ESMO Open最新文献

英文中文

43P Late toxicities after chemoradiotherapy for locally advanced cervical cancer: A large real-world cohort from Brazil 局部晚期宫颈癌放化疗后的晚期毒性：来自巴西的一个大型现实世界队列

IF 10.6 2区医学 Q1 ONCOLOGY

ESMO Open

Pub Date : 2026-07-01 Epub Date: 2026-07-02 DOI: 10.1016/j.esmoop.2026.108068

J.C. Martins, L.Y.S. Duraes, J.V.F. Carvalho, F.L. Eiriz, M.J. Folquito, G.D. Goldenberg, L.D.M. Graziano, V.P. Jatobá, A.L.D.S. Neto, L.G. Rebello, K.D. Rego, Y. Shinkado, M.D.P. Estevez Diz, R. Colombo Bonadio, H.D.A. Carvalho, S.R. Stuart, F. Gabrielli, S.C. Costa

引用次数: 0

46P Global burden and trend of cervical cancer in high-income countries: A 30-year analysis of disease dynamics 高收入国家宫颈癌的全球负担和趋势：30年疾病动态分析

IF 10.6 2区医学 Q1 ONCOLOGY

ESMO Open

Pub Date : 2026-07-01 Epub Date: 2026-07-02 DOI: 10.1016/j.esmoop.2026.108071

K. Jazieh, A. Zarif

引用次数: 0

12P Targeting α-adrenergic signaling in ovarian cancer progression: Therapeutic potential of quinazolines 12P靶向α-肾上腺素能信号在卵巢癌进展中的作用：喹唑啉类药物的治疗潜力

IF 10.6 2区医学 Q1 ONCOLOGY

ESMO Open

Pub Date : 2026-07-01 Epub Date: 2026-07-02 DOI: 10.1016/j.esmoop.2026.108037

M. Escar, F. Rodríguez, P. Caruana, M. Edwards, C. Soler, R. Munoz, I. Espadaler, M. Gámez, C. Martín Lorente, M.V. Cespedes

引用次数: 0

17P Single-cell profiling guides a disease-tailored TCR-based immunotherapy for epithelial ovarian cancer 17P单细胞分析指导基于疾病的基于tcr的上皮性卵巢癌免疫治疗

IF 10.6 2区医学 Q1 ONCOLOGY

ESMO Open

Pub Date : 2026-07-01 Epub Date: 2026-07-02 DOI: 10.1016/j.esmoop.2026.108042

M.C.C. Maffia, A. Simioni, E. Tassi, A. Bergamini, C. Balestrieri, Z. Magnani, B. Camisa, D. Abbati, L. Perani, G. Candotti, L. Bocciolone, G. Pavone, M. Candiani, M. Sant' Angelo, C. Doglioni, F. Sanvito, B. Shultes, A. Prodeus, E. Ruggiero, C. Bonini

引用次数: 0

19P Validation of 'SET' architectural patterns and tumor-infiltrating lymphocytes (TILs) as accessible biomarkers for predicting platinum sensitivity in high-grade serous ovarian cancer (HGSOC): Bridging the gap in resource-limited settings 验证“SET”结构模式和肿瘤浸润淋巴细胞（til）作为预测高级别浆液性卵巢癌（HGSOC）铂敏感性的可获得的生物标志物：弥合资源有限环境的差距

IF 10.6 2区医学 Q1 ONCOLOGY

ESMO Open

Pub Date : 2026-07-01 Epub Date: 2026-07-02 DOI: 10.1016/j.esmoop.2026.108044

A. Ghosh

引用次数: 0

34P Decoding cytokine signatures: Association of circulating interleukins with PFS in EGFR-mutant advanced NSCLC 34P解码细胞因子特征：egfr突变晚期非小细胞肺癌中循环白细胞介素与PFS的关系

IF 10.6 2区医学 Q1 ONCOLOGY

ESMO Open

Pub Date : 2026-07-01 Epub Date: 2026-07-03 DOI: 10.1016/j.esmoop.2026.107813

S. Meedimale, S.S. Panda, L. Moharana, G. Biswas, C. Mohana Vamsy, S. Harankhedkar

引用次数: 0

APOBEC mutational signatures predict immune checkpoint inhibitor benefit in TMB-low metastatic NSCLC independent of PD-L1 status APOBEC突变特征预测免疫检查点抑制剂在tmb -低转移性非小细胞肺癌中的益处，与PD-L1状态无关。

IF 10.6 2区医学 Q1 ONCOLOGY

ESMO Open

Pub Date : 2026-07-01 Epub Date: 2026-06-30 DOI: 10.1016/j.esmoop.2026.108305

A. Yaacov, A. Grinshpun, R. Gillis, A. Pomerantz, R. Basheer, N. Asna, N. Peled

Background

∼60%-70% of patients with metastatic non-small cell lung cancer (NSCLC) have relatively low tumor mutational burden (TMB), with limited biomarker-guided immunotherapy options beyond programmed death-ligand 1 (PD-L1) expression. APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) mutational signatures, defined by characteristic genomic footprints, are associated with higher TMB and a better response to immune checkpoint inhibitors (ICIs). However, whether APOBEC independently predicts ICI response in TMB-low tumors has not been established.

Materials and methods

We analyzed 857 ICI-treated and 1328 ICI-untreated TMB-low (<10 mut/Mb) patients with metastatic NSCLC from the MSK-CHORD cohort. APOBEC status was classified using MESiCA, a machine-learning algorithm for mutational signature detection from targeted gene panels. Predictive value was established through treatment interaction testing, multivariate adjustment, propensity score weighting, and landmark analyses. External validation included 82 TMB-low patients from published whole-exome sequencing studies.

Results

APOBEC-positive patients (n = 52, 6.1%) had significantly improved overall survival [median 33.7 versus 17.4 months; hazard ratio (HR) 0.60, 95% confidence interval (CI) 0.42-0.85, P = 0.004]. No such benefit was observed in ICI-untreated patients (HR 0.98, P = 0.85), with significant treatment interaction (P = 0.032), confirming a predictive rather than prognostic effect. APOBEC remained independently predictive after adjustment for PD-L1 status and age (adjusted HR 0.57, P = 0.002). The benefit was particularly pronounced in PD-L1-negative ICI-treated patients (HR 0.51, P = 0.002). The effect was robust across propensity score, landmark, and bootstrap analyses. External validation confirmed independent APOBEC benefit (adjusted HR 0.23, P = 0.020).

Conclusions

APOBEC mutational signatures represent a robust predictive biomarker for ICI response in TMB-low metastatic NSCLC, identifying responders particularly among PD-L1-negative patients where biomarker guidance is most needed, detectable from targeted gene panels used in routine clinical practice.

背景：约60%-70%的转移性非小细胞肺癌（NSCLC）患者具有相对较低的肿瘤突变负担（TMB），除了程序性死亡配体1 （PD-L1）表达外，生物标志物引导的免疫治疗选择有限。APOBEC（载脂蛋白B mRNA编辑酶，催化多肽样）突变特征，由特征基因组足迹定义，与更高的TMB和对免疫检查点抑制剂（ICIs）的更好反应相关。然而，APOBEC是否能独立预测TMB-low肿瘤的ICI反应尚未确定。材料和方法：我们分析了857例接受ici治疗的患者和1328例未经ici治疗的tmb低患者(结果：apobec阳性患者（n = 52, 6.1%）的总生存期显著提高[中位33.7 vs 17.4个月；风险比（HR） 0.60, 95%可信区间（CI） 0.42 ~ 0.85, P = 0.004。未接受ici治疗的患者未观察到这种获益（HR 0.98, P = 0.85），与显著的治疗相互作用（P = 0.032），证实了预测作用而非预后作用。调整PD-L1状态和年龄后，APOBEC仍然是独立预测指标（调整后的HR 0.57, P = 0.002）。在pd - l1阴性的ci治疗患者中，获益尤其明显（HR 0.51, P = 0.002）。在倾向评分、里程碑和自举分析中，效果是稳健的。外部验证证实独立的APOBEC获益（调整后HR 0.23, P = 0.020）。结论：APOBEC突变特征代表了tmb低转移性NSCLC中ICI反应的强大预测生物标志物，特别是在最需要生物标志物指导的pd - l1阴性患者中识别应答者，可从常规临床实践中使用的靶向基因面板中检测到。

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引用次数: 0

Molecular effects of ovarian stimulation for fertility preservation in breast cancer: a paired-biopsy analysis 卵巢刺激对乳腺癌生育能力保存的分子效应：一项成对活检分析。

IF 10.6 2区医学 Q1 ONCOLOGY

ESMO Open

Pub Date : 2026-07-01 Epub Date: 2026-07-07 DOI: 10.1016/j.esmoop.2026.108281

Y. Barral El Gaoui, F. Brasó-Maristany, A. Borrás Capó, G. Casals, I. Agustí, G. Altinier, N. Chic Ruche, P. Galván, S. Ganau, B. González-Farre, C. Salvador, S. Peon, M. Méndez, M. Vidal, A. Prat, D. Manau Trullás

Background

Fertility preservation is increasingly offered to young women diagnosed with breast cancer. Although available clinical evidence suggests that controlled ovarian stimulation (COS) does not compromise oncological outcomes, its direct biological effect on tumor tissue remains poorly defined.

Patients and methods

In this single-center, longitudinal, prospective paired-biopsy study, 21 premenopausal women (age <40 years) with stage II-III breast cancer underwent paired diagnostic and post-COS tumor biopsies at the Breast Cancer Unit, Clínic BCCC (October 2020-September 2024). COS was carried out with recombinant follicle-stimulating hormone plus concurrent letrozole (5 mg/day) using a random-start protocol. After oocyte retrieval, a second core tumor biopsy was obtained within 24 to 48 hours. Immunohistochemistry [estrogen receptor (ER), progesterone receptor (PR), Ki-67, human epidermal growth factor receptor 2 (HER2,) tumor-infiltrating lymphocytes (TILs)] and PAM50 gene-expression profiling were carried out. Paired analyses evaluated changes in protein markers, gene-by-gene expression, intrinsic subtype, and risk of recurrence (ROR) score, applying a false discovery rate (FDR) <5% for significance.

Results

No significant differences were detected in ER (P = 0.962), PR (P = 0.562), Ki-67 (P = 0.768), or TILs (P = 0.172) after COS. Post-stimulation Ki-67 was not associated with stimulation duration (r = 0.047; P = 0.839), total gonadotropin dose (r = 0.026; P = 0.911), or peak estradiol levels (r = 0.121; P = 0.610). Transcriptomic analysis identified downregulation of 11/72 genes (15.3%), including proliferation-associated genes CDC6, CENPF, EXO1, and RRM2, although none met significance thresholds after FDR correction. PAM50 intrinsic subtype remained stable (luminal A 23.8%, luminal B 28.6%, HER2-enriched 19.0%, basal-like 23.8%), with only two borderline shifts between luminal A and luminal B. Five mild ROR variations were observed (four decreases and one increase), all small in magnitude on the continuous scale.

Conclusions

COS with concurrent letrozole was not associated with short-term molecular changes in breast tumor tissue. These findings provide biological reassurance regarding the safety of COS for fertility preservation in young women with breast cancer.

背景：越来越多的诊断为乳腺癌的年轻女性选择保留生育能力。尽管现有的临床证据表明，可控卵巢刺激（COS）不会损害肿瘤预后，但其对肿瘤组织的直接生物学效应仍不明确。患者和方法：在这项单中心，纵向，前瞻性配对活检研究中，21名绝经前妇女（年龄）。结果：COS后ER (P = 0.962), PR (P = 0.562), Ki-67 （P = 0.768）或TILs （P = 0.172）无显著差异。刺激后Ki-67与刺激持续时间（r = 0.047; P = 0.839）、促性腺激素总剂量（r = 0.026; P = 0.911）或雌二醇峰值水平（r = 0.121; P = 0.610）无关。转录组学分析发现11/72个基因（15.3%）下调，包括增殖相关基因CDC6、CENPF、EXO1和RRM2，尽管在FDR校正后没有一个达到显著阈值。PAM50内在亚型保持稳定（管腔A 23.8%，管腔B 28.6%， her2富集19.0%，基底样23.8%），在管腔A和管腔B之间仅有2次边界移位，5次轻微ROR变化（4次降低，1次升高），在连续尺度上均较小。结论：来曲唑并发COS与乳腺肿瘤组织的短期分子变化无关。这些发现为年轻乳腺癌患者使用COS保存生育能力的安全性提供了生物学上的保证。

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引用次数: 0

Phase II study of trastuzumab-pkrb plus gedatolisib in patients with HER2-positive metastatic breast cancer who progressed after two or more HER2-directed therapies 曲妥珠单抗-pkrb联合gedatolisib治疗her2阳性转移性乳腺癌患者的II期研究，这些患者在接受两次或两次以上her2定向治疗后进展。

IF 10.6 2区医学 Q1 ONCOLOGY

ESMO Open

Pub Date : 2026-07-01 Epub Date: 2026-07-08 DOI: 10.1016/j.esmoop.2026.107706

J.W. Kim, Y.H. Park, S. Lee, H.K. Ahn, J. Bae, S. Park, H. Chae, J.H. Kim, K.-H. Lee, M.H. Kim, K.E. Lee, M.J. Kang, I.H. Park, Y.s. Chae, G.W. Lee, K.U. Park, E.M. Lee, J.H. Park, J.E. Kim, H.J. Kim, K.H. Park

Background

To evaluate the activity and safety of trastuzumab-pkrb plus gedatolisib in patients with treatment-refractory human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) harboring phosphatidylinositol 3-kinase (PI3K) pathway alterations.

Patients and methods

In this multicenter, single-arm phase II study, eligible patients had HER2-positive MBC with PI3K pathway aberrations identified by tumor or circulating cell-free DNA and had progressed after at least two prior HER2-directed therapies. Patients received trastuzumab-pkrb (8 mg/kg loading dose, then 6 mg/kg IV every 3 weeks) plus gedatolisib (180 mg IV on days 1, 8 and 15 of each 21-day cycle). The primary endpoint was objective response rate (ORR), 90% power with one-sided 5% type I error, assuming a 25% target for the combination therapy. The trial closed early after 44 patients due to changes in regulatory sponsorship.

Results

PI3K pathway alterations included PIK3CA kinase domain mutations (59%), helical domain mutations (25%), and PTEN deletions (5%). The ORR was 43.2% [95% confidence interval (CI) 28.3%-59.0%], with two complete and 17 partial responses. Disease control rate was 86.4%. Median progression-free survival (PFS) was 6.01 months (95% CI 5.03-7.69), and median overall survival (OS) was 24.74 months (95% CI 17.28-NA) after 32.05 months of follow-up. Oral mucositis (90.9%; 15.9% grade ≥3) and hyperglycemia (25.0%; 2.3% grade 3) were most frequent, and no treatment-related deaths occurred. Early circulating tumor DNA dynamics predicted PFS and OS.

Conclusion

Trastuzumab-pkrb plus gedatolisib demonstrated a 43.2% response rate and manageable toxicity, supporting dual HER2/PI3K pathway targeting in heavily pretreated HER2-positive MBC.

背景：评估曲妥珠单抗-pkrb联合格datolisib治疗难治性人表皮生长因子受体2 （HER2）阳性转移性乳腺癌（MBC）伴有磷脂酰肌醇3-激酶（PI3K）通路改变的患者的活性和安全性。患者和方法：在这项多中心、单臂II期研究中，符合条件的患者患有her2阳性MBC，经肿瘤或循环无细胞DNA鉴定为PI3K通路异常，并且在至少两次her2定向治疗后进展。患者接受曲妥珠单抗-pkrb（负荷剂量为8mg /kg，然后每3周静脉注射6mg /kg）加gedatolisib（每21天周期的第1、8和15天静脉注射180mg）。主要终点是客观缓解率（ORR）， 90%功率，单侧5% I型误差，假设联合治疗的目标为25%。由于监管资助的变化，该试验在44名患者后提前结束。结果：PI3K通路改变包括PIK3CA激酶结构域突变（59%）、螺旋结构域突变（25%）和PTEN缺失（5%）。ORR为43.2%[95%可信区间（CI） 28.3%-59.0%]， 2例完全缓解，17例部分缓解。疾病控制率为86.4%。随访32.05个月后，中位无进展生存期（PFS）为6.01个月（95% CI 5.03-7.69），中位总生存期（OS）为24.74个月（95% CI 17.28-NA）。口腔黏膜炎（90.9%，15.9%≥3级）和高血糖（25.0%，2.3% 3级）最为常见，未发生治疗相关死亡。早期循环肿瘤DNA动力学预测PFS和OS。结论：曲妥珠单抗-pkrb联合gedatolisib的缓解率为43.2%，毒性可控，支持HER2/PI3K双通路靶向治疗重度预处理的HER2阳性MBC。

{"title":"Phase II study of trastuzumab-pkrb plus gedatolisib in patients with HER2-positive metastatic breast cancer who progressed after two or more HER2-directed therapies","authors":"J.W. Kim, Y.H. Park, S. Lee, H.K. Ahn, J. Bae, S. Park, H. Chae, J.H. Kim, K.-H. Lee, M.H. Kim, K.E. Lee, M.J. Kang, I.H. Park, Y.s. Chae, G.W. Lee, K.U. Park, E.M. Lee, J.H. Park, J.E. Kim, H.J. Kim, K.H. Park","doi":"10.1016/j.esmoop.2026.107706","DOIUrl":"10.1016/j.esmoop.2026.107706","url":null,"abstract":"<div><h3>Background</h3><div>To evaluate the activity and safety of trastuzumab-pkrb plus gedatolisib in patients with treatment-refractory human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) harboring phosphatidylinositol 3-kinase (PI3K) pathway alterations.</div></div><div><h3>Patients and methods</h3><div>In this multicenter, single-arm phase II study, eligible patients had HER2-positive MBC with PI3K pathway aberrations identified by tumor or circulating cell-free DNA and had progressed after at least two prior HER2-directed therapies. Patients received trastuzumab-pkrb (8 mg/kg loading dose, then 6 mg/kg IV every 3 weeks) plus gedatolisib (180 mg IV on days 1, 8 and 15 of each 21-day cycle). The primary endpoint was objective response rate (ORR), 90% power with one-sided 5% type I error, assuming a 25% target for the combination therapy. The trial closed early after 44 patients due to changes in regulatory sponsorship.</div></div><div><h3>Results</h3><div>PI3K pathway alterations included <em>PIK3CA</em> kinase domain mutations (59%), helical domain mutations (25%), and <em>PTEN</em> deletions (5%). The ORR was 43.2% [95% confidence interval (CI) 28.3%-59.0%], with two complete and 17 partial responses. Disease control rate was 86.4%. Median progression-free survival (PFS) was 6.01 months (95% CI 5.03-7.69), and median overall survival (OS) was 24.74 months (95% CI 17.28-NA) after 32.05 months of follow-up. Oral mucositis (90.9%; 15.9% grade ≥3) and hyperglycemia (25.0%; 2.3% grade 3) were most frequent, and no treatment-related deaths occurred. Early circulating tumor DNA dynamics predicted PFS and OS.</div></div><div><h3>Conclusion</h3><div>Trastuzumab-pkrb plus gedatolisib demonstrated a 43.2% response rate and manageable toxicity, supporting dual HER2/PI3K pathway targeting in heavily pretreated HER2-positive MBC.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"11 7","pages":"Article 107706"},"PeriodicalIF":10.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148411078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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5P Functional masking of CD3 engagement via IL10 reprograms TCE-induced T cell dysfunction and enables durable solid tumor eradication 5P通过il - 10对CD3参与的功能屏蔽重新编程tce诱导的T细胞功能障碍，并实现持久的实体肿瘤根除

IF 10.6 2区医学 Q1 ONCOLOGY

ESMO Open

Pub Date : 2026-07-01 Epub Date: 2026-07-03 DOI: 10.1016/j.esmoop.2026.107783

Z. Yang, Y-X. Fu, X. Wang

引用次数: 0

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