Pub Date : 2025-02-05DOI: 10.1016/j.ejca.2024.115211
Signe Bergliot Nielsen , Nina Munk Lyhne , Maria Andersen , Christina Caroline Plaschke , Anita Birgitte Gothelf , Jørgen Johansen , Christian Maare , Mohammad Farhadi , Christian Godballe , Hanne Primdahl , Anne Ivalu Sander Holm , Jan Alsner , Thomas Kjærgaard , Jens Overgaard
Background
Diagnostic and therapeutic management of patients with head and neck squamous cell carcinoma of unknown primary (HNSCCUP) remains a challenge. The aim of the present phase IV study was to assess adherence to the current Danish guidelines and evaluate the treatment outcome in HNSCCUP patients.
Materials and methods
Prospectively collected data in the DAHANCA database from patients treated between 2014 and 2020 was evaluated. The median follow-up was 6.7 years. Treatment included definitive neck dissection (dND), primary (chemo-)radiotherapy ((C-)RT), neck dissection (ND) followed by postoperative (C-)RT (ND + (C-)PORT). Outcome were reported as five-year estimates of loco-regional failure (LRF), ultimate LRF (ULRF), disease specific mortality (DSM), overall survival (OS), and toxicity scores ≥ 3.
Results
A total of 288 patients were treated, of which 254 (88 %) received treatment with curative intent and were eligible for adherence assessment. These were allocated to dND (n = 60), (C-)RT (n = 81) and ND + (C-)PORT (n = 113). The HPV/p16 status was known in 94 % of patients with 109 (43 %) positive cases. The 5-year LRF, DSM, and OS for patients treated with curative intent was 22 %, 15 % and 73 %, and in patients with p16 positive disease 16 %, 5 %, and 85 %. The overall guideline adherence was 76 % (192/254). In the adherent group the LRF, ULRF, DSM, and OS were 22 %, 11 %, 16 %, and 73 %, respectively.
Conclusion
The study revealed good treatment outcome measures in HNSCCUP patients subject to the Danish guidelines, comparable to other head and neck cancer patients. The observed guideline-deviations did not affect outcome.
{"title":"Management of head and neck cancer of unknown primary: A phase IV study by DAHANCA","authors":"Signe Bergliot Nielsen , Nina Munk Lyhne , Maria Andersen , Christina Caroline Plaschke , Anita Birgitte Gothelf , Jørgen Johansen , Christian Maare , Mohammad Farhadi , Christian Godballe , Hanne Primdahl , Anne Ivalu Sander Holm , Jan Alsner , Thomas Kjærgaard , Jens Overgaard","doi":"10.1016/j.ejca.2024.115211","DOIUrl":"10.1016/j.ejca.2024.115211","url":null,"abstract":"<div><h3>Background</h3><div>Diagnostic and therapeutic management of patients with head and neck squamous cell carcinoma of unknown primary (HNSCCUP) remains a challenge. The aim of the present phase IV study was to assess adherence to the current Danish guidelines and evaluate the treatment outcome in HNSCCUP patients.</div></div><div><h3>Materials and methods</h3><div>Prospectively collected data in the DAHANCA database from patients treated between 2014 and 2020 was evaluated. The median follow-up was 6.7 years. Treatment included definitive neck dissection (dND), primary (chemo-)radiotherapy ((C-)RT), neck dissection (ND) followed by postoperative (C-)RT (ND + (C-)PORT). Outcome were reported as five-year estimates of loco-regional failure (LRF), ultimate LRF (ULRF), disease specific mortality (DSM), overall survival (OS), and toxicity scores ≥ 3.</div></div><div><h3>Results</h3><div>A total of 288 patients were treated, of which 254 (88 %) received treatment with curative intent and were eligible for adherence assessment. These were allocated to dND (n = 60), (C-)RT (n = 81) and ND + (C-)PORT (n = 113). The HPV/p16 status was known in 94 % of patients with 109 (43 %) positive cases. The 5-year LRF, DSM, and OS for patients treated with curative intent was 22 %, 15 % and 73 %, and in patients with p16 positive disease 16 %, 5 %, and 85 %. The overall guideline adherence was 76 % (192/254). In the adherent group the LRF, ULRF, DSM, and OS were 22 %, 11 %, 16 %, and 73 %, respectively.</div></div><div><h3>Conclusion</h3><div>The study revealed good treatment outcome measures in HNSCCUP patients subject to the Danish guidelines, comparable to other head and neck cancer patients. The observed guideline-deviations did not affect outcome.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"216 ","pages":"Article 115211"},"PeriodicalIF":7.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926612","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}
Pub Date : 2025-02-05DOI: 10.1016/j.ejca.2024.115196
F. Poumeaud , T. Valentin , N. Fares , B. Segier , S. Watson , B. Verret , C. Tlemsani , N. Penel , S. Lejeune , N. Firmin , A. Sabouret , J.-C. Thery , S. Bonvalot , E. Cottereau , E. Cauchin , A. Lancon , S. Nambot , H. Zattara , M. Coudert , E. Fourme , R. Guimbaud
Background
Sarcomas do not belong to the Lynch Syndrome (LS)-tumour spectrum. A growing body literature has reported sarcomas in patients with LS. Clinical and tumour characteristics of these patients remain unknown.
Patients and methods
We set up the first national retrospective study, SarcLynch, describing the pathological and clinical characteristics of sarcomas developed in patients with LS. Patients were identified from two national networks and included from 23 centres in France.
Results
Eighty-one patients participated in the SarcLynch study. Sixty-seven (83 %) tumours were soft-tissue sarcomas (STS) and 14 (17 %) bone sarcomas. Among STS, 59 (88 %) showed a pleomorphic component, with undifferentiated pleomorphic sarcoma (UPS) (36 %) and pleomorphic rhabdomyosarcoma (pRMS) (21 %) being the most represented subtypes. Sarcoma was the first neoplastic event in 32 patients (40 %). Thirty-two patients (40 %) were carriers of MSH2 germline pathogenic variants. Among patients who underwent an assessment of deficient mismatch repair (dMMR) by immunohistochemistry and/or molecular biology status, 75 % were dMMR by immunohistochemistry and 45 % were microsatellite instability high (MSI-H). Eight patients received immune checkpoint inhibitors and 4 (50 %) exhibited an objective response with 3 complete radiological response including 1 patient with pathological complete response. Duration of response ranged from 6 to 20 months.
Conclusions
SarcLynch, the largest multicentric series describing sarcomas developed in patients with LS, revealed an enrichment in patients with pleomorphic sarcomas – especially UPS and pRMS. This finding strongly supports screening for MMR status evaluation in these rare histotypes both for oncogenetic screening and therapeutic interest. Considering an objective response rate of 50 %, access to immunotherapy should be considered in these tumours.
{"title":"Sarcomas developed in patients with Lynch Syndrome are enriched in pleomorphic soft-tissue sarcomas and are sensitive to immunotherapy","authors":"F. Poumeaud , T. Valentin , N. Fares , B. Segier , S. Watson , B. Verret , C. Tlemsani , N. Penel , S. Lejeune , N. Firmin , A. Sabouret , J.-C. Thery , S. Bonvalot , E. Cottereau , E. Cauchin , A. Lancon , S. Nambot , H. Zattara , M. Coudert , E. Fourme , R. Guimbaud","doi":"10.1016/j.ejca.2024.115196","DOIUrl":"10.1016/j.ejca.2024.115196","url":null,"abstract":"<div><h3>Background</h3><div>Sarcomas do not belong to the Lynch Syndrome (LS)-tumour spectrum. A growing body literature has reported sarcomas in patients with LS. Clinical and tumour characteristics of these patients remain unknown.</div></div><div><h3>Patients and methods</h3><div>We set up the first national retrospective study, SarcLynch, describing the pathological and clinical characteristics of sarcomas developed in patients with LS. Patients were identified from two national networks and included from 23 centres in France.</div></div><div><h3>Results</h3><div>Eighty-one patients participated in the SarcLynch study. Sixty-seven (83 %) tumours were soft-tissue sarcomas (STS) and 14 (17 %) bone sarcomas. Among STS, 59 (88 %) showed a pleomorphic component, with undifferentiated pleomorphic sarcoma (UPS) (36 %) and pleomorphic rhabdomyosarcoma (pRMS) (21 %) being the most represented subtypes. Sarcoma was the first neoplastic event in 32 patients (40 %). Thirty-two patients (40 %) were carriers of <em>MSH2</em> germline pathogenic variants. Among patients who underwent an assessment of deficient mismatch repair (dMMR) by immunohistochemistry and/or molecular biology status, 75 % were dMMR by immunohistochemistry and 45 % were microsatellite instability high (MSI-H). Eight patients received immune checkpoint inhibitors and 4 (50 %) exhibited an objective response with 3 complete radiological response including 1 patient with pathological complete response. Duration of response ranged from 6 to 20 months.</div></div><div><h3>Conclusions</h3><div>SarcLynch, the largest multicentric series describing sarcomas developed in patients with LS, revealed an enrichment in patients with pleomorphic sarcomas – especially UPS and pRMS. This finding strongly supports screening for MMR status evaluation in these rare histotypes both for oncogenetic screening and therapeutic interest. Considering an objective response rate of 50 %, access to immunotherapy should be considered in these tumours.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"216 ","pages":"Article 115196"},"PeriodicalIF":7.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914044","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}
Pub Date : 2025-02-05DOI: 10.1016/j.ejca.2025.115221
Rik J. Verheijden , Mick J.M. van Eijs , Fernanda L. Paganelli , Marco C. Viveen , Malbert R.C. Rogers , Janetta Top , Anne M. May , Janneke H.H.M. van de Wijgert , Karijn P.M. Suijkerbuijk , on behalf of the UNICIT-consortium
Background
Multiple studies have suggested that gut microbiome may influence immune checkpoint inhibitor (ICI) efficacy, but its association with immune-related adverse events (irAEs) is less well studied. In this prospective cohort study, we assessed whether gut microbiome composition at start, or changes during ICI, are associated with severe irAEs.
Methods
Stool samples of cancer patients treated with anti-PD-1 ± anti-CTLA-4 were analyzed using 16S rRNA gene sequencing and metagenomic shotgun sequencing. Differences in alpha and beta diversity between patients with and without severe irAE were assessed, as well as differential relative abundance (RA) of taxa, MetaCyc pathways, and seven prespecified literature-based bacterial groups including pathobionts and Ruminococcaceae.
Findings
We analyzed 497 samples of 195 patients before and soon after starting ICI, at severe irAE onset and after starting immunosuppression. Mean RA of the pathobionts group was significantly higher in patients who developed a severe irAE (8.2 %) compared to those who did not (4.8 %; odds ratio 1.40; 95 %CI 1.07–1.87) at baseline, and also early during ICI treatment and at severe irAE onset. A significantly stronger decrease in RA of Ruminococcaceae after starting ICI was observed in patients who developed a severe irAE compared to those who did not. RAs of Ruminococcaceae, the genus Ruminococcus, and the species R. bromii and R. callidus were significantly lower at severe irAE onset compared to other time points.
Interpretation
Gut microbiome dysbiosis signaled by higher RA of pathobionts and decrease in RA of Ruminococcaceae may predispose to severe irAEs.
{"title":"Gut microbiome and immune checkpoint inhibitor toxicity","authors":"Rik J. Verheijden , Mick J.M. van Eijs , Fernanda L. Paganelli , Marco C. Viveen , Malbert R.C. Rogers , Janetta Top , Anne M. May , Janneke H.H.M. van de Wijgert , Karijn P.M. Suijkerbuijk , on behalf of the UNICIT-consortium","doi":"10.1016/j.ejca.2025.115221","DOIUrl":"10.1016/j.ejca.2025.115221","url":null,"abstract":"<div><h3>Background</h3><div>Multiple studies have suggested that gut microbiome may influence immune checkpoint inhibitor (ICI) efficacy, but its association with immune-related adverse events (irAEs) is less well studied. In this prospective cohort study, we assessed whether gut microbiome composition at start, or changes during ICI, are associated with severe irAEs.</div></div><div><h3>Methods</h3><div>Stool samples of cancer patients treated with anti-PD-1 ± anti-CTLA-4 were analyzed using 16S rRNA gene sequencing and metagenomic shotgun sequencing. Differences in alpha and beta diversity between patients with and without severe irAE were assessed, as well as differential relative abundance (RA) of taxa, MetaCyc pathways, and seven prespecified literature-based bacterial groups including pathobionts and Ruminococcaceae.</div></div><div><h3>Findings</h3><div>We analyzed 497 samples of 195 patients before and soon after starting ICI, at severe irAE onset and after starting immunosuppression. Mean RA of the pathobionts group was significantly higher in patients who developed a severe irAE (8.2 %) compared to those who did not (4.8 %; odds ratio 1.40; 95 %CI 1.07–1.87) at baseline, and also early during ICI treatment and at severe irAE onset. A significantly stronger decrease in RA of Ruminococcaceae after starting ICI was observed in patients who developed a severe irAE compared to those who did not. RAs of Ruminococcaceae, the genus <em>Ruminococcus</em>, and the species <em>R. bromii</em> and <em>R. callidus</em> were significantly lower at severe irAE onset compared to other time points.</div></div><div><h3>Interpretation</h3><div>Gut microbiome dysbiosis signaled by higher RA of pathobionts and decrease in RA of Ruminococcaceae may predispose to severe irAEs.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"216 ","pages":"Article 115221"},"PeriodicalIF":7.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964226","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}
Pub Date : 2025-02-05DOI: 10.1016/j.ejca.2024.115165
D. Di Carlo , M. Annereau , M. Vignes , L. Denis , N. Epaillard , S. Dumont , D. Guyon , A. Rieutord , S. Jacobs , V. Salomon , I. Yoldjian , F. Duperray , L. Brunel , X. Baiao , F. Lemos , E. Vauleon , M. Capra , S. Abbou , M. Touat , M. Sanson , J. Grill
Introduction
H3K27-altered diffuse midline gliomas (DMG) have limited therapeutic options and a very poor prognosis. Encouraging responses were observed in early clinical trials with ONC201. As ONC201 was unavailable in Europe, a compassionate use program supported by the French Authorities was launched for patients at progression after standard of care radiotherapy.
Methods
This program was developed by the French Society of Pediatric Oncology (SFCE) and Association des Neuro-Oncologues d′Expression Française in collaboration with the French National Agency For Medicines and Health Products Safety and Parents Associations.
Results
174 patients (102 children, 72 adults) from 14 countries were treated from November 2021 to August 2023 at Gustave Roussy Institut (Villejuif, France). 37 % received a second course of irradiation at the time of relapse. Median duration of treatment was 57 days or 1,9 months (mo) (range 1–456 days). Median OS since diagnosis for the whole cohort was 466 days or 15,5 mo (112–2612 days); 426 or 14,2 mo (112–2612 days) and 590 or 19,6 mo (range 160–1881) for children and adults, respectively (p = 0.001). Median OS after ONC201 start was 143 days or 4,7 mo (1–711 days) for the whole cohort. Univariate and multivariable analysis identified site (thalamus) and age (older) as favorable prognostic factors. Reirradiation was associated with significantly longer survival after ONC201 start only in children.
Conclusion
While the efficacy of ONC201 needs validation in a controlled randomized clinical trial, our real-life data support a better outcome for patients with thalamic tumors treated with ONC201. We demonstrated furthermore the feasibility of a successful academia-driven compassionate use program
h3k27改变的弥漫性中线胶质瘤（DMG）的治疗选择有限，预后非常差。在ONC201的早期临床试验中观察到令人鼓舞的反应。由于ONC201在欧洲无法获得，由法国当局支持的一项同情使用计划针对标准护理放疗后进展的患者启动。方法：该项目由法国儿科肿瘤学会（SFCE）和法国神经肿瘤表达协会与法国国家药品和健康产品安全局以及家长协会合作开发。结果：来自14个国家的174名患者（102名儿童，72名成人）于2021年11月至2023年8月在Gustave Roussy institute （Villejuif, France）接受了治疗。37%的患者在复发时接受了第二疗程的放疗。治疗中位持续时间为57天或1.9个月（范围1-456天）。自诊断以来，整个队列的中位生存期为466天或15.5个月（112-2612天）；儿童和成人分别为426或14.2个月（112-2612天）和590或19.6个月（160-1881天）（p = 0.001）。在整个队列中，ONC201开始后的中位OS为143天或4.7个月（1-711天）。单变量和多变量分析确定部位（丘脑）和年龄（老年）是有利的预后因素。仅在儿童中，ONC201开始后再照射与更长的生存期相关。结论：虽然ONC201的疗效需要在对照随机临床试验中验证，但我们的实际数据支持ONC201治疗丘脑肿瘤患者的更好结果。我们进一步证明了一个成功的学术驱动的同情心使用计划的可行性。
{"title":"Real life data of ONC201 (dordaviprone) in pediatric and adult H3K27-altered recurrent diffuse midline glioma: Results of an international academia-driven compassionate use program","authors":"D. Di Carlo , M. Annereau , M. Vignes , L. Denis , N. Epaillard , S. Dumont , D. Guyon , A. Rieutord , S. Jacobs , V. Salomon , I. Yoldjian , F. Duperray , L. Brunel , X. Baiao , F. Lemos , E. Vauleon , M. Capra , S. Abbou , M. Touat , M. Sanson , J. Grill","doi":"10.1016/j.ejca.2024.115165","DOIUrl":"10.1016/j.ejca.2024.115165","url":null,"abstract":"<div><h3>Introduction</h3><div>H3K27-altered diffuse midline gliomas (DMG) have limited therapeutic options and a very poor prognosis. Encouraging responses were observed in early clinical trials with ONC201. As ONC201 was unavailable in Europe, a compassionate use program supported by the French Authorities was launched for patients at progression after standard of care radiotherapy.</div></div><div><h3>Methods</h3><div>This program was developed by the French Society of Pediatric Oncology (SFCE) and Association des Neuro-Oncologues d′Expression Française in collaboration with the French National Agency For Medicines and Health Products Safety and Parents Associations.</div></div><div><h3>Results</h3><div>174 patients (102 children, 72 adults) from 14 countries were treated from November 2021 to August 2023 at Gustave Roussy Institut (Villejuif, France). 37 % received a second course of irradiation at the time of relapse. Median duration of treatment was 57 days or 1,9 months (mo) (range 1–456 days). Median OS since diagnosis for the whole cohort was 466 days or 15,5 mo (112–2612 days); 426 or 14,2 mo (112–2612 days) and 590 or 19,6 mo (range 160–1881) for children and adults, respectively (p = 0.001). Median OS after ONC201 start was 143 days or 4,7 mo (1–711 days) for the whole cohort. Univariate and multivariable analysis identified site (thalamus) and age (older) as favorable prognostic factors. Reirradiation was associated with significantly longer survival after ONC201 start only in children.</div></div><div><h3>Conclusion</h3><div>While the efficacy of ONC201 needs validation in a controlled randomized clinical trial, our real-life data support a better outcome for patients with thalamic tumors treated with ONC201. We demonstrated furthermore the feasibility of a successful academia-driven compassionate use program</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"216 ","pages":"Article 115165"},"PeriodicalIF":7.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863729","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}
Pub Date : 2025-02-05DOI: 10.1016/j.ejca.2024.115198
Johnny Duerinck , Philipp Karschnia , Marike Broekman , Jens Gempt , George E.D. Petrescu , Asgeir S. Jakola , Rachel Grossman , Roland Goldbrunner , Michael D. Jenkinson , Georg Widhalm , Marian Neidert , Thiebaud Picart , Caroline Quoilin , Thierry Gorlia , Emilie Le Rhun , Giuseppe Minniti , Matthias Preusser , Michael Weller
The Brain Tumor Group (BTG) of the European Organization for Research and Treatment of Cancer (EORTC) conducts academic clinical trials and translational research to improve clinical management of patients with primary and secondary brain tumors. The EORTC BTG has traditionally played an important role in providing evidence and thus advancing the field, albeit with a main focus on radiotherapy and pharmacotherapy in gliomas. Although examples of well-designed neuro-oncological surgical trials can be found, evidence in surgical neuro-oncology predominantly includes data from uncontrolled prospective series or retrospective cohorts. By means of a thorough literature and EORTC database review, we demonstrate, firstly, that while the pathway of the neuro-oncology patient most often starts with neurosurgery, its several aspects have traditionally been poorly acknowledged in clinical trials in neuro-oncology. We also show that the definitions and methods of assessment vary greatly between studies, limiting generalizability. The newly established Neurosurgery Committee of the EORTC BTG aims to address this gap by increasing the number of prospective surgical trials, but also the involvement of neurosurgeons in clinical trial design, promoting standardized terminology for description of the surgical aspects, including extent of resection. We will also explore alternative trial designs when randomization is deemed difficult, as well as focus on defining surgical quality indicators that influence outcome. By addressing these challenges, the committee aims to enhance the quality of neurosurgical evidence in neuro-oncology and define optimal surgical methods and standards of care. This should ultimately improve outcomes and quality of life for patients with brain tumors through evidence-based surgical interventions.
{"title":"Addressing the role of surgery in brain tumour trials: A report from the neurosurgery committee of the EORTC brain tumour group","authors":"Johnny Duerinck , Philipp Karschnia , Marike Broekman , Jens Gempt , George E.D. Petrescu , Asgeir S. Jakola , Rachel Grossman , Roland Goldbrunner , Michael D. Jenkinson , Georg Widhalm , Marian Neidert , Thiebaud Picart , Caroline Quoilin , Thierry Gorlia , Emilie Le Rhun , Giuseppe Minniti , Matthias Preusser , Michael Weller","doi":"10.1016/j.ejca.2024.115198","DOIUrl":"10.1016/j.ejca.2024.115198","url":null,"abstract":"<div><div>The Brain Tumor Group (BTG) of the European Organization for Research and Treatment of Cancer (EORTC) conducts academic clinical trials and translational research to improve clinical management of patients with primary and secondary brain tumors. The EORTC BTG has traditionally played an important role in providing evidence and thus advancing the field, albeit with a main focus on radiotherapy and pharmacotherapy in gliomas. Although examples of well-designed neuro-oncological surgical trials can be found, evidence in surgical neuro-oncology predominantly includes data from uncontrolled prospective series or retrospective cohorts. By means of a thorough literature and EORTC database review, we demonstrate, firstly, that while the pathway of the neuro-oncology patient most often starts with neurosurgery, its several aspects have traditionally been poorly acknowledged in clinical trials in neuro-oncology. We also show that the definitions and methods of assessment vary greatly between studies, limiting generalizability. The newly established Neurosurgery Committee of the EORTC BTG aims to address this gap by increasing the number of prospective surgical trials, but also the involvement of neurosurgeons in clinical trial design, promoting standardized terminology for description of the surgical aspects, including extent of resection. We will also explore alternative trial designs when randomization is deemed difficult, as well as focus on defining surgical quality indicators that influence outcome. By addressing these challenges, the committee aims to enhance the quality of neurosurgical evidence in neuro-oncology and define optimal surgical methods and standards of care. This should ultimately improve outcomes and quality of life for patients with brain tumors through evidence-based surgical interventions.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"216 ","pages":"Article 115198"},"PeriodicalIF":7.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893148","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}
Pub Date : 2025-02-05DOI: 10.1016/j.ejca.2024.115199
Frederik Marmé , Eva I. Krieghoff-Henning , Lennard Kiehl , Christoph Wies , Jan Hauke , Eric Hahnen , Philipp Harter , Philip C. Schouten , Tobias Brodkorb , Mohamad Kayali , Florian Heitz , Claudio Zamagni , Antonio González-Martin , Isabelle Treilleux , Stefan Kommoss , Katharina Prieske , Timo Gaiser , Stefan Fröhling , Isabelle Ray-Coquard , Eric Pujade-Lauraine , Titus J. Brinker
Purpose
Ovarian cancer patients with a Homologous Recombination Deficiency (HRD) often benefit from polyadenosine diphosphate–ribose polymerase (PARP) inhibitor maintenance therapy after response to platinum-based chemotherapy. HR status is currently analyzed via complex molecular tests. Predicting benefit from PARP inhibitors directly on histological whole slide images (WSIs) could be a fast and cheap alternative.
Patients and methods
We trained a Deep Learning (DL) model on H&E stained WSIs with “shrunken centroid” (SC) based HRD ground truth using the AGO-TR1 cohort (n = 208: 108 training, 100 test) and tested its ability to predict HRD as evaluated by the Myriad classifier and the benefit from olaparib in the PAOLA-1 cohort (n = 447) in a blinded manner.
Results
In contrast to the HRD prediction AUROC of 72 % on hold-out, our model only yielded an AUROC of 57 % external. Kaplan-Meier analysis showed that progression free survival (PFS) in the PARP inhibitor treated PAOLA-1 patients was significantly improved in the HRD positive group as defined by our model, but not in the HRD negative group. PFS improvement in PARP inhibitor-treated patients was substantially longer in our HRD positive group, hinting at a biologically meaningful prediction of benefit from PARP inhibitors.
Conclusion
Together, our results indicate that it might be possible to generate a predictor of benefit from PARP inhibitors based on the DL-mediated analysis of WSIs. However, further studies with larger cohorts and further methodological improvements will be necessary to generate a predictor with clinically useful accuracy across independent patient cohorts.
{"title":"Predicting benefit from PARP inhibitors using deep learning on H&E-stained ovarian cancer slides","authors":"Frederik Marmé , Eva I. Krieghoff-Henning , Lennard Kiehl , Christoph Wies , Jan Hauke , Eric Hahnen , Philipp Harter , Philip C. Schouten , Tobias Brodkorb , Mohamad Kayali , Florian Heitz , Claudio Zamagni , Antonio González-Martin , Isabelle Treilleux , Stefan Kommoss , Katharina Prieske , Timo Gaiser , Stefan Fröhling , Isabelle Ray-Coquard , Eric Pujade-Lauraine , Titus J. Brinker","doi":"10.1016/j.ejca.2024.115199","DOIUrl":"10.1016/j.ejca.2024.115199","url":null,"abstract":"<div><h3>Purpose</h3><div>Ovarian cancer patients with a Homologous Recombination Deficiency (HRD) often benefit from polyadenosine diphosphate–ribose polymerase (PARP) inhibitor maintenance therapy after response to platinum-based chemotherapy. HR status is currently analyzed via complex molecular tests. Predicting benefit from PARP inhibitors directly on histological whole slide images (WSIs) could be a fast and cheap alternative.</div></div><div><h3>Patients and methods</h3><div>We trained a Deep Learning (DL) model on H&E stained WSIs with “shrunken centroid” (SC) based HRD ground truth using the AGO-TR1 cohort (n = 208: 108 training, 100 test) and tested its ability to predict HRD as evaluated by the Myriad classifier and the benefit from olaparib in the PAOLA-1 cohort (n = 447) in a blinded manner.</div></div><div><h3>Results</h3><div>In contrast to the HRD prediction AUROC of 72 % on hold-out, our model only yielded an AUROC of 57 % external. Kaplan-Meier analysis showed that progression free survival (PFS) in the PARP inhibitor treated PAOLA-1 patients was significantly improved in the HRD positive group as defined by our model, but not in the HRD negative group. PFS improvement in PARP inhibitor-treated patients was substantially longer in our HRD positive group, hinting at a biologically meaningful prediction of benefit from PARP inhibitors.</div></div><div><h3>Conclusion</h3><div>Together, our results indicate that it might be possible to generate a predictor of benefit from PARP inhibitors based on the DL-mediated analysis of WSIs. However, further studies with larger cohorts and further methodological improvements will be necessary to generate a predictor with clinically useful accuracy across independent patient cohorts.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"216 ","pages":"Article 115199"},"PeriodicalIF":7.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914043","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}
Anaplastic Lymphoma Kinase (ALK) rearrangement is a rare alteration in differentiated thyroid carcinomas (DTCs). Due to its low prevalence, a few evidence are available about the use of ALK inhibitors in advanced DTCs.
Methods
We report the case of a striatin (STRN) - ALK translocated advanced thyroid carcinoma.
STRN – ALK translocation was detected by NGS – RNA analysis.
Results
A 74-year-old woman received first line alectinib for the treatment of a STRN - ALK translocated advanced thyroid carcinoma with symptomatic bilateral lung localizations.
The dose of alectinib was progressively reduced due to the toxicity, but the treatment is still ongoing after 17 months with complete radiological response and clinical benefit.
Conclusion
Here we report the first case in Europe of STRN - ALK translocated advanced thyroid carcinoma successfully treated with alectinib.
{"title":"Alectinib for the treatment of papillary thyroid carcinoma harbouring STRN – ALK fusion","authors":"Silvia Buriolla , Giulia Zapelloni , Claudia Cipri , Giacomo Pelizzari , Alessandro Follador , Francesco Cortiula","doi":"10.1016/j.ejca.2024.115193","DOIUrl":"10.1016/j.ejca.2024.115193","url":null,"abstract":"<div><h3>Background</h3><div>Anaplastic Lymphoma Kinase (<em>ALK</em>) rearrangement is a rare alteration in differentiated thyroid carcinomas (DTCs). Due to its low prevalence, a few evidence are available about the use of <em>ALK</em> inhibitors in advanced DTCs.</div></div><div><h3>Methods</h3><div>We report the case of a striatin (<em>STRN</em>) - <em>ALK</em> translocated advanced thyroid carcinoma.</div><div><em>STRN – ALK</em> translocation was detected by NGS – RNA analysis.</div></div><div><h3>Results</h3><div>A 74-year-old woman received first line alectinib for the treatment of a <em>STRN</em> - <em>ALK</em> translocated advanced thyroid carcinoma with symptomatic bilateral lung localizations.</div><div>The dose of alectinib was progressively reduced due to the toxicity, but the treatment is still ongoing after 17 months with complete radiological response and clinical benefit.</div></div><div><h3>Conclusion</h3><div>Here we report the first case in Europe of <em>STRN</em> - <em>ALK</em> translocated advanced thyroid carcinoma successfully treated with alectinib.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"216 ","pages":"Article 115193"},"PeriodicalIF":7.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893150","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}
Pub Date : 2025-02-05DOI: 10.1016/j.ejca.2025.115250
Yingfang Feng, Huilai Zhang, Xianhuo Wang
{"title":"Response to Letter Entitled “Elevated serum magnesium levels prompt favourable outcomes in cancer patients treated with immune checkpoint blockers”","authors":"Yingfang Feng, Huilai Zhang, Xianhuo Wang","doi":"10.1016/j.ejca.2025.115250","DOIUrl":"10.1016/j.ejca.2025.115250","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"216 ","pages":"Article 115250"},"PeriodicalIF":7.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022764","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}
Pub Date : 2025-02-05DOI: 10.1016/j.ejca.2024.115170
Cho-Han Chiang , Junmin Song , Kuan-Yu Chi , Yu-Cheng Chang , Nutchapon Xanthavanij , Yu Chang , Yuan Ping Hsia , Cho-Hung Chiang , Azin Ghamari , Kerry L. Reynolds , Shuwen Lin , Xiaocao “Haze” Xu , Tomas G. Neilan
Background
Immune checkpoint inhibitors (ICIs) are associated with an increased risk of major adverse cardiovascular events (MACE). Glucagon-like peptide-1 agonists (GLP1a), initially developed for type 2 diabetes mellitus (T2DM), have shown promising results in reducing cardiovascular events. We aimed to investigate the effect of GLP1a on cardiovascular events in patients receiving ICIs.
Methods
We conducted a retrospective, propensity score-matched cohort study using the TriNetX database. We identified adults with cancer and T2DM who received ICIs between April 2013 and May 2023. The primary efficacy outcome was incident MACE, defined as a composite of myocardial infarction, need for coronary revascularization, heart failure, ischemic stroke, and cardiac arrest. The secondary efficacy outcomes were the individual components of MACE as well as myocarditis and pericarditis. Safety outcomes included the occurrence of immune-related adverse events, serious adverse events related to GLP1a use, and all-cause mortality.
Results
We identified 7651 patients eligible for inclusion, among which 479 received GLP1a and 7172 received non-GLP1a diabetes medications. After matching (469 patients each), baseline characteristics were well-balanced. Over a median 12-month follow-up, the GLP1a cohort had a significantly lower MACE incidence than the non-GLP1a cohort (9.0 vs. 17.1 events per 100 patient-years) with a 54 % lower risk of MACE (Hazard ratio (HR),0.46 [95 % CI: 0.32–0.67]). There were reductions in myocardial infarction or need for coronary revascularization, heart failure, and all-cause mortality, with no differences in other cardiovascular events. GLP1a use did not increase risk of adverse events, including pancreatitis, biliary disease, bowel obstruction, gastroparesis, and immune-related adverse events.
Conclusion
GLP1a use in cancer patients with T2DM receiving ICIs was associated with reduced MACE and all-cause mortality without an increased risk in serious adverse events.
背景：免疫检查点抑制剂（ICIs）与主要不良心血管事件（MACE）风险增加相关。胰高血糖素样肽-1激动剂（GLP1a）最初是为2型糖尿病（T2DM）开发的，在减少心血管事件方面显示出有希望的结果。我们的目的是研究GLP1a对接受ICIs患者心血管事件的影响。方法：我们使用TriNetX数据库进行回顾性倾向评分匹配队列研究。我们确定了在2013年4月至2023年5月期间接受ICIs治疗的患有癌症和2型糖尿病的成年人。主要疗效指标是MACE的发生率，定义为心肌梗死、冠状动脉血运重建、心力衰竭、缺血性卒中和心脏骤停的综合指标。次要疗效结果是MACE的各个成分以及心肌炎和心包炎。安全性结局包括免疫相关不良事件的发生、与GLP1a使用相关的严重不良事件和全因死亡率。结果：我们确定了7651例符合纳入条件的患者，其中479例接受GLP1a治疗，7172例接受非GLP1a糖尿病药物治疗。匹配后（各469例），基线特征平衡良好。在中位12个月的随访中，GLP1a队列的MACE发生率显著低于非GLP1a队列（9.0 vs. 17.1事件/ 100患者年），MACE风险降低54%（风险比（HR），0.46 [95% CI: 0.32-0.67]）。心肌梗死、冠状动脉血运重建术、心力衰竭和全因死亡率均有降低，其他心血管事件无差异。GLP1a的使用不会增加不良事件的风险，包括胰腺炎、胆道疾病、肠梗阻、胃轻瘫和免疫相关不良事件。结论：GLP1a在接受ICIs治疗的T2DM癌症患者中使用与降低MACE和全因死亡率相关，且未增加严重不良事件的风险。
{"title":"Glucagon-like Peptide‐1 Agonists Reduce Cardiovascular Events in Cancer Patients on Immune Checkpoint Inhibitors","authors":"Cho-Han Chiang , Junmin Song , Kuan-Yu Chi , Yu-Cheng Chang , Nutchapon Xanthavanij , Yu Chang , Yuan Ping Hsia , Cho-Hung Chiang , Azin Ghamari , Kerry L. Reynolds , Shuwen Lin , Xiaocao “Haze” Xu , Tomas G. Neilan","doi":"10.1016/j.ejca.2024.115170","DOIUrl":"10.1016/j.ejca.2024.115170","url":null,"abstract":"<div><h3>Background</h3><div>Immune checkpoint inhibitors (ICIs) are associated with an increased risk of major adverse cardiovascular events (MACE). Glucagon-like peptide-1 agonists (GLP1a), initially developed for type 2 diabetes mellitus (T2DM), have shown promising results in reducing cardiovascular events. We aimed to investigate the effect of GLP1a on cardiovascular events in patients receiving ICIs.</div></div><div><h3>Methods</h3><div>We conducted a retrospective, propensity score-matched cohort study using the TriNetX database. We identified adults with cancer and T2DM who received ICIs between April 2013 and May 2023. The primary efficacy outcome was incident MACE, defined as a composite of myocardial infarction, need for coronary revascularization, heart failure, ischemic stroke, and cardiac arrest. The secondary efficacy outcomes were the individual components of MACE as well as myocarditis and pericarditis. Safety outcomes included the occurrence of immune-related adverse events, serious adverse events related to GLP1a use, and all-cause mortality.</div></div><div><h3>Results</h3><div>We identified 7651 patients eligible for inclusion, among which 479 received GLP1a and 7172 received non-GLP1a diabetes medications. After matching (469 patients each), baseline characteristics were well-balanced. Over a median 12-month follow-up, the GLP1a cohort had a significantly lower MACE incidence than the non-GLP1a cohort (9.0 vs. 17.1 events per 100 patient-years) with a 54 % lower risk of MACE (Hazard ratio (HR),0.46 [95 % CI: 0.32–0.67]). There were reductions in myocardial infarction or need for coronary revascularization, heart failure, and all-cause mortality, with no differences in other cardiovascular events. GLP1a use did not increase risk of adverse events, including pancreatitis, biliary disease, bowel obstruction, gastroparesis, and immune-related adverse events.</div></div><div><h3>Conclusion</h3><div>GLP1a use in cancer patients with T2DM receiving ICIs was associated with reduced MACE and all-cause mortality without an increased risk in serious adverse events.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"216 ","pages":"Article 115170"},"PeriodicalIF":7.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876427","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}
Pub Date : 2025-02-05DOI: 10.1016/j.ejca.2024.115195
Kin Lam Yu , Sj Shen
Hepatocellular carcinoma (HCC) is the third cause of cancer-related mortality worldwide. Current treatments include surgery and immunotherapy with variable response. Despite aggressive treatment, disease progression remains the biggest contributor to mortality. Thus, there is an urgent unmet need to improve current treatments through a better understanding of HCC tumourigenesis. The gut microbiota has been intensively examined in the context of HCC, with evidence showing gut modulation has the potential to modulate tumourigenesis and prognosis. In addition, recent literature suggests the presence of an intratumoural microbiota that may exert significant impacts on the development of solid tumours including HCC. By drawing parallels between the gut and hepatic/tumoural microbiota, we explore in the present review how the hepatic microbiota is established, its impact on tumourigenesis, and how modulation of the gut and hepatic microbiota may be key to improving current treatments of HCC. In particular, we highlight key bacteria that have been discovered in HCC tumours, and how they may affect the tumour immune microenvironment and HCC tumourigenesis. We then explore current therapies that target the intratumoural microbiota. With a deeper understanding of how the intratumoural microbiota is established, how different bacteria may be involved in HCC tumourigenesis, and how they can be targeted, we hope to spark future research in validating intratumoural microbiota as an avenue for improving treatment responses in HCC.
{"title":"Could intratumoural microbiota be key to unlocking treatment responses in hepatocellular carcinoma?","authors":"Kin Lam Yu , Sj Shen","doi":"10.1016/j.ejca.2024.115195","DOIUrl":"10.1016/j.ejca.2024.115195","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is the third cause of cancer-related mortality worldwide. Current treatments include surgery and immunotherapy with variable response. Despite aggressive treatment, disease progression remains the biggest contributor to mortality. Thus, there is an urgent unmet need to improve current treatments through a better understanding of HCC tumourigenesis. The gut microbiota has been intensively examined in the context of HCC, with evidence showing gut modulation has the potential to modulate tumourigenesis and prognosis. In addition, recent literature suggests the presence of an intratumoural microbiota that may exert significant impacts on the development of solid tumours including HCC. By drawing parallels between the gut and hepatic/tumoural microbiota, we explore in the present review how the hepatic microbiota is established, its impact on tumourigenesis, and how modulation of the gut and hepatic microbiota may be key to improving current treatments of HCC. In particular, we highlight key bacteria that have been discovered in HCC tumours, and how they may affect the tumour immune microenvironment and HCC tumourigenesis. We then explore current therapies that target the intratumoural microbiota. With a deeper understanding of how the intratumoural microbiota is established, how different bacteria may be involved in HCC tumourigenesis, and how they can be targeted, we hope to spark future research in validating intratumoural microbiota as an avenue for improving treatment responses in HCC.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"216 ","pages":"Article 115195"},"PeriodicalIF":7.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893156","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}
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