ESMO Open最新文献

{"title":"Longer survival with precision medicine in late-stage cancer patients.","authors":"C K Mapendano, A K Nøhr, M Sønderkær, A Pagh, A Carus, T Lörincz, C A Haslund, L Ø Poulsen, A Ernst, J S Bødker, S C Dahl, L Sunde, A H Brügmann, C Vesteghem, I S Pedersen, M Ladekarl","doi":"10.1016/j.esmoop.2024.104089","DOIUrl":"https://doi.org/10.1016/j.esmoop.2024.104089","url":null,"abstract":"<p><strong>Background: </strong>In a per-protocol analysis of molecularly profiled patients with treatment-refractory, end-stage cancer discussed at the National Molecular Tumor Board (NMTB), we aimed to assess the overall survival (OS) outcome of targeted treatment compared with no targeted treatment.</p><p><strong>Materials and methods: </strong>Patients were prospectively included at a single oncological center. Whole exome and RNA sequencing (tumor-normal) were carried out, and cases were presented at the NMTB for discussion of targeted treatment. Treatment was available through a basket trial, by compassionate use or in early clinical trials.</p><p><strong>Results: </strong>One hundred and ninety-six patients were included from 2020 to 2023. In all but three patients a driver variant was disclosed, while 42% had simultaneous affection of more than three oncogenic pathways. In 42% of patients a druggable target was identified but two-thirds did not receive the suggested treatment. The fraction of patients initiating treatment yearly rose from 8% to 22%. For patients treated (N = 30), the clinical benefit rate was 44% and median time on treatment was 3.5 months. Druggable targets were enriched in lung cancers, while patients receiving or not receiving targeted treatment had similar clinical characteristics. The median OS was longer for patients receiving targeted treatment (15 months), but similar for patients with no druggable target and suggested targeted treatment not initiated (5 and 6 months, respectively) (P = 0.004). In multivariate analysis, targeted treatment (hazard ratio 0.43, confidence interval 0.25-0.72), few metastatic sites, and adenocarcinoma histology were predictive of improved OS while alterations of the RTK/RAS pathway were prognostically unfavorable.</p><p><strong>Conclusions: </strong>Tissue-agnostic targeted treatment based on molecular tumor profiling is possible in an increasing fraction of end-stage cancer patients. In those who receive targeted treatment, results strongly suggest a significant survival benefit.</p>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 1","pages":"104089"},"PeriodicalIF":7.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ten-year update of HOBOE phase III trial comparing triptorelin plus either tamoxifen or letrozole or zoledronic acid + letrozole in premenopausal hormone receptor-positive early breast cancer patients.","authors":"A Gravina, P Gargiulo, M De Laurentiis, L Arenare, S De Placido, M Orditura, S Cinieri, F Riccardi, A S Ribecco, C Putzu, L Del Mastro, E Rossi, F Ciardiello, F Di Rella, F Nuzzo, C Pacilio, R Caputo, D Cianniello, V Forestieri, M Giuliano, G Arpino, L Orlando, C Mocerino, C Schettino, M C Piccirillo, C Gallo, F Perrone","doi":"10.1016/j.esmoop.2024.104085","DOIUrl":"https://doi.org/10.1016/j.esmoop.2024.104085","url":null,"abstract":"<p><strong>Background: </strong>The Hormonal Bone Effects (HOBOE) study tested whether adjuvant triptorelin plus either letrozole (L) or zoledronic acid (Z) plus L (ZL) was more effective than tamoxifen (T) in premenopausal patients with hormone receptor-positive (HR+) early breast cancer (BC). Here we report the long-term follow-up analysis.</p><p><strong>Patients and methods: </strong>HOBOE (ClinicalTrials.gov number NCT00412022) is an open-label, three-arm, randomised, phase III trial that involved 16 centres in Italy. One thousand and sixty-five premenopausal patients with HR+ early BC receiving triptorelin were randomly assigned (1 : 1 : 1) to adjuvant T, L or ZL for 5 years. Cancer recurrence, second breast or non-breast cancer and death were considered events for the intention-to-treat disease-free survival (DFS) analysis.</p><p><strong>Results: </strong>As of 24 October 2024 at a median follow-up of 9.2 years, 199 DFS events and 79 deaths were reported. Both ZL and L improved DFS over T, with a hazard ratio (HR) of 0.58 [95% confidence interval (CI) 0.41-0.82; P = 0.002] for ZL versus T and 0.69 (95% CI 0.49-0.97, P = 0.030) for L versus T. No statistically significant difference in OS was reported (global log-rank P = 0.103). The previously reported statistically significant interaction with human epidermal growth factor receptor 2 (HER2) status was confirmed for ZL versus T comparison (P = 0.007).</p><p><strong>Conclusion: </strong>In this updated analysis, L plus triptorelin, with or without Z, demonstrated a statistically significant DFS improvement over T plus triptorelin for the adjuvant treatment of early BC in premenopausal patients.</p>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 1","pages":"104085"},"PeriodicalIF":7.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Actionable mutations in early-stage ovarian cancer according to the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT): a descriptive analysis on a large prospective cohort.","authors":"F Camarda, L Mastrantoni, C Parrillo, A Minucci, F Persiani, D Giannarelli, T Pasciuto, F Giacomini, E De Paolis, M Manfredelli, C Marchetti, G F Zannoni, A Fagotti, G Scambia, C Nero","doi":"10.1016/j.esmoop.2024.104090","DOIUrl":"https://doi.org/10.1016/j.esmoop.2024.104090","url":null,"abstract":"<p><strong>Background: </strong>According to the European Society for Clinical Oncology (ESMO) guidelines, the therapeutic algorithm for early-stage epithelial ovarian carcinoma (EOC) is primarily based on grading and histotype. Adjuvant chemotherapy is usually recommended for high-grade tumors and for the International Federation of Gynecology and Obstetrics (FIGO) stage IB-IC; however, overtreatment remains a concern. Conversely, patients truly at higher risk of recurrence currently lack access to additional therapeutic strategies.</p><p><strong>Patients and methods: </strong>This study presents a descriptive analysis of early-stage EOC patients who were prospectively sequenced and stratified into high-, intermediate-, and low-risk groups based on clinicopathological features. Oncogenic alterations were identified using OncoKB and classified according to the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) Tier I-III. The prevalence of molecular findings was first reported for each risk subgroup, followed by an analysis on the cohort of patients who experienced relapse.</p><p><strong>Results: </strong>A total of 180 patients with FIGO stage I-II EOC were enrolled between January 2022 and December 2023; 126 patients (70%) had at least one ESCAT Tier I-III alteration (including 51% high risk, 35% intermediate risk, and 14% low risk); among them, approximately one-quarter (26%, 95% confidence interval 19% to 35%) had an ESCAT Tier I alteration. BRCA1 and BRCA2 alterations were observed in about one-quarter of patients, with BRCA2 often co-altered with POLE mutations (55%, P = 2.1 × 10^-4). Notably, almost all BRCA1 variants were found in high-risk patients. BRAF V600E mutation (ESCAT IC) was found in 2.4% of patients. PIK3CA variants were the most common Tier IIIA alterations found in 59% of patients. Among those who experienced recurrence, 60% had at least one ESCAT Tier I-III alteration, with PIK3CA mutations being the most frequent.</p><p><strong>Conclusions: </strong>These findings highlight the potential for actionable alterations in most early-stage EOC patients and support the exploration of chemotherapy-free regimens for low- to intermediate-risk groups, as well as targeted maintenance therapy for high-risk individuals.</p>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 1","pages":"104090"},"PeriodicalIF":7.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of two machine learning models to predict conversion from primary HER2-0 breast cancer to HER2-low metastases: a proof-of-concept study.","authors":"F Miglietta, A Collesei, C Vernieri, T Giarratano, C A Giorgi, F Girardi, G Griguolo, M Cacciatore, A Botticelli, A Vingiani, G Fotia, F Piacentini, D Massa, F Zanghì, M Marino, G Pruneri, M Fassan, A P Dei Tos, M V Dieci, V Guarneri","doi":"10.1016/j.esmoop.2024.104087","DOIUrl":"https://doi.org/10.1016/j.esmoop.2024.104087","url":null,"abstract":"<p><strong>Background: </strong>HER2-low expression has gained clinical relevance in breast cancer (BC) due to the availability of anti-HER2 antibody-drug conjugates for patients with HER2-low metastatic BC. The well-reported instability of HER2-low status during disease evolution highlights the need to identify patients with HER2-0 primary BC who may develop a HER2-low phenotype at relapse. In response to the urgency of maximizing treatment access, we utilized artificial intelligence to predict this occurrence.</p><p><strong>Patients and methods: </strong>We included a large multicentric retrospective cohort of patients with BC who underwent tissue resampling at relapse. The dataset was preprocessed to address relevant issues such as missing data, feature abundance, and target class imbalance. We then trained two models: one focused on explainability [Extreme Gradient Boosting (XGBoost)] and another aimed at performance (an ensemble of XGBoost and support vector machine).</p><p><strong>Results: </strong>A total of 1200 patients were included in this study. Among 386 patients with HER2-0 primary BC and matched HER2 status at relapse, 42.5% (n = 157) converted to a HER2-low phenotype. The explainable model achieved a balanced accuracy of 58%, with a sensitivity of 53% and a specificity of 64%. The most important variables for this model were primary BC phenotype [mean Shapley value (SHAP) 0.540], primary BC histological type (SHAP 0.101), grade (SHAP 0.182), and sites of relapse (SHAP 0.008-0.213). The ensemble model had a balanced accuracy of 64%, with a sensitivity of 75% and a specificity of 53%.</p><p><strong>Conclusions: </strong>This work represents one of the first proof-of-concept applications of machine learning models to predict a highly relevant phenomenon for drug access in modern BC oncology. Starting with an explainable model and subsequently integrating it with an ensemble approach enabled us to enhance performance while maintaining transparency, explainability, and intelligibility.</p>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 1","pages":"104087"},"PeriodicalIF":7.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Globalization of clinical trials in oncology: a worldwide quantitative analysis.","authors":"F Izarn, J Henry, S Besle, I Ray-Coquard, J-Y Blay, B Allignet","doi":"10.1016/j.esmoop.2024.104086","DOIUrl":"https://doi.org/10.1016/j.esmoop.2024.104086","url":null,"abstract":"<p><strong>Background: </strong>Over the past two decades, the globalization of oncology clinical trials has expanded, yet significant disparities persist across countries. This study aimed to evaluate these geographical inequalities, the evolution of trial phases, and the adherence to ethical standards according to the World Bank's income group.</p><p><strong>Materials and methods: </strong>The ClinicalTrials.gov database was searched and recorded in June 2024. We analyzed data from 87 748 oncology clinical trials conducted between 2000 and 2021, across high-income (HICs), upper-middle-income (UMICs), lower-middle-income (LMICs), and low-income countries. Key metrics included trial density, funding sources, registration timing, and trial phase distribution.</p><p><strong>Results: </strong>The number of oncology trials increased significantly, with a mean absolute annual rise of 266.6 trials, with China currently being the leading site of early- and validation-phase trials. While HICs still present the highest trial densities, UMICs showed a notable increase in early-phase trials, reflecting a shift in research dynamics. However, despite these advances, 76.4% of countries still had no new trials initiated by 2024. Additionally, ethical practices saw improvement from 2005 to 2021 with an increase in pre-commencement registration (from 9.2% to 58%, P < 0.0001), and more validation-phase trials with a survival variable as the primary outcome (from 40% to 59.6%, P < 0.0001).</p><p><strong>Conclusions: </strong>Despite the growth in oncology clinical trials, significant disparities in trial distribution and access remain, especially in LMICs. Continued investments in research infrastructure and adherence to ethical standards are crucial to ensure that clinical research benefits are equitably distributed, particularly in regions with the greatest need for advanced cancer therapies.</p>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 1","pages":"104086"},"PeriodicalIF":7.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the sarcoma center: establishing the Sarcoma HASM network-a Hub and Spoke Model network for global integrated and precision care.","authors":"B Fuchs, A Gronchi","doi":"10.1016/j.esmoop.2024.103734","DOIUrl":"10.1016/j.esmoop.2024.103734","url":null,"abstract":"<p><p>The landscape of sarcoma treatment has evolved significantly, transitioning from amputations to limb-sparing surgeries, underpinned by advancements in multidisciplinary strategies. The establishment of specialized sarcoma centers has been pivotal, though challenges in accessibility and expertise persist. This manuscript proposes the Sarcoma Hub and Spoke Model (HASM) network to address these issues, enhancing coordination and expanding access to specialized care. The HASM network centralizes complex case management at hubs while peripheral spokes manage routine diagnostics and treatments, optimizing resource use and ensuring patient-centered care. Integration with digital interoperable platforms facilitates real-time/real-world data exchange, supports multidisciplinary team meetings, and enables advanced predictive analytics such as Sarcoma Digital Twins and causal machine learning for personalized treatment. The Sarcoma Care Data Warehouse further enhances this model by aggregating comprehensive patient data, supporting quality assessment and continuous improvement. This innovative approach aims to set a new standard for sarcoma care, leveraging technology and collaborative expertise to improve outcomes globally.</p>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"103734"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791337","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":"Nivolumab plus relatlimab and nivolumab plus ipilimumab for patients with advanced renal cell carcinoma: results from the open-label, randomised, phase II FRACTION-RCC trial.","authors":"T K Choueiri, T M Kuzel, S S Tykodi, E Verzoni, H Kluger, S Nair, R Perets, S George, H Gurney, R K Pachynski, E Folefac, V Castonguay, C-H Lee, U Vaishampayan, W H Miller, P Bhagavatheeswaran, Y Wang, S Gupta, H DeSilva, C-W Lee, B Escudier, R J Motzer","doi":"10.1016/j.esmoop.2024.104073","DOIUrl":"10.1016/j.esmoop.2024.104073","url":null,"abstract":"<p><strong>Background: </strong>The Fast Real-time Assessment of Combination Therapies in Immuno-ONcology study in patients with aRCC (FRACTION-RCC) was designed to assess new immuno-oncology (IO) combinations in patients with advanced renal cell carcinoma (aRCC). We present results in IO-naive patients treated with nivolumab (NIVO) + relatlimab (RELA) or NIVO + ipilimumab (IPI) in track 1.</p><p><strong>Methods: </strong>The open-label, randomised, phase II FRACTION-RCC trial enrolled patients with aRCC from 32 hospitals and cancer centres across six countries. Patients were enrolled in track 1 (IO-naive) or track 2 (IO-experienced). IO-naive patients were stratified by previous tyrosine kinase inhibitor therapy and randomised to NIVO (240 mg) + RELA (80 mg) intravenously once every 2 weeks or NIVO (3 mg/kg) + IPI (1 mg/kg) intravenously once every 3 weeks for four doses, followed by NIVO (480 mg) once every 4 weeks, each up to ∼2 years. The primary endpoints were objective response by investigator (RECIST version 1.1), duration of response (DOR), and progression-free survival (PFS) rate at 24 weeks. Safety was a secondary endpoint; biomarker analyses were exploratory.</p><p><strong>Results: </strong>FRACTION-RCC enrolled patients between 2 February 2017 and 23 January 2020. In track 1, 30 patients each were treated with NIVO + RELA or NIVO + IPI (clinical database lock, 1 November 2021). With NIVO + RELA [median follow-up, 48.6 months; interquartile range (IQR) 46.9-51.7 months], objective response was 30% [95% confidence interval (CI) 15% to 49%], with 33 weeks (95% CI 16-53 weeks) median DOR. The PFS rate at 24 weeks was 43% (95% CI 25% to 60%). With NIVO + IPI (median follow-up, 48.7 months; IQR 47.1-52.0 months), the objective response was 20% (95% CI 8% to 39%), with the median DOR not reached (95% CI 33 weeks-not estimable). The PFS rate at 24 weeks was 49% (95% CI 29% to 66%). Higher baseline lymphocyte activation gene 3 (LAG-3) and programmed death-ligand 1 (PD-L1) expression levels were detected among track 1 NIVO + RELA responders. Grade 3-4 treatment-related adverse events were reported in 4/30 (13%) patients treated with NIVO + RELA and 10/30 (33%) patients treated with NIVO + IPI. No deaths were attributed to study treatments.</p><p><strong>Conclusions: </strong>Results showed antitumour activity and manageable safety with NIVO + RELA. Findings also support NIVO + IPI as an effective combination regimen in IO-naive patients with aRCC.</p>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"104073"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791345","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":"Uncertainties about the benefit-risk balance of oncology medicines assessed by the European Medicines Agency.","authors":"A C Taams, C A Herberts, A C G Egberts, N Zafiropoulos, F Pignatti, L T Bloem","doi":"10.1016/j.esmoop.2024.103991","DOIUrl":"10.1016/j.esmoop.2024.103991","url":null,"abstract":"<p><strong>Background: </strong>Drug regulators assess and describe uncertainties regarding treatment outcomes and the benefit-risk balance of newly authorised medicines. We aimed to evaluate the type and number of uncertainties described in the benefit-risk assessment for initial marketing authorisations of oncology medicines assessed by the European Medicines Agency (EMA). We also aimed to develop a systematic classification of uncertainties to contribute to improved communication about uncertainties.</p><p><strong>Materials and methods: </strong>We included all medicines containing a new active substance assessed by the EMA and granted an initial marketing authorisation by the European Commission in 2011-2022 for an oncology indication. We extracted characteristics of these oncology medicines and uncertainties described under the benefit-risk balance section of European public assessment reports. Uncertainties were categorised and their frequencies stratified according to time of marketing authorisation, and medicine and regulatory characteristics.</p><p><strong>Results: </strong>In total, 121 oncology medicines were included for which 800 (median 6, range 0-23) uncertainties were identified. Uncertainties were classified into five categories: safety (n = 404, 51%), efficacy (n = 322, 40%), pharmacology (n = 58, 7%), use in clinical practice (n = 10, 1%), and quality (n = 6, 1%). Among 27 subcategories, most uncertainties were related to specific adverse events (n = 156, 20%), effect size (n = 155, 20%), safety in subpopulations (n = 124, 16%), or efficacy in subpopulations (n = 88, 11%). The type of medicine (P = 0.012), type of marketing authorisation (P = 0.001), and year of marketing authorisation (P = 0.007) were associated with the number of uncertainties per medicine, with the highest number observed for cell and gene therapies [8 (3-23)], medicines granted conditional marketing authorisation [7 (3-23)], and medicines authorised in 2019-2022 [7 (2-23)].</p><p><strong>Conclusion: </strong>At the time of initial marketing authorisation of oncology medicines, uncertainties about their benefit-risk balance most often concerned safety aspects, followed by efficacy. The number of uncertainties was highest for cell and gene therapies, conditionally authorised medicines, and medicines authorised in recent years.</p>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"103991"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806032","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 clinical dilemma of high-risk stage II colon cancer: are we truly prepared to withdraw oxaliplatin?","authors":"J Taieb, A Gandini, J F Seligmann, C Gallois","doi":"10.1016/j.esmoop.2024.104072","DOIUrl":"10.1016/j.esmoop.2024.104072","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"104072"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766872","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":"Prognostic value of radiologic and pathological response in colorectal cancer liver metastases upon systemic induction treatment: subgroup analysis of the CAIRO5 trial.","authors":"M J G Bond, C Mijnals, K Bolhuis, M J van Amerongen, M R W Engelbrecht, J J Hermans, K P van Lienden, A M May, R-J Swijnenburg, C J A Punt","doi":"10.1016/j.esmoop.2024.104075","DOIUrl":"10.1016/j.esmoop.2024.104075","url":null,"abstract":"<p><strong>Background: </strong>RECIST may not be optimal for assessing treatment response with current systemic regimens. We evaluated RECIST, morphologic, and pathologically documented response (pathological response) in patients with initially unresectable colorectal cancer liver-only metastases (CRLM).</p><p><strong>Patients and methods: </strong>Four hundred and eighty-nine patients from the phase III CAIRO5 trial were included who were treated with FOLFOX/FOLFIRI/FOLFOXIRI and bevacizumab or panitumumab. The association of the different response tools with overall survival (OS) was evaluated for all patients, and with early recurrence (<6 months) for patients after complete local treatment.</p><p><strong>Results: </strong>In the overall population, suboptimal [hazard ratio (HR) 1.10, 95% confidence interval (CI) 0.83-1.47] and optimal (HR 0.95, 95% CI 0.74-1.22) morphologic response were not associated with OS compared with no response. RECIST partial response (HR 0.61, 95% CI 0.49-0.76) and progressive disease (HR 5.77, 95% CI 3.97-8.39) were associated with OS compared with stable disease. In 242 patients who underwent local treatment, suboptimal (HR 1.22, 95% CI 0.76-1.96) and optimal (HR 1.28, 95% CI 0.89-1.86) morphologic response were not associated with OS compared with no response. RECIST partial response was not significantly associated with OS (HR 0.73, 95% CI 0.52-1.01), whereas progressive disease was (HR 19.74, 95% CI 5.75-67.78), compared with stable disease. While major pathological response (HR 0.66, 95% CI 0.44-0.99) was associated with OS, partial pathological response (HR 0.82, 95% CI 0.57-1.19) was not, compared with no pathological response. Pathological response, but not morphologic response and RECIST, was significantly associated with early recurrence (P < 0.001) which occurred in 13/58 (22%) patients with major response, 29/61 (48%) patients with partial response, and 51/88 (58%) patients with no response.</p><p><strong>Conclusions: </strong>Our results show that RECIST but not morphologic response was prognostic for OS. In patients eligible for local treatment, neither RECIST nor morphologic response were associated with early recurrence. Pathological response was associated with early recurrence but is only available post-operatively. Hence, novel preoperative parameters are warranted to predict early recurrence and prevent potentially futile liver surgery.</p>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"104075"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817401","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}