UNASSIGNED: Lung cancer remains an important cause of cancer-related mortality in Singapore, with a greater proportion of non-smokers diagnosed with non-small cell lung cancer (NSCLC) in the past 2 decades. The higher prevalence of targetable genomic alterations in lung cancer diagnosed in Singapore compared with countries in the West, as well as the expanding therapeutic landscape for NSCLC in the era of precision medicine, are both factors that underscore the importance of efficient and effective molecular profiling.
UNASSIGNED: This article provides consensus recommendations for biomarker testing for early-stage to advanced NSCLC. These recommendations are made from a multidisciplinary group of lung cancer experts in Singapore with the aim of improving patient care and long-term outcomes.
UNASSIGNED: The recommendations address the considerations in both the advanced and early-stage settings, and take into account challenges in the implementation of biomarker testing as well as the limitations of available data. Biomarker testing for both tumour tissue and liquid biopsy are discussed.
UNASSIGNED: This consensus statement discusses the approaches and challenges of integrating molecular testing into clinical practice for patients with early- to late-stage NSCLC, and provides practical recommendations for biomarker testing for NSCLC patients in Singapore.

BACKGROUND: Recently, consensus molecular subtypes (CMSs) have been proposed as a robust transcriptome-based classification system for colorectal cancer (CRC). Tetraspanins (TSPANs) are transmembrane proteins. They have been associated with the development of numerous malignancies, including CRC, through their role as \"master organizers\" for multi-molecular membrane complexes. No previous study has investigated the correlation between TSPANs and CMS classification. Herein, we investigated the expression of TSPANs in patient-derived primary CRC tissues and their CMS classifications.
METHODS: RNA samples were derived from primary CRC tissues (n = 100 patients diagnosed with colorectal adenocarcinoma) and subjected to RNA sequencing for transcriptome-based CMS classification and TSPAN-relevant analyses. Immunohistochemistry (IHC) and immunofluorescence (IF) stains were conducted to observe the protein expression level. To evaluate the relative biological pathways, gene-set enrichment analysis was performed.
RESULTS: Of the highly expressed TSPAN genes in CRC tissues (TSPAN8, TSPAN29, and TSPAN30), TSPAN8 was notably overexpressed in CMS3-classified primary tissues. The overexpression of TSPAN8 protein in CMS3 CRC was also observed by IHC and IF staining. As a result of gene-set enrichment analysis, TSPAN8 may potentially play a role in organizing signaling complexes for kinase-based metabolic deregulation in CMS3 CRC.
CONCLUSIONS: The present study reports the overexpression of TSPAN8 in CMS3 CRC. This study proposes TSPAN8 as a subtype-specific biomarker for CMS3 CRC. This finding provides a foundation for future CMS-based studies of CRC, a complex disease and the second leading cause of cancer mortality worldwide.

Barrett\'s esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Endoscopic eradication therapy (EET) can be effective in eradicating BE and related neoplasia and has greater risk of harms and resource use than surveillance endoscopy. This clinical practice guideline aims to inform clinicians and patients by providing evidence-based practice recommendations for the use of EET in BE and related neoplasia.
The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients, conducted an evidence review, and used the Evidence-to-Decision Framework to develop recommendations regarding the use of EET in patients with BE under the following scenarios: presence of (1) high-grade dysplasia, (2) low-grade dysplasia, (3) no dysplasia, and (4) choice of stepwise endoscopic mucosal resection (EMR) or focal EMR plus ablation, and (5) endoscopic submucosal dissection vs EMR. Clinical recommendations were based on the balance between desirable and undesirable effects, patient values, costs, and health equity considerations.
The panel agreed on 5 recommendations for the use of EET in BE and related neoplasia. Based on the available evidence, the panel made a strong recommendation in favor of EET in patients with BE high-grade dysplasia and conditional recommendation against EET in BE without dysplasia. The panel made a conditional recommendation in favor of EET in BE low-grade dysplasia; patients with BE low-grade dysplasia who place a higher value on the potential harms and lower value on the benefits (which are uncertain) regarding reduction of esophageal cancer mortality could reasonably select surveillance endoscopy. In patients with visible lesions, a conditional recommendation was made in favor of focal EMR plus ablation over stepwise EMR. In patients with visible neoplastic lesions undergoing resection, the use of either endoscopic mucosal resection or endoscopic submucosal dissection was suggested based on lesion characteristics.
This document provides a comprehensive outline of the indications for EET in the management of BE and related neoplasia. Guidance is also provided regarding the considerations surrounding implementation of EET. Providers should engage in shared decision making based on patient preferences. Limitations and gaps in the evidence are highlighted to guide future research opportunities.

BACKGROUND: Hereditary adenomatous polyposis syndromes, including familial adenomatous polyposis and other rare adenomatous polyposis syndromes, increase the lifetime risk of colorectal and other cancers.
METHODS: A team of 38 experts convened to update the 2008 European recommendations for the clinical management of patients with adenomatous polyposis syndromes. Additionally, other rare monogenic adenomatous polyposis syndromes were reviewed and added. Eighty-nine clinically relevant questions were answered after a systematic review of the existing literature with grading of the evidence according to Grading of Recommendations, Assessment, Development, and Evaluation methodology. Two levels of consensus were identified: consensus threshold (≥67% of voting guideline committee members voting either \'Strongly agree\' or \'Agree\' during the Delphi rounds) and high threshold (consensus ≥ 80%).
RESULTS: One hundred and forty statements reached a high level of consensus concerning the management of hereditary adenomatous polyposis syndromes.
CONCLUSIONS: These updated guidelines provide current, comprehensive, and evidence-based practical recommendations for the management of surveillance and treatment of familial adenomatous polyposis patients, encompassing additionally MUTYH-associated polyposis, gastric adenocarcinoma and proximal polyposis of the stomach and other recently identified polyposis syndromes based on pathogenic variants in other genes than APC or MUTYH. Due to the rarity of these diseases, patients should be managed at specialized centres.

BACKGROUND: Esophagectomy in combination with perioperative multimodal therapy is the cornerstone of modern curative treatment for esophageal adenocarcinoma. The primary aim of this study was to assess the influence of textbook outcome (TO) as a composite quality performance indicator (QPI) and its perioperative parameters on survival in patients who underwent esophagectomy with curative intent.
METHODS: Consecutive patients who underwent an esophagectomy between January 2014 and December 2022 at Christchurch Hospital were identified from a prospectively maintained hospital database. Univariable and multivariable analyses were performed to assess prognostic factors for each composite and individual postoperative outcome. Survival analysis was performed to evaluate the influence of these outcomes on overall survival.
RESULTS: A total of 108 patients underwent an esophagectomy during the study period. The overall and Clavien-Dindo (CD) grade ≥ 3 postoperative complication rates were 62% and 26%, respectively. The anastomotic leak rate was 6.5% (n = 7). The TO rate, 30-day readmission rate, and 30-day mortality rate were 20%, 13%, and 1%, respectively. Resection margin and nodal disease were found to be independent prognostic factors for reduced survival.
CONCLUSIONS: TO as originally defined and its postoperative parameters of 30-day postoperative complications and 30-day readmission are validated QPIs of esophageal cancer surgery. Updating the postoperative complication parameter to include CD grade ≥ 3 complications resulted in a positive association between achieving TO and increased survival. Our findings support the call to redefine TO based on an update to this parameter, making it a more precise QPI of esophageal cancer surgery.

Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to 8% of gynecologic malignancies. Known risk factors for vulvar cancer include increasing age, infection with human papillomavirus, cigarette smoking, inflammatory conditions affecting the vulva, and immunodeficiency. Most vulvar neoplasias are diagnosed at early stages. Rarer histologies exist and include melanoma, extramammary Paget\'s disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell carcinoma, and sarcoma. This manuscript discusses recommendations outlined in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for treatments, surveillance, systemic therapy options, and gynecologic survivorship.

Due to the unique nature of its anatomical location, the adenocarcinoma of esophagogastric junction (AEG) has been a subject of controversy and disagreement including its definition, staging, and treatment strategies. Chinse expert Consensus on Surgical Treatment of Adenocarcinoma of Esophagogastric Junction in China (2018 Edition) had been released in September 2018 and had played a pioneering role in unifying thoracic and general surgeons in China on surgical treatment strategies for AEG. Over the past five years, the emergence of several clinical research results on AEG has provided new clinical evidence for the selection of key surgical treatment strategies. Therefore, to further standardize the surgical treatment of AEG in China, Chinese Expert Consensus on Surgical Treatment of Adenocarcinoma of Esophagogastric Junction in China (2024 Edition) was released in 2024 by Chinese expert panel including 25 gastrointestinal surgeons and 24 thoracic surgeons. Based on the highest-level clinical research evidence in recent 5 years, this consensus ultimately formulates 29 recommendations on hotspots and key points on surgical treatment of AEG and summary 5 issues that are still awaiting further exploration. This review will provide a summary and detailed interpretation of the recommendations outlined in this consensus.
食管胃结合部腺癌（AEG）由于解剖位置的特殊性，其定义、分期及治疗策略存在诸多分歧与争议。2018年9月，我国发布了首部《食管胃结合部腺癌外科治疗中国专家共识（2018年版）》，积极推动了胸外科和普通外科医师AEG外科治疗策略的规范性和一致性。5年来，多项AEG临床研究结果的呈现，为AEG的外科治疗关键环节策略的选择提供了新的临床证据。因此，为进一步提升我国AEG外科临床实践的诊疗水平，在中国医师协会内镜医师分会腹腔镜外科专业组、国际食管疾病学会中国分会（CSDE）、中国食管胃结合部腺癌研究协作组、中国抗癌协会胃癌专委会和中华医学会肿瘤分会胃肠肿瘤学组的共同牵头和组织下，由25名胃肠外科专家和24名胸外科专家组成2024版食管胃结合部腺癌外科治疗中国专家共识编审专家组进行讨论修订，主要基于近5年来高级别临床研究证据完成共识的更新。最终形成了29项AEG外科治疗相关的推荐陈述，并提出了5项尚待探索的外科问题。本文主要针对修订后的共识推荐陈述进行解读。.

The publication of Chinese expert consensus on the surgical treatment for adenocarcinoma of esophagogastric junction (2018 edition) has widely accelerated the standardization and homogenization on the surgical treatment of adenocarcinoma of esophagogastric junction (AEG). In China, the surgical outcomes of AEG, the universality and practicability of this consensus has also been affirmed after the clinical practice during the past 5 years. Due to the persistent increasing incidence of AEG, the specificity on anatomic site, clinicopathological characteristics, molecular biological characteristics, AEG had been always the hotspot of many clinical trials and more clinical evidences had been published. However, its definition, classification, staging, surgical approach, resection pattern, extent of lymphadenectomy, and the digestive tract reconstruction etc. remain controversial. In light of the above, it is necessary to update the 2018 edition of consensus. The Chinese expert consensus on the surgical treatment for adenocarcinoma of esophagogastric junction (2024 edition) is generated based on the currently available and best clinical evidence, the latest global guidelines or consensuses, and the opinions from the Chinese expert panel. The present consensus focuses on the key points of surgical treatment and issues in dispute, and provides scientific recommendations. The goal of this expert consensus was to improve the homogeneity in understanding and practice between Chinese thoracic and gastrointestinal surgeons, and to further standardize surgical treatment of AEG. Those pending issues in this consensus need high-quality clinical research to further investigate.
《食管胃结合部腺癌外科治疗中国专家共识（2018版）》自颁布以来，很大程度上促进了我国食管胃结合部腺癌（AEG）的规范化、同质化诊疗，提升了我国AEG的外科治疗水平。经过5年的临床实践，该共识普适性和可行性已得到广泛证实。鉴于AEG发病率持续上升的趋势及其解剖部位、临床病理特征和分子生物学特征的特殊性，AEG成为近5年来外科临床研究的热点之一，并不断有新的临床研究证据发表。但是，对于AEG的定义、分型、分期、手术路径、切除范围、淋巴结清扫规范和消化道重建等外科问题，仍旧存在争议。鉴于此，有必要对2018版的共识进行更新。《食管胃结合部腺癌外科治疗中国专家共识（2024版）》在前一版的基础上，整合并分析5年来新的最佳临床证据，参考最新国际指南与共识，结合我国外科专家组意见，针对AEG外科治疗关键环节，包括AEG的定义和分型、手术径路、手术方式、淋巴结清扫范围、消化道重建方式及外科围手术期治疗等存在争议的问题，提出相关推荐建议，以期更好地规范AEG的外科治疗方式。在本共识中未解决的相关问题，尚需积极开展高质量的临床研究，以逐步探索和解决。.

Diagnosis and therapy of esophageal carcinoma is challenging and requires a multidisciplinary approach. The purpose of the updated German guideline \"Diagnosis and Treatment of Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus-version 3.1\" is to provide practical and evidence-based advice for the management of patients with esophageal cancer. Recommendations were developed by a multidisciplinary expert panel based on an extensive and systematic evaluation of the published medical literature and the application of well-established methodologies (e.g. Oxford evidence grading scheme, grading of recommendations). Accurate diagnostic evaluation of the primary tumor as well as lymph node and distant metastases is required in order to guide patients to a stage-appropriate therapy after the initial diagnosis of esophageal cancer. In high-grade intraepithelial neoplasia or mucosal carcinoma endoscopic resection shall be performed. Whether endoscopic resection is the definitive therapeutic measure depends on the histopathological evaluation of the resection specimen. Esophagectomy should be performed minimally invasive or in combination with open procedures (hybrid technique). Because the prognosis in locally advanced esophageal carcinoma is poor with surgery alone, multimodality therapy is recommended. In locally advanced adenocarcinomas of the esophagus or esophagogastric junction, perioperative chemotherapy or preoperative radiochemotherapy should be administered. In locally advanced squamous cell carcinomas of the esophagus, preoperative radiochemotherapy followed by complete resection or definitive radiochemotherapy without surgery should be performed. In the case of residual tumor in the resection specimen after neoadjuvant radiochemotherapy and R0 resection of squamous cell carcinoma or adenocarcinoma, adjuvant immunotherapy with nivolumab should be given. Systemic palliative treatment options (chemotherapy, chemotherapy plus immunotherapy, immunotherapy alone) in unresectable or metastastic esophageal cancer depend on histology and are stratified according to PD-L1 and/or Her2 expression.

Prostate adenocarcinoma (PRAD) is a common cancer diagnosis among men globally, yet large gaps in our knowledge persist with respect to the molecular bases of its progression and aggression. It is mostly indolent and slow-growing, but aggressive prostate cancers need to be recognized early for optimising treatment, with a view to reducing mortality.
Based on TCGA transcriptomic data pertaining to PRAD and the associated clinical metadata, we determined the sample Gleason grade, and used it to execute: (i) Gleason-grade wise linear modeling, followed by five contrasts against controls and ten contrasts between grades; and (ii) Gleason-grade wise network modeling via weighted gene correlation network analysis (WGCNA). Candidate biomarkers were obtained from the above analysis and the consensus found. The consensus biomarkers were used as the feature space to train ML models for classifying a sample as benign, indolent or aggressive.
The statistical modeling yielded 77 Gleason grade-salient genes while the WGCNA algorithm yielded 1003 trait-specific key genes in grade-wise significant modules. Consensus analysis of the two approaches identified two genes in Grade-1 (SLC43A1 and PHGR1), 26 genes in Grade-4 (including LOC100128675, PPP1R3C, NECAB1, UBXN10, SERPINA5, CLU, RASL12, DGKG, FHL1, NCAM1, and CEND1), and seven genes in Grade-5 (CBX2, DPYS, FAM72B, SHCBP1, TMEM132A, TPX2, UBE2C). A RandomForest model trained and optimized on these 35 biomarkers for the ternary classification problem yielded a balanced accuracy ∼ 86% on external validation.
The consensus of multiple parallel computational strategies has unmasked candidate Gleason grade-specific biomarkers. PRADclass, a validated AI model featurizing these biomarkers achieved good performance, and could be trialed to predict the differentiation of prostate cancers. PRADclass is available for academic use at: https://apalania.shinyapps.io/pradclass (online) and https://github.com/apalania/pradclass (command-line interface).