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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}
Background: We aim to evaluate the efficacy and safety of anti-PD1 rechallenge in combination with chemotherapy in patients with metastatic nasopharyngeal carcinoma (mNPC) who have progressed on prior anti-PD1 therapy. Patients and Methods: We enrolled patients with mNPC who received chemotherapy combined with PD-1 immune-checkpoint inhibitors (ICIs) or chemotherapy alone after prior progression of anti-PD1 therapy. The primary endpoint was progress-free survival (PFS), and the secondary endpoints included overall survival (OS), disease control rate (DCR) and objective response rate (ORR). Results: A total of 96 patients were eligible between January 2015 and December 2020. Thirty-seven (38.5%) were in the PD-1 ICIs re-challenge group, while the remaining 59 patients (61.5%) were in the chemotherapy group. The ORR and DCR of PD-1 ICIs group and chemotherapy group were 37.8% vs 23.7% and 86.5% vs.74.5%, respectively. After a median follow-up period of 21.1 months (IQR 16.1– 28.7), the log-rank analysis demonstrated a significantly improved PFS in the PD-1 ICIs re-challenge group compared to the chemotherapy group (8.4 months [95% CI 4.3– 14.0] vs 5.0 months [95% CI 2.8– 7.2], P = 0.03). However, no significant difference in OS was observed between the two groups (28.3 vs 24.1 months, P = 0.09). The two groups had similar adverse reactions, but the incidence of grade 3 or 4 thrombocytopenia was significantly higher in the PD-1 ICIs re-challenge group (18.9% vs 3.4%, P = 0.025). Conclusion: mNPC patients who progressed from prior anti-PD1 therapy could benefit from the anti-PD1 rechallenge in combination with chemotherapy. However, further validation is needed.
研究背景我们旨在评估抗PD1再挑战联合化疗对既往抗PD1治疗进展的转移性鼻咽癌（mNPC）患者的疗效和安全性：我们招募了接受化疗联合PD-1免疫检查点抑制剂（ICIs）或单独化疗的mNPC患者。主要终点是无进展生存期（PFS），次要终点包括总生存期（OS）、疾病控制率（DCR）和客观反应率（ORR）：2015年1月至2020年12月期间，共有96名患者符合条件。PD-1 ICIs再挑战组有37人（38.5%），其余59人（61.5%）为化疗组。PD-1 ICIs组和化疗组的ORR和DCR分别为37.8% vs 23.7%和86.5% vs.74.5%。中位随访期为21.1个月（IQR 16.1- 28.7），对数秩分析显示，与化疗组相比，PD-1 ICIs再挑战组的PFS显著改善（8.4个月 [95% CI 4.3- 14.0] vs 5.0个月 [95% CI 2.8- 7.2]，P = 0.03）。不过，两组患者的 OS 无明显差异（28.3 个月 vs 24.1 个月，P = 0.09）。两组患者的不良反应相似，但PD-1 ICIs再挑战组的3级或4级血小板减少发生率明显更高（18.9% vs 3.4%，P = 0.025）。然而，还需要进一步的验证。
{"title":"Efficacy and Safety of Re-Challenging PD-1 Inhibitors in Second-Line Treatment in Metastatic Nasopharyngeal Carcinoma Previously Treated with Chemotherapy and PD-1 Inhibitors","authors":"Weixin Bei, Shuhui Dong, Guoying Liu, Lanfeng Lin, Yaofei Jiang, Nian Lu, Wangzhong Li, Hu Liang, Yanqun Xiang, Weixiong Xia","doi":"10.2147/cmar.s460716","DOIUrl":"https://doi.org/10.2147/cmar.s460716","url":null,"abstract":"<strong>Background:</strong> We aim to evaluate the efficacy and safety of anti-PD1 rechallenge in combination with chemotherapy in patients with metastatic nasopharyngeal carcinoma (mNPC) who have progressed on prior anti-PD1 therapy.<br/><strong>Patients and Methods:</strong> We enrolled patients with mNPC who received chemotherapy combined with PD-1 immune-checkpoint inhibitors (ICIs) or chemotherapy alone after prior progression of anti-PD1 therapy. The primary endpoint was progress-free survival (PFS), and the secondary endpoints included overall survival (OS), disease control rate (DCR) and objective response rate (ORR).<br/><strong>Results:</strong> A total of 96 patients were eligible between January 2015 and December 2020. Thirty-seven (38.5%) were in the PD-1 ICIs re-challenge group, while the remaining 59 patients (61.5%) were in the chemotherapy group. The ORR and DCR of PD-1 ICIs group and chemotherapy group were 37.8% vs 23.7% and 86.5% vs.74.5%, respectively. After a median follow-up period of 21.1 months (IQR 16.1– 28.7), the log-rank analysis demonstrated a significantly improved PFS in the PD-1 ICIs re-challenge group compared to the chemotherapy group (8.4 months [95% CI 4.3– 14.0] vs 5.0 months [95% CI 2.8– 7.2], <em>P =</em> 0.03). However, no significant difference in OS was observed between the two groups (28.3 vs 24.1 months, <em>P =</em> 0.09). The two groups had similar adverse reactions, but the incidence of grade 3 or 4 thrombocytopenia was significantly higher in the PD-1 ICIs re-challenge group (18.9% vs 3.4%, <em>P =</em> 0.025).<br/><strong>Conclusion:</strong> mNPC patients who progressed from prior anti-PD1 therapy could benefit from the anti-PD1 rechallenge in combination with chemotherapy. However, further validation is needed.<br/><br/>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141568114","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}
Purpose: To evaluate Ki67 expression and prognostic value during neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian cancer (EOC). Patients and Methods: 95 patients with advanced EOC receiving NACT followed by interval debulking surgery (IDS) were available for tissue samples from matched pre- and post-therapy specimens. The expression of Ki-67 was evaluated by immunohistochemistry and classified by percentage of stained cells. The optimal cutoff values of the Ki67 were assessed by receiver operating characteristic analysis. Kaplan-Meier analysis, the Log rank test, and Cox regression analysis were carried out to analyze survival. Results: Post-NACT Ki67 was an independent prognostic factor for recurrence by univariate (HR: 1.8, 95% CI: 1.1– 3.0, P-value: 0.023) and multivariate (HR: 1.88, 95% CI: 1.08– 3.26, P-value: 0.025) analysis. Residual disease > 1cm (HR: 2.69, 95% CI: 1.31– 5.54, P-value: 0.0070) and pre-treatment CA125 ≥ 1432 U/mL (HR: 2.00, 95% CI: 1.13– 3.55, P-value: 0.017) were also independent risk factors for progression-free survival (PFS) in multivariate analysis. Post-NACT Ki67 ≥ 20% was an independent risk factor for PFS, however, baseline Ki67 and Ki67 change did not suggest prognostic significance. In patients with high CA125, the median PFS for patients with high postKi67 (median PFS: 15.0 months, 95% CI: 13.4– 16.6 months) was significantly (P-value: 0.013) poorer compared to patients with low postKi67 (median PFS: 30.0 months, 95% CI: 13.5– 46.5 months). Conclusion: Post-NACT Ki67 ≥ 20% was an independent factor associated with poorer PFS in patients with advanced-stage EOC undergoing NACT followed by IDS. The combination of post-NACT Ki67 and pretreatment CA125 could better identify patients with poorer PFS in NACT-administered patients.
{"title":"Prognostic Value of Ki67 in Epithelial Ovarian Cancer: Post-Neoadjuvant Chemotherapy Ki67 Combined with CA125 Predicting Recurrence","authors":"Yuexi Liu, Qiuying Gu, Yao Xiao, Xing Wei, Jinlong Wang, Xiaolan Huang, Hua Linghu","doi":"10.2147/cmar.s469132","DOIUrl":"https://doi.org/10.2147/cmar.s469132","url":null,"abstract":"<strong>Purpose:</strong> To evaluate Ki67 expression and prognostic value during neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian cancer (EOC).<br/><strong>Patients and Methods:</strong> 95 patients with advanced EOC receiving NACT followed by interval debulking surgery (IDS) were available for tissue samples from matched pre- and post-therapy specimens. The expression of Ki-67 was evaluated by immunohistochemistry and classified by percentage of stained cells. The optimal cutoff values of the Ki67 were assessed by receiver operating characteristic analysis. Kaplan-Meier analysis, the Log rank test, and Cox regression analysis were carried out to analyze survival.<br/><strong>Results:</strong> Post-NACT Ki67 was an independent prognostic factor for recurrence by univariate (HR: 1.8, 95% CI: 1.1– 3.0, P-value: 0.023) and multivariate (HR: 1.88, 95% CI: 1.08– 3.26, P-value: 0.025) analysis. Residual disease > 1cm (HR: 2.69, 95% CI: 1.31– 5.54, P-value: 0.0070) and pre-treatment CA125 ≥ 1432 U/mL (HR: 2.00, 95% CI: 1.13– 3.55, P-value: 0.017) were also independent risk factors for progression-free survival (PFS) in multivariate analysis. Post-NACT Ki67 ≥ 20% was an independent risk factor for PFS, however, baseline Ki67 and Ki67 change did not suggest prognostic significance. In patients with high CA125, the median PFS for patients with high postKi67 (median PFS: 15.0 months, 95% CI: 13.4– 16.6 months) was significantly (P-value: 0.013) poorer compared to patients with low postKi67 (median PFS: 30.0 months, 95% CI: 13.5– 46.5 months).<br/><strong>Conclusion:</strong> Post-NACT Ki67 ≥ 20% was an independent factor associated with poorer PFS in patients with advanced-stage EOC undergoing NACT followed by IDS. The combination of post-NACT Ki67 and pretreatment CA125 could better identify patients with poorer PFS in NACT-administered patients.<br/><br/><strong>Keywords:</strong> interval debulking surgery, progression-free survival, overall survival, tumor marker<br/>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141568115","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}
Background: Immune imbalance appears to have a critical role in tumor growth according to emerging research. Peripheral lymphocyte subsets are considered to reflect the systemic immune response and clinical prognosis. The prognostic value of lymphocyte subpopulations in myelodysplastic syndrome (MDS) patients remains unclear. Methods: A total of 94 MDS patients were enrolled for the study. X-tile software was performed to determine the prognostic significance of various lymphocyte subpopulations, CD3, CD4, CD8, CD4/CD8 ratio, natural killer cell (NK) and CD19. Among them, the appropriate threshold of NK percent could be found only. Patients were divided into the high NK percent group and the low NK percent group. The prognostic significance was determined by univariate and multivariate Cox hazard models. Results: MDS patients with lower NK level had significantly shorter overall survival (OS). Based on univariate analysis, male gender (P = 0.030), lower HB (< 10 g/dl, P = 0.029), higher BM blast (> 5%, P < 0.0001), higher-risk IPSS-R cytogenetic (P = 0.032) and lower NK percent (P < 0.0001) were significantly associated with shorter OS. Multivariate Cox proportional hazards regression analysis indicated that low NK was also independent adverse prognostic factor for OS in MDS. Conclusion: Decreased NK level predicts poor prognosis independent of the IPSS-R and provide a novel evaluation factor for MDS patients.
背景：新的研究表明，免疫失衡似乎在肿瘤生长中起着关键作用。外周淋巴细胞亚群被认为能反映全身免疫反应和临床预后。骨髓增生异常综合征（MDS）患者淋巴细胞亚群的预后价值仍不明确：方法：本研究共纳入 94 名 MDS 患者。采用 X-tile 软件确定各种淋巴细胞亚群（CD3、CD4、CD8、CD4/CD8 比值、自然杀伤细胞（NK）和 CD19）的预后意义。其中，只有 NK 百分比能找到合适的阈值。患者被分为高 NK 百分比组和低 NK 百分比组。通过单变量和多变量 Cox 危险模型确定预后意义：结果：NK水平较低的MDS患者总生存期（OS）明显较短。单变量分析显示，男性（P = 0.030）、较低 HB（< 10 g/dl，P = 0.029）、较高 BM blast（> 5%，P < 0.0001）、较高风险 IPSS-R 细胞遗传学（P = 0.032）和较低 NK 百分比（P < 0.0001）与较短的 OS 显著相关。多变量考克斯比例危险回归分析表明，低NK也是MDS患者OS的独立不良预后因素：结论：NK水平降低可预测不良预后，与IPSS-R无关，为MDS患者提供了一个新的评估因素。
{"title":"Low Levels of Natural Killer Cell in Newly Diagnosed Myelodysplastic Syndromes Patients May Confer Poor Prognosis: A Retrospective Cohort Study","authors":"Shengping Gong, Cong Shi","doi":"10.2147/cmar.s469393","DOIUrl":"https://doi.org/10.2147/cmar.s469393","url":null,"abstract":"<strong>Background:</strong> Immune imbalance appears to have a critical role in tumor growth according to emerging research. Peripheral lymphocyte subsets are considered to reflect the systemic immune response and clinical prognosis. The prognostic value of lymphocyte subpopulations in myelodysplastic syndrome (MDS) patients remains unclear.<br/><strong>Methods:</strong> A total of 94 MDS patients were enrolled for the study. X-tile software was performed to determine the prognostic significance of various lymphocyte subpopulations, CD3, CD4, CD8, CD4/CD8 ratio, natural killer cell (NK) and CD19. Among them, the appropriate threshold of NK percent could be found only. Patients were divided into the high NK percent group and the low NK percent group. The prognostic significance was determined by univariate and multivariate Cox hazard models.<br/><strong>Results:</strong> MDS patients with lower NK level had significantly shorter overall survival (OS). Based on univariate analysis, male gender (<em>P</em> = 0.030), lower HB (< 10 g/dl, <em>P</em> = 0.029), higher BM blast (> 5%, <em>P</em> < 0.0001), higher-risk IPSS-R cytogenetic (<em>P</em> = 0.032) and lower NK percent (<em>P</em> < 0.0001) were significantly associated with shorter OS. Multivariate Cox proportional hazards regression analysis indicated that low NK was also independent adverse prognostic factor for OS in MDS.<br/><strong>Conclusion:</strong> Decreased NK level predicts poor prognosis independent of the IPSS-R and provide a novel evaluation factor for MDS patients.<br/><br/>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141526876","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}
Purpose: The purpose of this study was to investigate the predictive value of Pan-Immune-Inflammation Value (PIV) combined with the PILE score for immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) and to construct a nomogram prediction model to provide reference for clinical work. Patients and Methods: Patients with advanced NSCLC who received ICIs treatment in Qingdao Municipal Hospital from January 2019 to December 2021 were selected as the study subjects. The chi-square test, Kaplan-Meier survival analysis, and Cox proportional risk regression analysis were used to evaluate the prognosis. The results were visualized by a nomogram, and the performance of the model was judged by indicators such as the area under the subject operating characteristic curve (AUC) and C-index. The patients were divided into high- and low-risk groups by PILE score, and the prognosis of patients in different risk groups was evaluated. Results: Multivariate Cox regression analysis showed that immune-related adverse events (irAEs) were prognostic factors for overall survival (OS) improvement, and ECOG PS score ≥ 2, bone metastases before treatment, and high PIV expression were independent risk factors for OS. The C index of OS predicted by the nomogram model is 0.750 (95% CI: 0.677– 0.823), and the Calibration and ROC curves show that the model has good prediction performance. Compared with the low-risk group, patients in the high-risk group of PILE were associated with a higher inflammatory state and poorer physical condition, which often resulted in a poorer prognosis. Conclusion: PIV can be used as a prognostic indicator for patients with advanced NSCLC treated with ICIs, and a nomogram prediction model can be constructed to evaluate the survival prediction of patients, thus contributing to better clinical decision-making and prognosis assessment.
目的：本研究旨在探讨泛免疫炎症值（PIV）结合PILE评分对晚期非小细胞肺癌（NSCLC）患者免疫治疗的预测价值，并构建提名图预测模型，为临床工作提供参考：选取2019年1月至2021年12月在青岛市立医院接受ICIs治疗的晚期NSCLC患者作为研究对象。采用卡普兰-梅耶生存分析、Cox比例风险回归分析进行预后评估。结果通过提名图直观显示，并通过受试者工作特征曲线下面积（AUC）和C指数等指标判断模型的性能。根据 PILE 评分将患者分为高危和低危两组，并对不同风险组患者的预后进行评估：多变量Cox回归分析显示，免疫相关不良事件（irAEs）是总生存期（OS）改善的预后因素，ECOG PS评分≥2分、治疗前骨转移和PIV高表达是OS的独立危险因素。提名图模型预测 OS 的 C 指数为 0.750（95% CI：0.677- 0.823），校准曲线和 ROC 曲线显示该模型具有良好的预测性能。与低风险组相比，PILE 高风险组患者的炎症程度更高，身体状况更差，往往预后更差：PIV可作为接受ICIs治疗的晚期NSCLC患者的预后指标，并可构建提名图预测模型来评估患者的生存预测，从而有助于更好地进行临床决策和预后评估。 关键词：非小细胞肺癌；免疫检查点抑制剂；泛免疫炎症值；预后；提名图
{"title":"The Construction of a Nomogram Using the Pan-Immune-Inflammation Value Combined with a PILE Score for Immunotherapy Prediction Prognosis in Advanced NSCLC","authors":"Shixin Ma, Fei Li, Lunqing Wang","doi":"10.2147/cmar.s461964","DOIUrl":"https://doi.org/10.2147/cmar.s461964","url":null,"abstract":"<strong>Purpose:</strong> The purpose of this study was to investigate the predictive value of Pan-Immune-Inflammation Value (PIV) combined with the PILE score for immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) and to construct a nomogram prediction model to provide reference for clinical work.<br/><strong>Patients and Methods:</strong> Patients with advanced NSCLC who received ICIs treatment in Qingdao Municipal Hospital from January 2019 to December 2021 were selected as the study subjects. The chi-square test, Kaplan-Meier survival analysis, and Cox proportional risk regression analysis were used to evaluate the prognosis. The results were visualized by a nomogram, and the performance of the model was judged by indicators such as the area under the subject operating characteristic curve (AUC) and C-index. The patients were divided into high- and low-risk groups by PILE score, and the prognosis of patients in different risk groups was evaluated.<br/><strong>Results:</strong> Multivariate Cox regression analysis showed that immune-related adverse events (irAEs) were prognostic factors for overall survival (OS) improvement, and ECOG PS score ≥ 2, bone metastases before treatment, and high PIV expression were independent risk factors for OS. The C index of OS predicted by the nomogram model is 0.750 (95% CI: 0.677– 0.823), and the Calibration and ROC curves show that the model has good prediction performance. Compared with the low-risk group, patients in the high-risk group of PILE were associated with a higher inflammatory state and poorer physical condition, which often resulted in a poorer prognosis.<br/><strong>Conclusion:</strong> PIV can be used as a prognostic indicator for patients with advanced NSCLC treated with ICIs, and a nomogram prediction model can be constructed to evaluate the survival prediction of patients, thus contributing to better clinical decision-making and prognosis assessment.<br/><br/><strong>Keywords:</strong> non-small cell lung cancer, immune checkpoint inhibitors, pan-immune-inflammation value, prognosis, nomogram<br/>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141507811","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}
Pub Date : 2024-06-27eCollection Date: 2024-01-01DOI: 10.2147/CMAR.S468453
Raz Muhammed HamaSalih
Background: Doxorubicin (DOX) is used to treat various types of cancers. However, its use is restricted by cardiotoxicity, a leading cause of morbidity and mortality. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) may be associated with cardioprotective properties.
Purpose: This study aims to determine the protective effects of different semaglutide (SEM) doses on DOX-induced cardiotoxicity in a rat model.
Methodology: Thirty-five female Wistar rats were divided into five groups. The first group received distilled water as a negative control (NC); the positive control (PC) group received distilled water plus DOX; the third group (SL) received a low dose of SEM (0.06 mg/kg) plus DOX; the fourth group (SM) received a moderate dose of SEM (0.12 mg/kg) plus DOX; and the fifth group (SH) received a high dose of SEM (0.24 mg/kg) plus DOX. Blood samples were collected on day 8 to assess serum troponin, lactate dehydrogenase (LDH), creatine phosphokinase (CPK), total lipid profile, and vascular cell adhesion molecule 1 (VCAM-1). Cardiac tissue was sent for histopathological analysis.
Results: DOX increased the total cholesterol (TC), low-density lipoprotein (LDL), triglyceride (TG), LDH, and CKP levels. Moderate and high doses of semaglutide significantly reduced serum cholesterol levels (*p = 0.0199), (**p = 0.0077), respectively. A significant reduction (***p = 0.0013) in total body weight after treatment with SEM was observed in the SL group and a highly significant reduction (****p < 0.0001) was observed in the SM and SH groups. SEM at all doses reduced CPK levels. The SL group showed a significant reduction in troponin level (*p=0.0344). Serum LDH levels were reduced by all three SEM doses. The histopathological findings support the biochemical results.
Conclusion: Semaglutide may possess cardioprotective properties against DOX-induced cardiotoxicity in a rat model by decreasing serum biochemical markers of cardiotoxicity.
{"title":"Effects of Semaglutide in Doxorubicin-Induced Cardiac Toxicity in Wistar Albino Rats.","authors":"Raz Muhammed HamaSalih","doi":"10.2147/CMAR.S468453","DOIUrl":"10.2147/CMAR.S468453","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin (DOX) is used to treat various types of cancers. However, its use is restricted by cardiotoxicity, a leading cause of morbidity and mortality. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) may be associated with cardioprotective properties.</p><p><strong>Purpose: </strong>This study aims to determine the protective effects of different semaglutide (SEM) doses on DOX-induced cardiotoxicity in a rat model.</p><p><strong>Methodology: </strong>Thirty-five female Wistar rats were divided into five groups. The first group received distilled water as a negative control (NC); the positive control (PC) group received distilled water plus DOX; the third group (SL) received a low dose of SEM (0.06 mg/kg) plus DOX; the fourth group (SM) received a moderate dose of SEM (0.12 mg/kg) plus DOX; and the fifth group (SH) received a high dose of SEM (0.24 mg/kg) plus DOX. Blood samples were collected on day 8 to assess serum troponin, lactate dehydrogenase (LDH), creatine phosphokinase (CPK), total lipid profile, and vascular cell adhesion molecule 1 (VCAM-1). Cardiac tissue was sent for histopathological analysis.</p><p><strong>Results: </strong>DOX increased the total cholesterol (TC), low-density lipoprotein (LDL), triglyceride (TG), LDH, and CKP levels. Moderate and high doses of semaglutide significantly reduced serum cholesterol levels (*<i>p</i> = 0.0199), (**<i>p</i> = 0.0077), respectively. A significant reduction (***<i>p</i> = 0.0013) in total body weight after treatment with SEM was observed in the SL group and a highly significant reduction (****<i>p</i> < 0.0001) was observed in the SM and SH groups. SEM at all doses reduced CPK levels. The SL group showed a significant reduction in troponin level (*<i>p</i>=0.0344). Serum LDH levels were reduced by all three SEM doses. The histopathological findings support the biochemical results.</p><p><strong>Conclusion: </strong>Semaglutide may possess cardioprotective properties against DOX-induced cardiotoxicity in a rat model by decreasing serum biochemical markers of cardiotoxicity.</p>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-26eCollection Date: 2024-01-01DOI: 10.2147/CMAR.S463694
Li Ao Wang, Zhiming Zheng, Jia Zheng, Guifeng Zhang, Zheng Wang
Purpose: Low-grade gliomas (LGG) are common brain tumors with high mortality rates. Cancer cell invasion is a significant factor in tumor metastasis. Novel biomarkers are urgently needed to predict LGG prognosis effectively.
Methods: The data for LGG were obtained from the Bioinformatics database. A consensus clustering analysis was performed to identify molecular subtypes linked with invasion in LGG. Differential expression analysis was performed to identify differentially expressed genes (DEGs) between the identified clusters. Enrichment analyses were then conducted to explore the function for DEGs. Prognostic signatures were placed, and their predictive power was assessed. Furthermore, the invasion-related prognostic signature was validated using the CGGA dataset. Subsequently, clinical specimens were procured in order to validate the expression levels of the distinct genes examined in this research, and to further explore the impact of these genes on the glioma cell line LN229 and HS-683.
Results: Two invasion-related molecular subtypes of LGG were identified, and we sifted 163 DEGs between them. The enrichment analyses indicated that DEGs are mainly related to pattern specification process. Subsequently, 10 signature genes (IGF2BP2, SRY, CHI3L1, IGF2BP3, MEOX2, ABCC3, HOXC4, OTP, METTL7B, and EMILIN3) were sifted out to construct a risk model. Besides, the survival (OS) in the high-risk group was lower. The performance of the risk model was verified. Furthermore, a highly reliable nomogram was generated. Cellular experiments revealed the ability to promote cell viability, value-addedness, migratory ability, invasive ability, and colony-forming ability of the glioma cell line LN229 and HS-683. The qRT-PCR analysis of clinical glioma samples showed that these 10 genes were expressed at higher levels in high-grade gliomas than in low-grade gliomas, suggesting that these genes are associated with poor prognosis of gliomas.
Conclusion: Our study sifted out ten invasion-related biomarkers of LGG, providing a reference for treatments and prognostic prediction in LGG.
{"title":"The Potential Significance of the EMILIN3 Gene in Augmenting the Aggressiveness of Low-Grade Gliomas is Noteworthy.","authors":"Li Ao Wang, Zhiming Zheng, Jia Zheng, Guifeng Zhang, Zheng Wang","doi":"10.2147/CMAR.S463694","DOIUrl":"10.2147/CMAR.S463694","url":null,"abstract":"<p><strong>Purpose: </strong>Low-grade gliomas (LGG) are common brain tumors with high mortality rates. Cancer cell invasion is a significant factor in tumor metastasis. Novel biomarkers are urgently needed to predict LGG prognosis effectively.</p><p><strong>Methods: </strong>The data for LGG were obtained from the Bioinformatics database. A consensus clustering analysis was performed to identify molecular subtypes linked with invasion in LGG. Differential expression analysis was performed to identify differentially expressed genes (DEGs) between the identified clusters. Enrichment analyses were then conducted to explore the function for DEGs. Prognostic signatures were placed, and their predictive power was assessed. Furthermore, the invasion-related prognostic signature was validated using the CGGA dataset. Subsequently, clinical specimens were procured in order to validate the expression levels of the distinct genes examined in this research, and to further explore the impact of these genes on the glioma cell line LN229 and HS-683.</p><p><strong>Results: </strong>Two invasion-related molecular subtypes of LGG were identified, and we sifted 163 DEGs between them. The enrichment analyses indicated that DEGs are mainly related to pattern specification process. Subsequently, 10 signature genes (<i>IGF2BP2, SRY, CHI3L1, IGF2BP3, MEOX2, ABCC3, HOXC4, OTP, METTL7B</i>, and <i>EMILIN3</i>) were sifted out to construct a risk model. Besides, the survival (OS) in the high-risk group was lower. The performance of the risk model was verified. Furthermore, a highly reliable nomogram was generated. Cellular experiments revealed the ability to promote cell viability, value-addedness, migratory ability, invasive ability, and colony-forming ability of the glioma cell line LN229 and HS-683. The qRT-PCR analysis of clinical glioma samples showed that these 10 genes were expressed at higher levels in high-grade gliomas than in low-grade gliomas, suggesting that these genes are associated with poor prognosis of gliomas.</p><p><strong>Conclusion: </strong>Our study sifted out ten invasion-related biomarkers of LGG, providing a reference for treatments and prognostic prediction in LGG.</p>","PeriodicalId":9479,"journal":{"name":"Cancer Management and Research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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