Study protocol for VIdeo assisted thoracoscopic lobectomy versus conventional Open LobEcTomy for lung cancer, a UK multicentre randomised controlled trial with an internal pilot (the VIOLET study)

Eric Lim, Tim Batchelor, Michael Shackcloth, Joel Dunning, Niall McGonigle, Tim Brush, Lucy Dabner, Rosie Harris, Holly E Mckeon, Sangeetha Paramasivan, Daisy Elliott, Elizabeth A Stokes, Sarah Wordsworth, Jane Blazeby, Chris A Rogers, VIOLET Trialists, Eric Lim, Chris A Rogers, Tim Brush, Lucy Dabner, Dawn Phillips, Holly Mckeon, Chloe Beard, Rosie Harris, Daisy Elliott, Sangeetha Paramasivan, Alba Realpe Rojas, Sarah Wordsworth, Elizabeth Stokes, Jane Blazeby, Andrew G Nicholson, Sofina Begum, Simon Jordan, Paulo De Sousa, Monica Tavares Barbosa, Tim Batchelor, Eveline Internullo, Rakesh Krishnadas, Gianluca Casali, Doug West, Karen Bobruk, Catherine O'Donovan, Louise Flintoff, Amelia Lowe, Joanna Nicklin, Emma Heron, Jo Chambers, Becky Houlihan, Laura Beacham, Heather Hudson, Katy Tucker, Toni Farmery, Danielle Davis, Mike Shackcloth, Julius Asante-Siaw, Susannah Love, Sarah Feeney, Lindsey Murphy, Almudena Duran Rosas, Andrea Young, Joel Dunning, Ian Paul, Hyder Latif, Charlotte Jacobs, Alison Chilvers, Edward Stephenson, Martyn Cain, Nazalie Iqbal, Vladimir Anikin, Niall McGonigle, Claire Prendergast, Lisa Jones, Paula Rogers, Babu Naidu, Hazem Fallouh, Luis Hernandez, Maninder Kalkat, Richard Steyn, Nicola Oswald, Amy Kerr, Charlotte Ferris, Jo Webb, Joanne Taylor, Hollie Bancroft, Salma Kadiri, Zara Jalal Senior, Elizabeth Belcher, Dionisios Stavroulias, Francesco Di Chiara, Kathryn Saunders, May Havinden-Williams, Mark Ainsworth, Mahmoud Loubani, Syed Qadri, Karen Dobbs, Paul Atkin, Dominic Fellowes, Leanne Cox, Vipin Zamvar, Lucy Marshall, Fiona Strachan, Stacey Stewart, Ruth Langley, Joy Adamson, Ian Hunt, Peter B Licht, Arjun Nair, Chris Hall, Mike Cowen, Susan J Dutton, Alan Kirk, Keith Kerr, Rajesh Shah, Nagmi Qureshi, Tom Treasure, Eric Lim, Tim Batchelor, Michael Shackcloth, Joel Dunning, Niall McGonigle, Tim Brush, Lucy Dabner, Rosie Harris, Holly E Mckeon, Sangeetha Paramasivan, Daisy Elliott, Elizabeth A Stokes, Sarah Wordsworth, Jane Blazeby, Chris A Rogers, VIOLET Trialists, Eric Lim, Chris A Rogers, Tim Brush, Lucy Dabner, Dawn Phillips, Holly Mckeon, Chloe Beard, Rosie Harris, Daisy Elliott, Sangeetha Paramasivan, Alba Realpe Rojas, Sarah Wordsworth, Elizabeth Stokes, Jane Blazeby, Andrew G Nicholson, Sofina Begum, Simon Jordan, Paulo De Sousa, Monica Tavares Barbosa, Tim Batchelor, Eveline Internullo, Rakesh Krishnadas, Gianluca Casali, Doug West, Karen Bobruk, Catherine O'Donovan, Louise Flintoff, Amelia Lowe, Joanna Nicklin, Emma Heron, Jo Chambers, Becky Houlihan, Laura Beacham, Heather Hudson, Katy Tucker, Toni Farmery, Danielle Davis, Mike Shackcloth, Julius Asante-Siaw, Susannah Love, Sarah Feeney, Lindsey Murphy, Almudena Duran Rosas, Andrea Young, Joel Dunning, Ian Paul, Hyder Latif, Charlotte Jacobs, Alison Chilvers, Edward Stephenson, Martyn Cain, Nazalie Iqbal, Vladimir Anikin, Niall McGonigle, Claire Prendergast, Lisa Jones, Paula Rogers, Babu Naidu, Hazem Fallouh, Luis Hernandez, Maninder Kalkat, Richard Steyn, Nicola Oswald, Amy Kerr, Charlotte Ferris, Jo Webb, Joanne Taylor, Hollie Bancroft, Salma Kadiri, Zara Jalal Senior, Elizabeth Belcher, Dionisios Stavroulias, Francesco Di Chiara, Kathryn Saunders, May Havinden-Williams, Mark Ainsworth, Mahmoud Loubani, Syed Qadri, Karen Dobbs, Paul Atkin, Dominic Fellowes, Leanne Cox, Vipin Zamvar, Lucy Marshall, Fiona Strachan, Stacey Stewart, Ruth Langley, Joy Adamson, Ian Hunt, Peter B Licht, Arjun Nair, Chris Hall, Mike Cowen, Susan J Dutton, Alan Kirk, Keith Kerr, Rajesh Shah, Nagmi Qureshi, Tom Treasure

Abstract

Introduction: Lung cancer is a leading cause of cancer deaths worldwide and surgery remains the main treatment for early stage disease. Prior to the introduction of video-assisted thoracoscopic surgery (VATS), lung resection for cancer was undertaken through an open thoracotomy. To date, the evidence base supporting the different surgical approaches is based on non-randomised studies, small randomised trials and is focused mainly on short-term in-hospital outcomes.

Methods and analysis: The VIdeo assisted thoracoscopic lobectomy versus conventional Open LobEcTomy for lung cancer study is a UK multicentre parallel group randomised controlled trial (RCT) with blinding of outcome assessors and participants (to hospital discharge) comparing the effectiveness, cost-effectiveness and acceptability of VATS lobectomy versus open lobectomy for treatment of lung cancer. We will test the hypothesis that VATS lobectomy is superior to open lobectomy with respect to self-reported physical function 5 weeks after randomisation (approximately 1 month after surgery). Secondary outcomes include assessment of efficacy (hospital stay, pain, proportion and time to uptake of chemotherapy), measures of safety (adverse health events), oncological outcomes (proportion of patients upstaged to pathologic N2 (pN2) disease and disease-free survival), overall survival and health related quality of life to 1 year. The QuinteT Recruitment Intervention is integrated into the trial to optimise recruitment.

Ethics and dissemination: This trial has been approved by the UK (Dulwich) National Research Ethics Service Committee London. Findings will be written-up as methodology papers for conference presentation, and publication in peer-reviewed journals. Many aspects of the feasibility work will inform surgical RCTs in general and these will be reported at methodology meetings. We will also link with lung cancer clinical studies groups. The patient and public involvement group that works with the Respiratory Biomedical Research Unit at the Brompton Hospital will help identify how we can best publicise the findings.

Trial registration number: ISRCTN13472721.

Keywords: Cardiothoracic surgery; lobectomy; lung cancer; minimally invasive; open surgery; randomised controlled trial; video assisted.

Conflict of interest statement

Competing interests: Prof. Rogers reports grants from British Heart Foundation, during the conduct of the study;Dr. Dunning reports personal fees from Cambridge Medical Robotics, personal fees from LIVSMed, outside the submitted work;Dr. Stokes reports grants from UK National Institute for Health Research (Health Technology Assessment Programme), Department of Health and Social Care, during the conduct of the study;Prof. Wordsworth reports grants from UK National Institute for Health Research (Health Technology Assessment Programme), Department of Health and Social Care, during the conduct of the study;Prof. Lim reports personal fees from Abbott Molecular, personal fees from Glaxo Smith Kline, personal fees from Pfizer, personal fees from Norvatis, personal fees from Covidien, personal fees from Roche, personal fees from Lily Oncology, personal fees from Boehringer Ingelheim, personal fees from Medela, grants and personal fees from ScreenCell, personal fees from Ethicon, grants from Clearbridge Biomedics, grants from Guardant Health, outside the submitted work;Dr. Paramasivan reports grants from National Institute for Health Research (NIHR), during the conduct of the study;Dr. Batchelor reports personal fees from Medtronic, personal fees from Johnson & Johnson, personal fees from PulmonX, personal fees from AstraZeneca, outside the submitted work;Miss. Mckeon, Dr. McGonigle, Miss. Harris, Dr. Shackcloth, Dr. Elliot, Prof. Blazeby, Ms. Dabner, Mr. Brush have nothing to disclose

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1
Figure 1
The trial schema showing the recruitment pathway for phase 1 (pilot phase) of the VIOLET study. VATS, video-assisted thoracoscopic surgery; VIOLET, VIdeo assisted thoracoscopic lobectomy versus conventional Open LobEcTomy for lung cancer.
Figure 2
Figure 2
The trial schema showing the recruitment pathway for phase 2 of the VIOLET study. VATS, video-assisted thoracoscopic surgery; VIOLET, VIdeo assisted thoracoscopic lobectomy versus conventional Open LobEcTomy for lung cancer.

References

    1. Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Ann Thorac Surg 1995;60:615–23. discussion 22-3 10.1016/0003-4975(95)00537-U
    1. Altorki NK, Wang X, Wigle D, et al. . Perioperative mortality and morbidity after sublobar versus lobar resection for early-stage non-small-cell lung cancer: post-hoc analysis of an international, randomised, phase 3 trial (CALGB/Alliance 140503). Lancet Respir Med 2018;6:915–24. 10.1016/S2213-2600(18)30411-9
    1. The SCTS Thoracic Surgery Audit Group Society for cardiothoracic surgery in Great britain and Ireland. The thoracic surgery registry brief report audit years 2011-12 to 2013-14. Available:
    1. Yan TD, Black D, Bannon PG, et al. . Systematic review and meta-analysis of randomized and nonrandomized trials on safety and efficacy of video-assisted thoracic surgery lobectomy for early-stage Non–Small-Cell lung cancer. JCO 2009;27:2553–62. 10.1200/JCO.2008.18.2733
    1. Cao C, Manganas C, Ang SC, et al. . A meta-analysis of unmatched and matched patients comparing video-assisted thoracoscopic lobectomy and conventional open lobectomy. Ann Cardiothorac Surg 2012;1:16–23.
    1. Kirby TJ, Mack MJ, Landreneau RJ, et al. . Lobectomy—video-assisted thoracic surgery versus muscle-sparing thoracotomy: a randomized trial. J Thorac Cardiovasc Surg 1995;109:997–1002. discussion -2 10.1016/S0022-5223(95)70326-8
    1. Sugi K, Kaneda Y, Esato K. Video-Assisted thoracoscopic lobectomy achieves a satisfactory long-term prognosis in patients with clinical stage Ia lung cancer. World J Surg 2000;24:27–31. 10.1007/s002689910006
    1. Sugiura H, Morikawa T, Kaji M, et al. . Long-Term benefits for the quality of life after video-assisted thoracoscopic lobectomy in patients with lung cancer. Surg Laparosc Endosc Percutan Tech 1999;9:403–8. 10.1097/00129689-199912000-00007
    1. Bendixen M, Jørgensen OD, Kronborg C, et al. . Postoperative pain and quality of life after lobectomy via video-assisted thoracoscopic surgery or anterolateral thoracotomy for early stage lung cancer: a randomised controlled trial. Lancet Oncol 2016;17:836–44. 10.1016/S1470-2045(16)00173-X
    1. Long H, Tan Q, Luo Q, et al. . Thoracoscopic surgery versus thoracotomy for lung cancer: short-term outcomes of a randomized trial. Ann Thorac Surg 2018;105:386–92. 10.1016/j.athoracsur.2017.08.045
    1. Bendixen M, Kronborg C, Jørgensen OD, et al. . Cost–utility analysis of minimally invasive surgery for lung cancer: a randomized controlled trial. Eur J Cardiothorac Surg 2019;66 10.1093/ejcts/ezz064
    1. Pagès P-B, Abou Hanna H, Bertaux A-C, et al. . Medicoeconomic analysis of lobectomy using thoracoscopy versus thoracotomy for lung cancer: a study protocol for a multicentre randomised controlled trial (Lungsco01). BMJ Open 2017;7:e012963 10.1136/bmjopen-2016-012963
    1. Swanson SJ, Herndon JE, D'Amico TA, et al. . Video-Assisted thoracic surgery lobectomy: report of CALGB 39802—A prospective, Multi-Institution feasibility study. JCO 2007;25:4993–7. 10.1200/JCO.2007.12.6649
    1. Goldstraw P. International association for the study of lung cancer staging manual in thoracic oncology. Florida, USA: Editorial Rx Press, 2009.
    1. Speich B. Blinding in surgical randomized clinical trials in 2015. Ann Surg 2017;266:21–2. 10.1097/SLA.0000000000002242
    1. Wartolowska K, Beard D, Carr A. Blinding in trials of interventional procedures is possible and worthwhile. F1000Res 2017;6 10.12688/f1000research.12528.1
    1. Karanicolas PJ, Farrokhyar F, Bhandari M. Practical tips for surgical research: blinding: who, what, when, why, how? Can J Surg 2010;53:345–8.
    1. Bang H, Ni L, Davis CE. Assessment of blinding in clinical trials. Control Clin Trials 2004;25:143–56. 10.1016/j.cct.2003.10.016
    1. Maringwa JT, Quinten C, King M, et al. . Minimal important differences for interpreting health-related quality of life scores from the EORTC QLQ-C30 in lung cancer patients participating in randomized controlled trials. Support Care Cancer 2011;19:1753–60. 10.1007/s00520-010-1016-5
    1. EuroQol Group EuroQol--a new facility for the measurement of health-related quality of life. Health Policy 1990;16:199–208. 10.1016/0168-8510(90)90421-9
    1. Herdman M, Gudex C, Lloyd A, et al. . Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res 2011;20:1727–36. 10.1007/s11136-011-9903-x
    1. Healy P, Galvin S, Williamson PR, et al. . Identifying trial recruitment uncertainties using a James Lind Alliance Priority Setting Partnership - the PRioRiTy (Prioritising Recruitment in Randomised Trials) study. Trials 2018;19:147 10.1186/s13063-018-2544-4
    1. Treweek S, Mitchell E, Pitkethly M, et al. . Strategies to improve recruitment to randomised controlled trials. Cochrane Database Syst Rev 2010;1 10.1002/14651858.MR000013.pub5
    1. Ergina PL, Cook JA, Blazeby JM, et al. . Challenges in evaluating surgical innovation. Lancet 2009;374:1097–104. 10.1016/S0140-6736(09)61086-2
    1. Frampton S, Kneebone RL. John Wickham's New Surgery: 'Minimally Invasive Therapy', Innovation, and Approaches to Medical Practice in Twentieth-century Britain. Soc Hist Med 2017;30:544–66. 10.1093/shm/hkw074
    1. Schlich T, Tang CL. Patient choice and the history of minimally invasive surgery. Lancet 2016;388:1369–70. 10.1016/S0140-6736(16)31738-X
    1. Donovan JL, Athene Lane J, Peters TJ, et al. . Development of a complex intervention improved randomization and informed consent in a randomized controlled trial. J Clin Epidemiol 2009;62:29–36. 10.1016/j.jclinepi.2008.02.010
    1. Paramasivan S, Rogers CA, Welbourn R, et al. . Enabling recruitment success in bariatric surgical trials: pilot phase of the By-Band-Sleeve study. Int J Obes 2017;41:1654–61. 10.1038/ijo.2017.153
    1. Stein RC, Dunn JA, Bartlett JMS, et al. . Optima prelim: a randomised feasibility study of personalised care in the treatment of women with early breast cancer. Health Technol Assess 2016;20:1–202. 10.3310/hta20100
    1. Donovan JL, Paramasivan S, de Salis I, et al. . Clear obstacles and hidden challenges: understanding recruiter perspectives in six pragmatic randomised controlled trials. Trials 2014;15:5 10.1186/1745-6215-15-5
    1. Mills N, Donovan JL, Wade J, et al. . Exploring treatment preferences facilitated recruitment to randomized controlled trials. J Clin Epidemiol 2011;64:1127–36. 10.1016/j.jclinepi.2010.12.017
    1. Rooshenas L, Elliott D, Wade J, et al. . Conveying Equipoise during Recruitment for Clinical Trials: Qualitative Synthesis of Clinicians’ Practices across Six Randomised Controlled Trials. PLoS Med 2016;13:e1002147 10.1371/journal.pmed.1002147
    1. Beard DJ, Rees JL, Cook JA, et al. . Arthroscopic subacromial decompression for subacromial shoulder pain (CSAW): a multicentre, pragmatic, parallel group, placebo-controlled, three-group, randomised surgical trial. Lancet 2018;391:329–38. 10.1016/S0140-6736(17)32457-1
    1. Hamdy FC, Donovan JL, Lane JA, et al. . 10-Year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med 2016;375:1415–24. 10.1056/NEJMoa1606220
    1. Rooshenas L, Scott LJ, Blazeby JM, et al. . The quintet recruitment intervention supported five randomized trials to recruit to target: a mixed-methods evaluation. J Clin Epidemiol 2019;106:108–20. 10.1016/j.jclinepi.2018.10.004
    1. Donovan JL, Rooshenas L, Jepson M, et al. . Optimising recruitment and informed consent in randomised controlled trials: the development and implementation of the quintet recruitment intervention (QRI). Trials 2016;17:283 10.1186/s13063-016-1391-4
    1. National Institute for Health and Care Excellence Guide to the methods of technology appraisal 2013. London: National Institute for Health and Care Excellence, 2013.
    1. Dolan P. Modeling Valuations for EuroQol health states. Med Care 1997;35:1095–108. 10.1097/00005650-199711000-00002
    1. National Institute for Health and Care Excellence Position statement on use of the EQ-5D-5L valuation set for England (updated November 2018), 2018. Available: [Accessed 09 Jan 2019].
    1. van Hout B, Janssen MF, Feng Y-S, et al. . Interim scoring for the EQ-5D-5L: mapping the EQ-5D-5L to EQ-5D-3L value sets. Value in Health 2012;15:708–15. 10.1016/j.jval.2012.02.008
    1. White IR, Royston P, Wood AM. Multiple imputation using chained equations: issues and guidance for practice. Stat Med 2011;30:377–99. 10.1002/sim.4067
    1. Glaser BGS AL. The discovery of Grounded theory: strategies for qualitative research. Piscataway, NJ, USA: Transaction Publishers, 2009.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅