in Australia & Aotearoa New Zealand.	BACKGROUND: Oesophagectomy is a complex procedure, demanding a high degree of surgeon and institutional expertise. Many health systems globally have centralised oesophagectomy services to optimise patient outcomes. Australia and Aotearoa New Zealand have relatively small populations and face unique geographical and economical challenges for centralisation of care, resulting in multiple centres performing fewer procedures. This has implications for training and maintenance of skill among surgeons. The aim of this study is to assess training, workload and current practices among Australian and Aotearoa New Zealand oesophageal surgeons, for comparison to international data. METHODS AND RESULTS: An online survey was sent to surgeons through multiple means - A total of 59 complete responses were received. Majority of respondents performed < 10 oesophagectomies in 2023 (n = 35/59; 59%), while 90% of hospitals amongst respondents performed < 30 oesophagectomies (n = 53/59). Similar rates of minimally invasive and robotic-assisted surgery were observed; however minimally invasive surgery was more common among surgeons with < 10yrs practice compared to those with > 10yrs (p = 0.016). Robot-assisted surgery was only performed by 16% of respondents; access to robotic platforms and training the largest reported barrier. Intraoperative surgical techniques and preferences were comparable to international data. CONCLUSION: Overall, the study demonstrated contemporary oesophagectomy practices among Australian and Aotearoa New Zealand surgeons when compared with international practices. With continuous growth of minimally invasive and robotic-assisted surgery, early-career oesophageal surgeons must remain up to date with emerging technologies and practices to maintain optimal patient care.	esophagus
Hiatal hernia after open versus minimally invasive transthoracic oesophagectomy for cancer.	BACKGROUND: Hiatal hernia (HH) after oesophagectomy is a potentially life-threatening complication, more commonly observed after minimally invasive procedures. The aim of the study was to compare the incidence of HH after open versus minimally invasive oesophagectomy (MIO) for cancer, to identify risk factors for its onset, and analyse the technical differences between the approaches. METHODS: This was a retrospective study of patients who underwent transthoracic oesophagectomy for cancer over a 15-year period. Open and minimally invasive procedures were compared according to demographics, and operative and perioperative parameters. MIO included both laparoscopic and robotic operations. Risk factors for HH after oesophagectomy were analysed by calculating odds ratios of uni- and multivariable generalized linear models. RESULTS: A total of 898 patients operated on between 2008 and 2023 were included in the study. HH was observed in 1 of 490 patients (0.2%) in the open group and in 21 of 408 patients (5.2%) in the minimally invasive group (P < 0.001). At multivariable analysis, patients with an ASA score of II and III within the MIO group had a significantly lower risk of HH compared with ASA I subjects (P = 0.002 and P < 0.001, respectively). Omentectomy was performed in all open procedures but in none of the MIO. CONCLUSION: The rate of HH was significantly lower in patients who underwent open oesophagectomy. Omentectomy may prevent postoesophagectomy HH as it was the only additional technical difference between the groups. Multicentric randomized clinical trials are needed to assess whether omentectomy during MIO may reduce the occurrence of paraconduit HH.	esophagus
Organoid-based two-step drug screening for rapid identification of chemotherapy-resistant oesophageal squamous cell carcinoma and alternative therapies.	BACKGROUND: Despite guideline-directed therapies, most patients with advanced oesophageal squamous cell carcinoma (ESCC) derive limited benefit and are unable to tolerate iterative treatment modifications. Therefore, timely identification of resistant cases and the provision of alternative therapeutic options are urgently needed. METHODS: A large-scale patient-derived organoid model was established from locally advanced patients with ESCC who underwent perioperative chemotherapy and was validated for consistency with the parental tumours through histopathological, genomic and transcriptomic analysis. A novel two-step drug screening method based on growth rate inhibition (GR) was developed, and drug sensitivity results were compared with clinical outcomes. Additionally, in vivo assays were conducted to evaluate alternative therapies using the C(max)/GR100 index. RESULTS: ESCC organoids demonstrated high consistency with parental tumours in histopathology, genomics and transcriptomics. The two-step drug screening method revealed a strong correlation with clinical responses (sensitivity 80%, specificity 85.7%, overall accuracy 83.3%) and significantly shortened the experimental timeline compared with the traditional drug screening method (23.08 ± 2.42 days vs. 45.75 ± 7.19 days, p < .001). Furthermore, we proposed a novel drug selection strategy based on C(max)/GR100 values, which provides a theoretical foundation for drug repurposing and offers alternative treatment options for patients resistant to TP (taxol + cisplatin) therapy, thereby facilitating precise re-treatment in drug-resistant subgroups. CONCLUSIONS: This method exhibits strong clinical applicability, supporting more accurate and timely decision-making in ESCC management. The C(max)/GR100-based drug screening strategy can dynamically identify alternative sensitive drugs for patients who fail first-line therapies, enabling precise re-treatment. This approach provides a valuable tool for translating laboratory findings into clinical practice.	esophagus
The association of preneoadjuvant maximal standardized uptake value (SUVmax) and postneoadjuvant change in maximal standardized uptake value on 18-fluorodeoxyglucose positron emission tomography with survival after esophagectomy for cancer.	BACKGROUND: Currently, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is widely used in staging and restaging of esophageal cancer after neoadjuvant therapy. The maximal standardized uptake value (SUVmax) is a reproducible parameter that may predict survival. This study aimed to determine the prognostic significance of SUVmax and the change in SUVmax (ΔSUVmax) after neoadjuvant treatment on overall survival (OS) and disease-free survival (DFS). METHODS: FDG-PET data were obtained for patients who underwent radical esophagectomy between 2008 and 2021 across 3 esophageal cancer centers in Sydney, Australia. Receiver operating characteristic curves were used to calculate an optimal cutoff for SUVmax, separating the group into high and low SUVmax and high and low ΔSUVmax. RESULTS: A total of 344 patients (median age of 67 years, 80.5% male, and 78.7% with adenocarcinomas) with available FDG-PET data were included. The optimal cutoff values for SUVmax and ΔSUVmax were 9.05% and 22%, respectively. Compared with the low SUVmax group, the high SUVmax group had a lower median OS (87.3 vs 54.4 months; P <.001) and a lower median DFS (78.9 vs 42.7 months; P <.001). Compared with the low ΔSUVmax group, the high ΔSUVmax group had a higher median OS (56 vs 62 months; P =.031) but had a similar DFS. In univariate analysis, high SUVmax, high ΔSUVmax, T3 disease, and node negativity were associated with OS. In multivariate analysis, node negativity and ΔSUVmax were independent prognostic factors for OS. CONCLUSION: High pretreatment SUVmax was associated with reduced OS and DFS but was not an independent prognostic factor in multivariate analysis. In multivariate analysis, a decrease in SUVmax was an independent prognostic factor. Therefore, quantifiable parameters from FDG-PET are useful for prediction before radical esophagectomy.	esophagus
Lipidomic and transcriptomic analysis and its therapeutic implications in Chinese Kazakh patients with esophageal squamous cell carcinoma.	OBJECTIVE: To analyze the lipidomic profile of ESCC patients, link changes in cancer lipid metabolism to gene expression changes, and provide new insights into the diagnosis and treatment of ESCC patients in the Kazakh Xinjiang ethnic group. METHODS: By integrating the lipidome and transcriptome results, genes related to differential lipid metabolites in Kazakh ESCC patients were identified, and the effects of the key gene AMPK on lipid metabolism in ESCC cells were investigated by ultra-performance liquid chromatography/tandem mass spectrometry (UPLC‒MS/MS). RESULT: Through absolute lipid quantification analysis of two serum samples, 13 classes of lipids were detected, with triglycerides (TAGs) being the most abundant. Phosphatidylcholine (LPC), phosphatidylethanolamine (PE), and ceramide (Cer) were the lipid categories with significant differences between the two groups. Transcriptome analysis revealed that genes related to fatty acid synthesis, carnitine biosynthesis, and other lipid metabolism pathways were enriched in the tumor tissue. Integrative analysis of the two groups suggested that fatty acid synthesis, fatty acid metabolism, lipid degradation, cholesterol metabolism, and the AMPK signaling pathway were enriched in tumor tissue. UPLC‒MS/MS was used to perform targeted lipidomic analysis of AMPK-knockdown esophageal squamous cell carcinoma cells, suggesting that AMPK may be involved in the reprogramming of lipid metabolism in Kazakh ESCC patients. CONCLUSIONS: Lipid metabolic reprogramming occurs in the tumor tissue of Kazakh ESCC patients, and there is a correlation between AMPK activity and lipid metabolism, which suggests a potential therapeutic target for the treatment of Kazakh ESCC.	esophagus
Is Site of Radiation Therapy Associated With Pathologic Complete Response in Patients With Locally Advanced Esophageal Cancer?	IntroductionNeoadjuvant chemoradiation (CRT) is commonly used for esophageal cancer (EC), with pathologic complete response (pCR) linked to improved prognosis. pCR rates range from 25%-30% for adenocarcinoma to 50% for squamous cell carcinoma (SCC). High-volume centers (HVCs) often yield favorable outcomes across various cancers. This study examines whether CRT delivery at an HVC impacts pCR and ypN0 rates in EC patients undergoing esophagectomy.MethodsIn this retrospective cohort analysis, we identified patients with clinical stage T2+/N+ EC who received neoadjuvant CRT and esophagectomy from a prospectively maintained database (1996-2019). CRT was delivered at the HVC or a community center (CC), while all surgeries occurred at the HVC. Primary outcomes were pCR and ypN0.ResultsAmong 708 patients, median age was 65 years, with 83.6% male and 95.3% white. Most had adenocarcinoma (87.9%) in the distal esophagus or gastroesophageal junction. CRT was delivered at CCs in 64.8% and at HVC in 35.2%. Radiation dose was higher at the HVC (mean 5195 vs 4944 cGy, P < 0.001), with similar intensity-modulated radiation therapy use (83% vs 79%, P = 0.12). Overall pCR rate was 37.7%, without significant difference between HVC and CC (40.6% vs 36.2%, P = 0.25, multivariable adjusted OR 0.88, P = 0.47). SCC histology was associated with higher pCR (OR 2.39, P = 0.002). Among SCC patients, pCR rate was higher at HVC than CC (75.0% vs 50.0%, P = 0.03) but not significant in multivariable analysis (OR = 2.65, P = 0.11). Conversely, minimal histopathologic response (TRG3) was higher at CCs, not statistically different (17.9% vs 14.5%, P = 0.24). Rate of ypN0 was similar (HVC 70.7% vs CC 68.0%, P = 0.71) with no difference in ratio of positive to resected nodes (P = 0.94).ConclusionThere were no significant differences in pCR or ypN0 rates by CRT delivery site. pCR was higher for SCC histology at HVC, but did not reach statistical significance. Further research is warranted for SCC specifically.	esophagus