Pub Date : 2025-01-23DOI: 10.1016/s1470-2045(25)00023-3
Sharmila Devi
No Abstract
{"title":"Texan judge blocks US FDA changes on cigarette packaging","authors":"Sharmila Devi","doi":"10.1016/s1470-2045(25)00023-3","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00023-3","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"74 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026649","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 : 2025-01-21DOI: 10.1016/s1470-2045(24)00679-x
Richard S Finn, Baek-Yeol Ryoo, Chih-Hung Hsu, Daneng Li, Adam M Burgoyne, Christopher Cotter, Shreya Badhrinarayanan, Yulei Wang, Anqi Yin, Tirupathi Rao Edubilli, Sami Mahrus, Matthew H Secrest, Colby S Shemesh, Nancy Yu, Stephen P Hack, Edward Cha, Ed Gane
<h3>Background</h3>PD-L1 and VEGF blockade with atezolizumab plus bevacizumab has been shown to improve survival in unresectable hepatocellular carcinoma. TIGIT is an immune checkpoint regulator implicated in many cancers, including unresectable hepatocellular carcinoma. Here, we evaluate the clinical activity and safety of the addition of tiragolumab, an anti-TIGIT monoclonal antibody, to atezolizumab plus bevacizumab.<h3>Methods</h3>This randomised, open-label, phase 1b–2 umbrella study was conducted at 26 centres across China, France, Israel, New Zealand, South Korea, Taiwan, and the USA. Eligible patients were adults aged 18 years old or older with previously untreated locally advanced unresectable hepatocellular carcinoma, an Eastern Cooperative Oncology Group performance status of 0–1, Child-Pugh class A disease, and a life expectancy of at least 3 months. Eligible patients were randomly assigned (2:1) using permuted block randomisation to receive either tiragolumab 600 mg plus atezolizumab 1200 mg plus bevacizumab 15 mg/kg or atezolizumab 1200 mg plus bevacizumab 15 mg/kg, administered via intravenous infusion every 3 weeks on day 1 of each 21-day cycle. Patients received treatment until unacceptable toxic effects or loss of clinical benefit, whichever occurred first. The primary endpoint was objective response rate. Analysis of clinical activity was done in the efficacy-evaluable population (all patients who received at least one dose of each drug for their assigned treatment regimen) and safety was assessed in all patients who received any study treatment. The trial 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>NCT04524871</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 ongoing.<h3>Findings</h3>Between Aug 20, 2020, and Feb 10, 2022, we assessed 154 patients for eligibility and 59 eligible patients were randomly assigned to receive tiragolumab plus atezolizumab plus bevacizumab (n=41) or atezolizumab plus bevacizumab (n=18); one patient in the tiragolumab plus atezolizumab plus bevacizumab group experienced an adverse event before receiving any treatment and withdrew from the study. Median age was 65·0 years (IQR 61·0–73·0). 46 (79%) of 58 patients were male and 12 (21%) were female. Most patients were Asian (23 [40%]) or White (21 [36%]). At the time of clinical cutoff (Aug 21, 2023), median follow-up was 20·6 months (IQR 10·6–28·0) in the tiragolumab plus atezolizumab plus bevacizumab group and 14·0 months (4·2–18·5) in the atezolizumab plus bevacizumab group. The confirmed objective response rate was 43% (95% CI 27–59, n=17) in the tiragolum
{"title":"Tiragolumab in combination with atezolizumab and bevacizumab in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (MORPHEUS-Liver): a randomised, open-label, phase 1b–2, study","authors":"Richard S Finn, Baek-Yeol Ryoo, Chih-Hung Hsu, Daneng Li, Adam M Burgoyne, Christopher Cotter, Shreya Badhrinarayanan, Yulei Wang, Anqi Yin, Tirupathi Rao Edubilli, Sami Mahrus, Matthew H Secrest, Colby S Shemesh, Nancy Yu, Stephen P Hack, Edward Cha, Ed Gane","doi":"10.1016/s1470-2045(24)00679-x","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00679-x","url":null,"abstract":"<h3>Background</h3>PD-L1 and VEGF blockade with atezolizumab plus bevacizumab has been shown to improve survival in unresectable hepatocellular carcinoma. TIGIT is an immune checkpoint regulator implicated in many cancers, including unresectable hepatocellular carcinoma. Here, we evaluate the clinical activity and safety of the addition of tiragolumab, an anti-TIGIT monoclonal antibody, to atezolizumab plus bevacizumab.<h3>Methods</h3>This randomised, open-label, phase 1b–2 umbrella study was conducted at 26 centres across China, France, Israel, New Zealand, South Korea, Taiwan, and the USA. Eligible patients were adults aged 18 years old or older with previously untreated locally advanced unresectable hepatocellular carcinoma, an Eastern Cooperative Oncology Group performance status of 0–1, Child-Pugh class A disease, and a life expectancy of at least 3 months. Eligible patients were randomly assigned (2:1) using permuted block randomisation to receive either tiragolumab 600 mg plus atezolizumab 1200 mg plus bevacizumab 15 mg/kg or atezolizumab 1200 mg plus bevacizumab 15 mg/kg, administered via intravenous infusion every 3 weeks on day 1 of each 21-day cycle. Patients received treatment until unacceptable toxic effects or loss of clinical benefit, whichever occurred first. The primary endpoint was objective response rate. Analysis of clinical activity was done in the efficacy-evaluable population (all patients who received at least one dose of each drug for their assigned treatment regimen) and safety was assessed in all patients who received any study treatment. The trial 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>NCT04524871</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 ongoing.<h3>Findings</h3>Between Aug 20, 2020, and Feb 10, 2022, we assessed 154 patients for eligibility and 59 eligible patients were randomly assigned to receive tiragolumab plus atezolizumab plus bevacizumab (n=41) or atezolizumab plus bevacizumab (n=18); one patient in the tiragolumab plus atezolizumab plus bevacizumab group experienced an adverse event before receiving any treatment and withdrew from the study. Median age was 65·0 years (IQR 61·0–73·0). 46 (79%) of 58 patients were male and 12 (21%) were female. Most patients were Asian (23 [40%]) or White (21 [36%]). At the time of clinical cutoff (Aug 21, 2023), median follow-up was 20·6 months (IQR 10·6–28·0) in the tiragolumab plus atezolizumab plus bevacizumab group and 14·0 months (4·2–18·5) in the atezolizumab plus bevacizumab group. The confirmed objective response rate was 43% (95% CI 27–59, n=17) in the tiragolum","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991997","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 : 2025-01-21DOI: 10.1016/s1470-2045(24)00728-9
Jeffrey Sum Lung Wong, Carmen Chak-Lui Wong, Frances Sze Kei Sun, Thomas Yau
No Abstract
没有抽象的
{"title":"Insights into the future of first-line advanced hepatocellular carcinoma treatment","authors":"Jeffrey Sum Lung Wong, Carmen Chak-Lui Wong, Frances Sze Kei Sun, Thomas Yau","doi":"10.1016/s1470-2045(24)00728-9","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00728-9","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992383","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 : 2025-01-20DOI: 10.1016/s1470-2045(24)00734-4
Laura Stöffler, Dominik Paul Modest, Johann Pratschke, Philipp Konstantin Haber
No Abstract
没有抽象的
{"title":"Solidifying local ablation in the treatment of small-size colorectal liver metastasis","authors":"Laura Stöffler, Dominik Paul Modest, Johann Pratschke, Philipp Konstantin Haber","doi":"10.1016/s1470-2045(24)00734-4","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00734-4","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990765","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 : 2025-01-20DOI: 10.1016/s1470-2045(24)00660-0
Susan van der Lei, Robbert S Puijk, Madelon Dijkstra, Hannah H Schulz, Danielle J W Vos, Jan J J De Vries, Hester J Scheffer, Birgit I Lissenberg-Witte, Luca Aldrighetti, Mark Arntz, Maarten W Barentsz, Marc G Besselink, Bart Bracke, Rutger C G Bruijnen, Tineke E Buffart, Mark C Burgmans, Thierry Chapelle, Marielle M E Coolsen, Sanne W de Boer, Francesco de Cobelli, Martijn R Meijerink
<h3>Background</h3>For patients with small-size colorectal liver metastases, growing evidence suggests thermal ablation to be associated with fewer adverse events and faster recovery than resection while also challenging resection in terms of local control and overall survival. This study assessed the potential non-inferiority of thermal ablation compared with surgical resection in patients with small-size resectable colorectal liver metastases.<h3>Methods</h3>Adult patients (aged ≥18 years) from 14 centres in the Netherlands, Belgium, and Italy with ten or fewer small-size (≤3 cm) colorectal liver metastases, no extrahepatic metastases, and an Eastern Cooperative Oncology Group performance status of 0–2, were stratified per centre, and according to their disease burden, into low, intermediate, and high disease burden subgroups and randomly assigned 1:1 to receive either thermal ablation (experimental group) or surgical resection (control group) of all target colorectal liver metastases using the web-based module Castor electronic data capture with variable block sizes of 4, 6, and 8. Although at the operator's discretion, a minimally invasive approach in both treatment groups was recommended. The primary endpoint was overall survival, assessed in the intention-to-treat population. A hazard ratio (HR) of 1·30 was considered the upper limit of non-inferiority for the primary endpoint. A preplanned interim analysis with predefined stopping rules for futility (conditional power to prove the null hypothesis <20%) and early benefit (conditional power >90%, superior safety outcomes for the experimental group, and no difference or superiority regarding local control for the experimental group) was done 12 months after enrolment of 50% of the planned sample size. Safety was assessed per treatment group. This trial 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>NCT03088150</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>.<h3>Findings</h3>Between Aug 7, 2017, and Feb 14, 2024, 300 patients were randomly assigned to the experimental group (n=148, 100 male [68%] and 48 female [32%]; median age 67·9 years [IQR 29·2–85·7]) or to the control group (n=148, 107 male [72%] and 41 female [28%]; median age 65·1 [IQR 31·4–87·4]); four patients (two in each treatment group) were excluded after randomisation because they were found to have other disease pathology. Median follow-up at the prespecified interim analysis was 28·9 months (IQR 0·3–77·8). The trial was stopped early for meeting the predefined stopping rules: (1) a conditional likelihood to prove non-inferiority for over
{"title":"Thermal ablation versus surgical resection of small-size colorectal liver metastases (COLLISION): an international, randomised, controlled, phase 3 non-inferiority trial","authors":"Susan van der Lei, Robbert S Puijk, Madelon Dijkstra, Hannah H Schulz, Danielle J W Vos, Jan J J De Vries, Hester J Scheffer, Birgit I Lissenberg-Witte, Luca Aldrighetti, Mark Arntz, Maarten W Barentsz, Marc G Besselink, Bart Bracke, Rutger C G Bruijnen, Tineke E Buffart, Mark C Burgmans, Thierry Chapelle, Marielle M E Coolsen, Sanne W de Boer, Francesco de Cobelli, Martijn R Meijerink","doi":"10.1016/s1470-2045(24)00660-0","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00660-0","url":null,"abstract":"<h3>Background</h3>For patients with small-size colorectal liver metastases, growing evidence suggests thermal ablation to be associated with fewer adverse events and faster recovery than resection while also challenging resection in terms of local control and overall survival. This study assessed the potential non-inferiority of thermal ablation compared with surgical resection in patients with small-size resectable colorectal liver metastases.<h3>Methods</h3>Adult patients (aged ≥18 years) from 14 centres in the Netherlands, Belgium, and Italy with ten or fewer small-size (≤3 cm) colorectal liver metastases, no extrahepatic metastases, and an Eastern Cooperative Oncology Group performance status of 0–2, were stratified per centre, and according to their disease burden, into low, intermediate, and high disease burden subgroups and randomly assigned 1:1 to receive either thermal ablation (experimental group) or surgical resection (control group) of all target colorectal liver metastases using the web-based module Castor electronic data capture with variable block sizes of 4, 6, and 8. Although at the operator's discretion, a minimally invasive approach in both treatment groups was recommended. The primary endpoint was overall survival, assessed in the intention-to-treat population. A hazard ratio (HR) of 1·30 was considered the upper limit of non-inferiority for the primary endpoint. A preplanned interim analysis with predefined stopping rules for futility (conditional power to prove the null hypothesis <20%) and early benefit (conditional power >90%, superior safety outcomes for the experimental group, and no difference or superiority regarding local control for the experimental group) was done 12 months after enrolment of 50% of the planned sample size. Safety was assessed per treatment group. This trial 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>NCT03088150</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>.<h3>Findings</h3>Between Aug 7, 2017, and Feb 14, 2024, 300 patients were randomly assigned to the experimental group (n=148, 100 male [68%] and 48 female [32%]; median age 67·9 years [IQR 29·2–85·7]) or to the control group (n=148, 107 male [72%] and 41 female [28%]; median age 65·1 [IQR 31·4–87·4]); four patients (two in each treatment group) were excluded after randomisation because they were found to have other disease pathology. Median follow-up at the prespecified interim analysis was 28·9 months (IQR 0·3–77·8). The trial was stopped early for meeting the predefined stopping rules: (1) a conditional likelihood to prove non-inferiority for over","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990764","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 : 2025-01-17DOI: 10.1016/s1470-2045(24)00678-8
Fabio Y Moraes, Andre G Gouveia, Vanessa Freitas Bratti, Edward C Dee, Juliana Fernandes Pavoni, Laura M Carson, Cecília Félix Penido Mendes de Sousa, Richard Sullivan, Gustavo Nader Marta, Wilma M Hopman, Christopher M Booth, Ajay Aggarwal, Ahmedin Jemal, Timothy P Hanna, Brooke E Wilson, Gustavo Arruda Viani
<h3>Background</h3>The Linear Accelerator Shortage Index (LSI) is a practical tool for prioritising the deployment of linear accelerators (LINACs) in various regions within a country. The LSI reflects the ratio of LINAC demand to current availability. The aim of this study was to use the LSI to predict global LINAC needs and classify countries according to the degree of radiotherapy shortage (LINAC shortage grade).<h3>Methods</h3>In this cross-sectional, population-based study of globally representative, country-level data, we sourced regional LINAC distribution, numbers of radiotherapy centres, and cancer incidence data for 181 countries from the Directory of Radiotherapy Centers and Global Cancer Observatory 2022 databases. Current gross domestic product and gross national income per capita in US dollars were obtained from the World Bank. We calculated an LSI for each country to assess the relative demand and supply of radiotherapy by dividing LINAC use by 450 and multiplying by 100. An LSI of 100 or less indicates no shortage (450 or fewer patients per LINAC), whereas an LSI greater than 100 signals a shortage, with higher values indicating more severe deficits. We categorised countries by LINAC shortage grade: grade 0 (LSI ≤100, no shortage), grade 1 (LSI 101–130, low need), grade 2 (LSI 131–300, high need), grade 3 (LSI >300, excessive need), or grade 4 (no existing LINACs). We estimated LINAC requirements until 2045 using the LSI and Global Cancer Observatory data. We determined future investment costs according to the LSI for each country.<h3>Findings</h3>As of the data cutoff on Sept 15, 2024, the global median LSI was 130 (IQR 96–319), suggesting a shortage of 30% in radiotherapy capacity. Significant disparities in median LSI were observed across income levels: low-income countries had a median LSI of 1523 (528–2247), lower-middle-income countries 399 (183–685), upper-middle-income countries 133 (104–198), and high-income countries 96 (83–127; p<0·0001). The distribution of countries across LINAC shortage grades was 40 (22%) of 181 as grade 0, 32 (18%) as grade 1, 35 (19%) as grade 2, 38 (21%) as grade 3, and 36 (20%) as grade 4 (no LINACs). Most LINAC shortage grade 4 countries were low income (12 [33%]) or lower-middle income (16 [44%]). The median number of new LINACs needed per country by 2045 was estimated at 6 (1–13) for grade 0, 21 (4–102) for grade 1, 22 (8–80) for grade 2, 52 (26–113) for grade 3, and three (2–14) for grade 4. To meet these demands, also including the replacement of obsolete devices, an estimated 30 470 LINACs will be needed by 2045. The median total investment required for new and replacement machines and radiotherapy centres to meet the 2045 demand is projected at US$162 million (49–369) for grade 0, $216 million (54–772) for grade 1, $143 million (64–580) for grade 2, $238 million (126–561) for grade 3, and $16 million (9–59) for grade 4. A significant change in LINAC shortage grade composition between
{"title":"Global linear accelerator requirements and personalised country recommendations: a cross-sectional, population-based study","authors":"Fabio Y Moraes, Andre G Gouveia, Vanessa Freitas Bratti, Edward C Dee, Juliana Fernandes Pavoni, Laura M Carson, Cecília Félix Penido Mendes de Sousa, Richard Sullivan, Gustavo Nader Marta, Wilma M Hopman, Christopher M Booth, Ajay Aggarwal, Ahmedin Jemal, Timothy P Hanna, Brooke E Wilson, Gustavo Arruda Viani","doi":"10.1016/s1470-2045(24)00678-8","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00678-8","url":null,"abstract":"<h3>Background</h3>The Linear Accelerator Shortage Index (LSI) is a practical tool for prioritising the deployment of linear accelerators (LINACs) in various regions within a country. The LSI reflects the ratio of LINAC demand to current availability. The aim of this study was to use the LSI to predict global LINAC needs and classify countries according to the degree of radiotherapy shortage (LINAC shortage grade).<h3>Methods</h3>In this cross-sectional, population-based study of globally representative, country-level data, we sourced regional LINAC distribution, numbers of radiotherapy centres, and cancer incidence data for 181 countries from the Directory of Radiotherapy Centers and Global Cancer Observatory 2022 databases. Current gross domestic product and gross national income per capita in US dollars were obtained from the World Bank. We calculated an LSI for each country to assess the relative demand and supply of radiotherapy by dividing LINAC use by 450 and multiplying by 100. An LSI of 100 or less indicates no shortage (450 or fewer patients per LINAC), whereas an LSI greater than 100 signals a shortage, with higher values indicating more severe deficits. We categorised countries by LINAC shortage grade: grade 0 (LSI ≤100, no shortage), grade 1 (LSI 101–130, low need), grade 2 (LSI 131–300, high need), grade 3 (LSI >300, excessive need), or grade 4 (no existing LINACs). We estimated LINAC requirements until 2045 using the LSI and Global Cancer Observatory data. We determined future investment costs according to the LSI for each country.<h3>Findings</h3>As of the data cutoff on Sept 15, 2024, the global median LSI was 130 (IQR 96–319), suggesting a shortage of 30% in radiotherapy capacity. Significant disparities in median LSI were observed across income levels: low-income countries had a median LSI of 1523 (528–2247), lower-middle-income countries 399 (183–685), upper-middle-income countries 133 (104–198), and high-income countries 96 (83–127; p<0·0001). The distribution of countries across LINAC shortage grades was 40 (22%) of 181 as grade 0, 32 (18%) as grade 1, 35 (19%) as grade 2, 38 (21%) as grade 3, and 36 (20%) as grade 4 (no LINACs). Most LINAC shortage grade 4 countries were low income (12 [33%]) or lower-middle income (16 [44%]). The median number of new LINACs needed per country by 2045 was estimated at 6 (1–13) for grade 0, 21 (4–102) for grade 1, 22 (8–80) for grade 2, 52 (26–113) for grade 3, and three (2–14) for grade 4. To meet these demands, also including the replacement of obsolete devices, an estimated 30 470 LINACs will be needed by 2045. The median total investment required for new and replacement machines and radiotherapy centres to meet the 2045 demand is projected at US$162 million (49–369) for grade 0, $216 million (54–772) for grade 1, $143 million (64–580) for grade 2, $238 million (126–561) for grade 3, and $16 million (9–59) for grade 4. A significant change in LINAC shortage grade composition between","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"119 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988892","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 : 2025-01-16DOI: 10.1016/s1470-2045(25)00011-7
Karl Gruber
No Abstract
无摘要
{"title":"Cancer incidence associated with PFAS contamination of drinking water in the USA","authors":"Karl Gruber","doi":"10.1016/s1470-2045(25)00011-7","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00011-7","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987423","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 : 2025-01-16DOI: 10.1016/s1470-2045(25)00010-5
Sharmila Devi
No Abstract
没有抽象的
{"title":"Hiring freezes within the NHS impact cancer care","authors":"Sharmila Devi","doi":"10.1016/s1470-2045(25)00010-5","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00010-5","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987424","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}
<h3>Background</h3>Vascular endothelial growth factor (VEGF) is overexpressed in nasopharyngeal carcinoma and suppresses the anti-tumour immune response. Previous studies have shown that adding anti-VEGF treatment to PD-1 inhibition treatment strategies improves tumour response. We aimed to compare the efficacy of pembrolizumab, a PD-1 inhibitor, with or without bevacizumab, a VEGF inhibitor, in nasopharyngeal carcinoma.<h3>Methods</h3>In this randomised, open-label, phase 2 trial done at two hospitals (National University Cancer Institute and Tan Tock Seng Hospital) in Singapore, patients with platinum-resistant recurrent or metastatic nasophayngeal carcinoma were eligible if they were aged 21 years or older and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1. Patients were assigned (1:1; using random permuted blocks with varying sizes of 4 and 6) to receive either intravenous pembrolizumab (200 mg) every 21 days or a combination of pembrolizumab with intravenous bevacizumab (7·5 mg/kg) administered 1 week prior to each dose, until radiographic disease progression, unacceptable toxicity, completion of 32 cycles, or withdrawal of consent. The study was open label, therefore no masking of treatment assignment was implemented. The primary endpoint was objective response rate, assessed using RECIST (version 1.1) by independent radiologists and analysed in the intention-to-treat population (ie, all randomly assigned patients). This trial 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>NCT03813394</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 enrolment has closed.<h3>Findings</h3>Between May 13, 2019, and Dec 6, 2023, we assessed 60 individuals for eligibility, 12 were excluded, and 48 were randomly allocated to pembrolizumab alone (n=24) or a combination of bevacizumab and pembrolizumab (n=24). The median age was 56 years (IQR 48–65), and 40 (83%) of 48 patients were male and eight (17%) were female. The median follow-up was 28·3 months (IQR 15·1–55·9). The objective response rate was significantly higher in the bevacizumab and pembrolizumab group (58·3% [95% CI 36·6–77·9] than in the pembrolizumab group (12·5% [2·7–32·4]; unadjusted RR 4·67 [95% CI 1·54–14·18]; p=0·0010). Grade 3 treatment-related adverse events occurred in two (8%) of 24 patients in the pembrolizumab group and in seven (29%) of 24 patients in the bevacizumab and pembrolizumab group; the most common severe or grade 3–4 treatment-related adverse events were thrombosis or bleeding (four [17%] of 24 patients in the bevacizumab and pembrolizumab group <em>vs</em> none o
背景血管内皮生长因子（VEGF）在鼻咽癌中过度表达，并抑制抗肿瘤免疫反应。先前的研究表明，在 PD-1 抑制治疗策略中加入抗血管内皮生长因子治疗可改善肿瘤反应。我们旨在比较 PD-1 抑制剂 pembrolizumab 与血管内皮生长因子抑制剂贝伐珠单抗的疗效。方法 在新加坡的两家医院（国立大学癌症研究所和陈笃生医院）进行的这项随机、开放标签的 2 期试验中，铂耐药复发性或转移性鼻咽癌患者只要年龄在 21 岁或以上，且东部合作肿瘤学组（ECOG）表现状态为 0-1 级，就符合条件。患者被分配（1:1；使用4和6个不同大小的随机排列区块）接受静脉注射pembrolizumab（200毫克），每21天一次，或在每次给药前1周接受pembrolizumab与静脉注射贝伐珠单抗（7-5毫克/千克）的联合治疗，直至出现放射学疾病进展、不可接受的毒性、完成32个周期或撤销同意。该研究为开放标签研究，因此不对治疗分配进行掩蔽。主要终点是客观反应率，由独立放射科专家使用 RECIST（1.1 版）进行评估，并在意向治疗人群（即所有随机分配的患者）中进行分析。该试验已在ClinicalTrials.gov上注册，编号为NCT03813394，注册已结束。研究结果在2019年5月13日至2023年12月6日期间，我们评估了60人的资格，12人被排除在外，48人被随机分配到彭博利珠单抗（n=24）或贝伐单抗和彭博利珠单抗的组合（n=24）。中位年龄为 56 岁（IQR 48-65），48 名患者中有 40 名（83%）男性，8 名（17%）女性。中位随访时间为 28-3 个月（IQR 15-1-55-9）。贝伐单抗和pembrolizumab组的客观反应率（58-3% [95% CI 36-6-77-9]）明显高于pembrolizumab组（12-5% [2-7-32-4]；未调整RR 4-67 [95% CI 1-54-14-18]；P=0-0010）。Pembrolizumab组24例患者中有2例（8%）发生了3级治疗相关不良事件，贝伐珠单抗和Pembrolizumab组24例患者中有7例（29%）发生了3级治疗相关不良事件；最常见的严重或 3-4 级治疗相关不良事件是血栓或出血（贝伐单抗和 Pembrolizumab 组 24 名患者中有 4 例[17%]，而 Pembrolizumab 组 24 名患者中没有）、其他毒性反应包括转氨酶炎（无 vs 1 [4%]）、结肠炎（1 [4%] vs 无）、细胞减少症（无 vs 1 [4%]）、皮肤毒性（1 [4%] vs 无）、高血压（1 [4%] vs 无）和蛋白尿（1 [4%] vs 无）。两组患者均未出现4级治疗相关不良事件或治疗相关死亡病例。释义Pembrolizumab联合贝伐单抗治疗铂类耐药鼻咽癌比pembrolizumab单药疗效更好，且毒性可控。如果在三期试验中得到验证，这种联合疗法可能会成为这一患者群体的新治疗标准。
{"title":"Pembrolizumab with or without bevacizumab in platinum-resistant recurrent or metastatic nasopharyngeal carcinoma: a randomised, open-label, phase 2 trial","authors":"Wan-Qin Chong, Jia-Li Low, Joshua K Tay, Thi Bich Uyen Le, Grace Shi-Qing Goh, Kenneth Sooi, Hui-Lin Teo, Seng-Wee Cheo, Regina Tong-Xin Wong, Jens Samol, Ming-Yann Lim, Hao Li, Niranjan Shirgaonkar, Shumei Chia, Lingzhi Wang, Anil Gopinathan, Donovan Kum-Chuen Eu, Raymond King-Yin Tsang, Kwok-Seng Loh, Han-Chong Toh, Boon-Cher Goh","doi":"10.1016/s1470-2045(24)00677-6","DOIUrl":"https://doi.org/10.1016/s1470-2045(24)00677-6","url":null,"abstract":"<h3>Background</h3>Vascular endothelial growth factor (VEGF) is overexpressed in nasopharyngeal carcinoma and suppresses the anti-tumour immune response. Previous studies have shown that adding anti-VEGF treatment to PD-1 inhibition treatment strategies improves tumour response. We aimed to compare the efficacy of pembrolizumab, a PD-1 inhibitor, with or without bevacizumab, a VEGF inhibitor, in nasopharyngeal carcinoma.<h3>Methods</h3>In this randomised, open-label, phase 2 trial done at two hospitals (National University Cancer Institute and Tan Tock Seng Hospital) in Singapore, patients with platinum-resistant recurrent or metastatic nasophayngeal carcinoma were eligible if they were aged 21 years or older and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1. Patients were assigned (1:1; using random permuted blocks with varying sizes of 4 and 6) to receive either intravenous pembrolizumab (200 mg) every 21 days or a combination of pembrolizumab with intravenous bevacizumab (7·5 mg/kg) administered 1 week prior to each dose, until radiographic disease progression, unacceptable toxicity, completion of 32 cycles, or withdrawal of consent. The study was open label, therefore no masking of treatment assignment was implemented. The primary endpoint was objective response rate, assessed using RECIST (version 1.1) by independent radiologists and analysed in the intention-to-treat population (ie, all randomly assigned patients). This trial 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>NCT03813394</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 enrolment has closed.<h3>Findings</h3>Between May 13, 2019, and Dec 6, 2023, we assessed 60 individuals for eligibility, 12 were excluded, and 48 were randomly allocated to pembrolizumab alone (n=24) or a combination of bevacizumab and pembrolizumab (n=24). The median age was 56 years (IQR 48–65), and 40 (83%) of 48 patients were male and eight (17%) were female. The median follow-up was 28·3 months (IQR 15·1–55·9). The objective response rate was significantly higher in the bevacizumab and pembrolizumab group (58·3% [95% CI 36·6–77·9] than in the pembrolizumab group (12·5% [2·7–32·4]; unadjusted RR 4·67 [95% CI 1·54–14·18]; p=0·0010). Grade 3 treatment-related adverse events occurred in two (8%) of 24 patients in the pembrolizumab group and in seven (29%) of 24 patients in the bevacizumab and pembrolizumab group; the most common severe or grade 3–4 treatment-related adverse events were thrombosis or bleeding (four [17%] of 24 patients in the bevacizumab and pembrolizumab group <em>vs</em> none o","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986883","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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