ESMO Open最新文献

{"title":"Psychiatric disorders in adolescent and young adult cancer survivors in Korea","authors":"S.-M. Jeong ,&nbsp;D. Kang ,&nbsp;H. Kim ,&nbsp;K.H. Jeon ,&nbsp;H.L. Choi ,&nbsp;H.Y. Park ,&nbsp;S. Kim ,&nbsp;J. Cho ,&nbsp;D.W. Shin","doi":"10.1016/j.esmoop.2024.104101","DOIUrl":"10.1016/j.esmoop.2024.104101","url":null,"abstract":"<div><h3>Background</h3><div>Although adolescent and young adult (AYA) cancer survivors have an increased risk of psychiatric disorders, limited evidence has been suggested. We aimed to determine the risk of psychiatric disorders among AYA cancer survivors.</div></div><div><h3>Materials and methods</h3><div>A retrospective population-based cohort study based on the Korea National Health Insurance Service database was carried out. All men and women aged 15-39 years diagnosed with cancer between 2006 and 2019 (<em>N</em> = 88 965) were included and matched with controls (1 : 4). The prevalence ratios (PRs) of psychiatric disorders were calculated in cancer patients and compared with those in the control group every 6 months before and after cancer diagnosis.</div></div><div><h3>Results</h3><div>The mean age of the participants was 32.2 years and the majority were 30-39 years of age (72.9%). There was no difference in the PRs of psychiatric disorders between AYA cancer patients and the control group before cancer diagnosis, but it increased sharply after cancer diagnosis [PR 2.50, 95% confidence interval (CI) 2.42-2.58 in the first 6 months]. During a median follow-up of 6.5 years, 54 733 participants developed psychiatric disorders. The overall risk of psychiatric disorders among AYA cancer survivors compared with the control group had a sub-distribution hazard ratio of 1.42 (95% CI 1.39-1.45) after considering competing risks.</div></div><div><h3>Conclusions</h3><div>Our study confirmed a 42% increased risk of psychiatric disorders among AYA cancer survivors compared with controls across various cancer types. Our findings suggest that AYA cancer survivors require long-term psychological support following their cancer diagnosis.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104101"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058513","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":"Phase I trial of the combination of the pan-ErbB inhibitor neratinib and mTOR inhibitor everolimus in advanced cancer patients with ErbB family gene alterations","authors":"S.A. Piha-Paul ,&nbsp;C. Tseng ,&nbsp;H.T. Tran ,&nbsp;A. Naing ,&nbsp;E.E. Dumbrava ,&nbsp;D.D. Karp ,&nbsp;J. Rodon ,&nbsp;T.A. Yap ,&nbsp;K.P. Raghav ,&nbsp;S. Damodaran ,&nbsp;X. Le ,&nbsp;P.T. Soliman ,&nbsp;J. Lim ,&nbsp;F. Meric-Bernstam","doi":"10.1016/j.esmoop.2025.104136","DOIUrl":"10.1016/j.esmoop.2025.104136","url":null,"abstract":"<div><h3>Background</h3><div>The ErbB family of receptor tyrosine kinases are key targets for antitumor therapy. Although neratinib, a pan-ErbB kinase inhibitor, is approved in ErbB2-positive breast cancer, drug resistance is common. Preclinical data suggest that combining neratinib with the mTOR inhibitor everolimus may overcome such resistance.</div></div><div><h3>Patients and methods</h3><div>Our trial evaluated this combination’s safety and efficacy in advanced cancers with ErbB alterations. We conducted a phase I dose-escalation trial of neratinib and everolimus. Primary objectives were to assess safety, tolerability, and dose-limiting toxicities (DLTs) and establish the maximum tolerated dose (MTD). Secondary objectives included objective response by RECIST v1.1 and pharmacokinetic analyses.</div></div><div><h3>Results</h3><div>Twenty-two patients (median age 61, median of four prior therapies) with ErbB alterations (mutations 63.6%, amplification 36.3%, or ErbB2-overexpressed by immunohistochemistry 9.1%) were enrolled. Common tumor types included breast (31.8%), colorectal (18.2%), cervical (9.1%), and endometrial (9.1%) cancers. Frequent grade (G) 3 treatment-related adverse events were diarrhea (18.2%), anemia (9.1%), mucositis (9.1%), and acute kidney injury (9.1%). DLTs included G3 mucositis and diarrhea at dose level (DL) 5, and G3 increased creatinine at DL4. The MTD was DL4: neratinib 240 mg with everolimus 7.5 mg. The objective response rate was 19% with partial response in four patients. Stable disease ≥16 weeks was seen in two patients (9.5%), resulting in a clinical benefit rate of 28.6%.</div></div><div><h3>Conclusion</h3><div>Pharmacokinetic data indicated reduced neratinib clearance possibly due to CYP3A4 pathway saturation by everolimus. Combination therapy with neratinib and everolimus has a tolerable safety profile and clinical activity in ErbB-altered patients. ErbB family receptors and the PI3K pathway are commonly implicated in oncogenesis. This clinical study of neratinib and everolimus demonstrated favorable clinical activity and tolerability.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104136"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143132656","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":"Outcomes and prognostic indicators in daratumumab-refractory multiple myeloma: a multicenter real-world study of elotuzumab, pomalidomide, and dexamethasone in 247 patients","authors":"E.A. Martino ,&nbsp;S. Palmieri ,&nbsp;M. Galli ,&nbsp;D. Derudas ,&nbsp;R. Mina ,&nbsp;R. Della Pepa ,&nbsp;R. Zambello ,&nbsp;E. Vigna ,&nbsp;A. Bruzzese ,&nbsp;S. Mangiacavalli ,&nbsp;E. Zamagni ,&nbsp;C. Califano ,&nbsp;M. Musso ,&nbsp;C. Conticello ,&nbsp;C. Cerchione ,&nbsp;G. Mele ,&nbsp;N. Di Renzo ,&nbsp;M. Offidani ,&nbsp;G. Tarantini ,&nbsp;G.M. Casaluci ,&nbsp;M. Gentile","doi":"10.1016/j.esmoop.2024.104084","DOIUrl":"10.1016/j.esmoop.2024.104084","url":null,"abstract":"<div><h3>Background</h3><div>Daratumumab-refractory multiple myeloma (Dara-R MM) presents a significant treatment challenge. This study aimed to evaluate the efficacy and survival outcomes of elotuzumab, pomalidomide, and dexamethasone (EloPd) in a large, real-world cohort of patients with Dara-R MM, with particular focus on progression-free survival (PFS) and overall survival (OS).</div></div><div><h3>Materials and methods</h3><div>This retrospective analysis included 247 Dara-R MM patients treated with EloPd. All patients were also refractory to lenalidomide, with 51.4% to a proteasome inhibitor, thus classified as triple-class refractory (TCR). Survival risk-scoring systems for PFS (progression-free risk score-PRS_{<em>DaraR</em>}) and OS (survival risk score-SRS_{<em>DaraR</em>}) were developed to stratify patients based on their risk profiles.</div></div><div><h3>Results</h3><div>The overall response rate was 52.6%, with a median PFS and OS of 6.6 and 17.0 months, respectively. The International Staging System (ISS) stages II and III, low hemoglobin (Hb) levels, the last therapy being daratumumab, and symptomatic relapse were identified as significant independent predictors of shorter PFS in multivariable analysis. In addition to advanced ISS stages, low Hb levels (&lt;10.6 g/dl), symptomatic relapse, and refractory disease exhibited an independent negative impact on OS. Importantly, no significant differences in both PFS and OS were observed between TCR and non-TCR patients. Based on these multivariable analyses, we developed PRS_{<em>DaraR</em>} and SRS_{<em>DaraR</em>} according to the magnitude of the hazard ratio. In PRS_{<em>DaraR</em>}, 10.1% were low-risk, 41.3% intermediate, 43.3% high, and 5.3% very high-risk. The 12-month PFS probabilities were 86.3% (low), 67.6% (intermediate), 52.9% (high), and 31.8% (very high). For SRS_{<em>DaraR</em>}, 6.1% were low-risk, 47.8% intermediate, 19.4% high, and 26.7% very high. The 12-month OS probabilities were 90.9% (low), 75.7% (intermediate), 55.9% (high), and 32.6% (very high).</div></div><div><h3>Conclusions</h3><div>This study supports EloPd as an effective treatment option in Dara-R MM patients, providing valuable disease control and acting as a potential bridge to newer therapies, such as CAR-T and bispecific antibodies.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104084"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946613","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 in HER2-positive inflammatory breast cancer: correlative insights and comparative analysis with noninflammatory breast cancers☆","authors":"F. Lynce ,&nbsp;O. Martínez-Sáez ,&nbsp;B. Walbaum ,&nbsp;F. Brasó-Maristany ,&nbsp;A.G. Waks ,&nbsp;P. Villagrasa ,&nbsp;G. Villacampa Javierre ,&nbsp;E. Sanfeliu ,&nbsp;P. Galván ,&nbsp;L. Paré ,&nbsp;L.M. Anderson ,&nbsp;C.M. Perou ,&nbsp;J.S. Parker ,&nbsp;A. Vivancos ,&nbsp;M.K. DiLullo ,&nbsp;S. Pernas ,&nbsp;E.P. Winer ,&nbsp;B. Overmoyer ,&nbsp;E.A. Mittendorf ,&nbsp;C. Bueno-Muiño ,&nbsp;S.M. Tolaney","doi":"10.1016/j.esmoop.2024.104100","DOIUrl":"10.1016/j.esmoop.2024.104100","url":null,"abstract":"<div><h3>Background</h3><div>The HER2DX assay predicts long-term prognosis and pathologic complete response (pCR) in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving neoadjuvant systemic therapy but has not been evaluated in inflammatory breast cancer (IBC).</div></div><div><h3>Patients and methods</h3><div>HER2DX was analyzed in baseline biopsy tissues from 23 patients with stage III HER2-positive IBC on a phase II trial (NCT01796197) treated with neoadjuvant trastuzumab, pertuzumab, and paclitaxel (THP). To assess the assay’s predictive accuracy for pCR in IBC, clinical-pathological features and outcomes from this IBC cohort were compared with 156 patients with stage III HER2-positive non-IBC from four different cohorts. Comparative analyses included HER2DX scores, gene signatures, and expression of individual genes between patients with IBC and non-IBC.</div></div><div><h3>Results</h3><div>Notable differences in clinicopathological characteristics included higher pertuzumab and chemotherapy usage and lower axillary burden in patients with IBC compared with non-IBC. In the combined cohort (<em>n</em> = 179), HER2DX pCR score and pertuzumab use were significant predictors of pCR, but not IBC status. The pCR rates in patients treated with trastuzumab-based chemotherapy (including IBC and non-IBC) were 68.9%, 58.5%, and 16.3% in the HER2DX pCR-high, -medium, and -low groups, respectively. Comparative gene expression analysis indicated minor differences between IBC and non-IBC affecting individual <em>HER2</em>, immune, and proliferation genes.</div></div><div><h3>Conclusions</h3><div>The HER2DX pCR score could predict pCR in stage III HER2-positive IBC following treatment with de-escalated neoadjuvant systemic therapy and in stage III HER2-positive non-IBC. Elevated pCR rates in HER2-positive IBC with high HER2DX pCR scores suggest there may be a role for treatment de-escalation in these patients and confirmatory studies are justified.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104100"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002110","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":"Real-world outcomes of PARP inhibitor maintenance in advanced ovarian cancer: a focus on disease patterns and treatment modalities at recurrence","authors":"M. Loverro ,&nbsp;C. Marchetti ,&nbsp;V. Salutari ,&nbsp;D. Giannarelli ,&nbsp;L. Vertechy ,&nbsp;F.M. Capomacchia ,&nbsp;C. Caricato ,&nbsp;M. Campitelli ,&nbsp;C. Panico ,&nbsp;G. Avesani ,&nbsp;F. Cocciolillo ,&nbsp;A. Rosati ,&nbsp;G. Scambia ,&nbsp;A. Fagotti","doi":"10.1016/j.esmoop.2024.104119","DOIUrl":"10.1016/j.esmoop.2024.104119","url":null,"abstract":"<div><h3>Background</h3><div>The utilization of poly-ADP-ribose polymerase (PARP) inhibitors (PARPi) as a first-line maintenance therapy for advanced ovarian cancer has increased significantly, with ∼80% of patients potentially eligible. This expansion has led to a rise in the population experiencing platinum-sensitive recurrence, yet data on first recurrence during PARPi are limited. This real-world study from a high-volume referral center aims to elucidate recurrence rates, disease distribution, and treatment modalities at the time of progression in PARPi-treated patients.</div></div><div><h3>Materials and methods</h3><div>We analyzed our prospectively maintained database to identify patients receiving first-line PARPi maintenance from January 2019 to December 2022 at our institution.</div></div><div><h3>Results</h3><div>A total of 373 cases were identified, 51.5% of which had a <em>BRCA</em> mutation. With a median follow-up of 38 months, 44.8% of patients experienced recurrence, with 90.3% having a platinum-free interval exceeding 6 months. Recurrences were oligometastatic in 44.9% of cases, with <em>BRCA</em> mutations strongly predicting this pattern (hazard ratio 3.014, confidence interval 1.486-6.113, <em>P</em> = 0.002). The median progression-free survival was 39 months, significantly longer for <em>BRCA</em>-mutated and homologous recombination deficiency-positive patients. Over one-third of platinum-sensitive recurrent patients were candidates for local treatments, and PARPi administration was prolonged in 53.7%.</div></div><div><h3>Conclusions</h3><div>Despite the notable survival improvement, a significant proportion of the population will experience a platinum-sensitive recurrence on PARPi, for which local treatments are often a viable option. Our study highlights the need for further research to determine whether the ablation of oligometastatic sites has a significant impact on post-recurrence survival and to identify if there are patient categories that would benefit from personalized follow-up due to their susceptibility to oligometastatic recurrences and local treatments.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104119"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002152","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":"Follow-up after first-Line nivOlumab plus ipilimumab in patients with diffuse pleuRal mesotheliomA: a real-world Dutch cohort study—FLORA","authors":"L.H. Douma ,&nbsp;M.M. Hofman ,&nbsp;F. Zwierenga ,&nbsp;T.M.T. Zondervan ,&nbsp;A.I.G. Buma ,&nbsp;H. Schouwink ,&nbsp;D.W. Dumoulin ,&nbsp;J.A. Burgers ,&nbsp;I. Smesseim ,&nbsp;J.G.J.V. Aerts ,&nbsp;C.J. de Gooijer","doi":"10.1016/j.esmoop.2024.104123","DOIUrl":"10.1016/j.esmoop.2024.104123","url":null,"abstract":"<div><h3>Background</h3><div>Diffuse pleural mesothelioma (dPM) is an aggressive malignancy, primarily treated with palliative systemic therapy. Since 2022, nivolumab–ipilimumab (nivo/ipi) has replaced chemotherapy as the standard first-line treatment for dPM in the Netherlands. Chemotherapy remains a rational second-line treatment. The real-world effectiveness of second-line treatment after doublet immunotherapy remains unknown. The FLORA study aimed to provide an overview of treatment patterns in patients with dPM after first-line nivo/ipi and evaluate the effectiveness of second-line chemotherapy based on real-world data.</div></div><div><h3>Patients and methods</h3><div>FLORA was a Dutch multicenter retrospective cohort study. Clinical data were collected from the medical records. The primary endpoints were treatment patterns after nivo/ipi and median overall survival (mOS) of patients receiving second-line chemotherapy. The secondary endpoints were objective response rate (ORR), median progression-free survival (mPFS) of second-line chemotherapy, and subgroup analyses (Eastern Cooperative Oncology Group performance status and histological subtype). The study also updated the mOS for first-line nivo/ipi patients.</div></div><div><h3>Results</h3><div>Between May 2021 and July 2023, 277 patients with dPM receiving first-line nivo/ipi therapy were included. Sixty-eight percent of the patients were male, with a median age of 72 years (interquartile range 67-77 years). The histological subtypes were epithelioid (62%), sarcomatoid (22%), biphasic (13%), and unknown (3%). One hundred and two (47%) of the 218 patients with disease progression received second-line treatment, of whom 83 received second-line platinum–pemetrexed chemotherapy. The mOS and mPFS for second-line chemotherapy were 8.2 months ([95% confidence interval (CI) 7.4-9.1 months] and 5.6 months (95% CI 4.9-6.3 months), respectively, with an ORR of 37%. Poor performance score was the main reason for not receiving second-line treatment.</div></div><div><h3>Conclusion</h3><div>This study provides the first real-world data on subsequent treatment of patients with dPM with disease progression on nivo/ipi, resulting in an mOS of 8.2 months after second-line chemotherapy.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104123"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022647","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":"BRCA functional domains associated with high risk of multiple primary tumors and domain-related sensitivity to olaparib: the Prometheus Study","authors":"L. Incorvaia ,&nbsp;C. Marchetti ,&nbsp;C. Brando ,&nbsp;T.D. Bazan Russo ,&nbsp;M. Bono ,&nbsp;A. Perez ,&nbsp;L. Congedo ,&nbsp;R. Ergasti ,&nbsp;L. Castellana ,&nbsp;L. Insalaco ,&nbsp;S. Contino ,&nbsp;V. Gristina ,&nbsp;A. Galvano ,&nbsp;D. Fanale ,&nbsp;G. Badalamenti ,&nbsp;A. Russo ,&nbsp;G. Scambia ,&nbsp;V. Bazan","doi":"10.1016/j.esmoop.2024.104076","DOIUrl":"10.1016/j.esmoop.2024.104076","url":null,"abstract":"<div><h3>Background</h3><div>Germline pathogenic variants (gPVs) in the breast cancer susceptibility gene <em>1</em>/2 (<em>BRCA1</em>/2) genes confer high-penetrance susceptibility to breast cancer (BC) and ovarian cancer (OC). Although most female <em>BRCA</em> carriers develop only a single <em>BRCA</em>-associated tumor in their lifetime, a smaller subpopulation is diagnosed with multiple primary tumors (MPTs). The genetic factors influencing this risk remain unclear. Further, in patients with <em>BRCA</em>-mutated tumors, there appears to be a variability in the effectiveness of olaparib treatment.</div></div><div><h3>Patients and methods</h3><div>This real-world, multicenter, observational study aimed to determine whether the location of <em>BRCA</em> gPVs within functional domains (FDs) is associated with the development of MPTs and the magnitude of olaparib benefit. The study population comprised consecutive patients with OC who underwent hereditary cancer genetic testing between May 2015 and March 2023. MPT history was assessed based on mutated genes (<em>BRCA1</em> or <em>BRCA2</em>) and the location of the PVs within the FDs. Clinical outcomes of olaparib first-line maintenance therapy were evaluated according to <em>BRCA1/2</em> FD location.</div></div><div><h3>Results</h3><div>The frequency of MPT history in the overall population was 13.3% (118/882), and 20.4% in the <em>BRCA</em>-mutated subpopulation (68/333; <em>P</em> &lt; 0.001). We observed a significant association between the DNA-binding domain (DBD) FD of <em>BRCA2</em> and MPT. Specifically, 55.6% of <em>BRCA2-</em>mutated patients with PVs in the DBD had a history of BC as a second tumor. At a median follow-up of 48.5 months (95% confidence interval 10-70 months), the 48-month progression-free survival rates were 100.0% for patients with PVs in DBD, 91.7% for those with PVs in other FDs, and 36.4% for those with PVs in the RAD51-binding domain (RAD51-BD) of <em>BRCA2</em> (<em>P</em> = 0.01). Results in the <em>BRCA1</em> cohort were not statistically significant.</div></div><div><h3>Conclusions</h3><div>The results suggest that the location of PVs within <em>BRCA</em> FDs may influence the onset of multiple tumors and the benefit of olaparib in patients with <em>BRCA</em>-mutated OC. These findings could be relevant for cancer prevention efforts, particularly given the increasing number of cancer survivors. However, further understanding is needed before these results can inform clinical decisions.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104076"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028331","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 association between hospital volume and overall survival in adult AML patients treated with intensive chemotherapy","authors":"Z.L.R. Kaplan ,&nbsp;N. van Leeuwen ,&nbsp;D. van Klaveren ,&nbsp;F. Eijkenaar ,&nbsp;O. Visser ,&nbsp;E.F.M. Posthuma ,&nbsp;S. Zweegman ,&nbsp;G. Huls ,&nbsp;A. van Rhenen ,&nbsp;N.M.A. Blijlevens ,&nbsp;J.J. Cornelissen ,&nbsp;A.A. van de Loosdrecht ,&nbsp;J.H.F.M. Pruijt ,&nbsp;M.D. Levin ,&nbsp;M. Hoogendoorn ,&nbsp;V.E.P.P. Lemmens ,&nbsp;H.F. Lingsma ,&nbsp;A.G. Dinmohamed","doi":"10.1016/j.esmoop.2025.104152","DOIUrl":"10.1016/j.esmoop.2025.104152","url":null,"abstract":"<div><h3>Background</h3><div>Acute myeloid leukemia (AML) requires specialized care, particularly when administrating intensive remission induction chemotherapy (ICT). High-volume hospitals are presumed more adept at delivering this complex treatment, resulting in better overall survival (OS) rates. Despite its potential implications for quality improvement, research on the volume–outcome relationship in ICT administration for AML is scarce. This nationwide, population-based study in the Netherlands explored the volume–outcome relationship in AML.</div></div><div><h3>Materials and methods</h3><div>Data from the Netherlands Cancer Registry on adult (≥18 years of age) ICT-treated AML patients, diagnosed between 2014 and 2018, were analyzed. Hospital volume was assessed against OS using mixed-effects Cox regression, adjusting for patient and disease characteristics (i.e. case mix), with hospital as a random effect.</div></div><div><h3>Results</h3><div>Our study population consisted of a total of 1761 patients (57% male), with a median age of 61 years. The average annual number of ICT-treated patients varied across the 24 hospitals (range 1-56, median 13, and interquartile range 8-20 patients per hospital per year). Overall, an increase of 10 ICT-treated patients annually was associated with an 8% lower mortality risk [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.87-0.98, <em>P</em> = 0.01]. This association was not significant at 30-day (HR 1.02, 95% CI 0.89-1.17, <em>P</em> = 0.75) and 42-day (HR 0.96, 95% CI 0.85-1.08, <em>P</em> = 0.54) OS but became apparent after 100-day OS (HR 0.91, 95% CI 0.83-0.99, <em>P</em> = 0.05).</div></div><div><h3>Conclusions</h3><div>There is a volume–outcome association within AML care. This finding could support hospital volume as a metric in AML care. However, it should be acknowledged that centralizing care is a complex process with implications for health care providers and patients. Therefore, any move toward centralization must be judiciously balanced.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104152"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070777","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":"Efficacy, safety, and pharmacokinetics of eribulin as monotherapy or in combination with irinotecan for patients with pediatric rhabdomyosarcoma, non-rhabdomyosarcoma soft tissue sarcoma, or Ewing sarcoma","authors":"M. Casanova ,&nbsp;C.M. Albert ,&nbsp;F. Bautista ,&nbsp;S.C. Borinstein ,&nbsp;S. Bradfield ,&nbsp;A. Bukowinski ,&nbsp;Q. Campbell-Hewson ,&nbsp;D.S. Hawkins ,&nbsp;A. Kim ,&nbsp;G.M. Milano ,&nbsp;L.V. Marshall ,&nbsp;N. Pinto ,&nbsp;C.A. Pratilas ,&nbsp;A. Rubio-San-Simón ,&nbsp;R. Windsor ,&nbsp;O. Majid ,&nbsp;R. Scott ,&nbsp;Y. Jia ,&nbsp;C. Paoletti ,&nbsp;U. Kontny","doi":"10.1016/j.esmoop.2024.104129","DOIUrl":"10.1016/j.esmoop.2024.104129","url":null,"abstract":"<div><h3>Background</h3><div>In this report, we present results from studies of eribulin as monotherapy (Study 223) and in combination with irinotecan (the phase II part of Study 213) for patients with relapsed/refractory pediatric rhabdomyosarcoma (RMS), non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), or Ewing sarcoma (EWS).</div></div><div><h3>Patients and methods</h3><div>Studies 223 and 213 were phase II multicenter trials that enrolled pediatric patients with histologically confirmed disease. Treatment comprised 21-day cycles of eribulin mesylate 1.4 mg/m² on days 1 and 8 (Study 223) or eribulin 1.4 mg/m² on days 1 and 8 plus irinotecan 40 mg/m² on days 1-5 (Study 213). For both studies, the primary endpoints were objective response rate (ORR) and duration of response (DOR); secondary endpoint included safety.</div></div><div><h3>Results</h3><div>In Study 223, 21 patients (RMS, <em>n</em> = 8; NRSTS, <em>n</em> = 8; EWS, <em>n</em> = 5) were enrolled and treated. No responses were observed, resulting in early termination of enrollment. By the data cut-off date (22 February 2021), six patients (RMS, <em>n</em> = 3; NRSTS, <em>n</em> = 1; EWS, <em>n</em> = 2) had stable disease for ≥5 weeks. All patients had one or more treatment-emergent adverse event (TEAE), most commonly neutrophil count decreased (71.4%). In Study 213 (phase II part), 27 patients (RMS, <em>n</em> = 9; NRSTS, <em>n</em> = 9; EWS, <em>n</em> = 9) were enrolled/treated. By the data cut-off date (9 July 2021), three patients (one in each cohort) had had a response, resulting in an ORR of 11.1% and DORs of 2.9 (RMS), 1.4 (NRSTS), and 15.4 (EWS) months. All patients had one or more TEAE, most commonly diarrhea and neutrophil count decreased (51.9% each).</div></div><div><h3>Conclusions</h3><div>Eribulin, as monotherapy or combination therapy, exhibited a safety profile consistent with that observed previously in adult populations; however, efficacy in both studies was not considered adequate to advance investigation in these disease areas.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104129"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143132657","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":"Association between DNA damage repair alterations and outcomes to 177Lu-PSMA-617 in advanced prostate cancer","authors":"A. Rami ,&nbsp;N.S. Rashid ,&nbsp;C. Zhong ,&nbsp;W. Xie ,&nbsp;H. Stoltenberg ,&nbsp;E.J. Wheeler ,&nbsp;A. Wolanski ,&nbsp;J. Ritzer ,&nbsp;A.D. Choudhury ,&nbsp;M.-E. Taplin ,&nbsp;H. Jacene ,&nbsp;A.K. Tewari ,&nbsp;P. Ravi","doi":"10.1016/j.esmoop.2024.104131","DOIUrl":"10.1016/j.esmoop.2024.104131","url":null,"abstract":"<div><h3>Background</h3><div>¹⁷⁷Lu-prostate-specific membrane antigen (PSMA)-617 (LuPSMA) is a radionuclide therapy approved for patients with PSMA-avid metastatic castrate-resistant prostate cancer (mCRPC). We evaluated whether alterations in the DNA damage repair (DDR) pathway were associated with outcomes to LuPSMA.</div></div><div><h3>Patients and methods</h3><div>We identified an institutional cohort of men (<em>n</em> = 134) treated with ≥2 cycles of LuPSMA who had panel-based germline and/or tumor genomic sequencing. Mutations or two-copy losses in any of <em>BRCA1</em>, <em>BRCA2</em>, <em>ATM</em>, <em>CDK12</em>, <em>PALB2</em>, <em>RAD51</em>, and <em>MSH2</em> were considered DDR defects. The primary outcome was a ≥50% reduction in the prostate-specific antigen (PSA) level during LuPSMA therapy (PSA50); secondary outcomes were PSA progression-free survival (PSA-PFS) and overall survival (OS). Models were adjusted for age, number of prior systemic therapies, sites of metastasis, and log-transformed PSA at cycle 1.</div></div><div><h3>Results</h3><div>Thirty-four patients (25%) harbored DDR alterations, most commonly in <em>BRCA2</em> and <em>ATM</em> (both <em>n</em> = 13). The presence of a DDR defect was not associated with PSA50 [adjusted odds ratio 0.48 (0.20-1.09), <em>P</em> = 0.08], PSA-PFS [adjusted hazard ratio (HR) 1.29 (0.79-2.10), <em>P</em> = 0.30], or OS [adjusted HR 1.42 (0.74-2.72), <em>P</em> = 0.29], with a non-significant trend toward poorer outcomes among DDR-altered patients.</div></div><div><h3>Conclusions</h3><div>DDR alterations were not associated with outcomes following LuPSMA. This has implications for treatment sequencing in mCRPC, particularly in patients with DDR alterations.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 2","pages":"Article 104131"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028330","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}