Michelle M Dugan, Matthew C Perez, Lilit Karapetyan, Jonathan S Zager
Abstract: The treatment landscape for advanced and metastatic melanoma has drastically changed in recent years, with the advent of novel therapeutic options such as immune checkpoint inhibitors and targeted therapies offering remarkable efficacy and significantly improved patient outcomes compared to traditional approaches. Approximately 50% of melanomas harbor activating BRAF mutations, with over 90% resulting in BRAF V600E. Tumors treated with BRAF inhibitor monotherapy have a high rate of developing resistance within six months. Combination therapy with MEK inhibitors helped to mitigate this treatment resistance and led to improved outcomes. Due to the up-regulation of PD-1/PD-L1 receptors in tumors treated with BRAF/MEK inhibitor therapy, further studies included a third combination agent, anti-PD-1/PD-L1 inhibitors. This triple combination therapy may have superior efficacy and a manageable safety profile when compared with single or double agent therapy regimens.
Plain Language Summary: Effective treatment of advanced and metastatic melanoma can be challenging. Newer treatment methods for patients with BRAF-mutated tumors include a combination of drugs with different complementary mechanisms. These drugs include BRAF-inhibitors, MEK-inhibitors, and PD-1/PD-L1 inhibitors. When these three medications are used in combination, patients may have better response rates and survival outcomes, when compared to using just one or two of these medications together. Toxicity rates are higher with a triple-medication regimen, so careful patient selection is important to consider.
{"title":"Combination Atezolizumab, Cobimetinib, and Vemurafenib as a Treatment Option in BRAF V600 Mutation–Positive Melanoma: Patient Selection and Perspectives","authors":"Michelle M Dugan, Matthew C Perez, Lilit Karapetyan, Jonathan S Zager","doi":"10.2147/cmar.s325514","DOIUrl":"https://doi.org/10.2147/cmar.s325514","url":null,"abstract":"<strong>Abstract:</strong> The treatment landscape for advanced and metastatic melanoma has drastically changed in recent years, with the advent of novel therapeutic options such as immune checkpoint inhibitors and targeted therapies offering remarkable efficacy and significantly improved patient outcomes compared to traditional approaches. Approximately 50% of melanomas harbor activating BRAF mutations, with over 90% resulting in BRAF V600E. Tumors treated with BRAF inhibitor monotherapy have a high rate of developing resistance within six months. Combination therapy with MEK inhibitors helped to mitigate this treatment resistance and led to improved outcomes. Due to the up-regulation of PD-1/PD-L1 receptors in tumors treated with BRAF/MEK inhibitor therapy, further studies included a third combination agent, anti-PD-1/PD-L1 inhibitors. This triple combination therapy may have superior efficacy and a manageable safety profile when compared with single or double agent therapy regimens.<br/><br/><strong>Plain Language Summary:</strong> Effective treatment of advanced and metastatic melanoma can be challenging. Newer treatment methods for patients with BRAF-mutated tumors include a combination of drugs with different complementary mechanisms. These drugs include BRAF-inhibitors, MEK-inhibitors, and PD-1/PD-L1 inhibitors. When these three medications are used in combination, patients may have better response rates and survival outcomes, when compared to using just one or two of these medications together. Toxicity rates are higher with a triple-medication regimen, so careful patient selection is important to consider.<br/><br/><strong>Keywords:</strong> BRAF inhibitor, MEK inhibitor, metastatic melanoma, BRAF-mutant melanoma, combination BRAF therapy, triple therapy<br/>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":"170 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141867362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhenyu Li, Jimin Liu, Haishan Cui, Wenlong Qi, Yangyang Tong, Tan Wang
Abstract: The rising global morbidity and mortality rates of non-small cell lung cancer (NSCLC) underscore the urgent need for more effective treatments. Current therapeutic modalities—including surgery, radiotherapy, chemotherapy, and targeted therapy—face several limitations. Recently, Astragalus membranaceus, a traditional Chinese medicine (TCM), has captured significant attention due to its broad pharmacological properties, such as immune regulation, anti-inflammatory effects, and the modulation of reactive oxygen species (ROS) and enzyme activities. This review delivers a comprehensive summary of the most recent advancements and ongoing applications of Astragalus membranaceus in NSCLC treatment, underlining its potential for integration into existing treatment protocols. It also highlights essential areas for future research, including the elucidation of its molecular mechanisms, optimization of dosage and administration, and evaluation of its efficacy and safety alongside standard therapies, all of which could potentially improve therapeutic outcomes for NSCLC patients.
{"title":"Astragalus membranaceus: A Review of Its Antitumor Effects on Non-Small Cell Lung Cancer","authors":"Zhenyu Li, Jimin Liu, Haishan Cui, Wenlong Qi, Yangyang Tong, Tan Wang","doi":"10.2147/cmar.s466633","DOIUrl":"https://doi.org/10.2147/cmar.s466633","url":null,"abstract":"<strong>Abstract:</strong> The rising global morbidity and mortality rates of non-small cell lung cancer (NSCLC) underscore the urgent need for more effective treatments. Current therapeutic modalities—including surgery, radiotherapy, chemotherapy, and targeted therapy—face several limitations. Recently, <em>Astragalus membranaceus</em>, a traditional Chinese medicine (TCM), has captured significant attention due to its broad pharmacological properties, such as immune regulation, anti-inflammatory effects, and the modulation of reactive oxygen species (ROS) and enzyme activities. This review delivers a comprehensive summary of the most recent advancements and ongoing applications of <em>Astragalus membranaceus</em> in NSCLC treatment, underlining its potential for integration into existing treatment protocols. It also highlights essential areas for future research, including the elucidation of its molecular mechanisms, optimization of dosage and administration, and evaluation of its efficacy and safety alongside standard therapies, all of which could potentially improve therapeutic outcomes for NSCLC patients.<br/><br/><strong>Keywords:</strong> non-small cell lung cancer, <em>Astragalus membranaceus</em>, antitumor activity, immunoregulation, cisplatin<br/>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":"113 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141777855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yantao Yu, Chenkai Zhang, Qiannan Sun, Shantanu Baral, Jianyue Ding, Fanyu Zhao, Qing Yao, Shuyang Gao, Bin Liu, Daorong Wang
Background: Gastric cancer (GC) is a highly phenotypically heterogeneous disease and is caused by a combination of factors. Retinol binding protein 4 (RBP4) is a member of a family of lipid transport proteins that are involved in the transport of substances between cells and play a crucial role in a variety of cancers. However, the expression and role of RBP4 in GC remain unknown. Methods: In this study, we explored the expression, prognostic significance, immune microenvironment, drug responsiveness and function of associated signaling pathways of RBP4 in GC using web-based bioinformatics tools. Immunohistochemistry and real-time quantitative PCR were utilized to analyze the tissue and cell expression levels of RBP4. CCK-8, colony formation, EDU incorporation, wound healing and transwell assays were applied to demonstrate the effect of RBP4 on GC cell function. Flow cytometric detection of apoptosis after RBP4 knockdown. Nude mice xenograft model elucidates the role of RBP4 for GC in vivo. Related proteins of the RAS signaling pathway were analyzed by employing Western blot assays. Results: RBP4 is highly expressed in GC. RBP4 is closely associated with patient survival and sensitivity to a wide range of antitumor agents. Knockdown of RBP4 promoted apoptosis and inhibited cell proliferation, invasion and migration. RBP4 promotes GC tumorigenesis in vivo. Finally, RBP4 modulates the RAS/RAF/ERK axis. Conclusion: RBP4 may promote gastric carcinogenesis and development through the RAS/RAF/ERK axis and is expected to be a novel target for GC treatment.
{"title":"Retinol Binding Protein 4 Serves as a Potential Tumor Biomarker and Promotes Malignant Behavior in Gastric Cancer","authors":"Yantao Yu, Chenkai Zhang, Qiannan Sun, Shantanu Baral, Jianyue Ding, Fanyu Zhao, Qing Yao, Shuyang Gao, Bin Liu, Daorong Wang","doi":"10.2147/cmar.s480337","DOIUrl":"https://doi.org/10.2147/cmar.s480337","url":null,"abstract":"<strong>Background:</strong> Gastric cancer (GC) is a highly phenotypically heterogeneous disease and is caused by a combination of factors. Retinol binding protein 4 (RBP4) is a member of a family of lipid transport proteins that are involved in the transport of substances between cells and play a crucial role in a variety of cancers. However, the expression and role of RBP4 in GC remain unknown.<br/><strong>Methods:</strong> In this study, we explored the expression, prognostic significance, immune microenvironment, drug responsiveness and function of associated signaling pathways of RBP4 in GC using web-based bioinformatics tools. Immunohistochemistry and real-time quantitative PCR were utilized to analyze the tissue and cell expression levels of RBP4. CCK-8, colony formation, EDU incorporation, wound healing and transwell assays were applied to demonstrate the effect of RBP4 on GC cell function. Flow cytometric detection of apoptosis after RBP4 knockdown. Nude mice xenograft model elucidates the role of RBP4 for GC in vivo. Related proteins of the RAS signaling pathway were analyzed by employing Western blot assays.<br/><strong>Results:</strong> RBP4 is highly expressed in GC. RBP4 is closely associated with patient survival and sensitivity to a wide range of antitumor agents. Knockdown of RBP4 promoted apoptosis and inhibited cell proliferation, invasion and migration. RBP4 promotes GC tumorigenesis in vivo. Finally, RBP4 modulates the RAS/RAF/ERK axis.<br/><strong>Conclusion:</strong> RBP4 may promote gastric carcinogenesis and development through the RAS/RAF/ERK axis and is expected to be a novel target for GC treatment.<br/><br/>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":"24 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141777856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiajin Feng, Keming Chen, Haifu Tian, Al-qaisi Mohammed Abdulkarem, Yunshang Tuo, Xuehao Wang, Bincheng Huang, Yu Gao, Zhiyong Lv, Rui He, Guangyong Li
Objective: To explore the effectiveness of prostate biopsy density in predicting prostate cancer under cognitive and systematic biopsy mode in multi-parametric magnetic resonance imaging (mpMRI). Methods: A retrospective analysis was conducted on clinical data of 204 patients who were suspected of having prostate cancer with prostate-specific antigen (PSA) levels less than 50 ng mL− 1 and underwent cognitive and systematic biopsy through the perineal approach in our hospital from 2022 to 2023. Univariate and multivariate logistic regression analyses were used to evaluate the odds ratios of prostate biopsy density and relevant clinical indicators. Logistic regression analysis was performed to establish a predictive model combining indicators with predictive value. The predictive value of each indicator and the new model was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC). Results: The detection rate of prostate cancer in the study population was 32.35%. Multivariate analysis showed that age, PSAD, PI-RADS 2.1 score, and prostate biopsy density were independent predictors of prostate cancer. The ROC curve analysis revealed an AUC of 0.707 (95% CI 0.625– 0.790) for biopsy density, with a cutoff value of approximately 0.22 needle mL− 1. The best predictive model consisted of age, PSAD, PI-RADS 2.1 score, and biopsy density, with an AUC of 0.857. Conclusion: Biopsy density is associated with the detection of prostate cancer, with a critical value of 0.22 needle mL− 1. Combining biopsy density with other clinical indicators can significantly improve the ability to predict prostate cancer and avoid unnecessary prostate biopsy cores.
Keywords: prostate biopsy, multi-parametric magnetic resonance imaging, biopsy density, cognitive fusion, cancer prediction
{"title":"Investigation of the Effectiveness of Prostate Biopsy Density in Predicting Prostate Cancer Under Cognitive and Systematic Biopsy in Multi-Parametric Magnetic Resonance Imaging (mpMRI)","authors":"Jiajin Feng, Keming Chen, Haifu Tian, Al-qaisi Mohammed Abdulkarem, Yunshang Tuo, Xuehao Wang, Bincheng Huang, Yu Gao, Zhiyong Lv, Rui He, Guangyong Li","doi":"10.2147/cmar.s476636","DOIUrl":"https://doi.org/10.2147/cmar.s476636","url":null,"abstract":"<strong>Objective:</strong> To explore the effectiveness of prostate biopsy density in predicting prostate cancer under cognitive and systematic biopsy mode in multi-parametric magnetic resonance imaging (mpMRI).<br/><strong>Methods:</strong> A retrospective analysis was conducted on clinical data of 204 patients who were suspected of having prostate cancer with prostate-specific antigen (PSA) levels less than 50 ng mL<sup>− 1</sup> and underwent cognitive and systematic biopsy through the perineal approach in our hospital from 2022 to 2023. Univariate and multivariate logistic regression analyses were used to evaluate the odds ratios of prostate biopsy density and relevant clinical indicators. Logistic regression analysis was performed to establish a predictive model combining indicators with predictive value. The predictive value of each indicator and the new model was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC).<br/><strong>Results:</strong> The detection rate of prostate cancer in the study population was 32.35%. Multivariate analysis showed that age, PSAD, PI-RADS 2.1 score, and prostate biopsy density were independent predictors of prostate cancer. The ROC curve analysis revealed an AUC of 0.707 (95% CI 0.625– 0.790) for biopsy density, with a cutoff value of approximately 0.22 needle mL<sup>− 1</sup>. The best predictive model consisted of age, PSAD, PI-RADS 2.1 score, and biopsy density, with an AUC of 0.857.<br/><strong>Conclusion:</strong> Biopsy density is associated with the detection of prostate cancer, with a critical value of 0.22 needle mL<sup>− 1</sup>. Combining biopsy density with other clinical indicators can significantly improve the ability to predict prostate cancer and avoid unnecessary prostate biopsy cores.<br/><br/><strong>Keywords:</strong> prostate biopsy, multi-parametric magnetic resonance imaging, biopsy density, cognitive fusion, cancer prediction<br/>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":"21 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141777857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marta Julia Fernández-González, Anne-Catherine Radauer-Plank, Anja Borgmann-Staudt, Waldemar Geiger, Irena Goranova, Stephanie Klco-Brosius, Bernhard Ralla, Cornelia Stelzer, Ina Wilkemeyer, Magdalena Balcerek
Purpose: This retrospective cohort study assessed semen and testicular tissue quality from adult and adolescent cancer patients who had samples cryopreserved in the Cryobank of Charité-Universitätsmedizin before and/or after cancer treatment. Methods and Materials: Medical and cryopreservation data for all samples stored between 03/2004 and 05/2019 were collected retrospectively. Results: We included information on 601 samples cryopreserved from 506 cancer patients for whom oncologic treatment data were available. The majority of the samples were cryopreserved prior to cancer treatment (460/600, 77%, median 5 days before treatment). Semen quality had a predisposed reduction in those collected from adolescents with testicular and/or hematological malignancies. Analyses of the 140 (23%) samples cryopreserved after treatment initiation (median of 84 days) revealed decreased median concentration and motility following high gonadotoxic-risk treatment. Rate of oligoasthenozoospermia was comparable in samples collected prior to treatment with those provided during follow-up spermiograms within 1 year after treatment initiation (45.5% vs 45.5%). However, an increase was seen in samples collected 1– 2 (9.1% to 90.9%) and 2– 3 (50.0% to 100.0%) years after treatment initiation. Conclusion: Cancer diagnosis and treatment may impair spermatogenesis; therefore, patient counseling prior to cancer treatment by an oncologist and/or fertility specialist is crucial.
Keywords: cancer, fertility preservation, adolescent, men
{"title":"An Assessment of Cryopreserved Semen and Testicular Tissue Collected Before and After Cancer Treatment Initiation","authors":"Marta Julia Fernández-González, Anne-Catherine Radauer-Plank, Anja Borgmann-Staudt, Waldemar Geiger, Irena Goranova, Stephanie Klco-Brosius, Bernhard Ralla, Cornelia Stelzer, Ina Wilkemeyer, Magdalena Balcerek","doi":"10.2147/cmar.s460960","DOIUrl":"https://doi.org/10.2147/cmar.s460960","url":null,"abstract":"<strong>Purpose:</strong> This retrospective cohort study assessed semen and testicular tissue quality from adult and adolescent cancer patients who had samples cryopreserved in the Cryobank of Charité-Universitätsmedizin before and/or after cancer treatment.<br/><strong>Methods and Materials:</strong> Medical and cryopreservation data for all samples stored between 03/2004 and 05/2019 were collected retrospectively.<br/><strong>Results:</strong> We included information on 601 samples cryopreserved from 506 cancer patients for whom oncologic treatment data were available. The majority of the samples were cryopreserved prior to cancer treatment (460/600, 77%, median 5 days before treatment). Semen quality had a predisposed reduction in those collected from adolescents with testicular and/or hematological malignancies. Analyses of the 140 (23%) samples cryopreserved after treatment initiation (median of 84 days) revealed decreased median concentration and motility following high gonadotoxic-risk treatment. Rate of oligoasthenozoospermia was comparable in samples collected prior to treatment with those provided during follow-up spermiograms within 1 year after treatment initiation (45.5% vs 45.5%). However, an increase was seen in samples collected 1– 2 (9.1% to 90.9%) and 2– 3 (50.0% to 100.0%) years after treatment initiation.<br/><strong>Conclusion:</strong> Cancer diagnosis and treatment may impair spermatogenesis; therefore, patient counseling prior to cancer treatment by an oncologist and/or fertility specialist is crucial.<br/><br/><strong>Keywords:</strong> cancer, fertility preservation, adolescent, men<br/>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":"23 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141777894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Markus Joerger, Kira-Lee Koster, Tomas Janik, Floris A de Jong
<strong>Purpose:</strong> Immune checkpoint inhibitors (CPIs) have been widely adopted in a number of early and advanced malignancies. Histone deacetylase inhibitors (HDACis) and alkylating agents (AAs) have been suggested to potentiate the actions of CPIs on tumor cells. We conducted a comprehensive literature review to explore the potential synergistic activity between CPIs, AAs, and HDACis.<br/><strong>Patients and Methods:</strong> Clinical and non-clinical studies describing outcomes in patients with cancer receiving CPIs and either concomitant or sequential (pre- or post-CPI) AAs or HDACis were identified in PubMed using pre-defined search strings. Manual searches of key oncology congresses were similarly performed. All relevant articles and abstracts were manually screened for relevance, classified according to the specific anticancer agents used (CPIs, AAs, or HDACis), tumor entity, and whether treatment was concomitant or sequential.<br/><strong>Results:</strong> Overall, 227 unique clinical studies across a range of tumor types, both solid tumors and hematological malignancies, were identified. One hundred and fifty-nine publications on Phase I and II clinical studies together with 41 publications on Phase III studies were examined. The most commonly investigated tumor types were melanoma, triple-negative breast cancer, non-small cell lung cancer, and Hodgkin lymphoma. The randomized clinical studies identified, all of which reported on the combination of a CPI with an AA, demonstrated superior outcomes in the combination arm compared with CPI or AA monotherapy. Similarly, combination therapy with CPIs and HDACis demonstrated promising activity.<br/><strong>Conclusion:</strong> Sequential or concomitant administration of a CPI with an AA or an HDACi may improve outcomes for patients with a range of tumor types. There is a rationale to support further investigation into the potential for synergy between CPIs, alkylating agents and/or HDACis in both the non-clinical and clinical settings.<br/><br/><strong>Plain Language Summary:</strong> People being treated for cancer will often receive more than one drug at a time, and the concept of combining cancer drugs is frequently investigated as a potential opportunity to improve outcomes for patients. We reviewed the published literature for clinical trials and work undertaken in laboratories to explore whether combining targeted agents that stop cancer cells from multiplying (known as checkpoint inhibitors) with traditional chemotherapy that kills cancer cells could be a useful approach. We looked at evidence in publications where checkpoint inhibitors were used at the same time as chemotherapy, or given immediately before or after chemotherapy. The most important evidence came from clinical trials where outcomes for patients receiving combinations of treatment were directly compared with those from patients receiving a single treatment. These studies showed superior outcomes for patients who w
目的：免疫检查点抑制剂（CPIs）已被广泛用于一些早期和晚期恶性肿瘤。有人认为组蛋白去乙酰化酶抑制剂（HDACis）和烷化剂（AAs）能增强CPIs对肿瘤细胞的作用。我们进行了全面的文献综述，以探索 CPIs、AAs 和 HDACis 之间潜在的协同活性：使用预先定义的搜索字符串，在 PubMed 上查找描述癌症患者接受 CPIs 和同时或先后（CPI 之前或之后）接受 AAs 或 HDACis 治疗的临床和非临床研究。对主要肿瘤学大会也进行了类似的人工检索。人工筛选所有相关文章和摘要的相关性，并根据使用的特定抗癌药物（CPI、AA 或 HDACis）、肿瘤实体以及治疗是同时进行还是连续进行进行进行分类：总体而言，共发现了 227 项独特的临床研究，涉及多种肿瘤类型，包括实体瘤和血液恶性肿瘤。其中 159 篇发表于 I 期和 II 期临床研究，41 篇发表于 III 期研究。最常研究的肿瘤类型是黑色素瘤、三阴性乳腺癌、非小细胞肺癌和霍奇金淋巴瘤。已确定的随机临床研究均报告了 CPI 与 AA 的联合治疗，结果显示联合治疗组的疗效优于 CPI 或 AA 单药治疗组。同样，CPI 与 HDACis 的联合疗法也显示出良好的活性：结论：CPI 与 AA 或 HDACi 相继或同时给药可改善各种肿瘤类型患者的预后。有理由支持在非临床和临床环境中进一步研究 CPIs、烷化剂和/或 HDACis 之间的潜在协同作用。我们回顾了已发表的临床试验文献和实验室工作，以探讨将阻止癌细胞繁殖的靶向药物（称为检查点抑制剂）与杀死癌细胞的传统化疗相结合是否是一种有用的方法。我们研究了在化疗的同时使用检查点抑制剂或在化疗前后立即使用检查点抑制剂的出版物中的证据。最重要的证据来自临床试验，在这些试验中，接受联合治疗的患者的疗效与接受单一治疗的患者的疗效进行了直接比较。这些研究显示，与接受单一疗法的患者相比，接受联合抗癌药物治疗的患者疗效更佳。我们还发现有证据表明，加入另一类抗癌药物（组蛋白去乙酰化酶抑制剂）可能会使肿瘤对检查点抑制剂敏感。这些发现为研究烷化剂和/或组蛋白去乙酰化酶抑制剂与检查点抑制剂联合应用提供了理论依据。 关键词：组蛋白去乙酰化酶抑制剂；检查点抑制剂；烷化剂；协同作用；血液恶性肿瘤；实体瘤
{"title":"Combination Therapy with Immune Checkpoint Inhibitors and Histone Deacetylase Inhibitors or Alkylating Agents","authors":"Markus Joerger, Kira-Lee Koster, Tomas Janik, Floris A de Jong","doi":"10.2147/cmar.s464245","DOIUrl":"https://doi.org/10.2147/cmar.s464245","url":null,"abstract":"<strong>Purpose:</strong> Immune checkpoint inhibitors (CPIs) have been widely adopted in a number of early and advanced malignancies. Histone deacetylase inhibitors (HDACis) and alkylating agents (AAs) have been suggested to potentiate the actions of CPIs on tumor cells. We conducted a comprehensive literature review to explore the potential synergistic activity between CPIs, AAs, and HDACis.<br/><strong>Patients and Methods:</strong> Clinical and non-clinical studies describing outcomes in patients with cancer receiving CPIs and either concomitant or sequential (pre- or post-CPI) AAs or HDACis were identified in PubMed using pre-defined search strings. Manual searches of key oncology congresses were similarly performed. All relevant articles and abstracts were manually screened for relevance, classified according to the specific anticancer agents used (CPIs, AAs, or HDACis), tumor entity, and whether treatment was concomitant or sequential.<br/><strong>Results:</strong> Overall, 227 unique clinical studies across a range of tumor types, both solid tumors and hematological malignancies, were identified. One hundred and fifty-nine publications on Phase I and II clinical studies together with 41 publications on Phase III studies were examined. The most commonly investigated tumor types were melanoma, triple-negative breast cancer, non-small cell lung cancer, and Hodgkin lymphoma. The randomized clinical studies identified, all of which reported on the combination of a CPI with an AA, demonstrated superior outcomes in the combination arm compared with CPI or AA monotherapy. Similarly, combination therapy with CPIs and HDACis demonstrated promising activity.<br/><strong>Conclusion:</strong> Sequential or concomitant administration of a CPI with an AA or an HDACi may improve outcomes for patients with a range of tumor types. There is a rationale to support further investigation into the potential for synergy between CPIs, alkylating agents and/or HDACis in both the non-clinical and clinical settings.<br/><br/><strong>Plain Language Summary:</strong> People being treated for cancer will often receive more than one drug at a time, and the concept of combining cancer drugs is frequently investigated as a potential opportunity to improve outcomes for patients. We reviewed the published literature for clinical trials and work undertaken in laboratories to explore whether combining targeted agents that stop cancer cells from multiplying (known as checkpoint inhibitors) with traditional chemotherapy that kills cancer cells could be a useful approach. We looked at evidence in publications where checkpoint inhibitors were used at the same time as chemotherapy, or given immediately before or after chemotherapy. The most important evidence came from clinical trials where outcomes for patients receiving combinations of treatment were directly compared with those from patients receiving a single treatment. These studies showed superior outcomes for patients who w","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":"79 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141742709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenzhen Ge, Ning Wu, Chieh-I Chen, Timothy J Inocencio, Patrick R LaFontaine, Frank Seebach, Matthew Fury, James Harnett, Emily S Ruiz
Background: Prior to the Food and Drug Administration approval of cemiplimab in 2018, the median overall survival (OS) for adult patients with advanced CSCC receiving systemic therapy was approximately 8 to 15 months. Limited real-world data are available on cemiplimab for this indication in the US. Patients and Methods: This retrospective cohort study included US patients with advanced CSCC initiating cemiplimab monotherapy in a real-world database (2018– 2021). A clinical trial–like sub-cohort was identified using select criteria. Time to treatment discontinuation (TTD), time to next treatment (TTNT), and OS were estimated using Kaplan–Meier methods. Cox proportional hazard models were used to examine prognostic factors associated with OS in the main cohort. Results: The main cohort included 622 patients (n = 240 in the trial-like cohort). In the main cohort, the median age was 78 years, 77.8% were male, 21.4% were immunocompromised/immunosuppressed, and 63.8% had metastatic CSCC. Median (95% CI) TTD and TTNT were 8.0 (6.6– 9.0) months and 16.4 (13.3– 21.0) months, respectively, in the main cohort. Median (95% CI) OS was 24.8 (21.8– 29.1) months in the main cohort (not reached in the trial-like cohort). In multivariable analyses, age < 60 years (hazard ratio [HR], 0.37), Eastern Cooperative Oncology Group performance status < 3– 4 (HR range, 0.13– 0.57), and primary CSCC location in the head and neck only versus extremities only (HR, 0.59) were associated with better OS. Similar OS was observed between patients who had immunosuppressing/immunocompromising conditions and those without. Conclusion: These findings confirm the effectiveness of cemiplimab among a heterogenous, real-world advanced CSCC patient population and substantiate the efficacy of cemiplimab observed in clinical trials.
{"title":"Real-World Treatment Patterns and Outcomes of Cemiplimab in Patients with Advanced Cutaneous Squamous Cell Carcinoma Treated in US Oncology Practices","authors":"Wenzhen Ge, Ning Wu, Chieh-I Chen, Timothy J Inocencio, Patrick R LaFontaine, Frank Seebach, Matthew Fury, James Harnett, Emily S Ruiz","doi":"10.2147/cmar.s445910","DOIUrl":"https://doi.org/10.2147/cmar.s445910","url":null,"abstract":"<strong>Background:</strong> Prior to the Food and Drug Administration approval of cemiplimab in 2018, the median overall survival (OS) for adult patients with advanced CSCC receiving systemic therapy was approximately 8 to 15 months. Limited real-world data are available on cemiplimab for this indication in the US.<br/><strong>Patients and Methods:</strong> This retrospective cohort study included US patients with advanced CSCC initiating cemiplimab monotherapy in a real-world database (2018– 2021). A clinical trial–like sub-cohort was identified using select criteria. Time to treatment discontinuation (TTD), time to next treatment (TTNT), and OS were estimated using Kaplan–Meier methods. Cox proportional hazard models were used to examine prognostic factors associated with OS in the main cohort.<br/><strong>Results:</strong> The main cohort included 622 patients (n = 240 in the trial-like cohort). In the main cohort, the median age was 78 years, 77.8% were male, 21.4% were immunocompromised/immunosuppressed, and 63.8% had metastatic CSCC. Median (95% CI) TTD and TTNT were 8.0 (6.6– 9.0) months and 16.4 (13.3– 21.0) months, respectively, in the main cohort. Median (95% CI) OS was 24.8 (21.8– 29.1) months in the main cohort (not reached in the trial-like cohort). In multivariable analyses, age < 60 years (hazard ratio [HR], 0.37), Eastern Cooperative Oncology Group performance status < 3– 4 (HR range, 0.13– 0.57), and primary CSCC location in the head and neck only versus extremities only (HR, 0.59) were associated with better OS. Similar OS was observed between patients who had immunosuppressing/immunocompromising conditions and those without.<br/><strong>Conclusion:</strong> These findings confirm the effectiveness of cemiplimab among a heterogenous, real-world advanced CSCC patient population and substantiate the efficacy of cemiplimab observed in clinical trials.<br/><br/>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":"13 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141742588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David Baldwin, Jonathan Carmichael, Gordon Cook, Neal Navani, James Peach, Ruth Slater, Pete Wheatstone, Julia Wilkins, Nicola Allen-Delingpole, Cicely EP Kerr, Khalid Siddiqui
Abstract: Duration of overall survival in patients with cancer has lengthened due to earlier detection and improved treatments. However, these improvements have created challenges in assessing the impact of newer treatments, particularly those used early in the treatment pathway. As overall survival remains most decision-makers’ preferred primary endpoint, therapeutic innovations may take a long time to be introduced into clinical practice. Moreover, it is difficult to extrapolate findings to heterogeneous populations and address the concerns of patients wishing to evaluate everyday quality and extension of life. There is growing interest in the use of surrogate or interim endpoints to demonstrate robust treatment effects sooner than is possible with measurement of overall survival. It is hoped that they could speed up patients’ access to new drugs, combinations, and sequences, and inform treatment decision-making. However, while surrogate endpoints have been used by regulators for drug approvals, this has occurred on a case-by-case basis. Evidence standards are yet to be clearly defined for acceptability in health technology appraisals or to shape clinical practice. This article considers the relevance of the use of surrogate endpoints in cancer in the UK context, and explores whether collection and analysis of real-world UK data and evidence might contribute to validation.
Keywords: cancer, surrogate endpoints, real-world data, multiple myeloma, lung cancer, quality of life
{"title":"UK Stakeholder Perspectives on Surrogate Endpoints in Cancer, and the Potential for UK Real-World Datasets to Validate Their Use in Decision-Making","authors":"David Baldwin, Jonathan Carmichael, Gordon Cook, Neal Navani, James Peach, Ruth Slater, Pete Wheatstone, Julia Wilkins, Nicola Allen-Delingpole, Cicely EP Kerr, Khalid Siddiqui","doi":"10.2147/cmar.s441359","DOIUrl":"https://doi.org/10.2147/cmar.s441359","url":null,"abstract":"<strong>Abstract:</strong> Duration of overall survival in patients with cancer has lengthened due to earlier detection and improved treatments. However, these improvements have created challenges in assessing the impact of newer treatments, particularly those used early in the treatment pathway. As overall survival remains most decision-makers’ preferred primary endpoint, therapeutic innovations may take a long time to be introduced into clinical practice. Moreover, it is difficult to extrapolate findings to heterogeneous populations and address the concerns of patients wishing to evaluate everyday quality and extension of life. There is growing interest in the use of surrogate or interim endpoints to demonstrate robust treatment effects sooner than is possible with measurement of overall survival. It is hoped that they could speed up patients’ access to new drugs, combinations, and sequences, and inform treatment decision-making. However, while surrogate endpoints have been used by regulators for drug approvals, this has occurred on a case-by-case basis. Evidence standards are yet to be clearly defined for acceptability in health technology appraisals or to shape clinical practice. This article considers the relevance of the use of surrogate endpoints in cancer in the UK context, and explores whether collection and analysis of real-world UK data and evidence might contribute to validation.<br/><br/><strong>Keywords:</strong> cancer, surrogate endpoints, real-world data, multiple myeloma, lung cancer, quality of life<br/>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":"53 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Jiang, Yuanyuan Peng, Yingyi Wu, Qing Sun, Tebo Hua
Objective: To develop a clinical-radiomics model using a multimodal machine learning method for distinguishing ductal carcinoma in situ (DCIS) from breast fibromatosis. Methods: The clinical factors, ultrasound features, and related ultrasound images of 306 patients (198 DCIS patients) were retrospectively collected. Patients in the development and validation cohort were 184 and 122, respectively. The independent clinical and ultrasound factors identified by the multivariable logistic regression analysis were used for the clinical-ultrasound model construction. Then, the region of interest of breast lesions was delineated and radiomics features were extracted. Six machine learning algorithms were trained to develop a radiomics model. The algorithm with higher and more stable prediction ability was chosen to convert the output of the results into the Radscore. Further, the independent clinical predictors and Radscore were enrolled into the logistic regression analysis to generate a combined clinical-radiomics model. The receiver operating characteristic curve analysis, DeLong test, and decision curve analysis were adopted to compare the prediction ability and clinical efficacy of three different models. Results: Among the six classifiers, logistic regression model was selected as the final radiomics model. Besides, the combined clinical-radiomics model exhibited a superior ability in distinguishing DCIS from breast fibromatosis to the clinical-ultrasound model and the radiomics model. Conclusion: The combined model by integrating clinical-ultrasound factors and radiomics features performed well in predicting DCIS, which might promote prompt interventions to improve the early diagnosis and prognosis of the patients.
{"title":"Multimodal Machine Learning-Based Ductal Carcinoma in situ Prediction from Breast Fibromatosis","authors":"Yan Jiang, Yuanyuan Peng, Yingyi Wu, Qing Sun, Tebo Hua","doi":"10.2147/cmar.s467400","DOIUrl":"https://doi.org/10.2147/cmar.s467400","url":null,"abstract":"<strong>Objective:</strong> To develop a clinical-radiomics model using a multimodal machine learning method for distinguishing ductal carcinoma in situ (DCIS) from breast fibromatosis.<br/><strong>Methods:</strong> The clinical factors, ultrasound features, and related ultrasound images of 306 patients (198 DCIS patients) were retrospectively collected. Patients in the development and validation cohort were 184 and 122, respectively. The independent clinical and ultrasound factors identified by the multivariable logistic regression analysis were used for the clinical-ultrasound model construction. Then, the region of interest of breast lesions was delineated and radiomics features were extracted. Six machine learning algorithms were trained to develop a radiomics model. The algorithm with higher and more stable prediction ability was chosen to convert the output of the results into the Radscore. Further, the independent clinical predictors and Radscore were enrolled into the logistic regression analysis to generate a combined clinical-radiomics model. The receiver operating characteristic curve analysis, DeLong test, and decision curve analysis were adopted to compare the prediction ability and clinical efficacy of three different models.<br/><strong>Results:</strong> Among the six classifiers, logistic regression model was selected as the final radiomics model. Besides, the combined clinical-radiomics model exhibited a superior ability in distinguishing DCIS from breast fibromatosis to the clinical-ultrasound model and the radiomics model.<br/><strong>Conclusion:</strong> The combined model by integrating clinical-ultrasound factors and radiomics features performed well in predicting DCIS, which might promote prompt interventions to improve the early diagnosis and prognosis of the patients.<br/><br/><strong>Keywords:</strong> multimodal machine learning, clinical-ultrasound features, radiomics, ductal carcinoma in situ<br/>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":"96 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141609430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alvaro Osorio, Liliana Fernandez-Trujillo, Juan G Restrepo, Luz F Sua, Catalina Proaño, Valeria Zuñiga-Restrepo
Purpose: Lung cancer is the leading cause of cancer-related deaths worldwide. However, with the optimization of screening strategies and advances in treatment, mortality has been decreasing in recent years. In this study, we describe non-small cell lung cancer patients diagnosed between 2021 and 2022 at a high-complexity hospital in Latin America, as well as the immunohistochemistry techniques used to screen for ROS1 rearrangements, in the context of the recent approval of crizotinib for the treatment of ROS1 rearrangements in non-small cell lung cancer in Colombia. Methods: A descriptive cross-sectional study was conducted. Sociodemographic, clinical, and molecular pathology information from non-small cell lung cancer individuals who underwent immunohistochemistry to detect ROS1 rearrangements between 2021 and 2022 at Fundación Valle del Lili (Cali, Colombia) was recorded. The clinical outcomes of confirmed ROS1 rearrangements in non-small cell lung cancer patients were reported. Results: One hundred and thirty-six patients with non-small cell lung cancer were included. The median age at diagnosis was 69.8 years (interquartile range 61.9– 77.7). At diagnosis, 69.8% (n = 95) were at stage IV. ROS1 immunohistochemistry was performed using the monoclonal D4D6 antibody clone in 54.4% (n = 74) of the cases, while 45.6% (n = 62) were done with the monoclonal SP384 antibody clone. Two patients were confirmed to have ROS1 rearrangements in non-small cell lung cancer using next-generation sequencing and received crizotinib. On follow-up at months 5.3 and 7.0, one patient had a partial response, and the other had oligo-progression, respectively. Conclusion: Screening for ROS1 rearrangements in non-small cell lung cancer is imperative, as multiple prospective studies have shown improved clinical outcomes with tyrosine kinase inhibitors. Given the recent approval of crizotinib in Colombia, public health policies must be oriented toward early detection of driver mutations and prompt treatment. Additionally, future approvals of newly tested tyrosine kinase inhibitors should be anticipated.
目的：肺癌是全球癌症相关死亡的主要原因。然而，随着筛查策略的优化和治疗手段的进步，近年来死亡率一直在下降。在本研究中，我们介绍了 2021 年至 2022 年期间在拉丁美洲一家综合医院确诊的非小细胞肺癌患者，以及在哥伦比亚最近批准克唑替尼用于治疗非小细胞肺癌 ROS1 重排的背景下，用于筛查 ROS1 重排的免疫组化技术：进行了一项描述性横断面研究。记录了2021年至2022年期间在Fundación Valle del Lili（哥伦比亚卡利）接受免疫组化检测ROS1重排的非小细胞肺癌患者的社会人口学、临床和分子病理学信息。结果：结果：共纳入 136 名非小细胞肺癌患者。确诊时的中位年龄为 69.8 岁（四分位距为 61.9- 77.7）。确诊时，69.8%（n = 95）的患者处于 IV 期。54.4%的病例（n = 74）使用单克隆D4D6抗体克隆进行ROS1免疫组化，45.6%的病例（n = 62）使用单克隆SP384抗体克隆进行免疫组化。两名患者通过新一代测序被证实患有非小细胞肺癌ROS1重排，并接受了克唑替尼治疗。在5.3个月和7.0个月的随访中，一名患者出现部分反应，另一名患者出现寡反应进展：多项前瞻性研究显示，酪氨酸激酶抑制剂可改善临床疗效，因此筛查非小细胞肺癌的ROS1重排势在必行。鉴于哥伦比亚最近批准了克唑替尼，公共卫生政策必须以早期检测驱动基因突变和及时治疗为导向。关键词：非小细胞肺癌；ROS1；原癌基因受体酪氨酸激酶；免疫组化；新一代测序；酪氨酸激酶抑制剂
{"title":"Importance of Testing for ROS1 Rearrangements in Non-Small Cell Lung Cancer in the Era of Targeted Therapy in a Latin American Country","authors":"Alvaro Osorio, Liliana Fernandez-Trujillo, Juan G Restrepo, Luz F Sua, Catalina Proaño, Valeria Zuñiga-Restrepo","doi":"10.2147/cmar.s455809","DOIUrl":"https://doi.org/10.2147/cmar.s455809","url":null,"abstract":"<strong>Purpose:</strong> Lung cancer is the leading cause of cancer-related deaths worldwide. However, with the optimization of screening strategies and advances in treatment, mortality has been decreasing in recent years. In this study, we describe non-small cell lung cancer patients diagnosed between 2021 and 2022 at a high-complexity hospital in Latin America, as well as the immunohistochemistry techniques used to screen for <em>ROS1</em> rearrangements, in the context of the recent approval of crizotinib for the treatment of <em>ROS1</em> rearrangements in non-small cell lung cancer in Colombia.<br/><strong>Methods:</strong> A descriptive cross-sectional study was conducted. Sociodemographic, clinical, and molecular pathology information from non-small cell lung cancer individuals who underwent immunohistochemistry to detect <em>ROS1</em> rearrangements between 2021 and 2022 at Fundación Valle del Lili (Cali, Colombia) was recorded. The clinical outcomes of confirmed <em>ROS1</em> rearrangements in non-small cell lung cancer patients were reported.<br/><strong>Results:</strong> One hundred and thirty-six patients with non-small cell lung cancer were included. The median age at diagnosis was 69.8 years (interquartile range 61.9– 77.7). At diagnosis, 69.8% (n = 95) were at stage IV. <em>ROS1</em> immunohistochemistry was performed using the monoclonal D4D6 antibody clone in 54.4% (n = 74) of the cases, while 45.6% (n = 62) were done with the monoclonal SP384 antibody clone. Two patients were confirmed to have <em>ROS1</em> rearrangements in non-small cell lung cancer using next-generation sequencing and received crizotinib. On follow-up at months 5.3 and 7.0, one patient had a partial response, and the other had oligo-progression, respectively.<br/><strong>Conclusion:</strong> Screening for <em>ROS1</em> rearrangements in non-small cell lung cancer is imperative, as multiple prospective studies have shown improved clinical outcomes with tyrosine kinase inhibitors. Given the recent approval of crizotinib in Colombia, public health policies must be oriented toward early detection of driver mutations and prompt treatment. Additionally, future approvals of newly tested tyrosine kinase inhibitors should be anticipated.<br/><br/><strong>Keywords:</strong> non-small cell lung cancer, ROS1, proto-oncogene receptor tyrosine kinase, immunohistochemistry, next generation sequencing, tyrosine kinase inhibitor<br/>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":"37 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号