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{"title":"Neoadjuvant cadonilimab plus FLOT chemotherapy in locally advanced gastric/gastroesophageal junction adenocarcinoma: A multicenter, phase 2 study.","authors":"Bo Long, Huinian Zhou, Zeyuan Yu, Junmin Zhu, Hanteng Yang, Zeping Huang, Dengwen Wei, Shigong Chen, Xiaojun Yang, Xiaoning Zhao, Wenjuan Zhang, Hong Yan, Xiaoying Guan, Long Li, Gengyuan Zhang, Hongwei Yu, Shengfu Che, Zhongti Gao, Xiangyan Jiang, Changjiang Luo, Jie Mao, Da Zhao, Yumin Li, Zebin Jiang, Zuoyi Jiao","doi":"10.1016/j.medj.2024.10.008","DOIUrl":"10.1016/j.medj.2024.10.008","url":null,"abstract":"<p><strong>Background: </strong>Treatment with cadonilimab and chemotherapy has shown promise as a first-line treatment for gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. However, its application in neoadjuvant settings has not yet been documented.</p><p><strong>Methods: </strong>This multicenter, phase 2 trial (ChiCTR2200066893) was conducted at four hospitals across China. Treatment-naive patients with locally advanced G/GEJ adenocarcinoma (cT3/4, N+, M0) and who were human epidermal growth factor receptor 2 negative received 3-cycle or 4-cycle neoadjuvant treatment of cadonilimab plus FLOT (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy, followed by gastrectomy and 4-cycle adjuvant FLOT chemotherapy. The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints included major pathological response (MPR), overall response rate (ORR), disease control rate (DCR), R0 resection rate, downstaging rate, and safety.</p><p><strong>Findings: </strong>Between December 23, 2022, and December 15, 2023, 32 of 38 patients completed the scheduled treatment, achieving an R0 resection rate of 100% (32/32). The pCR rate was 21.1% (8/38, 90% confidence interval [CI]: 9.7-32.4), and the MPR rate was 44.7% (17/38, 90% CI: 30.9-58.5). Radiological evaluations were available for 28 of 38 patients by blinded independent central review. The ORR was 60.7% (17/28, 90% CI: 44.7-76.7), and the DCR was 100.0% (28/28, 90% CI: 100.0-100.0). Tumor downstaging occurred in 71.9% of patients (23/32), with consistent efficacy across all populations observed in the subgroup analysis. Grade 3 adverse events occurred in 31.6% of patients without severe safety issues.</p><p><strong>Conclusions: </strong>Neoadjuvant cadonilimab plus FLOT chemotherapy treatment exhibits promising efficacy with manageable toxicities in locally advanced G/GEJ adenocarcinoma, providing preliminary evidence for further investigation.</p><p><strong>Funding: </strong>This study was funded by Akeso Biopharma.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100531"},"PeriodicalIF":12.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629129","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":"A new standard for HCC: The high stakes of TACE-immunotherapy combinations.","authors":"Antonio D'Alessio, Lorenza Rimassa","doi":"10.1016/j.medj.2025.100635","DOIUrl":"10.1016/j.medj.2025.100635","url":null,"abstract":"<p><p>Transarterial chemoembolization (TACE) has long been the standard for intermediate-stage hepatocellular carcinoma (HCC), but two recent phase 3 trials have redefined treatment paradigms. The EMERALD-1¹ and LEAP-012² trials demonstrated significant progression-free survival improvement with TACE combined with durvalumab/bevacizumab or pembrolizumab/lenvatinib, respectively, but doubts remain regarding the patient selection and the toxicity of these novel combinations.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 3","pages":"100635"},"PeriodicalIF":12.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634801","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":"DHDH-mediated D-xylose metabolism induces immune evasion in triple-negative breast cancer.","authors":"Huai-Liang Wu, Yue Gong, Yun-Xiao Ling, Si-Yu Wu, Peng Ji, Qian Zhao, Li-Hua He, Zhi-Ming Shao, Yi-Zhou Jiang, Guang-Yu Liu","doi":"10.1016/j.medj.2024.10.012","DOIUrl":"10.1016/j.medj.2024.10.012","url":null,"abstract":"<p><strong>Background: </strong>Although the prognosis of triple-negative breast cancer (TNBC) has significantly improved in the era of immunotherapy, many TNBC patients are resistant to therapies, and their disease progresses rapidly. Deciphering the metabolic mechanisms regulating anticancer immunity will provide new insights into therapeutic strategies for TNBC.</p><p><strong>Methods: </strong>In this study, we performed bioinformatics analysis in our multi-omics TNBC database and identified that a metabolic enzyme, dihydrodiol dehydrogenase (DHDH), might promote the phenotype of \"cold tumor\" in TNBC. The biological function of DHDH was verified by in vitro and in vivo functional experiments, and the potential molecular mechanism of DHDH promoting TNBC immune escape was further explored.</p><p><strong>Findings: </strong>Mechanistically, DHDH mediated the synthesis and depletion of the substrate D-xylose and inhibited the activation of the proteasome subunit beta type 9 (PSMB9) and further induction of the immune response. We demonstrated that D-xylose supplementation could enhance the proliferation of CD8⁺ T cells and the expression of cytotoxic markers against cocultured DHDH-wild type (WT) cells. Consistently, D-xylose supplementation in vivo promoted CD8⁺ T cell infiltration and the expression of cytotoxic markers and increased the sensitivity of DHDH-overexpressing tumors to immune checkpoint blockade (ICB).</p><p><strong>Conclusions: </strong>Our findings reveal that a D-xylose-regulated PSMB9-dependent pathway governs tumor-intrinsic immunogenicity and, hence, the sensitivity to ICB, which may provide approaches to promote the \"cold-to-hot\" transition in TNBC.</p><p><strong>Funding: </strong>This study was funded by the National Key Research and Development Plan of China, Shanghai Science and Technology Commission, National Natural Science Foundation of China, and China Postdoctoral Science Foundation.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100535"},"PeriodicalIF":12.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629128","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":"Brewing up physician-scientists: An issue of percolation.","authors":"Luay Almassalha, Kyle L MacQuarrie","doi":"10.1016/j.medj.2025.100610","DOIUrl":"10.1016/j.medj.2025.100610","url":null,"abstract":"<p><p>Physician-scientists are a small proportion of the physician workforce. As early-career near-peer physician-scientists, we find value in the intersection of our expertise. This \"percolation\" overcomes both systemic and individual barriers. We propose that efforts to develop relationships between pairs of early-career physician-scientists would bolster the physician-scientist pipeline.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 3","pages":"100610"},"PeriodicalIF":12.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634728","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":"Dexmedetomidine decreases cerebral hyperperfusion incidence following carotid stenting: A double-blind, randomized controlled trial.","authors":"Enqiang Chang, Lingzhi Wu, Xinyi Li, Jinpeng Zhou, Hui Zhi, Min Sun, Guanyu Chen, Jiaqi Bi, Li Li, Tianxiao Li, Daqing Ma, Jiaqiang Zhang","doi":"10.1016/j.medj.2024.09.012","DOIUrl":"10.1016/j.medj.2024.09.012","url":null,"abstract":"<p><strong>Background: </strong>Cerebral hyperperfusion syndrome (CHS) is a severe complication after carotid artery stenting (CAS). Dexmedetomidine (Dex) is an α₂ adrenoceptor agonist with sedative, analgesic, and neuroprotective properties. This randomized, double-blind, placebo-controlled trial (ChiCTR1900024416) aims to investigate whether prophylactic low-dose Dex decreases CH-induced brain injury following CAS.</p><p><strong>Methods: </strong>After obtaining written informed consent, patients aged 18-80 who underwent CAS were enrolled between July 2019 and October 2022. Patients were randomly assigned to receive either intravenous Dex (0.1 μg/kg/h, until post-operative day 3) (n = 80) or placebo (normal saline) (n = 80). The primary endpoint was the incidence of CH and CHS assessed up to the third post-operative day. The secondary endpoints included National Institute of Health Stroke Scale (NIHSS) and Modified Rankin Scale (mRS) scores within 30 days of operation, extubation time, discharge from the hospital within 7 days post-operation, length of hospital stay post-operation, and all-cause 30-day mortality. Blood samples were collected before and after surgery for lipidomics, brain-derived neurotrophic factor (BDNF), and neurofilament light chain (Nfl) measurements. Acceptability, safety, and efficacy were evaluated by Cox model and logistic model.</p><p><strong>Findings: </strong>CH occurred in 30 (37.5%) of 80 patients who received a placebo compared to 9 (11.2%) of 80 patients given Dex (prevalence: odds ratio [OR]: 0.21, 95% confidence interval [CI]: 0.088-0.467; p < 0.001; incidence: hazard ratio [HR]: 0.27, 95% CI: 0.14-0.50; p < 0.001). CHS was significantly higher in the placebo group (13.75%) than in the Dex group (2.5%) (prevalence: [OR]: 0.161, 95% CI: 0.024-0.626; p = 0.020; incidence: [HR]: 0.17, 95% CI: 0.06-0.52; p = 0.009). Dex significantly upregulated BDNF, decreased Nfl, and uniquely increased lysophosphatidylethanolamine.</p><p><strong>Conclusions: </strong>A low prophylactic dose of Dex significantly reduced the incidence of CH and CHS up to 72 h after CAS.</p><p><strong>Funding: </strong>This work was funded by National Natural Science Foundation of China (no. 82271288) and the Henan Provincial Science and Technology Research Project (nos. 242300421192 and JQRC2023004).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100523"},"PeriodicalIF":12.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547983","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":"Effects of gut microbiota on immune checkpoint inhibitors in multi-cancer and as microbial biomarkers for predicting therapeutic response.","authors":"Yufeng Lin, Mingxu Xie, Harry Cheuk-Hay Lau, Ruijie Zeng, Ruyi Zhang, Luyao Wang, Qing Li, Yiwei Wang, Danyu Chen, Lanping Jiang, William Damsky, Jun Yu","doi":"10.1016/j.medj.2024.10.007","DOIUrl":"10.1016/j.medj.2024.10.007","url":null,"abstract":"<p><strong>Background: </strong>Gut bacteria are related to immune checkpoint inhibitors (ICIs). However, there is inconsistency in ICI-associated species, while the role of non-bacterial microbes in immunotherapy remains elusive. Here, we evaluated the association of trans-kingdom microbes with ICIs by multi-cohort multi-cancer analyses.</p><p><strong>Methods: </strong>We retrieved fecal metagenomes from 1,359 ICI recipients with four different cancers (metastatic melanoma [MM], non-small cell lung carcinoma [NSCLC], renal cell cancer [RCC], and hepatocellular carcinoma) from 12 published datasets. Microbiota composition was analyzed using the Wilcoxon rank test. The performance of microbial biomarkers in predicting ICI response was assessed by random forest. Key responder-associated microbes were functionally examined in vitro and in mice.</p><p><strong>Findings: </strong>Trans-kingdom gut microbiota (bacteria, eukaryotes, viruses, and archaea) was significantly different between ICI responders and non-responders in multi-cancer. Bacteria (Faecalibacterium prausnitzii, Coprococcus comes) and eukaryotes (Nemania serpens, Hyphopichia pseudoburtonii) were consistently enriched in responders of ≥2 cancer types or from ≥3 cohorts, contrasting with the depleted bacterium Hungatella hathewayi. Responder-associated species in each cancer were revealed, such as F. prausnitzii in MM and 6 species in NSCLC. These signature species influenced ICI efficacy by modulating CD8⁺ T cell activity in vitro and in mice. Moreover, bacterial and eukaryotic biomarkers showed great performance in predicting ICI response in patients from discovery and two validation cohorts (MM: area under the receiver operating characteristic curve [AUROC] = 72.27%-80.19%; NSCLC: AUROC = 72.70%-87.98%; RCC: AUROC = 83.33%-89.58%).</p><p><strong>Conclusions: </strong>This study identified trans-kingdom microbial signatures associated with ICI in multi-cancer and specific cancer types. Trans-kingdom microbial biomarkers are potential predictors of ICI response in patients with cancer.</p><p><strong>Funding: </strong>Funding information is shown in the acknowledgments.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100530"},"PeriodicalIF":12.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606524","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":"Bile acid metabolites predict multiple sclerosis progression and supplementation is safe in progressive disease.","authors":"Dimitrios C Ladakis, Kimystian L Harrison, Matthew D Smith, Krista Solem, Sachin Gadani, Larissa Jank, Soonmyung Hwang, Farzaneh Farhadi, Blake E Dewey, Kathryn C Fitzgerald, Elias S Sotirchos, Shiv Saidha, Peter A Calabresi, Pavan Bhargava","doi":"10.1016/j.medj.2024.09.011","DOIUrl":"10.1016/j.medj.2024.09.011","url":null,"abstract":"<p><strong>Background: </strong>Bile acid metabolism is altered in multiple sclerosis (MS) and tauroursodeoxycholic acid (TUDCA) supplementation ameliorated disease in mouse models of MS.</p><p><strong>Methods: </strong>Global metabolomics was performed in an observational cohort of people with MS, followed by pathway analysis to examine relationships between baseline metabolite levels and subsequent brain and retinal atrophy. A double-blind, placebo-controlled trial was completed in people with progressive MS (PMS), randomized to receive either TUDCA (2 g/day) or placebo for 16 weeks. Participants were followed with serial clinical and laboratory assessments. Primary outcomes were safety and tolerability of TUDCA, and exploratory outcomes included changes in clinical, laboratory, and gut microbiome parameters.</p><p><strong>Findings: </strong>In the observational cohort, higher primary bile acid levels at baseline predicted slower whole-brain atrophy, brain substructure atrophy, and specific retinal layer atrophy. In the clinical trial, 47 participants were included in our analyses (21 in placebo arm, 26 in TUDCA arm). Adverse events did not differ significantly between arms (p = 0.77). The TUDCA arm demonstrated increased serum levels of multiple bile acids. No significant differences were noted in clinical or fluid biomarker outcomes. Central memory CD4⁺ and Th1/17 cells decreased, while CD4⁺ naive cells increased in the TUDCA arm compared to placebo. Changes in the composition and function of gut microbiota were also noted between the two groups.</p><p><strong>Conclusions: </strong>Bile acid metabolism in MS is linked to brain and retinal atrophy. TUDCA supplementation in PMS is safe, tolerable, and has measurable biological effects that warrant further evaluation in larger trials with a longer treatment duration.</p><p><strong>Funding: </strong>National MS Society grant RG-1707-28601 to P.B., R01 NS082347 from the National Institute of Neurological Disorders and Stroke to P.A.C., and National MS Society grant RG-1606-08768 to S.S.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100522"},"PeriodicalIF":12.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509385","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":"Precision phenotyping for curating research cohorts of patients with unexplained post-acute sequelae of COVID-19.","authors":"Alaleh Azhir, Jonas Hügel, Jiazi Tian, Jingya Cheng, Ingrid V Bassett, Douglas S Bell, Elmer V Bernstam, Maha R Farhat, Darren W Henderson, Emily S Lau, Michele Morris, Yevgeniy R Semenov, Virginia A Triant, Shyam Visweswaran, Zachary H Strasser, Jeffrey G Klann, Shawn N Murphy, Hossein Estiri","doi":"10.1016/j.medj.2024.10.009","DOIUrl":"10.1016/j.medj.2024.10.009","url":null,"abstract":"<p><strong>Background: </strong>Scalable identification of patients with post-acute sequelae of COVID-19 (PASC) is challenging due to a lack of reproducible precision phenotyping algorithms, which has led to suboptimal accuracy, demographic biases, and underestimation of the PASC.</p><p><strong>Methods: </strong>In a retrospective case-control study, we developed a precision phenotyping algorithm for identifying cohorts of patients with PASC. We used longitudinal electronic health records data from over 295,000 patients from 14 hospitals and 20 community health centers in Massachusetts. The algorithm employs an attention mechanism to simultaneously exclude sequelae that prior conditions can explain and include infection-associated chronic conditions. We performed independent chart reviews to tune and validate the algorithm.</p><p><strong>Findings: </strong>The PASC phenotyping algorithm improves precision and prevalence estimation and reduces bias in identifying PASC cohorts compared to the ICD-10-CM code U09.9. The algorithm identified a cohort of over 24,000 patients with 79.9% precision. Our estimated prevalence of PASC was 22.8%, which is close to the national estimates for the region. We also provide in-depth analyses, encompassing identified lingering effects by organ, comorbidity profiles, and temporal differences in the risk of PASC.</p><p><strong>Conclusions: </strong>PASC precision phenotyping boasts superior precision and prevalence estimation while exhibiting less bias in identifying patients with PASC. The cohort derived from this algorithm will serve as a springboard for delving into the genetic, metabolomic, and clinical intricacies of PASC, surmounting the constraints of prior PASC cohort studies.</p><p><strong>Funding: </strong>This research was funded by the US National Institute of Allergy and Infectious Diseases (NIAID).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100532"},"PeriodicalIF":12.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629209","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":"Recurrent late-onset neutropenia following treatment with different B cell-depleting strategies in multiple sclerosis.","authors":"Maria Protopapa, Muriel Schraad, Katrin Pape, Falk Steffen, Livia Steenken, Frauke Zipp, Vinzenz Fleischer, Stefan Bittner","doi":"10.1016/j.medj.2024.10.006","DOIUrl":"10.1016/j.medj.2024.10.006","url":null,"abstract":"<p><strong>Background: </strong>As B cell-depleting therapies in multiple sclerosis (MS) have gained significant importance in the last several years, their long-term safety profile is of considerable clinical interest. Late-onset neutropenia (LON) is a rare, but potentially severe, adverse event that was first described in patients with rheumatic disorders under therapy with rituximab. Ofatumumab was approved in 2021 for the treatment of relapsing-remitting multiple sclerosis (RRMS). Neutropenia occurred in 0.2% of patients in clinical phase 3 trials, and to date, no cases of LON have been reported under ofatumumab treatment.</p><p><strong>Methods: </strong>Here, we report a case of repetitive symptomatic LON under ocrelizumab as well as ofatumumab treatment. Additionally, we review the literature on rare occurrences of LON in patients with MS, neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) undergoing B cell-depleting therapies, including rituximab, ocrelizumab, ofatumumab, inebilizumab, and ublituximab.</p><p><strong>Findings: </strong>In our case, the patient presented with repetitive symptomatic LON under ocrelizumab as well as ofatumumab treatment leading to febrile infections, subsequent use of antibiotics, and application of granulocyte-colony-stimulating factor. After repetitive episodes of LON under both B cell-depleting strategies, cladribine was subsequently initiated. A nine-month follow-up showed a normal neutrophil count and no evidence of disease activity.</p><p><strong>Conclusions: </strong>This case highlights the significance of symptomatic late-onset blood count changes under both ocrelizumab and ofatumumab and emphasizes the importance of continuous monitoring of the differential blood count under B cell-depleting treatment.</p><p><strong>Funding: </strong>This study was supported by the Deutsche Forschungsgemeinschaft (DFG; SFB CRC-TR-128 to F.Z., V.F., and S.B..; SFB 1080 and SFB CRC-1292 to F.Z..; and SFB/TRR 355 to S.B.) and the Hermann and Lilly Schilling Foundation (to S.B.).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100529"},"PeriodicalIF":12.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606527","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":"Combination of immune checkpoint blockade in metastatic colorectal cancers with microsatellite instability: A new standard of care?","authors":"Violaine Randrian, Benoit Rousseau","doi":"10.1016/j.medj.2025.100636","DOIUrl":"10.1016/j.medj.2025.100636","url":null,"abstract":"<p><p>Immunotherapy is highly efficient for the treatment of mismatch-repair-deficient metastatic colorectal cancer. Two recent articles¹^,² challenge the current paradigm of anti-PD-1 monotherapy for the frontline treatment of metastatic mismatch-repair-deficient colorectal cancer, as the combination of an anti-PD-1 and anti-CTLA-4 showed improved response rate and progression-free survival compared to chemotherapy or anti PD-1.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 3","pages":"100636"},"PeriodicalIF":12.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634760","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}