Markus Angerer, Bendix Hansen, Christian Wülfing, Klaus-Peter Dieckmann
Introduction: Paraneoplastic hyperthyroidism (PH) has been reported in patients with testicular germ cell tumors (GCTs), sporadically. This disorder is caused by extremely elevated serum levels of beta-human chorionic gonadotropin (bHCG). To date, little is known about the prevalence of PH, and its clinical features are poorly understood. The aim of the present study was to analyze the relative frequency and clinical features of PH in GCTs and evaluate their effects on therapeutic outcomes.
Methods: A cohort of 438 patients treated for testicular GCT from 2017 to 2023 was retrospectively analyzed for histology, age, clinical stage, and presence of PH. The clinical features of the patients with PH were evaluated descriptively. The relative frequency of PH was compared among the subgroups using descriptive statistical methods.
Results: Three patients with PH were identified; all had clinical symptoms of hyperthyroidism, suppressed serum levels of thyroid-stimulating hormone (TSH), and increased levels of tri-iodothyronin (fT3). All the patients had advanced, metastasized, and non-seminomatous GCTs. Serum bHCG levels ranged from 225,00 U/L to 1,520,000 U/L. The prevalence of PH was 0.7% in the entire GCT population and 60% in those with very high bHCG serum levels. All the patients received standard cisplatin-based chemotherapy along with thyrostatic treatment. The clinical symptoms of the hyperthyroidism rapidly disappeared. TSH levels normalized with decreasing bHCG levels. The PH treatment did not affect the therapeutic outcomes of the patients.
Conclusion: PH may occur in 0.7% of all patients with GCT but may be present in up to 60% of patients with very high levels of bHCG. Measuring serum levels of TSH and fT3 should be performed in addition to routine diagnostic measures in all patients with poor prognosis GCTs. Thyrostatic medication is recommended for patients with the clinical symptoms of hyperthyroidism. Early recognition of hyperthyroidism and prompt intervention will reduce comorbidity and help optimize therapeutic outcomes.
{"title":"Paraneoplastic Hyperthyroidism in Advanced Testicular Non-Seminomatous Germ Cell Tumors: Prevalence and Clinical Management.","authors":"Markus Angerer, Bendix Hansen, Christian Wülfing, Klaus-Peter Dieckmann","doi":"10.1159/000538634","DOIUrl":"10.1159/000538634","url":null,"abstract":"<p><strong>Introduction: </strong>Paraneoplastic hyperthyroidism (PH) has been reported in patients with testicular germ cell tumors (GCTs), sporadically. This disorder is caused by extremely elevated serum levels of beta-human chorionic gonadotropin (bHCG). To date, little is known about the prevalence of PH, and its clinical features are poorly understood. The aim of the present study was to analyze the relative frequency and clinical features of PH in GCTs and evaluate their effects on therapeutic outcomes.</p><p><strong>Methods: </strong>A cohort of 438 patients treated for testicular GCT from 2017 to 2023 was retrospectively analyzed for histology, age, clinical stage, and presence of PH. The clinical features of the patients with PH were evaluated descriptively. The relative frequency of PH was compared among the subgroups using descriptive statistical methods.</p><p><strong>Results: </strong>Three patients with PH were identified; all had clinical symptoms of hyperthyroidism, suppressed serum levels of thyroid-stimulating hormone (TSH), and increased levels of tri-iodothyronin (fT3). All the patients had advanced, metastasized, and non-seminomatous GCTs. Serum bHCG levels ranged from 225,00 U/L to 1,520,000 U/L. The prevalence of PH was 0.7% in the entire GCT population and 60% in those with very high bHCG serum levels. All the patients received standard cisplatin-based chemotherapy along with thyrostatic treatment. The clinical symptoms of the hyperthyroidism rapidly disappeared. TSH levels normalized with decreasing bHCG levels. The PH treatment did not affect the therapeutic outcomes of the patients.</p><p><strong>Conclusion: </strong>PH may occur in 0.7% of all patients with GCT but may be present in up to 60% of patients with very high levels of bHCG. Measuring serum levels of TSH and fT3 should be performed in addition to routine diagnostic measures in all patients with poor prognosis GCTs. Thyrostatic medication is recommended for patients with the clinical symptoms of hyperthyroidism. Early recognition of hyperthyroidism and prompt intervention will reduce comorbidity and help optimize therapeutic outcomes.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carolina Jaliffa, Uwe Rogel, Indrani Sen, Gad Singer
Introduction: Genomic characterization of serous ovarian carcinoma (SOC), which includes low-grade serous carcinoma (LGSC) and high-grade serous carcinoma (HGSC), remains necessary to improve efficacy of platinum-based chemotherapy. The aim of this study was to investigate the genomic variations in these SOC groups, also in relation to chemoresponse.
Methods: Forty-five samples of SOC were retrospectively analyzed by next-generation sequencing on DNA/RNA extracts from formalin-fixed, paraffin-embedded (FFPE) tumor samples obtained at diagnosis. HGSCs were classified as platinum-resistant and platinum-sensitive.
Results: In the LGSC group, 44% of the carcinomas had mutually exclusive variants in the RAS/RAF pathway, while additional likely oncogenic variants in the CDKN2A, SMARCA4, and YAP1 genes were observed in the remaining LGSCs. Tumor mutation burden (TMB) was significantly lower in the intrinsically chemoresistant LGSC group than in the HGSC group. In the HGSC cohort, TP53 variants were found in 90% and homologous recombination repair (HRR) pathway variants in 41% of the neoplasms. HGSCs of the chemoresistant group without classic mutations in the HRR pathway were characterized by additional variants in FGFR2 and with an FGFR3::TACC3 fusion. In addition, HGSCs showed MYC, CCNE1, and AKT2 gains that were almost exclusively observed in the chemosensitive HGSC group.
Conclusion: These results suggest that very low TMB and MYC, CCNE1, and AKT2 gains in SOC patients may be biomarkers related to platinum treatment efficacy. Thorough genomic characterization of SOCs prior to treatment might lead to more specific platinum-based chemotherapy strategies.
{"title":"Comprehensive Genomic Characterization in Ovarian Low-Grade and Chemosensitive and Chemoresistant High-Grade Serous Carcinomas.","authors":"Carolina Jaliffa, Uwe Rogel, Indrani Sen, Gad Singer","doi":"10.1159/000538948","DOIUrl":"10.1159/000538948","url":null,"abstract":"<p><strong>Introduction: </strong>Genomic characterization of serous ovarian carcinoma (SOC), which includes low-grade serous carcinoma (LGSC) and high-grade serous carcinoma (HGSC), remains necessary to improve efficacy of platinum-based chemotherapy. The aim of this study was to investigate the genomic variations in these SOC groups, also in relation to chemoresponse.</p><p><strong>Methods: </strong>Forty-five samples of SOC were retrospectively analyzed by next-generation sequencing on DNA/RNA extracts from formalin-fixed, paraffin-embedded (FFPE) tumor samples obtained at diagnosis. HGSCs were classified as platinum-resistant and platinum-sensitive.</p><p><strong>Results: </strong>In the LGSC group, 44% of the carcinomas had mutually exclusive variants in the RAS/RAF pathway, while additional likely oncogenic variants in the CDKN2A, SMARCA4, and YAP1 genes were observed in the remaining LGSCs. Tumor mutation burden (TMB) was significantly lower in the intrinsically chemoresistant LGSC group than in the HGSC group. In the HGSC cohort, TP53 variants were found in 90% and homologous recombination repair (HRR) pathway variants in 41% of the neoplasms. HGSCs of the chemoresistant group without classic mutations in the HRR pathway were characterized by additional variants in FGFR2 and with an FGFR3::TACC3 fusion. In addition, HGSCs showed MYC, CCNE1, and AKT2 gains that were almost exclusively observed in the chemosensitive HGSC group.</p><p><strong>Conclusion: </strong>These results suggest that very low TMB and MYC, CCNE1, and AKT2 gains in SOC patients may be biomarkers related to platinum treatment efficacy. Thorough genomic characterization of SOCs prior to treatment might lead to more specific platinum-based chemotherapy strategies.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elrazi A Ali, Neel Patel, Mazin Khalid, Rasha Kaddoura, Madhumathi Kalavar, Jacob Shani, Mohamed Yassin
Introduction: Chronic myeloid leukemia (CML) is a hematological malignancy with an excellent prognostic outcome. After the advancements in CML treatment and the introduction of different tyrosine kinase inhibitors (TKIs), the life expectancy of CML patients has become equivalent to that of the general population. As a result, coronary artery disease is anticipated to be the leading cause of death among CML patients. Moreover, TKI use is associated with a risk of endothelial dysfunction, thrombosis, and cardiovascular events, including myocardial infarction. In this study, we compare the outcomes of percutaneous coronary intervention (PCI) in patients with CML to their matched non-CML counterparts.
Method: This is a retrospective cohort study using the Nationwide Readmission Database from January 2016 to December 2020. Adults with or without CML hospitalized for acute myocardial infarction and underwent PCI were included. The patients were identified using ICD-10 codes. The primary outcomes were in-hospital mortality and 30-day readmission rates. The secondary outcomes were PCI complications rates.
Results: Out of 2,727,619 patients with myocardial infarction, 2,124 CML patients were identified. A total of 888 CML patients underwent PCI. CML patients were significantly older (mean age: 68.34 ± 11.14 vs. 64.40 ± 12.61 years, p < 0.001) than non-CML patients without a difference in sex distribution. Hypertension (85.45% vs. 78.64%), diabetes (45.48% vs. 37.29), stroke (11.84% vs. 7.78) at baseline were significantly higher in the CML group. Prior myocardial infarction events (20.51% vs. 15.17%) and prior PCI procedure (24.47% vs. 16.89%) were significantly higher in the CML group. CML patients had a significantly longer hospital stay (4.66 ± 4.40 vs. 3.75 ± 4.62 days, p = 0.001). The primary outcomes did not differ between the comparison groups. The risk of post-PCI complications did not differ between the comparison groups in the propensity matched analysis except for coronary artery dissection (odds ratio [OR]: 0.10; 95% confidence interval [CI]: 0.02-0.65, p = 0.016) and ischemic stroke (OR: 0.35; 95% CI: 0.14-0.93, p = 0.034) which were lower in the CML group.
Conclusion: This analysis showed no statistically significant difference in mortality, 30-day readmission, and post PCI complications rates between CML and non-CML patients. However, interestingly, CML patients may experience lower coronary artery dissection and ischemic stroke events than those without CML diagnosis.
{"title":"Myocardial Infarction in Chronic Myeloid Leukemia: Results from the Nationwide Readmission Database.","authors":"Elrazi A Ali, Neel Patel, Mazin Khalid, Rasha Kaddoura, Madhumathi Kalavar, Jacob Shani, Mohamed Yassin","doi":"10.1159/000539149","DOIUrl":"10.1159/000539149","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic myeloid leukemia (CML) is a hematological malignancy with an excellent prognostic outcome. After the advancements in CML treatment and the introduction of different tyrosine kinase inhibitors (TKIs), the life expectancy of CML patients has become equivalent to that of the general population. As a result, coronary artery disease is anticipated to be the leading cause of death among CML patients. Moreover, TKI use is associated with a risk of endothelial dysfunction, thrombosis, and cardiovascular events, including myocardial infarction. In this study, we compare the outcomes of percutaneous coronary intervention (PCI) in patients with CML to their matched non-CML counterparts.</p><p><strong>Method: </strong>This is a retrospective cohort study using the Nationwide Readmission Database from January 2016 to December 2020. Adults with or without CML hospitalized for acute myocardial infarction and underwent PCI were included. The patients were identified using ICD-10 codes. The primary outcomes were in-hospital mortality and 30-day readmission rates. The secondary outcomes were PCI complications rates.</p><p><strong>Results: </strong>Out of 2,727,619 patients with myocardial infarction, 2,124 CML patients were identified. A total of 888 CML patients underwent PCI. CML patients were significantly older (mean age: 68.34 ± 11.14 vs. 64.40 ± 12.61 years, p < 0.001) than non-CML patients without a difference in sex distribution. Hypertension (85.45% vs. 78.64%), diabetes (45.48% vs. 37.29), stroke (11.84% vs. 7.78) at baseline were significantly higher in the CML group. Prior myocardial infarction events (20.51% vs. 15.17%) and prior PCI procedure (24.47% vs. 16.89%) were significantly higher in the CML group. CML patients had a significantly longer hospital stay (4.66 ± 4.40 vs. 3.75 ± 4.62 days, p = 0.001). The primary outcomes did not differ between the comparison groups. The risk of post-PCI complications did not differ between the comparison groups in the propensity matched analysis except for coronary artery dissection (odds ratio [OR]: 0.10; 95% confidence interval [CI]: 0.02-0.65, p = 0.016) and ischemic stroke (OR: 0.35; 95% CI: 0.14-0.93, p = 0.034) which were lower in the CML group.</p><p><strong>Conclusion: </strong>This analysis showed no statistically significant difference in mortality, 30-day readmission, and post PCI complications rates between CML and non-CML patients. However, interestingly, CML patients may experience lower coronary artery dissection and ischemic stroke events than those without CML diagnosis.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140864731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chih-Yang Hsiao, Chang-Yi Lu, Hung-Ju Su, Kai-Wen Huang
Introduction: Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide. Lack of biomarkers for follow-up after treatment is a clinical challenge. DNA methylation has been proposed to be a potential biomarker in HCC. However, there is still lacking of evidence of its clinical use. This study aims to evaluate the value of using plasma Adenomatous Polyposis Coli promoter methylation level (APC-MET) as a potential biomarker in HCC treatment.
Method: A total of 96 patients with HCC at BCLC stage B underwent local tumor ablation treatment were prospectively included in this study. APC-MET was examined from the plasma of each patient before and 1 months after treatment. The prediction value of APC-MET for survival outcome and disease status after treatment were analyzed, and adjusted with alpha-fetoprotein and protein induced by vitamin K absence-II using cox regression analysis.
Results: Univariate cox regression analysis showed preoperative APC-MET >0 (HR, 2.9, 95% CI 1.05-8.05, p=0.041) and postoperative APC-MET >0 (HR, 3.47, 95% CI 1.16-10.4, p=0.026) were both predictors of death, and preoperative APC-MET >0 was a predictor of disease progression after treatment (HR, 2.04, 95% CI 1.21-3.44, p=0.007). In multivariate models, pre-op APC-MET >0 was a significant predictor of disease progression after adjusting with other two traditional biomarkers (HR, 1.82, 95% CI 1.05-3.17, p=0.034).
Conclusions: Hypermethylation of APC promoter appears to be a potential biomarker that could predict patient survival and disease progression outcome in patients with intermediate stage HCC after local ablation treatment.
简介肝细胞癌(HCC)是全球癌症死亡的主要原因。缺乏治疗后随访的生物标志物是一项临床挑战。DNA 甲基化被认为是 HCC 的潜在生物标志物。然而,目前仍缺乏其临床应用的证据。本研究旨在评估血浆腺瘤性息肉病大肠杆菌启动子甲基化水平(APC-MET)作为潜在生物标志物在HCC治疗中的价值:方法:本研究前瞻性地纳入了96例接受局部肿瘤消融治疗的BCLC B期HCC患者。方法:该研究共纳入了96名接受局部肿瘤消融治疗的BCLC B期HCC患者,并对每位患者治疗前和治疗后1个月的血浆中的APC-MET进行了检测。分析了APC-MET对治疗后生存结果和疾病状态的预测价值,并使用cox回归分析法对甲胎蛋白和维生素K缺失-II诱导的蛋白进行了调整:单变量cox回归分析显示,术前APC-MET>0(HR,2.9,95% CI 1.05-8.05,p=0.041)和术后APC-MET>0(HR,3.47,95% CI 1.16-10.4,p=0.026)都是死亡的预测因素,术前APC-MET>0是治疗后疾病进展的预测因素(HR,2.04,95% CI 1.21-3.44,p=0.007)。在多变量模型中,术前APC-MET>0与其他两个传统生物标志物进行调整后,仍能显著预测疾病进展(HR,1.82,95% CI 1.05-3.17,P=0.034):APC启动子的高甲基化似乎是一种潜在的生物标志物,可以预测局部消融治疗后中晚期HCC患者的生存和疾病进展情况。
{"title":"Plasma Cell-Free Adenomatous Polyposis Coli Gene Promoter Methylation as a Prognostic Biomarker for Hepatocellular Carcinoma.","authors":"Chih-Yang Hsiao, Chang-Yi Lu, Hung-Ju Su, Kai-Wen Huang","doi":"10.1159/000538455","DOIUrl":"https://doi.org/10.1159/000538455","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide. Lack of biomarkers for follow-up after treatment is a clinical challenge. DNA methylation has been proposed to be a potential biomarker in HCC. However, there is still lacking of evidence of its clinical use. This study aims to evaluate the value of using plasma Adenomatous Polyposis Coli promoter methylation level (APC-MET) as a potential biomarker in HCC treatment.</p><p><strong>Method: </strong>A total of 96 patients with HCC at BCLC stage B underwent local tumor ablation treatment were prospectively included in this study. APC-MET was examined from the plasma of each patient before and 1 months after treatment. The prediction value of APC-MET for survival outcome and disease status after treatment were analyzed, and adjusted with alpha-fetoprotein and protein induced by vitamin K absence-II using cox regression analysis.</p><p><strong>Results: </strong>Univariate cox regression analysis showed preoperative APC-MET >0 (HR, 2.9, 95% CI 1.05-8.05, p=0.041) and postoperative APC-MET >0 (HR, 3.47, 95% CI 1.16-10.4, p=0.026) were both predictors of death, and preoperative APC-MET >0 was a predictor of disease progression after treatment (HR, 2.04, 95% CI 1.21-3.44, p=0.007). In multivariate models, pre-op APC-MET >0 was a significant predictor of disease progression after adjusting with other two traditional biomarkers (HR, 1.82, 95% CI 1.05-3.17, p=0.034).</p><p><strong>Conclusions: </strong>Hypermethylation of APC promoter appears to be a potential biomarker that could predict patient survival and disease progression outcome in patients with intermediate stage HCC after local ablation treatment.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chih-Yang Hsiao, Yayun Ren, Elaine Chng, Dean Tai, Kai-Wen Huang
Background: There remains a lack of studies addressing the stromal background and fibrosis features and its prognostic value in liver cancer. qFibrosis can identify, quantify and visualize the fibrosis features from biopsy samples. In this study, we aim to demonstrate the prognostic value of histological features by using qFibrosis analysis in liver cancer patients.
Methods: Liver specimen from 201 patients with hepatocellular carcinoma underwent curative resection were imaged and assessed using qFibrosis system, and generated a total of 33 and 156 collagen parameters from tumor part and non-tumor liver tissue, respectively. We used these collagen parameters on patients to build two combined indexes, RFS-index and OS-index, in order to differentiate patients with early recurrence and early death, respectively. The models were validated using leave-one-out method.
Results: Both combined indexes had significant prediction value of patients' outcome. The RFS-index of 0.52 well differentiates patients with early recurrence (p < 0.001), and the OS-index of 0.73 well differentiates patients with early death during follow-up (p = 0.02).
Conclusions: Combined index calculated with qFibrosis from digital readout of fibrotic status of peri-tumor liver specimen in patients with HCC have prediction values for their disease and survival outcomes. These results demonstrated the potentials to transform histopathological features into quantifiable data that could be used to correlate with clinical outcome.
{"title":"Potential of using qFibrosis analysis to predict recurrent and survival outcome of patients with hepatocellular carcinoma after hepatic resection.","authors":"Chih-Yang Hsiao, Yayun Ren, Elaine Chng, Dean Tai, Kai-Wen Huang","doi":"10.1159/000538456","DOIUrl":"https://doi.org/10.1159/000538456","url":null,"abstract":"<p><strong>Background: </strong>There remains a lack of studies addressing the stromal background and fibrosis features and its prognostic value in liver cancer. qFibrosis can identify, quantify and visualize the fibrosis features from biopsy samples. In this study, we aim to demonstrate the prognostic value of histological features by using qFibrosis analysis in liver cancer patients.</p><p><strong>Methods: </strong>Liver specimen from 201 patients with hepatocellular carcinoma underwent curative resection were imaged and assessed using qFibrosis system, and generated a total of 33 and 156 collagen parameters from tumor part and non-tumor liver tissue, respectively. We used these collagen parameters on patients to build two combined indexes, RFS-index and OS-index, in order to differentiate patients with early recurrence and early death, respectively. The models were validated using leave-one-out method.</p><p><strong>Results: </strong>Both combined indexes had significant prediction value of patients' outcome. The RFS-index of 0.52 well differentiates patients with early recurrence (p < 0.001), and the OS-index of 0.73 well differentiates patients with early death during follow-up (p = 0.02).</p><p><strong>Conclusions: </strong>Combined index calculated with qFibrosis from digital readout of fibrotic status of peri-tumor liver specimen in patients with HCC have prediction values for their disease and survival outcomes. These results demonstrated the potentials to transform histopathological features into quantifiable data that could be used to correlate with clinical outcome.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tiffany Ting-Fong Liu, Jason Chia-Hsien Cheng, Yu-Hsuan Chen, Feng-Ming Hsu, Keng-Hsueh Lan, Chao-Yuan Huang, Chun-Wei Wang, Sung-Hsin Kuo
Introduction: The study explored the failure pattern and clinical outcomes in patients with ependymoma undergoing radiotherapy.
Methods: Between January 2004 and June 2022, we included 32 patients with ependymoma who underwent radiotherapy as part of the multimodality treatment at our institution. Of these, 27 (84.4%) underwent adjuvant radiotherapy, four received radiotherapy after local recurrence, and one received definitive CyberKnife radiotherapy (21 Gy in three fractions). The median prescribed dose was 54 Gy in patients who received conventional radiotherapy. We analyzed the local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and potential prognostic factors.
Results: The median age was 29.8 years. Approximately 28.1% were pediatric patients. Fifteen tumors (46.9%) were World Health Organization (WHO) grade II, 10 (31.3%) were WHO grade III, and seven (22.8%) were WHO grade I. Among them, 15 patients (46.9%) had posterior fossa tumors, 10 (31.3%) had supratentorial tumors, and seven (22.8%) had spinal tumors. Of the 31 patients who underwent upfront surgical resection, 19 (61.3%) underwent gross total resection or near total resection. Seventeen of 19 patients with first failures (89.5%) had isolated local recurrences. Of the 19 patients with disease progression, 11 (57.9%) were disease-free or had stable disease after salvage therapy, and five (26.3%) had disease-related mortality. Most of the first local recurrences after radiotherapy occurred in the infield (13 of 16, 81.3%). The 5-year LPFS, DMFS, PFS, and OS rates were 48.5%, 89.6%, 45.1%, and 88.4%, respectively, at a median follow-up of 6.25 years. Subtotal resection was associated with poorer LPFS and PFS in patients with intracranial ependymoma (hazard ratio = 3.69, p = 0.018 for LPFS; hazard ratio = 3.20, p = 0.029 for PFS).
Conclusion: Incorporating radiotherapy into multimodal treatment has led to favorable outcomes in patients with ependymoma, and the extent of resection is a prognostic factor for the local control of intracranial ependymoma.
{"title":"Treatment Outcomes of Patients with Ependymoma Receiving Radiotherapy: A Single Institution Experience.","authors":"Tiffany Ting-Fong Liu, Jason Chia-Hsien Cheng, Yu-Hsuan Chen, Feng-Ming Hsu, Keng-Hsueh Lan, Chao-Yuan Huang, Chun-Wei Wang, Sung-Hsin Kuo","doi":"10.1159/000538321","DOIUrl":"https://doi.org/10.1159/000538321","url":null,"abstract":"<p><strong>Introduction: </strong>The study explored the failure pattern and clinical outcomes in patients with ependymoma undergoing radiotherapy.</p><p><strong>Methods: </strong>Between January 2004 and June 2022, we included 32 patients with ependymoma who underwent radiotherapy as part of the multimodality treatment at our institution. Of these, 27 (84.4%) underwent adjuvant radiotherapy, four received radiotherapy after local recurrence, and one received definitive CyberKnife radiotherapy (21 Gy in three fractions). The median prescribed dose was 54 Gy in patients who received conventional radiotherapy. We analyzed the local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and potential prognostic factors.</p><p><strong>Results: </strong>The median age was 29.8 years. Approximately 28.1% were pediatric patients. Fifteen tumors (46.9%) were World Health Organization (WHO) grade II, 10 (31.3%) were WHO grade III, and seven (22.8%) were WHO grade I. Among them, 15 patients (46.9%) had posterior fossa tumors, 10 (31.3%) had supratentorial tumors, and seven (22.8%) had spinal tumors. Of the 31 patients who underwent upfront surgical resection, 19 (61.3%) underwent gross total resection or near total resection. Seventeen of 19 patients with first failures (89.5%) had isolated local recurrences. Of the 19 patients with disease progression, 11 (57.9%) were disease-free or had stable disease after salvage therapy, and five (26.3%) had disease-related mortality. Most of the first local recurrences after radiotherapy occurred in the infield (13 of 16, 81.3%). The 5-year LPFS, DMFS, PFS, and OS rates were 48.5%, 89.6%, 45.1%, and 88.4%, respectively, at a median follow-up of 6.25 years. Subtotal resection was associated with poorer LPFS and PFS in patients with intracranial ependymoma (hazard ratio = 3.69, p = 0.018 for LPFS; hazard ratio = 3.20, p = 0.029 for PFS).</p><p><strong>Conclusion: </strong>Incorporating radiotherapy into multimodal treatment has led to favorable outcomes in patients with ependymoma, and the extent of resection is a prognostic factor for the local control of intracranial ependymoma.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140111128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Myelodysplastic syndrome (MDS) is a heterogeneous disease characterized by cytopenia, marrow dysplasia and has a propensity to develop into acute myeloid leukemia (AML). The disease progression is majorly affected by genetic defects. However, about 40% - 50% of patients with MDS present with a normal karyotype and develop different courses of disease. Hence there remains a room to advance the biological understanding and to find molecular prognostic markers for cytogenetically normal (CN) MDS.
Methods: We performed a high-resolution CGH + SNP array along with NGS of 77 primary diagnosed MDS patients and also they were clinically followed up.
Results: Our study revealed 82 clinically significant genomic lesions (losses/gains) in 49% of MDS patients. CGH + SNP array reduced the proportion of normal karyotype by 30%. SNP array in combination with NGS confirmed the biallelic loss of function of the TP53 gene (2/6), which is a clinically relevant biomarker and new genetic-based MDS entity i.e. MDS-biTP53 as per the new WHO classification 2022. Genomic region 2p22.3 presented with frequent lesions and also with a more hazard ratio (2.7, 95% CI 0.37 - 21) when analyzed by Kaplan Meier survival analysis.
Conclusion: CGH + SNP array changed the cytogenetic and IPSS-R risk group in 18% and 13% of patients respectively with an improved prediction of prognosis. This study emphasizes the cytogenetic heterogeneity of MDS and highlights that abnormality with chromosome 2 may have a diagnostic and prognostic impact.
{"title":"Comprehensive study of chromosomal CNVs and genomic variations predicting overall survival in Myelodysplastic syndromes.","authors":"Nehakumari Maurya, Chandrakala Shanmukhaiah, Somprakash Dhangar, Manisha Madkaikar, Babu Rao Vundinti","doi":"10.1159/000536446","DOIUrl":"https://doi.org/10.1159/000536446","url":null,"abstract":"<p><strong>Introduction: </strong>Myelodysplastic syndrome (MDS) is a heterogeneous disease characterized by cytopenia, marrow dysplasia and has a propensity to develop into acute myeloid leukemia (AML). The disease progression is majorly affected by genetic defects. However, about 40% - 50% of patients with MDS present with a normal karyotype and develop different courses of disease. Hence there remains a room to advance the biological understanding and to find molecular prognostic markers for cytogenetically normal (CN) MDS.</p><p><strong>Methods: </strong>We performed a high-resolution CGH + SNP array along with NGS of 77 primary diagnosed MDS patients and also they were clinically followed up.</p><p><strong>Results: </strong>Our study revealed 82 clinically significant genomic lesions (losses/gains) in 49% of MDS patients. CGH + SNP array reduced the proportion of normal karyotype by 30%. SNP array in combination with NGS confirmed the biallelic loss of function of the TP53 gene (2/6), which is a clinically relevant biomarker and new genetic-based MDS entity i.e. MDS-biTP53 as per the new WHO classification 2022. Genomic region 2p22.3 presented with frequent lesions and also with a more hazard ratio (2.7, 95% CI 0.37 - 21) when analyzed by Kaplan Meier survival analysis.</p><p><strong>Conclusion: </strong>CGH + SNP array changed the cytogenetic and IPSS-R risk group in 18% and 13% of patients respectively with an improved prediction of prognosis. This study emphasizes the cytogenetic heterogeneity of MDS and highlights that abnormality with chromosome 2 may have a diagnostic and prognostic impact.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Additional considerations are required for the benefit-risk assessment of new drugs or indications in the setting of (neo)adjuvant cancer treatment as compared to the metastatic/advanced setting, possibly leading to different decision patterns for the (neo)adjuvant versus the metastatic and advanced setting within a health authority but also among different health authorities.
Methods: We analyzed regulatory decisions at the Swiss Agency for Therapeutic Products Swissmedic (SMC) for all oncology indications (mostly metastatic indications) and indications in the (neo)adjuvant setting and compared these to decisions taken by the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA).
Results: Comparing the positive and negative decisions within the Swiss Agency for Therapeutic Products Swissmedic (SMC) between July 2017 and Dec 2021 the approval rates were with 66.7% lower for (neo)adjuvant indications versus 88.4% in the metastatic and advanced indications. While the approval rates for metastatic and advanced New Active Substances (NAS) applications were similar at SMC as compared to the EMA and the FDA, they were lower for (neo)adjuvant applications at SMC as compared to the EMA and the FDA. The underlying reason in all cases with divergent decisions at SMC as compared to EMA and FDA was that no overall survival (OS) benefit as compared to control arm has been observed in the submitted data package.
Conclusion: Approval and consensus decision rates at SMC in comparison to EMA and FDA were lower for (neo)adjuvant indications but not for advanced and metastastic NAS oncology indications.
导言:与癌症转移/晚期治疗相比,在癌症(新)辅助治疗情况下对新药或适应症进行效益-风险评估时需要考虑更多因素,这可能导致在一个卫生部门内部以及不同卫生部门之间,癌症(新)辅助治疗与癌症转移和晚期治疗的决策模式有所不同:我们分析了瑞士治疗产品管理局(SMC)针对所有肿瘤适应症(主要是转移性适应症)和(新)辅助治疗适应症做出的监管决定,并将这些决定与欧洲药品管理局(EMA)和美国食品药品管理局(FDA)做出的决定进行了比较:比较瑞士治疗产品管理局(SMC)在2017年7月至2021年12月期间做出的积极和消极决定,(新)辅助适应症的批准率比转移性和晚期适应症低66.7%,而转移性和晚期适应症的批准率为88.4%。虽然 SMC 的转移性和晚期新活性物质(NAS)申请批准率与 EMA 和 FDA 相似,但 SMC 的(新)辅助适应症申请批准率却低于 EMA 和 FDA。与 EMA 和 FDA 相比,SMC 的决定出现分歧的根本原因是,在提交的数据包中未观察到与对照组相比有总生存期(OS)获益:结论:与 EMA 和 FDA 相比,SMC 对(新)辅助适应症的批准率和一致决定率较低,但对晚期和转移性 NAS 肿瘤适应症的批准率和一致决定率较低。
{"title":"Decision-making at Swissmedic, the Swiss regulatory agency, with a focus on (neo)adjuvant cancer treatments.","authors":"Matea Pavic, Qiyu Li, Stephanie Juritz, Arunas Gircys, Anita Wolfer, Ulrich-Peter Rohr","doi":"10.1159/000536541","DOIUrl":"https://doi.org/10.1159/000536541","url":null,"abstract":"<p><strong>Introduction: </strong>Additional considerations are required for the benefit-risk assessment of new drugs or indications in the setting of (neo)adjuvant cancer treatment as compared to the metastatic/advanced setting, possibly leading to different decision patterns for the (neo)adjuvant versus the metastatic and advanced setting within a health authority but also among different health authorities.</p><p><strong>Methods: </strong>We analyzed regulatory decisions at the Swiss Agency for Therapeutic Products Swissmedic (SMC) for all oncology indications (mostly metastatic indications) and indications in the (neo)adjuvant setting and compared these to decisions taken by the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA).</p><p><strong>Results: </strong>Comparing the positive and negative decisions within the Swiss Agency for Therapeutic Products Swissmedic (SMC) between July 2017 and Dec 2021 the approval rates were with 66.7% lower for (neo)adjuvant indications versus 88.4% in the metastatic and advanced indications. While the approval rates for metastatic and advanced New Active Substances (NAS) applications were similar at SMC as compared to the EMA and the FDA, they were lower for (neo)adjuvant applications at SMC as compared to the EMA and the FDA. The underlying reason in all cases with divergent decisions at SMC as compared to EMA and FDA was that no overall survival (OS) benefit as compared to control arm has been observed in the submitted data package.</p><p><strong>Conclusion: </strong>Approval and consensus decision rates at SMC in comparison to EMA and FDA were lower for (neo)adjuvant indications but not for advanced and metastastic NAS oncology indications.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Nuclear envelope spectrin repeat protein (Nesprin) 1 encoded by SYNE1, crucially regulates the morphology and functions of the cell. Mutations in the SYNE1 gene are associated with various diseases; however, their significance in renal cell carcinoma (RCC) remains unknown. In this study, we have investigated the association of SYNE1/Nesprin1 with the progression and prognosis of clear cell RCC (ccRCC).
Methods: In silico analyses of publicly available datasets of patients with RCC were performed. Based on the cohort data, Nesprin1 expression in nephrectomized tissue samples acquired from patients with ccRCC was analyzed using immunohistochemical staining. The invasion, migration, and proliferation of the SYNE1-knockdown human RCC cell lines were analyzed in vitro; moreover, RNA sequencing and Gene Set Enrichment Analysis were conducted to study the molecular mechanism underlying the association of SYNE1/Nesprin1 with prognosis of RCC.
Results: Patients with RCC-associated SYNE1 gene mutations exhibited significantly worse overall and progression-free survivals. Patients with Nesprin1-negative ccRCC tumors exhibit significantly poorer overall, cancer-specific, and recurrence-free survival rates than those recorded in the Nesprin1-positive group. SYNE1 knockdown enhanced the invasion and migration of RCC cells, however, it did not influence the proliferation of cells. RNA sequencing and Gene Set Enrichment Analysis revealed that SYNE1 knockdown significantly altered the expression of genes associated with oxidative phosphorylation. Consistently, patients with RCC exhibiting low SYNE1 expression, who were treated with the vascular endothelial growth factor receptor inhibitor sunitinib, had worse progression-free survival.
Conclusions: The results indicate that the expression of SYNE1/Nesprin1 and SYNE1 mutations in patients with RCC are closely linked to their prognosis and responsiveness to sunitinib treatment.
{"title":"Nesprin1 deficiency is associated with poor prognosis of renal cell carcinoma and resistance to sunitinib treatment.","authors":"Takafumi Fukushima, Kohei Kobatake, Kento Miura, Kenshiro Takemoto, Ryoken Yamanaka, Ryo Tasaka, Yuki Kohada, Shunsuke Miyamoto, Yohei Sekino, Hiroyuki Kitano, Keisuke Goto, Kenichiro Ikeda, Akihiro Goriki, Keisuke Hieda, Osamu Kaminuma, Nobuyuki Hinata","doi":"10.1159/000536539","DOIUrl":"https://doi.org/10.1159/000536539","url":null,"abstract":"<p><strong>Introduction: </strong>Nuclear envelope spectrin repeat protein (Nesprin) 1 encoded by SYNE1, crucially regulates the morphology and functions of the cell. Mutations in the SYNE1 gene are associated with various diseases; however, their significance in renal cell carcinoma (RCC) remains unknown. In this study, we have investigated the association of SYNE1/Nesprin1 with the progression and prognosis of clear cell RCC (ccRCC).</p><p><strong>Methods: </strong>In silico analyses of publicly available datasets of patients with RCC were performed. Based on the cohort data, Nesprin1 expression in nephrectomized tissue samples acquired from patients with ccRCC was analyzed using immunohistochemical staining. The invasion, migration, and proliferation of the SYNE1-knockdown human RCC cell lines were analyzed in vitro; moreover, RNA sequencing and Gene Set Enrichment Analysis were conducted to study the molecular mechanism underlying the association of SYNE1/Nesprin1 with prognosis of RCC.</p><p><strong>Results: </strong>Patients with RCC-associated SYNE1 gene mutations exhibited significantly worse overall and progression-free survivals. Patients with Nesprin1-negative ccRCC tumors exhibit significantly poorer overall, cancer-specific, and recurrence-free survival rates than those recorded in the Nesprin1-positive group. SYNE1 knockdown enhanced the invasion and migration of RCC cells, however, it did not influence the proliferation of cells. RNA sequencing and Gene Set Enrichment Analysis revealed that SYNE1 knockdown significantly altered the expression of genes associated with oxidative phosphorylation. Consistently, patients with RCC exhibiting low SYNE1 expression, who were treated with the vascular endothelial growth factor receptor inhibitor sunitinib, had worse progression-free survival.</p><p><strong>Conclusions: </strong>The results indicate that the expression of SYNE1/Nesprin1 and SYNE1 mutations in patients with RCC are closely linked to their prognosis and responsiveness to sunitinib treatment.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In a recent Hot Topics article, reimbursement rates for Medicare physicians are discussed, and how it will impact their practice.
在最近的一篇热门话题文章中,讨论了医疗保险医生的报销比例,以及这将如何影响他们的工作。
{"title":"Rising Prices and Lower Medicare Reimbursement Rates Create Outrage Among Clinicians.","authors":"Nora Janjan Md Mpsa Mba, Patrick J Silva","doi":"10.46883/2024.undefined","DOIUrl":"https://doi.org/10.46883/2024.undefined","url":null,"abstract":"In a recent Hot Topics article, reimbursement rates for Medicare physicians are discussed, and how it will impact their practice.","PeriodicalId":19497,"journal":{"name":"Oncology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140280628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}