{"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":null,"pages":null},"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}
Yoan Velut , Basilia Arqué , Marie Wislez , Hélène Blons , Barbara Burroni , Mathilde Prieto , Siméon Beau , Ludovic Fournel , Gary Birsen , Isabelle Cremer , Marco Alifano , Diane Damotte , Audrey Mansuet-Lupo
{"title":"The tumor immune microenvironment of SCLC is not associated with its molecular subtypes","authors":"Yoan Velut , Basilia Arqué , Marie Wislez , Hélène Blons , Barbara Burroni , Mathilde Prieto , Siméon Beau , Ludovic Fournel , Gary Birsen , Isabelle Cremer , Marco Alifano , Diane Damotte , 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 < 0.001), low expression of NEUROD1 (p = 0.047), high PD1 + cell density (p < 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":null,"pages":null},"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}
Fleur A. de Groot , Tim J.A. Dekker , Jeanette K. Doorduijn , Stefan Böhringer , Mirian Brink , Ruben A.L. de Groen , Lorraine M. de Haan , F.J. Sherida H. Woei-A-Jin , Troy Noordenbos , Aniko Sijs-Szabo , Mirjam A. Oudshoorn , King H. Lam , Arjan Diepstra , Liane C.J. te Boome , Valeska Terpstra , Lara H. Bohmer , Alina Nicolae , Eduardus F.M. Posthuma , Lianne Koens , Marc F. Durian , Joost S.P. Vermaat
{"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 , Tim J.A. Dekker , Jeanette K. Doorduijn , Stefan Böhringer , Mirian Brink , Ruben A.L. de Groen , Lorraine M. de Haan , F.J. Sherida H. Woei-A-Jin , Troy Noordenbos , Aniko Sijs-Szabo , Mirjam A. Oudshoorn , King H. Lam , Arjan Diepstra , Liane C.J. te Boome , Valeska Terpstra , Lara H. Bohmer , Alina Nicolae , Eduardus F.M. Posthuma , Lianne Koens , Marc F. Durian , 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/m<sup>2</sup>/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 > 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> < 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":null,"pages":null},"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 , Rossella Donghia , Valentina De Nunzio , Natasha Renna , Matteo Centonze , Giampiero De Leonardis , Vincenza Lorusso , Alessia Fantasia , Sergio Coletta , Dolores Stabile , Annalisa Ferro , Maria Notarnicola , Angela D. Ricci , Claudio Lotesoriere , Michael Lahn , Rosalba D’Alessandro , 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":null,"pages":null},"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}
Joo-Hyun Park , Jung Yong Hong , Kyungdo Han , Young Suk Park , Joon Oh Park , Ho Yeong Lim , Jay J. Shen
{"title":"Prediabetes persistence or remission and subsequent risk of gallbladder cancer: A nationwide cohort study","authors":"Joo-Hyun Park , Jung Yong Hong , Kyungdo Han , Young Suk Park , Joon Oh Park , Ho Yeong Lim , Jay J. Shen","doi":"10.1016/j.ejca.2024.114312","DOIUrl":"10.1016/j.ejca.2024.114312","url":null,"abstract":"<div><h3>Background & 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> < 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":null,"pages":null},"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}
Felix Carl Saalfeld , Johanna Möller , Petros Christopoulos , Carina Wenzel , Anna Rasokat , Xuejun Alice Wang , Ioannis Vathiotis , David König , Oliver Illini , Christian Grohé , Marcel Wiesweg , Claas Wesseler , Christoph Schubart , Natalie Pelusi , Gernot Rohde , Tobias R. Overbeck , Jutta Kirfel , Jürgen Alt , Diego Kauffmann-Guerrero , Frank Griesinger , Martin Wermke
{"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 , Johanna Möller , Petros Christopoulos , Carina Wenzel , Anna Rasokat , Xuejun Alice Wang , Ioannis Vathiotis , David König , Oliver Illini , Christian Grohé , Marcel Wiesweg , Claas Wesseler , Christoph Schubart , Natalie Pelusi , Gernot Rohde , Tobias R. Overbeck , Jutta Kirfel , Jürgen Alt , Diego Kauffmann-Guerrero , Frank Griesinger , 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":null,"pages":null},"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}
Yingfang Feng , Meng Gao , Xiyue Xu , Hengqi Liu , Ke Lu , Zheng Song , Jingwei Yu , Xia Liu , Xue Han , Lanfang Li , Lihua Qiu , Zhengzi Qian , Shiyong Zhou , Huilai Zhang , Xianhuo Wang
{"title":"Elevated serum magnesium levels prompt favourable outcomes in cancer patients treated with immune checkpoint blockers","authors":"Yingfang Feng , Meng Gao , Xiyue Xu , Hengqi Liu , Ke Lu , Zheng Song , Jingwei Yu , Xia Liu , Xue Han , Lanfang Li , Lihua Qiu , Zhengzi Qian , Shiyong Zhou , Huilai Zhang , 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 (Mg<sup>2+</sup> ≥ 0.79 mmol/L) had longer PFS and OS than those in low magnesium level group (Mg<sup>2+</sup> < 0.79 mmol/L). Univariate and multivariate analyses confirmed that the serum Mg<sup>2+</sup> 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":null,"pages":null},"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}
Oleksandr Dudnichenko , Konstantin Penkov , Meredith McKean , Mario Mandalà , Mariia Kukushkina , Timothy Panella , Tibor Csőszi , Paola Gerletti , Mahgull Thakur , Anna Polli , Alessandra di Pietro , Dirk Schadendorf
{"title":"First-line encorafenib plus binimetinib and pembrolizumab for advanced BRAF V600-mutant melanoma: Safety lead-in results from the randomized phase III STARBOARD study","authors":"Oleksandr Dudnichenko , Konstantin Penkov , Meredith McKean , Mario Mandalà , Mariia Kukushkina , Timothy Panella , Tibor Csőszi , Paola Gerletti , Mahgull Thakur , Anna Polli , Alessandra di Pietro , Dirk Schadendorf","doi":"10.1016/j.ejca.2024.115070","DOIUrl":"10.1016/j.ejca.2024.115070","url":null,"abstract":"<div><h3>Background</h3><div>BRAF inhibitors plus MEK inhibitors (BRAFi/MEKi) and immune checkpoint inhibitors (CPIs) are approved for BRAF V600-mutant advanced melanoma. Combinations of BRAFi/MEKi with CPIs may further improve outcomes and could offer additional treatment strategies.</div></div><div><h3>Methods</h3><div>STARBOARD (NCT04657991) is a phase III study with an initial safety lead-in (SLI) phase conducted to determine the recommended phase III dose (RP3D) for encorafenib in combination with binimetinib and pembrolizumab. Patients with untreated, unresectable locally advanced or metastatic BRAF V600E/K-mutant cutaneous melanoma received binimetinib 45 mg twice daily and pembrolizumab 200 mg every 3 weeks plus encorafenib 450 mg once daily (COMBO450 plus pembrolizumab) or 300 mg once daily (COMBO300 plus pembrolizumab). The primary endpoint was the incidence of dose-limiting toxicities (DLTs). Secondary endpoints included safety, objective response, time to response, and duration of response. Progression-free survival was assessed post hoc.</div></div><div><h3>Results</h3><div>In the SLI, the median follow-up duration was 19.4 months. Twenty patients received COMBO450 plus pembrolizumab and 17 received COMBO300 plus pembrolizumab. DLTs occurred in 1 of 17 DLT-evaluable patients in the COMBO450 plus pembrolizumab arm and in 2 of 17 DLT-evaluable patients in the COMBO300 plus pembrolizumab arm. No treatment-related deaths occurred in either treatment arm. The overall response rate was 65.0 % in the COMBO450 plus pembrolizumab arm and 47.1 % in the COMBO300 plus pembrolizumab arm.</div></div><div><h3>Conclusion</h3><div>The STARBOARD SLI showed that safety across the cohorts was generally comparable to the known safety profile of each agent. The standard dose regimen of COMBO450 plus pembrolizumab was chosen as the RP3D.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461038","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}
Susanne Singer , Eva Hammerlid , Iwona M. Tomaszewska , Cecilie D. Amdal , Bente B. Herlofson , Marcos Santos , Joaquim Castro Silva , Hisham Mehanna , Amy Fullerton , Teresa Young , Loreto Fernandez Gonzalez , Johanna Inhestern , Monica Pinto , Juan I. Arraras , Noam Yarom , Pierluigi Bonomo , Ingo Baumann , Razvan Galalae , Ourania Nicolatou-Galitis , Naomi Kiyota , Kristin Bjordal
{"title":"The european organisation for research and treatment of cancer head and neck cancer module (EORTC QLQ-HN43): Estimates for minimal important difference and minimal important change","authors":"Susanne Singer , Eva Hammerlid , Iwona M. Tomaszewska , Cecilie D. Amdal , Bente B. Herlofson , Marcos Santos , Joaquim Castro Silva , Hisham Mehanna , Amy Fullerton , Teresa Young , Loreto Fernandez Gonzalez , Johanna Inhestern , Monica Pinto , Juan I. Arraras , Noam Yarom , Pierluigi Bonomo , Ingo Baumann , Razvan Galalae , Ourania Nicolatou-Galitis , Naomi Kiyota , Kristin Bjordal","doi":"10.1016/j.ejca.2024.115062","DOIUrl":"10.1016/j.ejca.2024.115062","url":null,"abstract":"<div><h3>Introduction</h3><div>Minimal important change estimates (MIC) are useful for interpreting results of clinical research with quality of life (QoL) as an endpoint. For the European Organisation for Research and Treatment of Cancer head and neck cancer module, the EORTC QLQ-HN43, no such thresholds are established.</div></div><div><h3>Methods</h3><div>Head and neck cancer patients under active treatment (n = 503) from 15 countries completed the EORTC QLQ-HN43 three times (t1: before treatment, t2: three months after t1, t3: six months after t1). A subgroup completed a Subjective Significance Questionnaire (SSQ), indicating experienced change from the previous time point in four QoL domains. QoL was assumed to deteriorate after t1 and improve again until t3. The MIC was established using the average of mean differences in SSQ groups (MIC<sub>mean</sub>) and estimates based on logistic regressions (MIC<sub>predict</sub>). Additionally, minimal detectable changes (MDC) were computed using 0.5 standard deviation and standard error of the mean.</div></div><div><h3>Results</h3><div>For <em>swallowing</em>, <em>speech</em>, <em>dry mouth,</em> and <em>global QoL</em>, the MIC for deterioration were 13, 14, 26, and 10 respectively. The MIC for improvement were 8 (<em>swallowing</em>), 6 (<em>dry mouth</em>), and 5 (<em>global QoL</em>); no MIC for <em>speech</em> improvement can be presented because of insufficient correlation between change score and anchor. The MDC estimates for deterioration were 15, 14, 15, and 11. For improvement, the MDC estimates were 13, 14, 14, and 11.</div></div><div><h3>Conclusions</h3><div>Our results underline that no single MIC or MDC can be applied to all EORTC QLQ-HN43 scales, and that the MIC for deterioration seems larger than those for improvement.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438224","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}
Khaled Elsayad , Emmanuella Guenova , Chalid Assaf , Jan P. Nicolay , Franz Trautinger , Rudolf Stadler , Cora Waldstein , Tom Boterberg , Paul Meijnders , Youlia Kirova , Gabor Dobos , Victor Duque-Santana , Elena Riggenbach , Wael Elsheshtawy , Anne Niezink , Evangelia Papadavid , Julia Scarisbrick , Maarten Vermeer , Karen J. Neelis , Martine Bagot , Dora Correia
{"title":"Radiotherapy in cutaneous lymphomas: Recommendations from the EORTC cutaneous lymphoma tumour group","authors":"Khaled Elsayad , Emmanuella Guenova , Chalid Assaf , Jan P. Nicolay , Franz Trautinger , Rudolf Stadler , Cora Waldstein , Tom Boterberg , Paul Meijnders , Youlia Kirova , Gabor Dobos , Victor Duque-Santana , Elena Riggenbach , Wael Elsheshtawy , Anne Niezink , Evangelia Papadavid , Julia Scarisbrick , Maarten Vermeer , Karen J. Neelis , Martine Bagot , Dora Correia","doi":"10.1016/j.ejca.2024.115064","DOIUrl":"10.1016/j.ejca.2024.115064","url":null,"abstract":"<div><div>The number of primary cutaneous lymphoma patients receiving low-dose radiotherapy is increasing, though controlled clinical trials defining the standard radiation dose for each specific entity have not yet been completed. Radiation oncologists are left with making highly individualized decisions that would be better enriched by additional clinical evidence. In this expert opinion, we aim to provide a clear recommendation to improve the current practice of radiation oncology. In addition, existing literature has been reviewed to develop recommendations for all types of primary cutaneous lymphoma. A prospective trial is urgently needed to identify the factors influencing patient outcomes following different radiation doses.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":7.6,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441257","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}