Pub Date : 2024-07-01Epub Date: 2024-06-05DOI: 10.1016/S2213-2600(24)00183-8
James H Hull, Hege Clemm, Vibeke Backer, Michael Koehle, Margo Mountjoy, Martin Schwellnus, J Tod Olin
{"title":"Protecting respiratory health of athletes: an Olympic challenge.","authors":"James H Hull, Hege Clemm, Vibeke Backer, Michael Koehle, Margo Mountjoy, Martin Schwellnus, J Tod Olin","doi":"10.1016/S2213-2600(24)00183-8","DOIUrl":"10.1016/S2213-2600(24)00183-8","url":null,"abstract":"","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":null,"pages":null},"PeriodicalIF":38.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293933","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 : 2024-06-11DOI: 10.1016/S2213-2600(24)00190-5
Priya Venkatesan
{"title":"2024 American Thoracic Society International Conference.","authors":"Priya Venkatesan","doi":"10.1016/S2213-2600(24)00190-5","DOIUrl":"https://doi.org/10.1016/S2213-2600(24)00190-5","url":null,"abstract":"","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":null,"pages":null},"PeriodicalIF":76.2,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321986","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 : 2024-06-01Epub Date: 2024-05-10DOI: 10.1016/S2213-2600(24)00146-2
Federica Grosso, Luigi Cerbone, Alessandra Curioni-Fontecedro
{"title":"MARS 2 trial: the future of pleurectomy decortication in pleural mesothelioma.","authors":"Federica Grosso, Luigi Cerbone, Alessandra Curioni-Fontecedro","doi":"10.1016/S2213-2600(24)00146-2","DOIUrl":"10.1016/S2213-2600(24)00146-2","url":null,"abstract":"","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":null,"pages":null},"PeriodicalIF":38.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916775","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 : 2024-06-01Epub Date: 2024-05-08DOI: 10.1016/S2213-2600(24)00149-8
The Lancet Respiratory Medicine
{"title":"Tackling health disparities in asthma: a life-course challenge.","authors":"The Lancet Respiratory Medicine","doi":"10.1016/S2213-2600(24)00149-8","DOIUrl":"10.1016/S2213-2600(24)00149-8","url":null,"abstract":"","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":null,"pages":null},"PeriodicalIF":76.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908398","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 : 2024-06-01Epub Date: 2024-05-10DOI: 10.1016/S2213-2600(24)00111-5
Kevin G Blyth, Prasad S Adusumilli, Philippe Astoul, Liz Darlison, Y C Gary Lee, Aaron S Mansfield, Stefan J Marciniak, Nick Maskell, Vasiliki Panou, Tobias Peikert, Najib M Rahman, Marjorie G Zauderer, Daniel Sterman, Dean A Fennell
Most patients with pleural mesothelioma (PM) present with symptomatic pleural effusion. In some patients, PM is only detectable on the pleural surfaces, providing a strong rationale for intrapleural anticancer therapy. In modern prospective studies involving expert radiological staging and specialist multidisciplinary teams, the population incidence of stage I PM (an approximate surrogate of pleura-only PM) is higher than in historical retrospective series. In this Viewpoint, we advocate for the expansion of intrapleural trials to serve these patients, given the paucity of data supporting licensed systemic therapies in this setting and the uncertainties involved in surgical therapy. We begin by reviewing the unique anatomical and physiological features of the PM-bearing pleural space, before critically appraising the evidence for systemic therapies in stage I PM and previous intrapleural PM trials. We conclude with a summary of key challenges and potential solutions, including optimal trial designs, repurposing of indwelling pleural catheters, and new technologies.
{"title":"Leveraging the pleural space for anticancer therapies in pleural mesothelioma.","authors":"Kevin G Blyth, Prasad S Adusumilli, Philippe Astoul, Liz Darlison, Y C Gary Lee, Aaron S Mansfield, Stefan J Marciniak, Nick Maskell, Vasiliki Panou, Tobias Peikert, Najib M Rahman, Marjorie G Zauderer, Daniel Sterman, Dean A Fennell","doi":"10.1016/S2213-2600(24)00111-5","DOIUrl":"10.1016/S2213-2600(24)00111-5","url":null,"abstract":"<p><p>Most patients with pleural mesothelioma (PM) present with symptomatic pleural effusion. In some patients, PM is only detectable on the pleural surfaces, providing a strong rationale for intrapleural anticancer therapy. In modern prospective studies involving expert radiological staging and specialist multidisciplinary teams, the population incidence of stage I PM (an approximate surrogate of pleura-only PM) is higher than in historical retrospective series. In this Viewpoint, we advocate for the expansion of intrapleural trials to serve these patients, given the paucity of data supporting licensed systemic therapies in this setting and the uncertainties involved in surgical therapy. We begin by reviewing the unique anatomical and physiological features of the PM-bearing pleural space, before critically appraising the evidence for systemic therapies in stage I PM and previous intrapleural PM trials. We conclude with a summary of key challenges and potential solutions, including optimal trial designs, repurposing of indwelling pleural catheters, and new technologies.</p>","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":null,"pages":null},"PeriodicalIF":76.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916702","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 : 2024-06-01Epub Date: 2024-05-10DOI: 10.1016/S2213-2600(24)00119-X
Eric Lim, David Waller, Kelvin Lau, Jeremy Steele, Anthony Pope, Clinton Ali, Rocco Bilancia, Manjusha Keni, Sanjay Popat, Mary O'Brien, Nadza Tokaca, Nick Maskell, Louise Stadon, Dean Fennell, Louise Nelson, John Edwards, Sara Tenconi, Laura Socci, Robert C Rintoul, Kelly Wood, Amanda Stone, Dakshinamoorthy Muthukumar, Charlotte Ingle, Paul Taylor, Laura Cove-Smith, Raffaele Califano, Yvonne Summers, Zacharias Tasigiannopoulos, Andrea Bille, Riyaz Shah, Elizabeth Fuller, Andrew Macnair, Jonathan Shamash, Talal Mansy, Richard Milton, Pek Koh, Andreea Alina Ionescu, Sarah Treece, Amy Roy, Gary Middleton, Alan Kirk, Rosie A Harris, Kate Ashton, Barbara Warnes, Emma Bridgeman, Katherine Joyce, Nicola Mills, Daisy Elliott, Nicola Farrar, Elizabeth Stokes, Vikki Hughes, Andrew G Nicholson, Chris A Rogers
Background: Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was to compare outcomes after extended pleurectomy decortication plus chemotherapy versus chemotherapy alone.
Methods: MARS 2 was a phase 3, national, multicentre, open-label, parallel two-group, pragmatic, superiority randomised controlled trial conducted in the UK. The trial took place across 26 hospitals (21 recruiting only, one surgical only, and four recruiting and surgical). Following two cycles of chemotherapy, eligible participants with pleural mesothelioma were randomly assigned (1:1) to surgery and chemotherapy or chemotherapy alone using a secure web-based system. Individuals aged 16 years or older with resectable pleural mesothelioma and adequate organ and lung function were eligible for inclusion. Participants in the chemotherapy only group received two to four further cycles of chemotherapy, and participants in the surgery and chemotherapy group received pleurectomy decortication or extended pleurectomy decortication, followed by two to four further cycles of chemotherapy. It was not possible to mask allocation because the intervention was a major surgical procedure. The primary outcome was overall survival, defined as time from randomisation to death from any cause. Analyses were done on the intention-to-treat population for all outcomes, unless specified. This study is registered with ClinicalTrials.gov, NCT02040272, and is closed to new participants.
Findings: Between June 19, 2015, and Jan 21, 2021, of 1030 assessed for eligibility, 335 participants were randomly assigned (169 to surgery and chemotherapy, and 166 to chemotherapy alone). 291 (87%) participants were men and 44 (13%) women, and 288 (86%) were diagnosed with epithelioid mesothelioma. At a median follow-up of 22·4 months (IQR 11·3-30·8), median survival was shorter in the surgery and chemotherapy group (19·3 months [IQR 10·0-33·7]) than in the chemotherapy alone group (24·8 months [IQR 12·6-37·4]), and the difference in restricted mean survival time at 2 years was -1·9 months (95% CI -3·4 to -0·3, p=0·019). There were 318 serious adverse events (grade ≥3) in the surgery group and 169 in the chemotherapy group (incidence rate ratio 3·6 [95% CI 2·3 to 5·5], p<0·0001), with increased incidence of cardiac (30 vs 12; 3·01 [1·13 to 8·02]) and respiratory (84 vs 34; 2·62 [1·58 to 4·33]) disorders, infection (124 vs 53; 2·13 [1·36 to 3·33]), and additional surgical or medical procedures (15 vs eight; 2·41 [1·04 to 5·57]) in the surgery group.
Interpretation: Extended pleurectomy decortication was associated with worse survival to 2 years, and more serious adverse events for individuals with resectable pleural mesothelioma, compared with chemotherapy alone.
Funding: National Institute for Hea
背景:在随机试验中,从未对胸膜间皮瘤大体上完全切除的胸膜切除术进行过评估。本研究旨在比较胸膜切除术后加化疗与单纯化疗的疗效:MARS 2是一项在英国进行的全国性、多中心、开放标签、平行两组、务实、优势随机对照试验。该试验在 26 家医院进行(21 家医院只招收病人,1 家医院只做手术,4 家医院招收病人并做手术)。经过两个化疗周期后,符合条件的胸膜间皮瘤患者通过安全的网络系统被随机分配(1:1)接受手术和化疗或单纯化疗。年龄在16岁或16岁以上、患有可切除胸膜间皮瘤、器官和肺功能正常的患者均可参加。只接受化疗组的参与者将继续接受两到四个周期的化疗,而手术和化疗组的参与者将接受胸膜切除术或扩大胸膜切除术,然后再接受两到四个周期的化疗。由于干预是一项重大外科手术,因此无法掩盖分配情况。主要结果是总生存期,即从随机分配到任何原因死亡的时间。除特别说明外,所有结果的分析均在意向治疗人群中进行。该研究已在ClinicalTrials.gov注册,编号为NCT02040272,不再接受新参与者:2015年6月19日至2021年1月21日期间,在1030名通过资格评估的参与者中,335名参与者被随机分配(169名接受手术和化疗,166名接受单纯化疗)。291名(87%)参与者为男性,44名(13%)为女性,288名(86%)被诊断为上皮样间皮瘤。中位随访时间为22-4个月(IQR 11-3-30-8),手术和化疗组的中位生存期(19-3个月(IQR 10-0-33-7))短于单纯化疗组(24-8个月(IQR 12-6-37-4)),2年的限制性平均生存期差异为-1-9个月(95% CI -3-4至-0-3,P=0-019)。手术组有318例严重不良事件(≥3级),化疗组有169例(发生率比3-6[95% CI 2-3至5-5],P解释:与单纯化疗相比,扩展胸膜切除术与可切除胸膜间皮瘤患者更差的2年生存率和更多的严重不良事件有关:国家健康与护理研究所(NIHR)健康技术评估项目(15/188/31)、英国癌症研究中心可行性研究项目资助(A15895)。
{"title":"Extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (MARS 2): a phase 3 randomised controlled trial.","authors":"Eric Lim, David Waller, Kelvin Lau, Jeremy Steele, Anthony Pope, Clinton Ali, Rocco Bilancia, Manjusha Keni, Sanjay Popat, Mary O'Brien, Nadza Tokaca, Nick Maskell, Louise Stadon, Dean Fennell, Louise Nelson, John Edwards, Sara Tenconi, Laura Socci, Robert C Rintoul, Kelly Wood, Amanda Stone, Dakshinamoorthy Muthukumar, Charlotte Ingle, Paul Taylor, Laura Cove-Smith, Raffaele Califano, Yvonne Summers, Zacharias Tasigiannopoulos, Andrea Bille, Riyaz Shah, Elizabeth Fuller, Andrew Macnair, Jonathan Shamash, Talal Mansy, Richard Milton, Pek Koh, Andreea Alina Ionescu, Sarah Treece, Amy Roy, Gary Middleton, Alan Kirk, Rosie A Harris, Kate Ashton, Barbara Warnes, Emma Bridgeman, Katherine Joyce, Nicola Mills, Daisy Elliott, Nicola Farrar, Elizabeth Stokes, Vikki Hughes, Andrew G Nicholson, Chris A Rogers","doi":"10.1016/S2213-2600(24)00119-X","DOIUrl":"10.1016/S2213-2600(24)00119-X","url":null,"abstract":"<p><strong>Background: </strong>Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was to compare outcomes after extended pleurectomy decortication plus chemotherapy versus chemotherapy alone.</p><p><strong>Methods: </strong>MARS 2 was a phase 3, national, multicentre, open-label, parallel two-group, pragmatic, superiority randomised controlled trial conducted in the UK. The trial took place across 26 hospitals (21 recruiting only, one surgical only, and four recruiting and surgical). Following two cycles of chemotherapy, eligible participants with pleural mesothelioma were randomly assigned (1:1) to surgery and chemotherapy or chemotherapy alone using a secure web-based system. Individuals aged 16 years or older with resectable pleural mesothelioma and adequate organ and lung function were eligible for inclusion. Participants in the chemotherapy only group received two to four further cycles of chemotherapy, and participants in the surgery and chemotherapy group received pleurectomy decortication or extended pleurectomy decortication, followed by two to four further cycles of chemotherapy. It was not possible to mask allocation because the intervention was a major surgical procedure. The primary outcome was overall survival, defined as time from randomisation to death from any cause. Analyses were done on the intention-to-treat population for all outcomes, unless specified. This study is registered with ClinicalTrials.gov, NCT02040272, and is closed to new participants.</p><p><strong>Findings: </strong>Between June 19, 2015, and Jan 21, 2021, of 1030 assessed for eligibility, 335 participants were randomly assigned (169 to surgery and chemotherapy, and 166 to chemotherapy alone). 291 (87%) participants were men and 44 (13%) women, and 288 (86%) were diagnosed with epithelioid mesothelioma. At a median follow-up of 22·4 months (IQR 11·3-30·8), median survival was shorter in the surgery and chemotherapy group (19·3 months [IQR 10·0-33·7]) than in the chemotherapy alone group (24·8 months [IQR 12·6-37·4]), and the difference in restricted mean survival time at 2 years was -1·9 months (95% CI -3·4 to -0·3, p=0·019). There were 318 serious adverse events (grade ≥3) in the surgery group and 169 in the chemotherapy group (incidence rate ratio 3·6 [95% CI 2·3 to 5·5], p<0·0001), with increased incidence of cardiac (30 vs 12; 3·01 [1·13 to 8·02]) and respiratory (84 vs 34; 2·62 [1·58 to 4·33]) disorders, infection (124 vs 53; 2·13 [1·36 to 3·33]), and additional surgical or medical procedures (15 vs eight; 2·41 [1·04 to 5·57]) in the surgery group.</p><p><strong>Interpretation: </strong>Extended pleurectomy decortication was associated with worse survival to 2 years, and more serious adverse events for individuals with resectable pleural mesothelioma, compared with chemotherapy alone.</p><p><strong>Funding: </strong>National Institute for Hea","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":null,"pages":null},"PeriodicalIF":38.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11136673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916675","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 : 2024-06-01Epub Date: 2024-03-12DOI: 10.1016/S2213-2600(24)00010-9
Daniel P Steinfort, Gargi Kothari, Neil Wallace, Nicholas Hardcastle, Kanishka Rangamuwa, Edith M T Dieleman, Percy Lee, Peixuan Li, Julie A Simpson, Shaun Yo, Farzad Bashirdazeh, Phan Nguyen, Barton R Jennings, David Fielding, Laurence Crombag, Louis B Irving, Kazuhiro Yasufuku, Jouke T Annema, David E Ost, Shankar Siva
Background: Systematic mediastinal lymph node staging by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) improves accuracy of staging in patients with early-stage non-small-cell lung cancer (NSCLC). However, patients with locally advanced NSCLC commonly undergo only selective lymph node sampling. This study aimed to determine the proportion of patients with locally advanced NSCLC in whom systematic endoscopic mediastinal staging identified PET-occult lymph node metastases, and to describe the consequences of PET-occult disease on radiotherapy planning.
Methods: This prospective, international, multicentre, single-arm, international study was conducted at seven tertiary lung cancer centres in four countries (Australia, Canada, the Netherlands, and the USA). Patients aged 18 years or older with suspected or known locally advanced NSCLC underwent systematic endoscopic mediastinal lymph node staging before combination chemoradiotherapy or high-dose palliative radiotherapy. The primary endpoint was the proportion of participants with PET-occult mediastinal lymph node metastases shown following systematic endoscopic staging. The study was prospectively registered with Australian New Zealand Clinical Trials Registry, ACTRN12617000333314.
Findings: From Jan 30, 2018, to March 23, 2022, 155 patients underwent systematic endoscopic mediastinal lymph node staging and were eligible for analysis. 58 (37%) of patients were female and 97 (63%) were male. Discrepancy in extent of mediastinal disease identified by PET and EBUS-TBNA was observed in 57 (37% [95% CI 29-44]) patients. PET-occult lymph node metastases were identified in 18 (12% [7-17]) participants, including 16 (13% [7-19]) of 123 participants with clinical stage IIIA or cN2 NSCLC. Contralateral PET-occult N3 disease was identified in nine (7% [2-12]) of 128 participants staged cN0, cN1, or cN2. Identification of PET-occult disease resulted in clinically significant changes to treatment in all 18 patients. In silico dosimetry studies showed the median volume of PET-occult lymph nodes receiving the prescription dose of 60 Gy was only 10·1% (IQR 0·1-52·3). No serious adverse events following endoscopic staging were reported.
Interpretation: Our findings suggests that systematic endoscopic mediastinal staging in patients with locally advanced or unresectable NSCLC is more accurate than PET alone in defining extent of mediastinal involvement. Standard guideline-recommended PET-based radiotherapy planning results in suboptimal tumour coverage. Our findings indicate that systematic endoscopic staging should be routinely performed in patients with locally advanced NSCLC being considered for radiotherapy to accurately inform radiation planning and treatment decision making in patients with locally advanced NSCLC.
{"title":"Systematic endoscopic staging of mediastinum to guide radiotherapy planning in patients with locally advanced non-small-cell lung cancer (SEISMIC): an international, multicentre, single-arm, clinical trial.","authors":"Daniel P Steinfort, Gargi Kothari, Neil Wallace, Nicholas Hardcastle, Kanishka Rangamuwa, Edith M T Dieleman, Percy Lee, Peixuan Li, Julie A Simpson, Shaun Yo, Farzad Bashirdazeh, Phan Nguyen, Barton R Jennings, David Fielding, Laurence Crombag, Louis B Irving, Kazuhiro Yasufuku, Jouke T Annema, David E Ost, Shankar Siva","doi":"10.1016/S2213-2600(24)00010-9","DOIUrl":"10.1016/S2213-2600(24)00010-9","url":null,"abstract":"<p><strong>Background: </strong>Systematic mediastinal lymph node staging by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) improves accuracy of staging in patients with early-stage non-small-cell lung cancer (NSCLC). However, patients with locally advanced NSCLC commonly undergo only selective lymph node sampling. This study aimed to determine the proportion of patients with locally advanced NSCLC in whom systematic endoscopic mediastinal staging identified PET-occult lymph node metastases, and to describe the consequences of PET-occult disease on radiotherapy planning.</p><p><strong>Methods: </strong>This prospective, international, multicentre, single-arm, international study was conducted at seven tertiary lung cancer centres in four countries (Australia, Canada, the Netherlands, and the USA). Patients aged 18 years or older with suspected or known locally advanced NSCLC underwent systematic endoscopic mediastinal lymph node staging before combination chemoradiotherapy or high-dose palliative radiotherapy. The primary endpoint was the proportion of participants with PET-occult mediastinal lymph node metastases shown following systematic endoscopic staging. The study was prospectively registered with Australian New Zealand Clinical Trials Registry, ACTRN12617000333314.</p><p><strong>Findings: </strong>From Jan 30, 2018, to March 23, 2022, 155 patients underwent systematic endoscopic mediastinal lymph node staging and were eligible for analysis. 58 (37%) of patients were female and 97 (63%) were male. Discrepancy in extent of mediastinal disease identified by PET and EBUS-TBNA was observed in 57 (37% [95% CI 29-44]) patients. PET-occult lymph node metastases were identified in 18 (12% [7-17]) participants, including 16 (13% [7-19]) of 123 participants with clinical stage IIIA or cN2 NSCLC. Contralateral PET-occult N3 disease was identified in nine (7% [2-12]) of 128 participants staged cN0, cN1, or cN2. Identification of PET-occult disease resulted in clinically significant changes to treatment in all 18 patients. In silico dosimetry studies showed the median volume of PET-occult lymph nodes receiving the prescription dose of 60 Gy was only 10·1% (IQR 0·1-52·3). No serious adverse events following endoscopic staging were reported.</p><p><strong>Interpretation: </strong>Our findings suggests that systematic endoscopic mediastinal staging in patients with locally advanced or unresectable NSCLC is more accurate than PET alone in defining extent of mediastinal involvement. Standard guideline-recommended PET-based radiotherapy planning results in suboptimal tumour coverage. Our findings indicate that systematic endoscopic staging should be routinely performed in patients with locally advanced NSCLC being considered for radiotherapy to accurately inform radiation planning and treatment decision making in patients with locally advanced NSCLC.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":null,"pages":null},"PeriodicalIF":38.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140137509","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 : 2024-06-01Epub Date: 2024-03-26DOI: 10.1016/S2213-2600(24)00076-6
Rovina Ruslami, Federica Fregonese, Lika Apriani, Leila Barss, Nancy Bedingfield, Victor Chiang, Victoria J Cook, Dina Fisher, Eri Flores, Greg J Fox, James Johnston, Rachel K Lim, Richard Long, Catherine Paulsen, Thu Anh Nguyen, Nguyen Viet Nhung, Diana Gibson, Chantal Valiquette, Andrea Benedetti, Dick Menzies
Background: Tuberculosis preventive treatment (TPT) is a key component of tuberculosis elimination. To improve completion and reduce the burden for people and health systems, short, safe, and effective TPT regimens are needed. We aimed to compare safety and treatment completion of various doses and durations of rifampicin in people who were recommended to receive TPT.
Methods: This partially blinded, parallel-arm, non-inferiority, randomised, controlled, phase 2b trial was done at seven university-affiliated clinics in Canada, Indonesia, and Viet Nam. Participants aged 10 years or older were included if they had an indication for TPT according to WHO guidelines for Indonesia and Viet Nam, or Canadian guidelines for Canadian sites, and a positive tuberculin skin test or interferon-γ release assay. Participants were randomly assigned (1:1:1) to receive oral rifampicin at 10 mg/kg once daily for 4 months (standard-dose group), 20 mg/kg daily for 2 months (20 mg/kg group), or 30 mg/kg daily for 2 months (30 mg/kg group). The randomisation sequence was computer generated with blocks of variable size (three, six, and nine) and stratified by country for Indonesia and Viet Nam, and by city within Canada. Participants and investigators were masked to dose in high-dose groups, but unmasked to duration in all groups. The two co-primary outcomes were safety (in the safety population, in which participants received at least one dose of the study drug) and treatment completion (in the modified intention-to-treat [mITT] population, excluding those ineligible after randomisation). Protocol-defined adverse events were defined as grade 3 or worse, or rash or allergy of any grade, judged by an independent and masked panel as possibly or probably related to the study. A margin of 4% was used to assess non-inferiority. This study is registered with ClinicalTrials.gov, NCT03988933 (active).
Findings: Between Sept 1, 2019, and Sept 30, 2022, 1692 people were assessed for eligibility, 1376 were randomly assigned, and eight were excluded after randomisation. 1368 participants were included in the mITT population (454 in the standard group, 461 in the 20 mg/kg group, and 453 in the 30 mg/kg group). 589 (43%) participants were male and 779 (57%) were female. 372 (82%) in the standard-dose group, 329 (71%) in the 20 mg/kg group, and 293 (65%) in the 30 mg/kg group completed treatment. No participants in the standard-dose group, one (<1%) of 441 participants in the 20 mg/kg group, and four (1%) of 423 in the 30 mg/kg group developed grade 3 hepatotoxicity. Risk of protocol-defined adverse events was higher in the 30 mg/kg group than in the standard-dose group (adjusted risk difference 4·6% [95% CI 1·8 to 7·4]) or the 20 mg/kg group (5·1% [2·3 to 7·8]). There was no difference in the risk of adverse events between the 20 mg/kg and standard-dose groups (-0·5% [95% CI -2·4 to 1·5]; non-inferiority met). Completio
{"title":"High-dose, short-duration versus standard rifampicin for tuberculosis preventive treatment: a partially blinded, three-arm, non-inferiority, randomised, controlled trial.","authors":"Rovina Ruslami, Federica Fregonese, Lika Apriani, Leila Barss, Nancy Bedingfield, Victor Chiang, Victoria J Cook, Dina Fisher, Eri Flores, Greg J Fox, James Johnston, Rachel K Lim, Richard Long, Catherine Paulsen, Thu Anh Nguyen, Nguyen Viet Nhung, Diana Gibson, Chantal Valiquette, Andrea Benedetti, Dick Menzies","doi":"10.1016/S2213-2600(24)00076-6","DOIUrl":"10.1016/S2213-2600(24)00076-6","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis preventive treatment (TPT) is a key component of tuberculosis elimination. To improve completion and reduce the burden for people and health systems, short, safe, and effective TPT regimens are needed. We aimed to compare safety and treatment completion of various doses and durations of rifampicin in people who were recommended to receive TPT.</p><p><strong>Methods: </strong>This partially blinded, parallel-arm, non-inferiority, randomised, controlled, phase 2b trial was done at seven university-affiliated clinics in Canada, Indonesia, and Viet Nam. Participants aged 10 years or older were included if they had an indication for TPT according to WHO guidelines for Indonesia and Viet Nam, or Canadian guidelines for Canadian sites, and a positive tuberculin skin test or interferon-γ release assay. Participants were randomly assigned (1:1:1) to receive oral rifampicin at 10 mg/kg once daily for 4 months (standard-dose group), 20 mg/kg daily for 2 months (20 mg/kg group), or 30 mg/kg daily for 2 months (30 mg/kg group). The randomisation sequence was computer generated with blocks of variable size (three, six, and nine) and stratified by country for Indonesia and Viet Nam, and by city within Canada. Participants and investigators were masked to dose in high-dose groups, but unmasked to duration in all groups. The two co-primary outcomes were safety (in the safety population, in which participants received at least one dose of the study drug) and treatment completion (in the modified intention-to-treat [mITT] population, excluding those ineligible after randomisation). Protocol-defined adverse events were defined as grade 3 or worse, or rash or allergy of any grade, judged by an independent and masked panel as possibly or probably related to the study. A margin of 4% was used to assess non-inferiority. This study is registered with ClinicalTrials.gov, NCT03988933 (active).</p><p><strong>Findings: </strong>Between Sept 1, 2019, and Sept 30, 2022, 1692 people were assessed for eligibility, 1376 were randomly assigned, and eight were excluded after randomisation. 1368 participants were included in the mITT population (454 in the standard group, 461 in the 20 mg/kg group, and 453 in the 30 mg/kg group). 589 (43%) participants were male and 779 (57%) were female. 372 (82%) in the standard-dose group, 329 (71%) in the 20 mg/kg group, and 293 (65%) in the 30 mg/kg group completed treatment. No participants in the standard-dose group, one (<1%) of 441 participants in the 20 mg/kg group, and four (1%) of 423 in the 30 mg/kg group developed grade 3 hepatotoxicity. Risk of protocol-defined adverse events was higher in the 30 mg/kg group than in the standard-dose group (adjusted risk difference 4·6% [95% CI 1·8 to 7·4]) or the 20 mg/kg group (5·1% [2·3 to 7·8]). There was no difference in the risk of adverse events between the 20 mg/kg and standard-dose groups (-0·5% [95% CI -2·4 to 1·5]; non-inferiority met). Completio","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":null,"pages":null},"PeriodicalIF":38.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327393","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}