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Paraneoplastic Hyperthyroidism in Advanced Testicular Non-Seminomatous Germ Cell Tumors: Prevalence and Clinical Management. 晚期睾丸非肉芽肿性生殖细胞肿瘤中的副肿瘤性甲状腺功能亢进症:发病率和临床管理。
IF 3.5 3区 医学
Oncology Pub Date : 2024-05-06 DOI: 10.1159/000538634
Markus Angerer, Bendix Hansen, Christian Wülfing, Klaus-Peter Dieckmann
{"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}
引用次数: 0
Comprehensive Genomic Characterization in Ovarian Low-Grade and Chemosensitive and Chemoresistant High-Grade Serous Carcinomas. 卵巢低级别浆液性癌、化疗敏感性和化疗耐受性高级别浆液性癌的全面基因组特征研究
IF 3.5 3区 医学
Oncology Pub Date : 2024-05-03 DOI: 10.1159/000538948
Carolina Jaliffa, Uwe Rogel, Indrani Sen, Gad Singer
{"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}
引用次数: 0
Myocardial Infarction in Chronic Myeloid Leukemia: Results from the Nationwide Readmission Database. 慢性髓性白血病心肌梗死:来自全国再入院数据库的结果
IF 3.5 3区 医学
Oncology Pub Date : 2024-05-03 DOI: 10.1159/000539149
Elrazi A Ali, Neel Patel, Mazin Khalid, Rasha Kaddoura, Madhumathi Kalavar, Jacob Shani, Mohamed Yassin
{"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 &lt; 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}
引用次数: 0
Plasma Cell-Free Adenomatous Polyposis Coli Gene Promoter Methylation as a Prognostic Biomarker for Hepatocellular Carcinoma. 血浆细胞游离腺瘤性息肉病大肠杆菌基因启动子甲基化作为肝细胞癌的预后生物标志物
IF 3.5 3区 医学
Oncology Pub Date : 2024-03-25 DOI: 10.1159/000538455
Chih-Yang Hsiao, Chang-Yi Lu, Hung-Ju Su, Kai-Wen Huang
{"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}
引用次数: 0
Potential of using qFibrosis analysis to predict recurrent and survival outcome of patients with hepatocellular carcinoma after hepatic resection. 利用 qFibrosis 分析预测肝细胞癌患者肝切除术后复发和生存结果的潜力。
IF 3.5 3区 医学
Oncology Pub Date : 2024-03-25 DOI: 10.1159/000538456
Chih-Yang Hsiao, Yayun Ren, Elaine Chng, Dean Tai, Kai-Wen Huang
{"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}
引用次数: 0
Treatment Outcomes of Patients with Ependymoma Receiving Radiotherapy: A Single Institution Experience. Ependymoma 患者接受放射治疗的疗效:单个机构的经验
IF 3.5 3区 医学
Oncology Pub Date : 2024-03-12 DOI: 10.1159/000538321
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
{"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}
引用次数: 0
Comprehensive study of chromosomal CNVs and genomic variations predicting overall survival in Myelodysplastic syndromes. 预测骨髓增生异常综合征总生存率的染色体 CNV 和基因组变异综合研究
IF 3.5 3区 医学
Oncology Pub Date : 2024-03-05 DOI: 10.1159/000536446
Nehakumari Maurya, Chandrakala Shanmukhaiah, Somprakash Dhangar, Manisha Madkaikar, Babu Rao Vundinti
{"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}
引用次数: 0
Decision-making at Swissmedic, the Swiss regulatory agency, with a focus on (neo)adjuvant cancer treatments. 瑞士监管机构 Swissmedic 的决策,重点关注(新)辅助癌症治疗。
IF 3.5 3区 医学
Oncology Pub Date : 2024-03-05 DOI: 10.1159/000536541
Matea Pavic, Qiyu Li, Stephanie Juritz, Arunas Gircys, Anita Wolfer, Ulrich-Peter Rohr
{"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}
引用次数: 0
Nesprin1 deficiency is associated with poor prognosis of renal cell carcinoma and resistance to sunitinib treatment. Nesprin1缺乏症与肾细胞癌的不良预后和对舒尼替尼治疗的耐药性有关。
IF 3.5 3区 医学
Oncology Pub Date : 2024-03-05 DOI: 10.1159/000536539
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
{"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}
引用次数: 0
Rising Prices and Lower Medicare Reimbursement Rates Create Outrage Among Clinicians. 价格上涨和医疗保险报销比例降低引起临床医生的愤怒。
IF 3.5 3区 医学
Oncology Pub Date : 2024-03-01 DOI: 10.46883/2024.undefined
Nora Janjan Md Mpsa Mba, Patrick J Silva
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