ESMO Open最新文献

{"title":"Measuring financial distress in German cancer patients: development and validation of the Financial Distress of Cancer Assessment Tool (FIAT)","authors":"L. Richter ,&nbsp;S. Pauge ,&nbsp;K. Mehlis ,&nbsp;A. Zueger ,&nbsp;B. Surmann ,&nbsp;V. Mathies ,&nbsp;W. Greiner ,&nbsp;T. Ernst ,&nbsp;E.C. Winkler ,&nbsp;N. Menold","doi":"10.1016/j.esmoop.2024.103992","DOIUrl":"10.1016/j.esmoop.2024.103992","url":null,"abstract":"<div><h3>Background</h3><div>Cancer diagnosis and therapy can lead to significant financial distress for those affected, even in universal health care systems. We present the development and validation of a patient-reported outcome measure for financial distress in German cancer patients.</div></div><div><h3>Methods</h3><div>Validation of the newly developed instrument followed a two-step approach, including two quantitative paper–pencil surveys (<em>N1</em> = 111, <em>N2</em> = 267) with patients of all types of cancer and treatment status at two German university hospitals. Factorial validity, reliability, construct, and criterion validity were assessed using exploratory and confirmatory factor analysis, correlative and linear regression analysis.</div></div><div><h3>Results</h3><div>The Financial Distress of Cancer Assessment Tool (FIAT) comprises 19 items across three domains of subjective financial distress: (i) financial worries; (ii) dissatisfaction across various life domains, and (iii) challenging experiences with authorities and benefit providers (e.g. employment agency, health insurance). Confirmatory factor analysis confirmed the instrument’s factorial structure. Composite reliability (Raykov’s rho) ranges from 0.88 to 0.96, and retest reliability ranges from 0.64 to 0.75. Correlational analyses showed significant associations between FIAT scores and related constructs [e.g. correlations with the EORTC-QLQ-C30 financial distress subscale (Q28) ranging from 0.47 to 0.60], supporting its construct validity. Additionally, higher FIAT scores were significantly associated with lower health-related quality of life measured by Q29 and Q30 of the EORTC-QLQ-C30, with correlations ranging from −0.21 to −0.28. They were also positively correlated with depression (PHQ-4), with correlations ranging from 0.33 to 0.45, and anxiety (PHQ-4) with correlations ranging from 0.25 to 0.36, confirming its criterion validity.</div></div><div><h3>Conclusions</h3><div>The newly developed patient-reported outcome measure is the first reported measurement tool to assess financial distress in German cancer patients. The instrument can be used for research purposes and to enable the provision of coordinated support services.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103992"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746185","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":"Practical treatment strategies and novel therapies in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) advanced breast cancer.","authors":"K Fanucci, A Giordano, T Erick, S M Tolaney, S Sammons","doi":"10.1016/j.esmoop.2024.103997","DOIUrl":"10.1016/j.esmoop.2024.103997","url":null,"abstract":"<p><p>Mutations in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway occur in 30%-40% of patients with advanced hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) breast cancer. For most patients, endocrine therapy with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor is the first-line treatment. Recent studies indicate that adding inavolisib, a PI3Kα inhibitor, to palbociclib/fulvestrant benefits patients with endocrine-resistant HR+/HER2- metastatic breast cancer with a PIK3CA mutation. Alpelisib and capivasertib are both US Food and Drug Administration (FDA) approved in combination with fulvestrant in patients with endocrine-resistant HR+/HER2-, PIK3CA-mutant metastatic breast cancer, both with activity in the post-CDK4/6 setting. Capivasertib added to fulvestrant is the first AKT inhibitor to show a significant progression-free survival benefit with a trend for overall survival benefit and the only approved option for patients with phosphate and tensin homolog (PTEN) or AKT alterations. Toxicity profiles of all agents necessitate careful patient selection. Several mutant-selective and pan-mutant-selective novel inhibitors are under investigation with the potential to improve tolerability and efficacy.</p>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"103997"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823923","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":"Use and outcomes of trastuzumab deruxtecan in HER2-positive and HER2-low metastatic breast cancer in a real-world setting: a nationwide cohort study.","authors":"H Jourdain, A Di Meglio, I Mansouri, D Desplas, M Zureik, N Haddy","doi":"10.1016/j.esmoop.2024.104083","DOIUrl":"10.1016/j.esmoop.2024.104083","url":null,"abstract":"<p><strong>Background: </strong>Since 2020, trastuzumab deruxtecan (T-DXd) has been used in France for patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive or HER2-low metastatic breast cancer (mBC). We aimed to describe the clinical characteristics, outcomes, and potential toxicities among patients receiving T-DXd for HER2-positive and HER2-low mBC.</p><p><strong>Patients and methods: </strong>Using the French National Health Data System (SNDS), we identified patients who initiated T-DXd for mBC from 30 September 2020 to 30 September 2023. Follow-up data were available through 31 December 2023. Patients were categorized into three groups according to HER2 expression and line of treatment: HER2-positive mBC receiving T-DXd in the third (HER2+ 3L) or second line (HER2+ 2L) and HER2-low mBC receiving T-DXd in the second line (HER2-low2L). We describe their characteristics and report the Kaplan-Meier estimates of overall survival (OS) and incidence of hospitalization.</p><p><strong>Results: </strong>The cohort comprised 5890 patients, including 2010 (34.1%) HER2+ 3L, 1260 (21.4%) HER2+ 2L, and 2620 (44.5%) HER2-low2L. For the three respective groups, the median age at inclusion was 59 years [interquartile range (IQR) 51-69 years], 59 years (50-68 years), and 61 years (52-70 years); 34.8%, 30.2%, and 16.0% had brain metastases; 14.2%, 13.7%, and 13.4% had a current or history of cardiovascular disease. Median OS was 30.2 months [95% confidence interval (CI) 28.1-33.5 months] for HER2+ 3L patients, was not reached for HER2+ 2L patients, and was 16.8 months (95% CI 14.5 months-not reached) for HER2-low2L patients. The incidence of hospitalization for cardiac, respiratory, digestive, and hematological disorders was similar for HER2-positive patients treated in the second or third line, whereas HER2-low patients had higher incidence rates for these events.</p><p><strong>Conclusion: </strong>In this large French observational study, T-DXd users were older, had more comorbidities, and had more brain metastases than patients included in registration trials. The rapid expansion of clinical indications of T-DXd calls for proactive surveillance and timely management of potentially life-threatening T-DXd-related toxicity.</p>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"104083"},"PeriodicalIF":7.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812682","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":"Identifying predictors of treatment response and molecular changes induced by neoadjuvant chemotherapy and endocrine therapy in hormone receptor-positive/HER2-negative breast cancer: the NEOENDO translational study☆","authors":"F. Schettini ,&nbsp;F. Brasó-Maristany ,&nbsp;T. Pascual ,&nbsp;N. Lorman-Carbó ,&nbsp;S. Nucera ,&nbsp;M. Bergamino ,&nbsp;P. Galván ,&nbsp;B. Conte ,&nbsp;E. Seguí ,&nbsp;I. García Fructuoso ,&nbsp;R. Gómez Bravo ,&nbsp;A.B. Rodríguez ,&nbsp;O. Martínez-Sáez ,&nbsp;N. Chic ,&nbsp;M. Vidal ,&nbsp;B. Adamo ,&nbsp;B. González-Farre ,&nbsp;E. Sanfeliu ,&nbsp;I. Cebrecos ,&nbsp;E. Mensión ,&nbsp;A. Prat","doi":"10.1016/j.esmoop.2024.103989","DOIUrl":"10.1016/j.esmoop.2024.103989","url":null,"abstract":"<div><h3>Background</h3><div>Predictors of response to neoadjuvant chemotherapy (NACT) and endocrine therapy (NET) in hormone receptor-positive (HoR+)/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) are required. Also, pathological and molecular changes induced by both strategies and their impact on patients’ outcomes have not been reported so far.</div></div><div><h3>Patients and methods</h3><div>In a cohort of 186 patients with early-stage HoR+/HER2-negative BC treated with NACT or NET, we assessed the association of baseline main clinicopathological features and PAM50 gene expression (GE), intrinsic subtypes (IS) and risk-of-relapse (ROR-P) score with pathological outcomes according to treatment strategy. Molecular NACT/NET-induced changes were described and compared, along with their associations with event-free survival (EFS). Comparison of the two cohorts after propensity score matching (PSM) was used as sensitivity analysis. Molecular changes were confirmed in cell lines.</div></div><div><h3>Results</h3><div>NACT was associated with higher rates of residual cancer burden (RCB)-0/I than NET in the overall population (38.2% versus 13.5%, <em>P</em> &lt; 0.001) and after PSM (<em>P</em> = 0.036). PAM50 non-luminal IS were the only independent and positive predictor of RCB-0/I (<em>P</em> = 0.024) in the NACT cohort, while <em>MMP11</em> messenger RNA levels were the only independent and negative predictor (<em>P</em> = 0.014) in the NET cohort. Both treatments shifted the tumor types toward less aggressive forms (i.e. PAM50 luminal A/normal-like), lowered the risk of recurrence in terms of ROR-P, up-regulated selected immune genes and PAM50 basal-like-related genes/signature and significantly downregulated proliferation-/luminal-/HER2-related genes/signatures, though NACT more than NET. Molecular findings were confirmed after PSM. A net reduction in proliferation-related genes and ROR-P was confirmed in cell lines with chemotherapy and endocrine therapy. Different baseline molecular features associated with diverse kind of responses (ROR-P downstaging, Ki67 reduction or pathological responses) with NACT and NET. Decreasing ROR-P and transitioning the tumor subtype to resemble normal tissue (i.e. PAM50 normal-like) suggested improved EFS.</div></div><div><h3>Conclusions</h3><div>NACT was more effective in the molecular and dimensional tumor ‘downstaging’ than NET but baseline molecular features associated with differential responses according to treatment strategy. Examining baseline and post-treatment GE might help tailor more personalized and effective care.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103989"},"PeriodicalIF":7.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720974","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":"Maintenance with 5-FU/LV-aflibercept after induction with FOLFIRI-aflibercept versus FOLFIRI-aflibercept until progression as second-line treatment in older adults with metastatic colorectal cancer: the AFEMA phase II randomized trial","authors":"P. García-Alfonso ,&nbsp;E. Elez ,&nbsp;J. Soto-Alsar ,&nbsp;D. Páez ,&nbsp;A. Fernández-Montes ,&nbsp;B. Graña ,&nbsp;A. Salud ,&nbsp;A. Yubero ,&nbsp;M.A. Gómez-España ,&nbsp;I. Macías ,&nbsp;G. Quintero ,&nbsp;C. López-López ,&nbsp;T. Fernández-Rodríguez ,&nbsp;C. Grávalos ,&nbsp;E. González-Flores ,&nbsp;M. Guix ,&nbsp;B. García Paredes ,&nbsp;J.J. Reina ,&nbsp;J.R. Rodríguez Mowbray ,&nbsp;J. Sastre ,&nbsp;E. Aranda","doi":"10.1016/j.esmoop.2024.103986","DOIUrl":"10.1016/j.esmoop.2024.103986","url":null,"abstract":"<div><h3>Background</h3><div>The combination chemotherapy i.v. 5-fluorouracil (5-FU), irinotecan, and aflibercept (FOLFIRI-A) is a standard second-line treatment of metastatic colorectal cancer (mCRC). The aim was to assess maintenance treatment in second-line setting in older patients (aged ≥70 years) with mCRC.</div></div><div><h3>Patients and methods</h3><div>We evaluated FOLFIRI-A given for six cycles followed by maintenance with 5-FU/leucovorin (LV)-A (arm A) or FOLFIRI-A (arm B) until progression in older adults with mCRC in the AFEMA randomized, open-label, non-inferiority phase II trial (EudraCT2016-004076-21/NCT03279289). Patients aged ≥70 years who previously failed oxaliplatin-fluoropyrimidine were randomly allocated (1 : 1) to either arm A (experimental) or arm B (control). After enrolling 35 patients, the FOLFIRI dose was reduced to level 1 in both arms due to toxicity. The primary endpoint was median progression-free survival (PFS); and secondary endpoints were median overall survival, objective response rate, and safety. Non-inferiority required the upper confidence interval (CI) limit to not exceed a hazard ratio (HR) of 1.5 (one-sided <em>α</em> = 0.075, 80% power).</div></div><div><h3>Results</h3><div>A total of 170 patients were randomly allocated to arm A or arm B (<em>n</em> = 85 each). The median follow-up was 12.2 versus 10.9 months in arm A versus arm B. Most patients died (83.5% versus 88.2% in arm A versus arm B), mainly from disease progression. PFS non-inferiority was met (HR = 0.78, 95% CI 0.566-1.076, <em>P</em> = 0.131) with a median PFS of 6.1 versus 5.5 months in arm A versus arm B. Median overall survival was similar in arms A and B (12.2 and 11.5 months, respectively) (HR = 0.89, 95% CI 0.640-1.227, <em>P</em> = 0.467). During the maintenance phase, severe asthenia (4.5% versus 21.6%, <em>P</em> = 0.038), serious adverse events (SAEs) (17.8% versus 37.8%, <em>P</em> = 0.049), and treatment-related SAEs (6.7% versus 10.8%, <em>P</em> = 0.695) were reduced in arm A versus arm B.</div></div><div><h3>Conclusion</h3><div>In older adults, induction with six cycles of FOLFIRI-A plus maintenance with 5-FU/LV-A was non-inferior to FOLFIRI-A until progression. Severe asthenia, SAEs, and treatment-related SAEs were reduced with 5-FU/LV-A maintenance.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103986"},"PeriodicalIF":7.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721052","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":"Pazopanib in the real-world setting in soft tissue sarcomas: data from the Italian national registry","authors":"B. Vincenzi ,&nbsp;P.P. Olimpieri ,&nbsp;S. Celant ,&nbsp;A. Mazzocca ,&nbsp;A. Cortellini ,&nbsp;A. Comandone ,&nbsp;L. Tomassini ,&nbsp;S. Di Segni ,&nbsp;P. Russo ,&nbsp;P.G. Casali","doi":"10.1016/j.esmoop.2024.103995","DOIUrl":"10.1016/j.esmoop.2024.103995","url":null,"abstract":"<div><h3>Background</h3><div>Pazopanib is part of the therapeutic armamentarium for the treatment of patients with advanced non-adipocytic soft tissue sarcomas (STS) who have received prior chemotherapy, but its optimal use in STS histologies is still left to be further defined.</div></div><div><h3>Design and methods</h3><div>Data on STS patients treated with pazopanib in Italy have been prospectively collected from July 2013 to December 2019 through a drug monitoring registry managed by the Italian Medicines Agency (AIFA). This nationwide observational cohort study included patients with advanced STS who received pazopanib. Clinicians were mandatorily requested to fill in the AIFA monitoring registry in order to prescribe pazopanib.</div><div>Patients were recorded on the basis of their clinical characteristics, histological subtype captured at the time of treatment start, and clinical outcome. Primary outcome was time to treatment discontinuation (TTD). Secondary outcomes recorded were frequency of dose reduction and time to first dose reduction.</div></div><div><h3>Results</h3><div>We analyzed data from 1964 sarcoma patients. The most represented histological subtypes were leiomyosarcoma (44.7%), undifferentiated sarcomas/not otherwise specified (11.5%), and synovial sarcoma (8.1%). Overall, the median TTD was 106 days. The variables significantly associated to shorter TTD were Eastern Cooperative Oncology Group performance status (1-2 versus 0), the number of previous lines of treatment (2-4 versus 0-1) and prescribed dose (200 mg or 400 mg versus 800 mg, all once daily). Among the most represented (&gt;20 patients) histological subtypes, we also observed longer TTD in patients with histological diagnosis of malignant solitary fibrous tumor if compared with undifferentiated sarcoma not otherwise specified.</div></div><div><h3>Conclusions</h3><div>In this nationwide observational real-world study, the outcomes are similar to those reported in the pivotal trial (PALETTE study). Our study includes a significant number of patients with rare/ultra-rare sarcoma subtypes and underlines possible differences in treatment duration among these histologies.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103995"},"PeriodicalIF":7.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720973","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":"Lurbinectedin in extensive-stage small-cell lung cancer: a brief report of the IFCT-2105 LURBICLIN study☆","authors":"N. Girard ,&nbsp;F. Guisier ,&nbsp;A. Swalduz ,&nbsp;S. Van Hulst ,&nbsp;E. Pichon ,&nbsp;P. Lavaud ,&nbsp;L. Greillier ,&nbsp;A. Tiotiu ,&nbsp;A. Madroszyk ,&nbsp;O. Bylicki ,&nbsp;A. Canellas ,&nbsp;L. Belmont ,&nbsp;M. Zysman ,&nbsp;P.-A. Hauss ,&nbsp;B. Godbert ,&nbsp;C. Audigier-Valette ,&nbsp;C. Lebreton ,&nbsp;F. Morin ,&nbsp;V. Westeel","doi":"10.1016/j.esmoop.2024.103968","DOIUrl":"10.1016/j.esmoop.2024.103968","url":null,"abstract":"<div><h3>Background</h3><div>Small-cell lung cancer (SCLC) is a highly aggressive type of lung cancer. Lurbinectedin is recommended as second-/third-line treatment for advanced, previously treated SCLC.</div></div><div><h3>Materials and methods</h3><div>LURBICLIN is a nationwide, non-interventional, retrospective chart review study, based on the cohort of consecutive patients enrolled in the named patient use for lurbinectedin in France.</div></div><div><h3>Results</h3><div>A total of 312 patients were included. Lurbinectedin was delivered as second-line therapy in 138 (44%) patients. Grade 3-4 treatment-related adverse events were observed in 28 (9%) and 15 (5%) patients, respectively. Objective response rate (ORR) to lurbinectedin was 22% in the intention-to-treat population. After a median follow-up of 20.8 months, median progression-free survival (PFS) was 1.9 months [95% confidence interval (CI) 1.8-2.0 months]. At multivariate analysis, chemotherapy-free interval (CTFI) ≥ 90 days was an independent predictor of higher PFS [hazard ratio (HR) = 0.64, 95% CI 0.50-0.84, <em>P</em> &lt; 0.0001]. The median overall survival (OS) was 4.7 months (95% CI 4.0-5.4 months). At multivariate analysis, performance status &lt; 2 and CTFI ≥ 90 days were independent predictors of higher OS (HR = 0.71, 95% CI 0.53-0.95, <em>P</em> = 0.03; and HR = 0.58, 95% CI 0.44-0.76, <em>P</em> &lt; 0.0001, respectively). Overall, 147 (47%) patients had initiated subsequent systemic treatments.</div></div><div><h3>Conclusions</h3><div>LURBICLIN confirms the activity of lurbinectedin in patients with SCLC with a manageable safety profile. Lurbinectedin monotherapy provides an alternative option for SCLC patients.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 12","pages":"Article 103968"},"PeriodicalIF":7.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720975","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 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}