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The incidence and relative risk of major adverse cardiovascular events and hypertension in patients treated with immune checkpoint inhibitors plus tyrosine-kinase inhibitors for solid tumors: a systemic review and meta-analysis. 免疫检查点抑制剂加酪氨酸激酶抑制剂治疗实体瘤患者主要不良心血管事件和高血压的发生率和相对风险:系统综述和荟萃分析。
IF 3.3 3区 医学 Q2 Medicine Pub Date : 2024-07-01 Epub Date: 2024-06-16 DOI: 10.1080/14737140.2024.2357814
Chiara Ciccarese, Annunziato Anghelone, Alessio Stefani, Antonio Cigliola, Alessandro Strusi, Filippo D'Agostino, Emilio Bria, Roberto Iacovelli, Giampaolo Tortora

Introduction: Combinations of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) can be responsible for major adverse cardiovascular events (MACEs). We performed a meta-analysis to assess the relative risk (RR) of MACEs and hypertension in cancer patients treated with ICI+TKI combinations.

Research design and methods: We selected prospective trials through MEDLINE/PubMed, Cochrane Library, and ASCOMeeting abstracts. We calculated combined ORs, RRs, and 95% CIs using RevMansoftware for meta-analysis (v.5.2.3).

Results: Seven studies were selected for the analysis of MACEs (3849 patients). The incidence MACEs were 0.8% with ICI+TKI combinations, compared to 0.2% in the control arms for both any- and high-grade. ICI+TKI combinations significantly increased the risk of any- (OR = 3.21; p = 0.01) and high-grade MACEs (OR = 2.72; p = 0.05). Ten studies were selected for the analysis of hypertension (5744 patients). The incidence of treatment-related hypertension of any-grade and high-grade was41.3% (vs. 20.8%) and 26.1% (vs. 12.3%) with ICI+TKI combinations, respectively. ICI+TKI combinations significantly increased the risk of treatment-related hypertension of any-grade (RR = 2.10; p = 0.001), but not of high-grade (p = 0.11).

Conclusions: ICI+TKI combinations increase the risk of MACEs compared to controls, although the absolute incidence is eventually low. Routine cardiovascular monitoring in asymptomatic patients is therefore not recommended.

简介:免疫检查点抑制剂(ICIs)和酪氨酸激酶抑制剂(TKIs)的联合用药可能会导致重大不良心血管事件(MACEs)。我们进行了一项荟萃分析,以评估接受ICI+TKI联合治疗的癌症患者发生MACEs和高血压的相对风险(RR):我们通过 MEDLINE/PubMed、Cochrane 图书馆和 ASCOMeeting 摘要选择了前瞻性试验。我们使用RevMan荟萃分析软件(v.5.2.3)计算了合并ORs、RRs和95% CIs:我们选择了七项研究(3849 名患者)进行 MACEs 分析。ICI+TKI联合疗法的MACE发生率为0.8%,而对照组的任何级别和高级别MACE发生率均为0.2%。ICI+TKI 联合用药可显著增加任意MACE(OR=3.21;P=0.01)和高级别MACE(OR=2.72;P=0.05)的风险。高血压分析选取了十项研究(5744 名患者)。ICI+TKI联合疗法治疗相关的任何级别和高级别高血压发生率分别为41.3%(vs.20.8%)和26.1%(vs.12.3%)。ICI+TKI联合用药可显著增加任何级别治疗相关高血压的风险(RR = 2.10; p = 0.001),但不会增加高级别高血压的风险(p = 0.11):结论:与对照组相比,ICI+TKI 联合用药会增加 MACE 的风险,尽管绝对发生率最终较低。因此不建议对无症状患者进行常规心血管监测。
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引用次数: 0
The trend toward more target therapy in pancreatic ductal adenocarcinoma. 胰腺导管腺癌的靶向治疗呈上升趋势。
IF 3.3 3区 医学 Q2 Medicine Pub Date : 2024-07-01 Epub Date: 2024-05-23 DOI: 10.1080/14737140.2024.2357802
Chiara Deiana, Margherita Agostini, Giovanni Brandi, Elisa Giovannetti

Introduction: Despite the considerable progress made in cancer treatment through the development of target therapies, pancreatic ductal adenocarcinoma (PDAC) continues to exhibit resistance to this category of drugs. As a result, chemotherapy combination regimens remain the primary treatment approach for this aggressive cancer.

Areas covered: In this review, we provide an in-depth analysis of past and ongoing trials on both well-known and novel targets that are being explored in PDAC, including PARP, EGFR, HER2, KRAS, and its downstream and upstream pathways (such as RAF/MEK/ERK and PI3K/AKT/mTOR), JAK/STAT pathway, angiogenesis, metabolisms, epigenetic targets, claudin, and novel targets (such as P53 and plectin). We also provide a comprehensive overview of the significant trials for each target, allowing a thorough glimpse into the past and future of target therapy.

Expert opinion: The path toward implementing a target therapy capable of improving the overall survival of PDAC is still long, and it is unlikely that a monotherapy target drug will fulfill a meaningful role in addressing the complexity of this cancer. Thus, we discuss the future direction of target therapies in PDAC, trying to identify the more promising target and combination treatments, with a special focus on the more eagerly awaited ongoing trials.

导言:尽管通过开发靶向疗法在癌症治疗方面取得了长足进展,但胰腺导管腺癌(PDAC)仍对这类药物表现出抗药性。因此,化疗联合疗法仍是治疗这种侵袭性癌症的主要方法:在这篇综述中,我们深入分析了过去和正在进行的针对 PDAC 探索的知名和新型靶点的试验,包括 PARP、表皮生长因子受体、HER2、KRAS 及其上下游通路(如 RAF/MEK/ERK 和 PI3K/AKT/mTOR)、JAK/STAT 通路、血管生成、代谢、表观遗传靶点、Claudin 和新型靶点(如 P53 和 plectin)。我们还对每种靶点的重要试验进行了全面概述,让您对靶点疗法的过去和未来有一个全面的了解:实现能够改善 PDAC 总体生存率的靶向治疗的道路依然漫长,单一疗法的靶向药物不太可能在解决这种复杂癌症方面发挥有意义的作用。因此,我们讨论了PDAC靶向疗法的未来发展方向,试图找出更有前景的靶向疗法和联合疗法,并特别关注人们翘首以盼的正在进行的试验。
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引用次数: 0
Is there a link between talcum powder, oxidative stress, and ovarian cancer risk? 爽身粉、氧化应激和卵巢癌风险之间有联系吗?
IF 3.3 3区 医学 Q2 Medicine Pub Date : 2024-07-01 Epub Date: 2024-05-08 DOI: 10.1080/14737140.2024.2352506
Ghassan M Saed

Introduction: The link between talcum powder use and cancer, particularly ovarian cancer, has been a topic of scientific research and legal debate for several years. Studies have suggested a potential association between long-term talcum powder use in the genital area and an increased risk of ovarian cancer.

Areas covered: The following report includes up-to-date evidence to support the potential link between talcum powder use and the risk of developing ovarian cancer. The International Agency for Research on Cancer, which is part of the World Health Organization, classified talc-based body powder as possibly carcinogenic to humans when used in the female genital area. However, other studies have not consistently supported this association, and thus more research is needed to establish a clear and definitive link between talcum powder use and cancer. Despite this, recent molecular-level data have linked talc to alterations in redox balance, gene mutations, and inflammatory responses. Specifically, we have identified a role for talc to induce the pro-oxidant state, inhibit apoptosis, and more importantly induced cellular transformation in normal ovarian cells.

Expert opinion: We presented unequivocal evidence to support our opinion that talc is not biologically inert and induces molecular changes that mimic the hallmarks of cancer.

导言:使用爽身粉与癌症(尤其是卵巢癌)之间的联系多年来一直是科学研究和法律辩论的主题。研究表明,长期在生殖器部位使用爽身粉与卵巢癌风险增加之间存在潜在联系:以下报告包括支持使用爽身粉与罹患卵巢癌风险之间潜在联系的最新证据。隶属于世界卫生组织的国际癌症研究机构(International Agency for Research on Cancer)将滑石粉类爽身粉用于女性生殖器部位时可能对人体致癌。然而,其他研究并没有一致支持这种关联,因此需要更多的研究来确定使用爽身粉与癌症之间的明确联系。尽管如此,最近的分子水平数据已将滑石粉与氧化还原平衡的改变、基因突变和炎症反应联系起来。具体来说,我们发现滑石粉可诱导促氧化状态、抑制细胞凋亡,更重要的是可诱导正常卵巢细胞的细胞转化:我们提出了明确的证据来支持我们的观点,即滑石粉不是生物惰性的,它会诱导分子变化,从而模拟癌症的特征。
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引用次数: 0
Efficacy and safety of neoadjuvant therapy for HR-positive/HER2-negative early breast cancer: a Bayesian network meta-analysis. HR阳性/HER2阴性早期乳腺癌新辅助疗法的疗效和安全性:贝叶斯网络荟萃分析。
IF 3.3 3区 医学 Q2 Medicine Pub Date : 2024-07-01 Epub Date: 2024-05-17 DOI: 10.1080/14737140.2024.2350105
Ruiliang Chen, Yushuai Yu, Jie Zhang, Chuangui Song, Chuan Wang

Background: Neoadjuvant treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer is controversial and requires a comprehensive analysis for optimal therapy assessment. Therefore, a two-step Bayesian network meta-analysis (NMA) was performed to compare the efficacy and safety of different neoadjuvant regimens.

Research design and methods: Phase II/III randomized clinical trials comparing various neoadjuvant therapies for HR+/HER2- breast cancer were included. NMA and pairwise meta-analyses were conducted using Stata (version 14), R (version 4.2.3), and Review Manager 5.4.

Results: Twenty-eight studies (5,625 patients) were eligible. NMA of objective response rate (ORR) indicated the highest SUCRA for chemotherapy (CT) and chemotherapy with anthracycline (CT(A)). Pathologic complete response (PCR) NMA demonstrated significant PCR improvement with chemotherapy regimens containing programmed cell death protein-1 and programmed cell death ligand-1 inhibitors (PD-1i/PD-L1i) and poly ADP-ribose polymerase inhibitors (PARPi). Combined analysis considering both the ORR and safety highlighted CT(A)'s efficacy and toxicity balance.

Conclusions: CT(A) and CT showed improved ORR compared with alternative regimens. CT(A) combined with PD-1/PD-L1 or PARP inhibitors significantly increased PCR rates. Comprehensive assessment of both ORR and safety indicated that CT(A) represents an optimal neoadjuvant therapy for HR+/HER2- breast cancer, whereas AI + CDK4/6 inhibitors rank solely behind chemotherapy.

Registration: PROSPERO Registration: CRD42024538948. International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) registration number INPLASY202440092.

背景:激素受体阳性/人表皮生长因子受体2阴性(HR+/HER2-)乳腺癌的新辅助治疗存在争议,需要进行综合分析以评估最佳疗法。因此,我们进行了两步贝叶斯网络荟萃分析(NMA),以比较不同新辅助治疗方案的疗效和安全性:研究设计:纳入了比较HR+/HER2-乳腺癌各种新辅助疗法的II/III期随机临床试验。使用Stata(版本14)、R(版本4.2.3)和Review Manager 5.4进行了NMA和配对荟萃分析:28项研究(5625名患者)符合条件。客观反应率(ORR)的NMA显示,化疗(CT)和蒽环类药物化疗(CT(A))的SUCRA最高。病理完全反应(PCR)NMA显示,含有程序性细胞死亡蛋白-1和程序性细胞死亡配体-1抑制剂(PD-1i/PD-L1i)以及聚ADP-核糖聚合酶抑制剂(PARPi)的化疗方案能显著改善PCR。对ORR和安全性的综合分析突出了CT(A)的疗效和毒性平衡:结论:与其他方案相比,CT(A)和CT的ORR有所提高。CT(A)联合PD-1/PD-L1或PARP抑制剂可显著提高PCR率。对ORR和安全性的综合评估表明,CT(A)是治疗HR+/HER2-乳腺癌的最佳新辅助疗法,而AI+CDK4/6抑制剂仅次于化疗:国际注册系统综述和元分析协议平台(INPLASY)注册号:INPLASY202440092。
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引用次数: 0
The multidisciplinary management of locally advanced rectal cancer. 局部晚期直肠癌的多学科治疗。
IF 3.3 3区 医学 Q2 Medicine Pub Date : 2024-07-01 Epub Date: 2024-04-30 DOI: 10.1080/14737140.2024.2349137
Francesca De Felice, Michelangelo Miccini, Andrea Botticelli, Michela Roberto, Niccolò Petrucciani

Introduction: The classic paradigm for the management of locally advanced rectal cancer (LARC) consists of (chemo)radiotherapy (C)RT), total mesorectal excision, and adjuvant chemotherapy (CHT). At present, due to the high rate of distant metastasis (up to 30%), the total neoadjuvant therapy (TNT) with the administration of systemic CHT in the neoadjuvant setting has gained acceptance as standard of care.Our aim is to critically review the current literature on LARC management and summarize the different approaches recently proposed to improve clinical outcomes. It represents a starting step to develop an effective strategy that ultimately could harmonize the standard of care in daily clinical practice.

Areas covered: Studies reporting the impact of TNT approaches were deemed eligible. De-escalation strategies, including non-operative management (NOM) after TNT, as well as RT omission or systemic therapy alone, were also investigated.

Expert opinion: The year 2020 has seen promising new data from randomized phase III trials in the field of LARC management. Nowadays, TNT strategy has been accepted as the primary treatment for LARC. The role of de-escalation strategies is still unknown. The goal is to achieve better survival outcomes with improving quality of life. Only selected patients are likely to benefit from NOM or immunotherapy alone.

导言:治疗局部晚期直肠癌(LARC)的经典模式包括(化)放疗(C)RT、全直肠中胚层切除术和辅助化疗(CHT)。目前,由于远处转移率较高(高达 30%),在新辅助治疗中进行全身 CHT 的全新药辅助治疗(TNT)已被接受为标准治疗方法。我们的目的是批判性地回顾目前有关 LARC 治疗的文献,总结最近提出的改善临床疗效的不同方法。我们的目的是批判性地回顾目前有关 LARC 管理的文献,并总结最近提出的改善临床结果的不同方法,这是制定有效策略的第一步,最终可以协调日常临床实践中的护理标准:报告 TNT 方法影响的研究符合条件。专家意见:2020年,LARC治疗领域的随机III期试验取得了令人鼓舞的新数据。如今,TNT 策略已被接受为 LARC 的主要治疗方法。降级策略的作用尚不清楚。我们的目标是在改善生活质量的同时获得更好的生存结果。只有经过筛选的患者才有可能从单纯 NOM 或免疫疗法中获益。
{"title":"The multidisciplinary management of locally advanced rectal cancer.","authors":"Francesca De Felice, Michelangelo Miccini, Andrea Botticelli, Michela Roberto, Niccolò Petrucciani","doi":"10.1080/14737140.2024.2349137","DOIUrl":"10.1080/14737140.2024.2349137","url":null,"abstract":"<p><strong>Introduction: </strong>The classic paradigm for the management of locally advanced rectal cancer (LARC) consists of (chemo)radiotherapy (C)RT), total mesorectal excision, and adjuvant chemotherapy (CHT). At present, due to the high rate of distant metastasis (up to 30%), the total neoadjuvant therapy (TNT) with the administration of systemic CHT in the neoadjuvant setting has gained acceptance as standard of care.Our aim is to critically review the current literature on LARC management and summarize the different approaches recently proposed to improve clinical outcomes. It represents a starting step to develop an effective strategy that ultimately could harmonize the standard of care in daily clinical practice.</p><p><strong>Areas covered: </strong>Studies reporting the impact of TNT approaches were deemed eligible. De-escalation strategies, including non-operative management (NOM) after TNT, as well as RT omission or systemic therapy alone, were also investigated.</p><p><strong>Expert opinion: </strong>The year 2020 has seen promising new data from randomized phase III trials in the field of LARC management. Nowadays, TNT strategy has been accepted as the primary treatment for LARC. The role of de-escalation strategies is still unknown. The goal is to achieve better survival outcomes with improving quality of life. Only selected patients are likely to benefit from NOM or immunotherapy alone.</p>","PeriodicalId":12099,"journal":{"name":"Expert Review of Anticancer Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140853844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Safety and hematological toxicities of PARP inhibitors in patients with cancer: a systematic review of randomized controlled trials and a pharmacovigilance analysis. PARP 抑制剂对癌症患者的安全性和血液学毒性:随机对照试验的系统回顾和药物警戒分析。
IF 3.3 3区 医学 Q2 Medicine Pub Date : 2024-07-01 Epub Date: 2024-05-23 DOI: 10.1080/14737140.2024.2357822
Meng-Fei Dai, Xin Wang, Wen-Xiu Xin, Si-Si Kong, Wei-Ben Xu, Hai-Ying Ding, Luo Fang

Introduction: This study aimed to estimate the toxicities of PARP inhibitors (PARPis), based on randomized controlled trials (RCTs) and the FDA Adverse Event Reporting System (FAERS) database.

Methods: Four electronic databases were searched from inception to 16 April 2024, for RCTs of approved PARPis. The primary and secondary outcomes were grade 3-5 adverse events (AEs) and grade 3-5 hematological AE, respectively. We conducted network meta-analyses to calculate the relative risks (RRs) and 95% confidence intervals (CIs) of outcomes. A disproportionality analysis was conducted to estimate the signals of hematological AEs associated with PARPis from the FAERS database.

Results: Overall, 27 RCTs involving 11,067 patients with cancer were included. Olaparib had the best safety profile for any grade 3-5 AEs and hematological AEs among four approved PARPis. Olaparib did not increase the risk of thrombocytopenia (RR: 1.48; 95%CI: 0.64-3.39), but other PARPis did. Furthermore 14,780 hematological AE reports associated with PARPis were identified in the FAERS database, and all PARPis were associated with strong hematological AE signals. Hematological AEs mainly occurred within the first 3 months (80.84%) after PARPi initiation.

Conclusion: Olaparib had the best safety profile among five PARPis. PARPi-associated hematological AEs mainly occurred within the first 3 months.

Registration: PROSPERO (CRD42022385274).

简介:本研究旨在根据随机对照试验(RCTs)和美国食品药品管理局不良事件报告系统(FAERS)数据库估算 PARP 抑制剂(PARPis)的毒性:本研究旨在根据随机对照试验(RCT)和美国食品及药物管理局不良事件报告系统(FAERS)数据库估算PARP抑制剂(PARPis)的毒性:方法:在四个电子数据库中检索了从开始到 2024 年 4 月 16 日期间批准的 PARPis 的 RCT。主要和次要结果分别为 3-5 级不良事件(AEs)和 3-5 级血液学 AE。我们进行了网络荟萃分析,以计算结果的相对风险 (RR) 和 95% 置信区间 (CI)。我们还进行了一项比例失调分析,以估算FAERS数据库中与PARPis相关的血液学AE的信号:结果:共纳入了27项RCT,涉及11067名癌症患者。在已获批的四种PARPis中,奥拉帕利在3-5级AE和血液学AE方面的安全性最好。奥拉帕利不会增加血小板减少症的风险(RR:1.48;95%CI:0.64-3.39),但其他 PARPis 则会。此外,FAERS数据库中还发现了14780份与PARPis相关的血液学AE报告,所有PARPis都与强烈的血液学AE信号相关。血液学AE主要发生在开始使用PARPi后的头3个月内(80.84%):结论:在五种PARPi中,奥拉帕利的安全性最好。结论:在五种PARP中,奥拉帕利的安全性最好:PROCROPERO(CRD42022385274)。
{"title":"Safety and hematological toxicities of PARP inhibitors in patients with cancer: a systematic review of randomized controlled trials and a pharmacovigilance analysis.","authors":"Meng-Fei Dai, Xin Wang, Wen-Xiu Xin, Si-Si Kong, Wei-Ben Xu, Hai-Ying Ding, Luo Fang","doi":"10.1080/14737140.2024.2357822","DOIUrl":"10.1080/14737140.2024.2357822","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to estimate the toxicities of PARP inhibitors (PARPis), based on randomized controlled trials (RCTs) and the FDA Adverse Event Reporting System (FAERS) database.</p><p><strong>Methods: </strong>Four electronic databases were searched from inception to 16 April 2024, for RCTs of approved PARPis. The primary and secondary outcomes were grade 3-5 adverse events (AEs) and grade 3-5 hematological AE, respectively. We conducted network meta-analyses to calculate the relative risks (RRs) and 95% confidence intervals (CIs) of outcomes. A disproportionality analysis was conducted to estimate the signals of hematological AEs associated with PARPis from the FAERS database.</p><p><strong>Results: </strong>Overall, 27 RCTs involving 11,067 patients with cancer were included. Olaparib had the best safety profile for any grade 3-5 AEs and hematological AEs among four approved PARPis. Olaparib did not increase the risk of thrombocytopenia (RR: 1.48; 95%CI: 0.64-3.39), but other PARPis did. Furthermore 14,780 hematological AE reports associated with PARPis were identified in the FAERS database, and all PARPis were associated with strong hematological AE signals. Hematological AEs mainly occurred within the first 3 months (80.84%) after PARPi initiation.</p><p><strong>Conclusion: </strong>Olaparib had the best safety profile among five PARPis. PARPi-associated hematological AEs mainly occurred within the first 3 months.</p><p><strong>Registration: </strong>PROSPERO (CRD42022385274).</p>","PeriodicalId":12099,"journal":{"name":"Expert Review of Anticancer Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Current management of familial adenomatous polyposis. 家族性腺瘤性息肉病的当前治疗方法。
IF 3.3 3区 医学 Q2 Medicine Pub Date : 2024-06-01 Epub Date: 2024-05-26 DOI: 10.1080/14737140.2024.2344649
Sara Lauricella, Emanuele Rausa, Ilaria Pellegrini, Maria Teresa Ricci, Stefano Signoroni, Elena Palassini, Federica Cavalcoli, Patrizia Pasanisi, Chiara Colombo, Marco Vitellaro

Introduction: APC-associated polyposis is a rare hereditary disorder characterized by the development of multiple adenomas in the digestive tract. Individuals with APC-associated polyposis need to be managed by specialized multidisciplinary teams in dedicated centers.

Areas covered: The study aimed to review the literature on Familial adenomatous polyposis (FAP) to provide an update on diagnostic and surgical management while focusing on strategies to minimize the risk of desmoid-type fibromatosis, cancer in anorectal remnant, and postoperative complications. FAP individuals require a comprehensive approach that includes diagnosis, surveillance, preventive surgery, and addressing specific extracolonic concerns such as duodenal and desmoid tumors. Management should be personalized considering all factors: genotype, phenotype, and personal needs. Total colectomy and ileo-rectal anastomosis have been shown to yield superior QoL results when compared to Restorative Procto colectomy and ileopouch-anal anastomosis with acceptable oncological risk of developing cancer in the rectal stump if patients rigorously adhere to lifelong endoscopic surveillance. Additionally, a low-inflammatory diet may prevent adenomas and cancer by modulating systemic and tissue inflammatory indices.

Expert opinion: FAP management requires a multidisciplinary and personalized approach. Integrating genetic advances, innovative surveillance techniques, and emerging therapeutic modalities will contribute to improving outcomes and quality of life for FAP individuals.

简介APC相关性息肉病是一种罕见的遗传性疾病,其特征是消化道出现多发性腺瘤。APC相关性息肉病患者需要在专门的中心由专业的多学科团队进行管理:该研究旨在回顾有关家族性腺瘤性息肉病(FAP)的文献,提供诊断和手术治疗的最新信息,同时重点关注如何最大限度地降低发生类脂样纤维瘤病、肛门直肠残余癌和术后并发症的风险。FAP 患者需要全面的治疗方法,包括诊断、监测、预防性手术以及解决十二指肠和蜕膜肿瘤等结肠外的特殊问题。应综合考虑基因型、表型和个人需求等所有因素,进行个性化治疗。全结肠切除术和回肠直肠吻合术与恢复性直肠切除术和回肠肛门吻合术相比,如果患者严格遵守终生内镜监测,直肠残端发生癌症的肿瘤风险是可以接受的。此外,低炎饮食可通过调节全身和组织炎症指数来预防腺瘤和癌症:FAP 的治疗需要多学科和个性化的方法。专家观点:FAP 的治疗需要多学科和个性化的方法,整合基因进展、创新监测技术和新兴治疗模式将有助于改善 FAP 患者的治疗效果和生活质量。
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引用次数: 0
Establishing biomarkers for soft tissue sarcomas. 建立软组织肉瘤的生物标记。
IF 3.3 3区 医学 Q2 Medicine Pub Date : 2024-06-01 Epub Date: 2024-04-30 DOI: 10.1080/14737140.2024.2346187
Anna M Czarnecka, Paulina Chmiel, Piotr Błoński, Piotr Rutkowski

Introduction: Soft tissue sarcomas (STS) are a rare and diverse group of tumors. Curative options are limited to localized disease, with surgery being the mainstay. Advanced stages are associated with a poor prognosis. Currently, the prognosis of the patient is based on histological classification and clinical characteristics, with only a few biomarkers having entered clinical practice.

Areas covered: This article covers extensive recent research that has established novel potential biomarkers based on genomics, proteomics, and clinical characteristics. Validating and incorporating these biomarkers into clinical practice can improve prognosis, prediction of recurrence, and treatment response. Relevant literature was collected from PubMed, Scopus, and clinicaltrials.gov databases (November 2023).

Expert opinion: Currently, defining prognostic markers in soft tissue sarcomas remains challenging. More studies are required, especially to personalize treatment through advanced genetic profiling and analysis using individual tumor and patient characteristics.

简介软组织肉瘤(STS)是一种罕见的多种肿瘤。治疗方法仅限于局部疾病,手术是主要手段。晚期患者预后较差。目前,对患者预后的判断主要基于组织学分类和临床特征,只有少数生物标志物已进入临床实践:本文介绍了近期开展的大量研究,这些研究基于基因组学、蛋白质组学和临床特征建立了新的潜在生物标志物。验证这些生物标志物并将其纳入临床实践可改善预后、预测复发和治疗反应。相关文献来自 PubMed、Scopus 和 clinicaltrials.gov 数据库(2023 年 11 月):目前,确定软组织肉瘤的预后标志物仍具有挑战性。需要进行更多的研究,尤其是通过先进的基因谱分析和利用肿瘤及患者个体特征进行分析,实现个性化治疗。
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引用次数: 0
Antibody-drug conjugates, bispecific antibodies and CAR-T cells therapy in multiple myeloma. 多发性骨髓瘤的抗体药物共轭物、双特异性抗体和 CAR-T 细胞疗法。
IF 3.3 3区 医学 Q2 Medicine Pub Date : 2024-06-01 Epub Date: 2024-05-26 DOI: 10.1080/14737140.2024.2344647
Paola Tacchetti, Marco Talarico, Simona Barbato, Lucia Pantani, Katia Mancuso, Ilaria Rizzello, Elena Zamagni, Michele Cavo

Introduction: Modern immunotherapy approaches are revolutionizing the treatment scenario of relapsed/refractory (RR) multiple myeloma (MM) patients, providing an opportunity to reach deep level of responses and extend survival outcomes.

Areas covered: Antibody-drug conjugates (ADCs) and T-cell redirecting treatments, including bispecific antibodies (BsAbs) and chimeric antigen receptor (CAR) T cells therapy, have been recently introduced in the treatment of RRMM. Some agents have already received regulatory approval, while newer constructs, novel combinations, and applications in earlier lines of therapy are currently being explored. This review discusses the current landscape and possible development of ADCs, BsAbs and CAR-T cells immunotherapies.

Expert opinion: ADCs, BsAbs, and CAR-T therapy have demonstrated substantial activity in heavily pretreated, triple-class exposed (TCE) MM patients, and T-cell redirecting treatments represent new standards of care after third (European Medicines Agency, EMA), or fourth (Food and Drug Administration, FDA), line of therapy. All these three immunotherapies carry advantages and disadvantages, with different accessibility and new toxicities that require appropriate management and guidelines. Multiple on-going programs include combinations therapies and applications in earlier lines of treatment, as well as the development of novel agents or construct to enhance potency, reduce toxicity and facilitate administration. Sequencing is a challenge, with few data available and mechanisms of resistance still to be unraveled.

简介:现代免疫疗法正在彻底改变复发/难治性(RR)多发性骨髓瘤(MM)患者的治疗方案,为达到深层次应答和延长生存期提供了机会:抗体药物共轭物(ADC)和T细胞重定向疗法,包括双特异性抗体(BsAbs)和嵌合抗原受体(CAR)T细胞疗法,最近已被引入RRMM的治疗中。一些药物已获得监管部门的批准,而更新的构建物、新型组合以及在早期疗法中的应用目前正在探索之中。本综述讨论了ADCs、BsAbs和CAR-T细胞免疫疗法的现状和可能发展:ADCs、BsAbs和CAR-T疗法已在接受重度预处理、三类暴露(TCE)的MM患者中显示出巨大的活性,T细胞重定向疗法代表了第三(欧洲药品管理局,EMA)或第四(美国食品和药物管理局,FDA)线治疗后的新治疗标准。这三种免疫疗法各有利弊,具有不同的可及性和新的毒性,需要适当的管理和指导。目前正在进行的多个项目包括联合疗法和早期治疗方法的应用,以及新型制剂或构建物的开发,以提高效力、降低毒性和方便给药。测序是一项挑战,目前可用的数据很少,抗药性机制仍有待揭示。
{"title":"Antibody-drug conjugates, bispecific antibodies and CAR-T cells therapy in multiple myeloma.","authors":"Paola Tacchetti, Marco Talarico, Simona Barbato, Lucia Pantani, Katia Mancuso, Ilaria Rizzello, Elena Zamagni, Michele Cavo","doi":"10.1080/14737140.2024.2344647","DOIUrl":"10.1080/14737140.2024.2344647","url":null,"abstract":"<p><strong>Introduction: </strong>Modern immunotherapy approaches are revolutionizing the treatment scenario of relapsed/refractory (RR) multiple myeloma (MM) patients, providing an opportunity to reach deep level of responses and extend survival outcomes.</p><p><strong>Areas covered: </strong>Antibody-drug conjugates (ADCs) and T-cell redirecting treatments, including bispecific antibodies (BsAbs) and chimeric antigen receptor (CAR) T cells therapy, have been recently introduced in the treatment of RRMM. Some agents have already received regulatory approval, while newer constructs, novel combinations, and applications in earlier lines of therapy are currently being explored. This review discusses the current landscape and possible development of ADCs, BsAbs and CAR-T cells immunotherapies.</p><p><strong>Expert opinion: </strong>ADCs, BsAbs, and CAR-T therapy have demonstrated substantial activity in heavily pretreated, triple-class exposed (TCE) MM patients, and T-cell redirecting treatments represent new standards of care after third (European Medicines Agency, EMA), or fourth (Food and Drug Administration, FDA), line of therapy. All these three immunotherapies carry advantages and disadvantages, with different accessibility and new toxicities that require appropriate management and guidelines. Multiple on-going programs include combinations therapies and applications in earlier lines of treatment, as well as the development of novel agents or construct to enhance potency, reduce toxicity and facilitate administration. Sequencing is a challenge, with few data available and mechanisms of resistance still to be unraveled.</p>","PeriodicalId":12099,"journal":{"name":"Expert Review of Anticancer Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Radiation therapy for triple-negative breast cancer: from molecular insights to clinical perspectives. 三阴性乳腺癌的放射治疗:从分子洞察到临床视角。
IF 3.3 3区 医学 Q2 Medicine Pub Date : 2024-05-01 Epub Date: 2024-03-21 DOI: 10.1080/14737140.2024.2333320
Jongmyung Kim, Veronia Fahmy, Bruce G Haffty

Introduction: Triple-negative breast cancer (TNBC) lacks three common receptors, making traditional treatments less effective. This review highlights the importance of radiotherapy and emerging therapeutic strategies to enhance treatment outcomes in TNBC.

Areas covered: We conducted a literature search on PubMed for publications from 2000 to 2023 to discuss the critical role of radiotherapy in managing TNBC, emphasizing its applications from locoregional control to improving survival rates. The review explores molecular mechanisms underlying TNBC's radiotherapy response, including DNA damage repair and apoptosis, with a focus on BRCA1/2 mutations and Poly (ADP-ribose) polymerase (PARP) inhibition. We summarize preclinical and clinical research on radiosensitization strategies, from gene-targeted therapies to immunotherapy combinations, and the impact of post-mastectomy radiation therapy on locoregional control. The potential of personalized treatment approaches, integrating molecular profiling, targeted radiosensitizers, and the synergistic effects of radiotherapy with immunotherapy, is also discussed.

Expert opinion: Future TNBC treatment strategies should focus on precision medicine, integrating immunotherapy, developing novel radiosensitizers, and targeting biological pathways to overcome radioresistance. The integration of radiomics and artificial intelligence offers promising avenues for enhancing treatment personalization and efficacy, aiming to improve patient outcomes in TNBC.

简介三阴性乳腺癌(TNBC)缺乏三种常见受体,因此传统治疗效果较差。这篇综述强调了放疗和新兴治疗策略对提高 TNBC 治疗效果的重要性:我们在PubMed上检索了2000年至2023年发表的文献,讨论放疗在TNBC治疗中的关键作用,强调放疗在局部控制和提高生存率等方面的应用。综述探讨了 TNBC 放疗反应的分子机制,包括 DNA 损伤修复和细胞凋亡,重点关注 BRCA1/2 基因突变和聚(ADP-核糖)聚合酶(PARP)抑制。我们总结了从基因靶向疗法到免疫疗法组合等放射增敏策略的临床前和临床研究,以及乳房切除术后放疗对局部区域控制的影响。此外,还讨论了整合分子图谱、靶向放射增敏剂以及放疗与免疫疗法协同作用的个性化治疗方法的潜力:未来的 TNBC 治疗策略应侧重于精准医疗、整合免疫疗法、开发新型放射增敏剂以及靶向生物通路以克服放射抗性。放射组学与人工智能的结合为提高治疗的个性化和疗效提供了前景广阔的途径,旨在改善 TNBC 患者的预后。
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Expert Review of Anticancer Therapy
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