ESMO Gastrointestinal Oncology最新文献_第6页

Association between neutropenia and efficacy in patients with refractory mCRC receiving trifluridine/tipiracil + bevacizumab: post hoc analysis of the SUNLIGHT trial 接受trifluridine/tipiracil + bevacizumab治疗的难治性mCRC患者中性粒细胞减少与疗效之间的关系：SUNLIGHT试验的事后分析

ESMO Gastrointestinal Oncology

Pub Date : 2025-09-08 DOI: 10.1016/j.esmogo.2025.100234

G.W. Prager , E. Elez , M. Fakih , F. Ciardiello , E. Van Cutsem , L. Roby , W. Yao , E. Choucair , J. Taieb

Background

The efficacy of trifluridine/tipiracil (FTD/TPI) + bevacizumab compared with FTD/TPI for the treatment of refractory metastatic colorectal cancer (mCRC) was demonstrated in the SUNLIGHT trial. However, the association between neutropenia and neutrophil count decrease (NCD) and efficacy outcomes in the SUNLIGHT population has not yet been assessed.

Patients and methods

Patients with mCRC enrolled in SUNLIGHT had received no more than two prior treatment regimens and were randomised to receive either FTD/TPI + bevacizumab or FTD/TPI. In this post hoc analysis, overall survival (OS) and progression-free survival (PFS) were analysed in patients with severe (grade ≥3) neutropenia/NCD and in patients with no, or non-severe, neutropenia/NCD.

Results

Patients treated with FTD/TPI + bevacizumab with severe neutropenia/NCD had longer OS (hazard ratio [HR] 0.37 [95% confidence interval (CI) 0.26-0.52] P < 0.0001) and PFS (HR 0.41 [95% CI 0.31-0.55] P < 0.0001) than patients with non-severe or no neutropenia/NCD. Patients treated with FTD/TPI + bevacizumab had improved OS compared with patients treated with FTD/TPI in the severe neutropenia/NCD (HR 0.58 [95% CI 0.40-0.85] P = 0.0046) and non-severe or no neutropenia/NCD (HR 0.71 [95% CI 0.54-0.94] P = 0.0176) subgroups. Most cases of severe neutropenia/NCD occurred during the first two cycles of treatment, did not lead to dose reduction or interruption, and were effectively managed with or without the use of granulocyte colony-stimulating factor.

Conclusions

In SUNLIGHT, patients who developed severe neutropenia/NCD had improved OS and PFS in both treatment arms. Patients receiving FTD/TPI + bevacizumab had longer OS/PFS than patients receiving FTD/TPI, irrespective of the presence of severe neutropenia/NCD.

背景：与FTD/TPI相比，trifluridine/tipiracil (FTD/TPI) +贝伐单抗治疗难治性转移性结直肠癌（mCRC）的疗效在SUNLIGHT试验中得到证实。然而，中性粒细胞减少症和中性粒细胞计数减少（NCD）与SUNLIGHT人群疗效结局之间的关系尚未得到评估。患者和方法纳入sunshine的mCRC患者之前接受过不超过两种治疗方案，随机分配接受FTD/TPI +贝伐单抗或FTD/TPI。在这项事后分析中，对严重（≥3级）中性粒细胞减少症/非传染性疾病患者和无或非严重中性粒细胞减少症/非传染性疾病患者的总生存期（OS）和无进展生存期（PFS）进行了分析。结果FTD/TPI +贝伐单抗治疗严重中性粒细胞减少/NCD患者的OS（风险比[HR] 0.37[95%可信区间（CI） 0.26-0.52] P < 0.0001）和PFS （HR 0.41 [95% CI 0.31-0.55] P < 0.0001）均长于非严重或无中性粒细胞减少/NCD患者。与FTD/TPI +贝伐单抗治疗的患者相比，在严重中性粒细胞减少/NCD （HR 0.58 [95% CI 0.40-0.85] P = 0.0046）和非严重或无中性粒细胞减少/NCD （HR 0.71 [95% CI 0.54-0.94] P = 0.0176）亚组中，FTD/TPI +贝伐单抗治疗的患者OS改善。大多数严重中性粒细胞减少/非传染性疾病病例发生在治疗的前两个周期，没有导致剂量减少或中断，并且在使用或不使用粒细胞集落刺激因子的情况下得到有效控制。结论：在SUNLIGHT中，发生严重中性粒细胞减少/NCD的患者在两个治疗组的OS和PFS均有改善。无论是否存在严重中性粒细胞减少症/非传染性疾病，接受FTD/TPI +贝伐单抗的患者比接受FTD/TPI的患者有更长的OS/PFS。

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引用次数: 0

An open-label phase Ib/II study of trastuzumab deruxtecan combined with nivolumab and CAPOX for HER2-low gastroesophageal adenocarcinoma 曲妥珠单抗联合纳武单抗和CAPOX治疗低her2胃食管腺癌的开放标签Ib/II期研究

ESMO Gastrointestinal Oncology

Pub Date : 2025-09-01 DOI: 10.1016/j.esmogo.2025.100207

Y. Aoki , I. Nakayama , Y. Komura , M. Wakabayashi , S. Fukuoka , H. Hara , H. Shoji , M. Furuta , K. Minashi , A. Sato , N. Fuse , N. Sakamoto , T. Kuwata , K. Shitara

Background

Trastuzumab deruxtecan (T-DXd) is the standard of care for previously treated patients with HER2-positive metastatic gastroesophageal adenocarcinoma (mGEA). Exploratory analyses of the DESTINY-Gastric01 trial suggested preliminary antitumor activity of T-DXd in HER2-low mGEA. Additionally, preclinical studies have reported a synergistic effect between T-DXd and anti-programmed cell death protein 1 antibodies. Therefore, T-DXd combined with nivolumab and chemotherapy may provide therapeutic benefits for patients with HER2-low mGEA.

Trial design

EPOC2203 is a single-arm, phase Ib/II study evaluating the efficacy and safety of T-DXd combined with nivolumab and reduced-dose CAPOX as first-line treatment of patients with HER2-low mGEA. Phase Ib uses the traditional 3 + 3 design to determine the recommended phase II dose (RP2D). Patients will receive T-DXd (5.4 mg/kg, day 1) combined with nivolumab (360 mg/body, day 1) and CAPOX (capecitabine: 750 mg/m² twice daily, days 1-14 and oxaliplatin: 70 mg/m², day 1), every 3 weeks. The primary endpoints are the dose-limiting toxicity rate in phase Ib and the objective response rate (ORR) in phase II. Hypothesis testing assumes a null ORR of 58% and an alternative ORR of 80%. The planned sample size is 28 patients treated with RP2D.

背景：曲妥珠单抗德鲁西替康（T-DXd）是先前治疗的her2阳性转移性胃食管腺癌（mGEA）患者的标准治疗方案。DESTINY-Gastric01试验的探索性分析表明，T-DXd在her2低的mGEA中具有初步的抗肿瘤活性。此外，临床前研究已经报道了T-DXd和抗程序性细胞死亡蛋白1抗体之间的协同作用。因此，T-DXd联合纳武单抗和化疗可能为her2 -低mGEA患者提供治疗益处。poc2203是一项单臂Ib/II期研究，评估T-DXd联合纳武单抗和减剂量CAPOX作为her2低mGEA患者一线治疗的有效性和安全性。Ib期采用传统的3 + 3设计来确定推荐的II期剂量（RP2D）。患者将接受T-DXd （5.4 mg/kg，第1天）联合纳武单抗（360 mg/体，第1天）和CAPOX（卡培他滨：750 mg/m2，每日2次，第1-14天，奥沙利铂：70 mg/m2，第1天），每3周一次。主要终点是Ib期的剂量限制性毒性率和II期的客观缓解率（ORR）。假设检验假设零ORR为58%，替代ORR为80%。计划样本量为28例接受RP2D治疗的患者。

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引用次数: 0

Continuum of care and survival in patients with metastatic colorectal cancer: results of the real-world prospective, longitudinal cohort PROMETCO study 转移性结直肠癌患者的持续治疗和生存：真实世界前瞻性、纵向队列PROMETCO研究的结果

ESMO Gastrointestinal Oncology

Pub Date : 2025-09-01 DOI: 10.1016/j.esmogo.2025.100214

M. Koopman , R. Garcia-Carbonero , C. Pinto , A. Mitroshkin , G. Bodoky , L. Mineur , V. Bourgeois , M. Mare , A. Ruiz-Casado , A. Fernandez Montes , J.M. O’Connor , A. Sullivan , E. Choucair , B. Chevallier , F. Marti Marti , J.-B. Bachet

Background

PROMETCO is the first international, prospective study investigating the continuum of care, including prescribing patterns, efficacy and safety in patients with metastatic colorectal cancer (mCRC) at later therapy lines in a real-world setting.

Materials and methods

Adults with mCRC and two disease progressions since diagnosis of mCRC who were willing to receive subsequent treatment and gave informed consent were included. The study consisted of retrospective medical chart data collection pre-inclusion and a prospective observational period post-inclusion. Endpoint data presented include patient characteristics, treatment patterns and efficacy including progression-free survival (PFS) per treatment line and overall survival (OS).

Results

As of July 2023, 738 mCRC patients from 96 centres in 18 countries were recruited. 48.9% of patients had RAS-mutated and 5.0% BRAF-mutated mCRC. Between mCRC diagnosis and death or withdrawal, patients were frequently exposed to fluoropyrimidine (99.0%), irinotecan (96.2%), oxaliplatin (88.4%), anti-vascular endothelial growth factor (78.7%) and anti-epidermal growth factor receptor (40.1%). Median OS was 36.4, 7.1, and 6.6 months from mCRC diagnosis, inclusion into PROMETCO and third-line (3L) treatment initiation, respectively. Median PFS decreased significantly from first-line (9.2 months) to 3L (2.7 months) and remained consistent from 3L to sixth-line treatment (∼2.3 months). Median OS from diagnosis was 32.7, 26.8, and 40.6 months in RAS-mutated, BRAF-mutated, and RAS/BRAF wildtype mCRC patients, respectively.

Conclusions

PROMETCO provided information on real-world prescribing patterns and efficacy. OS from mCRC diagnosis and PFS from 3L and beyond were similar to previous long-term follow-up data from clinical trials.

prometco是第一个国际前瞻性研究，旨在调查转移性结直肠癌（mCRC）患者在现实世界中接受后期治疗的连续性治疗，包括处方模式、疗效和安全性。材料和方法纳入了自诊断为mCRC并有两种疾病进展的成年人，他们愿意接受后续治疗并给予知情同意。该研究包括纳入前的回顾性医学图表数据收集和纳入后的前瞻性观察期。终点数据包括患者特征、治疗模式和疗效，包括每条治疗线的无进展生存期（PFS）和总生存期（OS）。截至2023年7月，从18个国家的96个中心招募了738名mCRC患者。48.9%的患者发生ras突变，5.0%的患者发生braf突变。在mCRC诊断至死亡或停药期间，患者经常暴露于氟嘧啶（99.0%）、伊立替康（96.2%）、奥沙利铂（88.4%）、抗血管内皮生长因子（78.7%）和抗表皮生长因子受体（40.1%）。从mCRC诊断、纳入PROMETCO和三线（3L）治疗开始算起，中位OS分别为36.4、7.1和6.6个月。中位PFS从一线（9.2个月）显著下降到3L（2.7个月），从3L到六线治疗（~ 2.3个月）保持一致。RAS突变、BRAF突变和RAS/BRAF野生型mCRC患者自诊断起的中位生存期分别为32.7、26.8和40.6个月。结论prometco提供了真实世界的处方模式和疗效信息。mCRC诊断的OS和3L及以上的PFS与先前临床试验的长期随访数据相似。

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引用次数: 0

Preoperative immunotherapy with atezolizumab and tiragolumab in patients with colorectal liver metastases—the PURPLE trial 术前使用阿特唑单抗和替拉单抗对结直肠癌肝转移患者进行免疫治疗-紫试验

ESMO Gastrointestinal Oncology

Pub Date : 2025-09-01 DOI: 10.1016/j.esmogo.2025.100226

S. Kasper , E. Elez , U. Neumann , S. Lang , A.-K. Trampe , F. Salva , C. Dopazo , I. Virchow , S. Hartmann , K. Herrmann , J. Tabernero , A. Westendorf , M. Schuler , A. Schramm

Background

In colorectal cancer (CRC), the liver is the most common site of metastasis, which is the leading cause of CRC-related mortality. Hepatic resection offers long-term survival in some patients with CRC liver metastases (CRLM), but recurrence rates remain high (50%-75% within 2 years). Preoperative immunotherapy may induce tumor regression and improve long-term surgical outcomes. The PURPLE trial evaluates the feasibility, safety, and efficacy of short-term preoperative immunotherapy with the anti-programmed death-ligand 1 (PD-L1) antibody atezolizumab and the anti-T cell immunoreceptor with Ig and ITIM domains (TIGIT) antibody tiragolumab in patients with resectable CRLM.

Study design

PURPLE is an international, open-label, multicenter, randomized phase II ‘window of opportunity’ trial. Patients with resectable CRLM are randomized 2 : 1 to receive two cycles of atezolizumab (840 mg) plus tiragolumab (420 mg) before surgery (experimental arm) or immediate surgery (control arm). The primary endpoint is the percentage of patients with complete or major pathological regression of the resected metastases (tumor regression grade 1/2, Rubbia-Brandt criteria). The statistical design follows Simon’s two-stage approach with interim and final analyses comparing pathological response rates using descriptive and exploratory methods. Secondary endpoints include feasibility, safety, post-operative complications, and metabolic response by positron emission tomography. Exploratory studies characterize immune cell infiltration, tumor mutational burden, and circulating tumor DNA dynamics.

在结直肠癌（CRC）中，肝脏是最常见的转移部位，也是导致结直肠癌相关死亡的主要原因。肝切除术为一些CRC肝转移（CRLM）患者提供了长期生存，但复发率仍然很高（2年内为50%-75%）。术前免疫治疗可诱导肿瘤消退，改善远期手术效果。PURPLE试验评估了抗程序性死亡配体1 （PD-L1）抗体atezolizumab和抗t细胞免疫受体Ig和ITIM结构域（TIGIT）抗体tiragolumab在可切除的CRLM患者中的短期术前免疫治疗的可行性、安全性和有效性。研究设计：purple是一项国际、开放标签、多中心、随机II期“机会之窗”试验。可切除的CRLM患者随机分为2组：1组，术前（实验组）或即刻手术（对照组）接受atezolizumab (840mg) + tiragolumab （420mg）两个周期。主要终点是切除的转移灶完全或主要病理消退的患者百分比（肿瘤消退等级1/2，Rubbia-Brandt标准）。统计设计遵循Simon的两阶段方法，使用描述性和探索性方法进行中期和最终分析，比较病理反应率。次要终点包括可行性、安全性、术后并发症和正电子发射断层扫描的代谢反应。探索性研究表征了免疫细胞浸润、肿瘤突变负荷和循环肿瘤DNA动力学。

{"title":"Preoperative immunotherapy with atezolizumab and tiragolumab in patients with colorectal liver metastases—the PURPLE trial","authors":"S. Kasper , E. Elez , U. Neumann , S. Lang , A.-K. Trampe , F. Salva , C. Dopazo , I. Virchow , S. Hartmann , K. Herrmann , J. Tabernero , A. Westendorf , M. Schuler , A. Schramm","doi":"10.1016/j.esmogo.2025.100226","DOIUrl":"10.1016/j.esmogo.2025.100226","url":null,"abstract":"<div><h3>Background</h3><div>In colorectal cancer (CRC), the liver is the most common site of metastasis, which is the leading cause of CRC-related mortality. Hepatic resection offers long-term survival in some patients with CRC liver metastases (CRLM), but recurrence rates remain high (50%-75% within 2 years). Preoperative immunotherapy may induce tumor regression and improve long-term surgical outcomes. The PURPLE trial evaluates the feasibility, safety, and efficacy of short-term preoperative immunotherapy with the anti-programmed death-ligand 1 (PD-L1) antibody atezolizumab and the anti-T cell immunoreceptor with Ig and ITIM domains (TIGIT) antibody tiragolumab in patients with resectable CRLM.</div></div><div><h3>Study design</h3><div>PURPLE is an international, open-label, multicenter, randomized phase II ‘window of opportunity’ trial. Patients with resectable CRLM are randomized 2 : 1 to receive two cycles of atezolizumab (840 mg) plus tiragolumab (420 mg) before surgery (experimental arm) or immediate surgery (control arm). The primary endpoint is the percentage of patients with complete or major pathological regression of the resected metastases (tumor regression grade 1/2, Rubbia-Brandt criteria). The statistical design follows Simon’s two-stage approach with interim and final analyses comparing pathological response rates using descriptive and exploratory methods. Secondary endpoints include feasibility, safety, post-operative complications, and metabolic response by positron emission tomography. Exploratory studies characterize immune cell infiltration, tumor mutational burden, and circulating tumor DNA dynamics.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100226"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacological advances in cannabinoid-based therapies for pancreatic cancer: preclinical efficacy of CCL-106 and its epimers. 基于大麻素治疗胰腺癌的药理学进展：CCL-106及其外显子的临床前疗效。

ESMO Gastrointestinal Oncology

Pub Date : 2025-09-01 Epub Date: 2025-08-07 DOI: 10.1016/j.esmogo.2025.100211

K P Ray, W Cruces, Y Mzannar, A Aboukameel, S Motorwala, T Hadid, M N Al-Hallak, G A Ramirez, T T Tesfatsion, M L Docampo-Palacios, A C Collins, P G Jagtap, A S Azmi, H Y Khan

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal form of cancer with limited treatment options and poor survival rates. Cannabinoids have demonstrated antiproliferative and proapoptotic effects in various cancer types, including PDAC, making them promising therapeutic agents. However, clinical efficacy remains underexplored, particularly for cannabinoids like cannabidiol and tetrahydrocannabinol, which show limited activity against pancreatic cancer.

Materials and methods: We synthesized novel cannabinoid analogues, including CCL-106 and its epimers CCL-114 and CCL-115, which exhibit superior antitumor activity in both two-dimensional and three-dimensional pancreatic cancer models.

Results: These compounds demonstrated substantially lower concentration that causes 50% inhibition of growth (IC₅₀) values in human pancreatic cancer cell lines and enhanced tumor inhibition in pancreatic cancer cell-derived xenograft model without inducing systemic toxicity. Mechanistic studies revealed that the antiproliferative effects of these compounds are primarily mediated through CB2 and GPR55 receptor activation, alongside the generation of reactive oxygen species. Further, CCL-106 has been shown to significantly enhance the efficacy of the standard-of-care chemotherapeutic regimen gemcitabine/nab-paclitaxel in vitro. Moreover, the combination of CCL-106 with gemcitabine/nab-paclitaxel exhibited synergistic effects on growth inhibition of PDAC cells. Additionally, using a patient-derived xenograft model of PDAC, the antitumor efficacy of CCL-115 and CCL-114 in combination with gemcitabine and nab-paclitaxel was demonstrated.

Conclusions: These findings suggest that CCL-106 and its epimers hold potential as effective and less-toxic therapeutic options for PDAC treatment. Further clinical studies are warranted to explore their translational application.

背景：胰腺导管腺癌（PDAC）是一种侵袭性和致死性的癌症，治疗方案有限，生存率低。大麻素在包括PDAC在内的各种类型的癌症中显示出抗增殖和促凋亡作用，使其成为有希望的治疗药物。然而，临床疗效仍有待探索，特别是大麻二酚和四氢大麻酚等大麻素对胰腺癌的作用有限。材料和方法：我们合成了新的大麻素类似物，包括CCL-106及其外显子CCL-114和CCL-115，它们在二维和三维胰腺癌模型中都表现出优异的抗肿瘤活性。结果：这些化合物在人胰腺癌细胞系中显示出显著的低浓度，导致50%的生长抑制（IC50）值，并在胰腺癌细胞来源的异种移植模型中增强肿瘤抑制，而不引起全身毒性。机制研究表明，这些化合物的抗增殖作用主要通过CB2和GPR55受体激活介导，同时产生活性氧。此外，CCL-106已被证明能显著提高吉西他滨/nab-紫杉醇标准化疗方案的体外疗效。此外，CCL-106与吉西他滨/nab-紫杉醇联合使用对PDAC细胞的生长抑制具有协同作用。此外，通过患者来源的PDAC异种移植模型，证明了CCL-115和CCL-114联合吉西他滨和nab-紫杉醇的抗肿瘤效果。结论：这些发现表明，CCL-106及其外显子具有作为PDAC治疗有效且毒性较低的治疗选择的潜力。需要进一步的临床研究来探索其转化应用。

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引用次数: 0

Comprehensive genetic analysis in biliary tract cancer: a prospective single-center experience 胆道癌的综合基因分析：一项前瞻性的单中心研究

ESMO Gastrointestinal Oncology

Pub Date : 2025-08-29 DOI: 10.1016/j.esmogo.2025.100227

M. Rimini , S. Presi , K. Mohammadi , G.B. Pipitone , A.R. Raucci , F. Ratti , F. Pedica , S. Foti , S. Camera , M. Ferrara , L. Passeri , G. Vanella , F. Rossari , F. Lo Prinzi , M. Persano , F. Vitiello , M.G. Cangi , L. Pecciarini , P.G. Arcidiacono , F. Falcinelli , A. Casadei-Gardini

Background

Recent data reported a significant incidence of germline aberrations in biliary tract cancer (BTC) patients, even if conclusive data on that and on its clinical implication are lacking.

Methods

We selected patients for genetic counselling basing on four criteria: personal history of oncologic disease other than BTC; familial history of oncologic disease (considering relatives of first and second grade); patients ≤50 years old; patients presenting a somatic mutation in genes involved in DNA damage repair pathways and mismatch repair.

Results

A total of 22/150 patients met at least one criterion and were directed to genetic counselling. Of these, 17 received the germline test. Four patients carried a pathogenic variant. Some 18/22 patients received the somatic test on tissue samples. Patients who carried a germline pathogenic variant had the same variant also at a somatic level. No statistically significant differences were found in terms of incidence of germline pathogenic variants between patients diagnosed with BTC before the age of 50 years versus after the age of 50 years and in patients with intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma.

Conclusion

The present study is one of the first prospective experiences investigating the role of genetic counselling and germline testing in a BTC setting, thus suggesting several improvements in the selection criteria of patients directed to genetic counselling.

最近的数据报道了胆道癌（BTC）患者中生殖系畸变的显著发生率，尽管缺乏关于这一点及其临床意义的结论性数据。方法根据四项标准选择患者进行遗传咨询：除BTC外的其他肿瘤病史；肿瘤家族史（考虑一、二年级亲属）；患者年龄≤50岁；在参与DNA损伤修复途径和错配修复的基因中出现体细胞突变的患者。结果150例患者中有22例至少符合其中一项标准，并接受了遗传咨询。其中17人接受了生殖细胞测试。四名患者携带致病变异。18/22的患者接受了组织样本的体细胞检测。携带种系致病变异的患者在体细胞水平上也有相同的变异。在50岁前诊断为BTC的患者与50岁后诊断为BTC的患者以及肝内胆管癌和肝外胆管癌患者的种系致病变异发生率方面，未发现统计学差异。结论本研究是首次前瞻性研究遗传咨询和生殖系检测在BTC环境中的作用，从而提出了一些针对遗传咨询患者选择标准的改进。

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引用次数: 0

The increasing burden of early-onset pancreatic and biliary tract cancers: a review of risk factors 早发性胰腺和胆道癌症的负担日益加重：危险因素综述

ESMO Gastrointestinal Oncology

Pub Date : 2025-08-29 DOI: 10.1016/j.esmogo.2025.100204

A. Boilève , M. Brugel , M. Rémond , M. Valéry , M. Ducreux , A. Turpin , C. Smolenschi

The rising incidence of early-onset pancreatic and biliary tract cancers (PBTCs) challenges conventional assumptions that these malignancies primarily affect older populations. Although early-onset PBTCs have a similarly poor prognosis to later-onset cases, emerging evidence suggests that unique or mixed genetic, environmental, and lifestyle factors contribute to their distinct etiologies. This review synthesizes current data on the epidemiology, risk factors, and molecular features of early-onset (in individuals <50 years of age) pancreatic ductal adenocarcinoma and biliary tract cancers. Recent studies indicate a significant increase in early-onset PBTC incidence, with variations by sex, geographic region, and genetic predisposition. Hereditary factors, including BRCA1/2, CDKN2A, and mismatch repair gene mutations, contribute to familial clustering, while other nonhereditary risk factors such as obesity, smoking, pancreatitis, and diabetes seem to disproportionately impact younger patients.

Additionally, environmental exposures, including air pollution, pesticides, and endocrine-disrupting chemicals, are suggested to contribute to carcinogenesis, while changes in microbiota may cause inflammation, immune modulation, and treatment resistance. As the burden of early-onset PBTCs grows, refining screening strategies and integrating microbiome-based risk assessment into biobanking strategies will be critical. Future research should focus on age-stratified genetic risk profiling, microbiota-driven interventions, and personalized therapeutic approaches to improve early detection and patient outcomes.

早发性胰腺和胆道癌症（pbtc）发病率的上升挑战了这些恶性肿瘤主要影响老年人的传统假设。尽管早发性pbtc的预后与晚发性病例相似，但新出现的证据表明，独特或混合的遗传、环境和生活方式因素导致了其独特的病因。本文综述了早发性（50岁以上）胰腺导管腺癌和胆道癌的流行病学、危险因素和分子特征。最近的研究表明，早发性PBTC发病率显著增加，随性别、地理区域和遗传易感性而变化。遗传因素，包括BRCA1/2、CDKN2A和错配修复基因突变，有助于家族聚类，而其他非遗传风险因素，如肥胖、吸烟、胰腺炎和糖尿病，似乎不成比例地影响年轻患者。此外，环境暴露，包括空气污染、农药和内分泌干扰化学物质，被认为有助于致癌，而微生物群的变化可能导致炎症、免疫调节和治疗耐药性。随着早发性pbtc负担的增加，完善筛查策略并将基于微生物组的风险评估整合到生物库策略中将至关重要。未来的研究应该集中在年龄分层的遗传风险分析、微生物群驱动的干预和个性化的治疗方法上，以提高早期发现和患者的预后。

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引用次数: 0

Controversies in upper gastrointestinal cancers—the role of radiotherapy in borderline resectable pancreatic cancer 上消化道肿瘤的争议-放射治疗在交界性可切除胰腺癌中的作用

ESMO Gastrointestinal Oncology

Pub Date : 2025-08-28 DOI: 10.1016/j.esmogo.2025.100232

J. Dekervel , N. Sanford , B. Groot Koerkamp

引用次数: 0

ESMO podcast on upper gastrointestinal cancers—highlights in esophagogastric cancers from ASCO 2025 ESMO播客上消化道癌症- ASCO 2025中食道胃癌的亮点

ESMO Gastrointestinal Oncology

Pub Date : 2025-08-28 DOI: 10.1016/j.esmogo.2025.100233

J. Dekervel , T. Alcindor , S. Lorenzen , E. Smyth

引用次数: 0

Prognostic nutritional index as a prognostic marker in metastatic esophageal squamous-cell carcinoma treated with immune checkpoint inhibitor 免疫检查点抑制剂治疗转移性食管鳞状细胞癌的预后营养指标

ESMO Gastrointestinal Oncology

Pub Date : 2025-08-28 DOI: 10.1016/j.esmogo.2025.100222

K. Yoshino, M. Tamba, H. Osumi, S. Fukuoka, M. Ogura, S. Udagawa, K. Shimozaki, T. Wakatsuki, E. Shinozaki, K. Yamaguchi, K. Chin, A. Ooki

Background

The prognostic nutritional index (PNI) is an inflammation- and nutrition-based indicator that serves as a prognostic factor for various cancer types. This study aimed to evaluate the association between PNI and survival in patients with esophageal squamous-cell carcinoma (ESCC) receiving immune checkpoint inhibitor (ICI)-based therapies.

Materials and methods

This single-center retrospective study included two cohorts: 109 patients treated with nivolumab monotherapy as second-line or later therapy and 92 patients receiving first-line ICI-based treatments (ICI plus chemotherapy or nivolumab plus ipilimumab).

Results

In the nivolumab monotherapy cohort, higher PNI (PNI ≥ 40.5) was linked to longer overall survival (OS) compared with lower PNI (16.2 versus 5.5 months, P = 0.001). In the first-line cohort, 92 patients received ICI plus chemotherapy (n = 60) or nivolumab plus ipilimumab (n = 32). Higher PNI was linked to better OS in both the ICI plus chemotherapy (21.2 versus 7.7 months, P = 0.0008) and the nivolumab plus ipilimumab (not reached versus 10.2 months, P = 0.02) cohorts. Multivariate analysis identified PNI status as an independent prognostic factor in both cohorts. Dynamic changes in PNI (delta PNI ≥ 1.25) 1 month after treatment were linked to better progression-free survival in patients with lower PNI receiving nivolumab monotherapy or nivolumab plus ipilimumab but not in those receiving first-line ICI plus chemotherapy.

Conclusions

PNI and its dynamic changes may serve as useful indicators of prognosis in patients with ESCC receiving ICI-based therapies.

预后营养指数（PNI）是一种基于炎症和营养的指标，可作为各种癌症类型的预后因素。本研究旨在评估PNI与接受免疫检查点抑制剂（ICI）治疗的食管鳞状细胞癌（ESCC）患者生存率之间的关系。材料和方法这项单中心回顾性研究包括两个队列：109例患者接受纳武单抗单一治疗作为二线或后期治疗，92例患者接受一线ICI治疗（ICI加化疗或纳武单抗加伊匹单抗）。在纳武单抗单药治疗队列中，与PNI较低（16.2个月对5.5个月，P = 0.001）相比，PNI较高（PNI≥40.5）与更长的总生存期（OS）相关。在一线队列中，92例患者接受了ICI +化疗（n = 60）或nivolumab + ipilimumab （n = 32）。在ICI +化疗组（21.2个月vs 7.7个月，P = 0.0008）和nivolumab + ipilimumab组（未达到vs 10.2个月，P = 0.02）中，更高的PNI与更好的OS相关。多变量分析确定PNI状态是两个队列中独立的预后因素。治疗1个月后PNI的动态变化（δ PNI≥1.25）与接受纳武单抗单药或纳武单抗联合伊匹单抗的低PNI患者更好的无进展生存有关，但与接受一线ICI加化疗的患者无关。结论spni及其动态变化可作为ESCC患者接受ici治疗后预后的有效指标。

{"title":"Prognostic nutritional index as a prognostic marker in metastatic esophageal squamous-cell carcinoma treated with immune checkpoint inhibitor","authors":"K. Yoshino, M. Tamba, H. Osumi, S. Fukuoka, M. Ogura, S. Udagawa, K. Shimozaki, T. Wakatsuki, E. Shinozaki, K. Yamaguchi, K. Chin, A. Ooki","doi":"10.1016/j.esmogo.2025.100222","DOIUrl":"10.1016/j.esmogo.2025.100222","url":null,"abstract":"<div><h3>Background</h3><div>The prognostic nutritional index (PNI) is an inflammation- and nutrition-based indicator that serves as a prognostic factor for various cancer types. This study aimed to evaluate the association between PNI and survival in patients with esophageal squamous-cell carcinoma (ESCC) receiving immune checkpoint inhibitor (ICI)-based therapies.</div></div><div><h3>Materials and methods</h3><div>This single-center retrospective study included two cohorts: 109 patients treated with nivolumab monotherapy as second-line or later therapy and 92 patients receiving first-line ICI-based treatments (ICI plus chemotherapy or nivolumab plus ipilimumab).</div></div><div><h3>Results</h3><div>In the nivolumab monotherapy cohort, higher PNI (PNI ≥ 40.5) was linked to longer overall survival (OS) compared with lower PNI (16.2 versus 5.5 months, <em>P</em> = 0.001). In the first-line cohort, 92 patients received ICI plus chemotherapy (<em>n</em> = 60) or nivolumab plus ipilimumab (<em>n</em> = 32). Higher PNI was linked to better OS in both the ICI plus chemotherapy (21.2 versus 7.7 months, <em>P</em> = 0.0008) and the nivolumab plus ipilimumab (not reached versus 10.2 months, <em>P</em> = 0.02) cohorts. Multivariate analysis identified PNI status as an independent prognostic factor in both cohorts. Dynamic changes in PNI (delta PNI ≥ 1.25) 1 month after treatment were linked to better progression-free survival in patients with lower PNI receiving nivolumab monotherapy or nivolumab plus ipilimumab but not in those receiving first-line ICI plus chemotherapy.</div></div><div><h3>Conclusions</h3><div>PNI and its dynamic changes may serve as useful indicators of prognosis in patients with ESCC receiving ICI-based therapies.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100222"},"PeriodicalIF":0.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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