Pub Date : 2026-03-26Epub Date: 2026-02-17DOI: 10.1016/j.ejca.2026.116587
Anna Szumera-Ciećkiewicz , Piotr Donizy , Thibault Kervarrec , Witold Skrzyński , Llucia Alos , Natalia Castrejon-De-Anta , Filippo Ugolini , Jakub Mizera , Daniela Mihic-Probst , Martin G. Cook , Bastian Schilling , Piotr Rutkowski , Alexander M.M. Eggermont , Mario Mandalà , Daniela Massi , on behalf of EORTC Melanoma Group
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with a high risk of regional lymph-node metastasis. Accurate pathological evaluation of sentinel lymph nodes (SLN) is therefore critical for staging and clinical management, yet current practices remain heterogeneous across centres. An expert panel within the European Organisation for Research and Treatment of Cancer (EORTC) reviewed available evidence and contemporary practice to develop updated consensus guidance for the pathological assessment of SLN in MCC. The recommendations address specimen handling, lymph-node sectioning strategies, tumour-burden definitions, standardized reporting elements, and a pragmatic approach to ancillary immunohistochemistry (IHC). The proposed protocol provides clear guidance on SLN processing and sectioning to optimize the detection of micrometastatic disease, together with an algorithmic IHC framework that prioritizes sensitive screening markers followed by confirmatory stains to ensure reliable identification of occult nodal involvement. Emphasis is placed on consistent documentation of tumour burden and pN classification to support reproducible reporting and informed clinical decision-making.
{"title":"An updated European organization for research and treatment of cancer (EORTC) protocol for pathological evaluation of sentinel lymph nodes for merkel cell carcinoma (MCC)","authors":"Anna Szumera-Ciećkiewicz , Piotr Donizy , Thibault Kervarrec , Witold Skrzyński , Llucia Alos , Natalia Castrejon-De-Anta , Filippo Ugolini , Jakub Mizera , Daniela Mihic-Probst , Martin G. Cook , Bastian Schilling , Piotr Rutkowski , Alexander M.M. Eggermont , Mario Mandalà , Daniela Massi , on behalf of EORTC Melanoma Group","doi":"10.1016/j.ejca.2026.116587","DOIUrl":"10.1016/j.ejca.2026.116587","url":null,"abstract":"<div><div>Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with a high risk of regional lymph-node metastasis. Accurate pathological evaluation of sentinel lymph nodes (SLN) is therefore critical for staging and clinical management, yet current practices remain heterogeneous across centres. An expert panel within the European Organisation for Research and Treatment of Cancer (EORTC) reviewed available evidence and contemporary practice to develop updated consensus guidance for the pathological assessment of SLN in MCC. The recommendations address specimen handling, lymph-node sectioning strategies, tumour-burden definitions, standardized reporting elements, and a pragmatic approach to ancillary immunohistochemistry (IHC). The proposed protocol provides clear guidance on SLN processing and sectioning to optimize the detection of micrometastatic disease, together with an algorithmic IHC framework that prioritizes sensitive screening markers followed by confirmatory stains to ensure reliable identification of occult nodal involvement. Emphasis is placed on consistent documentation of tumour burden and pN classification to support reproducible reporting and informed clinical decision-making.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"237 ","pages":"Article 116587"},"PeriodicalIF":7.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147270235","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 : 2026-03-26Epub Date: 2026-02-20DOI: 10.1016/j.ejca.2026.116595
Lea Jessica Albrecht , Jana Garnier , Anne Zaremba , Lisa Brauch , Fiona Brunnert , Ricarda Rauschenberg , Andrea Forschner , Xiomara Garza Vazquez , Joanna Mangana , Michael Erdmann , Yenny Angela , Cindy Franklin , Julia Tietze , Georg Lodde , Alpaslan Tasdogan , Johanna A. Seier , Alexander Roesch , Selma Ugurel , Carola Berking , Ralf Gutzmer , Lisa Zimmer
Background
Patients with advanced melanoma progressing after immune checkpoint inhibition (ICI) and BRAF/MEK inhibition have limited therapeutic options. In the LEAP-004 trial, pembrolizumab plus lenvatinib demonstrated activity in PD-1-refractory melanoma. The combination has emerged as a potential option when approved therapies have been exhausted; however, real-world evidence regarding its efficacy remains limited.
Methods
This retrospective, multicenter DeCOG study included patients with advanced melanoma treated with anti-PD-1 plus lenvatinib after failure of anti-PD-1-based therapy at 11 major skin-cancer centers in Germany and Switzerland between October 2020 and March 2025.
Results
Overall, 120 patients were analyzed (median age 59 years); 70 % were male and 38 % had an ECOG performance status > 1. Most patients had ≥ 3 metastatic sites (69 %), brain metastases (42 %), and elevated LDH (58 %). Median follow-up was 13.4 months. Patients received a median of two prior systemic therapy lines; 98 % had been pretreated with ipilimumab/nivolumab, and 66 % exhibited primary resistance to prior ICI. The objective response rate was 23 %, with a median duration of response of 10 months; disease control rate was 47 %. Median progression-free survival (mPFS) was 4 months and median overall survival (mOS) was 10 months, with 12-month PFS and OS rates of 17 % and 42 %, respectively. Durable disease control beyond six months was observed in 23 % of patients, with mPFS of 21 months. Grade ≥ 3 treatment-related adverse events occurred in 21 % of patients.
Conclusions
In this real-world cohort, anti-PD-1 plus lenvatinib demonstrated meaningful efficacy in a subset of heavily pretreated patients, predominantly in those with BRAF wild-type melanoma.
{"title":"Real-world data on anti-PD-1 plus lenvatinib as a treatment option in pretreated advanced melanoma patients - a retrospective DeCOG study","authors":"Lea Jessica Albrecht , Jana Garnier , Anne Zaremba , Lisa Brauch , Fiona Brunnert , Ricarda Rauschenberg , Andrea Forschner , Xiomara Garza Vazquez , Joanna Mangana , Michael Erdmann , Yenny Angela , Cindy Franklin , Julia Tietze , Georg Lodde , Alpaslan Tasdogan , Johanna A. Seier , Alexander Roesch , Selma Ugurel , Carola Berking , Ralf Gutzmer , Lisa Zimmer","doi":"10.1016/j.ejca.2026.116595","DOIUrl":"10.1016/j.ejca.2026.116595","url":null,"abstract":"<div><h3>Background</h3><div>Patients with advanced melanoma progressing after immune checkpoint inhibition (ICI) and BRAF/MEK inhibition have limited therapeutic options. In the LEAP-004 trial, pembrolizumab plus lenvatinib demonstrated activity in PD-1-refractory melanoma. The combination has emerged as a potential option when approved therapies have been exhausted; however, real-world evidence regarding its efficacy remains limited.</div></div><div><h3>Methods</h3><div>This retrospective, multicenter DeCOG study included patients with advanced melanoma treated with anti-PD-1 plus lenvatinib after failure of anti-PD-1-based therapy at 11 major skin-cancer centers in Germany and Switzerland between October 2020 and March 2025.</div></div><div><h3>Results</h3><div>Overall, 120 patients were analyzed (median age 59 years); 70 % were male and 38 % had an ECOG performance status > 1. Most patients had ≥ 3 metastatic sites (69 %), brain metastases (42 %), and elevated LDH (58 %). Median follow-up was 13.4 months. Patients received a median of two prior systemic therapy lines; 98 % had been pretreated with ipilimumab/nivolumab, and 66 % exhibited primary resistance to prior ICI. The objective response rate was 23 %, with a median duration of response of 10 months; disease control rate was 47 %. Median progression-free survival (mPFS) was 4 months and median overall survival (mOS) was 10 months, with 12-month PFS and OS rates of 17 % and 42 %, respectively. Durable disease control beyond six months was observed in 23 % of patients, with mPFS of 21 months. Grade ≥ 3 treatment-related adverse events occurred in 21 % of patients.</div></div><div><h3>Conclusions</h3><div>In this real-world cohort, anti-PD-1 plus lenvatinib demonstrated meaningful efficacy in a subset of heavily pretreated patients, predominantly in those with BRAF wild-type melanoma.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"237 ","pages":"Article 116595"},"PeriodicalIF":7.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147303781","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 : 2026-03-26Epub Date: 2026-02-17DOI: 10.1016/j.ejca.2026.116592
Phillip J. Hopley , Ryan Peysner , Annabelle Boughey , Bharti Kewlani , Andrew M. Smith , Guruprasad P. Aithal , Kofi W. Oppong , Meg Finch-Jones , Zaed Hamady , Tejinderjit S. Athwal , James Milburn , Shyam Menon , Michael Chapman , Stephen P. Pereira , Mark Taylor , Guy Shingler , Christopher Briggs , Paula Ghaneh , Eithne Costello , William Greenhalf , Christopher M. Halloran
Background
Surveillance of individuals with a familial predisposition to pancreatic ductal adenocarcinoma (PDAC) is likely to increase overall survival. Our objective was to determine the impact of EUROPAC risk-stratification (Family Risk, FR), in such predisposed individuals.
Methods
Observational study of registered asymptomatic individuals undergoing surveillance for PDAC. Individuals without a known pathogenic variant (PV-), ineligible for genetic assessment in the NHS, in whom significant pancreatic lesions were found, were subjected to additional germline testing.
Results
Between January 2000 and April 2025, 893 individuals started surveillance, median age of 52 years. 508 individuals (404 PV- and 104 with a pathogenic variant (PV+)) in the 20 years prior to 2020 without stratification were compared to 385 (269 PV- and 116 PV+) in the five years from 2020 who had FR risk-stratification applied. Four (0·8 %) individuals had actionable pancreatic findings prior to risk stratification vs. 14 (3·6 %), who underwent risk-stratified surveillance (p = 0·001). Pancreatic lesions deemed operable were found in three (0·6 %) and 11 (3 %), p = 0·007, with two (0·4 %) and nine (2 %) undergoing resection, p = 0·009, respectively. PV- individuals with significant findings were subsequently found to contain mutations, many not in the UK genetics test directory, provided the FR was > 30. The median (IQR) time in surveillance prior to a lesion being detected was four (2 – 7) years. Overall, 78 % of EUROPAC detected precursor lesions or pancreatic cancers were stage II or lower.
Conclusion
The risk-stratified group (FR) identifies neoplastic pancreatic lesion in individuals, regardless of PV status suggesting the key usefulness of this approach.
{"title":"Risk-stratified surveillance for individuals in the UK at high risk of developing pancreatic cancer: Outcomes from the European Registry of Hereditary Pancreatic Diseases (EUROPAC)","authors":"Phillip J. Hopley , Ryan Peysner , Annabelle Boughey , Bharti Kewlani , Andrew M. Smith , Guruprasad P. Aithal , Kofi W. Oppong , Meg Finch-Jones , Zaed Hamady , Tejinderjit S. Athwal , James Milburn , Shyam Menon , Michael Chapman , Stephen P. Pereira , Mark Taylor , Guy Shingler , Christopher Briggs , Paula Ghaneh , Eithne Costello , William Greenhalf , Christopher M. Halloran","doi":"10.1016/j.ejca.2026.116592","DOIUrl":"10.1016/j.ejca.2026.116592","url":null,"abstract":"<div><h3>Background</h3><div>Surveillance of individuals with a familial predisposition to pancreatic ductal adenocarcinoma (PDAC) is likely to increase overall survival. Our objective was to determine the impact of EUROPAC risk-stratification (Family Risk, FR), in such predisposed individuals.</div></div><div><h3>Methods</h3><div>Observational study of registered asymptomatic individuals undergoing surveillance for PDAC. Individuals without a known pathogenic variant (PV-), ineligible for genetic assessment in the NHS, in whom significant pancreatic lesions were found, were subjected to additional germline testing.</div></div><div><h3>Results</h3><div>Between January 2000 and April 2025, 893 individuals started surveillance, median age of 52 years. 508 individuals (404 PV- and 104 with a pathogenic variant (PV+)) in the 20 years prior to 2020 without stratification were compared to 385 (269 PV- and 116 PV+) in the five years from 2020 who had FR risk-stratification applied. Four (0·8 %) individuals had actionable pancreatic findings prior to risk stratification vs. 14 (3·6 %), who underwent risk-stratified surveillance (<em>p</em> = 0·001). Pancreatic lesions deemed operable were found in three (0·6 %) and 11 (3 %), <em>p</em> = 0·007, with two (0·4 %) and nine (2 %) undergoing resection, <em>p</em> = 0·009, respectively. PV- individuals with significant findings were subsequently found to contain mutations, many not in the UK genetics test directory, provided the FR was > 30. The median (IQR) time in surveillance prior to a lesion being detected was four (2 – 7) years. Overall, 78 % of EUROPAC detected precursor lesions or pancreatic cancers were stage II or lower.</div></div><div><h3>Conclusion</h3><div>The risk-stratified group (FR) identifies neoplastic pancreatic lesion in individuals, regardless of PV status suggesting the key usefulness of this approach.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"237 ","pages":"Article 116592"},"PeriodicalIF":7.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147303813","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}
Recurrent glioblastoma multiforme (rGBM) arises after conventional treatment strategies for primary GBM (pGBM) fail, leading to a more aggressive, therapy-resistant phenotype, with an overall survival of ∼9 months. Current treatment strategies rely on apoptosis and are frequently ineffective. Moreover, ferroptosis has recently been identified as a potential alternative cell death pathway in glioma. Therefore, this study investigated the mechanisms and therapeutic potential of ferroptosis in rGBM at the glial cell type level.
Methods
We analyzed a publicly available single-cell datasets to profile tumor-specific glial cells and assess ferroptosis-related perturbations in rGBM versus pGBM. Network-based machine learning analyses were employed to highlight key ferroptosis drivers in rGBM. Finally, we employed network medicine, molecular docking, and molecular dynamics simulations to identify a potential therapeutic target.
Results
Network-based ranking captured a ferroptosis suppressor, ZFP36, in astrocytes, and pathway enrichment analysis of its interaction subnetwork revealed MAPK and metabolic pathways, supporting its role in tumor growth. Network medicine identified drugs targeting ZFP36, with proximity analysis showing that drug-binding MAP kinases are closer to ZFP36, suggesting that these drugs may also modulate ZFP36 activity. Furthermore, similarity analyses with known ferroptosis inducers identified 4-Phenoxy-N-(Pyridin-2-Ylmethyl)Benzamide as a potential drug target for ZFP36. Molecular docking and dynamics simulations showed that the drug binds to the druggable binding site of ZFP36, modulating its structure.
Conclusion
The findings of this study suggest that modulating ferroptosis suppressor ZFP36 could promote cell death in rGBM via the ferroptosis pathway.
{"title":"Single-cell systems network and machine learning dissection of ferroptosis in recurrent glioblastoma highlights astrocytic ZFP36 as a therapeutic hub for network medicine repurposing","authors":"Mahima Kishinani , Manoj Girish , Swati Sinha , Sainitin Donakonda","doi":"10.1016/j.ejca.2026.116591","DOIUrl":"10.1016/j.ejca.2026.116591","url":null,"abstract":"<div><h3>Background</h3><div>Recurrent glioblastoma multiforme (rGBM) arises after conventional treatment strategies for primary GBM (pGBM) fail, leading to a more aggressive, therapy-resistant phenotype, with an overall survival of ∼9 months. Current treatment strategies rely on apoptosis and are frequently ineffective. Moreover, ferroptosis has recently been identified as a potential alternative cell death pathway in glioma. Therefore, this study investigated the mechanisms and therapeutic potential of ferroptosis in rGBM at the glial cell type level.</div></div><div><h3>Methods</h3><div>We analyzed a publicly available single-cell datasets to profile tumor-specific glial cells and assess ferroptosis-related perturbations in rGBM versus pGBM. Network-based machine learning analyses were employed to highlight key ferroptosis drivers in rGBM. Finally, we employed network medicine, molecular docking, and molecular dynamics simulations to identify a potential therapeutic target.</div></div><div><h3>Results</h3><div>Network-based ranking captured a ferroptosis suppressor, <em>ZFP36</em>, in astrocytes, and pathway enrichment analysis of its interaction subnetwork revealed MAPK and metabolic pathways, supporting its role in tumor growth. Network medicine identified drugs targeting ZFP36, with proximity analysis showing that drug-binding MAP kinases are closer to ZFP36, suggesting that these drugs may also modulate ZFP36 activity. Furthermore, similarity analyses with known ferroptosis inducers identified 4-Phenoxy-N-(Pyridin-2-Ylmethyl)Benzamide as a potential drug target for ZFP36. Molecular docking and dynamics simulations showed that the drug binds to the druggable binding site of ZFP36, modulating its structure.</div></div><div><h3>Conclusion</h3><div>The findings of this study suggest that modulating ferroptosis suppressor ZFP36 could promote cell death in rGBM via the ferroptosis pathway.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"237 ","pages":"Article 116591"},"PeriodicalIF":7.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146226047","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 : 2026-03-26Epub Date: 2026-02-18DOI: 10.1016/j.ejca.2026.116585
Quentin Samaran , Thomas Bettuzzi , Emilie Sbidian
Background
Anti-PD-1 agents have demonstrated meaningful response rates in single-arm trials for advanced cutaneous squamous cell carcinoma (acSCC). However, no randomised or large-scale real-world studies have directly compared their effectiveness with cetuximab, used alone or in combination with chemotherapy, which has long been used off-label as first-line systemic therapy in this setting. This study compared survival outcomes with first-line anti-PD-1 therapy versus cetuximab using French nationwide data.
Methods
We conducted a retrospective nationwide population-based cohort study of the French national health data system (SNDS). Adults with acSCC initiating first-line systemic therapy between 2017 and 2023 were included; those with alternative diagnoses or prior systemic therapy were excluded. The primary endpoint was overall survival (OS); the secondary endpoint was switch-free survival (SFS), used as a proxy for progression-free survival. Cox models with stabilised inverse probability of treatment weighting were used. Predefined subgroup and sensitivity analyses were performed.
Results
Among 3006 patients (median age, 80 years; 74 % men), 2115 received anti-PD-1 (587 cemiplimab, 1118 pembrolizumab, 410 nivolumab) and 891 cetuximab. Median OS was 26 months with anti-PD-1 versus 14 with cetuximab (weighted HR, 0.79; 95 % CI, 0.69–0.90; p < 0.001). Median SFS was 22 versus 8 months (weighted HR, 0.59; 95 % CI, 0.52–0.67; p < 0.0001). Results were consistent across age, sex, and anti-PD-1 subgroups.
Conclusions
First-line anti-PD-1 therapy significantly improved overall and switch-free survival compared with cetuximab, used alone or in combination with chemotherapy. These findings provide robust real-world evidence supporting anti-PD-1 agents as the preferred first-line systemic treatment for acSCC in dermatologic oncology practice.
{"title":"Comparative effectiveness of first-line anti-PD-1 versus cetuximab in advanced cutaneous squamous cell carcinoma: A nationwide population-based study using the French national health data system","authors":"Quentin Samaran , Thomas Bettuzzi , Emilie Sbidian","doi":"10.1016/j.ejca.2026.116585","DOIUrl":"10.1016/j.ejca.2026.116585","url":null,"abstract":"<div><h3>Background</h3><div>Anti-PD-1 agents have demonstrated meaningful response rates in single-arm trials for advanced cutaneous squamous cell carcinoma (acSCC). However, no randomised or large-scale real-world studies have directly compared their effectiveness with cetuximab, used alone or in combination with chemotherapy, which has long been used off-label as first-line systemic therapy in this setting. This study compared survival outcomes with first-line anti-PD-1 therapy versus cetuximab using French nationwide data.</div></div><div><h3>Methods</h3><div>We conducted a retrospective nationwide population-based cohort study of the French national health data system (SNDS). Adults with acSCC initiating first-line systemic therapy between 2017 and 2023 were included; those with alternative diagnoses or prior systemic therapy were excluded. The primary endpoint was overall survival (OS); the secondary endpoint was switch-free survival (SFS), used as a proxy for progression-free survival. Cox models with stabilised inverse probability of treatment weighting were used. Predefined subgroup and sensitivity analyses were performed.</div></div><div><h3>Results</h3><div>Among 3006 patients (median age, 80 years; 74 % men), 2115 received anti-PD-1 (587 cemiplimab, 1118 pembrolizumab, 410 nivolumab) and 891 cetuximab. Median OS was 26 months with anti-PD-1 versus 14 with cetuximab (weighted HR, 0.79; 95 % CI, 0.69–0.90; p < 0.001). Median SFS was 22 versus 8 months (weighted HR, 0.59; 95 % CI, 0.52–0.67; p < 0.0001). Results were consistent across age, sex, and anti-PD-1 subgroups.</div></div><div><h3>Conclusions</h3><div>First-line anti-PD-1 therapy significantly improved overall and switch-free survival compared with cetuximab, used alone or in combination with chemotherapy. These findings provide robust real-world evidence supporting anti-PD-1 agents as the preferred first-line systemic treatment for acSCC in dermatologic oncology practice.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"237 ","pages":"Article 116585"},"PeriodicalIF":7.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257735","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 : 2026-03-26Epub Date: 2026-02-17DOI: 10.1016/j.ejca.2026.116581
Qunwei Chen , Xinyan Feng , Jingxian Wang , Huilin Zhu , Zhiyuan Bo , Binbin Wang , Zhengxiao Zhao
Advances in sequencing technology have elucidated the complex role of the gut microbiota in hepatocellular carcinoma (HCC). Communication between the gut and the liver occurs via the gut-liver axis, and dysbiosis of the gut microbiota has been implicated in both the promotion and suppression of HCC. Furthermore, through interactions with host metabolism and immune system, the gut microbiota significantly influences treatment responses and prognostic outcomes of HCC. Despite progress in therapeutic strategies, clinical efficacy remains suboptimal, underscoring the need for a deeper understanding of the gut microbiota's role. This review highlights the potential of gut microbiota as novel biomarkers for the diagnosis and prognostic prediction of HCC, and explores its therapeutic implications. We summarize current insights into the molecular mechanisms underlying the gut microbiota-HCC interplay, and emphasize the relationship between gut microbiota and the efficacy of various treatments, including surgery, chemotherapy, radiotherapy, immunotherapy, and targeted agents. Microbiome-targeting interventions like probiotics, fecal microbiota transplantation (FMT), and dietary changes as emerging adjuvant strategies are also discussed in detail to provide potential resources for advancing translational hepatology. Although challenges remain, this review aims to provide valuable perspectives for developing individualized therapeutic strategies in HCC management.
{"title":"Impact of gut microbiota on hepatocellular carcinoma: Pathogenesis, diagnosis, prognosis, and therapeutic prospective","authors":"Qunwei Chen , Xinyan Feng , Jingxian Wang , Huilin Zhu , Zhiyuan Bo , Binbin Wang , Zhengxiao Zhao","doi":"10.1016/j.ejca.2026.116581","DOIUrl":"10.1016/j.ejca.2026.116581","url":null,"abstract":"<div><div>Advances in sequencing technology have elucidated the complex role of the gut microbiota in hepatocellular carcinoma (HCC). Communication between the gut and the liver occurs via the gut-liver axis, and dysbiosis of the gut microbiota has been implicated in both the promotion and suppression of HCC. Furthermore, through interactions with host metabolism and immune system, the gut microbiota significantly influences treatment responses and prognostic outcomes of HCC. Despite progress in therapeutic strategies, clinical efficacy remains suboptimal, underscoring the need for a deeper understanding of the gut microbiota's role. This review highlights the potential of gut microbiota as novel biomarkers for the diagnosis and prognostic prediction of HCC, and explores its therapeutic implications. We summarize current insights into the molecular mechanisms underlying the gut microbiota-HCC interplay, and emphasize the relationship between gut microbiota and the efficacy of various treatments, including surgery, chemotherapy, radiotherapy, immunotherapy, and targeted agents. Microbiome-targeting interventions like probiotics, fecal microbiota transplantation (FMT), and dietary changes as emerging adjuvant strategies are also discussed in detail to provide potential resources for advancing translational hepatology. Although challenges remain, this review aims to provide valuable perspectives for developing individualized therapeutic strategies in HCC management.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"237 ","pages":"Article 116581"},"PeriodicalIF":7.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364460","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 : 2026-03-26Epub Date: 2026-02-16DOI: 10.1016/j.ejca.2026.116584
Sidsel Pedersen , Lotte B. Colmorn , Eva Ellebaek , Stine Gry Kristensen , Christina Ruhlmann , Troels Holz Borch , Marco Donia , Jens Fedder , Kirsten T. Macklon , Inge Marie Svane
Introduction
Immune checkpoint inhibitors (ICIs) have transformed cancer treatment and are increasingly used in the adjuvant and neoadjuvant setting for malignancies such as melanoma, which often affect younger adults. With improving survival, concerns about long-term safety, including potential effects on fertility, are growing.
Methods
We conducted a national, multicenter, prospective observational study of female patients < 45 years treated with adjuvant anti-PD-1 therapy for resectable stage III–IV melanoma from 2018 to 2024. Ovarian function was assessed at baseline and at 3, 6, 12, and 18 months after treatment initiation. Each visit included transvaginal ultrasound for antral follicle count (AFC) and serum analysis of anti-Müllerian hormone (AMH), estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and inhibin-B.
Results
Seventeen female patients were enrolled (mean age 28.9 years, range 17–38). Median follow-up was 5.1 years. Ovarian morphology and AFC remained normal and stable at all time points. No decline in AMH was observed during or after treatment. FSH, LH, estradiol, progesterone, and inhibin-B levels fluctuated within physiological ranges consistent with normal menstrual cycling. After completing adjuvant therapy, five patients had at least one child, and one was pregnant at data cut-off. Two patients developed endocrine immune-related toxicity (type 1 diabetes and hypophysitis); both conceived post-treatment.
Discussion
This prospective evaluation of ovarian function during and after adjuvant anti-PD-1 therapy in melanoma found no evidence of treatment-related ovarian insufficiency, including in patients with endocrine toxicities. These findings are important for counseling young patients receiving adjuvant therapy who may wish to conceive in the future.
{"title":"Impact of adjuvant anti-PD-1 immunotherapy on ovarian function in female patients with resectable melanoma: A prospective observational study","authors":"Sidsel Pedersen , Lotte B. Colmorn , Eva Ellebaek , Stine Gry Kristensen , Christina Ruhlmann , Troels Holz Borch , Marco Donia , Jens Fedder , Kirsten T. Macklon , Inge Marie Svane","doi":"10.1016/j.ejca.2026.116584","DOIUrl":"10.1016/j.ejca.2026.116584","url":null,"abstract":"<div><h3>Introduction</h3><div>Immune checkpoint inhibitors (ICIs) have transformed cancer treatment and are increasingly used in the adjuvant and neoadjuvant setting for malignancies such as melanoma, which often affect younger adults. With improving survival, concerns about long-term safety, including potential effects on fertility, are growing.</div></div><div><h3>Methods</h3><div>We conducted a national, multicenter, prospective observational study of female patients < 45 years treated with adjuvant anti-PD-1 therapy for resectable stage III–IV melanoma from 2018 to 2024. Ovarian function was assessed at baseline and at 3, 6, 12, and 18 months after treatment initiation. Each visit included transvaginal ultrasound for antral follicle count (AFC) and serum analysis of anti-Müllerian hormone (AMH), estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and inhibin-B.</div></div><div><h3>Results</h3><div>Seventeen female patients were enrolled (mean age 28.9 years, range 17–38). Median follow-up was 5.1 years. Ovarian morphology and AFC remained normal and stable at all time points. No decline in AMH was observed during or after treatment. FSH, LH, estradiol, progesterone, and inhibin-B levels fluctuated within physiological ranges consistent with normal menstrual cycling. After completing adjuvant therapy, five patients had at least one child, and one was pregnant at data cut-off. Two patients developed endocrine immune-related toxicity (type 1 diabetes and hypophysitis); both conceived post-treatment.</div></div><div><h3>Discussion</h3><div>This prospective evaluation of ovarian function during and after adjuvant anti-PD-1 therapy in melanoma found no evidence of treatment-related ovarian insufficiency, including in patients with endocrine toxicities. These findings are important for counseling young patients receiving adjuvant therapy who may wish to conceive in the future.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"237 ","pages":"Article 116584"},"PeriodicalIF":7.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146226052","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 : 2026-03-26Epub Date: 2026-02-17DOI: 10.1016/j.ejca.2026.116590
Eva Kalfala , Alexandra Meurgey , Clémence Hénon , Mehdi Brahmi , Maud Toulmonde , Pascaline Boudou-Rouquette , Emmanuelle Bompas , Nicolas Penel , Nelly Firmin , Florence Duffaud , Isabelle Desmoulins , Agnès Ducoulombier , Mathilde Cancel , Sarah Watson , Mohamed Khettab , Tiffany Darbas , Anne Kieffer , Cécile Guillemet , Justine Gantzer , Christophe Perrin , Armelle Dufresne
Background
Alveolar soft part sarcoma (ASPS) is an ultra-rare sarcoma with limited chemotherapy sensitivity affecting mostly young patients. Tyrosine kinase inhibitors (TKIs) and immunotherapy are therapeutic advances with promising results in this disease. The aim of this study was to describe the characteristics, management and survival of patients with ASPS in France.
Patients and Methods
The French NETSARC+ database was screened for all adult patients with ASPS managed in French sarcoma centers between 2010 and 2023.
Results
Sixty-four patients from 18 centers were analyzed. The 5-year overall survival (OS) of the entire cohort was 87.3 % (95 % CI, 75.0–93.8 %). Fifty-six percent of patients had localized tumors at diagnosis; all were treated surgically, and 47 % received perioperative radiotherapy. With a median follow-up of 91 months, their 5-year OS was 96.3 % (95 % CI, 76.5–99.5 %). Half of the patients experienced metastatic recurrence with a median metastasis-free survival of 87.9 months (95 % CI, 29.6-NE). In patients with metastases, the first-line systemic treatment yielded an overall response rate of 7 %, 26 %, and 40 % for chemotherapy, TKIs, and immunotherapy, respectively. The 5-year OS after metastasis diagnosis was 67.7 % (95 % CI: 50.5–80.0 %).
Conclusion
Our cohort reinforces existing data on clinical characteristics and demonstrated prolonged survival in both localized and metastatic stages. Among systemic treatments, immunotherapy achieved the highest response rates. We confirmed that ASPS may follow an indolent course in some cases and highlighted recent advances in its management, driven by standardized local treatments in reference centers and innovative systemic therapies.
{"title":"Natural history and treatment sensitivity of alveolar soft part sarcoma: A national multicenter analysis from the French sarcoma group","authors":"Eva Kalfala , Alexandra Meurgey , Clémence Hénon , Mehdi Brahmi , Maud Toulmonde , Pascaline Boudou-Rouquette , Emmanuelle Bompas , Nicolas Penel , Nelly Firmin , Florence Duffaud , Isabelle Desmoulins , Agnès Ducoulombier , Mathilde Cancel , Sarah Watson , Mohamed Khettab , Tiffany Darbas , Anne Kieffer , Cécile Guillemet , Justine Gantzer , Christophe Perrin , Armelle Dufresne","doi":"10.1016/j.ejca.2026.116590","DOIUrl":"10.1016/j.ejca.2026.116590","url":null,"abstract":"<div><h3>Background</h3><div>Alveolar soft part sarcoma (ASPS) is an ultra-rare sarcoma with limited chemotherapy sensitivity affecting mostly young patients. Tyrosine kinase inhibitors (TKIs) and immunotherapy are therapeutic advances with promising results in this disease. The aim of this study was to describe the characteristics, management and survival of patients with ASPS in France.</div></div><div><h3>Patients and Methods</h3><div>The French NETSARC+ database was screened for all adult patients with ASPS managed in French sarcoma centers between 2010 and 2023.</div></div><div><h3>Results</h3><div>Sixty-four patients from 18 centers were analyzed. The 5-year overall survival (OS) of the entire cohort was 87.3 % (95 % CI, 75.0–93.8 %). Fifty-six percent of patients had localized tumors at diagnosis; all were treated surgically, and 47 % received perioperative radiotherapy. With a median follow-up of 91 months, their 5-year OS was 96.3 % (95 % CI, 76.5–99.5 %). Half of the patients experienced metastatic recurrence with a median metastasis-free survival of 87.9 months (95 % CI, 29.6-NE). In patients with metastases, the first-line systemic treatment yielded an overall response rate of 7 %, 26 %, and 40 % for chemotherapy, TKIs, and immunotherapy, respectively. The 5-year OS after metastasis diagnosis was 67.7 % (95 % CI: 50.5–80.0 %).</div></div><div><h3>Conclusion</h3><div>Our cohort reinforces existing data on clinical characteristics and demonstrated prolonged survival in both localized and metastatic stages. Among systemic treatments, immunotherapy achieved the highest response rates. We confirmed that ASPS may follow an indolent course in some cases and highlighted recent advances in its management, driven by standardized local treatments in reference centers and innovative systemic therapies.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"237 ","pages":"Article 116590"},"PeriodicalIF":7.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257780","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 : 2026-03-26Epub Date: 2026-02-24DOI: 10.1016/j.ejca.2026.116597
V.D. de Jager , B.N. Cajiao Garcia , C.C.H.J. Kuijpers , G.H. de Bock , W.J. Maas , W. Timens , L.C. van Kempen , A.J. van der Wekken , E. Schuuring , S.M. Willems
{"title":"Corrigendum to “Regional differences in predictive biomarker testing rates for patients with metastatic NSCLC in the Netherlands” [Eur J Cancer 205 (2024)114125]","authors":"V.D. de Jager , B.N. Cajiao Garcia , C.C.H.J. Kuijpers , G.H. de Bock , W.J. Maas , W. Timens , L.C. van Kempen , A.J. van der Wekken , E. Schuuring , S.M. Willems","doi":"10.1016/j.ejca.2026.116597","DOIUrl":"10.1016/j.ejca.2026.116597","url":null,"abstract":"","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"237 ","pages":"Article 116597"},"PeriodicalIF":7.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147303701","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}
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