ESMO Open最新文献

{"title":"Corrigendum to “Moderate physical activity during neoadjuvant chemotherapy in breast cancer patients: effect on cancer-related inflammation and pathological complete response—the Neo-Runner study”","authors":"O. Garrone , M. Paccagnella , A. Abbona , F. Ruatta , P. Vanella , N. Denaro , G. Tomasello , N. Croce , F. Barbin , M.G. Rossino , C.A.M. La Porta , A. Sapino , V. Torri , A. Albini , M.C. Merlano","doi":"10.1016/j.esmoop.2024.103983","DOIUrl":"10.1016/j.esmoop.2024.103983","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 11","pages":"Article 103983"},"PeriodicalIF":7.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748645","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":"Diagnosing intravascular B-cell lymphoma using nanopore sequencing of cell-free DNA from cerebrospinal fluid","authors":"B.C. Schmidt , A.-K. Afflerbach , P. Ludewig , P. Dirksen , F.-O. Paulsen , T. Magnus , M. Alawi , U. Schüller , K. Weisel , C. Bokemeyer , M. Christopeit","doi":"10.1016/j.esmoop.2024.103974","DOIUrl":"10.1016/j.esmoop.2024.103974","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 11","pages":"Article 103974"},"PeriodicalIF":7.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544502","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":"Clinical outcomes of early-stage triple-negative breast cancer after neoadjuvant chemotherapy according to HER2-low status☆","authors":"A.S. Raghavendra ,&nbsp;D.B. Zakon ,&nbsp;Q. Jin ,&nbsp;A. Strahan ,&nbsp;M. Grimm ,&nbsp;M.E. Hughes ,&nbsp;M. Cherian ,&nbsp;J. Vincuilla ,&nbsp;T. Parker ,&nbsp;P. Tarantino ,&nbsp;E.A. Mittendorf ,&nbsp;T.A. King ,&nbsp;V. Valero ,&nbsp;D. Tripathy ,&nbsp;S.M. Tolaney ,&nbsp;N. Tayob ,&nbsp;N.U. Lin ,&nbsp;D.G. Stover ,&nbsp;C.H. Barcenas ,&nbsp;A.C. Garrido-Castro","doi":"10.1016/j.esmoop.2024.103973","DOIUrl":"10.1016/j.esmoop.2024.103973","url":null,"abstract":"<div><h3>Background</h3><div>The impact of human epidermal growth factor receptor 2 (HER2) expression determined by immunohistochemistry (IHC) on outcomes in early-stage triple-negative breast cancer (eTNBC) is unclear. Using a large, multi-institutional cohort, we evaluated outcomes by HER2 IHC status in patients with eTNBC who received neoadjuvant therapy (NAT).</div></div><div><h3>Patients and methods</h3><div>Patients with stage I-III TNBC who received NAT and underwent surgery from January 2016 to June 2019 were identified from three databases. HER2 expression was defined as low (IHC1+ or 2+/FISH not amplified) or HER2 IHC score 0 by local testing at diagnosis. Pathological complete response (pCR) rates were compared using logistic regression adjusted for multiple factors. Survival outcomes were estimated using Kaplan–Meier and Cox proportional hazards models.</div></div><div><h3>Results</h3><div>Among 977 consecutive patients, 388 (39.7%) had HER2-low and 589 (60.3%) had HER2 IHC score 0 tumors. Median age at eTNBC diagnosis was 50.3 years (range 21.0-83.4 years). At baseline, clinical nodal positivity rate was significantly higher in HER2-low (55.0%) versus HER2 IHC score 0 tumors (46.6%) (<em>P</em> = 0.011); pCR rates were similar (32.0% versus 32.6%; adjusted <em>P</em> = 0.924). At a median follow-up of 3.5 years, recurrence-free survival (RFS) did not vary significantly between HER2-low versus HER2 IHC score 0 among patients with pCR (adjusted <em>P</em> = 0.368) or residual disease (RD) after NAT (adjusted <em>P</em> = 0.573). Distant RFS and overall survival (OS) did not differ by HER2 category for patients with pCR [distant RFS (DRFS), adjusted <em>P</em> = 0.509; OS, adjusted <em>P</em> = 0.514] or RD (DRFS, adjusted <em>P</em> = 0.812; OS, <em>P</em> = 0.285). Discordance of tumor HER2 status was seen in 31.1% of HER2 IHC score 0 cases, with HER2 expression observed post-treatment; 34.8% of HER2-low cases showed discordance, with absent HER2 expression in RD.</div></div><div><h3>Conclusions</h3><div>In this large cohort of patients with eTNBC treated with NAT, HER2-low status was not associated with pCR or survival after adjusting for clinical factors. The discordance in HER2 IHC pre- and post-NAT likely reflects challenges in HER2 quantification and heterogeneity.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 11","pages":"Article 103973"},"PeriodicalIF":7.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142577984","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 “Phase II study of a trastuzumab biosimilar in combination with paclitaxel for HER2-positive recurrent or metastatic urothelial carcinoma: KCSG GU18-18”","authors":"M. Kim ,&nbsp;J.L. Lee ,&nbsp;S.J. Shin ,&nbsp;W.K. Bae ,&nbsp;H.J. Lee ,&nbsp;J.H. Byun ,&nbsp;Y.J. Choi ,&nbsp;J. Youk ,&nbsp;C.Y. Ock ,&nbsp;S. Kim ,&nbsp;H. Song ,&nbsp;K.H. Park ,&nbsp;B. Keam","doi":"10.1016/j.esmoop.2024.103708","DOIUrl":"10.1016/j.esmoop.2024.103708","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 11","pages":"Article 103708"},"PeriodicalIF":7.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phase I dose-escalation study of LRP5/6 antagonist BI 905677 in patients with advanced solid tumors","authors":"H.-J. Lenz ,&nbsp;G. Argilés ,&nbsp;M.J.A. de Jonge ,&nbsp;R. Yaeger ,&nbsp;T. Doi ,&nbsp;A. El-Khoueiry ,&nbsp;F. Eskens ,&nbsp;Y. Kuboki ,&nbsp;J. Bertulis ,&nbsp;S. Nazabadioko ,&nbsp;L. Pronk ,&nbsp;J. Tabernero","doi":"10.1016/j.esmoop.2024.103729","DOIUrl":"10.1016/j.esmoop.2024.103729","url":null,"abstract":"<div><h3>Background</h3><div>Aberrant Wnt pathway signaling has been implicated in the development of many cancers. Targeting of low-density lipoprotein receptor-related protein 5/6 (LRP5/6) co-receptors inhibits Wnt signaling and may be a novel therapy. BI 905677 is an LRP5/6 antagonist that has demonstrated preclinical antitumor activity.</div></div><div><h3>Patients and methods</h3><div>This (NCT03604445) was a phase I, dose-escalation study evaluating BI 905677 for patients with advanced solid tumors over two dosing schedules (A: i.v. infusion every 3 weeks, 3-week cycles; B: i.v. infusion every 2 weeks, 4-week cycles). Adult patients were eligible if they had exhausted treatment options and had an Eastern Cooperative Oncology Group performance status of 0-1. The primary endpoints were the maximum tolerated dose (MTD) and safety. Other endpoints were pharmacokinetics, pharmacodynamics, and efficacy.</div></div><div><h3>Results</h3><div>In total, 37 patients received BI 905677 over nine dose cohorts (0.05-3.6 mg/kg/every 3 weeks). Dose-limiting toxicities were only reported during cycle 1 in the 3.6 mg/kg cohort and the MTD was established at 2.8 mg/kg every 3 weeks. Enrollment for schedule B was not pursued. The most frequently reported adverse events were diarrhea (35.1%), vomiting (21.6%), and C-telopeptide increase (18.9%). All patients in the 3.6 mg/kg cohort experienced a dose-limiting toxicity, suggesting a narrow therapeutic index. Paired pre-treatment and on-treatment biopsies, where available, showed decreased Axin2 expression by reverse transcriptase polymerase chain reaction with treatment, suggesting target inhibition. Best response observed was stable disease in 14 (38%) patients.</div></div><div><h3>Conclusion</h3><div>The MTD of BI 905677 was set at 2.8 mg/kg every 3 weeks. BI 905677 was well tolerated but a narrow therapeutic range and minimal efficacy led to early termination of the trial.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 11","pages":"Article 103729"},"PeriodicalIF":7.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748563","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":"Molecular Tumor Board of the University Medical Center Groningen (UMCG-MTB): outcome of patients with rare or complex mutational profiles receiving MTB-advised targeted therapy","authors":"V.D. de Jager ,&nbsp;P. Plomp ,&nbsp;M.S. Paats ,&nbsp;S. van Helvert ,&nbsp;A.ter Elst ,&nbsp;A. van den Berg ,&nbsp;H.J. Dubbink ,&nbsp;W.H. van Geffen ,&nbsp;L. Zhang ,&nbsp;L.E.L. Hendriks ,&nbsp;T.J.N. Hiltermann ,&nbsp;B.I. Hiddinga ,&nbsp;L.B.M. Hijmering-Kappelle ,&nbsp;M. Jalving ,&nbsp;J. Kluiver ,&nbsp;B. Koopman ,&nbsp;M. van Kruchten ,&nbsp;E.M.J. van der Logt ,&nbsp;B. Piet ,&nbsp;J. van Putten ,&nbsp;A.J. van der Wekken","doi":"10.1016/j.esmoop.2024.103966","DOIUrl":"10.1016/j.esmoop.2024.103966","url":null,"abstract":"<div><h3>Purpose</h3><div>Molecular tumor boards (MTBs) are considered beneficial for treatment decision making for patients with cancer with uncommon, rare, or complex mutational profiles. The lack of international MTB guidelines results in significant variation in practices and recommendations. Therefore, periodic follow-up is necessary to assess and govern MTB functioning. The objective of this study was to determine the effectiveness of MTB treatment recommendations for patients with rare and complex mutational profiles as implemented in the MTB of the University Medical Center Groningen (UMCG-MTB) in 2019-2020.</div></div><div><h3>Patients and methods</h3><div>A retrospective follow-up study was carried out to determine the clinical outcome of patients with uncommon or rare (combinations of) molecular aberrations for whom targeted therapy was recommended as the next line of treatment by the UMCG-MTB in 2019 and 2020.</div></div><div><h3>Results</h3><div>The UMCG-MTB recommended targeted therapy as the next line of treatment in 132 of 327 patients: 37 in clinical trials, 67 in the on-label setting, and 28 in the off-label setting. For on- and off-label treatment recommendations, congruence of recommended and received treatment was 85% in patients with available follow-up (67/79). Treatment with on-label therapy resulted in a response rate of 50% (21/42), a median progression-free survival (PFS) of 6.3 months [interquartile range (IQR) 2.9-14.9 months], and median overall survival (OS) of 15.8 months (IQR 6.4-34.2 months). Treatment with off-label therapy resulted in a response rate of 53% (8/15), a median PFS of 5.1 months (IQR 1.9-7.3 months), and a median OS of 17.7 months (IQR 5.1-23.7 months).</div></div><div><h3>Conclusion</h3><div>Treatment with MTB-recommended next-line targeted therapy for patients with often heavily pretreated cancer with rare and complex mutational profiles resulted in positive overall responses in over half of patients. Off-label use of targeted therapies, for which there is sufficient rationale as determined by an MTB, is an effective treatment strategy. This study underlines the relevance of discussing patients with rare and complex mutational profiles in an MTB.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 11","pages":"Article 103966"},"PeriodicalIF":7.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578094","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 “Clinical relevance of gene mutations and rearrangements in advanced differentiated thyroid cancer”","authors":"M. Nannini ,&nbsp;A. Repaci ,&nbsp;M.C. Nigro ,&nbsp;A. Colapinto ,&nbsp;V. Vicennati ,&nbsp;T. Maloberti ,&nbsp;E. Gruppioni ,&nbsp;A. Altimari ,&nbsp;E. Solaroli ,&nbsp;E. Lodi Rizzini ,&nbsp;F. Monari ,&nbsp;A. De Leo ,&nbsp;S. Damiani ,&nbsp;U. Pagotto ,&nbsp;M.A. Pantaleo ,&nbsp;D. de Biase ,&nbsp;G. Tallini","doi":"10.1016/j.esmoop.2024.103704","DOIUrl":"10.1016/j.esmoop.2024.103704","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 11","pages":"Article 103704"},"PeriodicalIF":7.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748562","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":"PD-L1 thresholds predict efficacy of immune checkpoint inhibition in first-line treatment of advanced gastroesophageal adenocarcinoma. A systematic review and meta-analysis of seven phase III randomized trials","authors":"V. Formica ,&nbsp;C. Morelli ,&nbsp;L. Fornaro ,&nbsp;S. Riondino ,&nbsp;M. Rofei ,&nbsp;E. Fontana ,&nbsp;E.C. Smyth ,&nbsp;M. Roselli ,&nbsp;H.-T. Arkenau","doi":"10.1016/j.esmoop.2024.103967","DOIUrl":"10.1016/j.esmoop.2024.103967","url":null,"abstract":"<div><h3>Background</h3><div>High expression of programmed death-ligand 1 (PD-L1) has been recognized as a marker of improved efficacy of immunotherapy in gastroesophageal adenocarcinoma (GEA); however, the optimal PD-L1 cut-off is still debated. The aim of the present review was to analyze available phase III trials and to identify the appropriate PD-L1 expression cut-off for GEA.</div></div><div><h3>Methods</h3><div>Phase III trials investigating the efficacy of anti-programmed cell death protein 1 (PD-1) therapies in addition to standard chemotherapy versus standard chemotherapy in the first-line setting were selected. Progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) were the analyzed outcome measures. Pooled treatment effects were assessed in the unselected population and in subpopulations with different levels of PD-L1 expression.</div></div><div><h3>Results</h3><div>PD-1 blockade efficacy was found to consistently increase in a linear manner with higher combined positive score (CPS) of PD-L1 expression: pooled hazard ratio (HR) for OS and PFS and pooled odds ratio (OR) for ORR of 0.80, 0.75 and 1.51, respectively, in the unselected population versus 0.67, 0.63 and 1.90, respectively, in the CPS ≥10 population (all <em>P</em> values &lt; 0.0001). In the PD-L1-negative population (CPS &lt;1) a significant benefit of anti-PD-1 agents could not be demonstrated in terms of OS and PFS (<em>P</em> = 0.28 and 0.12, respectively), but it was seen in terms of ORR (<em>P</em> = 0.03). PD-1 blockade was effective in the CPS &lt;10 population (<em>P</em> value for pooled OS HR, PFS HR and response OR are all 0.01), while in the CPS &lt;5 population the effect was of borderline significance for OS (<em>P</em> = 0.07) and significant for PFS and ORR (<em>P</em> = 0.02 and 0.03, respectively).</div></div><div><h3>Conclusion</h3><div>The present meta-analysis confirmed that the benefit of PD-1 blockade in GEA patients is related to PD-L1 CPS, with increased benefit observed for higher CPS cut-offs and no OS benefit in the CPS &lt;1 subset. Overall, data indicate that PD-L1 CPS ≥5 could represent an acceptable cut-off to optimize the risk/benefit ratio of such agents. Our data suggest a potential clinical benefit of immunotherapy in selected patients within the CPS 1-4 population which needs further investigation.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 11","pages":"Article 103967"},"PeriodicalIF":7.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616911","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":"Impact of systemic therapy on clinical T1 small-cell neuroendocrine carcinoma of the bladder","authors":"A.A. Myers ,&nbsp;A.M. Fang ,&nbsp;M.J. Moussa ,&nbsp;H. Hwang ,&nbsp;N.R. Wilson ,&nbsp;M.T. Campbell ,&nbsp;P. Msaouel ,&nbsp;B.H. Lee ,&nbsp;C.C. Guo ,&nbsp;M. Zhang ,&nbsp;J. Zhao ,&nbsp;A.O. Siefker-Radtke ,&nbsp;A.M. Kamat ,&nbsp;O. Alhalabi","doi":"10.1016/j.esmoop.2024.103964","DOIUrl":"10.1016/j.esmoop.2024.103964","url":null,"abstract":"<div><h3>Background</h3><div>The purpose of this study was to analyze survival outcomes and pathologic response of patients with cT1N0 small-cell neuroendocrine carcinoma (SCNEC) of the bladder treated with neoadjuvant chemotherapy (neoCTX).</div></div><div><h3>Materials and methods</h3><div>All cases of bladder SCNEC treated at our institution from January 1996 to July 2023 were identified. cT1N0 was defined as transurethral resection pathology showing lamina propria invasion with present and uninvolved muscularis propria. Pathologic downstaging and recurrences were evaluated. Disease-free survival (DFS) and overall survival (OS) were analyzed using the Cox regression and Kaplan–Meier method.</div></div><div><h3>Results</h3><div>A total of 30 patients with cT1N0 bladder SCNEC were included. Median follow-up was 88 months [95% confidence interval (CI) 44-131 months]. NeoCTX was given to 21 (70%) patients with a median of 4 cycles (range 1-6 cycles). A total of 27 (90%) patients received definitive local therapy. In cT1 bladder SCNEC, neoCTX was associated with decreased odds of pathologic upstaging [odds ratio = 0.07 (95% CI 0.01-0.45), <em>P</em> = 0.004], decreased odds of relapse [odds ratio = 0.12 (95% CI 0.02-0.65), <em>P</em> = 0.01], improved DFS [hazard ratio (HR) 0.30, 95% CI 0.09-0.96, <em>P</em> = 0.04], and improved OS (HR 0.32, 95% CI 0.10-1.02, <em>P</em> = 0.05). Compared with cT2N0 treated with neoCTX, cT1N0 treated with neoCTX had improved median DFS (HR 0.44, 95% CI 0.19-1.03, <em>P</em> = 0.05) and improved median OS (HR 0.52, 95% CI 0.22-1.24, <em>P</em> = 0.14).</div></div><div><h3>Conclusions</h3><div>NeoCTX had suggestive benefit in patients with cT1 bladder SCNEC with decreased odds of pathologic upstaging, metastatic relapse, and improved survival.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 11","pages":"Article 103964"},"PeriodicalIF":7.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544503","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":"Disease-free survival as surrogate for overall survival in real-world settings for esophageal cancer: an analysis of SEER-Medicare data","authors":"J.A. Ajani ,&nbsp;L. Leung ,&nbsp;S. Kanters ,&nbsp;P. Singh ,&nbsp;M. Kurt ,&nbsp;I. Kim ,&nbsp;M.-M. Pourrahmat ,&nbsp;H.S. Friedman ,&nbsp;P. Navaratnam ,&nbsp;G. Reardon","doi":"10.1016/j.esmoop.2024.103934","DOIUrl":"10.1016/j.esmoop.2024.103934","url":null,"abstract":"<div><h3>Background</h3><div>Establishing surrogate endpoints for overall survival (OS) may expedite assessment of new therapies in esophageal cancer (EC) and gastroesophageal junction cancer (GEJC). This study aimed to evaluate disease-free survival (DFS) as a surrogate endpoint for OS.</div></div><div><h3>Methods</h3><div>Patients from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database aged ≥66 years with resection after primary diagnosis of stage 2 or 3 EC/GEJC between 2009 and 2017 were analyzed (<em>N</em> = 925; median follow-up 26.2 months). Surrogacy was assessed by evaluating individual level associations between DFS and OS using Spearman’s rank correlation and the association between treatment effects by Pearson’s correlation coefficient. To evaluate the association between treatment effects, patients were classified in synthetic clusters based on treatments received. Propensity score matching addressed imbalances in baseline characteristics between treatment and control groups in the clusters. Predictive performance of the surrogacy equation was assessed internally for the generated clusters via leave-one-out cross-validation and externally via predictions for 26 clinical trials of early-stage EC/GEJC.</div></div><div><h3>Results</h3><div>Patients were mostly male (84%), non-Hispanic white (89.3%), with median age 71.8 years, and cancer stages 2 (50.4%) and 3 (49.6%). Cancer types were adenocarcinoma (76.1%), squamous cell carcinoma (10.4%), and other types (13.5%). Most patients 766/925 (82.8%) received neoadjuvant therapy (680/766 chemoradiotherapy versus 86/766 chemotherapy alone) while 23.6% of the patients received adjuvant therapy. Within each treatment setting, most [705/766 (92.0%) of neoadjuvant therapy and 178/218 (81.7%) of adjuvant therapy] received multi-agent chemotherapy. The individual level correlation was 0.76 (95% confidence interval 0.70-0.80). The correlation between treatment effects was 0.96 (95% confidence interval 0.80-0.99) with a corresponding surrogate threshold effect of 0.71. Both internal (91%) and external (89%) validation of the model demonstrated high predictive accuracy.</div></div><div><h3>Conclusions</h3><div>Correlations between DFS and OS were meaningful at both individual and treatment effect level. The derived surrogacy equation enables reliable early assessments of OS benefit from the observed DFS benefit for early-stage EC/GEJC treatments in real-world settings.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"9 11","pages":"Article 103934"},"PeriodicalIF":7.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592571","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}