ESMO Open最新文献

{"title":"A machine learning-based analysis of nationwide cancer comprehensive genomic profiling data across cancer types to identify features associated with recommendation of genome-matched therapy","authors":"H. Ikushima ,&nbsp;K. Watanabe ,&nbsp;A. Shinozaki-Ushiku ,&nbsp;K. Oda ,&nbsp;H. Kage","doi":"10.1016/j.esmoop.2024.103998","DOIUrl":"10.1016/j.esmoop.2024.103998","url":null,"abstract":"<div><h3>Background</h3><div>The low probability of identifying druggable mutations through comprehensive genomic profiling (CGP) and its financial and time costs hinder its widespread adoption. To enhance the effectiveness and efficiency of cancer precision medicine, it is critical to identify patient characteristics that are most likely to benefit from CGP.</div></div><div><h3>Patients and methods</h3><div>This nationwide retrospective study employed machine learning models to predict the identification of genome-matched therapies by CGP, utilizing a national database covering 99.7% of the patients who underwent CGP in Japan from June 2019 to November 2023. Prediction models were constructed for the overall cancer population, specific cancer types, and adolescent and young adult (AYA) group. The SHapley Additive exPlanations (SHAP) algorithm was applied to elucidate clinical features contributing to model predictions.</div></div><div><h3>Results</h3><div>This study included 60 655 patients [mean age (standard deviation), 60.8 years (14.5 years); 50.1% males]. CGP identified at least one genome-matched therapy in 11 227 cases (18.5%). The best prediction model was eXtreme Gradient Boosting (XGBoost) with an area under the receiver operating characteristic curve of 0.819. Cancer type was the most important predictor (negative for pancreas and positive for breast and lung), followed by the age, presence of liver metastasis, and number of metastatic sites. Analysis of cancer type-specific models identified several organ-specific features, including the sex, interval between the cancer diagnosis and CGP, sampling site, and CGP panel. Among 3455 AYA patients, genome-matched therapies were identified in 459 patients (13.3%). The AYA-specific model achieved an area under the receiver operating characteristic curve of 0.768, with bone tumor identified as a negative predictor in addition to those identified in the overall cancer population model.</div></div><div><h3>Conclusion</h3><div>Several factors predicting the identification of genome-matched therapies through CGP were identified for the overall cancer population and cancer type-specific subpopulations. Expedited CGP is recommended for patients who match the identified profile to facilitate early targeted therapy.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103998"},"PeriodicalIF":7.1,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142698781","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":"Collagen signature adds prognostically significant information to staging for breast cancer","authors":"Z. Li ,&nbsp;D. Kang ,&nbsp;S. Xu ,&nbsp;G. Xi ,&nbsp;L. Li ,&nbsp;L. Zheng ,&nbsp;W. Guo ,&nbsp;F. Fu ,&nbsp;C. Wang ,&nbsp;J. Ma ,&nbsp;X. Han ,&nbsp;S. Xu ,&nbsp;J. Chen ,&nbsp;J. Chen","doi":"10.1016/j.esmoop.2024.103990","DOIUrl":"10.1016/j.esmoop.2024.103990","url":null,"abstract":"<div><h3>Background</h3><div>Tumor-associated collagen signature (TACS) is an independent prognostic factor for breast cancer. However, it is unclear whether the complete collagen signature, including TACS, the TACS-based collagen microscopic features (TCMF1), and the TACS-based nuclear features (TCMF2), can provide additional prognostic information for the current tumor–node–metastasis (TNM) staging system.</div></div><div><h3>Patients and methods</h3><div>We included 941 patients with breast cancer from three cohorts: the training (<em>n</em> = 355), internal (<em>n</em> = 334), and external validation cohorts (<em>n</em> = 252). TACS and TCMF1 were obtained by multiphoton microscopy (MPM). TCMF2 was extracted on the hematoxylin and eosin images colocated with MPM images. They were linearly combined to establish a complete collagen signature score for reclassifying current TNM staging into stage Ⅰ (II and Ⅲ)/low risk and stage Ⅰ (II and Ⅲ)/high risk.</div></div><div><h3>Results</h3><div>The low-risk collagen signatures ‘downstaged’ patients in stage II or Ⅲ, while the high-risk collagen signatures ‘upstaged’ patients with stage Ⅰ tumors. After incorporating the complete collagen signature into the current TNM staging system, the modified staging system had a higher ability to stratify patients [referent, Ⅰ-new; Ⅱ-new, hazard ratio (HR) 8.655, 6.136, and 4.699 in the training, internal validation, and external validation cohorts, respectively; Ⅲ-new, HR 14.855, 11.201, and 13.245 in the corresponding three cohorts, respectively] than the current TNM staging system (referent, Ⅰ; Ⅱ, HR 1.642, 1.853, and 1.371 in the corresponding three cohorts, respectively; Ⅲ, HR 4.131, 4.283, and 3.711 in the corresponding three cohorts, respectively). Furthermore, the modified staging system showed a higher area under the curve than the current TNM staging system (training cohort: 0.843 versus 0.683; internal validation cohort: 0.792 versus 0.661; and external validation cohort: 0.793 versus 0.646).</div></div><div><h3>Conclusions</h3><div>The complete collagen signature is an independent predictor of survival outcomes in breast cancer. It adds significant information about the biological behavior of the disease to staging for breast cancer.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103990"},"PeriodicalIF":7.1,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692354","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":"Challenges in using tumor mutational burden as a post-treatment biomarker","authors":"H. Taban ,&nbsp;Y. Ergun","doi":"10.1016/j.esmoop.2024.103999","DOIUrl":"10.1016/j.esmoop.2024.103999","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103999"},"PeriodicalIF":7.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675376","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 simple prognostic score to predict recurrence after pancreaticoduodenectomy for ampullary carcinoma: results from the French prospective FFCD-AC cohort","authors":"G. Roth ,&nbsp;A. Pellat ,&nbsp;G. Piessen ,&nbsp;K. le Malicot ,&nbsp;L. Schwarz ,&nbsp;C. Gallois ,&nbsp;D. Tougeron ,&nbsp;V. Hautefeuille ,&nbsp;M. Jary ,&nbsp;S. Benoist ,&nbsp;M. Amil ,&nbsp;R. Desgrippes ,&nbsp;M. Muller ,&nbsp;T. Lecomte ,&nbsp;M. Guillet ,&nbsp;C. Locher ,&nbsp;C. Genet ,&nbsp;S. Manfredi ,&nbsp;O. Bouché ,&nbsp;J. Taieb","doi":"10.1016/j.esmoop.2024.103988","DOIUrl":"10.1016/j.esmoop.2024.103988","url":null,"abstract":"<div><h3>Background</h3><div>Ampullary carcinoma (AC) is a rare and severe gastrointestinal cancer with a disease recurrence rate of around 40% after curative-intent surgery and for which the main prognostic factors and adjuvant treatment decision remain a matter of debate.</div></div><div><h3>Patients and methods</h3><div>The FFCD-AC cohort is a French nationwide prospective cohort, which included patients with non-metastatic resected AC. The primary objective of this study was to describe prognostic factors associated with disease-free survival (DFS) and overall survival (OS) after pancreaticoduodenectomy (PD) so as to propose a user-friendly score to better estimate the risk of recurrence. The secondary objective was to study the benefit of adjuvant therapy in terms of DFS and OS.</div></div><div><h3>Results</h3><div>Three hundred and seventy patients with resected AC were included. Median follow-up was 40.6 months. Median age was 68.5 years (32.0-87.0 years), 53.8% of patients were male and 56.1%/37.4%/6.5% had an Eastern Cooperative Oncology Group performance status 0/1/2, respectively. Pathological subtype was intestinal/pancreatobiliary/mixed-undetermined in 29.5%/40.5%/30.0% of patients, respectively. Adjuvant chemotherapy was carried out in 61% of patients. In multivariable analysis, stage III tumor [hazard ratio (HR) 2.86, (95% confidence interval {95% CI}: 1.89-4.17), <em>P</em> &lt; 0.0001], high tumor grade [HR 2.51, (95% CI: 1.42-4.43), <em>P</em> = 0.002] and non-intestinal subtype [HR 1.58, (95% CI: 1.00-2.49), <em>P</em> = 0.052] were associated with shorter DFS. A score based on these three parameters divided patients into low (<em>n</em> = 83), intermediate (<em>n</em> = 133) and high risk (<em>n</em> = 96) with median DFS not reached (NR)/73.1/15.2 months and a median OS NR/86.1/38.2 months, respectively. After propensity score matching, adjuvant chemotherapy was associated with longer DFS [HR 0.57, (95% CI: 0.45-0.72), <em>P</em> &lt; 0.0001] in the cohort.</div></div><div><h3>Conclusion</h3><div>Our integrated score based on three easy-to-collect items—lymph node invasion, tumor grade and non-intestinal subtypes—seems highly prognostic in resected AC and needs to be confirmed in an external validation dataset to help adjuvant treatment decision making.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103988"},"PeriodicalIF":7.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675375","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":"HER2DX genomic test in early-stage HER2-positive breast cancer","authors":"S.M. Tolaney ,&nbsp;N. Tung ,&nbsp;A.C. Wolff ,&nbsp;A. DeMichele ,&nbsp;J.M. Cejalvo ,&nbsp;O. Martínez-Sáez ,&nbsp;T. Pascual ,&nbsp;A.G. Waks ,&nbsp;M. Martín ,&nbsp;E. Ciruelos ,&nbsp;N. Harbeck ,&nbsp;L.A. Carey ,&nbsp;J. Cortés ,&nbsp;G. Curigliano ,&nbsp;A. Prat","doi":"10.1016/j.esmoop.2024.103987","DOIUrl":"10.1016/j.esmoop.2024.103987","url":null,"abstract":"<div><div>Therapies targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer significantly impact patient outcomes, quality of life, and health care systems. While chemotherapy and trastuzumab improve survival in early-stage HER2-positive breast cancer, variability in clinical and biological characteristics leads to different response to therapies and outcomes. Clinical guidelines provide general recommendations, but significant uncertainty persists in identifying an optimal treatment plan for individual patients. The HER2DX genomic test informs treatment decisions for stage 1-3 HER2-positive breast cancer by integrating biological factors and clinical factors (tumor size and nodal status). It provides three scores relevant to patient management: long-term prognosis (risk score), likelihood of achieving pathological complete response (pCR score), and <em>ERBB2</em> mRNA expression (ERBB2 score). This article offers an expert overview of HER2DX, covering score interpretation, clinical applications, ongoing studies, and future directions. By analyzing the genomic profiles of HER2-positive tumors, HER2DX provides independent information regarding therapeutic responses and disease prognosis, thereby enabling physicians to navigate the increasing complexity of managing patients with HER2-positive early breast cancer. Key findings show that HER2DX predicts relapse-free survival and probability of pCR to a variety of neoadjuvant therapy regimens, which aids in personalizing treatment plans that could reduce over-treatment and under-treatment. The article underscores expert recommendations to help integrate HER2DX into clinical practice, aiming to enhance decision making and clinical outcomes.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103987"},"PeriodicalIF":7.1,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142652310","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 tumor-infiltrating lymphocytes in distal extrahepatic bile duct carcinoma","authors":"S.-Y. Jun ,&nbsp;S. An ,&nbsp;S.-M. Hong ,&nbsp;J.-Y. Kim ,&nbsp;K.-P. Kim","doi":"10.1016/j.esmoop.2024.103969","DOIUrl":"10.1016/j.esmoop.2024.103969","url":null,"abstract":"<div><h3>Background</h3><div>The assessment of tumor-infiltrating lymphocytes (TILs) has led to the development of various immunotherapies beyond their predictive potential in gastrointestinal malignancies. However, the clinicopathologic and prognostic values of TILs have yet to be well elucidated in distal extrahepatic bile duct carcinoma (DBDC).</div></div><div><h3>Patients and methods</h3><div>We evaluated stromal TILs (sTILs) and intraepithelial TILs (iTILs) in 405 surgically resected DBDCs to analyze their correlations with overall survival (OS) and recurrence-free survival (RFS) and with clinicopathologic parameters according to the eighth edition of the American Joint Committee on Cancer scheme.</div></div><div><h3>Results</h3><div>High levels of sTIL density (sTIL^High; &gt;5%) and iTIL count (iTIL^High; &gt;3) were found in 245 (61%) and 74 cases (18%), respectively. sTIL^High was more commonly found in larger tumors (<em>P</em> = 0.048) diffusely involving both intra- and extrapancreatic bile ducts (<em>P</em> = 0.013), in tumors with lower T category (<em>P</em> = 0.002), and in tumors without pancreatic (<em>P</em> = 0.003) or duodenal invasion (<em>P</em> &lt; 0.001). iTIL^High was associated with tumors with papillary or nodular growth pattern (<em>P</em> &lt; 0.001) without perineural invasion (<em>P</em> = 0.006). Both sTIL^High and iTIL^High significantly predicted better OS (<em>P</em> = 0.009 and 0.036, respectively) and RFS (<em>P</em> = 0.003 and 0.026, respectively). sTIL consistently provided prognostic predictability in OS, even when tested with different quantitative cut-offs and prognostically stratified OS (<em>P</em> = 0.006) and RFS (<em>P</em> = 0.005) on multivariate analysis. The survival benefit of sTIL^High persisted regardless of the stage in both OS (<em>P =</em> 0.010 for lower stages I and II and <em>P</em> = 0.001 for higher stages III and IV) and RFS (<em>P =</em> 0.004 and 0.025 for lower- and higher-stage tumors, respectively).</div></div><div><h3>Conclusions</h3><div>sTILs were superior to iTILs in predicting survival, and it was shown to be a strong prognosticator for DBDC patients regardless of the stage. The utility of sTILs may extend beyond prognostication to aid in predicting therapeutic responses in DBDC patients.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 11","pages":"Article 103969"},"PeriodicalIF":7.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593152","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":"Corrigendum to “Under-reporting of subjective symptoms and its prognostic value: a pooled analysis of 12 cancer clinical trials”","authors":"L. Arenare ,&nbsp;R. Di Liello ,&nbsp;P. De Placido ,&nbsp;C. Gridelli ,&nbsp;A. Morabito ,&nbsp;S. Pignata ,&nbsp;F. Nuzzo ,&nbsp;A. Avallone ,&nbsp;E. Maiello ,&nbsp;P. Gargiulo ,&nbsp;C. Schettino ,&nbsp;A. Gravina ,&nbsp;C. Gallo ,&nbsp;P. Chiodini ,&nbsp;M. Di Maio ,&nbsp;F. Perrone ,&nbsp;M.C. Piccirillo","doi":"10.1016/j.esmoop.2024.103693","DOIUrl":"10.1016/j.esmoop.2024.103693","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 11","pages":"Article 103693"},"PeriodicalIF":7.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748561","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":"Bespoke ctDNA for longitudinal detection of molecular residual disease in high-risk melanoma patients","authors":"S. Genta ,&nbsp;D.V. Araujo ,&nbsp;K. Hueniken ,&nbsp;C. Pipinikas ,&nbsp;R. Ventura ,&nbsp;P. Rojas ,&nbsp;G. Jones ,&nbsp;M.O. Butler ,&nbsp;S.D. Saibil ,&nbsp;C. Yu ,&nbsp;A. Easson ,&nbsp;A. Covelli ,&nbsp;M.B. Sauder ,&nbsp;C. Fournier ,&nbsp;Z. Saeed Kamil ,&nbsp;P. Rogalla ,&nbsp;D.P. Arteaga ,&nbsp;O. Vornicova ,&nbsp;P. Spiliopoulou ,&nbsp;T.P. Muniz ,&nbsp;A. Spreafico","doi":"10.1016/j.esmoop.2024.103978","DOIUrl":"10.1016/j.esmoop.2024.103978","url":null,"abstract":"<div><h3>Background</h3><div>Locally advanced melanoma has a variable prognosis. Currently, there are no reliable criteria to stratify the risk of disease relapse and identify those patients who will benefit the most from adjuvant therapies. Circulating tumor DNA (ctDNA) is an emerging biomarker measuring the presence of tumor-derived DNA in blood.</div></div><div><h3>Patients and methods</h3><div>We used a bespoke, tumor-informed assay (RaDaR®, NeoGenomics, Inc.) to detect ctDNA in 276 prospectively collected plasma samples from 66 melanoma patients receiving definitive treatment. Collection time points included landmark (after completion of local treatment) and every 3-6 months for up to 2 years.</div></div><div><h3>Results</h3><div>ctDNA was detected in at least one plasma sample in 19 patients (29%), including 6/65 (9%) at landmark (post-surgical sample). Positive ctDNA at landmark was associated with shorter overall survival (OS; median OS 22.7 months versus not reached, log-rank <em>P</em> value = 0.01) and a trend towards a shorter relapse-free survival (RFS; median RFS 15.7 months versus not reached, log-rank <em>P</em> value = 0.07). In 10 patients, ctDNA detection preceded disease relapse by a median of 128 days (range 8-406 days).</div></div><div><h3>Conclusions</h3><div>Our data indicate that ctDNA detection after surgery can identify patients with worse prognosis, and serial ctDNA measurements may enable earlier identification of disease recurrence.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 11","pages":"Article 103978"},"PeriodicalIF":7.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644215","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":"Determining fitness for enfortumab vedotin and pembrolizumab in metastatic bladder cancer: the time to move beyond isolated comorbidity assessments","authors":"B.M. Russell ,&nbsp;D.E.C. Fein ,&nbsp;J. Bellmunt","doi":"10.1016/j.esmoop.2024.103985","DOIUrl":"10.1016/j.esmoop.2024.103985","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 11","pages":"Article 103985"},"PeriodicalIF":7.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616909","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":"Cancer care equality: for the interests of patients with cancer","authors":"Z. Zhu ,&nbsp;X. Pan","doi":"10.1016/j.esmoop.2024.103971","DOIUrl":"10.1016/j.esmoop.2024.103971","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 11","pages":"Article 103971"},"PeriodicalIF":7.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578093","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}