European Journal of Cancer最新文献

英文中文

First-line encorafenib plus binimetinib and pembrolizumab for advanced BRAF V600-mutant melanoma: Safety lead-in results from the randomized phase III STARBOARD study 晚期BRAF V600突变黑色素瘤一线恩戈非尼加比尼替尼和pembrolizumab治疗：随机III期STARBOARD研究的安全性先导研究结果。

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-11 DOI: 10.1016/j.ejca.2024.115070

Oleksandr Dudnichenko , Konstantin Penkov , Meredith McKean , Mario Mandalà , Mariia Kukushkina , Timothy Panella , Tibor Csőszi , Paola Gerletti , Mahgull Thakur , Anna Polli , Alessandra di Pietro , Dirk Schadendorf

Background

BRAF inhibitors plus MEK inhibitors (BRAFi/MEKi) and immune checkpoint inhibitors (CPIs) are approved for BRAF V600-mutant advanced melanoma. Combinations of BRAFi/MEKi with CPIs may further improve outcomes and could offer additional treatment strategies.

Methods

STARBOARD (NCT04657991) is a phase III study with an initial safety lead-in (SLI) phase conducted to determine the recommended phase III dose (RP3D) for encorafenib in combination with binimetinib and pembrolizumab. Patients with untreated, unresectable locally advanced or metastatic BRAF V600E/K-mutant cutaneous melanoma received binimetinib 45 mg twice daily and pembrolizumab 200 mg every 3 weeks plus encorafenib 450 mg once daily (COMBO450 plus pembrolizumab) or 300 mg once daily (COMBO300 plus pembrolizumab). The primary endpoint was the incidence of dose-limiting toxicities (DLTs). Secondary endpoints included safety, objective response, time to response, and duration of response. Progression-free survival was assessed post hoc.

Results

In the SLI, the median follow-up duration was 19.4 months. Twenty patients received COMBO450 plus pembrolizumab and 17 received COMBO300 plus pembrolizumab. DLTs occurred in 1 of 17 DLT-evaluable patients in the COMBO450 plus pembrolizumab arm and in 2 of 17 DLT-evaluable patients in the COMBO300 plus pembrolizumab arm. No treatment-related deaths occurred in either treatment arm. The overall response rate was 65.0 % in the COMBO450 plus pembrolizumab arm and 47.1 % in the COMBO300 plus pembrolizumab arm.

Conclusion

The STARBOARD SLI showed that safety across the cohorts was generally comparable to the known safety profile of each agent. The standard dose regimen of COMBO450 plus pembrolizumab was chosen as the RP3D.

背景：BRAF 抑制剂加 MEK 抑制剂（BRAFi/MEKi）和免疫检查点抑制剂（CPIs）被批准用于治疗 BRAF V600 突变的晚期黑色素瘤。BRAFi/MEKi与CPIs联用可进一步改善疗效，并提供更多治疗策略：STARBOARD (NCT04657991)是一项III期研究，其初始安全引导（SLI）阶段旨在确定安戈非尼联合binimetinib和pembrolizumab的III期推荐剂量（RP3D）。未经治疗、无法切除的局部晚期或转移性BRAF V600E/K突变皮肤黑色素瘤患者接受了每天两次、每次45毫克的比尼美替尼和每3周一次、每次200毫克的pembrolizumab，以及每天一次、每次450毫克的安戈非尼（COMBO450加pembrolizumab）或每天一次、每次300毫克的安戈非尼（COMBO300加pembrolizumab）。主要终点是剂量限制性毒性（DLT）的发生率。次要终点包括安全性、客观反应、反应时间和反应持续时间。无进展生存期进行了事后评估：在 SLI 中，中位随访时间为 19.4 个月。20名患者接受了COMBO450加pembrolizumab治疗，17名患者接受了COMBO300加pembrolizumab治疗。COMBO450加pembrolizumab治疗组的17例DLT有效患者中，有1例出现DLT；COMBO300加pembrolizumab治疗组的17例DLT有效患者中，有2例出现DLT。两个治疗组均未发生与治疗相关的死亡病例。COMBO450加pembrolizumab治疗组的总体应答率为65.0%，COMBO300加pembrolizumab治疗组的总体应答率为47.1%：STARBOARD SLI显示，各组群的安全性与每种药物的已知安全性基本相当。COMBO450加pembrolizumab的标准剂量方案被选为RP3D。

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引用次数: 0

The european organisation for research and treatment of cancer head and neck cancer module (EORTC QLQ-HN43): Estimates for minimal important difference and minimal important change 欧洲癌症研究和治疗组织头颈癌模块（EORTC QLQ-HN43）：最小重要差异和最小重要变化的估计值

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-09 DOI: 10.1016/j.ejca.2024.115062

Susanne Singer , Eva Hammerlid , Iwona M. Tomaszewska , Cecilie D. Amdal , Bente B. Herlofson , Marcos Santos , Joaquim Castro Silva , Hisham Mehanna , Amy Fullerton , Teresa Young , Loreto Fernandez Gonzalez , Johanna Inhestern , Monica Pinto , Juan I. Arraras , Noam Yarom , Pierluigi Bonomo , Ingo Baumann , Razvan Galalae , Ourania Nicolatou-Galitis , Naomi Kiyota , Kristin Bjordal

Introduction

Minimal important change estimates (MIC) are useful for interpreting results of clinical research with quality of life (QoL) as an endpoint. For the European Organisation for Research and Treatment of Cancer head and neck cancer module, the EORTC QLQ-HN43, no such thresholds are established.

Methods

Head and neck cancer patients under active treatment (n = 503) from 15 countries completed the EORTC QLQ-HN43 three times (t1: before treatment, t2: three months after t1, t3: six months after t1). A subgroup completed a Subjective Significance Questionnaire (SSQ), indicating experienced change from the previous time point in four QoL domains. QoL was assumed to deteriorate after t1 and improve again until t3. The MIC was established using the average of mean differences in SSQ groups (MIC_mean) and estimates based on logistic regressions (MIC_predict). Additionally, minimal detectable changes (MDC) were computed using 0.5 standard deviation and standard error of the mean.

Results

For swallowing, speech, dry mouth, and global QoL, the MIC for deterioration were 13, 14, 26, and 10 respectively. The MIC for improvement were 8 (swallowing), 6 (dry mouth), and 5 (global QoL); no MIC for speech improvement can be presented because of insufficient correlation between change score and anchor. The MDC estimates for deterioration were 15, 14, 15, and 11. For improvement, the MDC estimates were 13, 14, 14, and 11.

Conclusions

Our results underline that no single MIC or MDC can be applied to all EORTC QLQ-HN43 scales, and that the MIC for deterioration seems larger than those for improvement.

引言最小重要变化估计值（MIC）有助于解释以生活质量（QoL）为终点的临床研究结果。来自 15 个国家的正在接受积极治疗的头颈部癌症患者（n = 503）三次完成了 EORTC QLQ-HN43 模块（t1：治疗前，t2：t1 后三个月，t3：t1 后六个月）。一个亚组完成了主观意义问卷（SSQ），显示了与前一个时间点相比在四个 QoL 领域中经历的变化。假定 QoL 在 t1 之后恶化，并在 t3 之前再次改善。根据 SSQ 各组平均差异的平均值（MICmean）和基于逻辑回归的估计值（MICpredict）确定 MIC。结果在吞咽、言语、口干和整体 QoL 方面，恶化的 MIC 分别为 13、14、26 和 10。言语能力改善的 MIC 值分别为 8（吞咽）、6（口干）和 5（整体 QoL）；由于变化分数与锚点之间的相关性不足，因此无法提供言语能力改善的 MIC 值。恶化的 MDC 估计值分别为 15、14、15 和 11。结论我们的研究结果表明，没有任何一种 MIC 或 MDC 可适用于所有 EORTC QLQ-HN43 量表，恶化的 MIC 似乎大于改善的 MIC。

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引用次数: 0

Radiotherapy in cutaneous lymphomas: Recommendations from the EORTC cutaneous lymphoma tumour group 皮肤淋巴瘤的放射治疗：EORTC 皮肤淋巴瘤肿瘤小组的建议

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-08 DOI: 10.1016/j.ejca.2024.115064

Khaled Elsayad , Emmanuella Guenova , Chalid Assaf , Jan P. Nicolay , Franz Trautinger , Rudolf Stadler , Cora Waldstein , Tom Boterberg , Paul Meijnders , Youlia Kirova , Gabor Dobos , Victor Duque-Santana , Elena Riggenbach , Wael Elsheshtawy , Anne Niezink , Evangelia Papadavid , Julia Scarisbrick , Maarten Vermeer , Karen J. Neelis , Martine Bagot , Dora Correia

The number of primary cutaneous lymphoma patients receiving low-dose radiotherapy is increasing, though controlled clinical trials defining the standard radiation dose for each specific entity have not yet been completed. Radiation oncologists are left with making highly individualized decisions that would be better enriched by additional clinical evidence. In this expert opinion, we aim to provide a clear recommendation to improve the current practice of radiation oncology. In addition, existing literature has been reviewed to develop recommendations for all types of primary cutaneous lymphoma. A prospective trial is urgently needed to identify the factors influencing patient outcomes following different radiation doses.

接受低剂量放射治疗的原发性皮肤淋巴瘤患者人数在不断增加，但确定每种特定实体标准放射剂量的对照临床试验尚未完成。放射肿瘤专家只能做出高度个体化的决定，而更多的临床证据将更好地丰富这些决定。在这份专家意见中，我们旨在提供明确的建议，以改善目前的放射肿瘤学实践。此外，我们还回顾了现有文献，为所有类型的原发性皮肤淋巴瘤制定了建议。目前亟需进行前瞻性试验，以确定不同放射剂量对患者预后的影响因素。

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引用次数: 0

Risk factors for lymph node metastasis in women with FIGO 2018 IA cervical cancer with a horizontal spread of > 7 mm 患有 FIGO 2018 IA 宫颈癌且水平扩散范围大于 7 毫米的妇女发生淋巴结转移的风险因素。

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-05 DOI: 10.1016/j.ejca.2024.115063

Hans H.B. Wenzel , Tine H. Schnack , Maaike A. Van der Aa , Pernille T. Jensen , Claus K. Høgdall , Anna Norberg Hardie , Henrik Falconer , Ruud L.M. Bekkers , Dutch, dANish and sweDish gynaEcoLogIcal ONcology (DANDELION) research group

Background

In the FIGO 2018 classification, women with cervical cancer and a depth of invasion ≤ 5 mm and a horizontal spread of > 7 mm in excisional biopsy with tumour-free margins, are now classified as stage IA instead of IB. This stage shift may reduce the likelihood of surgical lymph node staging. It is therefore crucial to estimate the risk and risk factors of lymph node metastasis (pN+) in this group.

Methods

Women diagnosed with cervical cancer between 2005 and 2022 were identified from nationwide population-based registries from the Netherlands, Denmark, and Sweden. Inclusion criteria were squamous cell carcinoma or adenocarcinoma, FIGO 2009 stage IB1, a depth of invasion ≤ 5 mm and horizontal spread of > 7–≤ 40 mm. All cases underwent radical hysterectomy or radical trachelectomy, and surgical lymph node staging. Logistic regression was used to identify risk factors of pN+.

Results

We included 992 women (pN+ 4.1 %; n = 41). Lymphovascular space invasion (LVSI) was a significant risk factor of pN+ (odds ratio 4.26, 95 % confidence interval 2.24–8.32). Accordingly, the risk of pN+ was ≥ 7.3 % in LVSI-positive tumours. The risk was lowest in LVSI-negative tumours with a size of > 7–≤ 20 mm (2.2 %), although this varied by depth of invasion and histological subtype (pN+ range 0.6–5.1 %).

Conclusion

Women with LVSI-positive FIGO 2018 IA cervical cancer and a horizontal spread > 7 mm, should undergo surgical lymph node staging. In LVSI-negative tumours, lymph node staging should not be routinely performed; tumour size, depth of invasion and histology should be considered.

背景：在 FIGO 2018 分级中，患有宫颈癌且在切除活检中浸润深度≤5 毫米、水平扩散>7 毫米且边缘无肿瘤的女性，现在被归类为 IA 期而非 IB 期。这种分期的转变可能会降低手术淋巴结分期的可能性。因此，估算该群体淋巴结转移（pN+）的风险和风险因素至关重要：方法：从荷兰、丹麦和瑞典的全国性人口登记中筛选出 2005 年至 2022 年期间确诊为宫颈癌的女性。纳入标准为：鳞状细胞癌或腺癌、FIGO 2009 IB1 期、浸润深度≤ 5 毫米且水平扩散 > 7-≤ 40 毫米。所有病例均接受了根治性子宫切除术或根治性气管切除术，并进行了手术淋巴结分期。采用逻辑回归确定pN+的风险因素：我们共纳入992名妇女（pN+ 4.1 %；n = 41）。淋巴管间隙侵犯（LVSI）是pN+的重要风险因素（几率比4.26，95%置信区间2.24-8.32）。因此，LVSI阳性肿瘤的pN+风险≥7.3%。LVSI阴性、大小> 7-≤ 20 mm的肿瘤的pN+风险最低（2.2%），但这一风险因浸润深度和组织学亚型而异（pN+范围为0.6-5.1%）：结论：LVSI阳性的FIGO 2018 IA宫颈癌患者，水平扩散范围大于7毫米，应进行手术淋巴结分期。对于LVSI阴性的肿瘤，不应常规进行淋巴结分期；应考虑肿瘤大小、浸润深度和组织学。

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引用次数: 0

Short- and long-term immunosuppressive effects of melanoma influence the prognostic value of the sentinel lymph node status 黑色素瘤的短期和长期免疫抑制作用会影响前哨淋巴结状态的预后价值。

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer

Pub Date : 2024-10-04 DOI: 10.1016/j.ejca.2024.115054

Viola K. DeTemple , Cathrin Ritter , Nalini Srinivas , Ivelina Spassova , Thilo Gambichler , Svea Hüning , Nikolai Gräger , Ralf Gutzmer , Eva-Bettina Bröcker , Selma Ugurel , David Schrama , Jürgen C. Becker

Background

Presence of micrometastases in the sentinel lymph node (SLN) is currently used to assess prognosis of melanoma patients. The immunoactivity within the SLN is known to be influenced by the primary tumor (PT), which may in turn impact the SLNs’ metastatic state.

Aim

We characterize the temporal dependence and underlying mechanisms of the immunological effects of the PT on the SLN.

Methods

The prognostic value of SLN state as a function of PT removal time was evaluated. To put the results into a functional context, selected PTs and corresponding SLNs were analyzed for gene and protein expression patterns.

Results

In a cohort of 202 patients with known distant metastasis and similar PT prognostic characteristics, SLNs removed before or within one week after the PT (IM-SLN) had a higher incidence of micrometastases than those removed at least one week after the PT (DEL-SLN).

The immunoactivity in IM-SLN was found to be lower than in DEL-SLN. Specifically, in IM-SLNs, T helper 17 / regulatory T-cells were predominant, whereas in DEL-SLNs, cytotoxic γδT-cells were more frequent. The higher immune activity in DEL-SLNs was probably facilitated by CD209⁺ antigen-presenting cells. Indeed, in PT with high TGFβ expression CD209⁺ cells appear to be trapped and no increased immunoactivity was observed in DEL-SLN.

Conclusions

Presence of micrometastases in DEL-SLNs have a higher negative prognostic value as in IM-SLNs since they indicate not only a melanoma’s propensity to metastasize, but possibly also its capacity to escape immune responses.

背景：前哨淋巴结（SLN）是否存在微转移目前被用于评估黑色素瘤患者的预后。目的：我们研究了原发肿瘤（PT）对前哨淋巴结（SLN）免疫学影响的时间依赖性和内在机制：方法：我们评估了SLN状态作为PT切除时间函数的预后价值。为了将结果置于功能背景下，对选定的PT和相应的SLN进行了基因和蛋白质表达模式分析：结果：在202例已知有远处转移且PT预后特征相似的患者队列中，PT切除前或切除后一周内切除的SLN（IM-SLN）比PT切除后至少一周内切除的SLN（DEL-SLN）有更高的微转移发生率。研究发现，IM-SLN 的免疫活性低于 DEL-SLN。具体来说，在IM-SLN中，T辅助细胞17/调节性T细胞占主导地位，而在DEL-SLN中，细胞毒性γδT细胞更为常见。DEL-SLNs中较高的免疫活性可能是由CD209+抗原递呈细胞促成的。事实上，在TGFβ高表达的PT中，CD209+细胞似乎被困住了，在DEL-SLN中没有观察到免疫活性增加：结论：DEL-SLN 中存在微转移灶与 IM-SLN 中存在微转移灶相比，具有更高的负面预后价值，因为微转移灶不仅表明黑色素瘤具有转移倾向，还可能表明黑色素瘤具有逃避免疫反应的能力。

{"title":"Short- and long-term immunosuppressive effects of melanoma influence the prognostic value of the sentinel lymph node status","authors":"Viola K. DeTemple , Cathrin Ritter , Nalini Srinivas , Ivelina Spassova , Thilo Gambichler , Svea Hüning , Nikolai Gräger , Ralf Gutzmer , Eva-Bettina Bröcker , Selma Ugurel , David Schrama , Jürgen C. Becker","doi":"10.1016/j.ejca.2024.115054","DOIUrl":"10.1016/j.ejca.2024.115054","url":null,"abstract":"<div><h3>Background</h3><div>Presence of micrometastases in the sentinel lymph node (SLN) is currently used to assess prognosis of melanoma patients. The immunoactivity within the SLN is known to be influenced by the primary tumor (PT), which may in turn impact the SLNs’ metastatic state.</div></div><div><h3>Aim</h3><div>We characterize the temporal dependence and underlying mechanisms of the immunological effects of the PT on the SLN.</div></div><div><h3>Methods</h3><div>The prognostic value of SLN state as a function of PT removal time was evaluated. To put the results into a functional context, selected PTs and corresponding SLNs were analyzed for gene and protein expression patterns.</div></div><div><h3>Results</h3><div>In a cohort of 202 patients with known distant metastasis and similar PT prognostic characteristics, SLNs removed before or within one week after the PT (IM-SLN) had a higher incidence of micrometastases than those removed at least one week after the PT (DEL-SLN).</div><div>The immunoactivity in IM-SLN was found to be lower than in DEL-SLN. Specifically, in IM-SLNs, T helper 17 / regulatory T-cells were predominant, whereas in DEL-SLNs, cytotoxic γδT-cells were more frequent. The higher immune activity in DEL-SLNs was probably facilitated by CD209<sup>+</sup> antigen-presenting cells. Indeed, in PT with high TGFβ expression CD209<sup>+</sup> cells appear to be trapped and no increased immunoactivity was observed in DEL-SLN.</div></div><div><h3>Conclusions</h3><div>Presence of micrometastases in DEL-SLNs have a higher negative prognostic value as in IM-SLNs since they indicate not only a melanoma’s propensity to metastasize, but possibly also its capacity to escape immune responses.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"212 ","pages":"Article 115054"},"PeriodicalIF":7.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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Response to the Letter re: Real-world outcomes of Italian patients with advanced non-squamous lung cancer treated with first-line pembrolizumab plus platinum-pemetrexed 对 "关于意大利晚期非鳞状肺癌患者接受彭博利珠单抗加铂类-培美曲塞一线治疗的实际效果 "一文的回复。

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