Pub Date : 2025-02-03DOI: 10.1016/s1470-2045(24)00430-3
Jawad Fares, Edgar Petrosyan, Crismita Dmello, Rimas V Lukas, Roger Stupp, Maciej S Lesniak
Advances in molecular biology, genetics, and epigenetics have refined our understanding of metastatic brain cancer and underscored the need for better classification and targeted approaches. The heterogeneity of brain metastases highlights the differences from their primary source of origin and contributes to therapeutic resistance. Before colonising the brain, tumour cells acquire specialised proficiencies that enable them to capitalise on the unique microenvironment of the brain. The tumour cells further orchestrate key adaptations to adjust to the brain microenvironment by manipulating the blood–brain barrier, evading immune surveillance, rewiring metabolic profiles, and reprogramming astrocytes. These adaptations facilitate tumour survival, growth, and treatment resistance. Recognising metastatic brain cancer as a distinctive CNS disease, rather than an extension of the primary cancer, would support the development of rational approaches that target its molecular and genetic features and improve research funding in this area. Here, we delve into the distinct genetic and phenotypic characteristics of metastatic brain cancer, and reflect on how a change in the perception of this disease could accelerate the development of more effective therapies and drive continued progress in the field of neuro-oncology.
{"title":"Rethinking metastatic brain cancer as a CNS disease","authors":"Jawad Fares, Edgar Petrosyan, Crismita Dmello, Rimas V Lukas, Roger Stupp, Maciej S Lesniak","doi":"10.1016/s1470-2045(24)00430-3","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00430-3","url":null,"abstract":"Advances in molecular biology, genetics, and epigenetics have refined our understanding of metastatic brain cancer and underscored the need for better classification and targeted approaches. The heterogeneity of brain metastases highlights the differences from their primary source of origin and contributes to therapeutic resistance. Before colonising the brain, tumour cells acquire specialised proficiencies that enable them to capitalise on the unique microenvironment of the brain. The tumour cells further orchestrate key adaptations to adjust to the brain microenvironment by manipulating the blood–brain barrier, evading immune surveillance, rewiring metabolic profiles, and reprogramming astrocytes. These adaptations facilitate tumour survival, growth, and treatment resistance. Recognising metastatic brain cancer as a distinctive CNS disease, rather than an extension of the primary cancer, would support the development of rational approaches that target its molecular and genetic features and improve research funding in this area. Here, we delve into the distinct genetic and phenotypic characteristics of metastatic brain cancer, and reflect on how a change in the perception of this disease could accelerate the development of more effective therapies and drive continued progress in the field of neuro-oncology.","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-03DOI: 10.1016/s1470-2045(24)00732-0
Ingrid Glimelius
No Abstract
{"title":"Mantle cell lymphoma: is it time for risk-adapted treatment?","authors":"Ingrid Glimelius","doi":"10.1016/s1470-2045(24)00732-0","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00732-0","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"81 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-03DOI: 10.1016/s1470-2045(24)00682-x
Michael Wang, Wojciech Jurczak, Marek Trneny, David Belada, Tomasz Wrobel, Nilanjan Ghosh, Mary-Margaret Keating, Tom van Meerten, Ruben Fernandez Alvarez, Gottfried von Keudell, Catherine Thieblemont, Frederic Peyrade, Marc Andre, Marc Hoffmann, Edith Szafer-Glusman, Jennifer Lin, James P Dean, Jutta K Neuenburg, Constantine S Tam
<h3>Background</h3>The combination of ibrutinib and venetoclax leverages complementary mechanisms of action and has shown promising clinical activity in mantle cell lymphoma (MCL). This study evaluated the efficacy and safety of ibrutinib–venetoclax compared with ibrutinib–placebo in patients with relapsed or refractory MCL.<h3>Methods</h3>SYMPATICO is a multicentre, randomised, double-blind, placebo-controlled, phase 3 study performed at 84 hospitals in Europe, North America, and Asia–Pacific. Eligible patients were adults (aged ≥18 years) with pathologically confirmed relapsed or refractory MCL after one to five previous lines of therapy and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2. Patients were randomly assigned (1:1) to receive oral ibrutinib 560 mg once daily concurrently with oral venetoclax (5-week ramp-up to 400 mg once daily) or placebo for 2 years, then single-agent ibrutinib 560 mg once daily until disease progression or unacceptable toxicity. Randomisation and treatment assignment occurred via interactive response technology using a stratified permuted block scheme (block sizes of 2 and 4) with stratification by ECOG performance status, previous lines of therapy, and tumour lysis syndrome risk category. Patients and investigators were masked to treatment assignment. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered with <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>, <span><span>NCT03112174</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>, and is closed to enrolment.<h3>Findings</h3>Between April 26, 2018, and Aug 28, 2019, 267 patients were enrolled and randomly assigned; 134 to the ibrutinib–venetoclax group and 133 to the ibrutinib–placebo group. 211 (79%) of 267 patients were male and 56 (21%) were female. With a median follow-up of 51·2 months (IQR 48·2–55·3), median progression-free survival was 31·9 months (95% CI 22·8–47·0) in the ibrutinib–venetoclax group and 22·1 months (16·5–29·5) in the ibrutinib–placebo group (hazard ratio 0·65 [95% CI 0·47–0·88]; p=0·0052). The most common grade 3–4 adverse events were neutropenia (42 [31%] of 134 patients in the ibrutinib–venetoclax group <em>vs</em> 14 [11%] of 132 patients in the ibrutinib–placebo group), thrombocytopenia (17 [13%] <em>vs</em> ten [8%]), and pneumonia (16 [12%] <em>vs</em> 14 [11%]). Serious adverse events occurred in 81 (60%) of 134 patients in the ibrutinib–venetoclax group and in 79 (60%) of 132 patients in the
{"title":"Ibrutinib plus venetoclax in relapsed or refractory mantle cell lymphoma (SYMPATICO): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study","authors":"Michael Wang, Wojciech Jurczak, Marek Trneny, David Belada, Tomasz Wrobel, Nilanjan Ghosh, Mary-Margaret Keating, Tom van Meerten, Ruben Fernandez Alvarez, Gottfried von Keudell, Catherine Thieblemont, Frederic Peyrade, Marc Andre, Marc Hoffmann, Edith Szafer-Glusman, Jennifer Lin, James P Dean, Jutta K Neuenburg, Constantine S Tam","doi":"10.1016/s1470-2045(24)00682-x","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00682-x","url":null,"abstract":"<h3>Background</h3>The combination of ibrutinib and venetoclax leverages complementary mechanisms of action and has shown promising clinical activity in mantle cell lymphoma (MCL). This study evaluated the efficacy and safety of ibrutinib–venetoclax compared with ibrutinib–placebo in patients with relapsed or refractory MCL.<h3>Methods</h3>SYMPATICO is a multicentre, randomised, double-blind, placebo-controlled, phase 3 study performed at 84 hospitals in Europe, North America, and Asia–Pacific. Eligible patients were adults (aged ≥18 years) with pathologically confirmed relapsed or refractory MCL after one to five previous lines of therapy and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2. Patients were randomly assigned (1:1) to receive oral ibrutinib 560 mg once daily concurrently with oral venetoclax (5-week ramp-up to 400 mg once daily) or placebo for 2 years, then single-agent ibrutinib 560 mg once daily until disease progression or unacceptable toxicity. Randomisation and treatment assignment occurred via interactive response technology using a stratified permuted block scheme (block sizes of 2 and 4) with stratification by ECOG performance status, previous lines of therapy, and tumour lysis syndrome risk category. Patients and investigators were masked to treatment assignment. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>NCT03112174</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, and is closed to enrolment.<h3>Findings</h3>Between April 26, 2018, and Aug 28, 2019, 267 patients were enrolled and randomly assigned; 134 to the ibrutinib–venetoclax group and 133 to the ibrutinib–placebo group. 211 (79%) of 267 patients were male and 56 (21%) were female. With a median follow-up of 51·2 months (IQR 48·2–55·3), median progression-free survival was 31·9 months (95% CI 22·8–47·0) in the ibrutinib–venetoclax group and 22·1 months (16·5–29·5) in the ibrutinib–placebo group (hazard ratio 0·65 [95% CI 0·47–0·88]; p=0·0052). The most common grade 3–4 adverse events were neutropenia (42 [31%] of 134 patients in the ibrutinib–venetoclax group <em>vs</em> 14 [11%] of 132 patients in the ibrutinib–placebo group), thrombocytopenia (17 [13%] <em>vs</em> ten [8%]), and pneumonia (16 [12%] <em>vs</em> 14 [11%]). Serious adverse events occurred in 81 (60%) of 134 patients in the ibrutinib–venetoclax group and in 79 (60%) of 132 patients in the ","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-03DOI: 10.1016/s1470-2045(24)00729-0
Mengmeng Li, Qingfeng Liu, Xiaomei Chen
Section snippets
Contributors
All authors cared for the patient. QL and ML wrote the initial draft. XC reviewed the manuscript. All authors read and approved the final version. Written informed consent to publication was obtained.
Declaration of interests
We declare no competing interests.
{"title":"Bullous Wells syndrome in a patient with occult nasopharyngeal carcinoma","authors":"Mengmeng Li, Qingfeng Liu, Xiaomei Chen","doi":"10.1016/s1470-2045(24)00729-0","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00729-0","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Contributors</h2>All authors cared for the patient. QL and ML wrote the initial draft. XC reviewed the manuscript. All authors read and approved the final version. Written informed consent to publication was obtained.</section></section><section><section><h2>Declaration of interests</h2>We declare no competing interests.</section></section>","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-03DOI: 10.1016/s1470-2045(25)00025-7
No Abstract
{"title":"Fires and their smouldering health effects","authors":"","doi":"10.1016/s1470-2045(25)00025-7","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00025-7","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-03DOI: 10.1016/s1470-2045(24)00404-2
Colm Mac Eochagain, Nina Rosa Neuendorff, Karolina Gente, Jan Leipe, Marthe Verhaert, Christine Sam, Nienke de Glas, Sindhuja Kadambi, Beverly Canin, Fabio Gomes, Lore Decoster, Beatriz Korc-Grodzicki, Siri Rostoft, Nicolò Matteo Luca Battisti, Hans Wildiers
Immune checkpoint inhibitors (ICIs) have substantially advanced the treatment landscape for a wide variety of malignancies. Older adults represent a large and rapidly growing demographic, among whom ICIs are widely prescribed. Management of ICI-associated toxicity among older adults, particularly in the presence of frailty and comorbidity, poses unique challenges. In this Policy Review, developed by the International Society of Geriatric Oncology (SIOG), we offer an evidence-based framework for health-care providers, caregivers, and policy makers for treating older adults with ICIs, focusing on unique considerations for this population that are not adequately addressed by existing guidelines, and expanding them to encompass geriatric oncology principles.
{"title":"Management of immune checkpoint inhibitor-associated toxicities in older adults with cancer: recommendations from the International Society of Geriatric Oncology (SIOG)","authors":"Colm Mac Eochagain, Nina Rosa Neuendorff, Karolina Gente, Jan Leipe, Marthe Verhaert, Christine Sam, Nienke de Glas, Sindhuja Kadambi, Beverly Canin, Fabio Gomes, Lore Decoster, Beatriz Korc-Grodzicki, Siri Rostoft, Nicolò Matteo Luca Battisti, Hans Wildiers","doi":"10.1016/s1470-2045(24)00404-2","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00404-2","url":null,"abstract":"Immune checkpoint inhibitors (ICIs) have substantially advanced the treatment landscape for a wide variety of malignancies. Older adults represent a large and rapidly growing demographic, among whom ICIs are widely prescribed. Management of ICI-associated toxicity among older adults, particularly in the presence of frailty and comorbidity, poses unique challenges. In this Policy Review, developed by the International Society of Geriatric Oncology (SIOG), we offer an evidence-based framework for health-care providers, caregivers, and policy makers for treating older adults with ICIs, focusing on unique considerations for this population that are not adequately addressed by existing guidelines, and expanding them to encompass geriatric oncology principles.","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-03DOI: 10.1016/s1470-2045(25)00003-8
No Abstract
{"title":"Thank you to The Lancet Oncology's reviewers in 2024","authors":"","doi":"10.1016/s1470-2045(25)00003-8","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00003-8","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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