Pub Date : 2024-06-22DOI: 10.1016/j.critrevonc.2024.104425
Emily McCarthy , Victoria G. Marchese , Andrea G. Shipper , Kelly Rock , Cara Felter
Purpose
To identify causes of balance impairment in children undergoing treatment for cancer and childhood cancer survivors.
Methods
A systematic search was performed according to PRISMA guidelines. Studies were included if participants were 0–19 years of age with a current/past diagnosis of cancer, an objective balance measure was reported, and a cause of balance impairment was either stated or implied.
Results
The 64 full text studies included identified balance impairments as sequelae secondary to CNS tumors, and/or as an effect of medical treatment including chemotherapy, radiation, and/or surgery. Cancer treatment can result in damage to the visual, vestibular and/or somatosensory systems which in turn can contribute to balance dysfunction.
Conclusions
Balance impairments were caused by the cancer itself or the result of medical treatment. Oncology professionals are integral in recognition and treatment of factors affecting balance impairments in childhood cancer; however, further research is needed to identify interventions targeting specific causes of balance impairment.
{"title":"Identifying causes of balance impairment and exploring sensory contributions to balance in pediatric oncology: A scoping review","authors":"Emily McCarthy , Victoria G. Marchese , Andrea G. Shipper , Kelly Rock , Cara Felter","doi":"10.1016/j.critrevonc.2024.104425","DOIUrl":"10.1016/j.critrevonc.2024.104425","url":null,"abstract":"<div><h3>Purpose</h3><p>To identify causes of balance impairment in children undergoing treatment for cancer and childhood cancer survivors.</p></div><div><h3>Methods</h3><p>A systematic search was performed according to PRISMA guidelines. Studies were included if participants were 0–19 years of age with a current/past diagnosis of cancer, an objective balance measure was reported, and a cause of balance impairment was either stated or implied.</p></div><div><h3>Results</h3><p>The 64 full text studies included identified balance impairments as sequelae secondary to CNS tumors, and/or as an effect of medical treatment including chemotherapy, radiation, and/or surgery. Cancer treatment can result in damage to the visual, vestibular and/or somatosensory systems which in turn can contribute to balance dysfunction.</p></div><div><h3>Conclusions</h3><p>Balance impairments were caused by the cancer itself or the result of medical treatment. Oncology professionals are integral in recognition and treatment of factors affecting balance impairments in childhood cancer; however, further research is needed to identify interventions targeting specific causes of balance impairment.</p></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443912","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 : 2024-06-20DOI: 10.1016/j.critrevonc.2024.104426
Wenyu Li , Junjie Gu , Hongwei Fan , Li Zhang , Jun Guo , Lu Si
Immunotherapy has transformed the treatment of advanced melanoma. However, up to two-thirds of patients experience disease progression after initially achieving a response to immunotherapy. Furthermore, most research has focused on cutaneous melanoma rather than acral or mucosal melanoma, although the latter predominates in Asian populations. In this review, we examine and summarize current definitions of resistance to immunotherapy and the epidemiology of resistance to PD-1 inhibition. We also review the available literature on molecular mechanisms of resistance, including how the tumor mutational landscape and tumor microenvironments of immunotherapy-resistant acral and mucosal melanomas may influence resistance. Finally, we review strategies for overcoming resistance to PD-1 inhibition and summarize completed studies and ongoing clinical trials. Our review highlights that improving the understanding of resistance mechanisms, optimizing existing therapies and further studying high-risk populations would maximize the potential of immunotherapy and result in optimized treatment outcomes for patients with melanoma.
{"title":"Evolving cancer resistance to anti-PD-1/PD-L1 antibodies in melanoma: Comprehensive insights with future prospects","authors":"Wenyu Li , Junjie Gu , Hongwei Fan , Li Zhang , Jun Guo , Lu Si","doi":"10.1016/j.critrevonc.2024.104426","DOIUrl":"10.1016/j.critrevonc.2024.104426","url":null,"abstract":"<div><p>Immunotherapy has transformed the treatment of advanced melanoma. However, up to two-thirds of patients experience disease progression after initially achieving a response to immunotherapy. Furthermore, most research has focused on cutaneous melanoma rather than acral or mucosal melanoma, although the latter predominates in Asian populations. In this review, we examine and summarize current definitions of resistance to immunotherapy and the epidemiology of resistance to PD-1 inhibition. We also review the available literature on molecular mechanisms of resistance, including how the tumor mutational landscape and tumor microenvironments of immunotherapy-resistant acral and mucosal melanomas may influence resistance. Finally, we review strategies for overcoming resistance to PD-1 inhibition and summarize completed studies and ongoing clinical trials. Our review highlights that improving the understanding of resistance mechanisms, optimizing existing therapies and further studying high-risk populations would maximize the potential of immunotherapy and result in optimized treatment outcomes for patients with melanoma.</p></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141441254","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 : 2024-06-19DOI: 10.1016/j.critrevonc.2024.104420
Rachel Daher , Andrew Ruplin , Shilpa Gupta , Philippe E. Spiess , Ashish M. Kamat , Antonio Cigliola , Valentina Tateo , Chiara Mercinelli , Petros Grivas , Andrea Necchi
Context
Genitourinary cancers (GUCs) encompass malignancies affecting the urinary and reproductive systems, including renal cell carcinoma (RCC), urothelial carcinoma (UC), and prostate cancer (PC). With the rapidly evolving therapeutic domain of these cancers, cutaneous adverse events (AEs) remain among the most observed toxicities.
Objective
To explore the dermatologic AEs linked to novel GUC treatments, their underlying pathophysiology, clinical presentations, and risk factors.
Evidence acquisition
A narrative review of the literature from PubMed and Embase databases was conducted. The search strategy included dermatologic/cutaneous adverse events, risk factors, and pathophysiology in conjunction with the following classes of therapies; immune checkpoint inhibitors (ICIs), antiangiogenic therapies, enfortumab vedotin (EV), erdafitinib, and androgen receptor antagonists (ARAs).
Evidence synthesis
Maculopapular rash, pruritus, and alopecia are present among the five classes of therapies. ICIs demonstrate the highest incidence of severe drug AEs including Steven Johnson syndrome/toxic epidermal necrolysis. Unique cutaneous AEs present with specific therapies including hand-foot skin reaction and subungual splinter hemorrhage with antiangiogenic drugs, stomatitis/mucositis and onycholysis with erdafitinib. Incidence and type of cutaneous AE also differed within therapies in the same class as seen with apalutamide displaying the highest risk of cutaneous AEs within ARAs. Risk factors for development of cutaneous AEs can be general to therapies, or specific, and include age, immune status, BMI, and gender.
Conclusions
Dermatologic AEs may impact patients’ quality of life and increase the tendency to dose reduce, hold or discontinue life-saving therapies, underscoring the need for vigilant monitoring, early recognition, and collaborative management between medical oncologists, pharmacists, dermatologists and other specialists.
{"title":"The spectrum of cutaneous toxicities related to novel genitourinary cancer therapies","authors":"Rachel Daher , Andrew Ruplin , Shilpa Gupta , Philippe E. Spiess , Ashish M. Kamat , Antonio Cigliola , Valentina Tateo , Chiara Mercinelli , Petros Grivas , Andrea Necchi","doi":"10.1016/j.critrevonc.2024.104420","DOIUrl":"10.1016/j.critrevonc.2024.104420","url":null,"abstract":"<div><h3>Context</h3><p>Genitourinary cancers (GUCs) encompass malignancies affecting the urinary and reproductive systems, including renal cell carcinoma (RCC), urothelial carcinoma (UC), and prostate cancer (PC). With the rapidly evolving therapeutic domain of these cancers, cutaneous adverse events (AEs) remain among the most observed toxicities.</p></div><div><h3>Objective</h3><p>To explore the dermatologic AEs linked to novel GUC treatments, their underlying pathophysiology, clinical presentations, and risk factors.</p></div><div><h3>Evidence acquisition</h3><p>A narrative review of the literature from PubMed and Embase databases was conducted. The search strategy included <em>dermatologic/cutaneous adverse events, risk factors,</em> and <em>pathophysiology</em> in conjunction with the following classes of therapies; <em>immune checkpoint inhibitors (ICIs), antiangiogenic therapies, enfortumab vedotin (EV), erdafitinib,</em> and <em>androgen receptor</em> antagonists <em>(ARAs).</em></p></div><div><h3>Evidence synthesis</h3><p>Maculopapular rash, pruritus, and alopecia are present among the five classes of therapies. ICIs demonstrate the highest incidence of severe drug AEs including Steven Johnson syndrome/toxic epidermal necrolysis. Unique cutaneous AEs present with specific therapies including hand-foot skin reaction and subungual splinter hemorrhage with antiangiogenic drugs, stomatitis/mucositis and onycholysis with erdafitinib. Incidence and type of cutaneous AE also differed within therapies in the same class as seen with apalutamide displaying the highest risk of cutaneous AEs within ARAs. Risk factors for development of cutaneous AEs can be general to therapies, or specific, and include age, immune status, BMI, and gender.</p></div><div><h3>Conclusions</h3><p>Dermatologic AEs may impact patients’ quality of life and increase the tendency to dose reduce, hold or discontinue life-saving therapies, underscoring the need for vigilant monitoring, early recognition, and collaborative management between medical oncologists, pharmacists, dermatologists and other specialists.</p></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437938","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}
Triple-negative breast carcinoma (TNBC) is one of the most challenging subtypes of breast carcinoma and it has very limited therapeutic options as it is highly aggressive. The prognostic biomarkers are crucial for early diagnosis of the tumor, it also helps in anticipating the trajectory of the illness and optimizing the therapy options. Several therapeutic biomarkers are being used. Among them, the next-generation biomarkers that include Circulating tumor (ct) DNA, glycogen, lipid, and exosome biomarkers provide intriguing opportunities for enhancing the prognosis of TNBC. Lipid and glycogen biomarkers serve as essential details on the development of the tumor along with the efficacy of the treatment, as it exhibits metabolic alteration linked to TNBC. Several types of biomarkers have predictive abilities in TNBC. Elevated levels are associated with worse outcomes. ctDNA being a noninvasive biomarker reveals the genetic composition of the tumor, as well as helps to monitor the progression of the disease. Traditional therapies are ineffective in TNBC due to a lack of receptors, targeted drug delivery provides a tailored approach to overcome drug resistance and site-specific action by minimizing the side effects in TNBC treatment. This enhances therapeutic outcomes against the aggressive nature of breast cancer. This paper includes all the recent biomarkers which has been researched so far in TNBC and the state of art for TNBC which is explored.
{"title":"Next-generation biomarkers for prognostic and potential therapeutic enhancement in Triple negative breast cancer","authors":"Risav Banerjee , Indrajit Maitra , Trisha Bhattacharya , Manosi Banerjee , Gnanasambandan Ramanathan , Suresh kumar Rayala , Ganesh Venkatraman , Devi Rajeswari V","doi":"10.1016/j.critrevonc.2024.104417","DOIUrl":"10.1016/j.critrevonc.2024.104417","url":null,"abstract":"<div><p>Triple-negative breast carcinoma (TNBC) is one of the most challenging subtypes of breast carcinoma and it has very limited therapeutic options as it is highly aggressive. The prognostic biomarkers are crucial for early diagnosis of the tumor, it also helps in anticipating the trajectory of the illness and optimizing the therapy options. Several therapeutic biomarkers are being used. Among them, the next-generation biomarkers that include Circulating tumor (ct) DNA, glycogen, lipid, and exosome biomarkers provide intriguing opportunities for enhancing the prognosis of TNBC. Lipid and glycogen biomarkers serve as essential details on the development of the tumor along with the efficacy of the treatment, as it exhibits metabolic alteration linked to TNBC. Several types of biomarkers have predictive abilities in TNBC. Elevated levels are associated with worse outcomes. ctDNA being a noninvasive biomarker reveals the genetic composition of the tumor, as well as helps to monitor the progression of the disease. Traditional therapies are ineffective in TNBC due to a lack of receptors, targeted drug delivery provides a tailored approach to overcome drug resistance and site-specific action by minimizing the side effects in TNBC treatment. This enhances therapeutic outcomes against the aggressive nature of breast cancer. This paper includes all the recent biomarkers which has been researched so far in TNBC and the state of art for TNBC which is explored.</p></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141433629","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 : 2024-06-17DOI: 10.1016/j.critrevonc.2024.104423
Georgios Lavasidis , Mara Strongylis , Argyrios Tzamalis , Ioannis Tsinopoulos , Evangelia E. Ntzani
Intravitreal chemotherapy is used as a salvage therapy for retinoblastoma with persistent or recurrent vitreous seeding after primary treatment. To assess the safety of this technique, we conducted a systematic review of all studies reporting ocular toxicity data. Forty-eight trials involving 2751 eyes were included. The most common complications were cataract, retinal toxicity, and vitreous hemorrhage. However, severe and permanent adverse events were limited, while the risk of extraocular dissemination, a significant concern, was practically eliminated through preventive techniques. Globe salvage rates ranged from 29 % to 100 %. In conclusion, intravitreal chemotherapy seems to improve prognosis of eyes with advanced disease, with an acceptable safety profile. Nevertheless, most relevant studies are retrospective, and no randomized trials have been performed. Recognizing the challenges regarding the conduct of randomized studies for such a rare pediatric cancer, we believe that multicenter trials through international collaborations can significantly enhance the available information.
{"title":"Safety of intravitreal chemotherapy in the management of retinoblastoma: A systematic review of the literature","authors":"Georgios Lavasidis , Mara Strongylis , Argyrios Tzamalis , Ioannis Tsinopoulos , Evangelia E. Ntzani","doi":"10.1016/j.critrevonc.2024.104423","DOIUrl":"10.1016/j.critrevonc.2024.104423","url":null,"abstract":"<div><p>Intravitreal chemotherapy is used as a salvage therapy for retinoblastoma with persistent or recurrent vitreous seeding after primary treatment. To assess the safety of this technique, we conducted a systematic review of all studies reporting ocular toxicity data. Forty-eight trials involving 2751 eyes were included. The most common complications were cataract, retinal toxicity, and vitreous hemorrhage. However, severe and permanent adverse events were limited, while the risk of extraocular dissemination, a significant concern, was practically eliminated through preventive techniques. Globe salvage rates ranged from 29 % to 100 %. In conclusion, intravitreal chemotherapy seems to improve prognosis of eyes with advanced disease, with an acceptable safety profile. Nevertheless, most relevant studies are retrospective, and no randomized trials have been performed. Recognizing the challenges regarding the conduct of randomized studies for such a rare pediatric cancer, we believe that multicenter trials through international collaborations can significantly enhance the available information.</p></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":null,"pages":null},"PeriodicalIF":6.2,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141428522","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 : 2024-06-17DOI: 10.1016/j.critrevonc.2024.104422
Sophie Schellack , Clara Breidenbach , Oliver Rick , Christoph Kowalski
Of the 4.4 million people diagnosed with cancer in Europe each year, around 36 % are of working age. Return-to-work rates vary across Europe. Work is important for the individual, as well as for society, and this review aims to provide an overview of the predictors for the return to work (RTW) process in European cancer survivors of working age. A systematic literature search was conducted. The present review included quantitative and qualitative study designs published since 2013. In total, the review included 85 papers examining cancer survivors with various cancer diagnoses in 18 European countries. Identified predictive factors for RTW related to the social system, treatment, disease, health behavior, the individuals’ psychosocial, work, and sociodemographic situations. There is a need for a standardized definition and operationalization of RTW. Providers can use these results to identify survivors at risk and support cancer survivors in their RTW process.
{"title":"Predictive factors for return to work among cancer survivors in Europe: A systematic review","authors":"Sophie Schellack , Clara Breidenbach , Oliver Rick , Christoph Kowalski","doi":"10.1016/j.critrevonc.2024.104422","DOIUrl":"10.1016/j.critrevonc.2024.104422","url":null,"abstract":"<div><p>Of the 4.4 million people diagnosed with cancer in Europe each year, around 36 % are of working age. Return-to-work rates vary across Europe. Work is important for the individual, as well as for society, and this review aims to provide an overview of the predictors for the return to work (RTW) process in European cancer survivors of working age. A systematic literature search was conducted. The present review included quantitative and qualitative study designs published since 2013. In total, the review included 85 papers examining cancer survivors with various cancer diagnoses in 18 European countries. Identified predictive factors for RTW related to the social system, treatment, disease, health behavior, the individuals’ psychosocial, work, and sociodemographic situations. There is a need for a standardized definition and operationalization of RTW. Providers can use these results to identify survivors at risk and support cancer survivors in their RTW process.</p></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141428521","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 : 2024-06-15DOI: 10.1016/j.critrevonc.2024.104409
Jun Miyauchi
{"title":"Corrigendum to: The hematopoietic microenvironment of the fetal liver and transient abnormal myelopoiesis associated with Down syndrome: A review [Crit. Rev. Oncol. / Hematol., 199 (2024) 104382]","authors":"Jun Miyauchi","doi":"10.1016/j.critrevonc.2024.104409","DOIUrl":"10.1016/j.critrevonc.2024.104409","url":null,"abstract":"","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1040842824001525/pdfft?md5=7c1a21885e61558a13db5f30759b100c&pid=1-s2.0-S1040842824001525-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141332717","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 : 2024-06-14DOI: 10.1016/j.critrevonc.2024.104408
Francesca R. Mauro , Anna Maria Frustaci , Andrea Visentin , Candida Vitale , Michele Bartoletti , Chiara Oltolini , Emanuela Zappulo , Malgorzata Mikulska
Bruton tyrosine kinase inhibitors (BTKi) and the BCL-2 inhibitor venetoclax have significantly improved the prognosis of patients with chronic lymphocytic leukemia (CLL). However, the incidence of severe infections in patients receiving these agents needs to be better understood. Our review aimed to provide an overview of grade ≥3 infections in patients with CLL who received BTKi and venetoclax-based therapy in prospective trials. Infection rates were influenced by the age of patients and the duration of follow-up. For treatment-naive (TN) patients receiving BTKi, infection rates ranged between 11.4 % and 27.4 % and were close to 30 % in relapsed/refractory (R/R) patients. TN and R/R patients receiving fixed-duration venetoclax-based treatments showed variable rates, with maximum values around 20 %. Opportunistic and fatal infections were uncommon. In conclusion, infections remain a concern in patients with CLL receiving targeted agents. A better definition of factors increasing infection vulnerability could help identify those patients who require infection prophylaxis.
{"title":"Severe infections in patients with chronic lymphocytic leukemia included in trials investigating BTK and BCL2 inhibitors","authors":"Francesca R. Mauro , Anna Maria Frustaci , Andrea Visentin , Candida Vitale , Michele Bartoletti , Chiara Oltolini , Emanuela Zappulo , Malgorzata Mikulska","doi":"10.1016/j.critrevonc.2024.104408","DOIUrl":"10.1016/j.critrevonc.2024.104408","url":null,"abstract":"<div><p>Bruton tyrosine kinase inhibitors (BTKi) and the BCL-2 inhibitor venetoclax have significantly improved the prognosis of patients with chronic lymphocytic leukemia (CLL). However, the incidence of severe infections in patients receiving these agents needs to be better understood. Our review aimed to provide an overview of grade ≥3 infections in patients with CLL who received BTKi and venetoclax-based therapy in prospective trials. Infection rates were influenced by the age of patients and the duration of follow-up. For treatment-naive (TN) patients receiving BTKi, infection rates ranged between 11.4 % and 27.4 % and were close to 30 % in relapsed/refractory (R/R) patients. TN and R/R patients receiving fixed-duration venetoclax-based treatments showed variable rates, with maximum values around 20 %. Opportunistic and fatal infections were uncommon. In conclusion, infections remain a concern in patients with CLL receiving targeted agents. A better definition of factors increasing infection vulnerability could help identify those patients who require infection prophylaxis.</p></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141332718","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 : 2024-06-12DOI: 10.1016/j.critrevonc.2024.104416
Joel Veas Rodríguez , Ana Prieto , Ester Vilaprinyo , Marta Bonet , Marc Diez , Antonieta Salud , Robert Montal
Overall survival (OS) is the most meaningful endpoint in clinical trials. However, owing to their limitations, surrogate endpoints are commonly used and validation studies are required to assess their reliability. Analysis of phase III randomized controlled trials (RCTs) of advanced gastroesophageal cancer (AGC) with > 100 patients, correlation coefficients (r), and determination coefficients (R²) between OS and surrogates were evaluated through meta-analyses. Progression-free survival (PFS), time to progression (TTP), and objective response rate (ORR) were examined to determine their correlations with OS. Analysis of 65 phase III RCTs (29,766 subjects) showed a moderate correlation between PFS/TTP and OS (r = 0.77, R² = 0.59), while ORR correlation was low (r = 0.56, R² = 0.31). Excluding immunotherapy trials improved the PFS/TTP and OS correlations (r = 0.83, R² = 0.70). These findings suggest the potential use of PFS/TTP in AGC phase III investigations, disregarding the use of ORR as a surrogate endpoint.
总生存期(OS)是临床试验中最有意义的终点。然而,由于其局限性,代用终点被普遍使用,需要进行验证研究以评估其可靠性。通过荟萃分析,对患者人数大于 100 人的晚期胃食管癌 III 期随机对照试验(RCT)进行了分析,评估了 OS 与替代终点之间的相关系数(r)和决定系数(R²)。对无进展生存期(PFS)、进展时间(TTP)和客观反应率(ORR)进行了研究,以确定它们与 OS 的相关性。对 65 项 III 期 RCT(29,766 例受试者)的分析表明,PFS/TTP 与 OS 之间存在中度相关性(r = 0.77,R² = 0.59),而 ORR 相关性较低(r = 0.56,R² = 0.31)。排除免疫疗法试验后,PFS/TTP 和 OS 的相关性有所提高(r = 0.83,R² = 0.70)。这些研究结果表明,在AGC III期研究中,PFS/TTP具有潜在的应用价值,而无需将ORR作为替代终点。
{"title":"Surrogate endpoints in phase III randomized trials of advanced gastroesophageal cancer: A systematic review and meta-analysis","authors":"Joel Veas Rodríguez , Ana Prieto , Ester Vilaprinyo , Marta Bonet , Marc Diez , Antonieta Salud , Robert Montal","doi":"10.1016/j.critrevonc.2024.104416","DOIUrl":"10.1016/j.critrevonc.2024.104416","url":null,"abstract":"<div><p>Overall survival (OS) is the most meaningful endpoint in clinical trials. However, owing to their limitations, surrogate endpoints are commonly used and validation studies are required to assess their reliability. Analysis of phase III randomized controlled trials (RCTs) of advanced gastroesophageal cancer (AGC) with > 100 patients, correlation coefficients (<em>r</em>), and determination coefficients (<em>R²</em>) between OS and surrogates were evaluated through meta-analyses. Progression-free survival (PFS), time to progression (TTP), and objective response rate (ORR) were examined to determine their correlations with OS. Analysis of 65 phase III RCTs (29,766 subjects) showed a moderate correlation between PFS/TTP and OS (<em>r</em> = 0.77, <em>R²</em> = 0.59), while ORR correlation was low (<em>r</em> = 0.56, <em>R²</em> = 0.31). Excluding immunotherapy trials improved the PFS/TTP and OS correlations (<em>r</em> = 0.83, <em>R²</em> = 0.70). These findings suggest the potential use of PFS/TTP in AGC phase III investigations, disregarding the use of ORR as a surrogate endpoint.</p></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319363","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}