ESMO Open最新文献

{"title":"Adolescent and young adult (AYA) patient involvement and engagement in European health care and research projects: expanding the scope of patient advocacy","authors":"U. Košir ,&nbsp;F. Lysen ,&nbsp;N. Unterecker ,&nbsp;T. Deželak ,&nbsp;E. Sturesson ,&nbsp;I. Shakhnenko ,&nbsp;D. Stark ,&nbsp;K. Rizvi ,&nbsp;A.-S. Darlington ,&nbsp;L. Wee ,&nbsp;W.T.A. van der Graaf ,&nbsp;O. Husson","doi":"10.1016/j.esmoop.2025.104478","DOIUrl":"10.1016/j.esmoop.2025.104478","url":null,"abstract":"<div><div>Patient involvement and engagement (PI&amp;E) in health care and research has gained prominence, shifting towards person-centred approaches and shared decision making. Patients actively participating in health care design and research lead to better quality and efficiency of care. However, implementing meaningful PI&amp;E is challenging and requires adequate resources and evaluation frameworks so that it does not result in tokenism. This is particularly important when considering niche areas like adolescents and young adults (AYAs) with cancer. As AYAs’ unique needs continue to gain recognition, it is becoming increasingly important to incorporate their expertise and diverse perspectives in navigating care. Large-scale European consortia that focus specifically on AYAs offer opportunities to establish successful partnerships with AYAs in the design and creation of the next generation of equitable, diverse, and inclusive cancer care. Concrete actions for meaningful AYA PI&amp;E are discussed.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 3","pages":"Article 104478"},"PeriodicalIF":7.1,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PALB2 germline pathogenic variants: frequency, clinical features, and functional analysis of c.3350+5G>A variant in 3987 Korean cancer patients","authors":"M.-C. Kang ,&nbsp;S. Lee ,&nbsp;H. Kim ,&nbsp;H.-S. Kang ,&nbsp;S.-Y. Jung ,&nbsp;J.-A. Hwang ,&nbsp;J. Kwon ,&nbsp;K.S. Lee ,&nbsp;M.C. Lim ,&nbsp;S.-Y. Park ,&nbsp;S.H. Sim ,&nbsp;W. Choi ,&nbsp;J.E. Park ,&nbsp;E.-H. Cho ,&nbsp;S.-Y. Kong","doi":"10.1016/j.esmoop.2024.104132","DOIUrl":"10.1016/j.esmoop.2024.104132","url":null,"abstract":"<div><h3>Background</h3><div>Germline <em>PALB2</em> variants increase the risks of various cancers. However, these have not been comprehensively investigated in Korean patients with cancer. Our study aimed to evaluate the prevalence and clinical characteristics of <em>PALB2</em> germline variants in Korean patients with cancer and compare these findings with existing data.</div></div><div><h3>Patients and methods</h3><div>We analyzed the clinicopathological and germline next-generation sequencing data of 3987 patients with cancer from the National Cancer Center in Korea. Additionally, we carried out functional analysis of the <em>PALB2</em> splicing variant, c.3350+5G&gt;A.</div></div><div><h3>Results</h3><div>A total of 104 patients presented <em>PALB2</em> germline variants with eight pathogenic variants (PVs), 14 likely pathogenic variants (LPVs), and 82 variants of uncertain significance (VUS). <em>PALB2</em> PV/LPVs were detected at an overall frequency of 0.6% (22/3987) across all patients. Among patients with PV/LPVs, 95.5% were women, and 19 and 3 carriers were diagnosed with breast and ovarian cancer, respectively. Further, we reclassified c.3350+5G&gt;A as a PV rather than VUS, according to the American College of Medical Genetics and Genomics guidelines. Patients with <em>PALB2</em> PV/LPVs had a younger age at first cancer diagnosis (44.6 ± 10.1 years versus 50.2 ± 12.0 years, <em>P</em> = 0.019) and were more likely to have multiple primary organ cancer diagnoses (22.7% versus 8.3%, <em>P</em> = 0.032) compared with those without these variants.</div></div><div><h3>Conclusion</h3><div>Age at first cancer diagnosis and the presence of multiple primary organ cancers are key risk factors for suspected germline <em>PALB2</em> PV. Hence, strategies are required to improve adherence to the National Comprehensive Cancer Network guidelines for cancer screening and family genetic testing among Korean patients with cancer.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 3","pages":"Article 104132"},"PeriodicalIF":7.1,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quality-adjusted survival in patients with metastatic colorectal cancer treated with fruquintinib plus best supportive care: results from FRESCO-2","authors":"S. Stintzing ,&nbsp;J. Tabernero ,&nbsp;T. Satoh ,&nbsp;A. Dasari ,&nbsp;S. Lonardi ,&nbsp;C. Eng ,&nbsp;R. Garcia-Carbonero ,&nbsp;E. Elez ,&nbsp;T. Yoshino ,&nbsp;A.F. Sobrero ,&nbsp;J.C. Yao ,&nbsp;S. Kasper ,&nbsp;D. Arnold ,&nbsp;E. Basic ,&nbsp;M. Granold ,&nbsp;M. Petschulies ,&nbsp;L. Wu ,&nbsp;Y.-C. Chung ,&nbsp;L. Chen ,&nbsp;Z. Yang ,&nbsp;E. Van Cutsem","doi":"10.1016/j.esmoop.2025.104297","DOIUrl":"10.1016/j.esmoop.2025.104297","url":null,"abstract":"<div><h3>Background</h3><div>Treatment toxicity and disease-related symptoms of metastatic colorectal cancer (mCRC) can adversely affect quality of life (QoL). Maintaining QoL is an important treatment goal alongside improving survival outcomes. Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) measures the quality of patients’ survival by assessing the proportion of survival time that is free of symptoms/toxicity. The phase III FRESCO-2 study met its primary endpoint, demonstrating improved overall survival with fruquintinib plus best supportive care (BSC) versus placebo plus BSC [hazard ratio 0.66, 95% confidence interval (CI) 0.55-0.80, <em>P</em> &lt; 0.001]. This <em>post hoc</em> Q-TWiST analysis compared the benefit–risk of fruquintinib versus placebo in all patients randomized in FRESCO-2.</div></div><div><h3>Methods</h3><div>Patients with refractory mCRC in the USA, Europe, Japan, and Australia were randomized to receive fruquintinib (<em>n</em> = 461) or placebo (<em>n</em> = 230) plus BSC until disease progression or unacceptable toxicity. Patients’ survival time was partitioned as follows: time from randomization with grade 3/4 treatment-emergent adverse events (TEAEs) before progression (TOX); time from randomization to progression without grade 3/4 TEAEs (TWiST); and time from progression to death/censoring (REL). Q-TWiST was calculated as the combined utility-weighted mean durations of each health state, assuming utility coefficients of 1 for TWiST and 0.5 for TOX and REL.</div></div><div><h3>Results</h3><div>Q-TWiST was improved when fruquintinib (versus placebo) was added to BSC, with a between-treatment difference of 2.0 months (95% CI 1.5-2.6 months, <em>P</em> &lt; 0.05) and a relative improvement of 31.4%. This effect was primarily driven by the difference in the TWiST component [mean difference 2.1 months (95% CI 1.8-2.5 months), <em>P</em> &lt; 0.05]. Q-TWiST improvements were consistent in all subgroups, including by age, sex, liver metastases, and primary tumor site. The subgroup and sensitivity analysis results confirmed the robustness of the primary analysis findings.</div></div><div><h3>Conclusions</h3><div>Fruquintinib provides a clinically meaningful quality-adjusted survival benefit versus placebo in refractory mCRC.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 3","pages":"Article 104297"},"PeriodicalIF":7.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phase I, first-in-human trial of KO-947, an ERK1/2 inhibitor, in patients with advanced solid tumors","authors":"A.M. Schram ,&nbsp;V. Boni ,&nbsp;A.A. Adjei ,&nbsp;A.J. Olszanski ,&nbsp;M. Vieito ,&nbsp;J.H. Francis ,&nbsp;M. Kurman ,&nbsp;J.M. Ahsan ,&nbsp;B. Tomkinson ,&nbsp;E. Garralda","doi":"10.1016/j.esmoop.2025.104300","DOIUrl":"10.1016/j.esmoop.2025.104300","url":null,"abstract":"<div><h3>Background</h3><div>KO-947, a potent, intravenously administered, extracellular signal-regulated kinase (ERK) inhibitor, has demonstrated activity in preclinical models. This phase I trial of KO-947 evaluated maximum tolerated dose (MTD), safety, and pharmacokinetics in patients with relapsed/refractory solid tumors.</div></div><div><h3>Materials and methods</h3><div>This multicenter, open-label, dose-escalation study evaluated KO-947 0.45-11.3 mg/kg in three schedules. Schedules 1 (0.45-5.4 mg/kg, 1- to 2-hour infusion) and 2 (4.8-9.6 mg/kg, 4-hour infusion) were administered once weekly on a 28-day cycle. Schedule 3 (3.6-11.3 mg/kg, 4-hour infusion) was administered on days 1, 4, and 8 (and on days 11 and 15 for two patients) on a 21-day cycle. The primary objective was determination of MTD and/or recommended phase II dose. Safety analysis included adverse events of special interest (AESIs), namely ocular toxicities and infusion-related reactions (e.g. hypotension, corrected QT interval prolongation). Results from the dose-escalation portion of the phase I study are presented due to trial termination before preplanned cohort expansion cohorts.</div></div><div><h3>Results</h3><div>All 61 enrolled patients (schedules 1/2, <em>n</em> = 34, schedule 3, <em>n</em> = 27) discontinued treatment, mostly owing to disease progression (88% and 67%). The MTD for schedule 1 was 3.6 mg/kg; the maximum administered doses for schedules 2 and 3 were 9.6 and 11.3 mg/kg, respectively. Treatment-related adverse events occurred in 88% of patients in schedules 1/2, and 92% in schedule 3; most common were blurred vision (schedules 1/2, 50.0%; schedule 3, 33.3%). AESIs occurred in 50% of patients in schedules 1/2, and 82% in schedule 3. In all schedules, the best overall response was stable disease.</div></div><div><h3>Conclusions</h3><div>Intravenous KO-947 had a generally tolerable safety profile with minimal gastrointestinal toxicity compared with oral administration of other ERK inhibitors.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 3","pages":"Article 104300"},"PeriodicalIF":7.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-in-human phase I study to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity of PF-07209960 in patients with advanced or metastatic solid tumors","authors":"A. Naing ,&nbsp;M. McKean ,&nbsp;L.S. Rosen ,&nbsp;D. Sommerhalder ,&nbsp;N.M. Shaik ,&nbsp;I.-M. Wang ,&nbsp;C. Le Corre ,&nbsp;K.A. Kern ,&nbsp;N.H. Mishra ,&nbsp;S.K. Pal","doi":"10.1016/j.esmoop.2025.104291","DOIUrl":"10.1016/j.esmoop.2025.104291","url":null,"abstract":"<div><h3>Background</h3><div>PF-07209960 is an antibody–cytokine fusion molecule that consists of a single potency-reduced interleukin-15 (IL-15) mutein and a bivalent high-affinity anti-programmed cell death protein 1 (PD-1) full-length IgG. This phase I study (NCT04628780) evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and potential clinical benefits of PF-07209960 in patients with selected locally advanced or metastatic solid tumors for whom no standard therapy was available.</div></div><div><h3>Materials and methods</h3><div>Escalating doses (1-30 mg) of PF-07209960 were administered subcutaneously once every 2 weeks in 28-day cycles. The primary endpoints included dose-limiting toxicities (DLTs), adverse events (AEs), and laboratory abnormalities. The secondary endpoints included PK, anti-drug antibodies (ADA) and neutralizing antibodies (NAb) against PF-07209960, and tumor response assessed using RECIST version 1.1.</div></div><div><h3>Results</h3><div>Thirty-seven patients received treatment with PF-07209960 (1-, 3-, and 10-mg groups, <em>n</em> = 4 each; 15 mg, <em>n</em> = 3; 20 mg, <em>n</em> = 16; 30 mg, <em>n</em> = 6). The median age was 59.0 years (range 31-88 years). Six (22.2%) patients had DLTs. The most frequently reported treatment-related AEs (TRAEs) (≥50%) were general disorders and administration site condition [21 (56.8%)] and skin and subcutaneous tissue disorders [20 (54.1%)]. The most frequently reported grade ≥3 TRAE was anemia [5 (13.5%)]. Two patients with microsatellite-stable colorectal cancer had confirmed partial response, one each from the PF-07209960 20-mg and 30-mg cohorts, with a duration of response of 9.5 and 3 months, respectively. The rate of ADA was 93.9% (31/33), of which 63.6% (21/33) was treatment induced and 30.3% (10/33) was treatment boosted.</div></div><div><h3>Conclusion</h3><div>PF-07209960 was generally manageable, with potential antitumor activity in some patients.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 3","pages":"Article 104291"},"PeriodicalIF":7.1,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genomic landscape of metastatic clear-cell renal cell carcinoma and its prognostic value: a comprehensive analysis of a large real-world clinico-genomic database","authors":"M. Rizzo ,&nbsp;G. Pezzicoli ,&nbsp;C. Porta ,&nbsp;M. Povero ,&nbsp;L. Pradelli ,&nbsp;E. Sicari ,&nbsp;V.S. Barbiero ,&nbsp;C. Porta","doi":"10.1016/j.esmoop.2025.104294","DOIUrl":"10.1016/j.esmoop.2025.104294","url":null,"abstract":"<div><h3>Background</h3><div>Translating findings on the genomic landscape of metastatic clear-cell renal cell carcinoma (mccRCC) into clinical practice remains challenging. A better understanding of the molecular features of mccRCC could identify a prognostic and/or predictive role for ccRCC genomic alterations.</div></div><div><h3>Patients and methods</h3><div>In this real-world observational study based on the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine, Inc. clinico-genomic database (FH-FMI-CGDB), we investigate the frequency and co-occurrence of genomic alterations in mccRCC patients and assess their prognostic role. Patients (<em>n</em> = 858) were adults diagnosed with mccRCC, with FH electronic health records between 2011 and 2022.</div></div><div><h3>Results</h3><div>The top 10 mutated genes were <em>VHL</em> (73.9%), <em>PBRM1</em> (42.4%), <em>SETD2</em> (25.3%), <em>CDKN2A</em> (20.0%), <em>BAP1</em> (16.4%), <em>CDKN2B</em> (16.0%), <em>KDM5C</em> (14.5%), <em>TP53</em> (12.9%), <em>PTEN</em> (11.7%), and <em>TERT</em> (9.2%). Eight genes showed prognostic value: <em>CDKN2A</em>, <em>CDKN2B</em>, <em>TP53</em>, <em>PTEN</em>, <em>NF2</em>, <em>PIK3CA</em>, and <em>MTAP</em> were linked to worse prognosis, whereas <em>PBRM1</em> was associated with better overall survival (OS). Two of the three identified gene clusters had prognostic value: cluster 1 (<em>VHL</em>, <em>SETD2</em>, <em>PBRM1</em>, <em>KDM5C</em>, <em>NFE2L2</em>) correlated with better OS [adjusted hazard ratio (aHR) 0.63, <em>P</em> &lt; 0.001], whereas cluster 3 (<em>CDKN2A</em>, <em>CDKN2B</em>, <em>BAP1</em>, <em>NF2</em>, <em>MTAP</em>) correlated with shorter OS (aHR 1.36, <em>P</em> = 0.023).</div></div><div><h3>Conclusion</h3><div>We identified eight genes and two gene clusters with prognostic significance for mccRCC. Future research will explore the predictive value of gene clusters in various treatments.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 3","pages":"Article 104294"},"PeriodicalIF":7.1,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Palbociclib exposure in relation to efficacy and toxicity in patients with advanced breast cancer","authors":"S.M. Buijs ,&nbsp;M.I. Mohmaed Ali ,&nbsp;E. Oomen-de Hoop ,&nbsp;C.L. Braal ,&nbsp;N. Wortelboer ,&nbsp;A. van Ommen-Nijhof ,&nbsp;G.S. Sonke ,&nbsp;I.R. Konings ,&nbsp;A. Jager ,&nbsp;N. Steeghs ,&nbsp;H. Siebinga ,&nbsp;R.H.J. Mathijssen ,&nbsp;A.D.R. Huitema ,&nbsp;S.L.W. Koolen","doi":"10.1016/j.esmoop.2025.104290","DOIUrl":"10.1016/j.esmoop.2025.104290","url":null,"abstract":"<div><h3>Background</h3><div>Data on exposure–response or exposure–toxicity relationships of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are limited and inconclusive. We aimed to investigate whether there is an association between palbociclib exposure and progression-free survival (PFS), adverse events (AEs) and dose reductions.</div></div><div><h3>Materials and methods</h3><div>Data were retrieved from the prospective, multicentre SONIA trial in which patients with advanced estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer were randomised to receive CDK4/6i treatment in first versus second line. Blood for pharmacokinetics (PK) was taken at day 15 of cycles 1 and 2 during CDK4/6i treatment. Individual trough concentrations and plasma area under the curves of palbociclib were constructed using a population PK model. Associations with palbociclib exposure were tested using Cox regression for PFS and chi-square tests for AEs or dose reductions.</div></div><div><h3>Results</h3><div>PK data were available for 344 patients. No association between palbociclib exposure and PFS was found. Although patients with higher palbociclib exposure had more dose reductions during their entire CDK4/6i treatment course, this was not reflected by a higher incidence of grade 3-4 AEs in the first 3 months.</div></div><div><h3>Conclusion</h3><div>The absence of an association between palbociclib exposure and PFS and the presence of the association between palbociclib exposure and dose reductions suggest that dose reductions may safely be carried out in case of palbociclib-related toxicity.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 3","pages":"Article 104290"},"PeriodicalIF":7.1,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transarterial chemoembolisation with irinotecan (irinotecan-TACE) as salvage or post-inductive therapy for colorectal cancer liver metastases: effectiveness results from the CIREL study","authors":"D. Arnold ,&nbsp;P.L. Pereira ,&nbsp;R. Iezzi ,&nbsp;A. Gjoreski ,&nbsp;S. Spiliopoulos ,&nbsp;T. Helmberger ,&nbsp;F.M. Gomez ,&nbsp;T. de Baère ,&nbsp;O. Pellerin ,&nbsp;G. Maleux ,&nbsp;H. Prenen ,&nbsp;B. Sangro ,&nbsp;B. Zeka ,&nbsp;N.C. Kaufmann ,&nbsp;J. Taieb","doi":"10.1016/j.esmoop.2025.104292","DOIUrl":"10.1016/j.esmoop.2025.104292","url":null,"abstract":"<div><h3>Background</h3><div>A pan-European, prospective, observational study on the use of irinotecan-eluting transarterial chemoembolisation (irinotecan-TACE) was conducted to evaluate effectiveness outcomes in salvage and post-inductive/consolidation therapy settings of colorectal cancer liver metastases (CRLMs).</div></div><div><h3>Materials and methods</h3><div>One hundred and fifty-two patients were consecutively enrolled between February 2018 and August 2020. All patients received irinotecan-TACE for CRLMs. Response data were assessed by a central independent image review panel according to RECIST v1.1. Prognostic factors for overall survival (OS), hepatic progression-free survival (HPFS), and progression-free survival (PFS) were calculated using multivariable Cox regression. Health-related quality of life (HRQoL) at the first follow-up was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30).</div></div><div><h3>Results</h3><div>One hundred and fifty-two (median age 66 years, 61% male) patients were prospectively enrolled. Overall, the median OS was 14.5 months [95% confidence interval (CI) 11.6-17.0 months]. The median OS (95% CI) of irinotecan-TACE as salvage therapy was 9.9 months (7.4-12.8 months) and the median PFS was 3.8 months (2.9-4.7 months). The median OS for post-inductive/consolidation therapy when used with systemic therapy or thermal ablation was 19.1 months (16.2-24.2 months), the median PFS was 6.0 months (4.5-8.7 months), and the median HPFS was 8.7 months (6.9-10.6 months).Following a multivariable analysis, negative prognostic factors for OS were Eastern Cooperative Oncology Group performance status ≥2 [hazard ratio (HR) 4.3], &gt;50 mm lesion size (HR 2.1), progressive extrahepatic disease (HR 2.0), ≥2 prior systemic therapy lines (HR 2.4), &gt;50% liver involvement (HR 8.5), and treatment plan not completed (HR 2.0). For PFS, progressive disease outside the liver (HR 1.8) and liver involvement of 25%-50% (HR 2.0) or &gt;50% (HR 3.4) were identified as negative prognostic factors. HRQoL was generally stable or improved overall.</div></div><div><h3>Conclusions</h3><div>The results from the largest, pan-European, real-life study on irinotecan-TACE for CRLMs show a comparably long median OS when used as salvage therapy and promising HPFS when used with systemic therapy or thermal ablation as post-inductive/consolidation therapy. With its potential to maintain HRQoL, irinotecan-TACE could be further integrated into systemic treatment pathways.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 3","pages":"Article 104292"},"PeriodicalIF":7.1,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjuvant immunotherapy in the modern management of resectable melanoma: current status and outlook to 2028","authors":"M. Donia ,&nbsp;H. Jespersen ,&nbsp;M. Jalving ,&nbsp;R. Lee ,&nbsp;H. Eriksson ,&nbsp;C. Hoeller ,&nbsp;M. Hernberg ,&nbsp;I. Gavrilova ,&nbsp;L. Kandolf ,&nbsp;G. Liszkay ,&nbsp;H. Helgadottir ,&nbsp;A. Zhukavets ,&nbsp;D. Pianova ,&nbsp;I. Marquez-Rodas ,&nbsp;B. Neyns ,&nbsp;H. Westgeest ,&nbsp;I. Pourmir ,&nbsp;P. Sobczuk ,&nbsp;E. Ellebaek ,&nbsp;T. Amaral","doi":"10.1016/j.esmoop.2025.104295","DOIUrl":"10.1016/j.esmoop.2025.104295","url":null,"abstract":"<div><h3>Background</h3><div>Therapeutic advances have reshaped the treatment landscape for patients with resectable melanoma, particularly for those with stage IIB/C and stage III disease. In this article, we discuss the current status and future outlook of adjuvant immunotherapy for melanoma in Europe.</div></div><div><h3>Results</h3><div>Adjuvant immunotherapy offers significant benefits in terms of recurrence-free survival and distant metastasis-free survival. Uncertainties regarding overall survival (OS) benefits, however, remain. Trials such as Keynote-054, which are expected to provide crucial OS information, have delayed their final analyses until 2027. Additionally, real-world studies have raised questions about the correlation between recurrence-free survival/distant metastasis-free survival improvements observed in clinical trials and OS outcomes in routine clinical practice. These uncertainties have led to ongoing debates about the cost-effectiveness of adjuvant therapies, with disparities in reimbursement policies across Europe reflecting these concerns.</div></div><div><h3>Conclusion</h3><div>Looking ahead to 2028, adjuvant immunotherapy will remain a key option of comprehensive melanoma care, particularly for patients with stage IIB/C and stage III with micrometastatic disease, where neoadjuvant immunotherapy is not feasible.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 3","pages":"Article 104295"},"PeriodicalIF":7.1,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating radiomics, pathomics, and biopsy-adapted immunoscore for predicting distant metastasis in locally advanced rectal cancer","authors":"R. Zhao ,&nbsp;W. Shen ,&nbsp;W. Zhao ,&nbsp;W. Peng ,&nbsp;L. Wan ,&nbsp;S. Chen ,&nbsp;X. Liu ,&nbsp;S. Wang ,&nbsp;S. Zou ,&nbsp;R. Zhang ,&nbsp;H. Zhang","doi":"10.1016/j.esmoop.2024.104102","DOIUrl":"10.1016/j.esmoop.2024.104102","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to develop and validate a nomogram that utilized macro- and microscopic tumor characteristics at baseline, including radiomics, pathomics, and biopsy-adapted immunoscore (IS_B), to accurately predict distant metastasis (DM) in patients with locally advanced rectal cancer (LARC) who underwent neoadjuvant chemoradiotherapy (nCRT).</div></div><div><h3>Materials and methods</h3><div>In total, 201 patients with LARC (91 months of median follow-up) were enrolled. Radiomics features were extracted from apparent diffusion coefficient maps and T2-weighted images. Pathomics features including global pattern (features of the entire image) and local pattern (features of the tumor nuclei) were extracted from whole-slide images of hematoxylin–eosin-stained biopsy specimens. IS_B was calculated from the densities of CD3+ and CD8+ T cells in the tumor region using immunohistochemistry on biopsy specimens. The construction of a predictive model was carried out using the least absolute shrinkage and selection operator-Cox analysis, with performance metrics including the area under the curve (AUC) and concordance index (C-index) utilized for evaluation.</div></div><div><h3>Results</h3><div>Compared with patients with moderate and high IS_B, patients with low IS_B exhibited significantly higher risk scores for radiomics and pathomics signatures. The nomogram showed respective C-indexes of 0.902 and 0.848 for 5-year DM-free survival in the training and test sets, along with corresponding AUC values of 0.950 and 0.872. Patients could be efficiently categorized into low- and high-risk groups for developing DM using the nomogram.</div></div><div><h3>Conclusions</h3><div>The nomogram integrating macroscopic radiological information and microscopic pathological information is effective for risk stratification at baseline in LARC treated with nCRT.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 3","pages":"Article 104102"},"PeriodicalIF":7.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}