crossing96/oncoscreening huggingface dataset:
Diaphragm-Based Position Verification to Improve Daily Target Dose Coverage in Proton and Photon Radiation Therapy Treatment of Distal Esophageal Cancer.	PURPOSE: In modern conformal radiation therapy of distal esophageal cancer, target coverage can be affected by variations in the diaphragm position. We investigated if daily position verification (PV) extended by a diaphragm position correction would optimize target dose coverage for esophageal cancer treatment. METHODS AND MATERIALS: For 15 esophageal cancer patients, intensity modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) plans were computed. Displacements of the target volume were correlated with diaphragm displacements using repeated 4-dimensional computed tomography images to determine the correction needed to account for diaphragm variations. Afterwards, target coverage was evaluated for 3 PV approaches based on: (1) bony anatomy (PV_B), (2) bony anatomy corrected for the diaphragm position (PV_BD) and (3) target volume (PV_T). RESULTS: The cranial-caudal mean target displacement was congruent with almost half of the diaphragm displacement (y = 0.459x), which was used for the diaphragm correction in PV_BD. Target dose coverage using PV_B was adequate for most patients with diaphragm displacements up till 10 mm (≥94% of the dose in 98% of the volume [D(98%)]). For larger displacements, the target coverage was better maintained by PV_T and PV_BD. Overall, PV_BD accounted best for target displacements, especially in combination with tissue density variations (D(98%): IMPT 94% ± 5%, VMAT 96% ± 5%). Diaphragm displacements of more than 10 mm were observed in 22% of the cases. CONCLUSIONS: PV_B was sufficient to achieve adequate target dose coverage in case of small deviations in diaphragm position. However, large deviations of the diaphragm were best mitigated by PV_BD. To detect the cases where target dose coverage could be compromised due to diaphragm position variations, we recommend monitoring of the diaphragm position before treatment through online imaging.	esophagus
Thoracoscopic and laparoscopic resection of a huge oesophageal liposarcoma: a case report.	Oesophageal liposarcomas are particularly rare, accounting for 1.2-1.5% of all gastrointestinal liposarcomas. Surgical resection is the usual treatment. Endoscopic resection is minimally invasive but still controversial. This current case report describes a rare case of a large oesophageal liposarcoma in a 52-year-old male that presented with 10-year history of dysphagia for dry and solid food that was exacerbated by a recent common cold. Thoracoscopic and laparoscopic oesophagectomy was performed. He did not have any dysphagia or dyspnoea 1 week postoperatively. The excised specimen consisted of a polypoid mass measuring 21.0 cm × 5.1 cm. Histological examination confirmed that it was an oesophageal liposarcoma. At 1-year postoperatively, there was no sign of recurrence. Thoracoscopy and laparoscopy can be used to treat large oesophageal masses. Long-term follow-up is required as oesophageal liposarcomas tend to recur.	esophagus
Immunotherapy in Gastroesophageal Cancers: Current Evidence and Ongoing Trials.	Data supporting the use of immunotherapy in the treatment of gastroesophageal cancer continues to evolve. The promising results from adjuvant immunotherapy and trials combining immunotherapy plus chemotherapy in the 1L setting have led to broad US FDA approvals. Among the PD-L1 negative subgroups, the magnitude of benefit is diminished; effective therapy for this population remains an unmet need. A detailed biologic understanding of the PD-L1 negative (and low) population represents a barrier to developing effective combination therapies, although combination angiogenesis inhibitors and immunotherapy look encouraging. Early phase clinical trials, particularly with pembrolizumab plus lenvatinib (EPOC 1706), demonstrated a clear signal independent of PD-L1, and a confirmatory phase III trial of pembrolizumab plus lenvatinib is planned. Conceptually, it is important to think of immune checkpoint inhibitor therapy as targeted therapy, most active in clearly defined biomarker-selected populations. Pre-planned analyses have reliably shown a clear trend toward a greater magnitude of benefit in patients with higher PD-L1 expression, particularly CPS ≥ 5 and ≥ 10. Whether there is a linear relationship at higher cutoffs is not well known, though it likely represents smaller and smaller populations. Although beyond the scope of this clinically oriented review, recognition of the spatial and temporal heterogeneity in PD-L1 expression is important and repeat testing from progression samples across lines of therapy should be considered. Questions about additional predictive biomarkers, particularly plasma-derived, remain. Responses by tumor histology and location also differ, and special attention to these factors as well as MSI-H, HER2, and EBV subgroups in future trials is warranted. Questions regarding the incorporation of immunotherapy after progression on 1L immunotherapy plus chemotherapy combinations will arise as these combinations are used more frequently, and this represents a key area of future investigation. Overall, the role of immunotherapy continues to expand in GEA, and we welcome any additional tools for this difficult-to-treat group of cancers.	esophagus
Prognostic Significance of Negative Lymph Node Long Axis in Esophageal Cancer: Results From the Randomized Controlled UK MRC OE02 Trial.	OBJECTIVE: To analyze the relationship between negative lymph node (LNneg) size as a possible surrogate marker of the host antitumor immune response and overall survival (OS) in esophageal cancer (EC) patients. BACKGROUND: Lymph node (LN) status is a well-established prognostic factor in EC patients. An increased number of LNnegs is related to better survival in EC. Follicular hyperplasia in LNneg is associated with better survival in cancer-bearing mice and might explain increased LN size. METHODS: The long axis of 304 LNnegs was measured in hematoxylin-eosin stained sections from resection specimens of 367 OE02 trial patients (188 treated with surgery alone (S), 179 with neoadjuvant chemotherapy plus surgery (C+S)) as a surrogate of LN size. The relationship between LNneg size, LNneg microarchitecture, clinicopathological variables, and OS was analyzed. RESULTS: Large LNneg size was related to lower pN category ( P = 0.01) and lower frequency of lymphatic invasion ( P = 0.02) in S patients only. Irrespective of treatment, (y)pN0 patients with large LNneg had the best OS. (y)pN1 patients had the poorest OS irrespective of LNneg size ( P < 0.001). Large LNneg contained less lymphocytes ( P = 0.02) and had a higher germinal centers/lymphocyte ratio ( P = 0.05). CONCLUSIONS: This is the first study to investigate LNneg size in EC patients randomized to neoadjuvant chemotherapy followed by surgery or surgery alone. Our pilot study suggests that LNneg size is a surrogate marker of the host antitumor immune response and a potentially clinically useful new prognostic biomarker for (y)pN0 EC patients. Future studies need to confirm our results and explore underlying biological mechanisms.	esophagus
Inhibition of BRD4 Suppresses the Growth of Esophageal Squamous Cell Carcinoma.	BACKGROUND: Bromodomain-containing protein 4 (BRD4) binds acetylated lysine residues on histones to facilitate the epigenetic regulation of many genes, and it plays a key role in many cancer types. Despite many prior reports that have explored the importance of BRD4 in oncogenesis and the regulation of epigenetic memory, its role in esophageal squamous cell carcinoma (ESCC) progression is poorly understood. Here, we investigated BRD4 expression in human ESCC tissues to understand how it regulates the biology of these tumor cells. METHODS: BRD4 expression in ESCC tissues was measured via immunohistochemical staining. BRD4 inhibition in the Eca-109 and KYSE-150 ESCC cell lines was conducted to explore its functional role in these tumor cells. RESULTS: BRD4 overexpression was observed in ESCC tissues and cells, and inhibiting the function of the gene impaired the proliferative, invasive, and migratory activity of these cells while promoting their apoptosis. Cyclin D1 and c-Myc expression were also suppressed by BRD4 inhibition, and the expression of key epithelial-mesenchymal transition markers including E-cadherin and Vimentin was markedly altered by such inhibition. CONCLUSIONS: BRD4 plays key functional roles in the biology of ESCC, proposing that it could be a viable therapeutic target for treating this cancer type.	esophagus
Biological and clinical implications of metastasis-associated circular RNAs in oesophageal squamous cell carcinoma.	Oesophageal squamous cell carcinoma (OSCC) is a prevalent malignancy with high morbidity and mortality as a result of early metastasis and poor prognosis. Metastasis is a multistep process, involving various signalling pathways. Circular RNAs (circRNAs) are a class of covalently closed noncoding RNAs, the aberrant expression of which is reported to be involved in several biological events, including cell transformation, proliferation, migration, invasion, apoptosis and metastasis. Several studies have reported interactions between circRNAs and metastasis-associated signalling pathways. The abundance, stability and highly specific expression of candidate circRNAs make them potential biomarkers and therapeutic targets in OSCC. In this review article, we comprehensively describe metastasis-related circRNAs and their interactions with epithelial-mesenchymal transition-associated molecules. We also describe the molecular mechanisms and clinical relevance of circRNAs in OSCC progression and metastasis.	esophagus
Biomarkers for the prediction of esophageal cancer neoadjuvant chemoradiotherapy response: A systemic review.	Neoadjuvant chemoradiotherapy followed by surgery has been established as the standard treatment for locally advanced esophageal cancer. For patients with complete regression after neoadjuvant chemotherapy, active surveillance rather than planned surgery has been proposed as an organ preservation strategy. Reliable biomarkers to predict chemoradiation response is needed. We first summarized the previous reports of biomarkers with the potential to predict the treatment response of esophageal cancer neoadjuvant chemoradiotherapy. These traditional biomarkers are classified into three groups: genetic biomarkers, RNA biomarkers, and protein biomarkers. We then summarized some special types of biomarkers, including metabolites biomarkers, immune and tumor microenvironment biomarkers, and microbiome biomarkers.	esophagus
[Prevention of gastrointestinal cancer].	Throughout the past decades, considerable progress has been made in the (early) diagnosis and treatment of gastrointestinal cancers. However, the prognosis for advanced stages of gastrointestinal tumors remains limited for many patients and approximately one third of all tumor patients die as a result of gastrointestinal tumors. The prevention and early detection of gastrointestinal tumors is therefore of great importance.For this reason, we summarize the current state of knowledge and recommendations for the primary, secondary and tertiary prevention of esophageal, stomach, pancreas, liver and colorectal cancer in the following.	esophagus
Esophageal cancer in relation to alcohol drinking and tobacco use among men in Kerala, India - Karunagappally cohort.	BACKGROUND: In the Karunagappally cohort, esophageal cancer is the third most common cancer with an age-adjusted incidence rate of 6.2 per 100,000 person-years among men. The present study analyzed the risk of esophageal cancer in relation to alcohol drinking and tobacco use. METHODS: The study included 65,528 men aged 30-84 years in the Karunagappally cohort, India. RESULTS: Poisson regression analysis showed that alcohol drinking significantly increased (P = 0.027) the risk of esophageal cancer and the relative risk (RR) for current drinkers was 1.6, (95 % confidence interval (CI) = 1.1-2.3). The risk increased significantly in heavy alcohol drinkers (250 g of ethanol or above per day) (RR = 2.1, 95 % CI = 1.2-3.5) (P for trend = 0.014) and among current arrack consumers (RR = 1.8, 95 % CI = 0.99-3.29) (P for trend = 0.025). Current bidi and cigarette smokers showed an increase in the trend of cancer risk. A significantly higher risk was seen in those who had started smoking bidi before the age of 18 years, RR = 1.9 (95 % CI = 1.1-3.3) (P for trend = 0.044). Furthermore, increased RR for heavy bidi and cigarette smokers were 1.6 (95 % CI = 1.1-2.5) and 2.4 (95 % CI = 1.3-4.5), respectively. CONCLUSION: To the best of our knowledge, this is the first cohort study in India to report an increased esophageal cancer risk with respect to alcohol drinking.	esophagus
An autopsy case study of lymphocytic hypophysitis induced by nivolumab treatment for esophageal malignant melanoma.	Immune checkpoint inhibitors such as anti-cytotoxic T-lymphocyte antigen-4 and anti-programmed death-1 antibodies are effective against malignant tumors. However, they induce unique adverse events known as immune-related adverse events. Hypophysitis is one of the most frequent immune-related adverse events of anti-cytotoxic T-lymphocyte antigen-4 therapies. However, there have been few reports describing the pathological findings of hypophysitis induced by anti-programmed death-1 antibodies. The present case is the first autopsy case of hypophysitis induced by nivolumab monotherapy, an anti-programmed death-1 antibody. Pathologically, lymphocytes infiltrated the anterior lobe of the pituitary gland, and the number of pituitary cells, especially adrenocorticotropic hormone-positive cells, decreased. However, necrosis and remarkable fibrosis were not observed. Immunohistologically, some pituitary cells expressed programmed death-ligand 1. Lymphocytes were predominantly CD8-positive T cells, and CD68-positive macrophages and CD20-positive B-cells were also observed. IgG and C4d were deposited on pituitary cells, but IgG4 (a subclass of nivolumab) was not detected. These findings indicate that type IVc and type II hypersensitivity mechanisms may occur in hypophysitis induced by anti-programmed death-1 antibodies and that the inflammatory mechanisms underlying hypophysitis induced by anti-programmed death-1 and anti-cytotoxic T-lymphocyte antigen-4 antibodies are different.	esophagus
Association of Helicobacter pylori and gastric atrophy with adenocarcinoma of the esophagogastric junction in Taixing, China.	Gastric atrophy caused by Helicobacter pylori infection was suggested to influence the risk of adenocarcinoma of the esophagogastric junction (AEGJ), however, the evidence remains limited. We aimed to examine the associations of H. pylori infection and gastric atrophy (defined using serum pepsinogen [PG] I to PGII ratio) with AEGJ risk, based on a population-based case-control study in Taixing, China (2010-2014), with 349 histopathologically confirmed AEGJ cases and 1859 controls. We explored the potential effect modification by H. pylori serostatus and sex on the association of serum PGs with AEGJ risk. We used unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). H. pylori seropositivity was associated with an elevated AEGJ risk (OR = 1.95, 95% CI: 1.47-2.63). Neither CagA-positive nor VacA-positive strains dramatically changed this association. Gastric atrophy (PGI/PGII ratio ≤4) was positively associated with AEGJ risk (OR = 2.36, 95% CI: 1.72-3.22). The fully adjusted ORs for AEGJ progressively increased with the increasing levels of PGII (P-trend <.001). H. pylori showed nonsignificant effect modification (P-interaction = .385) on the association of gastric atrophy with AEGJ. In conclusion, H. pylori and gastric atrophy were positively associated with AEGJ risk. These results may contribute evidence to the ongoing research on gastric atrophy-related cancers and guide the prevention and control of AEGJ.	esophagus
Discovery, Optimization, and Structure-Activity Relationship Study of Novel and Potent RSK4 Inhibitors as Promising Agents for the Treatment of Esophageal Squamous Cell Carcinoma.	Ribosomal S6 protein kinase 4 (RSK4) was identified to be a promising target for the treatment of esophageal squamous cell carcinoma (ESCC) in our previous research, whose current treatments are primarily chemotherapy and radiotherapy due to the lack of targeted therapy. However, few potent and specific RSK4 inhibitors are reported. In this study, a series of 1,4-dihydro-2H-pyrimido[4,5-d][1,3]oxazin-2-ones derivatives were designed and synthesized as novel and potent RSK4 inhibitors. Compound 14f was identified with potent RSK4 inhibitory activity both in vitro and in vivo. 14f significantly inhibited the proliferation and invasion of ESCC cells in vitro with IC(50) values of 0.57 and 0.98 μM, respectively. It dose dependently inhibited the phosphorylation of RSK4 downstream substrates while exerting little effect on the substrates of RSK1-3 in ESCC cells. The markedly suppressed tumor growth and no observed toxicity to main organs in the ESCC xenograft mouse model suggested 14f to be a promising RSK4-targeting agent for ESCC treatment.	esophagus
Genomic and epigenomic evolution of acquired resistance to combination therapy in esophageal squamous cell carcinoma.	BACKGROUNDTargeted arterial infusion of verapamil combined with chemotherapy (TVCC) is an effective clinical interventional therapy for esophageal squamous cell carcinoma (ESCC), but multidrug resistance (MDR) remains the major cause of relapse or poor prognosis, and the underlying molecular mechanisms of MDR, temporal intratumoral heterogeneity, and clonal evolutionary processes of resistance have not been determined.METHODSTo elucidate the roles of genetic and epigenetic alterations in the evolution of acquired resistance during therapies, we performed whole-exome sequencing on 16 serial specimens from 7 patients with ESCC at every cycle of therapeutic intervention from 3 groups, complete response, partial response, and progressive disease, and we performed whole-genome bisulfite sequencing for 3 of these 7 patients, 1 patient from each group.RESULTSPatients with progressive disease exhibited a substantially higher genomic and epigenomic temporal heterogeneity. Subclonal expansions driven by the beneficial new mutations were observed during combined therapies, which explained the emergence of MDR. Notably, SLC7A8 was identified as a potentially novel MDR gene, and functional assays demonstrated that mutant SLC7A8 promoted the resistance phenotypes of ESCC cell lines. Promoter methylation dynamics during treatments revealed 8 drug resistance protein-coding genes characterized by hypomethylation in promoter regions. Intriguingly, promoter hypomethylation of SLC8A3 and mutant SLC7A8 were enriched in an identical pathway, protein digestion and absorption, indicating a potentially novel MDR mechanism during treatments.CONCLUSIONOur integrated multiomics investigations revealed the dynamics of temporal genetic and epigenetic inter- and intratumoral heterogeneity, clonal evolutionary processes, and epigenomic changes, providing potential MDR therapeutic targets in treatment-resistant patients with ESCC during combined therapies.FUNDINGNational Natural Science Foundation of China, Science Foundation of Peking University Cancer Hospital, CAMS Innovation Fund for Medical Sciences, Major Program of Shenzhen Bay Laboratory, Guangdong Basic and Applied Basic Research Foundation, and the third round of public welfare development and reform pilot projects of Beijing Municipal Medical Research Institutes.	esophagus
Metachronous carcinoma of the gastric tube following tumour-associated oesophagectomy.	INTRODUCTION: The prognosis of oesophageal carcinoma has improved during the last years. Thereby, the increasing survival has led to increasing occurrence of secondary gastric tube carcinoma (gastric conduit cancer, GTC) following oesophageal tumour resection. MATERIAL AND PATIENTS: A literature review (EMBASE, PubMed), spanning the years 2000 to 2020, identified 342 patients worldwide with a GTC following tumour-related oesophagectomy, of which 306 patients could be included for further analysis. RESULTS: The median age of 306 patients with GTC was 66.4 (39-80) years. 91.2% of patients (n = 279) were male. The median interval between oesophagectomy and GTC was 60.3 (4-236) months. 73.8% of patients (n = 226) were diagnosed as early cancer (EGC, T1) and 26.2% as advanced carcinoma (AGC, > T2; n = 80). Primary oesophagectomy was performed in 97.4% of patients (N = 298) for squamous cell carcinoma. AEG I carcinoma was present in only 5 patients (1.6%). In contrast, 99% (n = 303) of the GTC were found to be adenocarcinomas. One hundred eighty patients (58.8%) could be treated by endoscopic resection (ER). R0 resection was achieved in 82.8% (n = 149). The complication rate was 13.3% (n = 24) and the 30-day mortality 1.1% (n = 2) for ER. Eighty-three patients (27.1%) were treated surgically. These included 13 wedge resections, 25 partial resections and 45 total gastric graft resections with predominantly colon interposition. The R0 rate was 98.8% (n = 82). The postoperative morbidity was 24.1% (n = 20); the 90-day mortality was 6% (n = 5). In 43 patients (14%), palliative chemotherapy or radiotherapy or best supportive care took place. GTC diagnosed early in the EGC stage can be safely managed with ER. In cases of advanced GTC, surgical resection can be a potentially curative approach. Survival times of up to 120 months have been described after intervention for GTC.	esophagus
Dissecting esophageal squamous-cell carcinoma ecosystem by single-cell transcriptomic analysis.	Esophageal squamous-cell carcinoma (ESCC), one of the most prevalent and lethal malignant disease, has a complex but unknown tumor ecosystem. Here, we investigate the composition of ESCC tumors based on 208,659 single-cell transcriptomes derived from 60 individuals. We identify 8 common expression programs from malignant epithelial cells and discover 42 cell types, including 26 immune cell and 16 nonimmune stromal cell subtypes in the tumor microenvironment (TME), and analyse the interactions between cancer cells and other cells and the interactions among different cell types in the TME. Moreover, we link the cancer cell transcriptomes to the somatic mutations and identify several markers significantly associated with patients' survival, which may be relevant to precision care of ESCC patients. These results reveal the immunosuppressive status in the ESCC TME and further our understanding of ESCC.	esophagus