Ejc Supplements最新文献

{"title":"Clinical advancement in the management of mutant isocitrate dehydrogenase (IDH) cancers","authors":"John Bridgewater ,&nbsp;Ghazaleh Tabatabai ,&nbsp;Teresa Macarulla ,&nbsp;Silvia Stacchiotti","doi":"10.1016/j.ejcsup.2025.12.001","DOIUrl":"10.1016/j.ejcsup.2025.12.001","url":null,"abstract":"<div><div>The use of mutant isocitrate dehydrogenase (mIDH) inhibitors has been investigated and has shown significant improvement in survival outcomes in patients with a range of m<em>IDH</em> cancers, including acute myeloid leukaemia (AML), cholangiocarcinoma (CCA), glioma and conventional chondrosarcoma. In the phase 3 clinical trial ClarIDHy, patients with m<em>IDH1</em> CCA treated with ivosidenib had improved overall survival (OS) compared to those treated with placebo (hazard ratio [HR]: 0.79 [95% confidence interval [CI]: 0.56–1.12]; P=0.09). In the phase 3 AGILE study, patients with m<em>IDH1</em> AML treated with ivosidenib plus azacitidine showed improved OS compared to those treated with placebo plus azacitidine (HR: 0.42 [95% CI: 0.27–0.73]; P=0.001). In conventional chondrosarcoma, ivosidenib demonstrated efficacy in a phase 1 trial and the ongoing phase 3, placebo-controlled clinical trial CHONQUER will investigate the use of ivosidenib in patients with unresectable, progressive, conventional m<em>IDH1</em> chondrosarcoma. The phase 3 clinical trial INDIGO explored the use of vorasidenib for the treatment of Central Nervous System World Health Organization grade 2 m<em>IDH</em> glioma and showed that vorasidenib had a progression-free survival benefit over placebo in previously untreated patients (HR: 0.39 [95% CI: 0.27–0.56]; P&lt;0.0001). Across these studies, mIDH inhibitors were well-tolerated. Current efforts focus on further evaluating the efficacy and safety of mIDH inhibitors in different lines of therapy, in combination with other anti-neoplastic agents, and in other m<em>IDH</em> cancers.</div></div>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"17 ","pages":"Pages 11-19"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147556261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isocitrate dehydrogenase mutations as potential tumour agnostic targets","authors":"Teresa Macarulla ,&nbsp;Ghazaleh Tabatabai ,&nbsp;Silvia Stacchiotti ,&nbsp;John Bridgewater","doi":"10.1016/j.ejcsup.2025.12.002","DOIUrl":"10.1016/j.ejcsup.2025.12.002","url":null,"abstract":"<div><div>The isocitrate dehydrogenase (IDH) family of proteins comprises three important metabolic enzymes that convert isocitrate to alpha ketoglutarate (α-KG) via oxidative decarboxylation. The IDH enzymes play important roles in epigenetic regulation, DNA repair, and cellular metabolism and biosynthesis. In mutant <em>IDH</em> (m<em>IDH</em>) cells, α-KG is converted into the functional oncometabolite 2-hydroxyglutarate (2-HG) in a process that consumes the reduced form of nicotinamide adenine dinucleotide phosphate to generate its oxidised form. 2-HG competitively inhibits α-KG from binding to the active site of histone and DNA demethylases, leading to hypermethylation, which inhibits cellular differentiation and induces tumour cell proliferation. Increased 2-HG also has other effects on cellular biology, including altered metabolism, dysregulation of gene expression, alterations in the DNA damage repair pathway, inflammation, and cell death, therefore supporting and promoting tumorigenesis. m<em>IDH</em> genes are associated with a variety of cancers, including but not limited to, cholangiocarcinoma, acute myeloid leukaemia, glioma, and chondrosarcoma, and the incidences of m<em>IDH</em> in these cancers varies and is approximately 13%, 33%, 73%, and 56%, respectively. The biological effects of m<em>IDH</em> are distinct in different cancers, but the reason that m<em>IDH</em> promotes tumour development in some tissues and not others is not clear. m<em>IDH</em> has no definitive prognostic impact in these cancers, except glioma, in which it is a disease-defining marker due to its distinct prognostic significance. m<em>IDH1</em>/2 are actionable mutations that represent therapeutic targets, however available targeted therapies to treat m<em>IDH</em> cancers are lacking. This article discusses m<em>IDH</em> genes and their importance in each of these cancers.</div></div>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"17 ","pages":"Pages 1-10"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147556260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disclaimer","authors":"","doi":"10.1016/S1359-6349(26)00006-6","DOIUrl":"10.1016/S1359-6349(26)00006-6","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"17 ","pages":"Page ii"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147556263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Title page","authors":"","doi":"10.1016/S1359-6349(26)00004-2","DOIUrl":"10.1016/S1359-6349(26)00004-2","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"17 ","pages":"Page i"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147556262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"^99mTc/¹²³I Dual-Radionuclide Correction for Self-Scatter, Down-Scatter, and Tailing Effect for a CZT SPECT with Varying Tracer Distributions.","authors":"Alexandre F Velo, Peng Fan, Huidong Xie, Xiongchao Chen, Nabil Boutagy, Attila Feher, Albert J Sinusas, Michael Ljungberg, Chi Liu","doi":"10.1109/trpms.2023.3297443","DOIUrl":"10.1109/trpms.2023.3297443","url":null,"abstract":"<p><p>SPECT systems distinguish radionuclides by using multiple energy windows. For CZT detectors, the energy spectrum has a low energy tail leading to additional crosstalk between the radionuclides. Previous work developed models to correct the scatter and crosstalk for CZT-based dedicated cardiac systems with similar ^99mTc/¹²³I tracer distributions. These models estimate the primary and scatter components by solving a set of equations employing the MLEM approach. A penalty term is applied to ensure convergence. The present work estimates the penalty term for any ^99mTc/¹²³I activity level. An iterative approach incorporating Monte Carlo into the iterative image reconstruction loops was developed to estimate the penalty terms. We used SIMIND and XCAT phantoms in this study. Distribution of tracers in the myocardial tissue and blood pool were varied to simulate a dynamic acquisition. Evaluations of the estimated and the real penalty terms were performed using simulations and large animal data. The myocardium to blood pool ratio was calculated using ROIs in the myocardial tissue and the blood pool for quantitative analysis. All corrected images yielded a good agreement with the gold standard images. In conclusion, we developed a CZT crosstalk correction method for quantitative imaging of ^99mTc/¹²³I activity levels by dynamically estimating the penalty terms.</p>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"1 1","pages":"839-850"},"PeriodicalIF":4.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11090119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78505336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-COVID-19 Disparities in Telemedicine Use Among Louisiana Medicaid Beneficiaries.","authors":"Kevin Callison, Andrew Anderson, Yixue Shao, Thomas A LaVeist, Brigham Walker","doi":"10.1089/tmj.2022.0034","DOIUrl":"10.1089/tmj.2022.0034","url":null,"abstract":"<p><p><b><i>Background:</i></b> <i>We examine trends in telemedicine use by race, geography, and age among Louisiana Medicaid beneficiaries in the months preceding the COVID-19 pandemic.</i> <b><i>Methods:</i></b> <i>Using Louisiana Medicaid claims data from January 2018 through February 2020, we calculated a relative ratio of telemedicine use as the share of telemedicine claims by race, age, and geography and conducted two-sample</i> t<i>-tests.</i> <b><i>Results:</i></b> <i>In 2018, White beneficiaries used telemedicine at a relative ratio of 1.92 compared with Black beneficiaries (</i>p <i>< 0.001) and 2.02 compared with Hispanic beneficiaries (</i>p <i>< 0.001). Rural beneficiaries used telemedicine at a relative ratio of 1.27 (</i>p <i>< 0.001) compared with urban beneficiaries. Children and adolescents used telemedicine at a higher rate than other age groups. Racial and geographic disparities narrowed in the first months of 2020.</i> <b><i>Conclusions:</i></b> <i>Telemedicine use in Louisiana Medicaid was low but growing before the pandemic with narrowing disparities by race and geography and emerging disparities by age.</i></p>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"8 1","pages":""},"PeriodicalIF":4.7,"publicationDate":"2022-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78484182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The importance of basal-temporal white matter to pre- and post-surgical naming ability in temporal lobe epilepsy.","authors":"Erik Kaestner, Alena Stasenko, Sharona Ben-Haim, Jerry Shih, Brianna M Paul, Carrie R McDonald","doi":"10.1016/j.nicl.2022.102963","DOIUrl":"10.1016/j.nicl.2022.102963","url":null,"abstract":"<p><strong>Objective: </strong>Emerging research highlights the importance of basal-temporal cortex, centered on the fusiform gyrus, to both pre-surgical naming ability and post-surgical naming outcomes in temporal lobe epilepsy (TLE). In this study, we investigate whether integrity of the white matter network that interconnects this basal region to the distributed language network affects naming ability and risk for post-surgical naming decline.</p><p><strong>Methods: </strong>Patients with drug-resistant TLE were recruited from two epilepsy centers in a prospective longitudinal study. The pre-surgical dataset included 50 healthy controls, 47 left TLE (L-TLE), and 41 right TLE (R-TLE) patients. All participants completed pre-surgical T1- and diffusion-weighted MRI (dMRI), as well as neuropsychological tests of auditory and visual naming. Nineteen L-TLE and 18 R-TLE patients underwent anterior temporal lobectomy (ATL) and also completed post-surgical neuropsychological testing. Pre-surgical fractional anisotropy (FA) of the white matter directly beneath the fusiform neocortex (i.e., superficial white matter; SWM) and of deep white matter tracts with connections to the basal-temporal cortex [inferior longitudinal fasciculus (ILF) and inferior frontal occipital fasciculus (IFOF)] was calculated. Clinical variables, hippocampal volume, and FA of each white matter tract or region were examined in linear regressions with naming scores, or change in naming scores, as the primary outcomes.</p><p><strong>Results: </strong>Pre-surgically, higher FA in the bilateral ILF, bilateral IFOF, and left fusiform SWM was associated with better visual and auditory naming scores (all ps < 0.05 with FDR correction). In L-TLE, higher pre-surgical FA was also associated with less naming decline post-surgically, but results varied across tracts. When including only patients with typical language dominance, only integrity of the right fusiform SWM was associated with less visual naming decline (p = .0018).</p><p><strong>Discussion: </strong>Although a broad network of white matter network matter may contribute to naming ability pre-surgically, the reserve capacity of the contralateral (right) fusiform SWM may be important for mitigating visual naming decline following ATL in L-TLE. This shows that the study of the structural network interconnecting the basal-temporal region to the wider language network has implications for understanding both pre- and post-surgical naming in TLE.</p>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"5 1","pages":"102963"},"PeriodicalIF":3.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8888987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78408624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of [177Lu]Lu-DOTA-TATE in the treatment of gastroenteropancreatic neuroendocrine tumours: Results of a UK cost-effectiveness modelling study","authors":"Matthew Glover ,&nbsp;Martyn Caplin ,&nbsp;Oscar R. Leeuwenkamp ,&nbsp;Louise Longworth","doi":"10.1016/j.ejcsup.2021.06.003","DOIUrl":"10.1016/j.ejcsup.2021.06.003","url":null,"abstract":"<div><h3>Aim</h3><p>To evaluate the cost-effectiveness of [¹⁷⁷Lu]Lu-DOTA-TATE versus relevant comparators for the treatment of neuroendocrine tumours located in the gastrointestinal tract (GI-NETs) and the pancreas (P-NETs).</p></div><div><h3>Materials and methods</h3><p>A three-state partitioned survival model was developed to perform a cost-utility analysis of [¹⁷⁷Lu]Lu-DOTA-TATE versus standard of care (high dose Octreotide LAR), everolimus and sunitinib. Effectiveness data for SoC, everolimus and sunitinib were obtained from published Kaplan–Meier survival curves. Given a lack of head-to-head effectiveness data, matching adjusted indirect comparisons (MAICs) were performed to population-adjust [¹⁷⁷Lu]Lu-DOTA-TATE survival data based on prognostic factors and derive estimates of relative effectiveness. Health state utilities were estimated from real-world evidence. Drug acquisition costs were taken from nationally published sources (BNF, NICE), and administration costs were based on treatment protocols in [¹⁷⁷Lu]Lu-DOTA-TATE studies, combined with nationally published unit costs (PSSRU, DoH reference costs). Incidence of adverse events were estimated using published sources. A discount rate of 3.5% was applied to both utilities and costs, and deterministic and probabilistic sensitivity analyses were performed. Costs were included from an NHS perspective and presented in 2017/18 GBP (and PPP Euros for base case).</p></div><div><h3>Results</h3><p>In GI-NETs, the incremental cost-effectiveness ratio (ICER) of [¹⁷⁷Lu]Lu-DOTA-TATE compared to SoC and everolimus was £26,528 (€27,672) and £24,145 (€25,186) per QALY, respectively. In P-NETs, the ICER of [¹⁷⁷Lu]Lu-DOTA-TATE compared to SoC was £22,146 (€23,101) or £28,038 (€29,251) dependent on matched population, and £21,827 (€22,766) and £15,768 (€16,445) compared to everolimus and sunitinib, respectively.</p></div><div><h3>Conclusions</h3><p>At a willingness to pay threshold of £30,000, [¹⁷⁷Lu]Lu-DOTA-TATE is likely to be a cost-effective treatment option for GI-NET and P-NET patients versus relevant treatment comparators (NHS perspective).</p></div>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"16 ","pages":"Pages 14-23"},"PeriodicalIF":0.0,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8a/f0/main.PMC8591195.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39606055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can the peptide receptor radionuclide therapy [177Lu]Lu-DOTA-TATE provide a net benefit for NET patients?","authors":"Martyn E. Caplin","doi":"10.1016/j.ejcsup.2021.06.001","DOIUrl":"10.1016/j.ejcsup.2021.06.001","url":null,"abstract":"","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"16 ","pages":"Pages 1-4"},"PeriodicalIF":0.0,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0b/0c/main.PMC8591180.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39606052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matching-adjusted indirect treatment comparison of [177Lu]Lu-DOTA-TATE, everolimus and sunitinib in advanced, unresectable gastroenteropancreatic neuroendocrine tumours: Relative effectiveness of [177Lu]Lu-DOTA-TATE in gastroenteropancreatic neuroendocrine tumours","authors":"Mohid S. Khan ,&nbsp;Elaine Stamp ,&nbsp;Cormac Sammon ,&nbsp;Tessa Brabander ,&nbsp;Wouter W. de Herder ,&nbsp;Marianne E. Pavel","doi":"10.1016/j.ejcsup.2021.06.002","DOIUrl":"10.1016/j.ejcsup.2021.06.002","url":null,"abstract":"<div><p>Head-to-head comparisons of the efficacy of treatments for gastroenteropancreatic neuroendocrine tumours (GEP-NETs) have not yet been reported. This study used a series of matching-adjusted indirect comparisons to indirectly compare the effectiveness of [¹⁷⁷Lu]Lu-DOTA-TATE to everolimus, sunitinib and best supportive care (BSC) for extending progression-free survival and overall survival in patients with advanced, unresectable gastrointestinal (GI)-NETs and P-NETs. The results of the main analysis suggest that after accounting for differences in key prognostic variables, the hazard of progression was 62% (hazard ratio [HR], 0.38; confidence interval [CI]₉₅ 0.25–0.58) and 65% (HR 0.35 CI₉₅ 0.21–0.59) lower in patients with GI-NETs treated with [¹⁷⁷Lu]Lu-DOTA-TATE than in those treated with everolimus and BSC, respectively. Similarly, the hazard of progression was 64% (HR 0.36 CI₉₅ 0.18–0.70), 54% (HR 0.46 CI₉₅ 0.30–0.71) and 79–87% (HR 0.21 CI₉₅ 0.13–0.32; HR 0.13 CI₉₅ 0.08–0.22) lower in patients with P-NET treated with [¹⁷⁷Lu]Lu-DOTA-TATE than in those treated with sunitinib, everolimus and BSC, respectively. The hazard of death was 58% (HR 0.42 CI₉₅ 0.25–0.72), 47% (HR 0.53 CI₉₅ 0.33–0.87) and 44–64% (HR 0.56 CI₉₅ 0.36–0.90; HR 0.34 CI₉₅ 0.20–0.57) lower in P-patients with NET treated with [¹⁷⁷Lu]Lu-DOTA-TATE than in those treated with sunitinib, everolimus and BSC, respectively. While our results must be interpreted with caution given the non-randomised nature of the comparisons and the potential for residual confounding, the magnitude of the effect sizes we observe and their consistency across comparators suggest that [¹⁷⁷Lu]Lu-DOTA-TATE may be a more effective treatment option than everolimus, sunitinib and BSC in advanced, unresectable GEP-NETs.</p></div>","PeriodicalId":11675,"journal":{"name":"Ejc Supplements","volume":"16 ","pages":"Pages 5-13"},"PeriodicalIF":0.0,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a1/94/main.PMC8591206.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39606054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}