Pub Date : 2024-10-04DOI: 10.1016/j.critrevonc.2024.104529
Maria Mainou , Kalliopi Tsapa , Theodoros Michailidis , Konstantinos Malandris , Thomas Karagiannis , Ioannis Avgerinos , Aris Liakos , Maria Papaioannou , Evangelos Terpos , Vinay Prasad , Apostolos Tsapas
Purpose
Many clinical trials of therapeutic interventions for multiple myeloma do not use patient important outcomes and rely on the use of surrogate endpoints. The aim of this systematic review was to depict the landscape of randomized controlled trials in myeloma research and compile the endpoints utilized.
Methods
We searched Embase, PubMed, and the Cochrane Library for randomized controlled trials in myeloma published in English up to October 2023. We included trials exploring efficacy of therapeutic modalities for myeloma itself or supportive care interventions.
Results
A total of 2181 records, reporting data from 624 trials (448 comparing anti-myeloma treatments and 176 comparing supportive interventions) were deemed eligible. The most common primary outcome reported was disease response, followed by progression free survival (PFS) and overall survival (OS). Across all trials, 119 (19.1 %) used OS as the primary endpoint, while 316 (50.6 %) listed it as a secondary endpoint. Quality of life was less commonly prioritized, featured as primary endpoint only in seven studies (1.1 %) and as secondary endpoint in 115 studies (18.4 %). Studies funded by the pharmaceutical industry were more likely (Odds Ratio [OR] 3.85, 95 % CI 2.41–6.35) to use PFS as primary outcome. Similarly, studies with authors that had conflicts of interest with the funding source were more likely (OR 4.57, 95 % CI 2.72–7.92) to use PFS as the primary outcome.
Conclusion
While randomized controlled trials for multiple myeloma predominantly rely on surrogate endpoints, particularly PFS, the importance of OS as an outcome should not be overlooked.
目的：许多针对多发性骨髓瘤治疗干预措施的临床试验并未使用对患者有重要意义的结果，而是依赖于使用替代终点。本系统性综述旨在描述骨髓瘤研究中随机对照试验的情况，并汇编所使用的终点：我们检索了 Embase、PubMed 和 Cochrane 图书馆中截至 2023 年 10 月用英文发表的骨髓瘤随机对照试验。我们纳入了探讨骨髓瘤本身治疗方法或支持性护理干预措施疗效的试验：共有2181条记录被认为符合条件，这些记录报告了来自624项试验（448项比较了抗骨髓瘤治疗方法，176项比较了支持性干预措施）的数据。最常见的主要结果是疾病反应，其次是无进展生存期（PFS）和总生存期（OS）。在所有试验中，有119项（19.1%）将OS作为主要终点，316项（50.6%）将其列为次要终点。生活质量较少被优先考虑，仅有7项研究（1.1%）将其作为主要终点，115项研究（18.4%）将其作为次要终点。由制药业资助的研究更有可能将 PFS 作为主要结果（Odds Ratio [OR] 3.85，95% CI 2.41 至 6.35）。同样，作者与资助方存在利益冲突的研究更有可能（OR 4.57，95% CI 2.72-7.92）将PFS作为主要结果：尽管多发性骨髓瘤随机对照试验主要依赖于替代终点，尤其是PFS，但OS作为一个结果的重要性不容忽视。
{"title":"Outcomes in randomized controlled trials of therapeutic interventions for multiple myeloma: A systematic review","authors":"Maria Mainou , Kalliopi Tsapa , Theodoros Michailidis , Konstantinos Malandris , Thomas Karagiannis , Ioannis Avgerinos , Aris Liakos , Maria Papaioannou , Evangelos Terpos , Vinay Prasad , Apostolos Tsapas","doi":"10.1016/j.critrevonc.2024.104529","DOIUrl":"10.1016/j.critrevonc.2024.104529","url":null,"abstract":"<div><h3>Purpose</h3><div>Many clinical trials of therapeutic interventions for multiple myeloma do not use patient important outcomes and rely on the use of surrogate endpoints. The aim of this systematic review was to depict the landscape of randomized controlled trials in myeloma research and compile the endpoints utilized.</div></div><div><h3>Methods</h3><div>We searched Embase, PubMed, and the Cochrane Library for randomized controlled trials in myeloma published in English up to October 2023. We included trials exploring efficacy of therapeutic modalities for myeloma itself or supportive care interventions.</div></div><div><h3>Results</h3><div>A total of 2181 records, reporting data from 624 trials (448 comparing anti-myeloma treatments and 176 comparing supportive interventions) were deemed eligible. The most common primary outcome reported was disease response, followed by progression free survival (PFS) and overall survival (OS). Across all trials, 119 (19.1 %) used OS as the primary endpoint, while 316 (50.6 %) listed it as a secondary endpoint. Quality of life was less commonly prioritized, featured as primary endpoint only in seven studies (1.1 %) and as secondary endpoint in 115 studies (18.4 %). Studies funded by the pharmaceutical industry were more likely (Odds Ratio [OR] 3.85, 95 % CI 2.41–6.35) to use PFS as primary outcome. Similarly, studies with authors that had conflicts of interest with the funding source were more likely (OR 4.57, 95 % CI 2.72–7.92) to use PFS as the primary outcome.</div></div><div><h3>Conclusion</h3><div>While randomized controlled trials for multiple myeloma predominantly rely on surrogate endpoints, particularly PFS, the importance of OS as an outcome should not be overlooked.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"204 ","pages":"Article 104529"},"PeriodicalIF":5.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-26DOI: 10.1016/j.critrevonc.2024.104522
Qi Wang , Jianan Yu , Xuedong Sun , Jian Li , Shasha Cao , Yanjing Han , Haochen Wang , Zeran Yang , Jianjun Li , Caixia Hu , Yonghong Zhang , Long Jin
<div><h3>Purpose</h3><div>For patients with advanced or unresectable hepatocellular carcinoma (HCC), safe and effective therapies are urgently needed to improve their long-term prognosis. Although the guidelines recommend first-line treatments such as sorafenib, lenvatinib, and atezolizumab in combination with bevacizumab (T+A) and second-line treatments such as regorafenib, the efficacy comparison between drugs is lacking, that is, a treatment is not recommended as the optimal or alternative choice for a specific patient population. Therefore, we will conduct a high-quality network meta-analysis based on Phase III randomized controlled trials (RCTs) to systematically evaluate and compare overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and serious adverse events (SAE) of different treatment protocols in the context of first-line and second-line therapies, which are critical for clinical decision making and prognostic improvement in advanced HCC patients.</div></div><div><h3>Methods</h3><div>The studies of interest were Phase III RCTs evaluating the efficacy or safety of first- or second-line therapies in patients with unresectable or advanced HCC. Literature published in English from the four databases of PubMed, Embase, Cochrane Library, and Web of Science was comprehensively searched from the inception to May 23, 2022. Outcomes of interest included OS, PFS, ORR, and SAE. A league table was developed to show the results of the comparison between different treatments. A histogram of cumulative probability was drawn to discuss the ranking probability of treatments based on different outcomes. The effectiveness and safety of various treatments were comprehensively considered and the two-dimensional diagram was plotted to guide clinical practice. The Gemtc package in R Studio was used for network meta-analysis in a Bayesian framework.</div></div><div><h3>Results</h3><div>The results showed that HAIC-FO was superior to T+A regimen, regardless of OS, PFS or ORR. TACE combined with lenvatinib performed better than T+A in PFS, and ORR. In addition to the T+A regimen, Sintilimab combined with IBI305 and camrelizumab combined with apatinib were also associated with longer OS, PFS, and ORR, and their SAE incidence was not higher than that of T+A, especially for camrelizumab combined with apatinib, its safety was better than that of T+A regimen. There were no new treatments or combinations that were more effective than regorafenib. It was important to note that for PFS, the efficacy of apatinib and cabozantinib was not statistically different from that of regorafenib, so these two treatments could be used as alternative treatment options in cases where regorafenib was not tolerated or treatment failed.</div></div><div><h3>Conclusions</h3><div>We conducted a network meta-analysis to evaluate the efficacy and safety of multiple treatment modalities by integrating the results of direct and indirect comparisons. This study
目的：对于晚期或无法切除的肝细胞癌（HCC）患者，迫切需要安全有效的疗法来改善其长期预后。尽管指南推荐了索拉非尼、来伐替尼、阿替佐珠单抗联合贝伐单抗（T+A）等一线治疗方法和瑞戈非尼等二线治疗方法，但缺乏药物之间的疗效比较，也就是说，没有推荐某种治疗方法作为特定患者人群的最佳选择或替代选择。因此，我们将基于III期随机对照试验（RCT）开展一项高质量的网络荟萃分析，系统评估和比较一线和二线治疗方案中不同治疗方案的总生存期（OS）、无进展生存期（PFS）、客观应答率（ORR）和严重不良事件（SAE），这对晚期HCC患者的临床决策和预后改善至关重要：所关注的研究是评估不可切除或晚期 HCC 患者一线或二线疗法疗效或安全性的 III 期 RCT。全面检索了从开始到2022年5月23日在PubMed、Embase、Cochrane Library和Web of Science四个数据库中发表的英文文献。研究结果包括OS、PFS、ORR和SAE。为显示不同治疗方法之间的比较结果，编制了一个列表。绘制累积概率直方图，讨论基于不同结果的治疗方法的排名概率。综合考虑各种治疗方法的有效性和安全性，绘制出二维图表，以指导临床实践。使用R Studio中的Gemtc软件包在贝叶斯框架下进行网络荟萃分析：结果显示，无论OS、PFS还是ORR，HAIC-FO均优于T+A方案。TACE联合来伐替尼在PFS和ORR方面优于T+A。除T+A方案外，辛替利单抗联合IBI305和坎瑞珠单抗联合阿帕替尼也具有更长的OS、PFS和ORR，且SAE发生率不高于T+A方案，尤其是坎瑞珠单抗联合阿帕替尼，其安全性优于T+A方案。没有比瑞戈非尼更有效的新疗法或新组合。值得注意的是，在PFS方面，阿帕替尼和卡博替尼的疗效与瑞戈非尼没有统计学差异，因此在瑞戈非尼不能耐受或治疗失败的情况下，这两种治疗方法可作为替代治疗方案：我们进行了一项网络荟萃分析，通过整合直接和间接比较的结果来评估多种治疗方式的有效性和安全性。本研究纳入了高质量的多中心III期RCT，整理并总结了一线和二线治疗晚期或不可切除HCC的所有治疗方法，分别与T+A和瑞戈非尼进行了比较，并根据疗效和安全性进行了排序，以支持临床决策。
{"title":"Sequencing of systemic therapy in unresectable hepatocellular carcinoma: A systematic review and Bayesian network meta-analysis of randomized clinical trials","authors":"Qi Wang , Jianan Yu , Xuedong Sun , Jian Li , Shasha Cao , Yanjing Han , Haochen Wang , Zeran Yang , Jianjun Li , Caixia Hu , Yonghong Zhang , Long Jin","doi":"10.1016/j.critrevonc.2024.104522","DOIUrl":"10.1016/j.critrevonc.2024.104522","url":null,"abstract":"<div><h3>Purpose</h3><div>For patients with advanced or unresectable hepatocellular carcinoma (HCC), safe and effective therapies are urgently needed to improve their long-term prognosis. Although the guidelines recommend first-line treatments such as sorafenib, lenvatinib, and atezolizumab in combination with bevacizumab (T+A) and second-line treatments such as regorafenib, the efficacy comparison between drugs is lacking, that is, a treatment is not recommended as the optimal or alternative choice for a specific patient population. Therefore, we will conduct a high-quality network meta-analysis based on Phase III randomized controlled trials (RCTs) to systematically evaluate and compare overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and serious adverse events (SAE) of different treatment protocols in the context of first-line and second-line therapies, which are critical for clinical decision making and prognostic improvement in advanced HCC patients.</div></div><div><h3>Methods</h3><div>The studies of interest were Phase III RCTs evaluating the efficacy or safety of first- or second-line therapies in patients with unresectable or advanced HCC. Literature published in English from the four databases of PubMed, Embase, Cochrane Library, and Web of Science was comprehensively searched from the inception to May 23, 2022. Outcomes of interest included OS, PFS, ORR, and SAE. A league table was developed to show the results of the comparison between different treatments. A histogram of cumulative probability was drawn to discuss the ranking probability of treatments based on different outcomes. The effectiveness and safety of various treatments were comprehensively considered and the two-dimensional diagram was plotted to guide clinical practice. The Gemtc package in R Studio was used for network meta-analysis in a Bayesian framework.</div></div><div><h3>Results</h3><div>The results showed that HAIC-FO was superior to T+A regimen, regardless of OS, PFS or ORR. TACE combined with lenvatinib performed better than T+A in PFS, and ORR. In addition to the T+A regimen, Sintilimab combined with IBI305 and camrelizumab combined with apatinib were also associated with longer OS, PFS, and ORR, and their SAE incidence was not higher than that of T+A, especially for camrelizumab combined with apatinib, its safety was better than that of T+A regimen. There were no new treatments or combinations that were more effective than regorafenib. It was important to note that for PFS, the efficacy of apatinib and cabozantinib was not statistically different from that of regorafenib, so these two treatments could be used as alternative treatment options in cases where regorafenib was not tolerated or treatment failed.</div></div><div><h3>Conclusions</h3><div>We conducted a network meta-analysis to evaluate the efficacy and safety of multiple treatment modalities by integrating the results of direct and indirect comparisons. This study","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"204 ","pages":"Article 104522"},"PeriodicalIF":5.5,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-25DOI: 10.1016/j.critrevonc.2024.104514
Meng-Yao Xu , Na Zeng , Sheng Ma , Zi-Jin Hua , Si-Han Zhang , Ji-Cheng Xiang , Yi-Fan Xiong , Zhi-Yu Xia , Jian-Xuan Sun , Chen-Qian Liu , Jin-Zhou Xu , Ye An , Shao-Gang Wang , Qi Dong Xia
Prostate cancer (PCa) is a prevalent malignant tumor affecting the male reproductive system and there are mainly three widely accepted PCa surgery types in current clinical treatment: open radical prostatectomy (ORP), laparoscopic radical prostatectomy (LRP) and robot-assisted radical prostatectomy (RARP). Here, we aimed to evaluate the clinical effect of RARP for PCa patients compared with ORP and LRP based on the context of PCa encompass two dimensions: oncological outcomes (biochemical recurrence (BCR) and positive surgical margin (PSM)) and functional outcomes (urinary continence and recovery of erectile function) in this network meta-analysis (NMA). PubMed, Embase and Cochrane databases were systematically searched in January 7, 2024. 4 randomized controlled trials (RCTs) and 72 non-RCTs were included. RARP displayed significant positive effect on lower BCR and better recovery of erectile function but no significant differences existed among three surgery types for PSM and urinary continence.
{"title":"A clinical evaluation of robotic-assisted radical prostatectomy (RARP) in located prostate cancer: A systematic review and network meta-analysis","authors":"Meng-Yao Xu , Na Zeng , Sheng Ma , Zi-Jin Hua , Si-Han Zhang , Ji-Cheng Xiang , Yi-Fan Xiong , Zhi-Yu Xia , Jian-Xuan Sun , Chen-Qian Liu , Jin-Zhou Xu , Ye An , Shao-Gang Wang , Qi Dong Xia","doi":"10.1016/j.critrevonc.2024.104514","DOIUrl":"10.1016/j.critrevonc.2024.104514","url":null,"abstract":"<div><div>Prostate cancer (PCa) is a prevalent malignant tumor affecting the male reproductive system and there are mainly three widely accepted PCa surgery types in current clinical treatment: open radical prostatectomy (ORP), laparoscopic radical prostatectomy (LRP) and robot-assisted radical prostatectomy (RARP). Here, we aimed to evaluate the clinical effect of RARP for PCa patients compared with ORP and LRP based on the context of PCa encompass two dimensions: oncological outcomes (biochemical recurrence (BCR) and positive surgical margin (PSM)) and functional outcomes (urinary continence and recovery of erectile function) in this network meta-analysis (NMA). PubMed, Embase and Cochrane databases were systematically searched in January 7, 2024. 4 randomized controlled trials (RCTs) and 72 non-RCTs were included. RARP displayed significant positive effect on lower BCR and better recovery of erectile function but no significant differences existed among three surgery types for PSM and urinary continence.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"204 ","pages":"Article 104514"},"PeriodicalIF":5.5,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334449","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}
Pub Date : 2024-09-24DOI: 10.1016/j.critrevonc.2024.104519
Evelyn Lilian Beas-Lozano , Sergio Contreras , Maria Andrea Mac Donald-Jaramillo , Citlali Frayde-Aguilar , Javier Carrillo-Vidales , Salvador Jaime-Casas , Bertha Alejandra Martinez-Cannon
Cervical cancer is a significant global health issue, particularly in low- and middle-income countries. Women living with HIV (WLWH) are not only at higher risk of cervical cancer due to their increased susceptibility to high-risk human papillomavirus (HPV) infection and compromised immune status, but also higher mortality rates have been reported. Therefore, prevention, optimal screening, use of highly active antiretroviral therapy (HAART), and early access to treatment are of utmost importance in this population. While international guidelines for cervical cancer state no treatment differences should be made for WLWH, there is evidence that this population of patients represents a challenge in decision-making for medical oncologists, radiation oncologists, and surgical oncologists. This review summarizes the available evidence on the different treatment strategies for WLWH and invasive cervical cancer and highlights the need for special considerations in screening andprevention of cervical cancer in WLWH.
{"title":"Current management of cervical cancer in women living with HIV","authors":"Evelyn Lilian Beas-Lozano , Sergio Contreras , Maria Andrea Mac Donald-Jaramillo , Citlali Frayde-Aguilar , Javier Carrillo-Vidales , Salvador Jaime-Casas , Bertha Alejandra Martinez-Cannon","doi":"10.1016/j.critrevonc.2024.104519","DOIUrl":"10.1016/j.critrevonc.2024.104519","url":null,"abstract":"<div><div>Cervical cancer is a significant global health issue, particularly in low- and middle-income countries. Women living with HIV (WLWH) are not only at higher risk of cervical cancer due to their increased susceptibility to high-risk human papillomavirus (HPV) infection and compromised immune status, but also higher mortality rates have been reported. Therefore, prevention, optimal screening, use of highly active antiretroviral therapy (HAART), and early access to treatment are of utmost importance in this population. While international guidelines for cervical cancer state no treatment differences should be made for WLWH, there is evidence that this population of patients represents a challenge in decision-making for medical oncologists, radiation oncologists, and surgical oncologists. This review summarizes the available evidence on the different treatment strategies for WLWH and invasive cervical cancer and highlights the need for special considerations in screening andprevention of cervical cancer in WLWH.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"204 ","pages":"Article 104519"},"PeriodicalIF":5.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-24DOI: 10.1016/j.critrevonc.2024.104524
Annarita Peddio , Erica Pietroluongo , Maria Rosaria Lamia , Angelo Luciano , Aldo Caltavituro , Roberto Buonaiuto , Giovanna Pecoraro , Pietro De Placido , Giovannella Palmieri , Roberto Bianco , Mario Giuliano , Alberto Servetto
Neuroendocrine neoplasms (NENs) represent a diagnostic and therapeutic challenge, due to their heterogeneity and limited treatment options. Conventional imaging techniques and therapeutic strategies may become unreliable during follow-up, due to the tendency of these neoplasms to dedifferentiate over time. Therefore, novel diagnostic and therapeutic options are required for the management of NEN patients. Delta-like ligand 3 (DLL3), an inhibitory ligand of Notch receptor, has emerged as a potential target for novel diagnostic and therapeutic strategies in NENs, since overexpression of DLL3 has been associated with tumor progression, poor prognosis and dedifferentiation in several NENs. This narrative review examines the current evidence about DLL3, its structure, function and association with tumorigenesis in NENs. Ongoing studies exploring the role of DLL3 as an emerging diagnostic marker are reviewed. Promising therapeutic options, such as antibody-conjugated drugs, CAR-T cells and radioimmunoconjugates, are also discussed.
神经内分泌肿瘤（NENs）因其异质性和有限的治疗方案而成为诊断和治疗的难题。传统的成像技术和治疗策略在随访过程中可能会变得不可靠，因为这些肿瘤随着时间的推移容易发生再分化。因此，需要新的诊断和治疗方案来治疗 NEN 患者。δ样配体3（DLL3）是Notch受体的一种抑制性配体，它已成为NENs新型诊断和治疗策略的潜在靶点，因为在几种NENs中，DLL3的过度表达与肿瘤进展、预后不良和去分化有关。这篇叙述性综述探讨了有关 DLL3、其结构、功能以及与念珠菌病肿瘤发生相关性的现有证据。本文还回顾了正在进行的探索 DLL3 作为新兴诊断标志物的研究。还讨论了前景看好的治疗方案，如抗体结合药物、CAR-T 细胞和放射免疫结合剂。
{"title":"DLL3 as a potential diagnostic and therapeutic target in neuroendocrine neoplasms: A narrative review","authors":"Annarita Peddio , Erica Pietroluongo , Maria Rosaria Lamia , Angelo Luciano , Aldo Caltavituro , Roberto Buonaiuto , Giovanna Pecoraro , Pietro De Placido , Giovannella Palmieri , Roberto Bianco , Mario Giuliano , Alberto Servetto","doi":"10.1016/j.critrevonc.2024.104524","DOIUrl":"10.1016/j.critrevonc.2024.104524","url":null,"abstract":"<div><div>Neuroendocrine neoplasms (NENs) represent a diagnostic and therapeutic challenge, due to their heterogeneity and limited treatment options. Conventional imaging techniques and therapeutic strategies may become unreliable during follow-up, due to the tendency of these neoplasms to dedifferentiate over time. Therefore, novel diagnostic and therapeutic options are required for the management of NEN patients. Delta-like ligand 3 (DLL3), an inhibitory ligand of Notch receptor, has emerged as a potential target for novel diagnostic and therapeutic strategies in NENs, since overexpression of DLL3 has been associated with tumor progression, poor prognosis and dedifferentiation in several NENs. This narrative review examines the current evidence about DLL3, its structure, function and association with tumorigenesis in NENs. Ongoing studies exploring the role of DLL3 as an emerging diagnostic marker are reviewed. Promising therapeutic options, such as antibody-conjugated drugs, CAR-T cells and radioimmunoconjugates, are also discussed.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"204 ","pages":"Article 104524"},"PeriodicalIF":5.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334451","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}
Pub Date : 2024-09-24DOI: 10.1016/j.critrevonc.2024.104523
Julia Sprokkerieft , Justine N. van der Beek , Filippo Spreafico , Barbara Selle , Tanzina Chowdhury , Norbert Graf , Arnauld C. Verschuur , Rana Dandis , Axel Bex , James I. Geller , Godelieve A.M. Tytgat , Marry M. van den Heuvel-Eibrink
Renal cell carcinoma (RCC) is a very rare type of renal cancer in children and young adults. When metastasized or recurrent, no standards of care are available, and outcome is still poor. The tyrosine kinase inhibitor axitinib is approved for treatment of RCC in adults, but its effects in children and young adults with RCC remains unclear. Due to the histological and biological differences between children and adults, it is difficult to extrapolate knowledge on treatments from the adult to the pediatric and young adult setting. This paper summarizes the clinical characteristics and outcomes of patients with RCC who were treated with axitinib, with the aim to gain insight in the clinical efficacy of this compound in this young patient group.
{"title":"Outcome after treatment with axitinib in children, young adults, and adults with renal cell carcinoma: a narrative review","authors":"Julia Sprokkerieft , Justine N. van der Beek , Filippo Spreafico , Barbara Selle , Tanzina Chowdhury , Norbert Graf , Arnauld C. Verschuur , Rana Dandis , Axel Bex , James I. Geller , Godelieve A.M. Tytgat , Marry M. van den Heuvel-Eibrink","doi":"10.1016/j.critrevonc.2024.104523","DOIUrl":"10.1016/j.critrevonc.2024.104523","url":null,"abstract":"<div><div>Renal cell carcinoma (RCC) is a very rare type of renal cancer in children and young adults. When metastasized or recurrent, no standards of care are available, and outcome is still poor. The tyrosine kinase inhibitor axitinib is approved for treatment of RCC in adults, but its effects in children and young adults with RCC remains unclear. Due to the histological and biological differences between children and adults, it is difficult to extrapolate knowledge on treatments from the adult to the pediatric and young adult setting. This paper summarizes the clinical characteristics and outcomes of patients with RCC who were treated with axitinib, with the aim to gain insight in the clinical efficacy of this compound in this young patient group.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"204 ","pages":"Article 104523"},"PeriodicalIF":5.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334453","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}
In recent years, alternative methods to dark ink tattoos for patient positioning in radiotherapy have been explored. This review aims to analyse the evidence for alternative strategies to traditional dark tattoos. An electronic search was conducted in PubMed, EMBASE, Cochrane Library, Web of Sciences and SCOPUS. Twenty-one articles out of 383 titles fulfilled the selection criteria and were included in the review. These studies were categorized into tattoo-less methods (n=14), UV ink tattoos (n=4) and other techniques (n=3). In most of the selected articles (n=13) focusing on tattoo-less treatments, SGRT is used for patient positioning. These three alternative techniques to dark tattoos are used in different anatomical regions and treatment modalities, with breast cancer being the most prevalent. Tattoo-less techniques are a promising alternative to traditional tattoo-based methods for patient positioning. They have the potential to improve the patient experience and represent an area of ongoing innovation and improvement.
{"title":"Advancing patient setup: A comprehensive scoping review of tattoo-less techniques in radiation therapy","authors":"Andrea Lastrucci , Livia Marrazzo , Icro Meattini , Gabriele Simontacchi , Yannick Wandael , Cinzia Talamonti , Stefania Pallotta , Renzo Ricci , Lorenzo Livi","doi":"10.1016/j.critrevonc.2024.104518","DOIUrl":"10.1016/j.critrevonc.2024.104518","url":null,"abstract":"<div><div>In recent years, alternative methods to dark ink tattoos for patient positioning in radiotherapy have been explored. This review aims to analyse the evidence for alternative strategies to traditional dark tattoos. An electronic search was conducted in PubMed, EMBASE, Cochrane Library, Web of Sciences and SCOPUS. Twenty-one articles out of 383 titles fulfilled the selection criteria and were included in the review. These studies were categorized into tattoo-less methods (n=14), UV ink tattoos (n=4) and other techniques (n=3). In most of the selected articles (n=13) focusing on tattoo-less treatments, SGRT is used for patient positioning. These three alternative techniques to dark tattoos are used in different anatomical regions and treatment modalities, with breast cancer being the most prevalent. Tattoo-less techniques are a promising alternative to traditional tattoo-based methods for patient positioning. They have the potential to improve the patient experience and represent an area of ongoing innovation and improvement.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"204 ","pages":"Article 104518"},"PeriodicalIF":5.5,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1016/j.critrevonc.2024.104516
Armia Ahmadi-Hadad , Paula Catarina Carvalho de Queiroz , Francesco Schettini , Mario Giuliano
Triple-negative breast cancer (TNBC) exhibits a proclivity for early recurrence and development of metastasis. Moreover, drug resistance tends to arise few months following chemotherapeutic regimen with agents such as Doxorubicin, Paclitaxel, Docetaxel, and Cisplatin. miR-200 family and miR-205 are considered key regulators of metastasis by regulating the Epithelial-to-mesenchymal transition (EMT) via inhibiting ZEB1. Therefore, these microRNAs may offer therapeutic applications. Moreover, they hold potential for inhibiting chemoresistance and increasing chemosensitivity. These microRNAs are suppressed in TNBC cells. Increasing their levels, however, can inhibit EMT and improve progression-free survival (PFS). Besides using direct miRNA therapy via viral vectors, some drugs like Acetaminophen, or Tamoxifen are deemed useful for TNBC due to their ability to upregulate these miRNAs. In this review, by conducting an advanced search on PubMed, Embase, and Medline and selecting pertinent studies, we aimed to explore the potential applications of these microRNAs in controlling EMT and overcoming chemoresistance.
{"title":"Reawakening the master switches in triple-negative breast cancer: A strategic blueprint for confronting metastasis and chemoresistance via microRNA-200/205: A systematic review","authors":"Armia Ahmadi-Hadad , Paula Catarina Carvalho de Queiroz , Francesco Schettini , Mario Giuliano","doi":"10.1016/j.critrevonc.2024.104516","DOIUrl":"10.1016/j.critrevonc.2024.104516","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) exhibits a proclivity for early recurrence and development of metastasis. Moreover, drug resistance tends to arise few months following chemotherapeutic regimen with agents such as Doxorubicin, Paclitaxel, Docetaxel, and Cisplatin. miR-200 family and miR-205 are considered key regulators of metastasis by regulating the Epithelial-to-mesenchymal transition (EMT) via inhibiting ZEB1. Therefore, these microRNAs may offer therapeutic applications. Moreover, they hold potential for inhibiting chemoresistance and increasing chemosensitivity. These microRNAs are suppressed in TNBC cells. Increasing their levels, however, can inhibit EMT and improve progression-free survival (PFS). Besides using direct miRNA therapy via viral vectors, some drugs like Acetaminophen, or Tamoxifen are deemed useful for TNBC due to their ability to upregulate these miRNAs. In this review, by conducting an advanced search on PubMed, Embase, and Medline and selecting pertinent studies, we aimed to explore the potential applications of these microRNAs in controlling EMT and overcoming chemoresistance.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"204 ","pages":"Article 104516"},"PeriodicalIF":5.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303482","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}
Pub Date : 2024-09-19DOI: 10.1016/j.critrevonc.2024.104520
Ioannis Georgakopoulos , Vassilis Kouloulias , George Ntoumas , Dimitra Desse , Ioannis Koukourakis , Andromachi Kougioumtzopoulou , Andrianni Charpidou , Konstantinos N. Syrigos , Anna Zygogianni
The approval of tyrosine kinase inhibitors (TKIs) as first-line agents has revolutionised treatment of patients diagnosed with advanced non-small cell lung cancer (NSCLC) harboring targetable mutations, adding substantial overall survival (OS) benefit, compared to chemotherapy. However, the efficacy of these agents is inevitably diminished at a point in the disease course, either because of cellular resistance-mechanisms or due to affected pharmacokinetics, like low-central nervous system penetration. The aim of this article is to review existing evidence on the combined use of EGFR (epidermal growth factor)- or ALK (anaplastic lymphoma kinase)-specific TKIs and radiotherapy (RT) in advanced NSCLC setting, as an attempt to delay or overcome TKI-resistance and thus, to expand the time period during which patients derive benefit from a given line of targeted therapy. At present, combining RT with EGFR- or ALK-TKIs in the management of advanced, oncodriver-mutated NSCLC has shown quite promising results, with regards to PFS and OS, rendering prolongation of the TKI-derived benefit feasible, with generally tolerable toxicity. Future studies to confirm the observed efficacy and clarify possible safety issues as well as the appropriate treatment sequence and target volumes are needed, especially in the rapidly-evolving era of newer-generation TKIs.
{"title":"Combined use of radiotherapy and tyrosine kinase inhibitors in the management of metastatic non-small cell lung cancer: A literature review","authors":"Ioannis Georgakopoulos , Vassilis Kouloulias , George Ntoumas , Dimitra Desse , Ioannis Koukourakis , Andromachi Kougioumtzopoulou , Andrianni Charpidou , Konstantinos N. Syrigos , Anna Zygogianni","doi":"10.1016/j.critrevonc.2024.104520","DOIUrl":"10.1016/j.critrevonc.2024.104520","url":null,"abstract":"<div><div>The approval of tyrosine kinase inhibitors (TKIs) as first-line agents has revolutionised treatment of patients diagnosed with advanced non-small cell lung cancer (NSCLC) harboring targetable mutations, adding substantial overall survival (OS) benefit, compared to chemotherapy. However, the efficacy of these agents is inevitably diminished at a point in the disease course, either because of cellular resistance-mechanisms or due to affected pharmacokinetics, like low-central nervous system penetration. The aim of this article is to review existing evidence on the combined use of EGFR (epidermal growth factor)- or ALK (anaplastic lymphoma kinase)-specific TKIs and radiotherapy (RT) in advanced NSCLC setting, as an attempt to delay or overcome TKI-resistance and thus, to expand the time period during which patients derive benefit from a given line of targeted therapy. At present, combining RT with EGFR- or ALK-TKIs in the management of advanced, oncodriver-mutated NSCLC has shown quite promising results, with regards to PFS and OS, rendering prolongation of the TKI-derived benefit feasible, with generally tolerable toxicity. Future studies to confirm the observed efficacy and clarify possible safety issues as well as the appropriate treatment sequence and target volumes are needed, especially in the rapidly-evolving era of newer-generation TKIs.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"204 ","pages":"Article 104520"},"PeriodicalIF":5.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.1016/j.critrevonc.2024.104517
Ana Verena Silvany Sampaio de Miranda , Jessé Lopes da Silva , Diocésio Alves Pinto de Andrade , Larissa Müller Gomes , Marcela Bonalumi dos Santos , Gustavo Viani Arruda , Andreia Cristina de Melo
Purpose
This scoping review aims to evaluate the evidence for stereotactic body radiotherapy (SBRT) boost as a potential alternative for brachytherapy (BCT) in treating cervical cancer.
Material and methods
A comprehensive literature search was conducted across multiple databases. Studies investigating SBRT boost in cervical cancer patients who were either contraindicated for or refused BCT were included. The review examined SBRT efficacy and safety.
Results
Sixteen studies were included, encompassing prospective (n = 4) and retrospective cohort studies (n = 8), as well as phase I and II trials (n = 4). The most common SBRT boost dose was 25 Gray(Gy)/5 fractions (ranging from 18 to 40 Gy/3–5 fractions). Local control rates at 1-year, 3-year, and 5-year ranged from 86 % to 100 %, 78–92 %, and 81–92 %, respectively. Overall survival (OS) rates at 1-year, 3-year, and 5-year rates ranged from 49 % to 95 %, 50–77 %, and 50–69 %, respectively. Two studies reported a pathological complete response rate of 93 % and 94 % three months after the SBRT boost. Most studies reported low rates of late grade 3 or higher genitourinary (0–14 %) and gastrointestinal (0–26 %) toxicities. The overall incidence of rectovaginal fistulas ranged from 0 % to 13 %.
Conclusion
This scoping review suggests SBRT boost as a promising alternative to selected cervical cancer patients who cannot receive BCT. The results indicate a high local control with acceptable toxicity profiles. However, further research is needed to define optimal SBRT boost parameters, identify patient selection criteria, and address knowledge gaps regarding long-term outcomes and cost-effectiveness.
{"title":"Stereotactic body radiotherapy boost as an alternative to brachytherapy for cervical cancer: A scoping review","authors":"Ana Verena Silvany Sampaio de Miranda , Jessé Lopes da Silva , Diocésio Alves Pinto de Andrade , Larissa Müller Gomes , Marcela Bonalumi dos Santos , Gustavo Viani Arruda , Andreia Cristina de Melo","doi":"10.1016/j.critrevonc.2024.104517","DOIUrl":"10.1016/j.critrevonc.2024.104517","url":null,"abstract":"<div><h3>Purpose</h3><div>This scoping review aims to evaluate the evidence for stereotactic body radiotherapy (SBRT) boost as a potential alternative for brachytherapy (BCT) in treating cervical cancer.</div></div><div><h3>Material and methods</h3><div>A comprehensive literature search was conducted across multiple databases. Studies investigating SBRT boost in cervical cancer patients who were either contraindicated for or refused BCT were included. The review examined SBRT efficacy and safety.</div></div><div><h3>Results</h3><div>Sixteen studies were included, encompassing prospective (n = 4) and retrospective cohort studies (n = 8), as well as phase I and II trials (n = 4). The most common SBRT boost dose was 25 Gray(Gy)/5 fractions (ranging from 18 to 40 Gy/3–5 fractions). Local control rates at 1-year, 3-year, and 5-year ranged from 86 % to 100 %, 78–92 %, and 81–92 %, respectively. Overall survival (OS) rates at 1-year, 3-year, and 5-year rates ranged from 49 % to 95 %, 50–77 %, and 50–69 %, respectively. Two studies reported a pathological complete response rate of 93 % and 94 % three months after the SBRT boost. Most studies reported low rates of late grade 3 or higher genitourinary (0–14 %) and gastrointestinal (0–26 %) toxicities. The overall incidence of rectovaginal fistulas ranged from 0 % to 13 %.</div></div><div><h3>Conclusion</h3><div>This scoping review suggests SBRT boost as a promising alternative to selected cervical cancer patients who cannot receive BCT. The results indicate a high local control with acceptable toxicity profiles. However, further research is needed to define optimal SBRT boost parameters, identify patient selection criteria, and address knowledge gaps regarding long-term outcomes and cost-effectiveness.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"204 ","pages":"Article 104517"},"PeriodicalIF":5.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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