- Email: [email protected]
The CONVERT Trial: Interpretation, Journey and Lessons Learnt
Clinical Oncology xxx (2017) 1e3 Contents lists available at ScienceDirect
Clinical Oncology journal homepage: www.clinicaloncologyonline.net
Editorial
The CONVERT Trial: Interpretation, Journey and Lessons Learnt C. Faivre-Finn *y, S. Falk y, F. Blackhall *y * Division
of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK y The Christie NHS Foundation Trust, Manchester, UK Received 18 August 2017; accepted 25 August 2017
The current standard of care in patients with limitedstage small cell lung cancer (SCLC) is based on a randomised controlled trial that compared once-daily with twicedaily radiotherapy delivered concurrently with chemotherapy, showing the superiority of twice-daily radiotherapy in terms of survival [1]. However, since publication in 1999 there has been a lack of consensus regarding the routine use of twice-daily radiotherapy, despite its superiority, due to concerns regarding toxicity (i.e. one third of patients developing grade 3 radiation oesophagitis) and logistical issues. International guidelines highlighted the need for further trials in this group of patients, which led to the development of the CONVERT trial [2] in 2006 comparing twice-daily radiotherapy with a higher dose of radiotherapy delivered once daily, both given concurrently with chemotherapy. CONVERT is the largest study ever completed investigating chemoradiotherapy in SCLC and is the first randomised trial providing outcome data in patients staged with positron emission tomographycomputed tomography (PET-CT) and treated with modern radiotherapy techniques (i.e. three-dimensional conformal radiotherapy or intensity-modulated radiotherapy, no elective nodal irradiation). CONVERT recruited 547 patients in eight countries and was one of the first randomised studies in the UK to incorporate a radiotherapy quality assurance programme [3,4]. Overall survival outcomes did not differ between the two groups (P ¼ 0.14), but survival achieved in both groups was higher and toxicity much lower (>50% reduction) than previously reported in the literature. At a median follow-up of 45 months, 2 year overall survival was 56% (95% confidence interval 50e62) in the twice-daily group and 51% (95% confidence interval 45e57) in the once-daily group; 5 year Author for correspondence: C. Faivre-Finn, Department of Radiotherapy Related Research, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK. Tel: þ44-161-446-8200. E-mail address: corinne.fi[email protected] (C. Faivre-Finn).
survival was 34% (95% confidence interval 27e41) in the twice-daily group and 31% (95% confidence interval 25e37) in the once-daily group. There was no difference in grade 3e4 oesophagitis between the groups; 19% in the twice-daily group versus 19% in the once-daily group; grade 3e4 radiation pneumonitis was 3% in the twice-daily versus 2% in the once-daily group. As the trial was designed to show superiority of once-daily radiotherapy and was not powered to show equivalence, the implication is that twice-daily radiotherapy should continue to be considered the standard of care in this setting. However, the CONVERT trial should not be viewed as a ‘negative trial’, as it will help to standardise patient care, which is currently very variable [5]. Furthermore, the results of this practice-defining study show that in the era of modern radiotherapy techniques, the frequency and severity of acute and late radiation toxicities are lower than previously reported. However, we now conclude that the statistical hypothesis for CONVERT was in fact wrong. When CONVERT was developed there was a paucity of data on the outcome of patients receiving higher dose once-daily radiotherapy. At that time, once-daily radiotherapy was creeping into practice, prompting the trial management group to support a hypothesis that would deliver a clinically meaningful difference (i.e. 12% overall survival difference between the control and the experimental arms). We would like to highlight the time and effort taken to develop, set-up and recruit to a multicentre, academic trial. The CONVERT journey began in 2001, when a review of the literature identified a gap in radiotherapy research in SCLC. The last practice-changing trial in limited-stage SCLC had recruited patients between 1989 and 1992 [1] and the subsequent hiatus had left questions unanswered and the opportunity open for further research in this area. Over the following 6 years, pilot and phase II studies were carried out [6,7], the CONVERT protocol was developed (initially at the ECCO-AACR-EORTC-ESMO Methods in Clinical Cancer Research Workshop) [8], discussions with international
http://dx.doi.org/10.1016/j.clon.2017.09.002 0936-6555/Ó 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Faivre-Finn C, et al., The CONVERT Trial: Interpretation, Journey and Lessons Learnt, Clinical Oncology (2017), http://dx.doi.org/10.1016/j.clon.2017.09.002
2
C. Faivre-Finn et al. / Clinical Oncology xxx (2017) 1e3
colleagues and lung cancer groups were initiated, culminating in funding for a phase III trial being awarded in 2007 by Cancer Research UK. The first patient was randomised in 2008 and the last in 2013. The results of CONVERT were first presented at the American Society of Clinical Oncology conference in 2016. Overall, more than 15 years elapsed from the development, through to implementation and completion of this randomised controlled trial in an international academic setting. Recruitment was challenging, despite opening 94 centres across seven European countries and Canada between 2008 and 2013. Recruitment was slower than initial predictions, as only two centres were opened in 2008 and the incidence of SCLC was declining in Europe; however, as the number of sites opening increased over the next 4 years, recruitment improved steadily. In hindsight it was unnecessary to have opened so many centres to recruitment, as only 73 (77%) randomised at least one patient and 23 (24%) randomised only one or two patients. Ten sites recruited 49% of the total number, with a single site recruiting 20% of all patients. A lesson learnt would be to open fewer, more rigorously selected sites with proven track records of high recruitment into radiotherapy trials. A review of the original feasibility information provided by sites showed the predicted number of patients estimated to be included per year ranged from two to 25 (with an average of 6.4). In reality, recruiting sites randomised on average two patients per year, excluding one centre where an average of 17 patients per year were randomised. Another important lesson learnt is to factor in the speed of local set-up time at sites, which was often a lot slower than predicted. The time from the completion of feasibility forms to local site initiation ranged from 108 to 1387 days (median 605) and the time from local approval once granted to first patient randomised ranged from 5 to 1286 days (median 281). There were many in the community who predicted that an academic trial of this size and relative complexity would fail to recruit successfully. The recipe for success was the persistence and commitment of the trials team, and the support and collaboration of a large number of colleagues around the world as well as local teams and groups, including the Manchester Academic Health Science Centre trials co-ordination unit, radiotherapy quality assurance team, translational research team, trial steering committee, trial management group and data monitoring committee. CONVERT was presented on a regular basis at international meetings to ensure that it was at the forefront of thoracic oncologist’s minds. CONVERT has established a unique dataset that provides us with an opportunity to investigate many aspects of this disease relevant to modern practice. Analyses and papers in preparation include chemoradiotherapy outcomes in the elderly [9] and in early stage disease [10], the outcome of patients in high versus low volume centres and the outcome of quality assurance compliant versus non-quality assurance compliant centres. Other areas of interest include the impact of PET staging on outcome, the correlation of cone beam computed tomography changes and survival, the impact of heart dose on survival, the safety of using granulocyte colony
stimulating factor during concurrent chemoradiotherapy [11], the impact of the use of prophylactic antibiotics, prophylactic cranial irradiation and patterns of relapse. CONVERT also had a translational research substudy where blood (DNA, circulating tumour cells [CTC], plasma and serum) samples were collected from patients at baseline, day 22 and at relapse. Pretreatment tissue samples were also collected where available. Translational work is ongoing, but the results of the analysis of CTC count [12] before starting treatment is highly predictive for survival, with higher CTC numbers associated with significantly worse survival even in patients who are staged using PET. With respect to radiobiology, neither the starting time of repopulation nor the average cell number doubling time during radiotherapy is known for SCLC; CONVERT radiobiology data will be used to investigate this further. Finally, we aim to carry out a survey to investigate the impact of the CONVERT trial results on practice. In terms of future direction, there are a number of interesting ideas for further studies that have been generated since the CONVERT results were presented, including: dose escalation of the twice-daily arm of CONVERT, the investigation of hypofractionated radiotherapy and the stratification of patients based on CTC/cell-free DNA to validate the findings of our preliminary translational studies. The aim would be to identify patients who may not benefit from concurrent chemoradiotherapy or may need further consolidation systemic therapy.
Acknowledgements This research was funded by Cancer Research UK Clinical Trials Awards and Advisory Committee (grant reference number: C17052/A8154), French Ministry of Health, Pro Clinique (grant reference gramme Hospitalier de Recherche number: NAT 2007-28-01), Canadian Cancer Society Research Institute (grant reference number: #021039) and the European Organization for the Research and Treatment of Cancer (Cancer Research Fund, Lung Cancer and Radiation Oncology Groups). The authors would like to acknowledge the support and mentorship provided by Dr Andrew Turrisi since the idea of CONVERT was first established. The authors would also like to acknowledge the support of the National Cancer Research Institute Radiotherapy Trials Quality Assurance team (Nicki Groom and Dr Elena Wilson), The Manchester Academic Health Science Centre Clinical Trials Unit, Amy Bossons (CONVERT trial coordinator) and David Ryder (Manchester Academic Health Science Centre Trials Co-ordination Unit statistician), The National Institute for Health Research (NIHR) Christie Clinical Research Facility, Dr David Girling, Dr Steve Roberts, Professor Christian Manegold and Professor Robert Huddart (Independent Data Monitoring Committee Members), Professor Dirk De Ruysscher and Dr Jason Lester (Independent Members of the Trial Steering Committee).
References [1] Turrisi AT, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, et al. Twice-daily compared with once-daily thoracic
Please cite this article in press as: Faivre-Finn C, et al., The CONVERT Trial: Interpretation, Journey and Lessons Learnt, Clinical Oncology (2017), http://dx.doi.org/10.1016/j.clon.2017.09.002
C. Faivre-Finn et al. / Clinical Oncology xxx (2017) 1e3
[2]
[3]
[4]
[5]
[6]
[7]
radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 1999; 340(4):265e271. Faivre-Finn C, Snee M, Ashcroft L, Appel W, Barlesi F, Bhatnagar A, et al. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol 2017;18:1116e1125. http://dx. doi.org/10.1016/S1470-2045(17)30318-2. Groom N, Wilson E, Faivre-Finn C. Effect of accurate heart delineation on cardiac dose during the CONVERT Trial. Br J Radiol 2017;90(1073):20170036. Groom N, Wilson E, Lyn E, Faivre-Finn C. Is pre-trial quality assurance necessary? Experiences of the CONVERT phase III randomised trial for good performance status patients with limited-stage small cell lung cancer. Br J Radiol 2014;87(1037): 20130653. Komaki R, Khalid N, Langer CJ, Kong FM, Owen JB, Crozier CL, et al. Penetration of recommended procedures for lung cancer staging and management in the United States over 10 years: a quality research in radiation oncology survey. Int J Radiat Oncol Biol Phys 2013;85:1082e1089. Colaco R, Sheikh H, Lorigan P, Blackhall F, Hulse P, Califano R, et al. Omitting elective nodal irradiation during thoracic irradiation in limited-stage small cell lung cancer e evidence from a phase II trial. Lung Cancer 2012;76(1):72e77. Sheikh H, Colaco R, Lorigan P, Blackhall F, Califano R, Ashcroft L, et al. Is G-CSF safe during concurrent
[8]
[9]
[10]
[11]
[12]
3
chemotherapy and thoracic radiotherapy in patients with limited-stage small-cell lung cancer? Evidence from a phase II trial. Lung Cancer 2011;74(1):75e79. http://www.esmo.org/Conferences/Workshops-Courses/ Methods-in-Clinical-Cancer-Research-MCCR (accessed 10 August 2017). Christodoulou M, Blackhall F, Ashcroft L, Leylek A, Knegjens J, Remouchamps V, et al. Compliance and outcome of elderly patients treated in the concurrent once-daily versus twicedaily radiotherapy (Convert) trial. J Thorac Oncol 2017; 12(S1):S134. Salem A, Ashcroft L, Dagnault A, de Metz C, Hatton M, Locke I, et al. Early limited-stage small cell lung cancer: sub-group analysis of the concurrent once-daily versus twice-daily radiotherapy (CONVERT) trial. ELCC 07May2017. Ann Oncol 2017;28(Suppl_2):ii17eii20. http://dx.doi.org/10.1093/annonc/ mdx088.001. Gomes F, Faivre-Finn C, Fernandez-Gutierrez F, Ryder D, Bezjak A, Cardenal F, et al. Use of G-CSF and prophylactic antibiotics with concurrent chemo-radiotherapy in limitedstage small cell lung cancer: results from the phase III CONVERT trial. ELCC 07May2017. Ann Oncol 2017;28(Suppl_ 2):ii69eii70. http://dx.doi.org/10.1093/annonc/mdx195. Fernandez-Gutierrez F, Foy V, Burns K, Pierce J, Morris K, Priest L, et al. Prognostic value of circulating tumour cells in limited-disease small cell lung cancer patients treated on the Convert trial. J Thorac Oncol 2017;12(S1):S134.
Please cite this article in press as: Faivre-Finn C, et al., The CONVERT Trial: Interpretation, Journey and Lessons Learnt, Clinical Oncology (2017), http://dx.doi.org/10.1016/j.clon.2017.09.002
Clinical Oncology journal homepage: www.clinicaloncologyonline.net
Editorial
The CONVERT Trial: Interpretation, Journey and Lessons Learnt C. Faivre-Finn *y, S. Falk y, F. Blackhall *y * Division
of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK y The Christie NHS Foundation Trust, Manchester, UK Received 18 August 2017; accepted 25 August 2017
The current standard of care in patients with limitedstage small cell lung cancer (SCLC) is based on a randomised controlled trial that compared once-daily with twicedaily radiotherapy delivered concurrently with chemotherapy, showing the superiority of twice-daily radiotherapy in terms of survival [1]. However, since publication in 1999 there has been a lack of consensus regarding the routine use of twice-daily radiotherapy, despite its superiority, due to concerns regarding toxicity (i.e. one third of patients developing grade 3 radiation oesophagitis) and logistical issues. International guidelines highlighted the need for further trials in this group of patients, which led to the development of the CONVERT trial [2] in 2006 comparing twice-daily radiotherapy with a higher dose of radiotherapy delivered once daily, both given concurrently with chemotherapy. CONVERT is the largest study ever completed investigating chemoradiotherapy in SCLC and is the first randomised trial providing outcome data in patients staged with positron emission tomographycomputed tomography (PET-CT) and treated with modern radiotherapy techniques (i.e. three-dimensional conformal radiotherapy or intensity-modulated radiotherapy, no elective nodal irradiation). CONVERT recruited 547 patients in eight countries and was one of the first randomised studies in the UK to incorporate a radiotherapy quality assurance programme [3,4]. Overall survival outcomes did not differ between the two groups (P ¼ 0.14), but survival achieved in both groups was higher and toxicity much lower (>50% reduction) than previously reported in the literature. At a median follow-up of 45 months, 2 year overall survival was 56% (95% confidence interval 50e62) in the twice-daily group and 51% (95% confidence interval 45e57) in the once-daily group; 5 year Author for correspondence: C. Faivre-Finn, Department of Radiotherapy Related Research, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK. Tel: þ44-161-446-8200. E-mail address: corinne.fi[email protected] (C. Faivre-Finn).
survival was 34% (95% confidence interval 27e41) in the twice-daily group and 31% (95% confidence interval 25e37) in the once-daily group. There was no difference in grade 3e4 oesophagitis between the groups; 19% in the twice-daily group versus 19% in the once-daily group; grade 3e4 radiation pneumonitis was 3% in the twice-daily versus 2% in the once-daily group. As the trial was designed to show superiority of once-daily radiotherapy and was not powered to show equivalence, the implication is that twice-daily radiotherapy should continue to be considered the standard of care in this setting. However, the CONVERT trial should not be viewed as a ‘negative trial’, as it will help to standardise patient care, which is currently very variable [5]. Furthermore, the results of this practice-defining study show that in the era of modern radiotherapy techniques, the frequency and severity of acute and late radiation toxicities are lower than previously reported. However, we now conclude that the statistical hypothesis for CONVERT was in fact wrong. When CONVERT was developed there was a paucity of data on the outcome of patients receiving higher dose once-daily radiotherapy. At that time, once-daily radiotherapy was creeping into practice, prompting the trial management group to support a hypothesis that would deliver a clinically meaningful difference (i.e. 12% overall survival difference between the control and the experimental arms). We would like to highlight the time and effort taken to develop, set-up and recruit to a multicentre, academic trial. The CONVERT journey began in 2001, when a review of the literature identified a gap in radiotherapy research in SCLC. The last practice-changing trial in limited-stage SCLC had recruited patients between 1989 and 1992 [1] and the subsequent hiatus had left questions unanswered and the opportunity open for further research in this area. Over the following 6 years, pilot and phase II studies were carried out [6,7], the CONVERT protocol was developed (initially at the ECCO-AACR-EORTC-ESMO Methods in Clinical Cancer Research Workshop) [8], discussions with international
http://dx.doi.org/10.1016/j.clon.2017.09.002 0936-6555/Ó 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Faivre-Finn C, et al., The CONVERT Trial: Interpretation, Journey and Lessons Learnt, Clinical Oncology (2017), http://dx.doi.org/10.1016/j.clon.2017.09.002
2
C. Faivre-Finn et al. / Clinical Oncology xxx (2017) 1e3
colleagues and lung cancer groups were initiated, culminating in funding for a phase III trial being awarded in 2007 by Cancer Research UK. The first patient was randomised in 2008 and the last in 2013. The results of CONVERT were first presented at the American Society of Clinical Oncology conference in 2016. Overall, more than 15 years elapsed from the development, through to implementation and completion of this randomised controlled trial in an international academic setting. Recruitment was challenging, despite opening 94 centres across seven European countries and Canada between 2008 and 2013. Recruitment was slower than initial predictions, as only two centres were opened in 2008 and the incidence of SCLC was declining in Europe; however, as the number of sites opening increased over the next 4 years, recruitment improved steadily. In hindsight it was unnecessary to have opened so many centres to recruitment, as only 73 (77%) randomised at least one patient and 23 (24%) randomised only one or two patients. Ten sites recruited 49% of the total number, with a single site recruiting 20% of all patients. A lesson learnt would be to open fewer, more rigorously selected sites with proven track records of high recruitment into radiotherapy trials. A review of the original feasibility information provided by sites showed the predicted number of patients estimated to be included per year ranged from two to 25 (with an average of 6.4). In reality, recruiting sites randomised on average two patients per year, excluding one centre where an average of 17 patients per year were randomised. Another important lesson learnt is to factor in the speed of local set-up time at sites, which was often a lot slower than predicted. The time from the completion of feasibility forms to local site initiation ranged from 108 to 1387 days (median 605) and the time from local approval once granted to first patient randomised ranged from 5 to 1286 days (median 281). There were many in the community who predicted that an academic trial of this size and relative complexity would fail to recruit successfully. The recipe for success was the persistence and commitment of the trials team, and the support and collaboration of a large number of colleagues around the world as well as local teams and groups, including the Manchester Academic Health Science Centre trials co-ordination unit, radiotherapy quality assurance team, translational research team, trial steering committee, trial management group and data monitoring committee. CONVERT was presented on a regular basis at international meetings to ensure that it was at the forefront of thoracic oncologist’s minds. CONVERT has established a unique dataset that provides us with an opportunity to investigate many aspects of this disease relevant to modern practice. Analyses and papers in preparation include chemoradiotherapy outcomes in the elderly [9] and in early stage disease [10], the outcome of patients in high versus low volume centres and the outcome of quality assurance compliant versus non-quality assurance compliant centres. Other areas of interest include the impact of PET staging on outcome, the correlation of cone beam computed tomography changes and survival, the impact of heart dose on survival, the safety of using granulocyte colony
stimulating factor during concurrent chemoradiotherapy [11], the impact of the use of prophylactic antibiotics, prophylactic cranial irradiation and patterns of relapse. CONVERT also had a translational research substudy where blood (DNA, circulating tumour cells [CTC], plasma and serum) samples were collected from patients at baseline, day 22 and at relapse. Pretreatment tissue samples were also collected where available. Translational work is ongoing, but the results of the analysis of CTC count [12] before starting treatment is highly predictive for survival, with higher CTC numbers associated with significantly worse survival even in patients who are staged using PET. With respect to radiobiology, neither the starting time of repopulation nor the average cell number doubling time during radiotherapy is known for SCLC; CONVERT radiobiology data will be used to investigate this further. Finally, we aim to carry out a survey to investigate the impact of the CONVERT trial results on practice. In terms of future direction, there are a number of interesting ideas for further studies that have been generated since the CONVERT results were presented, including: dose escalation of the twice-daily arm of CONVERT, the investigation of hypofractionated radiotherapy and the stratification of patients based on CTC/cell-free DNA to validate the findings of our preliminary translational studies. The aim would be to identify patients who may not benefit from concurrent chemoradiotherapy or may need further consolidation systemic therapy.
Acknowledgements This research was funded by Cancer Research UK Clinical Trials Awards and Advisory Committee (grant reference number: C17052/A8154), French Ministry of Health, Pro Clinique (grant reference gramme Hospitalier de Recherche number: NAT 2007-28-01), Canadian Cancer Society Research Institute (grant reference number: #021039) and the European Organization for the Research and Treatment of Cancer (Cancer Research Fund, Lung Cancer and Radiation Oncology Groups). The authors would like to acknowledge the support and mentorship provided by Dr Andrew Turrisi since the idea of CONVERT was first established. The authors would also like to acknowledge the support of the National Cancer Research Institute Radiotherapy Trials Quality Assurance team (Nicki Groom and Dr Elena Wilson), The Manchester Academic Health Science Centre Clinical Trials Unit, Amy Bossons (CONVERT trial coordinator) and David Ryder (Manchester Academic Health Science Centre Trials Co-ordination Unit statistician), The National Institute for Health Research (NIHR) Christie Clinical Research Facility, Dr David Girling, Dr Steve Roberts, Professor Christian Manegold and Professor Robert Huddart (Independent Data Monitoring Committee Members), Professor Dirk De Ruysscher and Dr Jason Lester (Independent Members of the Trial Steering Committee).
References [1] Turrisi AT, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, et al. Twice-daily compared with once-daily thoracic
Please cite this article in press as: Faivre-Finn C, et al., The CONVERT Trial: Interpretation, Journey and Lessons Learnt, Clinical Oncology (2017), http://dx.doi.org/10.1016/j.clon.2017.09.002
C. Faivre-Finn et al. / Clinical Oncology xxx (2017) 1e3
[2]
[3]
[4]
[5]
[6]
[7]
radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 1999; 340(4):265e271. Faivre-Finn C, Snee M, Ashcroft L, Appel W, Barlesi F, Bhatnagar A, et al. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol 2017;18:1116e1125. http://dx. doi.org/10.1016/S1470-2045(17)30318-2. Groom N, Wilson E, Faivre-Finn C. Effect of accurate heart delineation on cardiac dose during the CONVERT Trial. Br J Radiol 2017;90(1073):20170036. Groom N, Wilson E, Lyn E, Faivre-Finn C. Is pre-trial quality assurance necessary? Experiences of the CONVERT phase III randomised trial for good performance status patients with limited-stage small cell lung cancer. Br J Radiol 2014;87(1037): 20130653. Komaki R, Khalid N, Langer CJ, Kong FM, Owen JB, Crozier CL, et al. Penetration of recommended procedures for lung cancer staging and management in the United States over 10 years: a quality research in radiation oncology survey. Int J Radiat Oncol Biol Phys 2013;85:1082e1089. Colaco R, Sheikh H, Lorigan P, Blackhall F, Hulse P, Califano R, et al. Omitting elective nodal irradiation during thoracic irradiation in limited-stage small cell lung cancer e evidence from a phase II trial. Lung Cancer 2012;76(1):72e77. Sheikh H, Colaco R, Lorigan P, Blackhall F, Califano R, Ashcroft L, et al. Is G-CSF safe during concurrent
[8]
[9]
[10]
[11]
[12]
3
chemotherapy and thoracic radiotherapy in patients with limited-stage small-cell lung cancer? Evidence from a phase II trial. Lung Cancer 2011;74(1):75e79. http://www.esmo.org/Conferences/Workshops-Courses/ Methods-in-Clinical-Cancer-Research-MCCR (accessed 10 August 2017). Christodoulou M, Blackhall F, Ashcroft L, Leylek A, Knegjens J, Remouchamps V, et al. Compliance and outcome of elderly patients treated in the concurrent once-daily versus twicedaily radiotherapy (Convert) trial. J Thorac Oncol 2017; 12(S1):S134. Salem A, Ashcroft L, Dagnault A, de Metz C, Hatton M, Locke I, et al. Early limited-stage small cell lung cancer: sub-group analysis of the concurrent once-daily versus twice-daily radiotherapy (CONVERT) trial. ELCC 07May2017. Ann Oncol 2017;28(Suppl_2):ii17eii20. http://dx.doi.org/10.1093/annonc/ mdx088.001. Gomes F, Faivre-Finn C, Fernandez-Gutierrez F, Ryder D, Bezjak A, Cardenal F, et al. Use of G-CSF and prophylactic antibiotics with concurrent chemo-radiotherapy in limitedstage small cell lung cancer: results from the phase III CONVERT trial. ELCC 07May2017. Ann Oncol 2017;28(Suppl_ 2):ii69eii70. http://dx.doi.org/10.1093/annonc/mdx195. Fernandez-Gutierrez F, Foy V, Burns K, Pierce J, Morris K, Priest L, et al. Prognostic value of circulating tumour cells in limited-disease small cell lung cancer patients treated on the Convert trial. J Thorac Oncol 2017;12(S1):S134.
Please cite this article in press as: Faivre-Finn C, et al., The CONVERT Trial: Interpretation, Journey and Lessons Learnt, Clinical Oncology (2017), http://dx.doi.org/10.1016/j.clon.2017.09.002