Pub Date : 2025-11-13DOI: 10.1016/j.ctrv.2025.103049
D. Miliziano , C. Sciortino , S. Manglaviti , M. Ganzinelli , A. Lopez-Gutierrez , M. Occhipinti , C. Proto , F. De Braud , B. Besse , G. Lo Russo , J. Remon
Thymic epithelial tumors (TETs) are rare thoracic malignancies for which surgical resection remains the mainstay treatment, even in advanced stages. For patients with metastatic disease, platinum-based chemotherapy represents the current standard of care in the first-line, with no standard treatment at progression. Much preclinical evidence supports a potential role of angiogenesis in the pathogenesis and progression of TETs. This biological rationale has led to assess the efficacy of several antiangiogenic agents, either in monotherapy or in combination in pre-treated metastatic TET, reporting a clinical meaningful outcome. Despite this efficacy several challenges remain such as the optimal place of angiogenic agents in the treatment sequence, whether they should be applied as monotherapy or in combination, as well as the potential clinical activity of sequential antiangiogenic agents with different mechanisms of action. In this review, we provide a comprehensive overview of the preclinical and clinical evidence supporting angiogenesis as a therapeutic target in TETs. We also propose potential treatment algorithms based on the current literature, while highlighting the ongoing challenges in defining optimal dosing strategies and treatment sequences in this rare disease.
{"title":"Angiogenesis and thymic epithelial tumors: from preclinical insights to different therapeutic lines and combination strategies","authors":"D. Miliziano , C. Sciortino , S. Manglaviti , M. Ganzinelli , A. Lopez-Gutierrez , M. Occhipinti , C. Proto , F. De Braud , B. Besse , G. Lo Russo , J. Remon","doi":"10.1016/j.ctrv.2025.103049","DOIUrl":"10.1016/j.ctrv.2025.103049","url":null,"abstract":"<div><div>Thymic epithelial tumors (TETs) are rare thoracic malignancies for which surgical resection remains the mainstay treatment, even in advanced stages. For patients with metastatic disease, platinum-based chemotherapy represents the current standard of care in the first-line, with no standard treatment at progression. Much preclinical evidence supports a potential role of angiogenesis in the pathogenesis and progression of TETs. This biological rationale has led to assess the efficacy of several antiangiogenic agents, either in monotherapy or in combination in pre-treated metastatic TET, reporting a clinical meaningful outcome. Despite this efficacy several challenges remain such as the optimal place of angiogenic agents in the treatment sequence, whether they should be applied as monotherapy or in combination, as well as the potential clinical activity of sequential antiangiogenic agents with different mechanisms of action. In this review, we provide a comprehensive overview of the preclinical and clinical evidence supporting angiogenesis as a therapeutic target in TETs. We also propose potential treatment algorithms based on the current literature, while highlighting the ongoing challenges in defining optimal dosing strategies and treatment sequences in this rare disease.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103049"},"PeriodicalIF":10.5,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145558607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-13DOI: 10.1016/j.ctrv.2025.103047
Shugo Yajima, Kohei Hirose, Hitoshi Masuda
Purpose
Urinary cell-free DNA (ucfDNA) offers a noninvasive approach for cancer detection, but its diagnostic utility in non-urothelial cancers remains unclear. We systematically evaluated the diagnostic and prognostic value of ucfDNA for these cancers and compared its performance with other liquid biopsies through network meta-analysis.
Experimental design
We conducted a systematic search of PubMed, Cochrane Library, and other databases for studies from 2010 to 2025 evaluating ucfDNA for diagnosing or predicting prognosis in non-urothelial cancers. Primary outcomes were pooled diagnostic sensitivity and specificity; secondary outcomes included prognostic hazard ratios (HRs). Study quality was assessed using QUADAS-2, and Bayesian hierarchical models were employed for robust estimates.
Results
Twenty-eight studies involving 4,423 participants were included. Overall pooled sensitivity was 0.80 (95 % CI, 0.75–0.85) and specificity was 0.96 (95 % CI, 0.88–0.98), with significant heterogeneity (I2 > 82 %). Subgroup analysis of studies targeting short amplicons (<70 bp) showed improved specificity of 0.98 and substantially reduced heterogeneity (I2 = 0 % for specificity). Limited post-treatment ucfDNA reduction was a strong predictor of poor prognosis (pooled HR, 2.76; 95 % CI, 1.94–3.91). Exploratory network meta-analysis in non-small cell lung cancer comparing urine, plasma, and sputum showed overlapping confidence intervals, though the limited available data and wide confidence intervals preclude definitive conclusions regarding comparative performance. Mutation-based assays demonstrated significantly higher specificity than methylation-based approaches (99 % vs. 72 %, P < 0.01).
Conclusions
ucfDNA demonstrates high diagnostic specificity for non-urothelial cancers and provides significant prognostic information. Optimizing assays for ultrashort DNA fragments is critical for enhancing performance and reducing variability. These findings support the potential utility of ucfDNA, particularly as a complementary tool alongside established liquid biopsies like plasma cfDNA, to enhance non-invasive cancer diagnosis and monitoring. Its role as a standalone diagnostic requires further validation, and method standardization remains essential for broad implementation.
{"title":"Diagnostic utility of urinary cell-free DNA in non-urothelial cancer: a systematic review, meta-analysis, & network meta-analysis","authors":"Shugo Yajima, Kohei Hirose, Hitoshi Masuda","doi":"10.1016/j.ctrv.2025.103047","DOIUrl":"10.1016/j.ctrv.2025.103047","url":null,"abstract":"<div><h3>Purpose</h3><div>Urinary cell-free DNA (ucfDNA) offers a noninvasive approach for cancer detection, but its diagnostic utility in non-urothelial cancers remains unclear. We systematically evaluated the diagnostic and prognostic value of ucfDNA for these cancers and compared its performance with other liquid biopsies through network <em>meta</em>-analysis.</div></div><div><h3>Experimental design</h3><div>We conducted a systematic search of PubMed, Cochrane Library, and other databases for studies from 2010 to 2025 evaluating ucfDNA for diagnosing or predicting prognosis in non-urothelial cancers. Primary outcomes were pooled diagnostic sensitivity and specificity; secondary outcomes included prognostic hazard ratios (HRs). Study quality was assessed using QUADAS-2, and Bayesian hierarchical models were employed for robust estimates.</div></div><div><h3>Results</h3><div>Twenty-eight studies involving 4,423 participants were included. Overall pooled sensitivity was 0.80 (95 % CI, 0.75–0.85) and specificity was 0.96 (95 % CI, 0.88–0.98), with significant heterogeneity (<em>I</em><sup>2</sup> > 82 %). Subgroup analysis of studies targeting short amplicons (<70 bp) showed improved specificity of 0.98 and substantially reduced heterogeneity (<em>I</em><sup>2</sup> = 0 % for specificity). Limited post-treatment ucfDNA reduction was a strong predictor of poor prognosis (pooled HR, 2.76; 95 % CI, 1.94–3.91). Exploratory network <em>meta</em>-analysis in non-small cell lung cancer comparing urine, plasma, and sputum showed overlapping confidence intervals, though the limited available data and wide confidence intervals preclude definitive conclusions regarding comparative performance. Mutation-based assays demonstrated significantly higher specificity than methylation-based approaches (99 % vs. 72 %, <em>P</em> < 0.01).</div></div><div><h3>Conclusions</h3><div>ucfDNA demonstrates high diagnostic specificity for non-urothelial cancers and provides significant prognostic information. Optimizing assays for ultrashort DNA fragments is critical for enhancing performance and reducing variability. These findings support the potential utility of ucfDNA, particularly as a complementary tool alongside established liquid biopsies like plasma cfDNA, to enhance non-invasive cancer diagnosis and monitoring. Its role as a standalone diagnostic requires further validation, and method standardization remains essential for broad implementation.</div></div><div><h3>Clinical trial registration</h3><div>PROSPERO CRD420251073863.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103047"},"PeriodicalIF":10.5,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-12DOI: 10.1016/j.ctrv.2025.103048
Liqiong Xue , Tingting Xu , Guochun Cao , Xiaozhong Chen , Meiyu Fang , Mei Feng , Lin Gui , Fei Han , Yaqian Han , Chuncheng Hao , Man Hu , Wenxiao Huang , Dongmei Ji , Hao Jiang , Shaojun Lin , Lei Liu , Zhigang Liu , Haijun Lu , Song Qu , Guoxin Ren , Chaosu Hu
Head and neck squamous cell carcinoma (HNSCC) is the most prevalent type of head and neck cancer; however, treatment outcomes and patient prognosis remain suboptimal. Although the survival of patients with HNSCC has improved with the widespread use of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) and immune checkpoint inhibitors (ICIs), there remains considerable potential for further improvement. Recent studies suggest that the combination of anti-EGFR monoclonal antibodies and ICIs demonstrates promising efficacy and safety, which has been recommended by international guidelines for patients with recurrent or metastatic disease. Nevertheless, the application of this combination therapy remains in the early stages of exploration, and numerous questions concerning its standardized clinical use remain unanswered, including the mechanisms underlying the synergistic effects of individual agents, therapeutic value across different patient populations, and safety considerations. The Expert Committee of Head and Neck Cancer of the Chinese Society of Clinical Oncology (CSCO) organized an expert panel to develop this expert consensus on the combination of anti-EGFR mAbs and ICIs in the treatment of HNSCC through multiple rounds of discussion based on evidence-based medicine and clinical practice experience. This consensus provides guidance on the mechanisms of treatment with anti-EGFR mAbs plus ICIs, stratified treatment approaches, applications in special populations, and safety management. It is hoped that this consensus will provide clearer and more practical guidance for clinicians, promote the rational application of this combination therapy in clinical practice, and offer more treatment options for patients with HNSCC.
{"title":"Expert consensus on the combination of Anti-EGFR monoclonal antibodies and immune checkpoint inhibitors in the treatment of head and neck squamous cell carcinoma","authors":"Liqiong Xue , Tingting Xu , Guochun Cao , Xiaozhong Chen , Meiyu Fang , Mei Feng , Lin Gui , Fei Han , Yaqian Han , Chuncheng Hao , Man Hu , Wenxiao Huang , Dongmei Ji , Hao Jiang , Shaojun Lin , Lei Liu , Zhigang Liu , Haijun Lu , Song Qu , Guoxin Ren , Chaosu Hu","doi":"10.1016/j.ctrv.2025.103048","DOIUrl":"10.1016/j.ctrv.2025.103048","url":null,"abstract":"<div><div>Head and neck squamous cell carcinoma (HNSCC) is the most prevalent type of head and neck cancer; however, treatment outcomes and patient prognosis remain suboptimal. Although the survival of patients with HNSCC has improved with the widespread use of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) and immune checkpoint inhibitors (ICIs), there remains considerable potential for further improvement. Recent studies suggest that the combination of anti-EGFR monoclonal antibodies and ICIs demonstrates promising efficacy and safety, which has been recommended by international guidelines for patients with recurrent or metastatic disease. Nevertheless, the application of this combination therapy remains in the early stages of exploration, and numerous questions concerning its standardized clinical use remain unanswered, including the mechanisms underlying the synergistic effects of individual agents, therapeutic value across different patient populations, and safety considerations. The Expert Committee of Head and Neck Cancer of the Chinese Society of Clinical Oncology (CSCO) organized an expert panel to develop this expert consensus on the combination of anti-EGFR mAbs and ICIs in the treatment of HNSCC through multiple rounds of discussion based on evidence-based medicine and clinical practice experience. This consensus provides guidance on the mechanisms of treatment with anti-EGFR mAbs plus ICIs, stratified treatment approaches, applications in special populations, and safety management. It is hoped that this consensus will provide clearer and more practical guidance for clinicians, promote the rational application of this combination therapy in clinical practice, and offer more treatment options for patients with HNSCC.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103048"},"PeriodicalIF":10.5,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145552052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-10DOI: 10.1016/j.ctrv.2025.103046
Reza Elahi , Yassine Alami Idrissi , Anwaar Saeed
Chimeric antigen receptor (CAR)-T cell therapy has transformed cancer immunotherapy, achieving durable complete remissions in hematologic cancers. Yet its translation to solid tumors like hepatocellular carcinoma (HCC), a leading cause of cancer-related deaths worldwide, faces formidable barriers, including immunosuppressive tumor microenvironments (TMEs), antigen heterogeneity, and risks of on-target/off-tumor toxicity. This review discusses the evolving role of CAR-T therapy in HCC across three domains: (1) foundational concepts in CAR-T design, mechanistic action, and antigen-targeting strategies; (2) breakthroughs from preclinical studies and early-phase clinical trials, such as glypican-3 (GPC3) and alpha-fetoprotein (AFP) directed CAR-T cells that have demonstrated preliminary safety and anti-tumor activity; and (3) innovative strategies to overcome TME-driven resistance, including metabolic reprogramming and stromal modulation. We highlight cutting-edge engineering solutions such as armored CAR-T cells engineered for cytokine support, dual-targeting constructs to mitigate antigen escape, and hypoxia-resistant designs alongside synergistic approaches combining CAR-T with immune checkpoint inhibitors or tyrosine kinase inhibitors. Furthermore, we dissect emerging tactics to disrupt TME immunosuppression. While CAR-T therapy holds promise for redefining HCC management, its success will depend on overcoming biological and logistical barriers through patient-tailored designs and robust translational pipelines. Future directions should prioritize biomarker-driven clinical trials, scalable manufacturing platforms, and integration with existing multimodal HCC therapies to maximize durable responses.
{"title":"CAR-T cell therapy in hepatocellular carcinoma: from mechanistic insights to clinical translation","authors":"Reza Elahi , Yassine Alami Idrissi , Anwaar Saeed","doi":"10.1016/j.ctrv.2025.103046","DOIUrl":"10.1016/j.ctrv.2025.103046","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR)-T cell therapy has transformed cancer immunotherapy, achieving durable complete remissions in hematologic cancers. Yet its translation to solid tumors like hepatocellular carcinoma (HCC), a leading cause of cancer-related deaths worldwide, faces formidable barriers, including immunosuppressive tumor microenvironments (TMEs), antigen heterogeneity, and risks of on-target/off-tumor toxicity. This review discusses the evolving role of CAR-T therapy in HCC across three domains: (1) foundational concepts in CAR-T design, mechanistic action, and antigen-targeting strategies; (2) breakthroughs from preclinical studies and early-phase clinical trials, such as glypican-3 (GPC3) and alpha-fetoprotein (AFP) directed CAR-T cells that have demonstrated preliminary safety and anti-tumor activity; and (3) innovative strategies to overcome TME-driven resistance, including metabolic reprogramming and stromal modulation. We highlight cutting-edge engineering solutions such as armored CAR-T cells engineered for cytokine support, dual-targeting constructs to mitigate antigen escape, and hypoxia-resistant designs alongside synergistic approaches combining CAR-T with immune checkpoint inhibitors or tyrosine kinase inhibitors. Furthermore, we dissect emerging tactics to disrupt TME immunosuppression. While CAR-T therapy holds promise for redefining HCC management, its success will depend on overcoming biological and logistical barriers through patient-tailored designs and robust translational pipelines. Future directions should prioritize biomarker-driven clinical trials, scalable manufacturing platforms, and integration with existing multimodal HCC therapies to maximize durable responses.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103046"},"PeriodicalIF":10.5,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-04DOI: 10.1016/j.ctrv.2025.103044
Haoxin Wang , Nan Gao , Lu Wang , Feiran Yang , Bin Liu , Xiwen Hu , Yufeng Zhao , Rui Sha , Xiurong Li , Huijie Li
EGFR-mutant lung adenocarcinoma (LUAD) that transforms into small-cell lung cancer (SCLC) following targeted therapy represents a clinically significant mechanism of acquired resistance, occurring in approximately 3–14 % of cases. This transformed variant, referred to as SCLC after transformation (SCLC-AT), follows an aggressive clinical course and carries a poor prognosis. SCLC-AT retains the original EGFR mutation but significantly down-regulates EGFR protein expression, eliminating its dependence on EGFR signaling while simultaneously acquiring a neuroendocrine phenotype. In nearly all cases, bi-allelic inactivation of both TP53 and RB1 is observed. In this overview, we provide a detailed examination of the molecular mechanisms underlying the transition from EGFR-mutant LUAD to SCLC. By integrating two primary biological concepts, clonal evolution and lineage reprogramming, we examine recent advances concerning the original cell or cells involved, as well as the genetic and epigenetic reprogramming and signaling pathway changes. While the transformation to SCLC is currently considered genetically and epigenetically irreversible, preclinical interventions targeting EZH2, AURKA, and DLL3 have shown potential in reversing the neuroendocrine phenotype or improving tumor immunogenicity. Future research should utilize single-cell and spatial multi-omics technologies to develop predictive models that can facilitate the early detection of impending transformation and guide precision therapies, ultimately enhancing patient outcomes.
{"title":"Transformation from EGFR-mutant lung adenocarcinoma to small-cell lung cancer: from clonal evolution to lineage reprogramming","authors":"Haoxin Wang , Nan Gao , Lu Wang , Feiran Yang , Bin Liu , Xiwen Hu , Yufeng Zhao , Rui Sha , Xiurong Li , Huijie Li","doi":"10.1016/j.ctrv.2025.103044","DOIUrl":"10.1016/j.ctrv.2025.103044","url":null,"abstract":"<div><div>EGFR-mutant lung adenocarcinoma (LUAD) that transforms into small-cell lung cancer (SCLC) following targeted therapy represents a clinically significant mechanism of acquired resistance, occurring in approximately 3–14 % of cases. This transformed variant, referred to as SCLC after transformation (SCLC-AT), follows an aggressive clinical course and carries a poor prognosis. SCLC-AT retains the original EGFR mutation but significantly down-regulates EGFR protein expression, eliminating its dependence on EGFR signaling while simultaneously acquiring a neuroendocrine phenotype. In nearly all cases, bi-allelic inactivation of both TP53 and RB1 is observed. In this overview, we provide a detailed examination of the molecular mechanisms underlying the transition from EGFR-mutant LUAD to SCLC. By integrating two primary biological concepts, clonal evolution and lineage reprogramming, we examine recent advances concerning the original cell or cells involved, as well as the genetic and epigenetic reprogramming and signaling pathway changes. While the transformation to SCLC is currently considered genetically and epigenetically irreversible, preclinical interventions targeting EZH2, AURKA, and DLL3 have shown potential in reversing the neuroendocrine phenotype or improving tumor immunogenicity. Future research should utilize single-cell and spatial multi-omics technologies to develop predictive models that can facilitate the early detection of impending transformation and guide precision therapies, ultimately enhancing patient outcomes.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103044"},"PeriodicalIF":10.5,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145463282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-04DOI: 10.1016/j.ctrv.2025.103045
Roberta Fazio , Alessandro Audisio , Giacomo Bregni , Daniel Sur , Valentina Daprà , Chiara Conti , Fatima-Zahra Abbassi , Nada Benhima , Irene Assaf , Lissandra Dal Lago , Demetris Papamichael , Jean-Luc Van Laethem , Everardo D. Saad , Francesco Sclafani
Older adults are underrepresented in clinical trials, and studies specifically focused on older cancer patients are uncommon. By screening PubMed, EMBASE and proceedings from international meetings, we searched for trials testing systemic therapies in solid cancer patients aged ≥70 years. We identified age-unselected trials testing the same intervention in the same setting. The primary objective was to assess the proportion of older-age-selected trials meeting the target accrual. Secondary objectives included the analysis of the use of geriatric assessment (GA) tools and quality of life (QoL) questionnaires, and the comparison between older-age-selected and matching age-unselected trials.
We included 313 trials (10.9 % phase I, 78.6 % phase I/II-II, and 10.5 % phase III). 7.7 % were published in 1990–2000, 40.3 % in 2001–2011, and 52.1 % in 2012–2023. Of 234 evaluable trials, 77.8 % enrolled ≥90 % of the required patients. Premature study discontinuation occurred in 50 cases (5.9 % phase I, 14.2 % phase II, 39.4 % phase III). Among 232 evaluable trials, 60.3 % met the primary endpoint (63.7 % phase I/II-II, 35.5 % phase III). GA and QoL analyses were carried out in 28.1 % and 23 % of trials, respectively. Corresponding age-unselected trials were identified for 154 older-age-selected trials. Compared with age-unselected trials, a lower proportion of older-age-selected trials met the target accrual (83.5 % vs 94.8 %, p = 0.035) or the primary endpoint (63.9 % vs 81.5 %, p = 0.022). In conclusion, older-age-selected trials are increasingly performed but rarely include GA and QoL analyses. Effective strategies to meet target accrual should be implemented especially for phase III trials, which suffer from high rates of premature discontinuation.
老年人在临床试验中的代表性不足,专门针对老年癌症患者的研究并不常见。通过筛选PubMed、EMBASE和国际会议的会议记录,我们检索了年龄≥70岁的实体癌患者进行全身治疗的试验。我们确定了在相同环境下测试相同干预措施的非年龄选择试验。主要目的是评估符合目标累积的老年人选择试验的比例。次要目标包括分析老年评估(GA)工具和生活质量(QoL)问卷的使用情况,以及老年年龄选择试验和匹配年龄未选择试验之间的比较。我们纳入了313项试验(10.9%为I期,78.6%为I/II-II期,10.5%为III期)。7.7%发表于1990-2000年,40.3%发表于2001-2011年,52.1%发表于2012-2023年。在234项可评价试验中,77.8%的试验纳入了≥90%的所需患者。50例患者过早终止研究(I期5.9%,II期14.2%,III期39.4%)。在232项可评价试验中,60.3%达到了主要终点(63.7%为I/II-II期,35.5%为III期)。分别在28.1%和23%的试验中进行GA和QoL分析。在154项老年选择试验中确定了相应的年龄未选择试验。与未选择年龄的试验相比,较低比例的年龄较大的试验满足了目标累积(83.5% vs 94.8%, p = 0.035)或主要终点(63.9% vs 81.5%, p = 0.022)。总之,老年人选择的试验越来越多,但很少包括GA和QoL分析。应该实施有效的策略来实现目标收益,特别是对于患有高过早终止率的III期试验。
{"title":"Clinical trials for older cancer patients: A systematic review","authors":"Roberta Fazio , Alessandro Audisio , Giacomo Bregni , Daniel Sur , Valentina Daprà , Chiara Conti , Fatima-Zahra Abbassi , Nada Benhima , Irene Assaf , Lissandra Dal Lago , Demetris Papamichael , Jean-Luc Van Laethem , Everardo D. Saad , Francesco Sclafani","doi":"10.1016/j.ctrv.2025.103045","DOIUrl":"10.1016/j.ctrv.2025.103045","url":null,"abstract":"<div><div>Older adults are underrepresented in clinical trials, and studies specifically focused on older cancer patients are uncommon. By screening PubMed, EMBASE and proceedings from international meetings, we searched for trials testing systemic therapies in solid cancer patients aged ≥70 years. We identified age-unselected trials testing the same intervention in the same setting. The primary objective was to assess the proportion of older-age-selected trials meeting the target accrual. Secondary objectives included the analysis of the use of geriatric assessment (GA) tools and quality of life (QoL) questionnaires, and the comparison between older-age-selected and matching age-unselected trials.</div><div>We included 313 trials (10.9 % phase I, 78.6 % phase I/II-II, and 10.5 % phase III). 7.7 % were published in 1990–2000, 40.3 % in 2001–2011, and 52.1 % in 2012–2023. Of 234 evaluable trials, 77.8 % enrolled ≥90 % of the required patients. Premature study discontinuation occurred in 50 cases (5.9 % phase I, 14.2 % phase II, 39.4 % phase III). Among 232 evaluable trials, 60.3 % met the primary endpoint (63.7 % phase I/II-II, 35.5 % phase III). GA and QoL analyses were carried out in 28.1 % and 23 % of trials, respectively. Corresponding age-unselected trials were identified for 154 older-age-selected trials. Compared with age-unselected trials, a lower proportion of older-age-selected trials met the target accrual (83.5 % vs 94.8 %, p = 0.035) or the primary endpoint (63.9 % vs 81.5 %, p = 0.022). In conclusion, older-age-selected trials are increasingly performed but rarely include GA and QoL analyses. Effective strategies to meet target accrual should be implemented especially for phase III trials, which suffer from high rates of premature discontinuation.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103045"},"PeriodicalIF":10.5,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145497803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-27DOI: 10.1016/j.ctrv.2025.103042
Jennifer Tasong, Rocco Sheldon, Avi Clements, Muhammad Temour Abid, Andrew Gan
Background
Thyroid cancer incidence has risen in recent years, with high mortality rates in aggressive subtypes. Clinical trials of immune checkpoint inhibitors (ICIs), indicate efficacy against a range of solid tumours. However, their role in the thyroid remains to be established. This systematic review (PROSPERO: CRD420250634944) assesses the effectiveness and safety of ICIs in thyroid cancer, reported following PRISMA guidelines.
Methods
Searches were performed in 6 databases (EMBASE, PubMed, CENTRAL, Scopus, Web of Science and Clinicaltrials.gov) from inception to 10th January 2025. All studies reporting efficacy outcomes for ICIs in thyroid cancer were included. Clinical trials databases were searched for the most recent results and ongoing trials. Study quality was assessed using the CASP checklist.
Results
Of 1,207 studies retrieved, 33 met the inclusion criteria. Of these trials, 14 investigated ICI plus tyrosine kinase inhibitors, and 5 studies each evaluated dual ICI combinations, ICI monotherapy, or ICIs plus chemotherapy or radiotherapy. Included studies reported variable efficacy and safety. Studies in anaplastic thyroid cancer (ATC) using biomarker-stratified ICI combinations demonstrated the greatest effectiveness. The safety profiles were generally manageable, with common adverse events including fatigue, anorexia, and increased lipase levels.
Conclusions
ICIs show promising responses in thyroid cancer, particularly in ATC. However, the current evidence is limited to non-randomised phase I-II studies, and no phase III trials have been conducted to date. Further investigation in larger, placebo-controlled trials is required to assess efficacy in clinical practice. Predictive biomarkers can help identify patients who may experience the greatest clinical benefit, maximising cost-effectiveness.
背景:近年来甲状腺癌发病率上升,侵袭性亚型死亡率高。免疫检查点抑制剂(ICIs)的临床试验表明,对一系列实体肿瘤有效。然而,它们在甲状腺中的作用仍有待确定。该系统综述(PROSPERO: CRD420250634944)评估了ICIs治疗甲状腺癌的有效性和安全性,报告遵循PRISMA指南。方法:在EMBASE、PubMed、CENTRAL、Scopus、Web of Science和Clinicaltrials.gov等6个数据库中进行检索,检索时间为2025年1月10日。所有报告ICIs治疗甲状腺癌疗效结果的研究均被纳入。在临床试验数据库中搜索最新的结果和正在进行的试验。使用CASP检查表评估研究质量。结果:在1207项研究中,33项符合纳入标准。在这些试验中,14项研究了ICI加酪氨酸激酶抑制剂,5项研究分别评估了双重ICI联合、ICI单药治疗或ICI加化疗或放疗。纳入的研究报告了不同的疗效和安全性。在间变性甲状腺癌(ATC)的研究中,使用生物标志物分层ICI组合显示出最大的效果。安全性一般是可控的,常见的不良事件包括疲劳、厌食症和脂肪酶水平升高。结论:ICIs在甲状腺癌,特别是ATC中显示出良好的疗效。然而,目前的证据仅限于非随机I-II期研究,迄今尚未进行III期试验。需要在更大规模的安慰剂对照试验中进行进一步的研究,以评估临床实践中的疗效。预测性生物标志物可以帮助识别可能获得最大临床效益的患者,从而最大限度地提高成本效益。
{"title":"Effectiveness of immune checkpoint inhibitor therapy in thyroid cancer: A systematic review","authors":"Jennifer Tasong, Rocco Sheldon, Avi Clements, Muhammad Temour Abid, Andrew Gan","doi":"10.1016/j.ctrv.2025.103042","DOIUrl":"10.1016/j.ctrv.2025.103042","url":null,"abstract":"<div><h3>Background</h3><div>Thyroid cancer incidence has risen in recent years, with high mortality rates in aggressive subtypes. Clinical trials of immune checkpoint inhibitors (ICIs), indicate efficacy against a range of solid tumours. However, their role in the thyroid remains to be established. This systematic review (PROSPERO: CRD420250634944) assesses the effectiveness and safety of ICIs in thyroid cancer, reported following PRISMA guidelines.</div></div><div><h3>Methods</h3><div>Searches were performed in 6 databases (EMBASE, PubMed, CENTRAL, Scopus, Web of Science and <span><span>Clinicaltrials.gov</span><svg><path></path></svg></span>) from inception to 10th January 2025. All studies reporting efficacy outcomes for ICIs in thyroid cancer were included. Clinical trials databases were searched for the most recent results and ongoing trials. Study quality was assessed using the CASP checklist.</div></div><div><h3>Results</h3><div>Of 1,207 studies retrieved, 33 met the inclusion criteria. Of these trials, 14 investigated ICI plus tyrosine kinase inhibitors, and 5 studies each evaluated dual ICI combinations, ICI monotherapy, or ICIs plus chemotherapy or radiotherapy. Included studies reported variable efficacy and safety. Studies in anaplastic thyroid cancer (ATC) using biomarker-stratified ICI combinations demonstrated the greatest effectiveness. The safety profiles were generally manageable, with common adverse events including fatigue, anorexia, and increased lipase levels.</div></div><div><h3>Conclusions</h3><div>ICIs show promising responses in thyroid cancer, particularly in ATC. However, the current evidence is limited to non-randomised phase I-II studies, and no phase III trials have been conducted to date. Further investigation in larger, placebo-controlled trials is required to assess efficacy in clinical practice. Predictive biomarkers can help identify patients who may experience the greatest clinical benefit, maximising cost-effectiveness.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103042"},"PeriodicalIF":10.5,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145454253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastric cancer (GC) remains a significant global health burden. Both Asian countries and Western nations, represented by Europe and North America, have long been pioneers in GC research and continue to lead advancements in the field. However, notable differences have historically existed between these regions in the treatment of resectable GC. In recent years, increasing convergence between Asian and Western approaches has emerged, driven by the growth of global collaborative studies. New definitive evidence suggests that the therapeutic landscape for resectable GC may undergo a significant transformation. In this review, we comprehensively examine the evolution of surgical approaches and perioperative chemotherapy strategies in Asia and the West. We summarize key clinical trials, highlight persistent survival disparities, and provide insight into current trends in perioperative management, including the recent advances in molecularly driven perioperative treatments. Finally, we outline key considerations for future multicenter perioperative trials to further guide global clinical practice.
{"title":"Evolving treatment strategies for resectable gastric cancer: Bridging Asia-West disparities toward personalized and integrated therapy","authors":"Xuesong Zhao , Qianyun Hao , Maria Alsina , Daniel Acosta , Florian Castet , Eduardo Terán , Kreina Vega Cano , Tamara Saurí , Ismael Macías , Takaki Yoshikawa , Sandra Castro , Hirokazu Shoji , Florian Lordick , Zhanlong Shen , Tian V. Tian , Teresa Macarulla","doi":"10.1016/j.ctrv.2025.103041","DOIUrl":"10.1016/j.ctrv.2025.103041","url":null,"abstract":"<div><div>Gastric cancer (GC) remains a significant global health burden. Both Asian countries and Western nations, represented by Europe and North America, have long been pioneers in GC research and continue to lead advancements in the field. However, notable differences have historically existed between these regions in the treatment of resectable GC. In recent years, increasing convergence between Asian and Western approaches has emerged, driven by the growth of global collaborative studies. New definitive evidence suggests that the therapeutic landscape for resectable GC may undergo a significant transformation. In this review, we comprehensively examine the evolution of surgical approaches and perioperative chemotherapy strategies in Asia and the West. We summarize key clinical trials, highlight persistent survival disparities, and provide insight into current trends in perioperative management, including the recent advances in molecularly driven perioperative treatments. Finally, we outline key considerations for future multicenter perioperative trials to further guide global clinical practice.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103041"},"PeriodicalIF":10.5,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145446936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-20DOI: 10.1016/j.ctrv.2025.103040
Sameh Hany Emile , Anjelli Wignakumar , Ajia Syed , Nir Horesh , Samer Hani Barsom , Zoe Garoufalia , Steven D. Wexner
Background
This umbrella review aimed to summarize and critically evaluate systematic reviews on the applications of circulating tumor DNA (ctDNA) and microRNA in colorectal cancer (CRC).
Methods
A PRISMA-compliant umbrella overview of systematic reviews was conducted. PubMed and Scopus were searched through October 2024 for systematic reviews that assessed the diagnostic and prognostic utility of ctDNA and microRNA in CRC. The diagnostic accuracy of ctDNA and microRNA in the detection of CRC and associated genetic mutations, and the association between ctDNA and disease recurrence and survival were assessed.
Results
26 systematic reviews were included. ctDNA had pooled sensitivity and specificity in detecting KRAS mutations of 75–83 % and 91–98 %, respectively. MicroRNA had a 59–76 % pooled sensitivity and 64–89 % pooled specificity in the detection of CRC. The detection of ctDNA after surgery for CRC was associated with increased recurrence, and the risk was higher when detection followed adjuvant chemotherapy. The detection of ctDNA was associated with an increased recurrence of colorectal metastases and worse overall survival. ctDNA was associated with an increased risk of rectal cancer recurrence and reduced odds of pathologic complete response when detected after neoadjuvant therapy and after surgery. The increased risk of recurrence associated with ctDNA was proportional to the disease stage; however, evidence on this observation is limited to one meta-analysis.
Conclusions
Detection of ctDNA before or after treatment of CRC, regardless of the stage, was associated with both increased recurrence and decreased survival. This negative impact was more notable when ctDNA was detected after locoregional treatment.
{"title":"An umbrella review of systematic reviews on the diagnostic and prognostic utility of circulating tumor DNA and MicroRNA in colorectal cancer","authors":"Sameh Hany Emile , Anjelli Wignakumar , Ajia Syed , Nir Horesh , Samer Hani Barsom , Zoe Garoufalia , Steven D. Wexner","doi":"10.1016/j.ctrv.2025.103040","DOIUrl":"10.1016/j.ctrv.2025.103040","url":null,"abstract":"<div><h3>Background</h3><div>This umbrella review aimed to summarize and critically evaluate systematic reviews on the applications of circulating tumor DNA (ctDNA) and microRNA in colorectal cancer (CRC).</div></div><div><h3>Methods</h3><div>A PRISMA-compliant umbrella overview of systematic reviews was conducted. PubMed and Scopus were searched through October 2024 for systematic reviews that assessed the diagnostic and prognostic utility of ctDNA and microRNA in CRC. The diagnostic accuracy of ctDNA and microRNA in the detection of CRC and associated genetic mutations, and the association between ctDNA and disease recurrence and survival were assessed.</div></div><div><h3>Results</h3><div>26 systematic reviews were included. ctDNA had pooled sensitivity and specificity in detecting KRAS mutations of 75–83 % and 91–98 %, respectively. MicroRNA had a 59–76 % pooled sensitivity and 64–89 % pooled specificity in the detection of CRC. The detection of ctDNA after surgery for CRC was associated with increased recurrence, and the risk was higher when detection followed adjuvant chemotherapy. The detection of ctDNA was associated with an increased recurrence of colorectal metastases and worse overall survival. ctDNA was associated with an increased risk of rectal cancer recurrence and reduced odds of pathologic complete response when detected after neoadjuvant therapy and after surgery. The increased risk of recurrence associated with ctDNA was proportional to the disease stage; however, evidence on this observation is limited to one meta-analysis.</div></div><div><h3>Conclusions</h3><div>Detection of ctDNA before or after treatment of CRC, regardless of the stage, was associated with both increased recurrence and decreased survival. This negative impact was more notable when ctDNA was detected after locoregional treatment.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103040"},"PeriodicalIF":10.5,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145360443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-20DOI: 10.1016/j.ctrv.2025.103028
Stephanie Kim , Kyle Sheth , Xiaoying Yu , Laura Porterfield , Elizabeth M. Vaughan
Background
Adenoid Cystic Carcinoma (ACC) is a rare, indolent subtype of triple-negative breast cancer, accounting for < 0.1 % of cases. The solid-basaloid subtype (SBACC), comprising approximately one-quarter of breast ACCs, has a poorer prognosis. While ACC is typically managed with surgery and is chemo-resistant, SBACC is more aggressive and often treated with chemotherapy and, more recently, immunotherapy—though supporting evidence remains limited.
Aim
To assess clinical characteristics and treatment outcomes of SBACC of the breast.
Methods
This study presents a case of breast SBACC and a systematic review of five databases (inception–September 10, 2024). Eligible studies reported clinical course, treatment, and outcomes. Exclusions included duplicates, non-SBACC focus, animal studies, and those lacking clinical or with only pathological data. Descriptive statistics were used for binary and categorical variables. Risk of bias was assessed using JBI tools, following PRISMA 2020 guidelines. The review is registered in PROSPERO.
Results
Nineteen studies and one new case (134 patients, aged 19–89) were included. Except for three patients who had with metastatic disease at diagnosis, the rest (97 %) were treated with surgery; 55.6 % received chemotherapy. Among nine patients given neoadjuvant chemotherapy and/or immunotherapy, none achieved complete pathological response, and most had poor outcomes. In non-metastatic cases with reported treatment (n = 99), younger age predicted recurrence (p = 0.032) but not chemotherapy receipt (p = 0.082). Chemotherapy did not reduce recurrence risk (p = 0.819). Mastectomy versus breast-conserving surgery with radiation had similar outcomes (p = 0.197).
Conclusions
Although limited data are available for this rare cancer, evidence for the efficacy of chemotherapy and immunotherapy for SBACC treatment is lacking. Treatment plans should be individualized to reduce the physical, psychological, and financial burdens on both patients and healthcare systems.
{"title":"Clinical course and treatment outcomes in solid-basaloid adenoid cystic carcinoma of the breast: A systematic review and case report","authors":"Stephanie Kim , Kyle Sheth , Xiaoying Yu , Laura Porterfield , Elizabeth M. Vaughan","doi":"10.1016/j.ctrv.2025.103028","DOIUrl":"10.1016/j.ctrv.2025.103028","url":null,"abstract":"<div><h3>Background</h3><div>Adenoid Cystic Carcinoma (ACC) is a rare, indolent subtype of triple-negative breast cancer, accounting for < 0.1 % of cases. The solid-basaloid subtype (SBACC), comprising approximately one-quarter of breast ACCs, has a poorer prognosis. While ACC is typically managed with surgery and is chemo-resistant, SBACC is more aggressive and often treated with chemotherapy and, more recently, immunotherapy—though supporting evidence remains limited.</div></div><div><h3>Aim</h3><div>To assess clinical characteristics and treatment outcomes of SBACC of the breast.</div></div><div><h3>Methods</h3><div>This study presents a case of breast SBACC and a systematic review of five databases (inception–September 10, 2024). Eligible studies reported clinical course, treatment, and outcomes. Exclusions included duplicates, non-SBACC focus, animal studies, and those lacking clinical or with only pathological data. Descriptive statistics were used for binary and categorical variables. Risk of bias was assessed using JBI tools, following PRISMA 2020 guidelines. The review is registered in PROSPERO.</div></div><div><h3>Results</h3><div>Nineteen studies and one new case (134 patients, aged 19–89) were included. Except for three patients who had with metastatic disease at diagnosis, the rest (97 %) were treated with surgery; 55.6 % received chemotherapy. Among nine patients given neoadjuvant chemotherapy and/or immunotherapy, none achieved complete pathological response, and most had poor outcomes. In non-metastatic cases with reported treatment (n = 99), younger age predicted recurrence (p = 0.032) but not chemotherapy receipt (p = 0.082). Chemotherapy did not reduce recurrence risk (p = 0.819). Mastectomy versus breast-conserving surgery with radiation had similar outcomes (p = 0.197).</div></div><div><h3>Conclusions</h3><div>Although limited data are available for this rare cancer, evidence for the efficacy of chemotherapy and immunotherapy for SBACC treatment is lacking. Treatment plans should be individualized to reduce the physical, psychological, and financial burdens on both patients and healthcare systems.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"141 ","pages":"Article 103028"},"PeriodicalIF":10.5,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145360768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}