European Journal of Cancer最新文献_第3页

Prognostic value of patient-reported outcomes in advanced or metastatic melanoma patients treated with immunotherapy: Findings from the CheckMate-067 study 接受免疫疗法治疗的晚期或转移性黑色素瘤患者患者报告结果的预后价值：CheckMate-067研究结果。

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-28 DOI: 10.1016/j.ejca.2024.115099

Dirk Schadendorf , Jennifer Lord-Bessen , Flavia Ejzykowicz , Ling Shi , Peiwen Yu , Swetha Srinivasan

Objective

Patient-reported outcomes (PROs) that predict survival in cancer patients have yet to be realized as practical tools for clinicians to make better treatment decisions. To identify such PROs in adults with advanced melanoma treated with immunotherapy, this study used 7.5-year follow-up data from CheckMate-067, a phase 3, randomized, double-blind study of nivolumab or nivolumab plus ipilimumab versus ipilimumab.

Methods

PRO data assessed using the European Organization of Research for the Treatment of Cancer Core-30 and EQ-5D-3L at baseline and during subsequent visits after treatment initiation were pooled across treatment arms. Associations between baseline PRO or change from baseline (CFB) scores with survival outcomes (progression-free survival [PFS], overall survival [OS], and melanoma-specific survival [MSS]) were examined using Cox proportional hazards models for PFS or OS and cause-specific hazard models for MSS.

Results

Baseline and CFB scores for most PRO domains, especially for physical functioning, global health status/quality of life (GHS/QoL), fatigue, and EQ-5D visual analog scale (VAS), were prognostic of all survival outcomes. Achieving meaningful improvement/maintenance of baseline PRO scores at 12 weeks following treatment initiation predicted better survival outcomes than with meaningful worsening from baseline.

Conclusions

PROs at baseline and during treatment, particularly for physical functioning, GHS/QoL, fatigue, and EQ-VAS, were prognostic of survival outcomes. This knowledge may accelerate development of prognostic tools to manage treatment in patients with previously untreated unresectable or metastatic melanoma who undergo immunotherapy.

目的：预测癌症患者生存期的患者报告结果（PROs）尚未成为临床医生做出更好治疗决策的实用工具。为了确定接受免疫疗法治疗的晚期黑色素瘤成人患者的此类PROs，本研究使用了CheckMate-067的7.5年随访数据，这是一项关于尼妥珠单抗或尼妥珠单抗加伊匹单抗与伊匹单抗的3期随机双盲研究：对各治疗组基线和治疗开始后的后续访问中使用欧洲癌症治疗研究组织Core-30和EQ-5D-3L评估的PRO数据进行了汇总。基线PRO评分或基线变化（CFB）评分与生存结果（无进展生存期[PFS]、总生存期[OS]和黑色素瘤特异性生存期[MSS]）之间的关系采用Cox比例危险模型（PFS或OS）和病因特异性危险模型（MSS）进行检验：大多数PRO领域的基线和CFB评分，尤其是身体机能、总体健康状况/生活质量（GHS/QoL）、疲劳和EQ-5D视觉模拟量表（VAS），对所有生存结果都有预后作用。在开始治疗后的12周内，如果基线PRO评分得到有意义的改善/维持，则预示着比基线有意义的恶化更好的生存结果：基线和治疗期间的PRO，尤其是身体功能、GHS/QoL、疲劳和EQ-VAS，对生存结果具有预示作用。这些知识可能会促进预后工具的开发，以管理接受免疫疗法的既往未经治疗的不可切除或转移性黑色素瘤患者的治疗。

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引用次数: 0

Liquid biopsy with plasma Epstein-Barr virus DNA characterizes biological relapse for the prediction of cancer recurrence in non-disseminated nasopharyngeal carcinoma 利用血浆 Epstein-Barr 病毒 DNA 进行液体活检可确定生物复发的特征，从而预测非扩散性鼻咽癌的复发情况

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-26 DOI: 10.1016/j.ejca.2024.115098

Qixian Zhang , Lin Zhu , Wenjiao Lv , Tingting Xu , Chunying Shen , Wei Qian , Peiyao Liu , Hongmei Ying , Xiayun He , Chaosu Hu , Xin Zhou , Xueguan Lu

Purpose

To investigate whether a bounce in plasma Epstein-Barr virus (EBV) DNA during posttreatment surveillance of nasopharyngeal carcinoma (NPC) informs the risk of clinical recurrence and its implication for early therapeutic intervention.

Methods

950 non-disseminated NPC patients with completed remission in 3 months after treatment were retrospectively screened. Detectable EBV DNA with no evidence of clinical relapse during follow-up was deemed as DNA bounce. The diagnostic and prognostic performance of EBV DNA bounce was assessed for subsequent failures.

Results

Tumor recurrence occurred in 6.6 %, 10.1 % and 65.8 % in the group with persistently negative EBV DNA, single positive test and ≥ 2 positive tests, respectively. EBV DNA bounce over twice was associated with worse disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) than the other two groups. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for the prediction of recurrence were 0.56, 0.95, 0.66, 0.93 and 0.90 using two positive tests, which were hence deemed as biological relapse. Serial cutoffs (EBV DNA 1 ≥ 40 copies/ml or EBV DNA 2 ≥100 copies/ml) further defined a high-risk subgroup with an eventual recurrence rate of 77.9 % and 3-year DFS of merely 20.5 %. Prophylactic medical intervention with capecitabine or S1 significantly improved the 3-year DFS when compared to those with observation.

Conclusions

The earliest two positive tests of EBV DNA represent a biomarker of biological relapse that allows early detection of clinical recurrence in EBV-related NPC. For high-risk biological relapse, preemptive intervention provides potential survival benefits.

目的研究在鼻咽癌（NPC）治疗后监测期间，血浆中爱泼斯坦-巴氏病毒（EBV）DNA的反弹是否能告知临床复发的风险及其对早期治疗干预的影响。可检测到 EBV DNA 且随访期间无临床复发证据的患者被视为 DNA 反弹。结果EBV DNA持续阴性组、单次检测阳性组和≥2次检测阳性组的肿瘤复发率分别为6.6%、10.1%和65.8%。与其他两组相比，EBV DNA反跳两次以上与更差的无病生存期（DFS）、无局部复发生存期（LRRFS）和无远处转移生存期（DMFS）相关。预测复发的灵敏度、特异性、阳性预测值（PPV）、阴性预测值（NPV）和准确度分别为 0.56、0.95、0.66、0.93 和 0.90（使用两次阳性测试，因此被视为生物学复发）。序列截断值（EBV DNA 1 ≥ 40拷贝/毫升或EBV DNA 2 ≥ 100拷贝/毫升）进一步定义了高风险亚组，其最终复发率为77.9%，3年DFS仅为20.5%。与观察组相比，使用卡培他滨或 S1 进行预防性医疗干预可显著改善 3 年 DFS。对于高风险的生物复发，先期干预可为患者带来潜在的生存益处。

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引用次数: 0

Incidence and prognosis of cutaneous melanoma in European adolescents and young adults (AYAs): EUROCARE-6 retrospective cohort results 欧洲青少年皮肤黑色素瘤的发病率和预后：EUROCARE-6回顾性队列结果。

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-24 DOI: 10.1016/j.ejca.2024.115079

Alice Indini , Fabio Didoné , Daniela Massi , Susana Puig , Jordi Rubio Casadevall , Damien Bennett , Alexander Katalinic , Arantza Sanvisens , Andrea Ferrari , Paolo Lasalvia , Elena Demuru , Rosalia Ragusa , Alexandra Mayer-da-Silva , Marcel Blum , Mohsen Mousavi , Claudia Kuehni , Ana Mihor , Mario Mandalà , Annalisa Trama , the EUROCARE-6 Working Group

Background

Cutaneous melanoma (CM) is rare in adolescents and young adults (AYA, 15–39 years at cancer diagnosis) and studies on CM in AYAs are scarce. Our aim is to update CM incidence and survival in European AYAs and to compare incidence and survival both with other age groups and over time.

Methods

We used the EUROCARE-6 database (108 cancer registries; 29 EU countries), calculating incidence rates (IR) per 100,000 individuals/year in the European population (years of diagnosis: 2006–2013), 5-year relative survival (RS), and 5-year RS conditional to surviving the first year after diagnosis, for the follow-up period 2010–2014 (cases diagnosed in 2006–2013).

Results

The IR of CM in AYA was greater in females than in males, standing at 7. CM IR was higher in the limbs and lower in the head and neck (H&N) and trunk in females compared to males. Five-year RS was 94 % in AYA and 80 % in older age groups. Survival was higher in limb than in H&N and trunk CM. The incidence of CM increased more in older age groups than in AYA. CM survival rose over time for all ages.

Conclusions

Differences in IR between males and females may be due to different behaviors and CM biology. The increase in survival can be attributed to healthcare improvements, early diagnosis, and locoregional surgical treatments. The incidence trends are reassuring in terms of tumor burden in AYA. Our findings support the idea that CM is more aggressive with increasing age and gender differences partially explain survival differences between age groups.

背景：皮肤黑色素瘤（CM）在青少年和年轻成人（AYA，确诊癌症时年龄为 15-39 岁）中非常罕见，有关青少年和年轻成人 CM 的研究也很少。我们的目的是更新欧洲青少年皮肤黑色素瘤的发病率和存活率，并与其他年龄组和不同时期的发病率和存活率进行比较：我们使用了EUROCARE-6数据库（108个癌症登记处；29个欧盟国家），计算了2010-2014年随访期间欧洲人口（诊断年份：2006-2013年）每10万人/年的发病率（IR）、5年相对存活率（RS）以及诊断后第一年存活的5年RS（2006-2013年诊断的病例）：与男性相比，女性四肢的CM IR较高，而头颈部和躯干的CM IR较低。青壮年的五年存活率为 94%，老年组为 80%。四肢中风的存活率高于头颈部和躯干中风。与青壮年相比，老年组的中风发病率增加得更多。随着时间的推移，所有年龄段的 CM 存活率均有所上升：男性和女性之间的 IR 差异可能是由于不同的行为和 CM 生物学特性造成的。存活率的提高可归因于医疗保健的改善、早期诊断和局部手术治疗。就青少年肿瘤负担而言，发病趋势令人欣慰。我们的研究结果支持这样一种观点，即随着年龄的增长，CM 的侵袭性更强，性别差异可部分解释不同年龄组之间的生存率差异。

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引用次数: 0

16S rRNA target sequencing of human tumors validates findings of Lachnoclostridium abundance in human melanomas that are heavily CD8+ T-cell infiltrated. 人类肿瘤的 16S rRNA 目标测序验证了在 CD8+ T 细胞大量浸润的人类黑色素瘤中大量存在拉氏梭菌的结论。

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-24 DOI: 10.1016/j.ejca.2024.115084

Lingeng Lu, Caroline Johnson, Sajid Khan, Harriet Kluger

引用次数: 0

Response to letter entitled: Re: Indirect comparison of capmatinib treatment from GEOMETRY mono-1 trial to SOC in German patients with locally advanced or metastatic NSCLC harboring METex14 skipping mutations. 对题为Re：在德国携带 METex14 跳过突变的局部晚期或转移性 NSCLC 患者中，将 GEOMETRY mono-1 试验中的卡马替尼治疗与 SOC 进行间接比较。

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-24 DOI: 10.1016/j.ejca.2024.115086

Anna Kron, Matthias Scheffler, Juergen Wolf

引用次数: 0

Resection of colorectal liver metastases with second-line aflibercept plus FOLFIRI: Results from the RESECTION prospective French cohort 结直肠肝转移灶切除术与二线aflibercept加FOLFIRI疗法：法国前瞻性队列RESECTION的研究结果

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-22 DOI: 10.1016/j.ejca.2024.115082

David Tougeron , Frederic Bibeau , Benoist Chibaudel , Stefano Kim , Thierry Nguyen , Jean-Marc Phelip , Dominique Mille , Mohamed Bouattour , David Tavan , Yves Rinaldi , Thierry Lecomte , Hervé Perrier , Dominique Spaeth , François-Xavier Caroli Bosc , Jean-Philippe Metges , Marc Ferec , Vincent Hautefeuille , Marion Deslandres-Cruchant , Jerome Danion , Pascal Hammel , René Adam

Aim

To evaluate R0/R1 resection rate in patients with colorectal liver metastases (CLM) treated with aflibercept plus FOLFIRI after failure of a prior oxaliplatin-based regimen in daily clinical practice.

Methods

This French, multicentre, prospective, observational cohort (NCT05178745) included patients with CLM (alone or predominant; up to 5 lung nodules <2 cm allowed) initiating aflibercept plus FOLFIRI every 2 weeks per physician choice. Primary endpoint was R0/R1 resection rate. Secondary endpoints included overall survival (OS), progression-free survival (PFS), radiological and pathological responses, and safety.

Results

A total of 137 patients (median age 65 years, RAS/BRAF mutant 57 %/9 %) were enrolled at 22 French sites. CLM (median 4) were synchronous in 82 %, bilobar in 71 % and located in liver only in 54 %. Overall, 17 % of patients had R0/R1 resection (21 % for patients with liver-only disease). A major pathological response per Blazer score was observed in 55 % of resected patients, along with significantly longer OS (median 34.8 vs 9.1 months, p < 0.0001) and PFS (median 11.4 vs 4.9 months, p < 0.0001) compared to non-resected patients. Post-operative complications occurred in 17 % of patients (all Dindo-Clavien grade I-II) and there was no post-operative deaths. Overall, 34 % had grade ≥ 3 adverse events, mainly general health deterioration and diarrhea.

Conclusions

Results suggest that aflibercept plus FOLFIRI, after failure of a prior oxaliplatin-based regimen, allows R0/R1 resection of CLM in almost 20 % of patients with a major pathological response in most cases and a median OS prolonged by more than 3-fold versus non-resected patients.

方法这项法国多中心、前瞻性、观察性队列研究（NCT05178745）纳入了结直肠肝转移（CLM）患者（单独或主要；最多允许5个肺结节<2 cm），根据医生的选择，每2周开始一次aflibercept加FOLFIRI治疗。主要终点是R0/R1切除率。次要终点包括总生存期（OS）、无进展生存期（PFS）、放射学和病理学反应以及安全性。结果共有137名患者（中位年龄65岁，RAS/BRAF突变57%/9%）在22个法国研究机构接受了治疗。82%的CLM（中位数为4）为同步，71%为双叶，54%仅位于肝脏。总体而言，17%的患者进行了R0/R1切除术（21%的患者只切除了肝脏）。根据 Blazer 评分，55% 的切除患者有主要病理反应，与未切除患者相比，OS（中位 34.8 个月 vs 9.1 个月，p < 0.0001）和 PFS（中位 11.4 个月 vs 4.9 个月，p < 0.0001）显著延长。17%的患者出现术后并发症（均为丁多-克拉维恩 I-II 级），无术后死亡病例。总的来说，34%的患者出现了≥3级的不良反应，主要是全身健康状况恶化和腹泻。结论结果表明，在既往奥沙利铂方案治疗失败后，aflibercept加FOLFIRI可使近20%的CLM患者进行R0/R1切除，大多数病例可获得主要病理反应，与未切除患者相比，中位OS延长了3倍以上。

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引用次数: 0

Classic Hodgkin Lymphoma: The LYSA pragmatic guidelines 典型霍奇金淋巴瘤：LYSA 实用指南

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-22 DOI: 10.1016/j.ejca.2024.115073

Cédric Rossi , Guillaume Manson , Amira Marouf , Aurélie Cabannes-Hamy , Emmanuelle Nicolas-Virelizier , Marie Maerevoet , Marion Alcantara , Lysiane Molina , Antony Ceraulo , Marilyne Poirée , Jean Galtier , Nadia Diop , Caroline Delette , Amandine Segot , Sydney Dubois , Agathe Waultier , Sophie Bernard , Robin Noël , Stéphanie Guidez , Milena Kohn , Hervé Ghesquières

Classic Hodgkin lymphoma (HL) is a distinct entity among hematological malignancies of B-cell origin. It is characterized by its unique histopathological features and generally favorable prognosis. Over the years, advancements in understanding its pathogenesis, coupled with refined diagnostic and evaluation modalities, as well as therapeutic strategies, have significantly transformed the landscape of HL management. In this article, we present a comprehensive set of recommendations for the management of HL, encompassing various aspects of diagnosis, risk stratification, evaluation, and treatment. These recommendations are based on the latest evidence-based guidelines, expert consensus opinions, and clinical trial data, aiming to provide clinicians with a practical framework for delivering optimal care to patients with HL.

经典霍奇金淋巴瘤（HL）是 B 细胞来源血液恶性肿瘤中的一种独特类型。它具有独特的组织病理学特征，预后一般良好。多年来，随着对其发病机制认识的不断深入、诊断和评估方法的不断完善以及治疗策略的不断改进，HL 的治疗格局发生了显著变化。在本文中，我们为 HL 的治疗提出了一套全面的建议，包括诊断、风险分层、评估和治疗等各个方面。这些建议基于最新的循证指南、专家共识意见和临床试验数据，旨在为临床医生提供一个切实可行的框架，为 HL 患者提供最佳治疗。

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引用次数: 0

Assessing the real-world effectiveness of 8 major metastatic breast cancer drugs using target trial emulation 利用靶向试验模拟评估 8 种主要转移性乳腺癌药物的实际疗效。

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-22 DOI: 10.1016/j.ejca.2024.115072

Alison Antoine , David Pérol , Mathieu Robain , Thomas Bachelot , Rémy Choquet , William Jacot , Béchir Ben Hadj Yahia , Thomas Grinda , Suzette Delaloge , Christine Lasset , Youenn Drouet

Background

Demonstration of trial emulation ability to benchmark randomised controlled trials (RCTs) from real-world data (RWD) is required to increase confidence in the use of routinely collected data for decision making in oncology.

Methods

To assess the frequency with which emulation findings align with RCTs regarding effect size on overall survival (OS) in metastatic breast cancer (MBC), 8 of 13 pre-selected pivotal RCTs in MBC were emulated using data from 32,598 patients enrolled in the French ESME-MBC cohort between January 1, 2008 and December 31, 2021. Adjustment methods and confounders were selected a priori for each emulation; stabilized weight was the reference method to mitigate confounding. Concordance in OS hazard ratios with associated 95 % confidence intervals between RCTs and emulations were assessed used predefined metrics based on statistical significance, estimates, and standardized differences.

Results

The effect sizes were consistent with RCT results in 7 out of the 8 emulations; 4 emulations achieved full statistical significance agreement; 5 emulations had a point estimate included in the RCT CI (estimate agreement); 6 emulations reported no significant differences between RCT and emulation (standardized difference agreement). Discrepancies related to residual confounders and significant shifts in prescription practices post-drug approval may arise in some cases.

Conclusion

Target trial emulation from RWD combined with appropriate adjustment can provide conclusions similar to RCTs in MBC. In oncology, this methodology offers opportunities for confirming the impact on long-term survival, for expanding indications in patients excluded from RCTs and for comparative effectiveness in single-arm trials using external control arms.

背景：需要展示试验仿真能力，以真实世界数据（RWD）作为随机对照试验（RCT）的基准，从而增强人们对使用常规收集的数据进行肿瘤决策的信心：为了评估在转移性乳腺癌（MBC）总生存期（OS）效应大小方面仿真结果与RCT一致的频率，我们利用2008年1月1日至2021年12月31日期间入组法国ESME-MBC队列的32598名患者的数据，对13项预选的MBC关键RCT中的8项进行了仿真。每次模拟都事先选择了调整方法和混杂因素；稳定权重是减轻混杂因素的参考方法。使用基于统计显著性、估计值和标准化差异的预定指标，评估了RCT与模拟之间OS危险比及相关95%置信区间的一致性：在 8 个仿真结果中，有 7 个仿真结果的效应大小与 RCT 结果一致；有 4 个仿真结果的统计显著性完全一致；有 5 个仿真结果的点估计值包含在 RCT CI 中（估计值一致）；有 6 个仿真结果显示 RCT 与仿真结果之间无显著差异（标准化差异一致）。在某些情况下，可能会出现与残余混杂因素和药物批准后处方做法的重大变化有关的差异：结论：RWD 的目标试验仿真结合适当的调整，可以在 MBC 中得出与 RCT 相似的结论。在肿瘤学领域，这种方法可用于确认对长期生存的影响、扩大被 RCT 排除在外的患者的适应症以及在使用外部对照臂的单臂试验中进行疗效比较。

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引用次数: 0

Intensified alkylating chemotherapy for patients with oligometastatic breast cancer harboring homologous recombination deficiency: Primary outcomes from the randomized phase III OLIGO study 对携带同源重组缺陷的寡转移性乳腺癌患者进行强化烷化化疗：随机III期OLIGO研究的主要结果

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-20 DOI: 10.1016/j.ejca.2024.115083

A. van Ommen-Nijhof , T.G. Steenbruggen , T.G. Wiersma , S. Balduzzi , A. Daletzakis , M.J. Holtkamp , M. Delfos , M. Schot , K. Beelen , E.J.M. Siemerink , J. Heijns , I.A. Mandjes , J. Wesseling , E.H. Rosenberg , M.J.T. Vrancken Peeters , S.C. Linn , G.S. Sonke

Background

Oligometastatic breast cancer (OMBC) is a clinical entity with a prospect of long-term survival, but uncertainty remains on its optimal treatment. We studied whether intensified alkylating chemotherapy (IACT) improves long-term outcome compared to conventional-dose chemotherapy (CDCT) as part of a multimodality approach for patients with OMBC harboring homologous recombination deficiency (HRD).

Patients and methods

Eligible patients had HER2-negative OMBC, harboring HRD, with ≤ 3 distant metastases, pathologic proof of distant disease and a favorable response to three cycles CDCT. Participants were randomized 1:1 to continue with either CDCT or IACT. IACT consisted of one mobilization course followed by two cycles of mini-CTC (carboplatin, thiotepa and cyclophosphamide) supported by peripheral blood progenitor cell reinfusion. Primary outcome was event-free survival (EFS). Secondary endpoints included overall survival (OS), quality of life and safety.

Results

Seventy-five patients were randomized to either IACT (n = 36) or CDCT (n = 39). Twenty-three (31 %) patients had hormone receptor-positive disease and 52 (69 %) had triple-negative disease. Median EFS in the IACT-group was 28 months (95 % confidence interval [CI] 21-not reached [NR]) versus 25 months (95 %CI 14-NR) in the CDCT-group (hazard ratio [HR] for recurrence or death 0.78, 95 %CI 0.42–1.42). Median OS was 67 months (95 %CI 37-NR) in the IACT-group and 36 (95 %CI 26-NR) in the CDCT-group (HR 0.74, 95 %CI 0.37–1.48).

Conclusions

The entire study population experienced long-term survival, with median OS well over five years. IACT compared to CDCT did not improve outcome in patients with OMBC harboring study-defined HRD. The optimal therapy for patients with OMBC requires further study.

Trial Registration

ClinicalTrials.gov: NCT01646034

背景转移性乳腺癌（OMBC）是一种具有长期生存前景的临床实体，但其最佳治疗方法仍不确定。我们研究了与常规剂量化疗（CDCT）相比，强化烷化化疗（IACT）作为多模式疗法的一部分，是否能改善携带同源重组缺陷（HRD）的OMBC患者的长期预后。患者和方法符合条件的患者为HER2阴性OMBC，携带HRD，远处转移灶≤3个，病理证明有远处疾病，对三个周期的CDCT有良好反应。参试者按1:1比例随机选择继续接受CDCT或IACT治疗。IACT包括一个动员疗程，然后是两个周期的迷你CTC（卡铂、硫替帕和环磷酰胺），并辅以外周血祖细胞再灌注。主要结果是无事件生存期（EFS）。结果75名患者随机接受了IACT（36人）或CDCT（39人）治疗。23名患者（31%）激素受体阳性，52名患者（69%）三阴性。IACT组的中位生存期为28个月（95%置信区间[CI] 21-未达[NR]），而CDCT组为25个月（95%CI 14-NR）（复发或死亡危险比[HR]0.78，95%CI 0.42-1.42）。IACT 组的中位 OS 为 67 个月（95 %CI 37-NR），CDCT 组为 36 个月（95 %CI 26-NR）（HR 0.74，95 %CI 0.37-1.48）。与CDCT相比，IACT并不能改善研究定义的HRD的OMBC患者的预后。OMBC患者的最佳疗法需要进一步研究：NCT01646034

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引用次数: 0

Immune marker expression and prognosis of early breast cancer expressing HER3 表达 HER3 的早期乳腺癌的免疫标记表达和预后。

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-20 DOI: 10.1016/j.ejca.2024.115081

Dae-Won Lee , Han Suk Ryu , Ilias P. Nikas , Jiwon Koh , Tae-Yong Kim , Hong Kyu Kim , Han-Byoel Lee , Hyeong-Gon Moon , Wonshik Han , Kyung-Hun Lee , Seock-Ah Im

Introduction

There is a strong rationale for targeting HER3, as HER3 contributes to tumorigenesis and treatment resistance. However, the prognostic role of HER3 and their association with immunoregulatory protein expression has not been established.

Methods

The main objective of this study was to investigate the prognostic role of HER3 expression and identify immunoregulatory marker expression according to HER3 status. HER3 expression and 10 immunoregulatory protein (PD-1/PD-L1/PD-L2/IDO/TIM-3/OX40/OX40L/B7-H2/B7-H3/B7-H4) expression was identified in 320 stage I-III breast cancer patients who received curative surgery at Seoul National University Hospital in 2008. The median follow-up duration was 88.8 months. Criteria for HER3 IHC was adopted from HER2 IHC score and only those with 3 + was considered positive.

Results

Among 320 patients, 213 (67.2 %) had luminal A disease, 30 (9.5 %) had luminal B disease, 28 (8.8 %) had HER2-positive disease, and 46 (14.5 %) had triple negative disease. HER3 expression was shown in 153 patients (47.8 %). Tumors with HER3-expression had more immunogenic tumor microenvironment compared to HER3-negative tumor. In addition, patients with HER3 expression had favorable 5-year relapse free survival compared to HER3-negative patients (5-year RFS 92.5 % vs. 85.2 %, p = 0.038). However, in the multivariate analysis, HER3 expression was not a prognostic factor, but expression of immunoregulatory protein was a prognostic factor.

Conclusions

This study identified immunoregulatory protein expression according to HER3 status in breast cancer patients. As tumor with HER3 expression have more immunogenic microenvironment, investigating combination treatment of HER3 targeting agent and immunotherapy in HER3 expressing breast cancer may be promising.

导言：以 HER3 为靶点有很强的合理性，因为 HER3 会导致肿瘤发生和耐药性。然而，HER3的预后作用及其与免疫调节蛋白表达的关联尚未确定：本研究的主要目的是研究 HER3 表达的预后作用，并根据 HER3 状态确定免疫调节标志物的表达。2008年，在首尔国立大学医院接受根治性手术的320名I-III期乳腺癌患者中，HER3表达和10种免疫调节蛋白（PD-1/PD-L1/PD-L2/IDO/TIM-3/OX40/OX40L/B7-H2/B7-H3/B7-H4）表达得到了确认。中位随访时间为 88.8 个月。HER3 IHC 的标准采用 HER2 IHC 的评分，只有 3 + 的患者才被视为阳性：在 320 例患者中，213 例（67.2%）为管腔 A 型疾病，30 例（9.5%）为管腔 B 型疾病，28 例（8.8%）为 HER2 阳性疾病，46 例（14.5%）为三阴性疾病。153名患者（47.8%）有HER3表达。与HER3阴性肿瘤相比，HER3表达的肿瘤具有更强的免疫原性肿瘤微环境。此外，与 HER3 阴性患者相比，HER3 表达患者的 5 年无复发生存率更高（5 年 RFS 92.5% 对 85.2%，P = 0.038）。然而，在多变量分析中，HER3表达不是预后因素，但免疫调节蛋白的表达是预后因素：这项研究根据乳腺癌患者的 HER3 状态确定了免疫调节蛋白的表达。由于HER3表达的肿瘤具有更强的免疫原性微环境，研究HER3靶向药物和免疫疗法联合治疗HER3表达的乳腺癌可能很有前景。

{"title":"Immune marker expression and prognosis of early breast cancer expressing HER3","authors":"Dae-Won Lee , Han Suk Ryu , Ilias P. Nikas , Jiwon Koh , Tae-Yong Kim , Hong Kyu Kim , Han-Byoel Lee , Hyeong-Gon Moon , Wonshik Han , Kyung-Hun Lee , Seock-Ah Im","doi":"10.1016/j.ejca.2024.115081","DOIUrl":"10.1016/j.ejca.2024.115081","url":null,"abstract":"<div><h3>Introduction</h3><div>There is a strong rationale for targeting HER3, as HER3 contributes to tumorigenesis and treatment resistance. However, the prognostic role of HER3 and their association with immunoregulatory protein expression has not been established.</div></div><div><h3>Methods</h3><div>The main objective of this study was to investigate the prognostic role of HER3 expression and identify immunoregulatory marker expression according to HER3 status. HER3 expression and 10 immunoregulatory protein (PD-1/PD-L1/PD-L2/IDO/TIM-3/OX40/OX40L/B7-H2/B7-H3/B7-H4) expression was identified in 320 stage I-III breast cancer patients who received curative surgery at Seoul National University Hospital in 2008. The median follow-up duration was 88.8 months. Criteria for HER3 IHC was adopted from HER2 IHC score and only those with 3 + was considered positive.</div></div><div><h3>Results</h3><div>Among 320 patients, 213 (67.2 %) had luminal A disease, 30 (9.5 %) had luminal B disease, 28 (8.8 %) had HER2-positive disease, and 46 (14.5 %) had triple negative disease. HER3 expression was shown in 153 patients (47.8 %). Tumors with HER3-expression had more immunogenic tumor microenvironment compared to HER3-negative tumor. In addition, patients with HER3 expression had favorable 5-year relapse free survival compared to HER3-negative patients (5-year RFS 92.5 % <em>vs.</em> 85.2 %, <em>p</em> = 0.038). However, in the multivariate analysis, HER3 expression was not a prognostic factor, but expression of immunoregulatory protein was a prognostic factor.</div></div><div><h3>Conclusions</h3><div>This study identified immunoregulatory protein expression according to HER3 status in breast cancer patients. As tumor with HER3 expression have more immunogenic microenvironment, investigating combination treatment of HER3 targeting agent and immunotherapy in HER3 expressing breast cancer may be promising.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"213 ","pages":"Article 115081"},"PeriodicalIF":7.6,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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