Annals of Oncology最新文献

{"title":"Copenhagen Prospective Personalized Oncology (CoPPO) - Impact of comprehensive genomic profiling in more than 2000 patients in a Phase I setting.","authors":"L Belcaid, M Højgaard, I Tuxen, I Spanggaard, U Lassen, L Robinson, M Rossing, F Bagger, L B Ahlborn, A Y Schmidt, J P Hasselby, E Santoni-Rugiu, F C Nielsen, C W Yde, K Rohrberg","doi":"10.1016/j.annonc.2025.04.004","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.04.004","url":null,"abstract":"<p><strong>Purpose: </strong>Targeted therapy based on the molecular characterization of tumors has been among the most remarkable advances in cancer medicine. Here, we report the impact of almost 10 years of comprehensive genomic profiling in more than 2000 patients with advanced solid tumors at the Phase 1 unit, Department of Oncology, Rigshospitalet, Copenhagen, Denmark.</p><p><strong>Materials and methods: </strong>A prospective, single-center, single-arm open-label study (NCT02290522) was conducted, enrolling patients with advanced cancer referred to a Phase I Unit. Fresh tumor tissue was obtained for whole genome or exome sequencing (germline and somatic), RNA sequencing and SNP array. In cases where fresh tumor tissue was unavailable, archived formalin-fixed paraffin-embedded tumor tissue or circulating tumor DNA extracted from plasma were obtained for targeted panels. Genomic reports were reviewed and discussed by a multidisciplinary tumor board and actionable alterations were classified according to the ESMO scale for the clinical actionability of molecular targets (ESCAT). When possible, patients were treated with regimen matched to the genomic profile.</p><p><strong>Results: </strong>A total of 2147 patients with advanced cancer and exhausted treatment options were enrolled from April 2013 to December 2021. Genomic profiles were obtained in 1866 patients (87%). At least one actionable target was identified in 1062 patients (57%) with a total of 1614 actionable alterations including high RNA CEACAM5 expression (N=559, 35%), homologous recombination deficiency (HRD) alteration (N=314, 20%) and tumor mutational burden-high (N=84, 5%). Overall, 256 patients (24% of the patients with an actionable target) were treated with targeted therapy and among these 14 patients were treated with more than one line of targeted therapy. In total, 274 targeted treatment regimens were initiated, and 259 treatments were evaluable with an overall response (OR) rate of 25% (CI95%: 0.20 - 0.30). ESCAT I/II was associated with improved OR, along with better progression-free survival (PFS) and overall survival (OS).</p><p><strong>Conclusion: </strong>This large-scale study demonstrates that genomic profiling is efficient to identify actionable targets and to match patients to targeted therapies.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962903","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":"Corrigendum to \"Genomic and transcriptional heterogeneity of multifocal hepatocellular carcinoma\": [Annals of Oncology 30 (2019):990-997].","authors":"L X Xu, M H He, Z H Dai, J Yu, J G Wang, X C Li, B B Jiang, Z F Ke, T H Su, Z W Peng, Y Guo, Z B Chen, S L Chen, S Peng, M Kuang","doi":"10.1016/j.annonc.2025.03.020","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.03.020","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958243","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":"The unjustified fear of erdafitinib-induced central serous retinopathy.","authors":"P-P Schauwvlieghe, F Peeters, M Strijbos, C Vulsteke","doi":"10.1016/j.annonc.2025.04.002","DOIUrl":"10.1016/j.annonc.2025.04.002","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957555","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":"Reply to the Letter to the Editor by Perez et al. regarding \"Survival among patients treated with total mesorectal excision or selective watch-and-wait after total neoadjuvant therapy: a pooled analysis of the CAO/ARO/AIO-12 and OPRA randomized phase II trials\".","authors":"J Garcia-Aguilar, H Williams, E Fokas, C Rodel","doi":"10.1016/j.annonc.2025.03.004","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.03.004","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958244","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":"Real-world effectiveness comparison of first-line palbociclib, ribociclib or abemaciclib plus endocrine therapy in advanced HR-positive/HER2-negative BC patients: results from the multicenter PALMARES-2 study.","authors":"L Provenzano, M V Dieci, G Curigliano, M Giuliano, A Botticelli, M Lambertini, G Rizzo, R Pedersini, M Sirico, N La Verde, A Gennari, A Zambelli, A Toss, M Piras, M Giordano, B Tagliaferri, D Generali, D Sartori, D Miliziano, A Menichetti, F Ligorio, C Zurlo, G Griguolo, P P Berton Giachetti, V Faso, C Corti, E Chiappe, S Scagnoli, S Pisegna, C Capasso, C De Angelis, G Arpino, C Criscitiello, V Guarneri, G Pruneri, L Mariani, C Vernieri","doi":"10.1016/j.annonc.2025.03.023","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.03.023","url":null,"abstract":"<p><strong>Background: </strong>The cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) palbociclib, ribociclib and abemaciclib in combination with endocrine therapy (ET) are the standard-of-care, first-line treatment for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (HR-positive/HER2-negative aBC). However, no large head-to-head comparisons of the three CDK4/6is have been conducted so far.</p><p><strong>Patients and methods: </strong>We carried out a multicenter, observational, population-based study to compare the effectiveness of first-line palbociclib, ribociclib and abemaciclib in combination with ET in consecutive HR-positive/HER2-negative aBC patients who initiated the treatment between January 2016 and September 2023 in 18 Italian cancer centers. The primary study endpoint was real-world progression-free survival (rwPFS). Multivariable Cox regression models were used to adjust the association between individual CDK4/6i and rwPFS for clinically relevant variables.</p><p><strong>Results: </strong>Of 1982 patients enrolled in the PALMARES-2 study, 789, 736 and 457 patients received palbociclib, ribociclib and abemaciclib, respectively. Median rwPFS was 34.1 months. In the whole study cohort, abemaciclib and ribociclib were associated with better rwPFS when compared with palbociclib [adjusted hazard ratio (aHR) 0.76, 95% confidence interval (CI) 0.63-0.92, P = 0.004 and aHR 0.83, 95% CI 0.73-0.95, P = 0.007, respectively]. In patients with endocrine-sensitive disease, only abemaciclib was associated with better rwPFS when compared with palbociclib. On the contrary, abemaciclib and ribociclib were more effective than palbociclib in patients who were premenopausal or had endocrine-resistant or luminal B-like disease, while abemaciclib was more effective than ribociclib and palbociclib in patients with de novo metastatic disease, and more effective than palbociclib in patients with poorer Eastern Cooperative Oncology Group performance status. The three CDK4/6is were similarly effective in patients who were older or had bone-only disease.</p><p><strong>Conclusions: </strong>Palbociclib, ribociclib and abemaciclib have different real-world effectiveness in HR-positive/HER2-negative aBC patients. Our findings can support clinicians in choosing the most appropriate CDK4/6i in specific clinical contexts.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963075","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":"Regorafenib as maintenance therapy after first-line doxorubicin-based chemotherapy in advanced non-adipocytic soft tissue sarcomas patients: a double-blind randomised trial.","authors":"N Penel, A Italiano, J Wallet, L Chaigneau, B Verret, N Firmin, S Watson, T Valentin, E Bompas, F Bertucci, M Brahmi, C Henon, A Brunot, M Spalato-Ceruso, M Vanseymortier, E Heyman-Decoupigny, T Ryckewaert, M C Le Deley, C Perrin, J Y Blay","doi":"10.1016/j.annonc.2025.03.024","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.03.024","url":null,"abstract":"<p><strong>Background: </strong>There is no approved maintenance therapy in advanced non-adipocytic soft tissue sarcomas (STS). We explore here the role of regorafenib as a potential maintenance therapy after first-line treatment.</p><p><strong>Patients and methods: </strong>EREMISS (NCT03793361) was a double-blind, placebo-controlled, comparative, 1 : 1 randomised phase II trial assessing the activity and safety of regorafenib (120 mg/day, 3 weeks on/1 week off) in patients with non-adipocytic STS, who had stable disease or partial response after six cycles of doxorubicin-based chemotherapy as first-line treatment of advanced disease. The primary endpoint was progression-free survival (PFS) according to RECIST 1.1 evaluated by blinded central review. Based on the following assumptions: PFS (placebo) = 4 months, expected PFS (regorafenib) = 7 months, hazard ratio (HR) = 0.57, one-sided α = 0.05 and β = 0.10, 110 events and 126 patients were required. This study was supported by French National Cancer Institute, a patient advocacy group and Bayer HealthCare.</p><p><strong>Results: </strong>The study population consisted of 126 patients enrolled in 17 centres from May 2019 to November 2022. Female patients accounted for 55% of total enrolment. The median age was 58 years (range 18-85 years). The most common histological subtype was leiomyosarcoma (59%). The primary objective was assessable in 122 patients (109 events). Median PFS by blinded central review was 3.5 (placebo) versus 5.6 months (regorafenib) (HR = 0.53, 95% CI 0.36-0.78; P = 0.001). Median overall survival was 20.5 versus 27.6 months (HR = 0.78, 95% CI 0.50-1.22, P = 0.28). The proportion of patients with grade ≥3 adverse events was 4.8% (placebo) versus 56.3% (regorafenib). The most common grade ≥3 clinical adverse events in the regorafenib arm were asthenia (9%), arterial hypertension (8%), and rash (8%).</p><p><strong>Conclusion: </strong>This trial met its primary objective, regorafenib significantly delayed disease progression after first-line treatment in advanced non-adipocytic STS. This was associated with a non-significant trend of overall survival improvement.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973572","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":"Efficacy of adjuvant therapy in patients with stage IIIA cutaneous melanoma.","authors":"P Grover, S N Lo, I Li, A M J Kuijpers, F Kreidieh, A Williamson, T Amaral, F Dimitriou, J Placzke, K Olino, M G Vitale, P Saiag, R Gutzmer, C Allayous, R Olofsson Bagge, J Mattsson, N Asher, T J Carter, T M Meniawy, A R Lawless, J A Czapla, L Warburton, C Gaudy-Marqueste, J J Grob, R G Collins, E Zhang, J I Kessels, B Neyns, I Mehmi, O Hamid, M Julve, A J S Furness, K A Margolin, S Lev-Ari, J M Ressler, W Haque, M A Khattak, A Wicky, R Roberts-Thomson, A Arance, G Warrier, M D Schollenberger, P Parente, E Chatziioannou, E J Lipson, O Michielin, J S Weber, C Hoeller, J Larkin, M B Atkins, R Essner, D B Johnson, R J Sullivan, P Nathan, J Schachter, C Lebbe, P A Ascierto, H Kluger, P Rutkowski, R Dummer, C Garbe, P C Lorigan, E Burton, H A Tawbi, J Haanen, M S Carlino, A M Menzies, G V Long","doi":"10.1016/j.annonc.2025.03.021","DOIUrl":"10.1016/j.annonc.2025.03.021","url":null,"abstract":"<p><strong>Background: </strong>Patients with resected American Joint Committee on Cancer eighth edition (AJCC v8) stage IIIA melanoma have been underrepresented in clinical trials of adjuvant drug therapy. The benefit of adjuvant targeted therapy and immunotherapy in this population is unclear.</p><p><strong>Patients and methods: </strong>In this multicentre, retrospective study, patients with stage IIIA melanoma (AJCC v8) who received adjuvant pembrolizumab or nivolumab [anti-programmed cell death protein 1 (PD-1)], BRAF/MEK-targeted therapy dabrafenib + trametinib (TT) or no adjuvant treatment [observation (OBS)] were included. Recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and toxicity rates were examined.</p><p><strong>Results: </strong>A total of 628 patients from 34 centres across Australia, Europe and the United States were identified-256 in anti-PD-1, 80 in TT and 292 in OBS. The median follow-up was 2.6 years (interquartile range 1.6-3.4 years). The presence of some key poor prognostic variables was significantly higher in anti-PD-1 compared with OBS. The 2-year RFS was 79.3% [95% confidence interval (CI) 74.1% to 84.8%] for anti-PD-1, 98.6% (95% CI 96.0% to 100%) for TT and 84.3% (95% CI 79.9% to 89.0%) for OBS. The 2-year DMFS was 88.4% (95% CI 84.3% to 92.8%) in anti-PD-1, 100% in TT and 91.1% (95% CI 87.7% to 94.7%) in OBS. Higher Breslow thickness and higher mitotic rate were associated with higher risk of recurrence in anti-PD-1 and OBS (P < 0.05). Rates of ≥grade 3 toxicities were 10.9% with anti-PD-1 and 17.5% with TT; discontinuation due to toxicity occurred in 13.3% and 21.2%, respectively. Rates of unresolved toxicity at last follow-up were 26.9% in the anti-PD-1 group and 12.5% in the TT group.</p><p><strong>Conclusions: </strong>Stage IIIA melanoma has a modest risk of recurrence. Adjuvant anti-PD-1 did not significantly improve RFS or DMFS compared with OBS alone. Adjuvant TT appears promising over anti-PD-1 or OBS. Outcomes after adjuvant therapy in this population needs further study in larger datasets with longer follow-up or prospective randomised trials.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974418","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":"Safety of adoptive therapy with tumor-infiltrating lymphocytes and high-dose recombinant interleukin-2 in advanced cutaneous melanoma: a systematic review and meta-analysis.","authors":"S Martín-Lluesma, U Dafni, K Vervita, D Karlis, G Dimopoulou, Z Tsourti, G Villacampa, V Galvao, J Lostes, E Muñoz-Couselo, M Rotxés, X Villalobos, S Muñoz, J B A G Haanen, I M Svane, J M Piulats, J Martin-Liberal, A Gros, G Coukos, E Garralda","doi":"10.1016/j.annonc.2025.04.001","DOIUrl":"https://doi.org/10.1016/j.annonc.2025.04.001","url":null,"abstract":"<p><strong>Background: </strong>Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) has consistently shown efficacy in advanced melanoma. Its combination with non-myeloablative but lymphodepleting (NMA-LD) chemotherapy and high-dose interleukin-2 (HD-IL-2) inevitably lead to severe treatment-related adverse events. The systematic recording of the observed toxicities, which is the aim of the present meta-analysis, will further enhance the implementation and management of this treatment schema.</p><p><strong>Methods: </strong>A comprehensive search was conducted in PubMed up to 29 February 2024. In this meta-analysis we focused on studies of treatment-refractory advanced cutaneous melanoma with TILs administered in combination with NMA-LD chemotherapy and HD-IL-2 (≥600,000 IU/kg). Our primary endpoint was severe adverse events (AEs) of grade 3 or higher. The safety data was consistently coded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Findings are synthesized using tables, while pooled estimates for groups of AEs of particular interest are derived from random effect models.</p><p><strong>Results: </strong>A total of 12 HD-IL-2 studies, of 670 patients, with available toxicity information were included in this meta-analysis. Blood toxicities were identified as the most common AEs. In the frame of the formal meta-analysis the pooled estimate of the probability of febrile neutropenia was 60% (95%CI: 36%-83%). The total pooled estimate for the probability of severe \"immunologic reaction\" events, was 4% (95% CI: 1%- 6%), while the respective probability for experiencing a severe AE in MedDRA SOC category 'Infections and infestations' was 8% (95% CI: 4%- 11%). In addition, in total, 9 fatal (grade 5) AEs have been reported, mostly stated as not attributed to the treatment or attributed to NMA/HD-IL-2.</p><p><strong>Conclusions: </strong>TIL-ACT, a new approved and promising therapy for melanoma patients, presents a distinctive toxicity profile that is currently manageable with supportive care methods, with reported toxicities mainly arising from NMA-LD chemotherapy and HD-IL-2, and a low risk of severe immunologic reaction events. Continued systematic recording and publication of adverse events, even the rare ones, and its relation to treatment components, are essential to move the field forward.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969141","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":"Neoadjuvant treatment of HER2-positive breast cancer: has the era of antibody-drug conjugates arrived?","authors":"A Papakonstantinou, T Foukakis","doi":"10.1016/j.annonc.2025.03.022","DOIUrl":"10.1016/j.annonc.2025.03.022","url":null,"abstract":"","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802373","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":"Circulating tumor DNA clearance as a predictive biomarker of pathologic complete response in patients with solid tumors treated with neoadjuvant immune checkpoint inhibitors: a systematic review and meta-analysis.","authors":"C Valenza, E F Saldanha, Y Gong, P De Placido, D Gritsch, H Ortiz, D Trapani, F Conforti, C Cremolini, S Peters, J Mateo, V Subbiah, H A Parsons, A H Partridge, G Curigliano","doi":"10.1016/j.annonc.2025.03.019","DOIUrl":"10.1016/j.annonc.2025.03.019","url":null,"abstract":"<p><strong>Background: </strong>In patients with solid tumors undergoing neoadjuvant immune checkpoint inhibitor (ICI) therapy, identifying biomarkers to predict pathologic complete response (pCR) preoperatively could enhance treatment modulation. Circulating tumor DNA (ctDNA) clearance is a potential predictor of pCR, though its analytical and clinical validity has yet to be established. This systematic review and meta-analysis aims to assess the role of ctDNA clearance as a predictor of pCR in patients with solid tumors treated with neoadjuvant ICIs.</p><p><strong>Materials and methods: </strong>A systematic search of PubMed, EMBASE and conference proceedings up to 5 August 2024 was carried out to identify phase Ib, II or III clinical trials investigating ctDNA clearance and pCR in patients with solid tumors and detectable ctDNA, undergoing neoadjuvant therapy with ICIs. Using a bivariate model, we estimated the pooled sensitivity and specificity of ctDNA clearance in predicting pCR, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio, with 95% confidence intervals (CIs).</p><p><strong>Results: </strong>Thirteen trials involving 380 patients with detectable ctDNA at baseline were included. ctDNA was assessed with a tumor-informed approach in 11 (85%) trials. Overall, 38% of patients achieved pCR and 73% had ctDNA clearance before/at the surgery. Pooled sensitivity was 0.98 (95% CI 0.86-1.00), specificity was 0.53 (95% CI 0.37-0.69), positive likelihood ratio was 2.09 (95% CI 1.48-2.93), negative likelihood ratio was 0.04 (95% CI 0.01-0.26), diagnostic odds ratio was 57.36 (95% CI 8.12-405.12). Significant heterogeneity was observed across studies (I² ∼70% for all metrics), indicating considerable variability in the diagnostic performance.</p><p><strong>Conclusion: </strong>The lack of ctDNA clearance may identify patients unlikely to have a pCR. Instead, the confirmatory power of ctDNA clearance is limited by low specificity and high heterogeneity due to the variability of the assays, and warrants further study. Therefore, clinicians should not rely on the use of ctDNA clearance to inform treatment decisions in the neoadjuvant setting.</p>","PeriodicalId":8000,"journal":{"name":"Annals of Oncology","volume":" ","pages":""},"PeriodicalIF":56.7,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787507","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}