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Clinical and molecular characteristics of early-onset pancreatic and biliary cancers 早发性胰腺和胆道癌的临床和分子特征
Pub Date : 2026-01-14 DOI: 10.1016/j.esmogo.2025.100271
C. Smolenschi , M. Rémond , M. Valéry , M. Brugel , M. Ducreux , A. Turpin , A. Boilève
Biliary tract cancer and pancreatic cancer are aggressive malignancies, typically diagnosed in patients >50 years of age. Lately, <50 years of age has been rising, presenting unique challenges and clinical features that distinguish them from late-onset cases.
Here, we review the clinical, biological, and molecular characteristics of early-onset biliary tract cancer and pancreatic cancer and compare them with their late-onset counterparts. We also examine treatment patterns, efficacy, and the potential role of targeted therapies, as well as the potential psychological and social effects on younger patients, with particular emphasis on fertility. We therefore offer insights into the unique challenges and therapeutic strategies in managing early-onset disease.
胆道癌和胰腺癌是侵袭性恶性肿瘤,通常在50岁以上的患者中诊断出来。最近,50岁的患者人数不断上升,呈现出独特的挑战和临床特征,使其与晚发病例区分开来。在这里,我们回顾了早发性胆道癌和胰腺癌的临床、生物学和分子特征,并将它们与晚发性胆道癌进行了比较。我们还研究了治疗模式、疗效和靶向治疗的潜在作用,以及对年轻患者的潜在心理和社会影响,特别强调生育能力。因此,我们提供了独特的挑战和治疗策略,在管理早发性疾病的见解。
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引用次数: 0
Stereotactic body radiotherapy in early-stage hepatocellular carcinoma: a systematic review and meta-analysis 立体定向放射治疗早期肝细胞癌:系统回顾和荟萃分析
Pub Date : 2026-01-14 DOI: 10.1016/j.esmogo.2025.100281
J.K. van Vulpen , M.C. Verwijs , F.K. Gommers , R.A.H. van Eijck van Heslinga , S. van Meer , C.J.R. Verstraete , J. Hagendoorn , M.G.E.H. Lam , N. Haj Mohammad , M.L.J. Smits , M.N.G.J.A. Braat , M.P.W. Intven , J. de Bruijne

Background

First-line treatment strategies for (very) early-stage hepatocellular carcinoma (HCC) include liver transplantation, surgical resection and thermal ablation. Stereotactic body radiotherapy (SBRT) has recently been included in the European Association for the Study of the Liver Clinical Practice Guidelines on the management of hepatocellular carcinoma as an alternative ablative strategy. We aimed to carry out a systematic review and meta-analysis on oncological outcomes and toxicity of SBRT focused on early-stage HCC treatment.

Materials and methods

We carried out a systematic literature search in PubMed, Embase, and the Cochrane Library from inception throughout October 2022. Studies of SBRT targeting treatment-naive (very) early-stage HCC (BCLC 0/A) patients were included.

Results

One prospective and 15 retrospective studies were included in this review. In aggregate, SBRT in 1249 patients resulted in a 1-, 2-, and 3-year local control rate of 94% (95% CI 92%-97%), 89% (95% CI 85%-93%), and 79% (95% CI 68%-90%), respectively. The pooled results of the 1-, 2-, and 3-year overall survival rate were 90% (95% CI 85%-94%), 75% (95% CI 63%-87%), and 59% (95% CI 45%-73%), respectively. Grade ≥3 toxicity was observed in 2% of patients (95% CI 0%-4%).

Conclusion

This systematic review and meta-analysis showed that SBRT is an effective and safe treatment modality for treatment-naive patients with early-stage HCC. The data support incorporation of SBRT as a treatment option in the treatment algorithms for (very) early-stage HCC.
背景:(极)早期肝细胞癌(HCC)的一线治疗策略包括肝移植、手术切除和热消融。立体定向放射治疗(SBRT)最近被纳入欧洲肝脏临床实践研究协会关于肝细胞癌管理的指导方针,作为一种替代消融策略。我们的目的是对早期HCC治疗的SBRT的肿瘤预后和毒性进行系统回顾和荟萃分析。材料和方法从2022年10月开始,我们在PubMed、Embase和Cochrane图书馆进行了系统的文献检索。纳入了针对未接受治疗(极)早期HCC (BCLC 0/A)患者的SBRT研究。结果本综述纳入1项前瞻性研究和15项回顾性研究。总的来说,1249例SBRT患者的1年、2年和3年局部控制率分别为94% (95% CI 92%-97%)、89% (95% CI 85%-93%)和79% (95% CI 68%-90%)。1年、2年和3年总生存率的汇总结果分别为90% (95% CI 85%-94%)、75% (95% CI 63%-87%)和59% (95% CI 45%-73%)。在2%的患者中观察到≥3级毒性(95% CI 0%-4%)。结论本系统综述和荟萃分析显示,SBRT是一种有效且安全的治疗方式,适用于未接受治疗的早期HCC患者。数据支持将SBRT作为一种治疗方案纳入(非常)早期HCC的治疗算法。
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引用次数: 0
The outcomes of elderly patients with localized squamous-cell carcinoma of the anal canal treated with chemoradiation 老年局限性肛管鳞状细胞癌放化疗的疗效观察
Pub Date : 2026-01-08 DOI: 10.1016/j.esmogo.2025.100282
M.P.G. Camandaroba, S. Aguiar Jr., V. Souza e Silva, R.P. Riechelmann

Background

Squamous-cell carcinoma of the anal canal (SCCA) is a rare gastrointestinal malignancy, and its incidence is increasing among the aging population. This study aims to examine treatment efficacy and toxicity in elderly patients and to compare treatment outcomes between elderly and non-elderly patients to inform optimal management strategies for SCCA in older adults.

Patients and methods

This retrospective study evaluates clinical outcomes in elderly (≥70 years) versus non-elderly (<70 years) patients with localized SCCA treated with definitive chemoradiotherapy or radiotherapy alone. The primary endpoints were overall survival (OS) and disease-free survival (DFS), whereas secondary endpoints were cancer-specific survival (CSS), complete response rates and grade 3 or 4 toxicity profiles. Statistical analyses were conducted using descriptive statistics, Kaplan–Meier methods, and Cox proportional hazards models.

Results

The study analyzed 269 patients. Elderly patients had a median age of 77.3 (range 70-83) years and presented with a higher burden of comorbidities and a lower prevalence of human immunodeficiency virus. No significant differences in treatment types or toxicity rates were observed between the groups. The median DFS for elderly patients was 103 months versus 128 months for non-elderly patients (P = 0.43). CSS rates were comparable, showing a rate of 83% at five years for the elderly compared with 85% for non-elderly patients (P = 0.74). Cox regression analyses revealed that cancer stage and treatment completion were significant predictors of DFS and OS.

Conclusion

This study highlights that while elderly patients with SCCA experience similar survival outcomes to their younger counterparts, age-related factors and comorbidities require careful management to optimize treatment efficacy while minimizing toxicity.
肛管鳞状细胞癌(SCCA)是一种罕见的胃肠道恶性肿瘤,其发病率在老龄化人群中呈上升趋势。本研究旨在检查老年患者的治疗效果和毒性,并比较老年和非老年患者的治疗结果,为老年人SCCA的最佳治疗策略提供信息。患者和方法本回顾性研究评估老年人(≥70岁)与非老年人(≤70岁)局限性SCCA患者接受明确放化疗或单独放疗的临床结果。主要终点是总生存期(OS)和无病生存期(DFS),而次要终点是癌症特异性生存期(CSS)、完全缓解率和3级或4级毒性谱。采用描述性统计、Kaplan-Meier方法和Cox比例风险模型进行统计分析。结果本研究分析了269例患者。老年患者的中位年龄为77.3岁(范围70-83岁),合并症负担较高,人类免疫缺陷病毒患病率较低。两组在治疗方式和毒性发生率上均无显著差异。老年患者的中位DFS为103个月,非老年患者为128个月(P = 0.43)。CSS率具有可比性,显示老年人5年时的发生率为83%,而非老年患者为85% (P = 0.74)。Cox回归分析显示,肿瘤分期和治疗完成程度是DFS和OS的显著预测因子。结论本研究强调,尽管老年SCCA患者的生存结果与年轻患者相似,但年龄相关因素和合并症需要仔细管理,以优化治疗效果,同时将毒性降到最低。
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引用次数: 0
Corrigendum to “Feasibility of stereotactic radiotherapy with pembrolizumab in patients with deficient mismatch repair/microsatellite unstable metastatic colorectal cancer” “派姆单抗立体定向放疗治疗失配修复缺陷/微卫星不稳定转移性结直肠癌的可行性”的勘误表
Pub Date : 2026-01-06 DOI: 10.1016/j.esmogo.2025.100279
A. Gandini , V. Martelli , L. Belgioia , S. Puglisi , M. Cremante , V. Murianni , A. Damassi , C. Pirrone , F. Catalano , M. Grassi , L. Trevisan , S. Vagge , V. Andretta , S. Mammoliti , D. Comandini , G. Fornarini , A. Pessino , A. Pastorino , S. Sciallero , A. Puccini , A.F. Sobrero
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引用次数: 0
Clinical outcomes of carbon-ion radiotherapy for residual or recurrent hepatocellular carcinoma after transarterial chemoembolization 碳离子放射治疗经动脉化疗栓塞后残余或复发肝癌的临床疗效
Pub Date : 2026-01-06 DOI: 10.1016/j.esmogo.2025.100280
Y. Sekiguchi , K. Shibuya , S. Tomogane , Y. Miyasaka , S. Kakizaki , M. Okamoto , K. Araki , K. Shirabe , T. Ohno

Background

Transarterial chemoembolization (TACE) or embolization (TAE) for hepatocellular carcinoma (HCC) is often followed by an incomplete response or local recurrence, necessitating effective salvage therapies. Carbon-ion radiotherapy (CIRT) offers potential radiobiological advantages for treating TACE-refractory tumors. This study aimed to evaluate the efficacy and safety of CIRT for residual or recurrent HCC after TACE/TAE.

Patients and methods

We retrospectively analyzed 99 patients (106 lesions) treated with CIRT between 2010 and 2021. Eligible patients had residual or recurrent HCC after 52.8-60.0 Gy [relative biological effectiveness (RBE)] in 4 fractions, or 60.0 Gy (RBE) in 12 fractions for tumors near critical structures. Efficacy endpoints were local control (LC), overall survival (OS), and progression-free survival (PFS). Toxicities were graded using the Common Terminology Criteria for Adverse Events version 4.0, and liver function was monitored using Child–Pugh and albumin–bilirubin (ALBI) scores.

Results

At a median follow-up of 38 months, the 3-year OS, PFS, and LC rates were 70.3%, 34.8%, and 90.7%, respectively. On multivariate analysis, larger tumor size (≥3.5 cm) and poorer baseline liver function (modified ALBI grade ≥2b) were significant predictors of worse OS. The treatment was well tolerated; severe (grade ≥3) late toxicities were rare, including two cases of encephalopathy. There was no statistically significant deterioration in Child–Pugh or ALBI scores following treatment.

Conclusions

CIRT is a safe and effective salvage therapy for TACE-refractory HCC, offering excellent LC, favorable survival outcomes, and preserved liver function.
背景:经动脉化疗栓塞(TACE)或栓塞(TAE)治疗肝细胞癌(HCC)通常会出现不完全缓解或局部复发,需要有效的补救性治疗。碳离子放射治疗(CIRT)为治疗tace难治性肿瘤提供了潜在的放射生物学优势。本研究旨在评估CIRT治疗TACE/TAE术后残留或复发HCC的疗效和安全性。患者和方法我们回顾性分析了2010年至2021年间接受CIRT治疗的99例患者(106个病变)。符合条件的患者在52.8-60.0 Gy[相对生物有效性(RBE)]后有4组HCC残留或复发,在靠近关键结构的肿瘤中有12组肿瘤达到60.0 Gy (RBE)。疗效终点为局部控制(LC)、总生存期(OS)和无进展生存期(PFS)。使用不良事件通用术语标准4.0版对毒性进行分级,使用Child-Pugh和白蛋白-胆红素(ALBI)评分监测肝功能。结果中位随访38个月,3年OS、PFS和LC率分别为70.3%、34.8%和90.7%。在多变量分析中,较大的肿瘤大小(≥3.5 cm)和较差的基线肝功能(改良ALBI分级≥2b)是较差OS的显著预测因子。治疗耐受性良好;严重(≥3级)晚期毒性罕见,包括2例脑病。治疗后Child-Pugh评分和ALBI评分均无统计学意义的恶化。结论scirt是一种安全有效的tace难治性HCC救救性治疗方法,具有良好的LC、良好的生存预后和肝功能保护。
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引用次数: 0
A review of established and new developments in local therapies for liver cancer 肝癌局部治疗的新进展及新进展综述
Pub Date : 2026-01-06 DOI: 10.1016/j.esmogo.2025.100283
P. Seda , R. Abbey , L. Peng , I. Ezeaku , S.T. Laroia , H. Aziz
Liver cancer, especially hepatocellular carcinoma (HCC), which accounts for ∼75%-85% of primary liver cancers, remains a major global health challenge. Because of its high incidence, late diagnosis, and limited curative options, local therapies have become increasingly popular for the multidisciplinary management of HCC, especially in early and intermediate Barcelona Clinic Liver Cancer stages or in medically inoperable patients. This review examines a landscape of local treatment modalities for HCC encompassing radiofrequency ablation, microwave ablation, cryoablation, irreversible electroporation, histotripsy, transarterial chemoembolization, transarterial radioembolization, and stereotactic body radiotherapy. We also highlight their respective advantages and disadvantages, compare their survival outcomes, and identify current gaps in the literature, including the need for further comparisons between safety profiles and efficacy, and the growing landscape that is using different local therapies in a sequential or combinatorial fashion. Emphasis is placed on treatment decisions tailored to tumor burden, liver function, and patient-specific considerations. Expanding access to advanced local therapies in resource-limited settings remains a global priority.
肝癌,特别是占原发性肝癌约75%-85%的肝细胞癌(HCC),仍然是一个主要的全球健康挑战。由于其发病率高、诊断晚、治疗选择有限,局部治疗在HCC的多学科治疗中越来越受欢迎,特别是在早期和中期巴塞罗那临床肝癌阶段或医学上不能手术的患者中。本文综述了肝癌的局部治疗方式,包括射频消融、微波消融、冷冻消融、不可逆电穿孔、组织切片、经动脉化疗栓塞、经动脉放射栓塞和立体定向全身放疗。我们还强调了它们各自的优点和缺点,比较了它们的生存结果,并确定了当前文献中的空白,包括安全性和有效性之间进一步比较的需要,以及以顺序或组合方式使用不同局部治疗的日益增长的前景。重点放在治疗决定量身定制的肿瘤负担,肝功能和患者的具体考虑。在资源有限的环境中扩大获得先进的当地疗法仍然是全球的优先事项。
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引用次数: 0
Clinicopathologic correlates of claudin 18.2 expression in esophagogastric cancer at multiple expression levels claudin 18.2在食管胃癌中多表达水平的临床病理相关性
Pub Date : 2026-01-06 DOI: 10.1016/j.esmogo.2025.100278
C.H. Maeng , A. Alkashash , A. Sy , H. Barnes , S. Bannon , C. Simms , M.R. Strickland , J.N. Glickman , S.J. Klempner

Background

Claudin-18 isoform 2 (CLDN18.2) is a validated therapeutic target in gastric cancer (GC) and gastroesophageal junction cancer (GEJ). The approved antibody zolbetuximab requires higher expression levels (≥75% of tumor cells with 2-3+ membranous staining), yet broader thresholds are increasingly explored. Data on clinicopathologic correlates and biomarker overlap at lower cut-offs remain limited.

Patients and methods

We retrospectively analyzed patients with esophageal cancer (EC), GEJ, or GC who underwent CLDN18.2 immunohistochemistry at a single high-volume center (2023-2025). CLDN18.2 positivity was defined using three thresholds: (i) stringent (75% threshold: ≥75% of tumor cells with 2-3+ staining); (ii) broader (H-score 25; ≥1+ intensity in ≥25% of cells); and (iii) the lowest (H-score 10; ≥1+ intensity in ≥10% of cells). Associations between CLDN18.2 and clinicopathologic variables, including histology and standard biomarkers [human epidermal growth factor receptor 2 (HER2), programmed death-ligand 1 (PD-L1), and mismatch repair (MMR)], were assessed.

Results

In total, 149 patients were included: 43 EC (28.9%), 46 GEJ (30.9%), and 60 GC (40.3%). CLDN18.2 positivity rates were 48.3%, 71.1%, and 73.8% at the 75%, H-score 25, and H-score 10 thresholds, respectively. CLDN18.2 positivity significantly correlated with tumor location, highest in GC and followed by GEJ and EC across thresholds. At the lowest cut-off, positivity was 85.0% in GC, 69.6% in GEJ, and 62.8% in EC (P = 0.030). Histological subtypes were also associated across thresholds: poorly cohesive carcinoma (PCC) demonstrated significantly higher positivity than non-PCC. No significant associations were found with HER2, PD-L1 combined positive score, or MMR. Triple positivity for CLDN18.2, HER2, and PD-L1 was rare (≤5.5%).

Conclusion

CLDN18.2 expression in upper gastrointestinal cancers was significantly associated with gastric origin and PCC histology, independent of HER2 and PD-L1 status. Broadening the threshold for positivity identified nearly three-quarters of patients as CLDN18.2 positive, underscoring the impact of selection cut points on trial eligibility. These findings highlight the potential to expand patient access to CLDN18.2-targeted therapies using lower thresholds.
cldn18亚型2 (CLDN18.2)是胃癌(GC)和胃食管结癌(GEJ)的有效治疗靶点。获得批准的抗体zolbetuximab要求更高的表达水平(≥75%的2-3+膜染色肿瘤细胞),但越来越多的人正在探索更广泛的阈值。临床病理相关数据和生物标志物重叠的下限仍然有限。患者和方法回顾性分析食管癌(EC)、GEJ或GC患者在单个高容量中心(2023-2025)接受CLDN18.2免疫组织化学治疗。CLDN18.2阳性的定义采用三个阈值:(i)严格(75%阈值:≥75%的肿瘤细胞2-3+染色);(ii)更宽(h评分25,≥1+强度≥25%的细胞);(iii)最低(h评分为10,≥10%的细胞强度≥1+)。评估了CLDN18.2与临床病理变量(包括组织学和标准生物标志物[人表皮生长因子受体2 (HER2)、程序性死亡配体1 (PD-L1)和错配修复(MMR)])之间的关系。结果共纳入149例患者:EC 43例(28.9%),GEJ 46例(30.9%),GC 60例(40.3%)。在75%、H-score 25和H-score 10阈值下,CLDN18.2阳性率分别为48.3%、71.1%和73.8%。CLDN18.2阳性与肿瘤位置显著相关,在胃癌中最高,其次是GEJ和EC。在最低临界值下,GC阳性率为85.0%,GEJ阳性率为69.6%,EC阳性率为62.8% (P = 0.030)。组织学亚型也跨阈值相关:低黏结癌(PCC)的阳性率明显高于非PCC。未发现与HER2、PD-L1联合阳性评分或MMR有显著相关性。结论CLDN18.2在上消化道肿瘤中的表达与胃源性和PCC组织学相关,与HER2和PD-L1状态无关。扩大阳性阈值确定了近四分之三的患者为CLDN18.2阳性,强调了选择切割点对试验资格的影响。这些发现强调了使用较低阈值扩大患者获得cldn18.2靶向治疗的潜力。
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引用次数: 0
Growth differentiation factor-15 (GDF-15) in localized pancreatic adenocarcinoma treated with multiagent chemotherapy: a biomarker analysis from the NEOLAP trial (AIO-PAK-0113) 生长分化因子-15 (GDF-15)在多药化疗治疗的局部胰腺腺癌中的作用:NEOLAP试验(aio - pak0113)的生物标志物分析
Pub Date : 2025-12-15 DOI: 10.1016/j.esmogo.2025.100274
B. Kimmel , S.T. Löhnert , F. Wedekink , M. Günther , S. Ormanns , I. Hartlapp , J. Siveke , G. Siegler , S. Boeck , H. Algül , U. Martens , F. Kullmann , T. Ettrich , S. Held , F. Anger , C.-T. Germer , V. Heinemann , J. Wischhusen , V. Kunzmann

Background

The prognostic and predictive role of growth differentiation factor-15 (GDF-15) in localized, non-metastatic pancreatic ductal adenocarcinoma (PDAC) has not yet been explored.

Patients and methods

During the prospective randomized phase II NEOLAP-1 (AIO-PAK-0113) trial for patients with therapy-naive locally advanced (borderline or unresectable) PDAC, blood (n = 131) and tumor tissue samples (n = 39) were collected. Using paired baseline and post-induction chemotherapy (ICT) samples, circulating GDF-15 (cGDF-15) levels were quantified by enzyme-linked immunosorbent assay, and local GDF-15 tumor expression (tGDF-15) was assessed by immunohistochemistry.

Results

Lower baseline cGDF-15 levels (≤0.8 ng/ml) were significantly associated with increased median overall survival [21.92 (95% CI 19.73-24.16) versus 12.68 [95% confidence interval (CI) 10.56-14.81] months, P < 0.001, and significantly higher secondary R0 resection rates (36.5% versus 13.9%, P = 0.0051). In contrast to CA 19-9, cGDF-15 levels significantly increased after ICT [median 1.0 ng/ml [interquartile range (IQR) 0.62-1.5 ng/ml] at baseline versus median 2.37 ng/ml (IQR 1.32-4.43 ng/ml) at week 16], especially after treatment using platinum-based agents. In initial tumor specimens, GDF-15 expression was rare and predominantly confined to tumor cells. tGDF-15 correlated with high cGDF-15 levels at baseline [median 1.8 ng/ml (1.13-2.34 ng/ml) in positive tumor specimens, versus 0.76 ng/ml (0.55-1.17 ng/ml) in negative tumor specimens; P = 0.0087]. Similarly to cGDF-15, tGDF-15 expression increased after ICT (from 10% to 41% positive tumor specimens).

Conclusions

High cGDF-15 levels at baseline are a negative prognostic and predictive biomarker in localized, non-metastatic PDAC. Considering that GDF-15 is further up-regulated by neoadjuvant multiagent chemotherapy, our data, together with recent findings on clinical effects of GDF-15, provide a strong rationale for upfront therapeutic GDF-15 blockade in localized PDAC.
生长分化因子-15 (GDF-15)在局部非转移性胰腺导管腺癌(PDAC)中的预后和预测作用尚未探讨。患者和方法在前瞻性随机II期NEOLAP-1 (AIO-PAK-0113)试验中,收集了未接受治疗的局部晚期(交界性或不可切除)PDAC患者的血液(n = 131)和肿瘤组织样本(n = 39)。使用配对基线和诱导化疗后(ICT)样本,通过酶联免疫吸附法定量循环GDF-15 (cGDF-15)水平,并通过免疫组织化学评估局部GDF-15肿瘤表达(tGDF-15)。结果较低的基线cGDF-15水平(≤0.8 ng/ml)与中位总生存期的增加显著相关[21.92 (95% CI 19.73-24.16)对12.68[95%可信区间(CI) 10.56-14.81]个月,P < 0.001],并与继发R0切除率的增加显著相关(36.5%对13.9%,P = 0.0051)。与CA 19-9相比,ICT后cGDF-15水平显著升高[基线时中位数为1.0 ng/ml[四分位数范围(IQR) 0.62-1.5 ng/ml],而第16周时中位数为2.37 ng/ml (IQR为1.32-4.43 ng/ml)],特别是在使用铂类药物治疗后。在初始肿瘤标本中,GDF-15的表达很少,并且主要局限于肿瘤细胞。tGDF-15与基线时高cGDF-15水平相关[阳性肿瘤标本中位数为1.8 ng/ml (1.13-2.34 ng/ml),阴性肿瘤标本中位数为0.76 ng/ml (0.55-1.17 ng/ml);P = 0.0087]。与cGDF-15类似,ICT后tGDF-15的表达增加(从10%到41%的肿瘤标本阳性)。结论基线时高cGDF-15水平是局部非转移性PDAC的阴性预后和预测性生物标志物。考虑到GDF-15在新辅助多药化疗中进一步上调,我们的数据以及最近关于GDF-15临床效果的研究结果,为局部PDAC的前期治疗性阻断GDF-15提供了强有力的理论依据。
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引用次数: 0
Impact of diabetes mellitus on treatment efficacy in patients with advanced pancreatic cancer: the Italian, multicenter, observational PANCAKE study 糖尿病对晚期胰腺癌患者治疗疗效的影响:意大利多中心观察性PANCAKE研究
Pub Date : 2025-12-15 DOI: 10.1016/j.esmogo.2025.100276
P. Andena , G. Tine , F. Nichetti , A. Pretta , L. Bartalini , S. Ljevar , A. Michelotti , L. Salvatore , M. Prisciandaro , A. Franza , G. Grelli , P. Ziranu , M. Bensi , V. Mazzaferro , J. Coppa , C. Sciortino , G. Zapelloni , C. Pircher , S.K. Garattini , C. Vivaldi , M. Niger

Background

Diabetes mellitus (DM) is a known risk factor for pancreatic ductal adenocarcinoma (PDAC). Preclinical evidence suggests higher glucose levels may enhance chemotherapy injury to PDAC cells. Clinical evidence of DM’s impact in patients with PDAC receiving palliative treatment remains conflicting, however.

Materials and methods

PANCAKE, an Italian multicenter observational study, assessed the impact of DM and blood glucose levels on progression-free survival during first-line treatment and overall survival (OS) in patients with advanced PDAC.

Results

Among 663 patients with available baseline and on-treatment glycemic values, DM was confirmed in 193 patients (29.1%). Pre-existing DM was associated with a modest but significant OS benefit [median OS 11.6 versus 10.3 months, adjusted hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.67-0.99; P = 0.036]. This benefit was significantly associated with the chemotherapy regimen: it was observed only in patients treated with first-line gemcitabine–nab-paclitaxel, but not with FOLFIRINOX. A longitudinal, Bayesian joint modelling approach accounting for the concomitant use of glucose-lowering medications confirmed a statistically significant, but clinically modest prognostic effect of glycemic trends, as a 10 mg/dl-point increase from baseline blood glucose values resulted associated with a 4% reduction in the risk of death (HR for OS 0.9967, 95% CI 0.9939-0.9995).

Conclusions

DM and higher blood glucose levels show a statistically significant, though clinically modest, impact on the OS of patients affected by advanced PDAC, which may be differential according to the chemotherapy regimen. This evidence lays the foundations to guide future studies on pharmacological and dietary approaches targeting tumor metabolism in this setting.
背景:糖尿病(DM)是胰腺导管腺癌(PDAC)的已知危险因素。临床前证据表明,较高的葡萄糖水平可能会增加化疗对PDAC细胞的损伤。然而,糖尿病对接受姑息治疗的PDAC患者的影响的临床证据仍然存在冲突。意大利一项多中心观察性研究spancake评估了糖尿病和血糖水平对晚期PDAC患者一线治疗期间无进展生存期和总生存期(OS)的影响。结果在663例基线和治疗时血糖值可用的患者中,有193例(29.1%)确诊为糖尿病。既往存在糖尿病与中度但显著的生存获益相关[中位生存期11.6 vs 10.3个月,调整风险比(HR) 0.82, 95%可信区间(CI) 0.67-0.99;P = 0.036]。这一益处与化疗方案显著相关:仅在一线吉西他滨- nab-紫杉醇治疗的患者中观察到,而在FOLFIRINOX治疗的患者中没有观察到。考虑到同时使用降糖药物的纵向贝叶斯联合建模方法证实了血糖趋势具有统计学意义,但临床适度的预后影响,因为从基线血糖值增加10 mg/dl点导致死亡风险降低4%(风险比为0.9967,95% CI为0.9939-0.9995)。结论sdm和高血糖水平对晚期PDAC患者OS的影响具有统计学意义,但临床表现不明显,且可能因化疗方案不同而有所差异。这一证据为指导未来针对这种情况下肿瘤代谢的药理学和饮食方法的研究奠定了基础。
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引用次数: 0
Highlights in oesophagogastric cancers from ESMO congress 2025 2025年ESMO大会上的食道胃癌亮点
Pub Date : 2025-12-15 DOI: 10.1016/j.esmogo.2025.100275
A. Petrillo , F. Pietrantonio , T. Fleitas-Kanonnikoff
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引用次数: 0
期刊
ESMO Gastrointestinal Oncology
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