British Journal of Cancer最新文献

{"title":"A phase 1 study to assess the safety, tolerability and effectiveness of PV-10 (Rose Bengal Sodium) in neuroendocrine tumours metastatic to the liver.","authors":"Timothy Price, Laura Depauw, Gabrielle Cehic, Eric Wachter, Ruben Sebben, Jessica Reid, Susan Neuhaus, Anas Alawawdeh, Ian D Kirkwood, Rahul Solanki, Mark McGregor, Lisa Leopardi, Dominic Rodrigues, Guy Maddern","doi":"10.1038/s41416-025-02976-9","DOIUrl":"10.1038/s41416-025-02976-9","url":null,"abstract":"<p><strong>Background: </strong>Metastatic neuroendocrine neoplasms (mNEN) require new treatment options. Intralesional (IL) PV-10 is an autolytic chemotherapy that may elicit an adaptive immune response.</p><p><strong>Methods: </strong>This phase 1 study evaluated IL PV-10 administered percutaneously to hepatic lesions in patients with progressive mNEN. IL PV-10 was injected in a single lesion per treatment cycle. A treatment cycle could be repeated after ≥ 6 weeks if multiple targetable lesions were present. The primary endpoint was safety.</p><p><strong>Results: </strong>Twelve patients were enrolled with a median age of 66 years (range 47-79). All patients had progressive disease at enrolment and received prior somatostatin analogues; 10 patients had peptide receptor radionuclide therapy (PRRT) treatment. One lesion was injected per cycle for all 12 patients. Reported grade 3 side effects were photosensitivity (1 patient), face oedema (1 patient), elevated transaminases (1 patient), hypertension (2 patients). Response rate was 42% of injected lesions with patient-level disease control of 84%, PFS 9.4 months and median OS 24.0 months.</p><p><strong>Conclusions: </strong>IL PV-10 elicited no safety concerns. Encouraging evidence of local and systemic disease control was seen in a heavily pre-treated, progressing mNEN population.</p><p><strong>Clinical trial registration number: </strong>NCT02693067.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reflections from the 2024 cambridge symposium on oesophageal cancer.","authors":"Dylan P McClurg, Christopher M Jones, Rebecca C Fitzgerald, Massimiliano di Pietro, J Robert O'Neill","doi":"10.1038/s41416-025-02986-7","DOIUrl":"https://doi.org/10.1038/s41416-025-02986-7","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic profiling of blood platelets identifies a diagnostic signature for pancreatic cancer.","authors":"Weiping Ji, Yichun Xiong, Wei Yang, Zhuo Shao, Xiaoling Guo, Gang Jin, Jianzhong Su, Meng Zhou","doi":"10.1038/s41416-025-02980-z","DOIUrl":"10.1038/s41416-025-02980-z","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer (PaCa) is a deadly malignancy that is often diagnosed at an advanced stage, limiting treatment and reducing survival. There is an urgent need for convenient and accurate diagnostic markers for the early detection of PaCa.</p><p><strong>Methods: </strong>In this multicenter case-control study, we performed transcriptome analysis of 673 platelet samples from different in-house and public cohorts. RNA sequencing and RT-qPCR were used to discover and validate potential platelet biomarkers. A multi-gene signature was developed using binomial generalized linear model and independently validated in multicenter cohorts.</p><p><strong>Results: </strong>Two platelet RNAs, SCN1B and MAGOHB, consistently showed robust altered expression patterns between PaCa and healthy controls across cohorts, as confirmed by both RNA sequencing and RT-qPCR. The diagnostic two-RNA signature, PLA2Sig, demonstrated remarkable performance in detecting PaCa, with area under the receiver operating characteristic curve (AUC) values of 0.808, 0.900, 0.783, and 0.830 across multicenter cohorts. Furthermore, PLA2Sig effectively identified resectable stage I&II PaCa cases with an AUC of 0.812. Notably, PLA2Sig outperformed the traditional serum markers carcinoembryonic antigen and carbohydrate antigen 19-9 in distinguishing PaCa from healthy controls, and is complementary to established blood-based screening biomarkers.</p><p><strong>Conclusion: </strong>These findings provide preliminary but promising evidence for the potential utility of platelet RNAs as an alternative non-invasive liquid biopsy tool for the early detection of PaCa.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imatinib alternating with regorafenib compared to imatinib alone for the first-line treatment of advanced gastrointestinal stromal tumor: The AGITG ALT-GIST intergroup randomized phase II trial.","authors":"Desmond Yip, John Zalcberg, Jean-Yves Blay, Mikael Eriksson, David Espinoza, Timothy Price, Sandrine Marreaud, Antoine Italiano, Neeltje Steeghs, Kjetil Boye, Craig Underhill, Val Gebski, John Simes, Hans Gelderblom, Heikki Joensuu","doi":"10.1038/s41416-025-02983-w","DOIUrl":"https://doi.org/10.1038/s41416-025-02983-w","url":null,"abstract":"<p><strong>Background: </strong>To determine if an alternating regimen of the tyrosine kinase inhibitors imatinib and regorafenib improved outcomes in patients with advanced gastrointestinal stromal tumors.</p><p><strong>Methods: </strong>ALTGIST (NCT02365441) was a randomized phase II study of standard treatment of imatinib (Arm A) compared with an experimental alternating regimen of imatinib and regorafenib (Arm B). Primary outcome was best objective tumor response (OTR) at nine months.</p><p><strong>Results: </strong>Seventy-six eligible patients (Arm A 36, Arm B 40) enrolled were evaluable. Median follow-up was 46.0 months (range 6.5-64.6). Best responses and OTR were similar at 9 months. Eighteen (50.0%) Arm A patients and twelve (30.0%) Arm B patients discontinued treatment due to progressive disease. No Arm A patients stopped protocol therapy due to unacceptable toxicity, with 12 (30.0%) stopping in Arm B. Twelve (33.2%) Arm A patients and 12 (30.0%) Arm B patients experienced at least one serious adverse event, mostly grade 3. Secondary endpoints of PFS at 1 and OS at 1 year were not statistically different.</p><p><strong>Conclusions: </strong>Alternation of imatinib and regorafenib did not impact on 9 months objective response nor on the secondary objectives of PFS and OS. Patients in the alternating arm experienced more toxicity and protocol discontinuations.</p><p><strong>Clinical trial registration: </strong>NCT02365441.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prompt initiation of durvalumab and tremelimumab for unresectable hepatocellular carcinoma in patients with chronic active hepatitis B: a phase 2 clinical trial.","authors":"Yu-Yun Shao, Ching-Tso Chen, Chien-Huai Chuang, Tung-Hung Su, Ming-Chih Ho, Tai-Chung Tseng, Tsung-Hao Liu, Tsung-Che Wu, Ann-Lii Cheng, Chih-Hung Hsu","doi":"10.1038/s41416-025-02978-7","DOIUrl":"https://doi.org/10.1038/s41416-025-02978-7","url":null,"abstract":"<p><strong>Background: </strong>Chronic hepatitis B virus (HBV) infection is an etiology of HCC, but clinical trials using immune checkpoint inhibitors (ICIs) usually exclude patients with chronic active hepatitis B (serum HBV viral load > 2000 IU/mL). This study examined the safety and efficacy of concurrently administering the ICI and anti-HBV medications in this patient population.</p><p><strong>Methods: </strong>In this single-arm phase 2 clinical trial, we enrolled patients with advanced HCC and untreated chronic active hepatitis B. Patients received 1500 mg of durvalumab every 4 weeks alone or in combination with 300 mg of tremelimumab on day 1 (the STRIDE regimen). Anti-HBV treatment with entecavir was simultaneously initiated. The primary endpoint was the rate of HBV reactivation.</p><p><strong>Results: </strong>We enrolled 30 patients, whose mean baseline HBV viral load was 770,986 IU/mL. No patients experienced HBV reactivation or HBV-associated hepatitis. Hepatitis flare was noted in 8 (26.7%) patients, but none of them were associated with HBV reactivation. The objective tumor response rate was 10% and 25% for the durvalumab treatment alone and the STRIDE regimen, respectively.</p><p><strong>Conclusion: </strong>For patients with chronic active hepatitis B, ICI therapy could be promptly initiated as long as anti-HBV medications were administered simultaneously.</p><p><strong>Clinical trial registration: </strong>NCT04294498.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Claudin18.2-positive gastric cancer-specific changes in neoadjuvant chemotherapy-driven immunosuppressive tumor microenvironment.","authors":"Chikanori Tsutsumi, Kenoki Ohuchida, Yutaka Yamada, Yuki Shimada, Masaki Imamura, Kiwa Son, Yuki Mochida, Naoki Katayama, Chika Iwamoto, Nobuhiro Torata, Kohei Horioka, Koji Shindo, Yusuke Mizuuchi, Naoki Ikenaga, Kohei Nakata, Hideya Onishi, Yoshinao Oda, Masafumi Nakamura","doi":"10.1038/s41416-025-02981-y","DOIUrl":"10.1038/s41416-025-02981-y","url":null,"abstract":"<p><strong>Background: </strong>Claudin 18 isoform 2 (CLDN18.2) is a potential therapeutic target in gastric cancer (GC). However, combining chemotherapy with anti-CLDN18.2 antibodies has shown limited efficacy in CLDN18.2-positive GC, and chemotherapy-induced changes in the tumor microenvironment (TME) remain unclear.</p><p><strong>Methods: </strong>This study analyzed 37 GC samples, including 11 CLDN18.2-positive cases, using single-cell RNA sequencing and multiplex immunofluorescence to assess chemotherapy-driven TME changes in CLDN18.2-positive GC.</p><p><strong>Results: </strong>In chemotherapy-treated CLDN18.2-positive GC, cytotoxic natural killer (NK) cells displayed antibody-dependent cytotoxicity (ADCC)-related genes at lower levels than in untreated CLDN18.2-positive GC, while regulatory T cells (Tregs) and tumor-associated macrophages (TAMs) showed TGFB1 expression at higher levels. Additionally, NK cells, Tregs, and TAMs were more abundant in chemotherapy-treated than untreated CLDN18.2-positive GC. These chemotherapy-induced changes were absent in CLDN18.2-negative GC. Cell-cell interaction analysis identified unique interactions in chemotherapy-treated CLDN18.2-positive GC, including CCL5-CCR5 signaling between cytotoxic NK cells (Sender) and effector Tregs (Receptor) and TGFB1-TGFBR signaling between effector Tregs (Sender) and TAMs (Receptor). Cytotoxic NK cells expressed CCL5 at higher levels, CCR5-positive Tregs were more prevalent, and TAMs exhibited higher TGF-β receptor signature scores in chemotherapy-treated than untreated CLDN18.2-positive GC.</p><p><strong>Conclusions: </strong>Our findings indicate that chemotherapy can drive immunosuppressive TME modifications specific to CLDN18.2-positive GC.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune profiling of gastric adenocarcinomas in EU and LATAM countries identifies global differences in immune subgroups and microbiome influence.","authors":"Tessa S Groen-van Schooten, Manuel Cabeza-Segura, Rui M Ferreira, Carolina Martínez-Ciarpaglini, Rita Barros, João Santos-Antunes, Andreia Costa, Edith A Fernández-Figueroa, Leonardo Lino-Silva, Angélica Ixtaccihuatl Hernandez-Guerrero, Erika Ruiz-García, Carmelo Caballero, Hugo Boggino, Cinthia Gauna, Daniel Cantero, Berenice Freile, Federico Esteso, Juan O Connor, Arnoldo Riquelme, Gareth Owen, Erick Riquelme, Juan Carlos Roa, Gonzalo Latorre, Marcelo Garrido, Fiorella Ruiz-Pace, Marc Diez García, Maria Alsina, Florian Lordick, Judith Farrés, Juan Antonio Carbonell-Asins, Rossana Villagrasa, Rita Pereira, Roos E Pouw, Elena Jimenez-Martí, Ana Miralles, Rodrigo Dientsmann, Ceu Figueiredo, Fatima Carneiro, Andrés Cervantes, Sarah Derks, Tania Fleitas","doi":"10.1038/s41416-025-02979-6","DOIUrl":"https://doi.org/10.1038/s41416-025-02979-6","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) patients from European (EU) and especially Latin American (LATAM) countries are underrepresented in previous large-scale multi-omic studies that have identified clinically relevant subgroups. The LEGACY study aimed to profile the molecular and immunological features of GCs from EU and LATAM countries.</p><p><strong>Methods: </strong>Tumor biopsies from 95 EU and 56 LATAM GCs were profiled with immunohistochemistry (CD3, CD8, FOXP3, PD-L1, MSI and HER2), Nanostring mRNA expression analyses, and microbiome sequencing.</p><p><strong>Results: </strong>Immune profiling identified four distinct immune clusters: a T cell dominant cluster with enriched activation pathways, a macrophage dominant cluster and an immune excluded microenvironment which were equally distributed among the countries. A fourth cluster of mostly Mexican patients consisted of excessive T cell numbers accompanied by enhanced cytokine signaling in absence of enhanced antigen presentation and cytotoxicity signatures and a strong association with H. pylori infection.</p><p><strong>Discussion: </strong>Both EU and LATAM countries have GCs with a T cell inflamed microenvironment that might benefit from checkpoint inhibition. We identified a highly inflamed GC subgroup that lacked antigen presentation and cytotoxicity associated with H. pylori CagA-positive strains, suggesting their contribution to tumor immune tolerance. Future studies are needed to unravel whether these cancers benefit from immunotherapy as well.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR-NK cell therapy combined with checkpoint inhibition induces an NKT cell response in glioblastoma.","authors":"F Strassheimer, P Elleringmann, G Ludmirski, B Roller, J Macas, T Alekseeva, P Cakmak, B Aliraj, H Krenzlin, M C Demes, I C Mildenberger, T Tonn, K J Weber, Y Reiss, K H Plate, A Weigert, W S Wels, J P Steinbach, M C Burger","doi":"10.1038/s41416-025-02977-8","DOIUrl":"https://doi.org/10.1038/s41416-025-02977-8","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma is the most aggressive primary brain tumor with limited efficacy of established therapies, and a pronounced immunosuppressive tumor microenvironment. Targeting HER2 with local immunotherapy allows for high tumor specificity in the brain with physiologically very low expression. Monotherapy with CAR-NK cells targeted against HER2 has previously shown efficacy in medium-sized GL261/HER2 tumors.</p><p><strong>Methods: </strong>Advanced GL261/HER2 tumors were treated by local CAR-NK cell injection combined with systemic anti-PD-1 checkpoint blockade. Tumor growth and survival were monitored. In-depth characterization of the microenvironment was performed by multiplex immune fluorescence, spectral flow cytometry and RNAseq.</p><p><strong>Results: </strong>Untreated GL261/HER2 tumors were characterized by local immunosuppression and high PD-L1 expression. Combined treatment with NK-92/5.28.z and systemic anti-PD-1 induced robust anti-tumor response and long-term survival. Multiplex immunofluorescence and spectral flow cytometry showed increased CD4⁺ T cell infiltration in mice treated with CAR-NK cell and anti-PD-1 combination therapy. A cluster of T cells specifically emerging in the combination therapy group expressed markers of NKT cells, which was further verified by immunofluorescence staining.</p><p><strong>Conclusion: </strong>The combination therapy reverted the immunosuppressive tumor microenvironment with increased T and NKT cell infiltration. This resulted in successful treatment of advanced orthotopic tumors refractory to CAR-NK cell monotherapy.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overall survival with maintenance olaparib in platinum-sensitive relapsed ovarian cancer by somatic or germline BRCA and homologous recombination repair mutation status.","authors":"Sandro Pignata, Amit Oza, Geoff Hall, Beatriz Pardo, Radoslaw Madry, David Cibula, Jaroslav Klat, Ana Montes, Rosalind Glasspool, Nicoletta Colombo, Imre Pete, Ana Herrero Ibáñez, Margarita Romeo, Rumyana Ilieva, Constanta Timcheva, Massimo Di Maio, Zahid Bashir, Rosie Taylor, Alan Barnicle, Andrew Clamp","doi":"10.1038/s41416-025-02966-x","DOIUrl":"https://doi.org/10.1038/s41416-025-02966-x","url":null,"abstract":"<p><strong>Background: </strong>The open-label, single-arm, multicentre ORZORA trial (NCT02476968) evaluated maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSR OC) with a germline (g) or somatic (s) BRCA1 and/or BRCA2 mutation (BRCAm) or a non-BRCA homologous recombination repair mutation (non-BRCA HRRm).</p><p><strong>Methods: </strong>Patients were in response to platinum-based chemotherapy after ≥2 prior lines of treatment and underwent prospective central screening for tumour BRCA status, then central gBRCAm testing to determine sBRCAm or gBRCAm status. An exploratory cohort evaluated non-BRCA HRRm in 13 predefined genes. Patients received olaparib 400 mg (capsules) twice daily until investigator-assessed disease progression. Secondary endpoints included overall survival (OS) and safety.</p><p><strong>Results: </strong>177 patients received olaparib. At the final data cutoff (25 June 2021), median OS from study enrolment was 46.8 (95% confidence interval [CI] 37.9-54.4), 43.2 (31.7-NC [not calculated]), 47.4 (37.9-NC) and 44.9 (28.9-NC) months in the BRCAm, sBRCAm, gBRCAm and non-BRCA HRRm cohorts, respectively. No new safety signals were identified.</p><p><strong>Conclusion: </strong>Maintenance olaparib showed consistent clinical activity in the BRCAm and sBRCAm cohorts; exploratory analysis suggested similar activity in the non-BRCA HRRm cohort. These findings highlight that patients with PSR OC, beyond those with gBRCAm, may benefit from maintenance olaparib.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ctDNA variations according to treatment intensity in first-line metastatic colorectal cancer.","authors":"Adrien Grancher, Ludivine Beaussire-Trouvay, Virginie Vernon, Marie Dutherage, Valérie Blondin, Caroline Elie, Karine Bouhier-Leporrier, Marie-Pierre Galais, Tifenn Clabaut, Anne-Laure Bignon, Aurélie Parzy, Alice Gangloff, Lilian Schwarz, Emilie Lévêque, Jean-Christophe Sabourin, Pierre Michel, Nasrin Vasseur, David Sefrioui, André Gilibert, Frédéric Di Fiore","doi":"10.1038/s41416-025-02971-0","DOIUrl":"https://doi.org/10.1038/s41416-025-02971-0","url":null,"abstract":"<p><strong>Background: </strong>Circulating tumor DNA variations (∆ctDNA) were reported to be associated with treatment efficacy in metastatic colorectal cancer (mCRC). The present study evaluated ∆ctDNA according to first-line treatment intensity.</p><p><strong>Methods: </strong>Patients from two prospective ctDNA collections were divided into Group ≤ 2 drugs and Group ≥ 3 drugs. ∆ctDNA were analysed from baseline to cycle 3 or 4 (C_3-4) according to three predefined subgroups: ∆ctDNA ≥ 80%_{_ undetectable}, ∆ctDNA ≥ 80%_{_ detectable}, and ∆ctDNA < 80%. Impact of ∆ctDNA on progression-free survival (PFS) and overall survival (OS) were analysed.</p><p><strong>Results: </strong>Pretreatment ctDNA was detected in 129/152 (84.9%) of patients. A ∆ctDNA ≥ 80%_{_undetectable} was more frequent in Group ≥ 3 than ≤ 2 drugs (respectively 51.5% vs. 32.7%, p = 0.015). Patients with ∆ctDNA ≥ 80%_{_undetectable} had longer survival than other ∆ctDNA subgroups, in Group ≥ 3 drugs (mPFS 11.5 vs 7.8 vs 6.3 months, p = 0.02: mOS 30.2 vs 18.1 vs 16.4 month, p = 0.04) and in Group ≤ 2 drugs (mPFS 8.4 vs 6.0 vs 5.3 months, p = 0.05; mOS 29.6 vs 14.6 vs 14.6 months, p = 0.007).</p><p><strong>Discussion: </strong>Early ∆ctDNA are associated to treatment intensity in first line mCRC with a significant impact on prognosis.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}