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Bowel Function in Survivors of Rectal Cancer Managed with Watch-and-Wait Versus Surgery. 观察等待与手术治疗对直肠癌幸存者肠功能的影响。
IF 1.6 Q4 ONCOLOGY Pub Date : 2026-01-26 DOI: 10.1007/s12029-025-01389-4
Sina Vatandoust, Luigi Sposato, David Wattchow, John Leung, Amitesh Roy, Dayan de Fontgalland, Paul Hollington, Gang Chen, Shahid Ullah, Michael Z Michael, Christos S Karapetis

Background: Sphincter-preserving surgery for rectal cancer is associated with long-term bowel dysfunction, yet data on outcomes in patients managed with watch-and-wait is limited. This study compared bowel function in rectal cancer survivors managed with watch-and-wait versus sphincter-preserving surgery and evaluated the performance of two instruments: the Memorial Sloan Kettering Bowel Function Instrument (MSK-BFI) and the Low Anterior Resection Syndrome (LARS) score within each cohort.

Patients and methods: In this cross-sectional study, rectal cancer survivors treated with long-course chemoradiotherapy between 2011 and 2019 at Flinders Medical Centre were recruited. Participants without stomas completed the MSK-BFI, LARS, and comorbidity questionnaires. Demographics and clinical data were obtained from medical records. Outcomes were compared between the sustained watch-and-wait (WW) and surgical (SURG) cohorts. Associations were examined using regression models. Instrument comparisons were performed in each cohort using factor analysis.

Results: Of the 190 eligible survivors, 67 participants were included (WW, n=33; SURG, n=34). Surgery was associated with significantly worse bowel function across MSK-BFI domains and higher rates of Any LARS (91% vs. 67%) and Major LARS (70% vs. 36%). Female sex was independently associated with poorer bowel function. Factor analysis revealed that one factor accounted for bowel function in the SURG cohort, whereas two factors were required in the WW cohort, indicating greater complexity.

Conclusion: Surgery and female sex are associated with significantly worse bowel function in rectal cancer survivors. The WW cohort demonstrated more complex symptom patterns, supporting concurrent use of MSK-BFI and LARS until a WW-specific tool is developed. A larger, prospective study is underway to investigate the findings further.

背景:直肠癌保括约肌手术与长期肠功能障碍相关,但观察等待治疗患者的结果数据有限。本研究比较了观察等待与保留括约肌手术治疗的直肠癌幸存者的肠功能,并评估了两种仪器的性能:纪念斯隆-凯特琳肠功能仪(MSK-BFI)和低前切除术综合征(LARS)评分。患者和方法:在这项横断面研究中,招募了2011年至2019年在弗林德斯医学中心接受长期放化疗的直肠癌幸存者。无造口者完成MSK-BFI、LARS和合并症问卷调查。人口统计学和临床数据来自医疗记录。比较持续观察等待组(WW)和手术组(SURG)的结果。使用回归模型检验相关性。采用因子分析对每个队列进行仪器比较。结果:在190名符合条件的幸存者中,纳入了67名参与者(WW, n=33; SURG, n=34)。手术与MSK-BFI结构域的肠功能明显恶化以及任何LARS(91%对67%)和主要LARS(70%对36%)的较高发生率相关。女性与肠道功能较差独立相关。因子分析显示,在SURG队列中,一个因素影响肠功能,而在WW队列中,需要两个因素,这表明复杂性更大。结论:手术和女性与直肠癌幸存者的肠功能明显恶化相关。WW队列显示出更复杂的症状模式,支持同时使用MSK-BFI和LARS,直到开发出WW特异性工具。一项更大的前瞻性研究正在进行中,以进一步调查这些发现。
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引用次数: 0
Yttrium-90 Transarterial Radioembolization for Intrahepatic Cholangiocarcinoma: A Comprehensive Review. 经动脉放射栓塞治疗肝内胆管癌的研究综述。
IF 1.6 Q4 ONCOLOGY Pub Date : 2026-01-26 DOI: 10.1007/s12029-026-01398-x
Arsalan Nadeem, Saad Abu Zahra, Ashima Kundu, Aparna Kalyan, Daniel Borja-Cacho, Zachary Dietch, Laura Kulik, Andrew C Gordon, Robert J Lewandowski

Intrahepatic cholangiocarcinoma (iCCA) represents an aggressive primary hepatic malignancy with limited non-surgical therapeutic options. This review examines the evolution of transarterial radioembolization (TARE) with Yttrium-90 microspheres from palliative intervention to curative-intent therapy, driven by advances over the past few decades. Partition-model dosimetry demonstrates superior survival compared to empiric approaches (14.9 versus 5.5 months, P < 0.001), establishing the critical importance of individualized treatment planning. In first-line settings, multimodal strategies combining TARE with systemic therapy achieve median overall survival of 32.5 months, with intensive protocols demonstrating objective response rates of 39-85% and downstaging to curative resection in 22-54% of patients. Ablative radiation segmentectomy delivers tumor doses exceeding 190 Gy, achieving objective response rates of 94%, median survival of up to 72 months in early-stage disease. TARE-based bridging to liver transplantation yields 5-year survival of 57% from time of transplant listing. Optimal outcomes are observed for tumor burden below 25%, preserved hepatic function, favorable performance status, and personalized dosimetry delivering ≥205 Gy to tumor. Contemporary TARE represents a transformative paradigm in liver-directed therapy for appropriately selected iCCA patients.

肝内胆管癌(iCCA)是一种侵袭性原发性肝脏恶性肿瘤,非手术治疗选择有限。本文回顾了在过去几十年的进展推动下,使用钇-90微球经动脉放射栓塞(TARE)从姑息性干预到治疗性治疗的演变。与经验方法相比,分割模型剂量法显示了更高的生存期(14.9个月对5.5个月,P
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引用次数: 0
Retrospective Analysis of HAIP Therapy in Metastatic Colorectal Cancer: Efficacy, Safety, and Prognostic Factors. HAIP治疗转移性结直肠癌的回顾性分析:疗效、安全性和预后因素。
IF 1.6 Q4 ONCOLOGY Pub Date : 2026-01-21 DOI: 10.1007/s12029-026-01403-3
Allante Milsap, Matthew Sawyer, Syed Kazmi, Radhika Kainthla, Amy Jones, Salwan Al Mutar, Timothy Brown, Nilesh Verma
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引用次数: 0
Synergistic Effect of Fecal Microbiota Transplantation, γδT Cell Immunotherapy, and Pembrolizumab in Refractory Advanced Pancreatic Cancer: A Case Report. 粪便微生物群移植、γδT细胞免疫治疗和派姆单抗治疗难治性晚期胰腺癌的协同作用:1例报告。
IF 1.6 Q4 ONCOLOGY Pub Date : 2026-01-20 DOI: 10.1007/s12029-025-01368-9
Mohammed Alnaggar, Yongshun Chen, Cuimin Wang, Shengzhou Wang, Fangfang Zhu, Yonggan Lin, Fuad A Abdu, Li Gong

Background: Pancreatic cancer (PC) remains one of the most lethal malignancies with limited treatment options, particularly in advanced stages. Emerging immunotherapeutic strategies, such as Gamma Delta (γδ) T cell therapy paired with microbiota management, have demonstrated promise.

Case presentation: We report a case of a 75-year-old male diagnosed with advanced-stage and poorly differentiated PC who demonstrated significant clinical improvement following a novel therapeutic approach combining fecal microbiota transplantation (FMT), γδ T cell therapy, and pembrolizumab. Initial chemotherapy and radiotherapy were discontinued due to adverse effects. Pre-treatment the CA19-9 (1206 U/mL), tumor markers were significantly elevated with CEA, CA15-3 and CA125 all within normal limits. No pathogenic mutations (e.g., BRCA1/2, PALB2) were identified. A comprehensive assessment revealed tumor progression, immunosuppression, and gut microbiota dysbiosis, resulting in FMT and γδ T cell therapy being introduced alongside pembrolizumab.

Outcomes: The combination therapy resulted in the clearance of circulating tumor cells (CTCs), normalization of CA19-9 to 72 U/mL, improved clinical symptoms, and a marked reduction in tumor size, as confirmed by CT. Tolerability was excellent with no serious adverse events occurred.

Conclusion: This case suggests that FMT combined with γδ T cell therapy may be a promising immunotherapeutic strategy for advanced PC. Further studies are needed to validate these findings.

背景:胰腺癌(PC)仍然是最致命的恶性肿瘤之一,治疗选择有限,特别是在晚期。新兴的免疫治疗策略,如γδ (γδ) T细胞治疗与微生物群管理相结合,已经证明了前景。病例介绍:我们报告了一例75岁的男性诊断为晚期和低分化PC,在采用粪便微生物群移植(FMT)、γδ T细胞治疗和派姆单抗相结合的新型治疗方法后,临床表现出显著改善。最初的化疗和放疗因不良反应而停止。治疗前CA19-9 (1206 U/mL)、肿瘤标志物显著升高,CEA、CA15-3、CA125均在正常范围内。未发现致病性突变(如BRCA1/2、PALB2)。综合评估显示肿瘤进展、免疫抑制和肠道微生物群失调,导致FMT和γδ T细胞治疗与派姆单抗一起引入。结果:经CT证实,联合治疗可清除循环肿瘤细胞(CTCs),使CA19-9正常化至72 U/mL,改善临床症状,肿瘤大小明显缩小。耐受性极好,无严重不良事件发生。结论:本病例提示FMT联合γδ T细胞治疗可能是一种有前景的晚期PC免疫治疗策略。需要进一步的研究来验证这些发现。
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引用次数: 0
Colorectal Cancer in China, 1990 to 2023: Trends, Modifiable Risks, and Prevention Priorities Based on Global Burden of Disease 2023 Estimates. 1990 - 2023年中国结直肠癌:趋势、可调整风险和基于2023年全球疾病负担估算的预防重点
IF 1.6 Q4 ONCOLOGY Pub Date : 2026-01-20 DOI: 10.1007/s12029-026-01400-6
Shuai Wang, Jingbo Lv, Li Wang, Hao Wu, Xueyuan Cao

Background: We analyzed China's colorectal cancer (CRC) burden from 1990 to 2023, focusing on incidence, mortality, disability-adjusted life years (DALYs), prevalence, and risk-attributable burden, to assess temporal trends and evaluate future prevention needs.

Methods: Using Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 estimates, we summarized all-age numbers and age-standardized rates (ASR) by sex. Joinpoint log-linear models calculated the average annual percent change (AAPC), and risk-attributable deaths and DALYs were profiled for 2023. And we conducted a brief sensitivity comparison of trends for 2010-2019 and 2019-2023 for both sexes combined. All results are model-based estimates and are reported with uncertainty intervals (UIs).

Results: In 2023, China was estimated to have 611,364 incident CRC cases (95% UI 493,490-771,955), 258,088 deaths (225,359-305,788), 3,375,669 prevalent cases (2,710,191-4,159,613), and 6,279,382 DALYs (5,563,225-7,428,441). Over 1990-2023, ASIR and ASPR increased, while ASMR and ASDR declined. Males consistently had higher rates than females, and burden rose steeply with age. AAPCs showed an increase in incidence across the 15-49, 50-74, and ≥ 75 years age groups, particularly in those aged 75 years and older. Mortality and DALY rates declined at younger ages and were stable at ≥ 75. In 2023, the risk-attributable CRC burden was concentrated in dietary risks and metabolic and behavioural risks, including high fasting plasma glucose, smoking, alcohol use, and low physical activity. The brief pre- and post-2019 comparison suggested broadly similar directions with wide uncertainty.

Conclusions: GBD 2023 estimates indicate that CRC remains a growing challenge in China, with rising ASIR and ASPR despite declining ASMR and ASDR. Prevention and screening planning should prioritise modifiable risks and strengthen service resilience, while interpreting model-based estimates in light of their uncertainty.

背景:我们分析了1990年至2023年中国结直肠癌(CRC)负担,重点关注发病率、死亡率、残疾调整生命年(DALYs)、患病率和风险归因负担,以评估时间趋势并评估未来的预防需求。方法:使用全球疾病、损伤和危险因素负担研究(GBD) 2023的估计值,我们按性别总结了所有年龄数字和年龄标准化率(ASR)。Joinpoint对数线性模型计算了平均年百分比变化(AAPC),并对2023年的风险归因死亡和伤残调整年进行了分析。我们对2010-2019年和2019-2023年两性趋势进行了简短的敏感性比较。所有结果都是基于模型的估计,并以不确定区间(ui)报告。结果:2023年,中国估计有611,364例CRC病例(95% UI 493,490-771,955), 258,088例死亡(225,359-305,788),3,375,669例流行病例(2,710,191-4,159,613)和6,279,382例DALYs(5,563,225-7,428,441)。1990-2023年间,ASIR和ASPR上升,而ASMR和ASDR下降。男性的发病率始终高于女性,而且随着年龄的增长,负担急剧上升。AAPCs在15-49岁、50-74岁和≥75岁年龄组的发病率增加,特别是在75岁及以上年龄组。年龄越小,死亡率和DALY率下降,≥75岁时稳定。2023年,可归因于风险的结直肠癌负担集中在饮食风险、代谢和行为风险,包括空腹血糖过高、吸烟、饮酒和体力活动不足。2019年前后的简短比较表明,方向大致相似,但存在很大的不确定性。结论:GBD 2023估计表明,CRC在中国仍然是一个越来越大的挑战,尽管ASMR和ASDR下降,但ASIR和ASPR上升。预防和筛查规划应优先考虑可改变的风险,并加强服务复原力,同时根据其不确定性解释基于模型的估计。
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引用次数: 0
Real-world Predictors of Early Mortality and Treatment Discontinuation in HCC Patients Treated with Atezolizumab-Bevacizumab. 阿特唑单抗-贝伐单抗治疗HCC患者早期死亡率和停药的现实预测因素
IF 1.6 Q4 ONCOLOGY Pub Date : 2026-01-20 DOI: 10.1007/s12029-025-01375-w
Palma Fedele, Matteo Landriscina, Antonio Di Stasi, Arianna Gadaleta-Caldarola, Guido Giordano, Vincenzo Emanuele Chiuri, Mariachiara Masucci, Giulia Villano, Rosaria Martina, Federica Fumai, Giovanni Santacroce, Angelo Nacci, Antonella Licchetta, Vincenzo Dadduzio, Gennaro Gadaleta-Caldarola
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引用次数: 0
A Bibliometric Analysis of Research Trends and Collaborative Networks in Gastric Cancer and Helicobacter Pylori Studies. 胃癌和幽门螺杆菌研究的研究趋势和合作网络的文献计量学分析。
IF 1.6 Q4 ONCOLOGY Pub Date : 2026-01-20 DOI: 10.1007/s12029-025-01382-x
Yi Yu, Feihu Bai, Dekui Zhang, Yonggang Tian

Background: Gastric cancer (GC) remains a significant global health burden, with Helicobacter pylori (H. pylori) infection being a major etiological factor. Despite extensive research, a comprehensive overview of the temporal evolution of research output, collaborative networks among countries and institutions, and shifting research foci in this field is lacking.

Methods: We conducted a bibliometric analysis utilizing the Citexs database and its analytics platform. Literature pertaining to GC and H. pylori published between January 2004 and December 2023 was retrieved and subjected to data mining and visualization to delineate research trends and hotspots.

Results: Analysis of 12,789 publications revealed a generally upward trend in annual output. The United States was the most productive country, while The American Journal of Gastroenterology was the leading journal. Baylor College of Medicine was the most prolific institution, and Yoshio Yamaoka was the most productive author. Keyword and thematic analysis identified core research areas, including H. pylori, gastritis, the cytotoxin-associated gene A (CagA), and GC itself. At the mechanistic level, current research focuses heavily on genes such as CXCL8, TNF, and NFKB1.

Conclusion: Future studies should prioritize deeper exploration of these core themes and pivotal signaling pathways to potentially facilitate advances in the prevention and treatment of H. pylori-associated GC.

背景:胃癌(GC)仍然是一个重要的全球健康负担,幽门螺杆菌(H. pylori)感染是一个主要的病因。尽管进行了广泛的研究,但缺乏对研究产出的时间演变,国家和机构之间的合作网络以及该领域研究重点转移的全面概述。方法:利用Citexs数据库及其分析平台进行文献计量学分析。检索2004年1月至2023年12月期间发表的有关GC和幽门螺杆菌的文献,并进行数据挖掘和可视化,以描绘研究趋势和热点。结果:对12789份出版物的分析显示,年出版量总体呈上升趋势。美国是产量最高的国家,而《美国胃肠病学杂志》(The American Journal of Gastroenterology)是领先的杂志。贝勒医学院是最多产的机构,山冈义夫是最多产的作者。关键词和主题分析确定了核心研究领域,包括幽门螺杆菌、胃炎、细胞毒素相关基因A (CagA)和GC本身。在机制层面,目前的研究主要集中在CXCL8、TNF和NFKB1等基因上。结论:未来的研究应优先深入探索这些核心主题和关键信号通路,以潜在地促进幽门螺杆菌相关GC的预防和治疗进展。
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引用次数: 0
A Prospective, Cross-Sectional, Multicenter Study Evaluating a Multi-Target Blood Protein in Vitro Diagnostic Test for Colorectal Cancer. 一项评估结直肠癌多靶点血蛋白体外诊断试验的前瞻性、横断面、多中心研究。
IF 1.6 Q4 ONCOLOGY Pub Date : 2026-01-16 DOI: 10.1007/s12029-025-01373-y
Emily Y He, Guy A van Hazel, Andrew M Sloss, Stephen Pianko, Gregor J Brown, Philip R Clingan, Rajvinder Singh, Ann C Solterbeck, Robert Traficante, Louise Formby-Miller, Trevor Lockett, Finlay Macrae

Purpose: Earlier detection of colorectal cancer (CRC) can improve survival rates. A simple, effective blood test may help improve screening participation. The multi-target blood protein (MTBP; ColoSTAT®) test and algorithm uses concentrations of five protein biomarkers of CRC and patient's sex and age to generate a CRC likelihood score. We compared the performance of the MTBP test in detecting CRC to colonoscopy, the 'gold standard'.

Methods: This cross-sectional, multicenter study enrolled participants into two cohorts: participants recently colonoscopically diagnosed with CRC and progressing to surgery or neoadjuvant treatment (Cohort 1), and participants with no CRC history who were scheduled for colonoscopy (Cohort 2). Due to COVID-19 pandemic-related recruitment delays, Cohort 1 was supplemented with bio-banked blood samples (BBS) from patients with clinically confirmed CRC. Performance goals for sensitivity and specificity of the MTBP test compared to colonoscopy were ≥ 73% (lower 95% confidence limit [LCL] > 60%) and ≥ 90% (LCL > 80%), respectively.

Results: Cohort 1 included 29 patients, Cohort 2 enrolled 768 patients and 192 BBS were included. Median age when providing samples was 64 years (range, 40-85 years); 53.4% were female. Definitive MTBP test results were obtained from 657 samples. 112 and 389 samples met the criteria for inclusion in the primary sensitivity and specificity analyses, respectively. The sensitivity of ColoSTAT® for detection of all-stage CRC compared to colonoscopy was 81.3% (95%CL 73.0%-87.4%) and the specificity, 91.0% (95%CL 87.7%-93.5%).

Conclusions: The MTBP test met pre-specified primary performance endpoints and warrants further evaluation in clinical populations at elevated risk of CRC.

目的:早期发现结直肠癌(CRC)可提高生存率。一项简单有效的血液检查可能有助于提高筛查的参与率。多靶点血液蛋白(MTBP; ColoSTAT®)测试和算法使用CRC的五种蛋白质生物标志物的浓度和患者的性别和年龄来生成CRC的可能性评分。我们比较了MTBP检测CRC与结肠镜检查的表现,结肠镜检查是“金标准”。方法:这项横断面、多中心研究将参与者分为两个队列:最近结肠镜检查诊断为结直肠癌并正在进行手术或新辅助治疗的参与者(队列1),以及没有结直肠癌病史的参与者(队列2),计划进行结肠镜检查。由于COVID-19大流行相关的招募延迟,队列1补充了临床确诊的结直肠癌患者的生物库血液样本(BBS)。与结肠镜检查相比,MTBP检查的敏感性和特异性的性能目标分别为≥73%(95%置信下限[LCL] > 60%)和≥90% (LCL > 80%)。结果:队列1纳入29例患者,队列2纳入768例患者,其中包括192例BBS患者。提供样本时的中位年龄为64岁(范围40-85岁);53.4%为女性。从657个样本中获得了确定的MTBP检测结果。112例和389例样本分别符合纳入主要敏感性和特异性分析的标准。与结肠镜检查相比,ColoSTAT®检测全期结直肠癌的敏感性为81.3% (95%CL 73.0%-87.4%),特异性为91.0% (95%CL 87.7%-93.5%)。结论:MTBP测试满足预先指定的主要性能终点,值得在CRC风险升高的临床人群中进一步评估。
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引用次数: 0
Incidence, Risk Factors, and Management of Radiotherapy-Related Skin Toxicity in Rectoanal Cancer Patients: a Systematic Review and Meta-Analysis. 直肠直肠癌患者放射相关皮肤毒性的发生率、危险因素和管理:系统回顾和荟萃分析。
IF 1.6 Q4 ONCOLOGY Pub Date : 2026-01-15 DOI: 10.1007/s12029-025-01387-6
Yingge He, Mengzhe Wang, Changqing Gao, Yonghui Hao, Shuning He, Liqi Li

Background: Radiotherapy is essential for rectoanal cancer, but pelvic anatomy and high radiation doses increase radiodermatitis risk, potentially compromising treatment efficacy. No specific meta-analysis exists for this group.

Methods: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science up to September 2025. Pooled meta-analysis, network meta-analysis, and dose-effect meta-analysis were performed on 50 included studies (n = 4,892).

Results: The overall radiodermatitis incidence was 58.7% (95% CI: 55.2%-62.1%), including severe (Grade ≥ 3, 12.3%) and moist desquamation (34.5%). Key independent risk factors (P < 0.05) were tumor distance ≤ 5 cm from anal verge (OR = 2.86), stoma absence (OR = 3.12), total dose > 50 Gy (OR = 2.59), concurrent chemotherapy (OR = 2.73), HIV infection (OR = 5.82), 3D-CRT vs. IMRT (OR = 8.76), and tumor skin invasion (OR = 36.0). Effective interventions included spray-type skin protectants (SUCRA = 92.3%), volumetric modulated arc therapy (VMAT; OR = 0.29 vs. 3D-CRT), recombinant human epidermal growth factor, and amifostine. A dose inflection point occurred at 50 Gy, with a 29% increased risk of severe dermatitis per additional 5 Gy above this threshold.

Conclusions: Skin toxicity is common in rectoanal cancer radiotherapy and linked to tumor, treatment, and patient factors. Optimized techniques (e.g., VMAT) combined with spray-type protectants enable precision management, improving outcomes.

背景:放疗是治疗直肠癌的必要手段,但骨盆解剖和高剂量放疗会增加放射性皮炎的风险,可能影响治疗效果。没有针对这一群体的具体荟萃分析。方法:系统检索到2025年9月的PubMed、Embase、Cochrane Library和Web of Science。对纳入的50项研究(n = 4,892)进行了汇总荟萃分析、网络荟萃分析和剂量效应荟萃分析。结果:放射性皮炎总发病率为58.7% (95% CI: 55.2% ~ 62.1%),其中重度(≥3级)12.3%,湿性脱屑34.5%。关键独立危险因素(p50 Gy (OR = 2.59)、同期化疗(OR = 2.73)、HIV感染(OR = 5.82)、3D-CRT vs. IMRT (OR = 8.76)、肿瘤皮肤侵袭(OR = 36.0)。有效的干预措施包括喷雾型皮肤保护剂(SUCRA = 92.3%)、体积调节电弧疗法(VMAT; OR = 0.29 vs. 3D-CRT)、重组人表皮生长因子和氨磷汀。剂量拐点出现在50戈瑞,在此阈值之上每增加5戈瑞,严重皮炎的风险增加29%。结论:皮肤毒性在直肠肿瘤放疗中很常见,并与肿瘤、治疗和患者因素有关。优化的技术(如VMAT)与喷雾型保护剂相结合,实现了精确管理,改善了结果。
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引用次数: 0
Molecular Testing for Intrahepatic Cholangiocarcinoma: What, When, How? 肝内胆管癌的分子检测:什么,何时,如何?
IF 1.6 Q4 ONCOLOGY Pub Date : 2026-01-15 DOI: 10.1007/s12029-026-01397-y
Maryam Barsch, Elaine-Pashupati Dopfer, Anne Maria Schultheis, Michael Quante

Purpose: Intrahepatic cholangiocarcinoma (iCCA) represents a biologically heterogeneous subgroup of biliary tract cancer (BTC) with a 5-year survival below 20%. Delayed diagnosis, intrinsic aggressiveness, and extensive intertumoral and intratumoral heterogeneity at the clinical, histopathological, and genomic level all contribute to this dismal outcome. Increasingly, treatment decisions in advanced iCCA depend on the identification of actionable molecular alterations, including FGFR2 fusions or rearrangements, IDH1 mutations, HER2 amplifications, NTRK fusions, and microsatellite instability (MSI-high) and/or mismatch repair deficiency (dMMR).

Methods: A narrative review of the current literature was conducted, focusing on (i) what molecular alterations are clinically relevant today, (ii) when molecular profiling should be performed, and (iii) how testing should be technically implemented in routine clinical practice. Results iCCA, particularly the small-duct subtype, harbors a high prevalence of therapeutically actionable molecular alterations, in contrast to extrahepatic cholangiocarcinoma and gallbladder carcinoma. Early and comprehensive molecular profiling enables access to approved targeted therapies, molecularly stratified second-line treatments, and clinical trials. Combined DNA- and RNA-based next-generation sequencing, complemented by immunohistochemistry and in situ hybridization, provides the most reliable diagnostic framework.

Conclusion: Molecular testing has become an essential component of modern iCCA management. Broad, early, and technically integrated molecular profiling-ideally performed at initial diagnosis and interpreted in an interdisciplinary (molecular) tumor board-is critical to fully realize the potential of precision oncology in BTC.

目的:肝内胆管癌(iCCA)是胆道癌(BTC)的一个生物学异质性亚组,5年生存率低于20%。延迟的诊断,内在的侵袭性,广泛的肿瘤间和肿瘤内的异质性在临床,组织病理学和基因组水平都导致了这一令人沮丧的结果。晚期iCCA的治疗决策越来越依赖于可操作分子改变的识别,包括FGFR2融合或重排、IDH1突变、HER2扩增、NTRK融合、微卫星不稳定性(MSI-high)和/或错配修复缺陷(dMMR)。方法:对当前文献进行叙述性回顾,重点关注(i)当今与临床相关的分子改变,(ii)何时应该进行分子谱分析,以及(iii)如何在常规临床实践中技术上实施测试。结果:与肝外胆管癌和胆囊癌相比,iCCA,尤其是小管亚型,具有高发生率的可治疗性分子改变。早期和全面的分子谱分析使获得批准的靶向治疗、分子分层二线治疗和临床试验成为可能。结合DNA和rna为基础的下一代测序,辅以免疫组织化学和原位杂交,提供了最可靠的诊断框架。结论:分子检测已成为现代iCCA管理的重要组成部分。广泛的、早期的、技术上集成的分子谱分析——理想的是在初始诊断时进行,并在跨学科(分子)肿瘤委员会中进行解释——对于充分发挥BTC精确肿瘤学的潜力至关重要。
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引用次数: 0
期刊
Journal of Gastrointestinal Cancer
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