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High tumor mutation burden mitigates the negative impact of chemotherapy history on immune checkpoint blockade therapy 高肿瘤突变负荷减轻了化疗史对免疫检查点阻断治疗的负面影响
IF 3 3区 医学 Q2 ONCOLOGY Pub Date : 2025-03-12 DOI: 10.1053/j.seminoncol.2025.01.003
Ming Zheng MD, PhD
Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small-cell lung cancer (NSCLC) accounting for the majority of cases. Immune checkpoint inhibitor (ICI) therapy, particularly with PD-1 inhibitors like nivolumab, has become a critical treatment option for advanced NSCLC. ICI therapy has revolutionized treatment, but prior chemotherapy may diminish ICI treatment efficacy. Tumor mutation burden (TMB) has emerged as a crucial predictor of ICI response, yet its interaction with chemotherapy history in ICI therapy is not fully understood. In this study, I investigate the impact of chemotherapy history on ICI treatment outcomes, focusing on TMB as a potential mitigating factor. Analyzing data from 512 patients with advanced NSCLC treated with PD-1/PD-L1 or CTLA-4 inhibitors, this sudy found that prior chemotherapy significantly reduced objective response rates (ORR) to ICI therapy, particularly in patients with low TMB (<15 mut/Mb). However, in patients with high TMB (≥15 mut/Mb), the negative impact of chemotherapy history on ICI treatment efficacy is minimal, suggesting that high TMB mitigates chemotherapy-induced resistance to ICI therapy. Furthermore, while chemotherapy history is associated with worse overall survival (OS) and progression-free survival (PFS) following ICI therapy in low-TMB patients, no such association is observed in high-TMB patients. These findings highlight the importance of TMB as a predictive biomarker, emphasizing the need for optimal treatment sequencing and personalized therapeutic strategies to overcome chemotherapy-induced immune resistance and maximize ICI treatment efficacy. These results suggest that ICI therapy may be more beneficial as a first-line treatment, particularly for patients with low TMB.
肺癌仍然是全球癌症相关死亡的主要原因,非小细胞肺癌(NSCLC)占大多数病例。免疫检查点抑制剂(ICI)治疗,特别是PD-1抑制剂如nivolumab,已成为晚期NSCLC的关键治疗选择。ICI治疗是一种革命性的治疗方法,但先前的化疗可能会降低ICI治疗的效果。肿瘤突变负荷(Tumor mutation burden, TMB)已成为ICI反应的重要预测指标,但其与ICI治疗中化疗史的相互作用尚不完全清楚。在本研究中,我研究了化疗史对ICI治疗结果的影响,重点关注TMB作为潜在的缓解因素。本研究分析了512例接受PD-1/PD-L1或CTLA-4抑制剂治疗的晚期非小细胞肺癌患者的数据,发现既往化疗显著降低了对ICI治疗的客观缓解率(ORR),特别是低TMB (<15 mut/Mb)患者。然而,在高TMB(≥15 mut/Mb)的患者中,化疗史对ICI治疗疗效的负面影响很小,这表明高TMB减轻了化疗诱导的ICI治疗耐药。此外,虽然化疗史与低tmb患者ICI治疗后的总生存期(OS)和无进展生存期(PFS)较差相关,但在高tmb患者中没有观察到这种关联。这些发现强调了TMB作为一种预测性生物标志物的重要性,强调了优化治疗序列和个性化治疗策略的必要性,以克服化疗诱导的免疫抵抗并最大化ICI治疗效果。这些结果表明,ICI治疗作为一线治疗可能更有益,特别是对于低TMB患者。
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引用次数: 0
Plant polyphenols in gastric cancer: Nature's healing touch 胃癌中的植物多酚:大自然的治愈之触
IF 3 3区 医学 Q2 ONCOLOGY Pub Date : 2025-03-11 DOI: 10.1053/j.seminoncol.2025.01.002
Chengu Niu , Jing Zhang , Patrick I. Okolo III , Ebubekir Daglilar
Globally, gastric cancer ranks as the fifth most common cancer and is the third most common cause of malignancy-associated mortality. Although surgery is the primary treatment option for gastric cancer, adjuvant chemotherapy improves survival in patients following surgery. Proverbially, plant polyphenols have many beneficial health effects, including anticancer properties. Extensive studies have shown that plant polyphenols exhibit potential anticancer effects against gastric cancer in vitro and in vivo, as well as very few human studies. However, this topic has not yet been reviewed. The present review shows that the potential anticancer effect of plant polyphenols on gastric cancer was preliminarily attributed to their antiproliferative, antimetastatic, and antiangiogenic effects and modulations of apoptosis, autophagy, and intracellular reactive oxygen species. Moreover, conventional therapeutics combined with plant polyphenols make gastric cancer cells more sensitive to conventional therapy. We also discuss challenges and opportunities in translating plant polyphenol-based therapy to clinical applications. The content provided in this review is of interest to pharmacologists, ethnobotanists, and oncologists who are involved in phytomedicine.
在全球范围内,胃癌在最常见的癌症中排名第五,是恶性肿瘤相关死亡的第三大常见原因。虽然手术是胃癌的主要治疗选择,但辅助化疗可以提高手术后患者的生存率。众所周知,植物多酚具有许多有益健康的作用,包括抗癌特性。大量研究表明,植物多酚类物质在体外和体内对胃癌具有潜在的抗癌作用,但人体研究很少。然而,这一主题尚未得到审查。目前的研究表明,植物多酚对胃癌的潜在抗癌作用初步归因于其抗增殖、抗转移、抗血管生成以及调节细胞凋亡、自噬和细胞内活性氧的作用。此外,常规疗法联合植物多酚使胃癌细胞对常规疗法更敏感。我们还讨论了将植物多酚为基础的治疗转化为临床应用的挑战和机遇。本综述提供的内容对从事植物医学研究的药理学家、民族植物学家和肿瘤学家很有兴趣。
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引用次数: 0
Fingerprint change as a consequence of anticancer treatments: A systematic integrative review 指纹变化作为抗癌治疗的结果:一个系统的综合评价
IF 3 3区 医学 Q2 ONCOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.seminoncol.2025.152335
Silvia Belloni , Arianna Magon , Rita de Sanctis , Paola Tiberio , Gianluca Conte , Cristina Arrigoni , Rosario Caruso

Objective

While it is widely acknowledged that fingerprint recognition has played an essential part in policing and forensic science, little is known about fingerprint alterations in medical science, specifically as a consequence of anticancer treatments. Thus, we aimed to analyze the extent of evidence between cancer treatments and fingerprint alterations in adults with cancer.

Methods

A systematic integrative review was conducted according to the PRISMA statement and the Cochrane guidelines for conducting a systematic review. PubMed, CINAHL, Web of Science, and Scopus were searched from the inception between August and November 2024. The quality appraisal was conducted to evaluate the methodological quality of the included articles, selecting the most appropriate tool based on the publication type and study design.

Results

Of 176 records, we selected five experimental studies articles and nine case reports publications. A correlation between specific anticancer treatments (capecitabine, taxanes, and tyrosine kinase inhibitors) and fingerprint alterations has been documented in individuals with various cancer diagnoses (mainly advanced breast and colorectal cancers). The majority of articles were of moderate to low quality.

Conclusions

Although fingerprint alteration as a consequence of specific anticancer treatments has been documented, further large and well-designed experimental studies are necessary to quantify the phenomenon burden in relation to specific anticancer regimens and populations.

Prospero registration n

(CRD42024581192).
虽然人们普遍认为指纹识别在警务和法医科学中发挥了重要作用,但在医学科学中,特别是在抗癌治疗中,指纹的改变却鲜为人知。因此,我们的目的是分析癌症治疗和成人癌症患者指纹改变之间的证据程度。方法根据PRISMA声明和Cochrane系统评价指南进行系统综合评价。PubMed, CINAHL, Web of Science和Scopus从2024年8月至11月开始检索。进行质量评价以评价纳入文章的方法学质量,根据发表类型和研究设计选择最合适的工具。结果从176篇文献中,我们选择了5篇实验研究文章和9篇病例报告出版物。特异性抗癌治疗(卡培他滨、紫杉烷和酪氨酸激酶抑制剂)与指纹改变之间的相关性已经在各种癌症诊断(主要是晚期乳腺癌和结直肠癌)的个体中得到证实。大多数文章的质量都是中等到低的。结论:虽然指纹改变是特定抗癌治疗的结果,但需要进一步的大规模和精心设计的实验研究来量化与特定抗癌方案和人群相关的现象负担。普洛斯彼罗注册n(CRD42024581192)。
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引用次数: 0
Colorectal cancer in Ethiopia: Epidemiological trends, diagnostic and laboratory capacities, and challenges 埃塞俄比亚的结直肠癌:流行病学趋势、诊断和实验室能力以及挑战。
IF 3 3区 医学 Q2 ONCOLOGY Pub Date : 2025-02-01 DOI: 10.1053/j.seminoncol.2024.09.002
Gashaw Getaneh Dagnaw , Haileyesus Dejene
Colorectal cancer (CRC) refers to cancer that develops in the colon or rectum, parts of the large intestine. It ranks as the third most prevalent form of cancer globally. Colorectal cancer is responsible for the morbidity of millions and the loss of hundreds of thousands of lives worldwide although the incidence varies significantly depending on geographical location. In recent years, CRC has decreased in high-income countries due to technological advancements in diagnosis and treatment. However, there is an increased occurrence of CRC morbidity and mortality in low- and middle-income countries. Colorectal cancer is becoming an emerging public health concern in Ethiopia. We noticed that the incidence rates have been lower compared to more developed countries, but recent years have seen a noticeable increase. This rise is attributed to factors such as changes in diet, lifestyle, and an aging population. Common risk factors include dietary shifts towards processed foods and red meat, physical inactivity, obesity, smoking, and alcohol consumption. Unfortunately, in Ethiopia, screening programs for CRC are not widespread, and limited access to diagnostic facilities, lack of public awareness, and insufficient healthcare infrastructure contribute to late-stage diagnoses or left without diagnosis. Treatment options, including surgery, chemotherapy, and radiotherapy, are available but not uniformly accessible across the country, posing challenges for timely and effective treatment. Addressing colorectal cancer in Ethiopia requires a comprehensive approach to enhance public awareness, improve screening and early detection, expand treatment facilities, and train healthcare professionals to provide effective care.
大肠癌(CRC)是指发生在大肠的结肠或直肠部位的癌症。它在全球癌症发病率中排名第三。结肠直肠癌导致全球数百万人发病,数十万人丧生,但不同地理位置的发病率差异很大。近年来,由于诊断和治疗技术的进步,高收入国家的结直肠癌发病率有所下降。然而,在中低收入国家,结直肠癌的发病率和死亡率却在上升。在埃塞俄比亚,结直肠癌正成为一个新的公共卫生问题。我们注意到,与更发达的国家相比,埃塞俄比亚的发病率一直较低,但近年来发病率明显上升。这种上升可归因于饮食、生活方式的改变以及人口老龄化等因素。常见的风险因素包括饮食转向加工食品和红肉、缺乏运动、肥胖、吸烟和饮酒。遗憾的是,在埃塞俄比亚,儿童癌症筛查计划并不普及,诊断设施有限、公众意识缺乏以及医疗基础设施不足,都是导致晚期诊断或未确诊的原因。包括手术、化疗和放疗在内的治疗方案虽已提供,但在全国范围内并不普及,这给及时有效的治疗带来了挑战。要解决埃塞俄比亚的结直肠癌问题,需要采取全面的方法来提高公众意识,改善筛查和早期检测,扩大治疗设施,并培训医疗保健专业人员以提供有效的护理。
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引用次数: 0
The critical role of NLRP3 in drug resistance of cancers: Focus on the molecular mechanisms and possible therapeutics NLRP3在癌症耐药中的关键作用:关注分子机制和可能的治疗方法
IF 3 3区 医学 Q2 ONCOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.seminoncol.2025.152337
Beena Briget Kuriakose , Ahmed Hussein Zwamel , Ayad Abdulrazzaq Mutar , Subasini Uthirapathy , Ashok Kumar Bishoyi , K. Satyam Naidu , Ahmed Hjazi , Prashant Nakash , Renu Arya , Sami G. Almalki
Nod-like receptor protein 3 (NLRP3) is a member of the leucine-rich repeat-containing protein (NLR) canonical inflammasome family. It regulates the pathophysiology of cancer by facilitating immune responses and apoptotic proteins. Furthermore, it has been observed that chemotherapy activates NLRP3 in human malignancies. The secretion of IL-1β and IL-22 to promote cancer spread may be triggered by NLRP3 activation. Furthermore, earlier studies have exhibited that NLRP3 may cause medication resistance when used in cancer treatments given that cell viability may be regulated by NLRP3 depletion. Additionally, clinical studies have demonstrated correlation between NLRP3 expression, lymphogenesis, and cancer metastasis. Various NLRP3 agonists may cause the EMT process, stimulate IL-1β and Wnt/β-catenin signaling, and alter miRNA function in drug-resistant cells. This review seeks to clarify the possibility involvement of NLRP3-related pathways in the control of cancer cells' resistance to widely used treatment approaches, such as chemotherapy. In the end, an improved perception of the corresponding mechanisms behind NLRP3′s tumor-supporting activities will help NLRP3-based treatments advance in the future.
nod样受体蛋白3 (NLRP3)是富亮氨酸重复序列蛋白(NLR)典型炎性小体家族的一员。它通过促进免疫反应和凋亡蛋白调节癌症的病理生理。此外,已经观察到化疗在人类恶性肿瘤中激活NLRP3。IL-1β和IL-22的分泌促进肿瘤扩散可能是由NLRP3激活引发的。此外,早期的研究表明,NLRP3在用于癌症治疗时可能会引起耐药,因为细胞活力可能通过NLRP3的耗尽来调节。此外,临床研究已经证实NLRP3的表达、淋巴发生和肿瘤转移之间存在相关性。各种NLRP3激动剂可能引起EMT过程,刺激IL-1β和Wnt/β-catenin信号传导,并改变耐药细胞的miRNA功能。本综述旨在阐明nlrp3相关通路在控制癌细胞对广泛使用的治疗方法(如化疗)的耐药性中的可能性。最后,对NLRP3肿瘤支持活动背后相应机制的进一步了解将有助于未来基于NLRP3的治疗方法的发展。
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引用次数: 0
Gender-Based Differences in the Efficacy of Anti-EGFR/BRAF/MEK Targeted Therapy in Patients with BRAF-Mutated Metastatic Colorectal Cancer 抗egfr /BRAF/MEK靶向治疗BRAF突变转移性结直肠癌患者疗效的性别差异
IF 3 3区 医学 Q2 ONCOLOGY Pub Date : 2025-02-01 DOI: 10.1053/j.seminoncol.2024.10.004
Laura Pala MD , Tommaso De Pas MD , Emilia Cocorocchio MD , Chiara Catania MD , Giovanni Ceresoli MD , Daniele Laszlo MD , Emma Zattarin MD , Giovanna Rossi MD , Fabio Conforti MD

Objectives

We previously showed that men with melanoma harboring BRAF mutations had significantly lower benefit from targeted therapy as compared with women Here we explored the hypothesis that such gender-based dimorphism in the efficacy of BRAF-pathway blockade extends to other tumor histotypes carrying pathogenic BRAF-mutations.

Methods

We retrospectively analyzed data from a cohort of patients with advanced colorectal-cancer (CRC) harboring BRAF V600E mutations, treated with anti-EGFR/BRAF/MEK targeted therapy. The primary objective was to assess the association between gender and outcome of patients treated with targeted therapy, in terms of overall response rate (ORR), progression-free survival (PFS) and overall survival (OS).A multivariable Cox proportional hazard regression model was used to assess the association between gender and PFS and OS, adjusted for other relevant clinical, pathological and molecular prognostic factors, including ECOG PS (0 vs 1-2), primary tumor site (right-side vs left-side), microsatellite instability status (instable [MSI] vs stable [MSS]), number of metastatic sites at treatment start, treatment type (double targeted therapy [ie, anti-EGFR + anti-BRAF] vs triple targeted therapy [ie, anti-EGFR + anti-BRAF + anti-MEK]) and mutational status of the RNF43 gene (wild type vs mutated).

Results

Ninety-eight patients with advanced CRC were included in the analysis: 59 (60%) were women and 39 (40%) men. The ORR was 43.1% in women vs only 23.7% in men (p-value = .05). Multivariable analysis adjusted for relevant clinical, pathological, and molecular variables associated with patients’ prognosis, showed a significantly shorter PFS and OS in men as compared with women: the adjusted-HR was, respectively, 1.65 (95%CI,1.00-2.69; p = .04) for PFS and 1.83 (95%CI,1.08-3.08; p-value = .02) for OS.

Conclusions

We confirmed a significant gender-based dimorphism in the efficacy of anti-EGFR/BRAF/MEK therapy in patients with advanced-CRC harboring BRAF mutations that warrant further investigation.
目的:我们之前的研究表明,与女性相比,携带BRAF突变的男性黑色素瘤患者从靶向治疗中获得的益处明显较低。在这里,我们探索了这样一种假设,即BRAF通路阻断疗效的性别二型性延伸到其他携带致病性BRAF突变的肿瘤组织型。方法:我们回顾性分析了一组携带BRAF V600E突变的晚期结直肠癌(CRC)患者的数据,这些患者接受了抗egfr /BRAF/MEK靶向治疗。主要目的是评估性别与接受靶向治疗的患者预后之间的关系,包括总缓解率(ORR)、无进展生存期(PFS)和总生存期(OS)。使用多变量Cox比例风险回归模型评估性别与PFS和OS之间的关系,并根据其他相关临床、病理和分子预后因素进行调整,包括ECOG PS (0 vs 1-2)、原发肿瘤部位(右侧vs左侧)、微卫星不稳定状态(不稳定[MSI] vs稳定[MSS])、治疗开始时转移部位数量、治疗类型(双靶向治疗[即抗egfr + 抗braf] vs三联靶向治疗[即,抗egfr + 抗braf + 抗mek])和RNF43基因的突变状态(野生型与突变型)。结果:98例晚期结直肠癌患者纳入分析:女性59例(60%),男性39例(40%)。女性的ORR为43.1%,而男性只有23.7% (p值 = .05)。多变量分析校正了与患者预后相关的临床、病理和分子变量,结果显示男性的PFS和OS明显短于女性:调整后的hr分别为1.65 (95%CI,1.00-2.69;p = .04),1.83 (95%CI,1.08-3.08;p值 = .02)。结论:我们证实,在携带BRAF突变的晚期结直肠癌患者中,抗egfr /BRAF/MEK治疗的疗效存在显著的基于性别的二型性,值得进一步研究。
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引用次数: 0
Obesity correlates to the microsatellite instability of endometrial cancer: A retrospective observational study 肥胖与子宫内膜癌微卫星不稳定性相关:一项回顾性观察研究
IF 3 3区 医学 Q2 ONCOLOGY Pub Date : 2025-02-01 DOI: 10.1053/j.seminoncol.2025.01.001
Carlo Ronsini , Eleonora Braca , Mario Fordellone , Federica Zito Marino , Stefania Napolitano , Antonio Raffone , Luigi Cobellis , Pasquale De Franciscis

Objective

To investigate the relationship between obesity and Microsatellite Instability (MSI) in endometrial cancer (EC), determine which mismatch repair (MMR) protein loss is influenced by obesity, and assess the correlation between BMI and MSI probability.

Methods

This retrospective cohort study included 89 endometrial cancer patients treated at the Gynaecologic oncology unit of the University of Campania “Luigi Vanvitelli” from August 2023 to October 2024, and stratified by BMI: normal weight (n = 26), overweight (n = 31), obese (n = 26), and severely obese (n = 6). Microsatellite instability (MSI) was determined through immunohistochemical assessment of mismatch repair (MMR) protein expression: MLH1, PMS2, MSH2, and MSH6. Tumors were considered MSI if at least one of the four MMR proteins showed loss of expression. Univariate and multivariate logistic regression models were constructed to evaluate the correlation between BMI and MSI

Results

89 patients were enrolled. Obese and severely obese groups showed significantly higher MSI rates (50 % each) compared to normoweight (12 %) and overweight (29 %) groups (P = .013). MLH1 and PMS2 loss of expression were significantly higher in obese and severely obese women (MLH1: P = .003; PMS2: P = .014). Univariate logistic regression showed a significant positive correlation between BMI and MSI (OR 1.02, 95 % CI 1.01–1.04, P = .007). In multivariate analysis, adjusting for grading, stage, histotype, and age, BMI maintained a significant positive correlation with MSI (OR 1.02, 95 % CI 1.01–1.04, P = .048).

Conclusions

This study demonstrates a significant association between obesity and MSI in EC, particularly affecting MLH1 and PMS2 expression. The findings suggest that obesity may contribute to EC development also through MMR deficiency.
目的探讨肥胖与子宫内膜癌(EC)微卫星不稳定性(Microsatellite Instability, MSI)的关系,确定哪些错配修复(mismatch repair, MMR)蛋白丢失受肥胖影响,并评估BMI与MSI概率的相关性。方法回顾性队列研究纳入2023年8月至2024年10月在坎帕尼亚大学Luigi Vanvitelli妇科肿瘤科接受治疗的89例子宫内膜癌患者,按体重指数(BMI)分层:正常体重(n = 26)、超重(n = 31)、肥胖(n = 26)和严重肥胖(n = 6)。微卫星不稳定性(MSI)通过免疫组化评估错配修复(MMR)蛋白表达:MLH1、PMS2、MSH2和MSH6来确定。如果四种MMR蛋白中至少有一种表达缺失,则认为肿瘤为MSI。建立单因素和多因素logistic回归模型来评估BMI与msi的相关性。与正常体重组(12%)和超重组(29%)相比,肥胖和严重肥胖组的MSI率(各为50%)显著高于超重组(P = .013)。肥胖和严重肥胖女性中MLH1和PMS2的表达缺失明显更高(MLH1: P = .003;PMS2: P = .014)。单因素logistic回归显示BMI与MSI呈正相关(OR 1.02, 95% CI 1.01-1.04, P = .007)。在多变量分析中,调整分级、分期、组织型和年龄,BMI与MSI保持显著正相关(OR 1.02, 95% CI 1.01-1.04, P = .048)。结论肥胖与EC中MSI存在显著相关性,尤其是影响MLH1和PMS2的表达。研究结果表明,肥胖也可能通过MMR缺乏导致EC的发展。
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引用次数: 0
The likelihood of being helped or harmed obtained from clinical trial results for cancer therapy: Can it really help? 从癌症治疗的临床试验结果中获得的帮助或伤害的可能性:它真的有帮助吗?
IF 3 3区 医学 Q2 ONCOLOGY Pub Date : 2025-02-01 DOI: 10.1053/j.seminoncol.2024.12.001
Giuseppe Bronte
The majority of cancer clinical trials leading to therapeutic approval focus on outcomes such as objective tumor responses, progression-free survival (PFS), and overall survival (OS). However, it is equally important to assess toxicity, especially when comparing standard therapies with experimental ones. Clinical trials often fail to synthesize the relationship between efficacy and adverse event frequency, partly due to differences in measurement units. To address this, the number needed to treat (NNT) and number needed to harm (NNH) can be used as standardized measures. NNT represents the number of patients required to benefit from a treatment, while NNH indicates the number needed to experience harm. These metrics allow for a more balanced evaluation of therapeutic efficacy and toxicity. By calculating NNT for PFS or OS and NNH for adverse events, we can assess the therapeutic benefit relative to potential harm. The likelihood of being helped or harmed (LHH) combines these metrics into a ratio that expresses the balance between benefit and toxicity. Ideally, LHH values greater than 1 indicate a favorable balance toward efficacy. Though LHH has been applied mainly to psychotropic drugs, it was used in oncology sometimes. For example, studies in advanced non–small cell lung cancer and breast cancer have demonstrated LHH's utility in comparing treatments. Whereas LHH calculation has some limitations, it offers a valuable tool for explaining treatment risks and benefits to patients. It also could guide clinical trial design in cancer therapy.
导致治疗批准的大多数癌症临床试验关注的是客观肿瘤反应、无进展生存期(PFS)和总生存期(OS)等结果。然而,评估毒性同样重要,特别是在比较标准疗法和实验疗法时。临床试验往往不能综合疗效与不良事件发生频率之间的关系,部分原因是测量单位的差异。为了解决这个问题,治疗所需的数量(NNT)和伤害所需的数量(NNH)可以作为标准化措施。NNT表示需要从治疗中受益的患者数量,而NNH表示需要经历伤害的患者数量。这些指标允许对治疗效果和毒性进行更平衡的评估。通过计算PFS或OS的NNT和不良事件的NNH,我们可以评估相对于潜在危害的治疗益处。被帮助或被伤害的可能性(LHH)将这些指标组合成一个比率,表达了益处和毒性之间的平衡。理想情况下,LHH值大于1表明对疗效的有利平衡。虽然LHH主要应用于精神药物,但有时也用于肿瘤。例如,对晚期非小细胞肺癌和乳腺癌的研究已经证明了LHH在比较治疗方面的效用。尽管LHH的计算有一定的局限性,但它为解释治疗的风险和对患者的益处提供了有价值的工具。它还可以指导癌症治疗的临床试验设计。
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引用次数: 0
Chemotherapy plus immunotherapy as first line combination in older patients with extensive stage small cell lung cancer: A systematic review and meta-analysis 化疗加免疫治疗作为广泛期小细胞肺癌老年患者的一线治疗方案:系统综述与荟萃分析。
IF 3 3区 医学 Q2 ONCOLOGY Pub Date : 2025-02-01 DOI: 10.1053/j.seminoncol.2024.11.001
Valentina Bertaglia , Fausto Petrelli , Lorenzo Dottorini , Simona Carnio , Anna Maria Morelli , Alessandro Nepote , Antonio Maccioni , Mario Scartozzi , Cinzia Solinas , Silvia Novello

Background

Small-cell lung cancer (SCLC) accounts for 10%–15% of all lung cancers. At diagnosis, nearly two thirds of patients with SCLC have extensive stage (ES), with a median overall survival (OS) less than 12 months. The combination of protein-death-1/protein-death-ligand-1 (PD-1/PD-L1) immune checkpoint inhibitors (ICIs) with first-line platinum plus etoposide chemotherapy has changed the therapeutic landscape for ES-SCLC. Older adults represent most of the cancers diagnosed and deaths by age group, with an expected increase over the next decade. In the real-world setting, about 30%–40% of patients with a diagnosis of SCLC are reported to be over 70-years-old at the time of diagnosis. However, this subgroup of patients is underrepresented in clinical trials. Based on this evidence, we performed this systematic review to define the activity of ICIs plus chemotherapy in older patients with previously untreated ES-SCLC.

Methods

This systematic review was carried out in accordance with the statement in the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A systematic search on multiple electronic databases was conducted from inception to the end of April to identify randomized trials that prospectively evaluated chemotherapy ± PD-1/PD-L1 ICIs. When more than one report of the same study was available, the most recent data (with longer follow-up and/or higher number of patients) was considered. The primary endpoint of the study was efficacy, in terms of overall survival, progression-free survival, and disease control rate.

Results

We selected six randomized clinical trials that enrolled 3396 patients in the meta-analysis. In the experimental arm, 670 patients were 65 years of age and older compared to 504 in the control arm. In the subgroup of patients ≥65 years, adding ICIs to chemotherapy led to a significant benefit in OS [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.72-0.90). There was moderate but not-significant heterogenity among the trials (I2 = 47%, P = 0.07).

Conclusion

This systematic review found that the combination of chemotherapy plus ICIs improved OS among older patients with ES-SCLC. Biomarker and comprehensive geriatric assessment are needed to improve the identification and selection of patients with cancer that are uniformly defined as older.
背景:小细胞肺癌(SCLC)占所有肺癌的10%-15%。在诊断时,近三分之二的SCLC患者具有广泛分期(ES),中位总生存期(OS)小于12个月。蛋白-死亡-1/蛋白-死亡-配体-1 (PD-1/PD-L1)免疫检查点抑制剂(ICIs)联合一线铂+依托泊苷化疗改变了ES-SCLC的治疗前景。按年龄组划分的癌症确诊和死亡病例中,老年人占大多数,预计今后十年这一数字还会增加。在现实环境中,约30%-40%被诊断为SCLC的患者在诊断时年龄超过70岁。然而,这一亚组患者在临床试验中代表性不足。基于这一证据,我们进行了这项系统综述,以确定先前未经治疗的老年ES-SCLC患者的ICIs加化疗的活性。方法:本系统评价按照系统评价和荟萃分析首选报告项目(PRISMA)指南中的声明进行。从开始到4月底,对多个电子数据库进行了系统检索,以确定前瞻性评价化疗±PD-1/PD-L1 ICIs的随机试验。当同一研究的多个报告可用时,考虑最新的数据(随访时间较长和/或患者人数较多)。该研究的主要终点是疗效,即总生存期、无进展生存期和疾病控制率。结果:我们在meta分析中选择了6项随机临床试验,共纳入3396例患者。在实验组中,670名患者年龄在65岁及以上,而对照组为504名。在≥65岁的患者亚组中,在化疗中加入ICIs可显著改善OS[风险比(HR) 0.80, 95%可信区间(CI) 0.72-0.90]。试验间存在中度但不显著的异质性(I2 = 47%,P = 0.07)。结论:本系统综述发现化疗联合ICIs可改善老年ES-SCLC患者的OS。需要生物标志物和全面的老年评估来改进对被统一定义为老年的癌症患者的识别和选择。
{"title":"Chemotherapy plus immunotherapy as first line combination in older patients with extensive stage small cell lung cancer: A systematic review and meta-analysis","authors":"Valentina Bertaglia ,&nbsp;Fausto Petrelli ,&nbsp;Lorenzo Dottorini ,&nbsp;Simona Carnio ,&nbsp;Anna Maria Morelli ,&nbsp;Alessandro Nepote ,&nbsp;Antonio Maccioni ,&nbsp;Mario Scartozzi ,&nbsp;Cinzia Solinas ,&nbsp;Silvia Novello","doi":"10.1053/j.seminoncol.2024.11.001","DOIUrl":"10.1053/j.seminoncol.2024.11.001","url":null,"abstract":"<div><h3>Background</h3><div>Small-cell lung cancer (SCLC) accounts for 10%–15% of all lung cancers. At diagnosis, nearly two thirds of patients with SCLC have extensive stage (ES), with a median overall survival (OS) less than 12 months. The combination of protein-death-1/protein-death-ligand-1 (PD-1/PD-L1) immune checkpoint inhibitors (ICIs) with first-line platinum plus etoposide chemotherapy has changed the therapeutic landscape for ES-SCLC. Older adults represent most of the cancers diagnosed and deaths by age group, with an expected increase over the next decade. In the real-world setting, about 30%–40% of patients with a diagnosis of SCLC are reported to be over 70-years-old at the time of diagnosis. However, this subgroup of patients is underrepresented in clinical trials. Based on this evidence, we performed this systematic review to define the activity of ICIs plus chemotherapy in older patients with previously untreated ES-SCLC.</div></div><div><h3>Methods</h3><div>This systematic review was carried out in accordance with the statement in the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A systematic search on multiple electronic databases was conducted from inception to the end of April to identify randomized trials that prospectively evaluated chemotherapy <span><math><mo>±</mo></math></span> PD-1/PD-L1 ICIs. When more than one report of the same study was available, the most recent data (with longer follow-up and/or higher number of patients) was considered. The primary endpoint of the study was efficacy, in terms of overall survival, progression-free survival, and disease control rate.</div></div><div><h3>Results</h3><div>We selected six randomized clinical trials that enrolled 3396 patients in the meta-analysis. In the experimental arm, 670 patients were 65 years of age and older compared to 504 in the control arm. In the subgroup of patients ≥65 years, adding ICIs to chemotherapy led to a significant benefit in OS [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.72-0.90). There was moderate but not-significant heterogenity among the trials (I<sup>2</sup> = 47%, <em>P</em> = 0.07).</div></div><div><h3>Conclusion</h3><div>This systematic review found that the combination of chemotherapy plus ICIs improved OS among older patients with ES-SCLC. Biomarker and comprehensive geriatric assessment are needed to improve the identification and selection of patients with cancer that are uniformly defined as older.</div></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"52 1","pages":"Pages 14-18"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pioneering the Future of Oncology: A New Vision for Seminars in Oncology 开创肿瘤学的未来:肿瘤学研讨会的新愿景
IF 3 3区 医学 Q2 ONCOLOGY Pub Date : 2025-02-01 DOI: 10.1053/S0093-7754(25)00032-6
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引用次数: 0
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Seminars in oncology
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