European Journal of Cancer最新文献

{"title":"Prospective single-arm multicenter interventional study of surgical resection for liver metastasis from gastric cancer; 3-year overall and recurrence-free survival","authors":"Kazumasa Fujitani ,&nbsp;Yukinori Kurokawa ,&nbsp;Ryohei Wada ,&nbsp;Atsushi Takeno ,&nbsp;Ryohei Kawabata ,&nbsp;Takeshi Omori ,&nbsp;Hiroshi Imamura ,&nbsp;Motohiro Hirao ,&nbsp;Shunji Endo ,&nbsp;Junji Kawada ,&nbsp;Jeong Ho Moon ,&nbsp;Shuji Takiguchi ,&nbsp;Masaki Mori ,&nbsp;Hidetoshi Eguchi ,&nbsp;Yuichiro Doki ,&nbsp;on behalf of the Osaka University Clinical Research Group for Gastroenterological Surgery","doi":"10.1016/j.ejca.2024.115080","DOIUrl":"10.1016/j.ejca.2024.115080","url":null,"abstract":"<div><h3>Objective</h3><div>Potential benefit of surgical resection for liver metastasis from gastric cancer (LMGC) remains controversial because most previous studies were retrospective. We evaluated the outcomes of surgical resection following chemotherapy for LMGC in a prospective single-arm multicenter interventional study.</div></div><div><h3>Methods</h3><div>Patients with synchronous or metachronous LMGC received 2–4 cycles of standard chemotherapy and proceeded to surgical resection if restaging showed a non-progressive disease with a chance of R0 resection. The primary endpoint was 3-year OS of R0 patients, with RFS as secondary. Prognostic factors for R0 patients were evaluated by multivariable Cox regression analysis.</div></div><div><h3>Results</h3><div>Seventy patients were enrolled between 2011 and 2019. Two patients were ineligible, and 20 discontinued treatment before surgery. Of the 48 patients eventually undergoing surgery, 43 accomplished R0 resection of the primary and/or metastatic GC, while 1 ended in R2 resection and 4 were considered ineligible. Median and 3-year OS for R0 patients were 39.8 months (95 % confidence interval [CI], 26.9 to not reached) and 58.1 % (95 % CI, 43.1–71.8), respectively, while median and 3-year RFS were 14.9 months (95 % CI 7.9–34.0) and 34.9 % (95 % CI 22.2–50.1), respectively. On multivariable analysis, both multiple liver metastases and positive nodal status (pN1–3) were negatively associated with OS (multiple liver metastases: hazard ratio [HR] 2.71 (95 % CI, 1.16–6.35), <em>P</em> = 0.022; pN1–3: HR 9.11 (95 % CI, 1.22–68.2), <em>P</em> = 0.031).</div></div><div><h3>Conclusion</h3><div>R0 resection following chemotherapy for LMGC yielded promising survival, with multiple liver metastases and positive nodal status being significant indicators of poor prognosis. Clinical trial registration number: UMIN 000011445 (https://www.umin.ac.jp/ctr/).</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"213 ","pages":"Article 115080"},"PeriodicalIF":7.6,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blinded independent central review versus local investigator assessment of PFS in RCTs of immunotherapy in advanced cancers: A systematic review and meta-analysis","authors":"Simeone D’Ambrosio ,&nbsp;Fabio Salomone ,&nbsp;Filippo Vitale ,&nbsp;Annarita Avanzo ,&nbsp;Angela Viggiano ,&nbsp;Luigi Liguori ,&nbsp;Roberto Ferrara ,&nbsp;Antonio Nuccio ,&nbsp;Giuseppe Viscardi ,&nbsp;Fabiana Napolitano ,&nbsp;Antonio Santaniello ,&nbsp;Luigi Formisano ,&nbsp;Roberto Bianco ,&nbsp;Alberto Servetto","doi":"10.1016/j.ejca.2024.115077","DOIUrl":"10.1016/j.ejca.2024.115077","url":null,"abstract":"<div><h3>Background</h3><div>Assessment of Progression-free survival (PFS) events by investigators might be inaccurate in randomized controlled trials (RCTs) with open-label design. We explored differences in PFS evaluated by blinded independent central review (BICR) or local investigator assessment (IA) in trials testing immunotherapy (IO) in advanced cancers.</div></div><div><h3>Methods</h3><div>We systematically reviewed articles of RCTs investigating IO in advanced tumors, published in PubMed-indexed journals up to December 2023. For each RCT, we collected PFS results by BICR and by local IA. We calculated the discrepancy index (DI) as the ratio of BICR and IA Hazard Ratios (HR_BICR/HR_IA) for PFS. An overall DI and relative confidence interval (CI) were calculated using a fixed-effect model weighted for the inverse of variance.</div></div><div><h3>Findings</h3><div>Only 32/140 (22.9 %) RCTs reported both BICR and local IA PFS data, including 17,054 patients. PFS was the sole primary endpoint in 19/32 (59.4 %) and a co-primary endpoint 9/32 (28.2 %) trials. The study design was open label or double-blind in 17/32 (53.1 %) and 15/32 (46.9 %) RCTs, respectively. The overall DI was 1.07 (95 % CI 1.01–1.13; I² =0, p = 0.02), revealing a more optimistic analysis of results in favor of local IA. In the 17 open-label trials, the overall DI was 1.09 (95 % CI 1.02–1.17, I2 =0, p = 0.02), revealing a more favorable interpretation of PFS results by local investigators.</div></div><div><h3>Interpretation</h3><div>We found a statistically significant difference between BICR and local IA of PFS in trials of IO in cancer. These results suggest that the double assessment is recommended in RCTs testing IO, especially in open-label trials.</div></div><div><h3>Funding</h3><div>This work was supported by the <span>MFAG</span> <span><span>27826–2022</span></span> grant (Dr. Alberto Servetto).</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"213 ","pages":"Article 115077"},"PeriodicalIF":7.6,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: Safety analyses from the randomized, placebo-controlled, phase III TALAPRO-2 study","authors":"Arun A. Azad ,&nbsp;Karim Fizazi ,&nbsp;Nobuaki Matsubara ,&nbsp;Fred Saad ,&nbsp;Ugo De Giorgi ,&nbsp;Jae Young Joung ,&nbsp;Peter C.C. Fong ,&nbsp;Robert J. Jones ,&nbsp;Stefanie Zschäbitz ,&nbsp;Jan Oldenburg ,&nbsp;Neal D. Shore ,&nbsp;Curtis Dunshee ,&nbsp;Joan Carles ,&nbsp;Andre P. Fay ,&nbsp;Xun Lin ,&nbsp;Liza DeAnnuntis ,&nbsp;Nicola Di Santo ,&nbsp;Michael A. Zielinski ,&nbsp;Neeraj Agarwal","doi":"10.1016/j.ejca.2024.115078","DOIUrl":"10.1016/j.ejca.2024.115078","url":null,"abstract":"<div><h3>Background</h3><div>This detailed analysis further characterizes the safety profile of talazoparib plus enzalutamide in the ongoing randomized, phase III TALAPRO-2 study in patients with metastatic castration-resistant prostate cancer (mCRPC). In both the all-comers and homologous recombination repair (HRR)-deficient populations, talazoparib plus enzalutamide significantly improved radiographic progression-free survival compared with placebo plus enzalutamide.</div></div><div><h3>Methods</h3><div>The talazoparib plus enzalutamide safety populations in TALAPRO-2 included 398 patients from cohort 1 (all-comers, unselected for HRR gene alterations) and 198 patients from the combined HRR-deficient population (patients from the all-comers population with HRR gene alterations plus subsequently enrolled patients with HRR gene alterations; cohort 2). Patients received talazoparib 0.5 mg (0.35 mg, moderate renal impairment) and enzalutamide 160 mg once daily. Safety analyses evaluated common treatment-emergent adverse events (TEAE), their type, severity, timing, seriousness, and relationship to study treatment.</div></div><div><h3>Results</h3><div>In the all-comers (n = 398) and HRR-deficient populations (n = 198), all-cause grade 3/4 (G3/4) TEAEs with talazoparib plus enzalutamide were reported in 71.9 % and 66.2 % of patients, respectively. Most common G3/4 hematologic TEAEs were anemia (46.7 % and 40.9 %, respectively), neutropenia (18.3 % and 18.7 %), and thrombocytopenia (7.3 % and 7.1 %). Median time to event was 3.3 and 3.3 months for G3/4 anemia, 2.3 and 2.3 months for G3/4 neutropenia, and 2.3 and 1.5 months for G3/4 thrombocytopenia. Maximum hemoglobin reduction occurred after 13 and 15 weeks of treatment. 18.8 % and 10.1 % of patients discontinued talazoparib. TEAEs were managed with dose interruption (62.1 % and 57.6 %), reduction (52.8 % and 52.0 %), hematologic supportive care (13.1 % and 10.6 %), and packed red blood cell transfusions (39.2 % and 35.9 %).</div></div><div><h3>Conclusion</h3><div>Talazoparib plus enzalutamide had a generally manageable safety profile in patients with mCRPC within the all-comers and the HRR-deficient populations.</div></div><div><h3>ClinicalTrials.gov Identifier</h3><div>NCT03395197</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"213 ","pages":"Article 115078"},"PeriodicalIF":7.6,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do regulations and policies undermine the social value of independent academic research?","authors":"Denis Lacombe, Fábio Cardoso Borges","doi":"10.1016/j.ejca.2024.115076","DOIUrl":"https://doi.org/10.1016/j.ejca.2024.115076","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":" ","pages":"115076"},"PeriodicalIF":7.6,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The tumor immune microenvironment of SCLC is not associated with its molecular subtypes","authors":"Yoan Velut ,&nbsp;Basilia Arqué ,&nbsp;Marie Wislez ,&nbsp;Hélène Blons ,&nbsp;Barbara Burroni ,&nbsp;Mathilde Prieto ,&nbsp;Siméon Beau ,&nbsp;Ludovic Fournel ,&nbsp;Gary Birsen ,&nbsp;Isabelle Cremer ,&nbsp;Marco Alifano ,&nbsp;Diane Damotte ,&nbsp;Audrey Mansuet-Lupo","doi":"10.1016/j.ejca.2024.115067","DOIUrl":"10.1016/j.ejca.2024.115067","url":null,"abstract":"<div><h3>Introduction</h3><div>Small-cell lung carcinoma (SCLC) is a high-grade neuroendocrine carcinoma of poor prognosis. Although immune checkpoint blockers have shown promising results in advanced SCLC, the tumor immune microenvironment (TME) remains poorly understood, with no validated prognostic or predictive biomarkers of efficacy.</div></div><div><h3>Methods</h3><div>This retrospective study included surgically samples from 48 SCLC patients between 2009 and 2018. We assessed the TME using two quantitative 7-plex immunofluorescence panels focusing on T and B cells, and compared it to NSCLC (N = 10). Molecular subtypes were determined by assessing the expression of ASCL1, NEUROD1 and YAP1 using immunohistochemistry.</div></div><div><h3>Results</h3><div>Immune-hot SCLC were defined as those exhibiting the highest immune cell and immune-related marker densities. They were associated with longer overall survival, significantly more frequently detected at early stages, and exhibited high PD-L1 expression in immune cells, but were not associated with molecular subtypes. Compared to NSCLC, SCLC had significantly lower densities of CD20 + cells and higher density of PD1 + cells, with no significant differences in CD4 + , CD8 + and plasma cell densities. In univariate analysis, the highest OS was significantly associated with early stage (p &lt; 0.001), low expression of NEUROD1 (p = 0.047), high PD1 + cell density (p &lt; 0.001) and high PD-L1 immune cell expression (p = 0.04). Only stage and PD1 + cell density emerged as independent prognostic markers.</div></div><div><h3>Conclusion</h3><div>SCLC TME is highly heterogeneous. Immune-hot tumors were associated with OS but not with molecular classification. PD1 expression and PD-L1 expression by immune cells may thus serve as a prognostic marker.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"212 ","pages":"Article 115067"},"PeriodicalIF":7.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics and survival outcomes of patients with primary central nervous system lymphoma treated with high-dose methotrexate-based polychemotherapy and consolidation therapies","authors":"Fleur A. de Groot ,&nbsp;Tim J.A. Dekker ,&nbsp;Jeanette K. Doorduijn ,&nbsp;Stefan Böhringer ,&nbsp;Mirian Brink ,&nbsp;Ruben A.L. de Groen ,&nbsp;Lorraine M. de Haan ,&nbsp;F.J. Sherida H. Woei-A-Jin ,&nbsp;Troy Noordenbos ,&nbsp;Aniko Sijs-Szabo ,&nbsp;Mirjam A. Oudshoorn ,&nbsp;King H. Lam ,&nbsp;Arjan Diepstra ,&nbsp;Liane C.J. te Boome ,&nbsp;Valeska Terpstra ,&nbsp;Lara H. Bohmer ,&nbsp;Alina Nicolae ,&nbsp;Eduardus F.M. Posthuma ,&nbsp;Lianne Koens ,&nbsp;Marc F. Durian ,&nbsp;Joost S.P. Vermaat","doi":"10.1016/j.ejca.2024.115068","DOIUrl":"10.1016/j.ejca.2024.115068","url":null,"abstract":"<div><div>Given the rarity of primary central nervous system lymphoma (PCNSL), evaluations of different high-dose methotrexate-(HD-MTX)-based treatment regimens is sparse. This retrospective, multicenter study evaluates clinical characteristics and outcomes (progression-free, overall and disease-specific survival) after five HD-MTX-based polychemotherapeutic regimens and two consolidation therapies. 346 patients with histologically confirmed PCNSL, treated with ≥ 1 cycle HD-MTX-based strategies (≥3g/m²/cycle) were included. The regimens included MATRIX (HD-MTX, HD-AraC, thiotepa, and rituximab), (R)MBVP±HD-AraC (HD-MTX, teniposide/etoposide, carmustine, prednisolone, ± HD-AraC, ± rituximab), (R)MP (HD-MTX, procarbazine, ± rituximab), and a combination of HD-MTX and HD-AraC. The overall response rate after induction was 69 %, 28 % complete remission and progressive disease was observed in 100 (29 %) patients. 126 (36 %) patients received consolidation, including high-dose-BCNU-thiotepa with autologous stem cell transplantation (HD-BCNU-TT/ASCT, n = 59 (17 %)) or whole brain radiotherapy (WBRT, n = 67 (19 %)). Clinical characteristics associated with adverse mortality risk by multivariable prognostication contained age &gt; 60 years (HR 1.61, <em>p</em> = 0.011), elevated LDH (HR 1.75, <em>p</em> = 0.004) and WHO status ≥ 2 (HR 1.56, <em>p</em> = 0.010). Independently, induction regimens containing HD-AraC demonstrated survival benefit compared to induction regimens without HD-AraC (HR 0.59, <em>p</em> = 0.002). Without preference for HD-BCNU-TT/ASCT or WBRT, a favorable effect of consolidation (HR 0.44 and HR 0.42, <em>p</em> &lt; 0.001) was confirmed, also with consolidation as time-dependent variable. Competing risk analysis showed similar low incidence of lymphoma-unrelated deaths in consolidated and unconsolidated patients. This study confirms that age, elevated LDH and WHO status increase the mortality risk. HD-AraC containing treatment regimens and consolidation with HD-BCU-TT/ASCT or WBRT were associated with superior survival, including a favorable low incidence of lymphoma-unrelated deaths.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"213 ","pages":"Article 115068"},"PeriodicalIF":7.6,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High levels of autotaxin and lysophosphatidic acid predict poor outcome in treatment of resectable gastric carcinoma","authors":"Annalisa Schirizzi ,&nbsp;Rossella Donghia ,&nbsp;Valentina De Nunzio ,&nbsp;Natasha Renna ,&nbsp;Matteo Centonze ,&nbsp;Giampiero De Leonardis ,&nbsp;Vincenza Lorusso ,&nbsp;Alessia Fantasia ,&nbsp;Sergio Coletta ,&nbsp;Dolores Stabile ,&nbsp;Annalisa Ferro ,&nbsp;Maria Notarnicola ,&nbsp;Angela D. Ricci ,&nbsp;Claudio Lotesoriere ,&nbsp;Michael Lahn ,&nbsp;Rosalba D’Alessandro ,&nbsp;Gianluigi Giannelli","doi":"10.1016/j.ejca.2024.115066","DOIUrl":"10.1016/j.ejca.2024.115066","url":null,"abstract":"<div><h3>Background</h3><div>Although early-stage gastric cancer is a candidate for curative surgical resection, the absence of specific early symptoms results in a late diagnosis and consequently most patients present advanced or metastatic disease. Identifying noveland tumor-specific biomarkers is needed to increase early detection and match patients to the appropriate treatment. The present study focused on the possible prognostic role of Ectonucleotide Pyrophosphatase/Phosphodiesterase 2 (<em>ENPP2</em>)/Autotaxin (ATX) and lysophosphatidic acid (LPA) in Gastro-Esophageal Adenocarcinoma (GEA). High levels of ATX/LPA are associated with several malignancies including gastrointestinal tumors.</div></div><div><h3>Methods</h3><div>Using a bioinformatics analysis, the incidence of <em>ENPP2</em> mutations together with its expression in the tumor tissues and the correlation between the presence of mutations and the survival rate were examined in databases of GEA patients. Furthermore, circulating levels of ATX and LPA were studied retrospectively and longitudinally both in patients receiving frontal surgery and in patients receiving preoperative chemotherapy.</div></div><div><h3>Results</h3><div>Overall findings suggested that although <em>ENPP2</em> mutations occur at low incidence, their presence was associated with a particular poor Overall Survival (OS). Furthermore, removal of the tumour by surgery resulted in a decrease in serum ATX and LPA levels within five days, regardless of any previous chemotherapy. Basal circulating ATX were associated with the aggressive diffuse GEA and could be considered of negative prognostic value, mainly in combination models with circulating Carcino-Embryonic Antigen (CEA).</div></div><div><h3>Conclusions</h3><div>Based on these observations, clinical trials with ATX-targeted drugs and standard chemotherapy regimens may benefit from selecting GEA patients based on their levels of ATX, LPA and CEA.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"213 ","pages":"Article 115066"},"PeriodicalIF":7.6,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediabetes persistence or remission and subsequent risk of gallbladder cancer: A nationwide cohort study","authors":"Joo-Hyun Park ,&nbsp;Jung Yong Hong ,&nbsp;Kyungdo Han ,&nbsp;Young Suk Park ,&nbsp;Joon Oh Park ,&nbsp;Ho Yeong Lim ,&nbsp;Jay J. Shen","doi":"10.1016/j.ejca.2024.114312","DOIUrl":"10.1016/j.ejca.2024.114312","url":null,"abstract":"<div><h3>Background &amp; aims</h3><div>Hyperglycemia is associated with an increased risk of gallbladder cancer (GBC), potentially by inhibiting gallbladder motility and inducing prolonged cholestasis. Although intermediate hyperglycemia (or prediabetes) is highly reversible, evidence is lacking about whether prediabetes persistence or remission is associated with an altered GBC risk.</div></div><div><h3>Methods</h3><div>This nationwide cohort study included 6058,662 adults without diabetes or cancer who underwent national health examinations twice in 2-year intervals between 2009 (S1) and 2011 (S2) and were followed-up until 2018. Prediabetes was defined as a fasting plasma glucose level of 100–125 mg/dL. We categorized changes in prediabetes status into: stable normoglycemia, new-onset prediabetes, prediabetes remission, and persistent prediabetes groups. GBC risk was estimated using Cox proportional hazards models, after adjusting for potential confounders.</div></div><div><h3>Results</h3><div>During 38.6 million person-years (median 6.4 years) of follow-up, 1349 new GBC cases were identified. Among 1409,474 individuals with prediabetes at S1, 768,515 achieved prediabetes remission at S2, outnumbering the 640,959 individuals with persistent prediabetes. GBC incidence probability was consistently higher among individuals with persistent prediabetes than in individuals with stable normoglycemia or prediabetes remission (all log-rank <em>P</em> &lt; 0.01). Compared with stable normoglycemia, persistent prediabetes was associated with increased GBC risk (adjusted hazard ratio [aHR], 95 % CI: 1.21, 1.04 to 1.41). The aHRs of GBC were 1.14 (95 % CI, 0.99 to 1.33) and 1.03 (95 % CI, 0.88 to 1.21) for new-onset prediabetes and prediabetes remission, respectively.</div></div><div><h3>Conclusions</h3><div>Individuals with persistent prediabetes had a significantly increased risk of GBC, whereas those with prediabetes remission had no increased risk. Achieving prediabetes remission has a significant potential to reduce the risk of GBC.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"213 ","pages":"Article 114312"},"PeriodicalIF":7.6,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small cell transformation in EGFR-mutated non-small cell lung cancer: DLL3 expression and efficacy of immune checkpoint inhibitors or tyrosine kinase inhibitors combined with chemotherapy","authors":"Felix Carl Saalfeld ,&nbsp;Johanna Möller ,&nbsp;Petros Christopoulos ,&nbsp;Carina Wenzel ,&nbsp;Anna Rasokat ,&nbsp;Xuejun Alice Wang ,&nbsp;Ioannis Vathiotis ,&nbsp;David König ,&nbsp;Oliver Illini ,&nbsp;Christian Grohé ,&nbsp;Marcel Wiesweg ,&nbsp;Claas Wesseler ,&nbsp;Christoph Schubart ,&nbsp;Natalie Pelusi ,&nbsp;Gernot Rohde ,&nbsp;Tobias R. Overbeck ,&nbsp;Jutta Kirfel ,&nbsp;Jürgen Alt ,&nbsp;Diego Kauffmann-Guerrero ,&nbsp;Frank Griesinger ,&nbsp;Martin Wermke","doi":"10.1016/j.ejca.2024.115065","DOIUrl":"10.1016/j.ejca.2024.115065","url":null,"abstract":"<div><h3>Introduction</h3><div>Small cell transformation (SCT) is a typical mechanism of adaptive resistance to third generation epidermal growth factor receptor inhibitors (EGFRi) which have become the standard of care for EGFR-driven non-small cell lung cancer (EGFR+ NSCLC). Little is known about the optimal management of SCT patients. This study aimed to compare outcomes under platinum/etoposide chemotherapy alone (<em>chemo</em>) or in combination with EGFR inhibitors <em>(EGFRi+chemo)</em> or immune checkpoint inhibitors <em>(ICI+chemo)</em>. In addition, DLL3 expression was explored as potential novel therapeutic target.</div></div><div><h3>Methods</h3><div>We conducted a retrospective study on patients with EGFR+ NSCLC and SCT treated at 19 centers in Europe and the United States. A total of 47 patients were included of whom 17 received <em>chemo</em>, 20 <em>ICI+chemo,</em> and 10 <em>EGFRi+chemo</em>. We analyzed DLL3 expression by immunohistochemistry.</div></div><div><h3>Results</h3><div>In the entire cohort, median overall survival (OS) from start of first SCT therapy was 11 months (95 % confidence interval [95 %CI] 9.1–12.9) and median progression-free survival (PFS) was 5 months (95 %CI 4.2–5.8). Median PFS was similar in all three groups (<em>chemo</em> and <em>ICI+chemo</em> 4 months, <em>EGFRi+chemo</em> 6 months), and 12-months PFS was 12 % (95 %CI 2 %−31 %), 13 % (95 %CI 0 %−43 %), and 0 % for <em>ICI+chemo, EGFRi+chemo</em>, and <em>chemo,</em> respectively. Median OS in the <em>ICI+chemo</em> group was 13 months (95 %CI 5.5–20.5) compared to 10 months (95 %CI 7.6–12.4) with <em>chemo</em> and <em>EGFRi+chemo</em> (95 %CI 8.1–11.9), respectively. Before and after SCT, 0 % and 93 % of tumors were DLL3-positive.</div></div><div><h3>Conclusions</h3><div>Our results suggest that <em>ICI+chemo</em> and DLL3-targeting agents are worth further exploration in EGFR+ NSCLC undergoing SCT.</div></div><div><h3>Presented elsewhere</h3><div>Part of this work has been presented at ESMO annual meeting in Madrid, Spain in October 2023 (Poster 1336 P).</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"213 ","pages":"Article 115065"},"PeriodicalIF":7.6,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated serum magnesium levels prompt favourable outcomes in cancer patients treated with immune checkpoint blockers","authors":"Yingfang Feng ,&nbsp;Meng Gao ,&nbsp;Xiyue Xu ,&nbsp;Hengqi Liu ,&nbsp;Ke Lu ,&nbsp;Zheng Song ,&nbsp;Jingwei Yu ,&nbsp;Xia Liu ,&nbsp;Xue Han ,&nbsp;Lanfang Li ,&nbsp;Lihua Qiu ,&nbsp;Zhengzi Qian ,&nbsp;Shiyong Zhou ,&nbsp;Huilai Zhang ,&nbsp;Xianhuo Wang","doi":"10.1016/j.ejca.2024.115069","DOIUrl":"10.1016/j.ejca.2024.115069","url":null,"abstract":"<div><h3>Background</h3><div>Magnesium deficiency influences the activation and cytotoxicity of immune cells. Nevertheless, whether serum magnesium levels influence the clinical outcomes of immune checkpoint blockers (ICBs) treatment still remains ambiguous. There is an urgent need for clinical research to elucidate the relationship between serum magnesium levels and the outcomes of ICB therapy. Such insights could offer new perspectives on immunotherapy for cancer.</div></div><div><h3>Methods</h3><div>A multi-center retrospective study involving in pan-cancer patients treated with ICBs at three large cancer centers from August 2012 to May 2023 was conducted. The primary objective was to assess the correlation between serum magnesium levels and therapeutic response in patients receiving ICBs, and further evaluate the associations between serum magnesium levels and progression-free survival (PFS) and overall survival (OS).</div></div><div><h3>Results</h3><div>A total of 1441 patients treated with ICBs, including 1042 with lung cancer, 270 with esophageal cancer, and 129 with Hodgkin lymphoma, were enrolled in this study. We found that patients with elevated serum magnesium levels exhibited a favourable response to ICBs treatment. The optimal cut-off point for serum magnesium level (0.79 mmol/L) was applied for stratifying patients into distinct groups. In the three tumor cohorts, patients in high magnesium level group (Mg²⁺ ≥ 0.79 mmol/L) had longer PFS and OS than those in low magnesium level group (Mg²⁺ &lt; 0.79 mmol/L). Univariate and multivariate analyses confirmed that the serum Mg²⁺ level serves as an independent prognostic factor for cancer patients receiving ICBs therapy.</div></div><div><h3>Conclusion</h3><div>Our multi-center study demonstrated that among patients receiving ICBs therapy, those with elevated serum magnesium levels exhibit significantly better clinical outcomes than those with low serum magnesium levels. Further prospective validation studies are needed to confirm these findings.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"213 ","pages":"Article 115069"},"PeriodicalIF":7.6,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142535301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}