Pub Date : 2024-01-01DOI: 10.1177/15330338241264847
Henrik Hauswald, Michael Schempp, Pauline Liebig, Sebastian Hoefel, Jürgen Debus, Peter E Huber, Felix Zwicker
Background: This retrospective study aimed to investigate the outcomes and adverse events (AEs) associated with adjuvant radiotherapy with helical tomotherapy (hT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). Methods: Twenty-eight patients with DCIS underwent postoperative hT between 2011 and 2020. hT was chosen since it provided optimal target coverage and tolerable organ-at-risk doses to the lungs and heart when tangential 3-dimensional conformal radiotherapy (3D-CRT) was presumed to provide unfavorable dosimetry. The median total (single) dose was 50.4 Gy (1.8 Gy). The median time between BCS and the start of hT was 5 weeks (range, 4-38 weeks). Statistical analysis included local recurrence-free survival, overall survival (OS), and secondary cancer-free survival. AEs were classified according to the Common Toxicity Criteria for Adverse Events, version 5. Results: The patients' median age was 58 years. The median follow-up period was 61 months (range, 3-123 months). The 1-, 3-, and 5-year OS rates were 100% each. None of the patients developed secondary cancer, local recurrence, or invasive breast cancer during follow-up. The most common acute AEs were dermatitis (n = 27), fatigue (n = 4), hyperpigmentation (n = 3), and thrombocytopenia (n = 4). The late AE primarily included surgical scars (n = 7) and hyperpigmentation (n = 5). None of the patients experienced acute or late AEs > grade 3. The mean conformity and homogeneity indices were 0.9 (range, 0.86-0.96) and 0.056 (range, 0.05-0.06), respectively. Conclusion: hT after BCS for DCIS is a feasible and safe form of adjuvant radiotherapy for patients in whom 3D-CRT is contraindicated due to unfavorable dosimetry. During follow-up, there were no recurrences, invasive breast cancer diagnoses, or secondary cancers, while the adverse effects were mild.
{"title":"Long-term Outcome After Helical Tomotherapy Following Breast Conserving Surgery for Ductal Carcinoma In Situ.","authors":"Henrik Hauswald, Michael Schempp, Pauline Liebig, Sebastian Hoefel, Jürgen Debus, Peter E Huber, Felix Zwicker","doi":"10.1177/15330338241264847","DOIUrl":"10.1177/15330338241264847","url":null,"abstract":"<p><p><b>Background:</b> This retrospective study aimed to investigate the outcomes and adverse events (AEs) associated with adjuvant radiotherapy with helical tomotherapy (hT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). <b>Methods:</b> Twenty-eight patients with DCIS underwent postoperative hT between 2011 and 2020. hT was chosen since it provided optimal target coverage and tolerable organ-at-risk doses to the lungs and heart when tangential 3-dimensional conformal radiotherapy (3D-CRT) was presumed to provide unfavorable dosimetry. The median total (single) dose was 50.4 Gy (1.8 Gy). The median time between BCS and the start of hT was 5 weeks (range, 4-38 weeks). Statistical analysis included local recurrence-free survival, overall survival (OS), and secondary cancer-free survival. AEs were classified according to the Common Toxicity Criteria for Adverse Events, version 5. <b>Results:</b> The patients' median age was 58 years. The median follow-up period was 61 months (range, 3-123 months). The 1-, 3-, and 5-year OS rates were 100% each. None of the patients developed secondary cancer, local recurrence, or invasive breast cancer during follow-up. The most common acute AEs were dermatitis (n = 27), fatigue (n = 4), hyperpigmentation (n = 3), and thrombocytopenia (n = 4). The late AE primarily included surgical scars (n = 7) and hyperpigmentation (n = 5). None of the patients experienced acute or late AEs > grade 3. The mean conformity and homogeneity indices were 0.9 (range, 0.86-0.96) and 0.056 (range, 0.05-0.06), respectively. <b>Conclusion:</b> hT after BCS for DCIS is a feasible and safe form of adjuvant radiotherapy for patients in whom 3D-CRT is contraindicated due to unfavorable dosimetry. During follow-up, there were no recurrences, invasive breast cancer diagnoses, or secondary cancers, while the adverse effects were mild.</p>","PeriodicalId":22203,"journal":{"name":"Technology in Cancer Research & Treatment","volume":"23 ","pages":"15330338241264847"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752864","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 : 2024-01-01DOI: 10.1177/15330338241272038
Lingling Yan, Yingjie Xu, Jianrong Dai
Purpose: This study aims to investigate the influence of the magnetic field on treatment plan quality using typical phantom test cases, which encompass a circle target test case, AAPM TG119 test cases (prostate, head-and-neck, C-shape, multi-target test cases), and a lung test case.
Materials and methods: For the typical phantom test cases, two plans were formulated. The first plan underwent optimization in the presence of a 1.5 Tesla magnetic field (1.5 T plan). The second plan was re-optimized without a magnetic field (0 T plan), utilizing the same optimization conditions as the first plan. The two plans were compared based on various parameters, including con-formity index (CI), homogeneity index (HI), fit index (FI) and dose coverage of the planning target volume (PTV), dose delivered to organs at risk (OARs) and normal tissue (NT), monitor unit (MU). A plan-quality metric (PQM) scoring procedure was employed. For the 1.5 T plans, dose verifications were performed using an MR-compatible ArcCHECK phantom.
Results: A smaller dose influence of the magnetic field was found for the circle target, prostate, head-and-neck, and C-shape test cases, compared with the multi-target and lung test cases. In the multi-target test case, the significant dose influence was on the inferior PTV, followed by the superior PTV. There was a relatively large dose influence on the PTV and OARs for lung test case. No statistically significant differences in PQM and MUs were observed. For the 1.5 T plans, gamma passing rates were all higher than 95% with criteria of 2 mm/3% and 2 mm/2%.
Conclusion: The presence of a 1.5 T magnetic field had a relatively large impact on dose parameters in the multi-target and lung test cases compared with other test cases. However, there were no significant influences on the plan-quality metric, MU and dose accuracy for all test cases.
目的:本研究旨在使用典型的模型试验案例(包括圆形目标试验案例、AAPM TG119 试验案例(前列腺、头颈部、C 形、多目标试验案例)和肺部试验案例)研究磁场对治疗计划质量的影响:针对典型的模型试验案例,制定了两个计划。第一个方案在 1.5 特斯拉磁场(1.5 特斯拉方案)下进行了优化。第二个方案在没有磁场(0 T 方案)的情况下重新优化,优化条件与第一个方案相同。两个计划根据各种参数进行比较,包括一致性指数(CI)、均匀性指数(HI)、拟合指数(FI)和计划目标容积(PTV)的剂量覆盖率、危险器官(OAR)和正常组织(NT)的剂量、监测单位(MU)。采用了计划质量度量(PQM)评分程序。对于 1.5 T 计划,使用磁共振兼容 ArcCHECK 模型进行了剂量验证:结果:与多目标和肺部测试病例相比,发现磁场对圆形目标、前列腺、头颈部和 C 型测试病例的剂量影响较小。在多靶测试病例中,下PTV受到的剂量影响最大,其次是上PTV。在肺部测试病例中,PTV 和 OAR 受到的剂量影响相对较大。在 PQM 和 MU 方面没有观察到有统计学意义的差异。对于 1.5 T 计划,伽马通过率均高于 95%,标准为 2 mm/3% 和 2 mm/2%:结论:与其他测试病例相比,1.5 T 磁场的存在对多目标和肺部测试病例的剂量参数影响相对较大。然而,在所有测试病例中,对计划质量指标、MU 和剂量准确性没有明显影响。
{"title":"Impact of 1.5 T Magnetic Field on Treatment Plan Quality in MR-Guided Radiotherapy: Typical Phantom Test Cases.","authors":"Lingling Yan, Yingjie Xu, Jianrong Dai","doi":"10.1177/15330338241272038","DOIUrl":"10.1177/15330338241272038","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to investigate the influence of the magnetic field on treatment plan quality using typical phantom test cases, which encompass a circle target test case, AAPM TG119 test cases (prostate, head-and-neck, C-shape, multi-target test cases), and a lung test case.</p><p><strong>Materials and methods: </strong>For the typical phantom test cases, two plans were formulated. The first plan underwent optimization in the presence of a 1.5 Tesla magnetic field (1.5 T plan). The second plan was re-optimized without a magnetic field (0 T plan), utilizing the same optimization conditions as the first plan. The two plans were compared based on various parameters, including con-formity index (CI), homogeneity index (HI), fit index (FI) and dose coverage of the planning target volume (PTV), dose delivered to organs at risk (OARs) and normal tissue (NT), monitor unit (MU). A plan-quality metric (PQM) scoring procedure was employed. For the 1.5 T plans, dose verifications were performed using an MR-compatible ArcCHECK phantom.</p><p><strong>Results: </strong>A smaller dose influence of the magnetic field was found for the circle target, prostate, head-and-neck, and C-shape test cases, compared with the multi-target and lung test cases. In the multi-target test case, the significant dose influence was on the inferior PTV, followed by the superior PTV. There was a relatively large dose influence on the PTV and OARs for lung test case. No statistically significant differences in PQM and MUs were observed. For the 1.5 T plans, gamma passing rates were all higher than 95% with criteria of 2 mm/3% and 2 mm/2%.</p><p><strong>Conclusion: </strong>The presence of a 1.5 T magnetic field had a relatively large impact on dose parameters in the multi-target and lung test cases compared with other test cases. However, there were no significant influences on the plan-quality metric, MU and dose accuracy for all test cases.</p>","PeriodicalId":22203,"journal":{"name":"Technology in Cancer Research & Treatment","volume":"23 ","pages":"15330338241272038"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11307342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898280","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}
Objective: To investigate the effect of various frequencies of bolus use on the superficial dose of volumetric modulated arc therapy after modified radical mastectomy for breast cancer.
Methods: Based on the computed tomography images of a female anthropomorphic breast phantom, a 0.5 cm silicone-based 3D-printed bolus was created. Nine points evenly distributed on the breast skin were selected for assessing the skin dose, and a volume of subcutaneous lymphatic drainage of the breast (noted as ROI2-3) was delineated for assessing the chest wall dose. The treatment plans with and without bolus (plan_wb and plan_nb) were separately designed using the prescription of 50 Gy in 25 fractions following the standard dose constraints of the adjacent organ at risk. To characterize the accuracy of treatment planning system (TPS) dose calculations, the doses of the nine points were measured five times by thermoluminescence dosimeters (TLDs) and then were compared with the TPS calculated dose.
Results: Compared with Plan_nb (144.46 ± 10.32 cGy), the breast skin dose for plan_wb (208.75 ± 4.55 cGy) was significantly increased (t = -18.56, P < 0.001). The deviation of skin dose was smaller for Plan_wb, and the uniformity was significantly improved. The calculated value of TPS was in good agreement with the measured value of TLD, and the maximum deviation was within 5%. Skin and ROI2-3 doses were significantly increased with increasing frequencies of bolus applications. The mean dose of the breast skin and ROI2-3 for 15 and 23 times bolus applications were 45.33 Gy, 50.88 Gy and 50.36 Gy, 52.39 Gy, respectively.
Conclusion: 3D printing bolus can improve the radiation dose and the accuracy of the planned dose. Setting Plan_wb to 15 times for T1-3N+ breast cancer patients and 23 times for T4N+ breast cancer patients can meet the clinical need. Quantitative analysis of the bolus application frequency for different tumor stages can provide a reference for clinical practice.
{"title":"Superficial Dosimetry Study of the Frequency of Bolus Using in Volumetric Modulated Arc Therapy after Modified Radical Mastectomy.","authors":"Lingling Tian, Ronghu Mao, Dingjie Li, Wei Guo, Bing Li, Zhaoyang Lou, Leiming Guo","doi":"10.1177/15330338241264848","DOIUrl":"10.1177/15330338241264848","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the effect of various frequencies of bolus use on the superficial dose of volumetric modulated arc therapy after modified radical mastectomy for breast cancer.</p><p><strong>Methods: </strong>Based on the computed tomography images of a female anthropomorphic breast phantom, a 0.5 cm silicone-based 3D-printed bolus was created. Nine points evenly distributed on the breast skin were selected for assessing the skin dose, and a volume of subcutaneous lymphatic drainage of the breast (noted as ROI2-3) was delineated for assessing the chest wall dose. The treatment plans with and without bolus (plan_wb and plan_nb) were separately designed using the prescription of 50 Gy in 25 fractions following the standard dose constraints of the adjacent organ at risk. To characterize the accuracy of treatment planning system (TPS) dose calculations, the doses of the nine points were measured five times by thermoluminescence dosimeters (TLDs) and then were compared with the TPS calculated dose.</p><p><strong>Results: </strong>Compared with Plan_nb (144.46 ± 10.32 cGy), the breast skin dose for plan_wb (208.75 ± 4.55 cGy) was significantly increased (t = -18.56, <i>P</i> < 0.001). The deviation of skin dose was smaller for Plan_wb, and the uniformity was significantly improved. The calculated value of TPS was in good agreement with the measured value of TLD, and the maximum deviation was within 5%. Skin and ROI2-3 doses were significantly increased with increasing frequencies of bolus applications. The mean dose of the breast skin and ROI2-3 for 15 and 23 times bolus applications were 45.33 Gy, 50.88 Gy and 50.36 Gy, 52.39 Gy, respectively.</p><p><strong>Conclusion: </strong>3D printing bolus can improve the radiation dose and the accuracy of the planned dose. Setting Plan_wb to 15 times for T1-3N+ breast cancer patients and 23 times for T4N+ breast cancer patients can meet the clinical need. Quantitative analysis of the bolus application frequency for different tumor stages can provide a reference for clinical practice.</p>","PeriodicalId":22203,"journal":{"name":"Technology in Cancer Research & Treatment","volume":"23 ","pages":"15330338241264848"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11322943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917471","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}
Background: Gastric intestinal metaplasia(GIM) is an independent risk factor for GC, however, its pathogenesis is still unclear. Ferroptosis is a new type of programmed cell death, which may be involved in the process of GIM. The purpose of this study was to analyze the expression of ferroptosis-related genes (FRGs) in GIM tissues and to explore the relationship between ferroptosis and GIM.
Method: The results of GIM tissue full transcriptome sequencing were downloaded from Gene Expression Omnibus(GEO) database. R software (V4.2.0) and R packages were used for screening and enrichment analysis of differentially expressed genes(DEGs). The key genes were screened by least absolute shrinkage and selection operator(LASSO) and support vector machine-recursive feature elimination(SVM-RFE) algorithm. Receiver operating characteristic(ROC) curve was used to evaluate the diagnostic efficacy of key genes in GIM. Clinical samples were used to further validate hub genes.
Results: A total of 12 differentially expressed ferroptosis-related genes (DEFRGs) were identified. Using two machine learning algorithms, GOT1, ALDH3A2, ACSF2 and SESN2 were identified as key genes. The area under ROC curve (AUC) of GOT1, ALDH3A2, ACSF2 and SESN2 in the training set were 0.906, 0.955, 0.899 and 0.962 respectively, and the AUC in the verification set were 0.776, 0.676, 0.773 and 0.880, respectively. Clinical samples verified the differential expression of GOT1, ACSF2, and SESN2 in GIM.
Conclusion: We found that there was a significant correlation between ferroptosis and GIM. GOT1, ACSF2 and SESN2 can be used as diagnostic markers to effectively identify GIM.
{"title":"Machine Learning Identify Ferroptosis-Related Genes as Potential Diagnostic Biomarkers for Gastric Intestinal Metaplasia.","authors":"Tingting Li, Qi Yang, Yun Liu, Yueping Jin, Biao Song, Qin Sun, Siyuan Wei, Jing Wu, Xuejun Li","doi":"10.1177/15330338241272036","DOIUrl":"10.1177/15330338241272036","url":null,"abstract":"<p><strong>Background: </strong>Gastric intestinal metaplasia(GIM) is an independent risk factor for GC, however, its pathogenesis is still unclear. Ferroptosis is a new type of programmed cell death, which may be involved in the process of GIM. The purpose of this study was to analyze the expression of ferroptosis-related genes (FRGs) in GIM tissues and to explore the relationship between ferroptosis and GIM.</p><p><strong>Method: </strong>The results of GIM tissue full transcriptome sequencing were downloaded from Gene Expression Omnibus(GEO) database. R software (V4.2.0) and R packages were used for screening and enrichment analysis of differentially expressed genes(DEGs). The key genes were screened by least absolute shrinkage and selection operator(LASSO) and support vector machine-recursive feature elimination(SVM-RFE) algorithm. Receiver operating characteristic(ROC) curve was used to evaluate the diagnostic efficacy of key genes in GIM. Clinical samples were used to further validate hub genes.</p><p><strong>Results: </strong>A total of 12 differentially expressed ferroptosis-related genes (DEFRGs) were identified. Using two machine learning algorithms, GOT1, ALDH3A2, ACSF2 and SESN2 were identified as key genes. The area under ROC curve (AUC) of GOT1, ALDH3A2, ACSF2 and SESN2 in the training set were 0.906, 0.955, 0.899 and 0.962 respectively, and the AUC in the verification set were 0.776, 0.676, 0.773 and 0.880, respectively. Clinical samples verified the differential expression of GOT1, ACSF2, and SESN2 in GIM.</p><p><strong>Conclusion: </strong>We found that there was a significant correlation between ferroptosis and GIM. GOT1, ACSF2 and SESN2 can be used as diagnostic markers to effectively identify GIM.</p>","PeriodicalId":22203,"journal":{"name":"Technology in Cancer Research & Treatment","volume":"23 ","pages":"15330338241272036"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018620","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}
There are no standard third-line or beyond treatments for patients with driver mutation-positive advanced lung adenocarcinoma (LUAD). Anlotinib was approved as a third-line multitarget drug in China in 2018. Limited data are available regarding the efficacy and safety of anlotinib compared with chemotherapy. To investigate the efficacy and safety of anlotinib compared with traditional chemotherapy in patients with epidermal growth factor receptor (EGFR)-positive advanced LUAD. We conducted a retrospective study of 83 EGFR mutation-positive patients with advanced LUAD between 2011 and 2022. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints, whereas the objective response rate (ORR) and disease control rate (DCR) were the secondary endpoints. Anlotinib-related adverse events (AEs) were recorded to evaluate the safety of anlotinib. 39 patients with LUAD received anlotinib and 44 patients with LUAD received chemotherapy were enrolled in the study. Patients treated with anlotinib exhibited longer PFS (11.2 vs 4.5 months, P < .01) and OS (18.8 vs 15.8 months, P < .05) than patients treated with chemotherapy. There were no significant differences in ORR (7.9% vs 20.5%, P = .129) or DCR (100% vs 93.2%, P = .120) between the two groups. Anlotinib-related AEs grading 3-4 level were observed in 2 (5.1%) patients, no anlotinib-related death was recorded. Cox regression analyses of PFS and OS showed that brain metastases and age < 30 years at diagnosis had negative effects on clinical outcomes. Anlotinib is effective and safe in patients with EGFR-positive advanced LUAD. Patients without brain metastases had better clinical outcomes.
对于驱动基因突变阳性的晚期肺腺癌(LUAD)患者,目前尚无标准的三线或三线以上治疗方案。2018年,安罗替尼在中国获批成为三线多靶点药物。与化疗相比,安罗替尼的疗效和安全性数据有限。为了研究安罗替尼与传统化疗相比在表皮生长因子受体(EGFR)阳性晚期LUAD患者中的疗效和安全性。我们对2011年至2022年间83例表皮生长因子受体突变阳性的晚期LUAD患者进行了回顾性研究。无进展生存期(PFS)和总生存期(OS)为主要终点,客观反应率(ORR)和疾病控制率(DCR)为次要终点。该研究记录了与安罗替尼相关的不良事件(AEs),以评估安罗替尼的安全性。39名LUAD患者接受了安罗替尼治疗,44名LUAD患者接受了化疗。两组患者接受安罗替尼治疗后,PFS(11.2个月 vs 4.5个月,P = .129)或DCR(100% vs 93.2%,P = .120)均有所延长。2例(5.1%)患者出现了与安罗替尼相关的3-4级AE,无安罗替尼相关死亡记录。PFS和OS的Cox回归分析显示,脑转移和年龄
{"title":"Efficacy and Safety of Anlotinib in EGFR-Positive Patients with Advanced Lung Adenocarcinoma Compared with Chemotherapy: A Retrospective Study.","authors":"Cuihong Cai, Qian Shen, Jingjing Shao, Jingjing Qu, Shuangshuang Zhou, Jianya Zhou","doi":"10.1177/15330338241279111","DOIUrl":"10.1177/15330338241279111","url":null,"abstract":"<p><p>There are no standard third-line or beyond treatments for patients with driver mutation-positive advanced lung adenocarcinoma (LUAD). Anlotinib was approved as a third-line multitarget drug in China in 2018. Limited data are available regarding the efficacy and safety of anlotinib compared with chemotherapy. To investigate the efficacy and safety of anlotinib compared with traditional chemotherapy in patients with epidermal growth factor receptor (EGFR)-positive advanced LUAD. We conducted a retrospective study of 83 EGFR mutation-positive patients with advanced LUAD between 2011 and 2022. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints, whereas the objective response rate (ORR) and disease control rate (DCR) were the secondary endpoints. Anlotinib-related adverse events (AEs) were recorded to evaluate the safety of anlotinib. 39 patients with LUAD received anlotinib and 44 patients with LUAD received chemotherapy were enrolled in the study. Patients treated with anlotinib exhibited longer PFS (11.2 vs 4.5 months, <i>P </i>< .01) and OS (18.8 vs 15.8 months, <i>P </i>< .05) than patients treated with chemotherapy. There were no significant differences in ORR (7.9% vs 20.5%, <i>P </i>= .129) or DCR (100% vs 93.2%, <i>P </i>= .120) between the two groups. Anlotinib-related AEs grading 3-4 level were observed in 2 (5.1%) patients, no anlotinib-related death was recorded. Cox regression analyses of PFS and OS showed that brain metastases and age < 30 years at diagnosis had negative effects on clinical outcomes. Anlotinib is effective and safe in patients with EGFR-positive advanced LUAD. Patients without brain metastases had better clinical outcomes.</p>","PeriodicalId":22203,"journal":{"name":"Technology in Cancer Research & Treatment","volume":"23 ","pages":"15330338241279111"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11342426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037085","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 : 2024-01-01DOI: 10.1177/15330338241285097
Kangkang Li, Kuiwu Ren, Sen Du, Xiang Gao, Jiangtao Yu
Liver cancer a leading cause of cancer-related deaths worldwide, yet understanding of its development mechanism remains limited, and treatment barriers present substantial challenges. Owing to the heterogeneity of tumors, traditional 2D culture models are inadequate for capturing the complexity and diversity of tumor biology and understanding of the disease. Organoids have garnered considerable attention because of their ability to self-renew and develop functional structures in vitro that closely resemble those of human organs. This review explores the history of liver organoids, their cellular origins, techniques of constructing tumor microenvironments that recapitulate liver cancer organoids, and the biological and clinical applications of liver and liver cancer organoids and explores the current challenges related to liver cancer organoid applications and potentially valuable solutions, with the aim of facilitating the construction of in vitro clinical models of liver cancer therapeutic research.
{"title":"Development of Liver Cancer Organoids: Reproducing Tumor Microenvironment and Advancing Research for Liver Cancer Treatment.","authors":"Kangkang Li, Kuiwu Ren, Sen Du, Xiang Gao, Jiangtao Yu","doi":"10.1177/15330338241285097","DOIUrl":"10.1177/15330338241285097","url":null,"abstract":"<p><p>Liver cancer a leading cause of cancer-related deaths worldwide, yet understanding of its development mechanism remains limited, and treatment barriers present substantial challenges. Owing to the heterogeneity of tumors, traditional 2D culture models are inadequate for capturing the complexity and diversity of tumor biology and understanding of the disease. Organoids have garnered considerable attention because of their ability to self-renew and develop functional structures <i>in vitro</i> that closely resemble those of human organs. This review explores the history of liver organoids, their cellular origins, techniques of constructing tumor microenvironments that recapitulate liver cancer organoids, and the biological and clinical applications of liver and liver cancer organoids and explores the current challenges related to liver cancer organoid applications and potentially valuable solutions, with the aim of facilitating the construction of <i>in vitro</i> clinical models of liver cancer therapeutic research.</p>","PeriodicalId":22203,"journal":{"name":"Technology in Cancer Research & Treatment","volume":"23 ","pages":"15330338241285097"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372933","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 : 2024-01-01DOI: 10.1177/15330338241288907
Sara El Zaitouni, Abdelilah Laraqui, Meriem Ghaouti, Asmae Benzekri, Fouad Kettani, Youssra Boustany, Soukaina Benmokhtar, Hafsa Lamrani Alaoui, Hicham El Annaz, Rachid Abi, Mohamed Rida Tagajdid, Safae El Kochri, Bouchra El Mchichi, El Arbi Bouaiti, Idriss Amine Lahlou, Rabii Ameziane El Hassani, Khalid Ennibi
Objectives: We retrospectively analyzed the next-generation sequencing (NGS) results from diagnosed NSCLC patients to identify and compare genomic alterations of NSCLC between Moroccan patients and the Cancer Genome Atlas (TCGA). We also aimed to investigate the distribution and frequency of concurrent genomic alterations.
Methods: From December 2022 to December 2023, a retrospective study of 76 formalin-fixed paraffin-embedded (FFPE) samples have been profiled using the Oncomine™ Precision Assay on the Ion Torrent™ Genexus™ Integrated Sequencer across the panel of 50 key genes that are applicable for the selection of targeted therapy.
Results: Seventy of the 76 FFPE sequenced samples carried at least one genetic alteration in the tested genes. The study identified 234 genetic alterations in 18 genes. Targetable genetic alterations in EGFR, KRAS, MET, BRAF, ALK, RET and ROS1 were identified in 84.3% of tumors. EGFR and KRAS mutations were frequently reported, occurring in 24.3% and 22.9% of cases, respectively. The untargetable genetic alterations were found in 74.3% of the specimens in FGFR3, TP53, ERBB2, PIK3CA, CDKN2A, PDL1, FGFR1, PTEN, CHEK2 and ERBB3. There were additional uncommon/rare mutations in EGFR, BRAF, RET and ROS1. Comparing the prevalence of selected mutated genes in the NSCLC patients from the TCGA database identified substantial differences in EGFR (24.3%, vs14.97%), KRAS (22.9%, vs 25.99%), and TP53 (34.3%, vs 50.94%). ALK, ROS1, and RET gene rearrangements were detected in 4.3% of the 70 tumors tested. The ALK/RET/MET/ROS1/EML4 fusions were detected in 11.4% of samples. Co-alterations occurred in 67.1% of specimens. Co-occurring driver gene mutations were observed in 44.3%. TP53 mutations co-occurred driver gene mutations in 30% of tumors. Three cases (4.3%) harbored concurrent FGFR3, TP53, and PIK3CA alterations.
Conclusion: Our results regarding the proportion of samples with actionable mutations demonstrate the value of NGS testing for NSCLC patients in a real-world clinical diagnostic setting.
{"title":"Genetic Profiling of Non-Small Cell Lung Cancer in Moroccan Patients by Targeted Next-Generation Sequencing.","authors":"Sara El Zaitouni, Abdelilah Laraqui, Meriem Ghaouti, Asmae Benzekri, Fouad Kettani, Youssra Boustany, Soukaina Benmokhtar, Hafsa Lamrani Alaoui, Hicham El Annaz, Rachid Abi, Mohamed Rida Tagajdid, Safae El Kochri, Bouchra El Mchichi, El Arbi Bouaiti, Idriss Amine Lahlou, Rabii Ameziane El Hassani, Khalid Ennibi","doi":"10.1177/15330338241288907","DOIUrl":"10.1177/15330338241288907","url":null,"abstract":"<p><strong>Objectives: </strong>We retrospectively analyzed the next-generation sequencing (NGS) results from diagnosed NSCLC patients to identify and compare genomic alterations of NSCLC between Moroccan patients and the Cancer Genome Atlas (TCGA). We also aimed to investigate the distribution and frequency of concurrent genomic alterations.</p><p><strong>Methods: </strong>From December 2022 to December 2023, a retrospective study of 76 formalin-fixed paraffin-embedded (FFPE) samples have been profiled using the Oncomine™ Precision Assay on the Ion Torrent™ Genexus™ Integrated Sequencer across the panel of 50 key genes that are applicable for the selection of targeted therapy.</p><p><strong>Results: </strong>Seventy of the 76 FFPE sequenced samples carried at least one genetic alteration in the tested genes. The study identified 234 genetic alterations in 18 genes. Targetable genetic alterations in <i>EGFR</i>, <i>KRAS</i>, <i>MET</i>, <i>BRAF</i>, <i>ALK</i>, <i>RET</i> and <i>ROS1</i> were identified in 84.3% of tumors. <i>EGFR</i> and <i>KRAS</i> mutations were frequently reported, occurring in 24.3% and 22.9% of cases, respectively. The untargetable genetic alterations were found in 74.3% of the specimens in <i>FGFR3</i>, <i>TP53</i>, <i>ERBB2</i>, <i>PIK3CA</i>, <i>CDKN2A</i>, <i>PDL1</i>, <i>FGFR1</i>, <i>PTEN</i>, <i>CHEK2</i> and <i>ERBB3</i>. There were additional uncommon/rare mutations in <i>EGFR</i>, <i>BRAF</i>, <i>RET</i> and <i>ROS1</i>. Comparing the prevalence of selected mutated genes in the NSCLC patients from the TCGA database identified substantial differences in <i>EGFR</i> (24.3%, <i>vs</i>14.97%), <i>KRAS</i> (22.9%, <i>vs</i> 25.99%), and <i>TP53</i> (34.3%, <i>vs</i> 50.94%). <i>ALK</i>, <i>ROS1</i>, and <i>RET</i> gene rearrangements were detected in 4.3% of the 70 tumors tested. The <i>ALK</i>/<i>RET</i>/<i>MET</i>/<i>ROS1</i>/<i>EML4</i> fusions were detected in 11.4% of samples. Co-alterations occurred in 67.1% of specimens. Co-occurring driver gene mutations were observed in 44.3%. TP53 mutations co-occurred driver gene mutations in 30% of tumors. Three cases (4.3%) harbored concurrent <i>FGFR3</i>, <i>TP53</i>, and <i>PIK3CA</i> alterations.</p><p><strong>Conclusion: </strong>Our results regarding the proportion of samples with actionable mutations demonstrate the value of NGS testing for NSCLC patients in a real-world clinical diagnostic setting.</p>","PeriodicalId":22203,"journal":{"name":"Technology in Cancer Research & Treatment","volume":"23 ","pages":"15330338241288907"},"PeriodicalIF":2.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372934","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 : 2024-01-01DOI: 10.1177/15330338241250315
Long Hai, Shuaiwei Liu, Lina Ma, Xiangchun Ding, Xiaoyang Bai, Xia Luo
Background: This is a retrospective study aimed at comparing the clinical efficacy and safety between drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE) and conventional TACE (C-TACE) in the treatment of unresectable hepatocellular carcinoma. Methods: From July 2019 to April 2021, we enrolled 282 patients with unresectable hepatocellular carcinoma who were admitted to our hospital, of which 179 and 103 were in the DEB-TACE and C-TACE groups, respectively. General information was collected, and treatment effects were evaluated following the modified Response Evaluation Criteria in Solid Tumors. To compare the indexes of liver and kidney function, routine blood and coagulation were collected before treatment, and 1 day, 1 month, 3 months, and 6 months postoperatively. Postoperative adverse reactions (ie, fever, nausea, vomiting, anorexia, abdominal pain) were recorded to evaluate the safety of treatment. The two groups' progression-free survival and overall survival were also calculated to assess the treatment effect. Results: Preoperatively, the bilirubin, transaminase, and absolute neutrophil values between the two groups were not statistically significant (P > .05). At 1 month postoperatively, the absolute neutrophil values were significantly higher in the DEB-TACE group than those in the C-TACE group (P < .05). At 3 months postoperatively, AST, total bilirubin, and direct bilirubin levels were significantly elevated in the DEB-TACE group (P < .05), compared with the C-TACE group. However, at 6 months postoperatively, total and direct bilirubin levels in the C-TACE group were higher than those in the DEB-TACE group, showing a statistically significant difference (P < .05). For patients undergoing DEB-TACE, the survival risk was lower compared to those undergoing C-TACE. The survival risk of patients undergoing DEB-TACE was lower than that of C-TACE within 20 months postoperatively. The survival risk of patients undergoing DEB-TACE was lower than that of patients undergoing C-TACE. Conclusion: DEB-TACE may be superior to C-TACE in terms of safety and efficacy in the treatment of unresectable hepatocellular carcinoma.
背景:这是一项回顾性研究,旨在比较药物洗脱珠经导管动脉化疗栓塞术(DEB-TACE)和传统TACE(C-TACE)治疗不可切除肝细胞癌的临床疗效和安全性。研究方法自2019年7月至2021年4月,我们纳入了我院收治的282例不可切除肝细胞癌患者,其中DEB-TACE组和C-TACE组分别为179例和103例。我们收集了患者的一般信息,并根据修改后的实体瘤反应评价标准评估了治疗效果。为了比较肝肾功能指标,在治疗前、术后1天、1个月、3个月和6个月采集了血常规和凝血指标。记录术后不良反应(即发热、恶心、呕吐、厌食、腹痛),以评估治疗的安全性。此外,还计算了两组患者的无进展生存期和总生存期,以评估治疗效果。结果术前,两组胆红素、转氨酶和中性粒细胞绝对值差异无统计学意义(P > .05)。术后 1 个月,DEB-TACE 组的中性粒细胞绝对值明显高于 C-TACE 组(P P P P 结论:DEB-TACE 可能比 C-TACE 更有效:在治疗不可切除肝细胞癌方面,DEB-TACE 的安全性和有效性可能优于 C-TACE。
{"title":"Comparative Study of the Short-Term Efficacy and Safety between DEB-TACE and C-TACE in the Treatment of Unresectable Hepatocellular Carcinoma, a Retrospective Study.","authors":"Long Hai, Shuaiwei Liu, Lina Ma, Xiangchun Ding, Xiaoyang Bai, Xia Luo","doi":"10.1177/15330338241250315","DOIUrl":"10.1177/15330338241250315","url":null,"abstract":"<p><p><b>Background:</b> This is a retrospective study aimed at comparing the clinical efficacy and safety between drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE) and conventional TACE (C-TACE) in the treatment of unresectable hepatocellular carcinoma. <b>Methods:</b> From July 2019 to April 2021, we enrolled 282 patients with unresectable hepatocellular carcinoma who were admitted to our hospital, of which 179 and 103 were in the DEB-TACE and C-TACE groups, respectively. General information was collected, and treatment effects were evaluated following the modified Response Evaluation Criteria in Solid Tumors. To compare the indexes of liver and kidney function, routine blood and coagulation were collected before treatment, and 1 day, 1 month, 3 months, and 6 months postoperatively. Postoperative adverse reactions (ie, fever, nausea, vomiting, anorexia, abdominal pain) were recorded to evaluate the safety of treatment. The two groups' progression-free survival and overall survival were also calculated to assess the treatment effect. <b>Results:</b> Preoperatively, the bilirubin, transaminase, and absolute neutrophil values between the two groups were not statistically significant (<i>P</i> > .05). At 1 month postoperatively, the absolute neutrophil values were significantly higher in the DEB-TACE group than those in the C-TACE group (<i>P</i> < .05). At 3 months postoperatively, AST, total bilirubin, and direct bilirubin levels were significantly elevated in the DEB-TACE group (<i>P</i> < .05), compared with the C-TACE group. However, at 6 months postoperatively, total and direct bilirubin levels in the C-TACE group were higher than those in the DEB-TACE group, showing a statistically significant difference (<i>P</i> < .05). For patients undergoing DEB-TACE, the survival risk was lower compared to those undergoing C-TACE. The survival risk of patients undergoing DEB-TACE was lower than that of C-TACE within 20 months postoperatively. The survival risk of patients undergoing DEB-TACE was lower than that of patients undergoing C-TACE. <b>Conclusion:</b> DEB-TACE may be superior to C-TACE in terms of safety and efficacy in the treatment of unresectable hepatocellular carcinoma.</p>","PeriodicalId":22203,"journal":{"name":"Technology in Cancer Research & Treatment","volume":"23 ","pages":"15330338241250315"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11113029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077007","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 : 2024-01-01DOI: 10.1177/15330338241258570
Lingling Lv, Yuqing Huang, Qiong Li, Yuan Wu, Lan Zheng
Background: Colon adenocarcinoma (COAD) has increasing incidence and is one of the most common malignant tumors. The mitochondria involved in cell energy metabolism, oxygen free radical generation, and cell apoptosis play important roles in tumorigenesis and progression. The relationship between mitochondrial genes and COAD remains largely unknown. Methods: COAD data including 512 samples were set out from the UCSC Xena database. The nuclear mitochondrial-related genes (NMRGs)-related risk prognostic model and prognostic nomogram were constructed, and NMRGs-related gene mutation and the immune environment were analyzed using bioinformatics methods. Then, a liver metastasis model of colorectal cancer was constructed and protein expression was detected using Western blot assay. Results: A prognostic model for COAD was constructed. Comparing the prognostic model dataset and the validation dataset showed considerable correlation in both risk grouping and prognosis. Based on the risk score (RS) model, the samples of the prognostic dataset were divided into high risk group and low risk group. Moreover, pathologic N and T stage and tumor recurrence in the two risk groups were significantly different. The four prognostic factors, including age and pathologic T stage in the nomogram survival model also showed excellent predictive performance. An optimal combination of nine differentially expressed NMRGs was finally obtained, including LARS2, PARS2, ETHE1, LRPPRC, TMEM70, AARS2, ACAD9, VARS2, and ATP8A2. The high-RS group had more inflamed immune features, including T and CD4+ memory cell activation. Besides, mitochondria-associated LRPPRC and LARS2 expression levels were increased in vivo xenograft construction and liver metastases assays. Conclusion: This study established a comprehensive prognostic model for COAD, incorporating nine genes associated with nuclear-mitochondrial functions. This model demonstrates superior predictive performance across four prognostic factors: age, pathological T stage, tumor recurrence, and overall prognosis. It is anticipated to be an effective model for enhancing the prognosis and treatment of COAD.
背景:结肠腺癌(COAD)的发病率越来越高,是最常见的恶性肿瘤之一。参与细胞能量代谢、氧自由基生成和细胞凋亡的线粒体在肿瘤发生和发展过程中发挥着重要作用。线粒体基因与 COAD 之间的关系在很大程度上仍然未知。研究方法从加州大学圣地亚哥分校 Xena 数据库中收集了包括 512 个样本的 COAD 数据。构建了线粒体相关基因(NMRGs)相关风险预后模型和预后提名图,并利用生物信息学方法分析了NMRGs相关基因突变和免疫环境。然后,构建了结直肠癌肝转移模型,并利用 Western 印迹法检测了蛋白表达。结果构建了 COAD 的预后模型。预后模型数据集与验证数据集的比较显示,在风险分组和预后方面都有相当大的相关性。根据风险评分(RS)模型,预后数据集中的样本被分为高风险组和低风险组。此外,两个风险组的病理 N 和 T 分期以及肿瘤复发率也有显著差异。在提名图生存模型中,包括年龄和病理 T 分期在内的四个预后因素也显示出卓越的预测性能。最终得到了九个差异表达 NMRGs 的最佳组合,包括 LARS2、PARS2、ETHE1、LRPPRC、TMEM70、AARS2、ACAD9、VARS2 和 ATP8A2。高RS组有更多的炎症免疫特征,包括T细胞和CD4+记忆细胞活化。此外,在体内异种移植和肝转移试验中,线粒体相关 LRPPRC 和 LARS2 的表达水平也有所增加。结论本研究建立了一个全面的 COAD 预后模型,纳入了 9 个与核-线粒体功能相关的基因。该模型在年龄、病理 T 分期、肿瘤复发和总体预后这四个预后因素上都表现出了卓越的预测能力。预计它将成为改善 COAD 预后和治疗的有效模型。
{"title":"A Comprehensive Prognostic Model for Colon Adenocarcinoma Depending on Nuclear-Mitochondrial-Related Genes.","authors":"Lingling Lv, Yuqing Huang, Qiong Li, Yuan Wu, Lan Zheng","doi":"10.1177/15330338241258570","DOIUrl":"10.1177/15330338241258570","url":null,"abstract":"<p><p><b>Background:</b> Colon adenocarcinoma (COAD) has increasing incidence and is one of the most common malignant tumors. The mitochondria involved in cell energy metabolism, oxygen free radical generation, and cell apoptosis play important roles in tumorigenesis and progression. The relationship between mitochondrial genes and COAD remains largely unknown. <b>Methods:</b> COAD data including 512 samples were set out from the UCSC Xena database. The nuclear mitochondrial-related genes (NMRGs)-related risk prognostic model and prognostic nomogram were constructed, and NMRGs-related gene mutation and the immune environment were analyzed using bioinformatics methods. Then, a liver metastasis model of colorectal cancer was constructed and protein expression was detected using Western blot assay. <b>Results:</b> A prognostic model for COAD was constructed. Comparing the prognostic model dataset and the validation dataset showed considerable correlation in both risk grouping and prognosis. Based on the risk score (RS) model, the samples of the prognostic dataset were divided into high risk group and low risk group. Moreover, pathologic N and T stage and tumor recurrence in the two risk groups were significantly different. The four prognostic factors, including age and pathologic T stage in the nomogram survival model also showed excellent predictive performance. An optimal combination of nine differentially expressed NMRGs was finally obtained, including <i>LARS2</i>, <i>PARS2</i>, <i>ETHE1</i>, <i>LRPPRC</i>, <i>TMEM70</i>, <i>AARS2</i>, <i>ACAD9</i>, <i>VARS2</i>, and <i>ATP8A2</i>. The high-RS group had more inflamed immune features, including T and CD4<sup>+</sup> memory cell activation. Besides, mitochondria-associated LRPPRC and LARS2 expression levels were increased in vivo xenograft construction and liver metastases assays. <b>Conclusion:</b> This study established a comprehensive prognostic model for COAD, incorporating nine genes associated with nuclear-mitochondrial functions. This model demonstrates superior predictive performance across four prognostic factors: age, pathological T stage, tumor recurrence, and overall prognosis. It is anticipated to be an effective model for enhancing the prognosis and treatment of COAD.</p>","PeriodicalId":22203,"journal":{"name":"Technology in Cancer Research & Treatment","volume":"23 ","pages":"15330338241258570"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238251","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}
Background: Severe delayed diarrhea and hematological toxicity limit the use of irinotecan. Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) is a critical enzyme in irinotecan metabolism. The study aims to investigate the safety and efficacy of irinotecan under the guidance of the pre-treatment UGT1A1 genotype in the second-line treatment of gastric cancer. Methods: This study involved 110 patients. Irinotecan was injected intravenously every 3 weeks, and the dose of irinotecan was determined by polymorphism of the UGT1A1 gene, which was divided into three groups (125 mg/m2: GG type; 100 mg/m2: GA type; 75 mg/m2: AA type). The primary end point was overall survival (OS), the secondary end points were progression-free survival (PFS) and safety. Results: One hundred and seven patients received irinotecan treatment and three patients with AA type received paclitaxel treatment. Among 107 patients, there were no significant differences in PFS (4.8 m vs 4.9 m vs 4.4 m; p = 0.5249) and OS (9.3 m vs 9.3 m vs NA; p = 0.6821) among patients with GG/GA/AA subtypes after dose adjustment. For the patient with homozygosity mutation, treatment was switched to paclitaxel. There were no significant differences in PFS and OS among patients with different alleles or after dose adjustment (p > 0.05). There was a significant difference in the risk of delayed diarrhea (p = 0.000), leukopenia (p = 0.003) and neutropenia (p = 0.000) in patients with different UGT1A1*6 genotypes, while no difference in patients with different UGT1A1*28 genotypes. Additionally, grade 3/4 diarrhea, neutropenia, and leukopenia were significantly more common in AA genotype patients compared to GG (2%, 19%, 24%) or GA (23%, 31%, 31%) genotype patients. Conclusion: Individual irinotecan treatment shows encouraging survival and tolerability outcomes in patients with GG/GA subtype. Irinotecan may be not suitable for patients with AA subtype.
背景:严重的迟发性腹泻和血液毒性限制了伊立替康的使用。二磷酸尿苷葡萄糖醛酸转移酶 1A1 (UGT1A1) 是伊立替康代谢过程中的一个关键酶。本研究旨在探讨在治疗前 UGT1A1 基因型的指导下,伊立替康在胃癌二线治疗中的安全性和有效性。研究方法本研究涉及 110 名患者。伊立替康每3周静脉注射一次,根据UGT1A1基因的多态性确定伊立替康的剂量,分为三组(125 mg/m2:GG型;100 mg/m2:GA型;75 mg/m2:AA型)。主要终点为总生存期(OS),次要终点为无进展生存期(PFS)和安全性。结果107 名患者接受了伊立替康治疗,3 名 AA 型患者接受了紫杉醇治疗。在107名患者中,剂量调整后,GG/GA/AA亚型患者的PFS(4.8 m vs 4.9 m vs 4.4 m;P = 0.5249)和OS(9.3 m vs 9.3 m vs NA;P = 0.6821)无明显差异。对于同基因突变的患者,则改用紫杉醇治疗。不同等位基因或剂量调整后,患者的 PFS 和 OS 无明显差异(P > 0.05)。不同UGT1A1*6基因型的患者发生迟发性腹泻(p = 0.000)、白细胞减少症(p = 0.003)和中性粒细胞减少症(p = 0.000)的风险有明显差异,而不同UGT1A1*28基因型的患者则无差异。此外,与 GG(2%、19%、24%)或 GA(23%、31%、31%)基因型患者相比,AA 基因型患者中 3/4 级腹泻、中性粒细胞减少症和白细胞减少症的发生率明显更高。结论单独伊立替康治疗在GG/GA亚型患者中显示出令人鼓舞的生存率和耐受性。伊立替康可能不适合 AA 亚型患者。
{"title":"Individual Irinotecan Therapy Under the Guidance of Pre-Treated <i>UGT1A1</i>*<i>6</i> Genotyping in Gastric Cancer.","authors":"Huifang Lv, Caiyun Nie, Yunduan He, Beibei Chen, Yingjun Liu, Junling Zhang, Xiaobing Chen","doi":"10.1177/15330338241236658","DOIUrl":"10.1177/15330338241236658","url":null,"abstract":"<p><p><b>Background:</b> Severe delayed diarrhea and hematological toxicity limit the use of irinotecan. Uridine diphosphate glucuronosyltransferase 1A1 (<i>UGT1A1</i>) is a critical enzyme in irinotecan metabolism. The study aims to investigate the safety and efficacy of irinotecan under the guidance of the pre-treatment <i>UGT1A1</i> genotype in the second-line treatment of gastric cancer. <b>Methods:</b> This study involved 110 patients. Irinotecan was injected intravenously every 3 weeks, and the dose of irinotecan was determined by polymorphism of the <i>UGT1A1</i> gene, which was divided into three groups (125 mg/m<sup>2</sup>: GG type; 100 mg/m<sup>2</sup>: GA type; 75 mg/m<sup>2</sup>: AA type). The primary end point was overall survival (OS), the secondary end points were progression-free survival (PFS) and safety. <b>Results:</b> One hundred and seven patients received irinotecan treatment and three patients with AA type received paclitaxel treatment. Among 107 patients, there were no significant differences in PFS (4.8 m vs 4.9 m vs 4.4 m; <i>p </i>= 0.5249) and OS (9.3 m vs 9.3 m vs NA; <i>p </i>= 0.6821) among patients with GG/GA/AA subtypes after dose adjustment. For the patient with homozygosity mutation, treatment was switched to paclitaxel. There were no significant differences in PFS and OS among patients with different alleles or after dose adjustment (<i>p </i>> 0.05). There was a significant difference in the risk of delayed diarrhea (<i>p </i>= 0.000), leukopenia (<i>p </i>= 0.003) and neutropenia (<i>p </i>= 0.000) in patients with different <i>UGT1A1*6</i> genotypes, while no difference in patients with different <i>UGT1A1*</i>28 genotypes. Additionally, grade 3/4 diarrhea, neutropenia, and leukopenia were significantly more common in AA genotype patients compared to GG (2%, 19%, 24%) or GA (23%, 31%, 31%) genotype patients. <b>Conclusion:</b> Individual irinotecan treatment shows encouraging survival and tolerability outcomes in patients with GG/GA subtype. Irinotecan may be not suitable for patients with AA subtype.</p>","PeriodicalId":22203,"journal":{"name":"Technology in Cancer Research & Treatment","volume":"23 ","pages":"15330338241236658"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10946077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144068","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}