Pub Date : 2025-02-01DOI: 10.1016/j.ejca.2025.115278
Denice Kamp , Anne M. May , Antoine Adenis , Andreia Capela , Sarah Derks , Francesca De Felice , Nina Fokter Dovnik , Cinta Hierro , Aysegul Ilhan-Mutlu , Florian Lordick , Radka Lordick Obermannova , Angelica Petrillo , Alberto Puccini , Ana Raimundo , Giandomenico Roviello , Alexander Siebenhüner , Marije Slingerland , Elizabeth C. Smyth , Hanneke W.M. van Laarhoven , Nadia Haj Mohammad
Background
The enhanced application of imaging techniques is resulting in the diagnosis of more patients with asymptomatic metastatic esophagogastric cancer (mEGC). We conducted a Delphi study to gather insights from European experts on the optimal timing for initiating palliative systemic therapy for these patients.
Methods
An online survey featured 14 scenarios where physicians chose their preferred timing for initiating systemic therapy: immediate(<3 weeks) or deferred. The standard scenario was a 65-year-old male, WHO/ECOG 0 with asymptomatic mEGC, 2 metastases in each lung, HER2 -, PDL1-CPS 2. In every subsequent case, one characteristic was modified. To investigate the fortitude of the physicians’ preference for an immediate start, scenarios also included a patient who was motivated to start but preferred to defer if the physician deemed it judicious. Consensus was defined as ≥ 75 % agreement; scenarios without consensus were re-evaluated in Delphi round 2.
Results
Thirty-nine physicians participated in the first round, and 33 in the second round. Consensus to start treatment immediately was reached in 12 (86 %) scenarios. When patients preferred to defer, the consensus was to still advise to start palliative systemic treatment immediately in half (n = 7) of the scenarios. Only 2 scenarios (pre-existent WHO/ECOG 2 or 78 years old) reached the consensus that treatment could be deferred.
Conclusions
In asymptomatic mEGC, immediate start of treatment is preferred by European experts. Consensus was established that treatment can be deferred for patients who prefer deferral and either have a pre-existent WHO/ECOG performance status of 2 or are of advanced age.
{"title":"Optimal timing for initiating first-line palliative systemic therapy in asymptomatic metastatic esophagogastric cancer: Insights from a European Delphi study","authors":"Denice Kamp , Anne M. May , Antoine Adenis , Andreia Capela , Sarah Derks , Francesca De Felice , Nina Fokter Dovnik , Cinta Hierro , Aysegul Ilhan-Mutlu , Florian Lordick , Radka Lordick Obermannova , Angelica Petrillo , Alberto Puccini , Ana Raimundo , Giandomenico Roviello , Alexander Siebenhüner , Marije Slingerland , Elizabeth C. Smyth , Hanneke W.M. van Laarhoven , Nadia Haj Mohammad","doi":"10.1016/j.ejca.2025.115278","DOIUrl":"10.1016/j.ejca.2025.115278","url":null,"abstract":"<div><h3>Background</h3><div>The enhanced application of imaging techniques is resulting in the diagnosis of more patients with asymptomatic metastatic esophagogastric cancer (mEGC). We conducted a Delphi study to gather insights from European experts on the optimal timing for initiating palliative systemic therapy for these patients.</div></div><div><h3>Methods</h3><div>An online survey featured 14 scenarios where physicians chose their preferred timing for initiating systemic therapy: immediate(<3 weeks) or deferred. The standard scenario was a 65-year-old male, WHO/ECOG 0 with asymptomatic mEGC, 2 metastases in each lung, HER2 -, PDL1-CPS 2. In every subsequent case, one characteristic was modified. To investigate the fortitude of the physicians’ preference for an immediate start, scenarios also included a patient who was motivated to start but preferred to defer if the physician deemed it judicious. Consensus was defined as ≥ 75 % agreement; scenarios without consensus were re-evaluated in Delphi round 2.</div></div><div><h3>Results</h3><div>Thirty-nine physicians participated in the first round, and 33 in the second round. Consensus to start treatment immediately was reached in 12 (86 %) scenarios. When patients preferred to defer, the consensus was to still advise to start palliative systemic treatment immediately in half (n = 7) of the scenarios. Only 2 scenarios (pre-existent WHO/ECOG 2 or 78 years old) reached the consensus that treatment could be deferred.</div></div><div><h3>Conclusions</h3><div>In asymptomatic mEGC, immediate start of treatment is preferred by European experts. Consensus was established that treatment can be deferred for patients who prefer deferral and either have a pre-existent WHO/ECOG performance status of 2 or are of advanced age.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"218 ","pages":"Article 115278"},"PeriodicalIF":7.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143300057","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 : 2025-01-31DOI: 10.1016/j.ejca.2025.115264
James L. Mulshine , Bruce Pyenson , Cheryl Healton , Carolyn Aldige , Riccardo S. Avila , Torsten Blum , Matthew Cham , Harry J. de Koning , Sean B. Fain , John K. Field , Raja Flores , Maryellen L. Giger , Ilya Gipp , Frederic W. Grannis , Jan Willem C. Gratama , Ella A. Kazerooni , Karen Kelly , Harriet L. Lancaster , Luis Montuenga , Kyle J. Myers , Matthijs Oudkerk
Large-scale lung cancer screening implementation combined with improvements in early detection techniques for three major tobacco-related diseases presents a rare opportunity to markedly improve population health outcomes for millions of people. Chest CT enables routine detection of early lung cancer as well as characterizing coronary calcium and detecting early emphysema in the course of lung cancer screening. Integrated preventive care centered on comprehensive chest CT screening has the potential to bring large benefits across co-morbid diseases with a common etiology. The current one-disease/ silo paradigm of medical practice is an obstacle to maximizing chest CT screening’s benefits.
The large potential for improved health outcomes across the world demands careful public health, quality assurance, and health policy considerations. A systematic analysis of imaging and health data from ongoing chest CT screening could accelerate this paradigm shift through sustained optimization of screening detection, quantitation and management for the three most lethal tobacco-related co-morbidities. To coordinate this effort to advance progress with implementing the full benefit of comprehensive chest CT screening, a new multi- disciplinary professional and advocacy consortium has been developed to foster collaboration to realize the future of multi-disease chest CT screening.
{"title":"Paradigm shift in early detection: Lung cancer screening to comprehensive CT screening","authors":"James L. Mulshine , Bruce Pyenson , Cheryl Healton , Carolyn Aldige , Riccardo S. Avila , Torsten Blum , Matthew Cham , Harry J. de Koning , Sean B. Fain , John K. Field , Raja Flores , Maryellen L. Giger , Ilya Gipp , Frederic W. Grannis , Jan Willem C. Gratama , Ella A. Kazerooni , Karen Kelly , Harriet L. Lancaster , Luis Montuenga , Kyle J. Myers , Matthijs Oudkerk","doi":"10.1016/j.ejca.2025.115264","DOIUrl":"10.1016/j.ejca.2025.115264","url":null,"abstract":"<div><div>Large-scale lung cancer screening implementation combined with improvements in early detection techniques for three major tobacco-related diseases presents a rare opportunity to markedly improve population health outcomes for millions of people. Chest CT enables routine detection of early lung cancer as well as characterizing coronary calcium and detecting early emphysema in the course of lung cancer screening. Integrated preventive care centered on comprehensive chest CT screening has the potential to bring large benefits across co-morbid diseases with a common etiology. The current one-disease/ silo paradigm of medical practice is an obstacle to maximizing chest CT screening’s benefits.</div><div>The large potential for improved health outcomes across the world demands careful public health, quality assurance, and health policy considerations. A systematic analysis of imaging and health data from ongoing chest CT screening could accelerate this paradigm shift through sustained optimization of screening detection, quantitation and management for the three most lethal tobacco-related co-morbidities. To coordinate this effort to advance progress with implementing the full benefit of comprehensive chest CT screening, a new multi- disciplinary professional and advocacy consortium has been developed to foster collaboration to realize the future of multi-disease chest CT screening.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"218 ","pages":"Article 115264"},"PeriodicalIF":7.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143098571","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}
In recent years, new therapeutic approaches have emerged in addition to classical neoadjuvant (chemo)radiotherapy for the treatment of locally advanced rectal cancer (LARC): total neoadjuvant treatment, non-operative management, and radiotherapy-free strategy. While the introduction of these approaches in a relatively short timeframe has quickly increased our therapeutic armamentarium, on the other hand it has complicated the decision-making process regarding the choice of the most appropriate treatment strategy for each patient with LARC. Therefore, a tool to interpret the evidence from clinical trials and to translate them into daily practice is highly demanded. In the present review, we address how these new developments are changing the multimodal treatment of LARC and offer an algorithm to integrate them into clinical practice.
{"title":"Total neoadjuvant treatment, non-operative management and radiotherapy-free strategies: New approaches for the management of proficient mismatch repair/microsatellite stable locally advanced rectal cancer. A narrative review and evidence-based algorithm","authors":"Roberto Moretto , Chiara Boccaccio , Matteo Landi , Gianluca Masi , Chiara Cremolini","doi":"10.1016/j.ejca.2025.115261","DOIUrl":"10.1016/j.ejca.2025.115261","url":null,"abstract":"<div><div>In recent years, new therapeutic approaches have emerged in addition to classical neoadjuvant (chemo)radiotherapy for the treatment of locally advanced rectal cancer (LARC): total neoadjuvant treatment, non-operative management, and radiotherapy-free strategy. While the introduction of these approaches in a relatively short timeframe has quickly increased our therapeutic armamentarium, on the other hand it has complicated the decision-making process regarding the choice of the most appropriate treatment strategy for each patient with LARC. Therefore, a tool to interpret the evidence from clinical trials and to translate them into daily practice is highly demanded. In the present review, we address how these new developments are changing the multimodal treatment of LARC and offer an algorithm to integrate them into clinical practice.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"218 ","pages":"Article 115261"},"PeriodicalIF":7.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143149439","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 : 2025-01-30DOI: 10.1016/j.ejca.2025.115265
Philippe Saiag , Celeste Lebbe , Lieve Brochez , Jean-François Emile , Ana Maria Forsea , Catherine Harwood , Axel Hauschild , Antoine Italiano , Lidija Kandolf , Nicole WJ Kelleners-Smeets , Aimilios Lallas , Ulrike Leiter , Beatriz Llombart , Caterina Longo , Josep Malvehy , Zeljko Mijuskovic , David Moreno-Ramirez , Klara Mosterd , Luca Tagliaferri , Selma Ugurel , Claus Garbe
Dermatofibrosarcoma protuberans (DFSP) is a cutaneous fibroblastic tumour that is locally aggressive, with a tendency for local recurrence, but rarely metastasizes. A collaboration of multi-disciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), the European Union of Medical Specialists (UEMS) and the European Academy of Dermatology and Venereology (EADV) was formed to update recommendations on DFSP diagnosis and treatment, based on current literature reviews and the experts' consensus. Diagnosis is suspected clinically and confirmed by pathology report, which should specify whether a transformation in higher-grade fibrosarcoma occurred. Detection of specific chromosomal translocations and/or fusion gene transcripts is useful to confirm diagnosis. Treatment is mainly surgical, intending to achieve complete resection of the tumour. To reduce the recurrence rate, the treatment of choice in DFSP is micrographically controlled surgery. Standard excision with a lateral safety margin of 2–3 cm is an acceptable alternative where only standard histopathological procedures are available. Imatinib is approved in Europe for treating inoperable primary tumours, locally inoperable recurrent disease, and metastatic DFSP. Use of imatinib has also been reported in extensive, difficult-to-operate tumours for preoperative reduction of tumour size, but clinical trials or large register data are required to confirm the usefulness of this approach. Therapeutic decisions for patients with fibrosarcomatous DFSP should be primarily made by an interdisciplinary oncology team ('tumour board').
{"title":"Diagnosis and treatment of dermatofibrosarcoma protuberans. European interdisciplinary guideline – update 2024","authors":"Philippe Saiag , Celeste Lebbe , Lieve Brochez , Jean-François Emile , Ana Maria Forsea , Catherine Harwood , Axel Hauschild , Antoine Italiano , Lidija Kandolf , Nicole WJ Kelleners-Smeets , Aimilios Lallas , Ulrike Leiter , Beatriz Llombart , Caterina Longo , Josep Malvehy , Zeljko Mijuskovic , David Moreno-Ramirez , Klara Mosterd , Luca Tagliaferri , Selma Ugurel , Claus Garbe","doi":"10.1016/j.ejca.2025.115265","DOIUrl":"10.1016/j.ejca.2025.115265","url":null,"abstract":"<div><div>Dermatofibrosarcoma protuberans (DFSP) is a cutaneous fibroblastic tumour that is locally aggressive, with a tendency for local recurrence, but rarely metastasizes. A collaboration of multi-disciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), the European Union of Medical Specialists (UEMS) and the European Academy of Dermatology and Venereology (EADV) was formed to update recommendations on DFSP diagnosis and treatment, based on current literature reviews and the experts' consensus. Diagnosis is suspected clinically and confirmed by pathology report, which should specify whether a transformation in higher-grade fibrosarcoma occurred. Detection of specific chromosomal translocations and/or fusion gene transcripts is useful to confirm diagnosis. Treatment is mainly surgical, intending to achieve complete resection of the tumour. To reduce the recurrence rate, the treatment of choice in DFSP is micrographically controlled surgery. Standard excision with a lateral safety margin of 2–3 cm is an acceptable alternative where only standard histopathological procedures are available. Imatinib is approved in Europe for treating inoperable primary tumours, locally inoperable recurrent disease, and metastatic DFSP. Use of imatinib has also been reported in extensive, difficult-to-operate tumours for preoperative reduction of tumour size, but clinical trials or large register data are required to confirm the usefulness of this approach. Therapeutic decisions for patients with fibrosarcomatous DFSP should be primarily made by an interdisciplinary oncology team ('tumour board').</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"218 ","pages":"Article 115265"},"PeriodicalIF":7.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143149438","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 : 2025-01-30DOI: 10.1016/j.ejca.2025.115266
Fabian Acker , Martin Reck , Daniel Martin , Stefan Rieken , Sophie Heinzen , Maximilian Rost , Lukas Aguinarte , Hanna Schulte , Hubert Serve , Thomas Oellerich , Martin Sebastian , Friederike C. Althoff
Background
In patients with unresectable, stage III non-small cell lung cancer (NSCLC), durvalumab maintenance after concurrent chemoradiotherapy (cCRT) was shown to improve survival over placebo. As subgroup analyses indicated better outcomes with earlier start of durvalumab, several trials evaluated concomitant checkpoint inhibition (CPI) with cCRT. However, this may introduce an increased risk of treatment-related pulmonary toxicity.
Methods
We conducted a systematic review and meta-analysis of clinical trials of combined cCRT plus CPI followed by CPI maintenance in patients with stage III NSCLC. Endpoints included incidence of pneumonitis by any cause, objective response rate (ORR), progression-free (PFS), and overall survival (OS).
Results
A total of 7 trials comprising 653 patients were included. In trials of single-agent CPI with cCRT, pneumonitis occurred in 33 % of patients (95 % confidence interval [CI], 28–39) with 7 % (5−9) having CTCAE grade 3–5. In one trial, double CPI (PD-1 and CTLA4) plus cCRT was associated with excessive pneumonitis-related mortality of 16 % (4−40). Across all trials, ORR was 69 % (63−76). Median PFS and OS were 16.3 (95 % CI, 14.0–20.5) and 39.5 months (35.3–45.9), respectively. Three-year PFS and OS were 36.8 % (95 % CI, 32.7–41.4) and 53.1 % (49.1–57.4). Sensitivity analysis showed that induction chemoimmunotherapy prior cCRT plus CPI was associated with improved PFS of 48.0 % at 3 years (95 % CI, 40.7–56.7) in one trial.
Discussion
Addition of single-agent CPI to cCRT is manageable in selected patients with stage III NSCLC. Efficacy outcomes appear to be in line with previous data of cCRT followed by CPI maintenance.
{"title":"Efficacy and safety of immune checkpoint inhibition combined with concurrent chemoradiotherapy in patients with stage III unresectable non-small cell lung cancer: A systematic review and meta-analysis","authors":"Fabian Acker , Martin Reck , Daniel Martin , Stefan Rieken , Sophie Heinzen , Maximilian Rost , Lukas Aguinarte , Hanna Schulte , Hubert Serve , Thomas Oellerich , Martin Sebastian , Friederike C. Althoff","doi":"10.1016/j.ejca.2025.115266","DOIUrl":"10.1016/j.ejca.2025.115266","url":null,"abstract":"<div><h3>Background</h3><div>In patients with unresectable, stage III non-small cell lung cancer (NSCLC), durvalumab maintenance after concurrent chemoradiotherapy (cCRT) was shown to improve survival over placebo. As subgroup analyses indicated better outcomes with earlier start of durvalumab, several trials evaluated concomitant checkpoint inhibition (CPI) with cCRT. However, this may introduce an increased risk of treatment-related pulmonary toxicity.</div></div><div><h3>Methods</h3><div>We conducted a systematic review and meta-analysis of clinical trials of combined cCRT plus CPI followed by CPI maintenance in patients with stage III NSCLC. Endpoints included incidence of pneumonitis by any cause, objective response rate (ORR), progression-free (PFS), and overall survival (OS).</div></div><div><h3>Results</h3><div>A total of 7 trials comprising 653 patients were included. In trials of single-agent CPI with cCRT, pneumonitis occurred in 33 % of patients (95 % confidence interval [CI], 28–39) with 7 % (5−9) having CTCAE grade 3–5. In one trial, double CPI (PD-1 and CTLA4) plus cCRT was associated with excessive pneumonitis-related mortality of 16 % (4−40). Across all trials, ORR was 69 % (63−76). Median PFS and OS were 16.3 (95 % CI, 14.0–20.5) and 39.5 months (35.3–45.9), respectively. Three-year PFS and OS were 36.8 % (95 % CI, 32.7–41.4) and 53.1 % (49.1–57.4). Sensitivity analysis showed that induction chemoimmunotherapy prior cCRT plus CPI was associated with improved PFS of 48.0 % at 3 years (95 % CI, 40.7–56.7) in one trial.</div></div><div><h3>Discussion</h3><div>Addition of single-agent CPI to cCRT is manageable in selected patients with stage III NSCLC. Efficacy outcomes appear to be in line with previous data of cCRT followed by CPI maintenance.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"218 ","pages":"Article 115266"},"PeriodicalIF":7.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078927","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 : 2025-01-30DOI: 10.1016/j.ejca.2025.115273
Xu Wang , April W. Mao , Sirui Pan , Dawei Wang , Lili He , Hannes Vogel , Jian-Hua Mao , William Weiss , Tao Li , Hang Chang
Background
The heterogeneity of Neuroblastoma (NB) leads to variation in response to treatment and outcomes. The aim of the current study is to discover AI-empowered cellular morphometric biomarkers (CMBs), to establish the corresponding CMB risk score (CMBRS), CMB risk group (CMBRG), large language model driven CMB risk score (CMB-LLM-RS), and large language model driven CMB risk group (CMB-LLM-RG), and to investigate and validate their prognostic and predictive power in NB.
Methods
In this study, the retrospective cohort enrolled 84 primary NBs between 1/2020 and 12/2021, followed up through 11/22/2024; the prospective cohort enrolled 67 primary NBs between 1/2022 and 7/2023, followed up through 11/22/2024.
Results
We identified 9 CMBs from a retrospective NB cohort, enabling the CMBRS, CMBRG, CMB-LLM-RS, and CMB-LLM-RG. Both CMBRG and CMB-LLM-RG are significantly associated with prognosis (p < 0.0001) and treatment response (p < 0.0001). Furthermore, we double-blindly validated the predictive power of CMBRG and CMB-LLM-RG in a prospective NB cohort, which confirms their potential value in real clinical settings. Importantly, CMBRG provides clinical value independent of the International Neuroblastoma Risk Group (INRG) classification system in both retrospective and prospective NB cohorts (p < 0.05); and the combination of CMBRG and INRG significantly increases prognostic and predictive performance for NB patients.
Conclusions
These findings suggest that CMBRG and CMB-LLM-RG have prognostic and predictive value for NB and warrants evaluation in larger multicenter cohorts.
{"title":"Cellular morphometric biomarkers and large language model predict prognosis and treatment response in neuroblastoma patients: A retrospective and double-blind prospective single arm clinical study","authors":"Xu Wang , April W. Mao , Sirui Pan , Dawei Wang , Lili He , Hannes Vogel , Jian-Hua Mao , William Weiss , Tao Li , Hang Chang","doi":"10.1016/j.ejca.2025.115273","DOIUrl":"10.1016/j.ejca.2025.115273","url":null,"abstract":"<div><h3>Background</h3><div>The heterogeneity of Neuroblastoma (NB) leads to variation in response to treatment and outcomes. The aim of the current study is to discover AI-empowered cellular morphometric biomarkers (CMBs), to establish the corresponding CMB risk score (CMBRS), CMB risk group (CMBRG), large language model driven CMB risk score (CMB-LLM-RS), and large language model driven CMB risk group (CMB-LLM-RG), and to investigate and validate their prognostic and predictive power in NB.</div></div><div><h3>Methods</h3><div>In this study, the retrospective cohort enrolled 84 primary NBs between 1/2020 and 12/2021, followed up through 11/22/2024; the prospective cohort enrolled 67 primary NBs between 1/2022 and 7/2023, followed up through 11/22/2024.</div></div><div><h3>Results</h3><div>We identified 9 CMBs from a retrospective NB cohort, enabling the CMBRS, CMBRG, CMB-LLM-RS, and CMB-LLM-RG. Both CMBRG and CMB-LLM-RG are significantly associated with prognosis (p < 0.0001) and treatment response (p < 0.0001). Furthermore, we double-blindly validated the predictive power of CMBRG and CMB-LLM-RG in a prospective NB cohort, which confirms their potential value in real clinical settings. Importantly, CMBRG provides clinical value independent of the International Neuroblastoma Risk Group (INRG) classification system in both retrospective and prospective NB cohorts (p < 0.05); and the combination of CMBRG and INRG significantly increases prognostic and predictive performance for NB patients.</div></div><div><h3>Conclusions</h3><div>These findings suggest that CMBRG and CMB-LLM-RG have prognostic and predictive value for NB and warrants evaluation in larger multicenter cohorts.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"218 ","pages":"Article 115273"},"PeriodicalIF":7.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143149440","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 : 2025-01-29DOI: 10.1016/j.ejca.2025.115268
Alberto Sobrero , Arvind Dasari , Jeneth Aquino , Sara Lonardi , Rocio Garcia-Carbonero , Elena Elez , Takayuki Yoshino , James Yao , Pilar Garcia-Alfonso , Judit Kocsis , Antonio Cubillo Gracian , Andrea Sartore-Bianchi , Taroh Satoh , Violaine Randrian , Jiri Tomasek , Geoff Chong , Timothy Price , Ziji Yu , Ashley Geiger , Lucy Chen , Cathy Eng
Introduction
Maintaining or improving health-related quality of life (HRQoL) is as important as extending survival in metastatic colorectal cancer. We report an HRQoL analysis from FRESCO-2 (NCT04322539).
Methods
Patients were randomized to fruquintinib +best supportive care (BSC; n = 461) or placebo +BSC (n = 230). Instruments of EORTC QLQ-C30 and 5-level EQ-5D, and ECOG performance status (PS) were assessed. Changes from baseline scores for QLQ-C30 and EQ-5D were evaluated and minimally important difference thresholds were used to define stable, improved, or deteriorated QoL. Time to deterioration (TTD) was assessed.
Results
With fruquintinib versus placebo, baseline QLQ-C30 global health status (GHS) and EQ-5D visual analog scale (VAS) scores were 65.2 versus 64.6 and 67.0 versus 66.6, respectively. Least-squares mean changes from baseline fluctuated throughout treatment. At end of treatment (EOT), mean scores with fruquintinib versus placebo were 53.8 versus 52.3 (QLQ-C30 GHS) and 58.9 versus 58.5 (EQ-5D VAS). For QLQ-C30 GHS, 38.3 % versus 36.5 % of patients receiving fruquintinib versus placebo had stable or improved scores at EOT; median TTD was 2.1 versus 1.8 months (HR, 0.9; 95 % CI, 0.7–1.0). For EQ-5D VAS, 47.9 % versus 42.7 % had stable or improved scores at EOT; median TTD was 2.6 versus 1.9 months (HR, 0.8; 95 % CI, 0.6–0.9). Median TTD to ECOG PS ≥ 2 or death within 30+ /7 days after EOT was 6.6 versus 2.9 months with fruquintinib versus placebo (HR, 0.6; 95 % CI, 0.4–0.7).
Conclusions
Fruquintinib delayed TTD of ECOG PS and did not negatively impact HRQoL versus placebo.
{"title":"Health-related quality of life associated with fruquintinib in patients with metastatic colorectal cancer: Results from the FRESCO-2 study","authors":"Alberto Sobrero , Arvind Dasari , Jeneth Aquino , Sara Lonardi , Rocio Garcia-Carbonero , Elena Elez , Takayuki Yoshino , James Yao , Pilar Garcia-Alfonso , Judit Kocsis , Antonio Cubillo Gracian , Andrea Sartore-Bianchi , Taroh Satoh , Violaine Randrian , Jiri Tomasek , Geoff Chong , Timothy Price , Ziji Yu , Ashley Geiger , Lucy Chen , Cathy Eng","doi":"10.1016/j.ejca.2025.115268","DOIUrl":"10.1016/j.ejca.2025.115268","url":null,"abstract":"<div><h3>Introduction</h3><div>Maintaining or improving health-related quality of life (HRQoL) is as important as extending survival in metastatic colorectal cancer. We report an HRQoL analysis from FRESCO-2 (NCT04322539).</div></div><div><h3>Methods</h3><div>Patients were randomized to fruquintinib +best supportive care (BSC; n = 461) or placebo +BSC (n = 230). Instruments of EORTC QLQ-C30 and 5-level EQ-5D, and ECOG performance status (PS) were assessed. Changes from baseline scores for QLQ-C30 and EQ-5D were evaluated and minimally important difference thresholds were used to define stable, improved, or deteriorated QoL. Time to deterioration (TTD) was assessed.</div></div><div><h3>Results</h3><div>With fruquintinib versus placebo, baseline QLQ-C30 global health status (GHS) and EQ-5D visual analog scale (VAS) scores were 65.2 versus 64.6 and 67.0 versus 66.6, respectively. Least-squares mean changes from baseline fluctuated throughout treatment. At end of treatment (EOT), mean scores with fruquintinib versus placebo were 53.8 versus 52.3 (QLQ-C30 GHS) and 58.9 versus 58.5 (EQ-5D VAS). For QLQ-C30 GHS, 38.3 % versus 36.5 % of patients receiving fruquintinib versus placebo had stable or improved scores at EOT; median TTD was 2.1 versus 1.8 months (HR, 0.9; 95 % CI, 0.7–1.0). For EQ-5D VAS, 47.9 % versus 42.7 % had stable or improved scores at EOT; median TTD was 2.6 versus 1.9 months (HR, 0.8; 95 % CI, 0.6–0.9). Median TTD to ECOG PS ≥ 2 or death within 30+ /7 days after EOT was 6.6 versus 2.9 months with fruquintinib versus placebo (HR, 0.6; 95 % CI, 0.4–0.7).</div></div><div><h3>Conclusions</h3><div>Fruquintinib delayed TTD of ECOG PS and did not negatively impact HRQoL versus placebo.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"218 ","pages":"Article 115268"},"PeriodicalIF":7.6,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395311","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 : 2025-01-29DOI: 10.1016/j.ejca.2025.115267
Clara Meier, Angela Brieger
Tumors are structures of high complexity. Plurality of their structural and functional components - heterogeneity, diversity, directionality, interdependence and integration of signaling pathways - seem to follow isolated local rules, whereby a superordinate structure remains largely unknown. Understanding the complexity of cancer is the mainstay in finding determinants and developing effective therapies. Interleukin 8 (IL-8) is a potent pro-inflammatory chemokine that is significantly elevated in many different tumor entities. In contrast to its initially postulated anti-tumor properties, an increasing number of studies have been published in recent years linking this chemokine with tumor-promoting features and poor prognosis. This review summarizes the current state and diversity of the role of IL-8 in the development of cancer.
{"title":"The role of IL-8 in cancer development and its impact on immunotherapy resistance","authors":"Clara Meier, Angela Brieger","doi":"10.1016/j.ejca.2025.115267","DOIUrl":"10.1016/j.ejca.2025.115267","url":null,"abstract":"<div><div>Tumors are structures of high complexity. Plurality of their structural and functional components - heterogeneity, diversity, directionality, interdependence and integration of signaling pathways - seem to follow isolated local rules, whereby a superordinate structure remains largely unknown. Understanding the complexity of cancer is the mainstay in finding determinants and developing effective therapies. Interleukin 8 (IL-8) is a potent pro-inflammatory chemokine that is significantly elevated in many different tumor entities. In contrast to its initially postulated anti-tumor properties, an increasing number of studies have been published in recent years linking this chemokine with tumor-promoting features and poor prognosis. This review summarizes the current state and diversity of the role of IL-8 in the development of cancer.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"218 ","pages":"Article 115267"},"PeriodicalIF":7.6,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122409","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 : 2025-01-27DOI: 10.1016/j.ejca.2025.115262
Taroh Satoh , Philippe Barthélémy , Lucia Nogova , Kazunori Honda , Hidekazu Hirano , Keun-Wook Lee , Sun Young Rha , Min-Hee Ryu , Joon Oh Park , Toshihiko Doi , Jaffer Ajani , Nanae Hangai , Jill Kremer , Mark Mina , Mei Liu , Kohei Shitara
Background and aims
Aberrant fibroblast growth factor receptor (FGFR)-driven signaling, predominantly arising from FGFR2 amplification, plays a key role in gastric cancer pathogenesis. This open-label, phase 2 study evaluated the efficacy and safety of futibatinib, an irreversible FGFR1–4 inhibitor, in patients with gastric or gastroesophageal junction (GEJ) cancer harboring FGFR2 amplifications.
Methods
Patients were treated with futibatinib 20 mg orally once daily in a 28-day cycle. The primary endpoint was objective response rate (ORR) per independent central review. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.
Results
Among 28 treated patients, the ORR per independent central review was 17.9 %, comprising five patients with a partial response (median duration of response, 3.9 months), and an additional nine patients with stable disease for a disease control rate of 50.0 %. Median PFS per independent central review and median OS were 2.9 and 5.9 months, respectively. The most common treatment-related adverse events (any grade) were hyperphosphatemia (89.3 %), decreased appetite (32.1 %), and increased aspartate aminotransferase (21.4 %). Only one (3.6 %) patient discontinued study treatment due to an adverse event.
Futibatinib demonstrated modest antitumor activity with a safety profile consistent with previous reports in patients with gastric or GEJ cancer harboring FGFR2 amplifications, potentially warranting further investigation.
{"title":"Phase 2 study of futibatinib in patients with gastric or gastroesophageal junction cancer harboring FGFR2 amplifications","authors":"Taroh Satoh , Philippe Barthélémy , Lucia Nogova , Kazunori Honda , Hidekazu Hirano , Keun-Wook Lee , Sun Young Rha , Min-Hee Ryu , Joon Oh Park , Toshihiko Doi , Jaffer Ajani , Nanae Hangai , Jill Kremer , Mark Mina , Mei Liu , Kohei Shitara","doi":"10.1016/j.ejca.2025.115262","DOIUrl":"10.1016/j.ejca.2025.115262","url":null,"abstract":"<div><h3>Background and aims</h3><div>Aberrant fibroblast growth factor receptor (FGFR)-driven signaling, predominantly arising from <em>FGFR2</em> amplification, plays a key role in gastric cancer pathogenesis. This open-label, phase 2 study evaluated the efficacy and safety of futibatinib, an irreversible FGFR1–4 inhibitor, in patients with gastric or gastroesophageal junction (GEJ) cancer harboring <em>FGFR2</em> amplifications.</div></div><div><h3>Methods</h3><div>Patients were treated with futibatinib 20 mg orally once daily in a 28-day cycle. The primary endpoint was objective response rate (ORR) per independent central review. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.</div></div><div><h3>Results</h3><div>Among 28 treated patients, the ORR per independent central review was 17.9 %, comprising five patients with a partial response (median duration of response, 3.9 months), and an additional nine patients with stable disease for a disease control rate of 50.0 %. Median PFS per independent central review and median OS were 2.9 and 5.9 months, respectively. The most common treatment-related adverse events (any grade) were hyperphosphatemia (89.3 %), decreased appetite (32.1 %), and increased aspartate aminotransferase (21.4 %). Only one (3.6 %) patient discontinued study treatment due to an adverse event.</div><div>Futibatinib demonstrated modest antitumor activity with a safety profile consistent with previous reports in patients with gastric or GEJ cancer harboring <em>FGFR2</em> amplifications, potentially warranting further investigation.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"218 ","pages":"Article 115262"},"PeriodicalIF":7.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143300056","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 : 2025-01-27DOI: 10.1016/j.ejca.2025.115258
Zhuang Li , Jiali Peng , Bingxin Zhang , Chen Zhao , Zhongshao Chen , Huimin Xiao , Zhaoyang Zhang , Xinyue Ma , Feng Gao , Rui Xin , Wenwei Wang , Shuaixin Wang , Lingliya Tang , Yawen Zhang , Beihua Kong , Li Li , Aijun Yin
Objectives
Substantial lymphovascular space invasion (LVSI) has been incorporated into the 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial carcinoma. This study aims to evaluate whether classifying LVSI into substantial LVSI (≥5 involved vessels) and no/focal LVSI (≤4 involved vessels) provides meaningful prognostic differentiation in early-stage endometrial carcinoma.
Methods
We retrospectively enrolled patients with FIGO 2009 stage I–II endometrial carcinoma who underwent surgical staging between January 2013 and August 2020. LVSI was graded as no LVSI, focal LVSI (1–4 involved vessels), or substantial LVSI (≥5 involved vessels), following the World Health Organization 2020 definition.
Results
Among 1796 patients, 112 (6.2 %) had substantial LVSI, 170 (9.5 %) had focal LVSI, and 1514 (84.3 %) had no LVSI. The 5-year progression-free survival (PFS) rates were 81.7 % for substantial LVSI, 89.9 % for focal LVSI, and 95.0 % for no LVSI (P < 0.001). Multivariate analysis found that substantial LVSI was an independent predictor of worse PFS (substantial vs. no LVSI: HR 2.49, P < 0.001; substantial vs. focal LVSI: HR 1.90, P = 0.047). No statistically significant difference in PFS was observed between patients with focal LVSI and those with no LVSI (HR 1.31, P = 0.321). The overall survival (OS) analysis showed consistent results.
Conclusions
Substantial LVSI is an independent prognostic factor for PFS and OS in early-stage endometrial carcinoma, while focal LVSI shows similar outcomes to no LVSI. Our findings support the use of substantial LVSI (≥5 involved vessels) as a key determinant for risk stratification and staging, aligning with the FIGO 2023 staging system recommendations.
{"title":"The prognostic and clinical significance of substantial lymphovascular space invasion in early-stage endometrial carcinoma","authors":"Zhuang Li , Jiali Peng , Bingxin Zhang , Chen Zhao , Zhongshao Chen , Huimin Xiao , Zhaoyang Zhang , Xinyue Ma , Feng Gao , Rui Xin , Wenwei Wang , Shuaixin Wang , Lingliya Tang , Yawen Zhang , Beihua Kong , Li Li , Aijun Yin","doi":"10.1016/j.ejca.2025.115258","DOIUrl":"10.1016/j.ejca.2025.115258","url":null,"abstract":"<div><h3>Objectives</h3><div>Substantial lymphovascular space invasion (LVSI) has been incorporated into the 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial carcinoma. This study aims to evaluate whether classifying LVSI into substantial LVSI (≥5 involved vessels) and no/focal LVSI (≤4 involved vessels) provides meaningful prognostic differentiation in early-stage endometrial carcinoma.</div></div><div><h3>Methods</h3><div>We retrospectively enrolled patients with FIGO 2009 stage I–II endometrial carcinoma who underwent surgical staging between January 2013 and August 2020. LVSI was graded as no LVSI, focal LVSI (1–4 involved vessels), or substantial LVSI (≥5 involved vessels), following the World Health Organization 2020 definition.</div></div><div><h3>Results</h3><div>Among 1796 patients, 112 (6.2 %) had substantial LVSI, 170 (9.5 %) had focal LVSI, and 1514 (84.3 %) had no LVSI. The 5-year progression-free survival (PFS) rates were 81.7 % for substantial LVSI, 89.9 % for focal LVSI, and 95.0 % for no LVSI (<em>P</em> < 0.001). Multivariate analysis found that substantial LVSI was an independent predictor of worse PFS (substantial vs. no LVSI: HR 2.49, <em>P</em> < 0.001; substantial vs. focal LVSI: HR 1.90, <em>P</em> = 0.047). No statistically significant difference in PFS was observed between patients with focal LVSI and those with no LVSI (HR 1.31, <em>P</em> = 0.321). The overall survival (OS) analysis showed consistent results.</div></div><div><h3>Conclusions</h3><div>Substantial LVSI is an independent prognostic factor for PFS and OS in early-stage endometrial carcinoma, while focal LVSI shows similar outcomes to no LVSI. Our findings support the use of substantial LVSI (≥5 involved vessels) as a key determinant for risk stratification and staging, aligning with the FIGO 2023 staging system recommendations.</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":"218 ","pages":"Article 115258"},"PeriodicalIF":7.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078965","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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