Phase 3 Trial of Stereotactic Body Radiotherapy in Localized Prostate Cancer.

Humans Male Prostatic Neoplasms / radiotherapy Radiosurgery / adverse effects Aged Prostate-Specific Antigen / blood Middle Aged Neoplasm Grading Aged, 80 and over Intention to Treat Analysis Neoplasm Staging Kaplan-Meier Estimate Treatment Failure

Journal

The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562

Informations de publication

Date de publication:
17 Oct 2024
Historique:
medline: 16 10 2024
pubmed: 16 10 2024
entrez: 16 10 2024
Statut: ppublish

Résumé

Whether stereotactic body radiotherapy (SBRT) is noninferior to conventionally or moderately hypofractionated regimens with respect to biochemical or clinical failure in patients with localized prostate cancer is unclear. We conducted a phase 3, international, open-label, randomized, controlled trial. Men with stage T1 or T2 prostate cancer, a Gleason score of 3+4 or less, and a prostate-specific antigen (PSA) level of no more than 20 ng per milliliter were randomly assigned (in a 1:1 ratio) to receive SBRT (36.25 Gy in 5 fractions over a period of 1 or 2 weeks) or control radiotherapy (78 Gy in 39 fractions over a period of 7.5 weeks or 62 Gy in 20 fractions over a period of 4 weeks). Androgen-deprivation therapy was not permitted. The primary end point was freedom from biochemical or clinical failure, with a critical hazard ratio for noninferiority of 1.45. The analysis was performed in the intention-to-treat population. A total of 874 patients underwent randomization at 38 centers (433 patients in the SBRT group and 441 in the control radiotherapy group) between August 2012 and January 2018. The median age of the patients was 69.8 years, and the median PSA level was 8.0 ng per milliliter; the National Comprehensive Cancer Network risk category was low for 8.4% of the patients and intermediate for 91.6%. At a median follow-up of 74.0 months, the 5-year incidence of freedom from biochemical or clinical failure was 95.8% (95% confidence interval [CI], 93.3 to 97.4) in the SBRT group and 94.6% (95% CI, 91.9 to 96.4) in the control radiotherapy group (unadjusted hazard ratio for biochemical or clinical failure, 0.73; 90% CI, 0.48 to 1.12; P = 0.004 for noninferiority), which indicated the noninferiority of SBRT. At 5 years, the cumulative incidence of late Radiation Therapy Oncology Group (RTOG) grade 2 or higher genitourinary toxic effects was 26.9% (95% CI, 22.8 to 31.5) with SBRT and 18.3% (95% CI, 14.8 to 22.5) with control radiotherapy (P<0.001), and the cumulative incidence of late RTOG grade 2 or higher gastrointestinal toxic effects was 10.7% (95% CI, 8.1 to 14.2) and 10.2% (95% CI, 7.7 to 13.5), respectively (P = 0.94). Five-fraction SBRT was noninferior to control radiotherapy with respect to biochemical or clinical failure and may be an efficacious treatment option for patients with low-to-intermediate-risk localized prostate cancer as defined in this trial. (Funded by Accuray and others; PACE-B ClinicalTrials.gov number, NCT01584258.).

Sections du résumé

BACKGROUND BACKGROUND
Whether stereotactic body radiotherapy (SBRT) is noninferior to conventionally or moderately hypofractionated regimens with respect to biochemical or clinical failure in patients with localized prostate cancer is unclear.
METHODS METHODS
We conducted a phase 3, international, open-label, randomized, controlled trial. Men with stage T1 or T2 prostate cancer, a Gleason score of 3+4 or less, and a prostate-specific antigen (PSA) level of no more than 20 ng per milliliter were randomly assigned (in a 1:1 ratio) to receive SBRT (36.25 Gy in 5 fractions over a period of 1 or 2 weeks) or control radiotherapy (78 Gy in 39 fractions over a period of 7.5 weeks or 62 Gy in 20 fractions over a period of 4 weeks). Androgen-deprivation therapy was not permitted. The primary end point was freedom from biochemical or clinical failure, with a critical hazard ratio for noninferiority of 1.45. The analysis was performed in the intention-to-treat population.
RESULTS RESULTS
A total of 874 patients underwent randomization at 38 centers (433 patients in the SBRT group and 441 in the control radiotherapy group) between August 2012 and January 2018. The median age of the patients was 69.8 years, and the median PSA level was 8.0 ng per milliliter; the National Comprehensive Cancer Network risk category was low for 8.4% of the patients and intermediate for 91.6%. At a median follow-up of 74.0 months, the 5-year incidence of freedom from biochemical or clinical failure was 95.8% (95% confidence interval [CI], 93.3 to 97.4) in the SBRT group and 94.6% (95% CI, 91.9 to 96.4) in the control radiotherapy group (unadjusted hazard ratio for biochemical or clinical failure, 0.73; 90% CI, 0.48 to 1.12; P = 0.004 for noninferiority), which indicated the noninferiority of SBRT. At 5 years, the cumulative incidence of late Radiation Therapy Oncology Group (RTOG) grade 2 or higher genitourinary toxic effects was 26.9% (95% CI, 22.8 to 31.5) with SBRT and 18.3% (95% CI, 14.8 to 22.5) with control radiotherapy (P<0.001), and the cumulative incidence of late RTOG grade 2 or higher gastrointestinal toxic effects was 10.7% (95% CI, 8.1 to 14.2) and 10.2% (95% CI, 7.7 to 13.5), respectively (P = 0.94).
CONCLUSIONS CONCLUSIONS
Five-fraction SBRT was noninferior to control radiotherapy with respect to biochemical or clinical failure and may be an efficacious treatment option for patients with low-to-intermediate-risk localized prostate cancer as defined in this trial. (Funded by Accuray and others; PACE-B ClinicalTrials.gov number, NCT01584258.).

Identifiants

DOI: 10.1056/NEJMoa2403365 PMID: 39413377
pubmed: 39413377
doi: 10.1056/NEJMoa2403365
doi:

Substances chimiques

Prostate-Specific Antigen EC 3.4.21.77

Banques de données

ClinicalTrials.gov
['NCT01584258']

Types de publication

Journal Article Clinical Trial, Phase III Randomized Controlled Trial Multicenter Study Equivalence Trial Comparative Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

1413-1425

Informations de copyright

Copyright © 2024 Massachusetts Medical Society.

Auteurs

Nicholas van As (N)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

Clare Griffin (C)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

Alison Tree (A)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

Jaymini Patel (J)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

Peter Ostler (P)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

Hans van der Voet (H)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

Andrew Loblaw (A)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

William Chu (W)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

Daniel Ford (D)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

Shaun Tolan (S)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

Suneil Jain (S)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).
ORCID: 0000-0001-7429-4791

Philip Camilleri (P)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

Kiran Kancherla (K)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

John Frew (J)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

Andrew Chan (A)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

Olivia Naismith (O)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

John Armstrong (J)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

John Staffurth (J)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

Alexander Martin (A)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

Ian Dayes (I)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

Paula Wells (P)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

Derek Price (D)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

Emily Williamson (E)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

Julia Pugh (J)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

Georgina Manning (G)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

Stephanie Brown (S)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

Stephanie Burnett (S)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

Emma Hall (E)

From the Royal Marsden Hospital (N.A., A.T., O.N.), the Institute of Cancer Research (N.A., C.G., A.T., J. Patel, E.W., J. Pugh, G.M., S. Brown, S. Burnett, E.H.), St. Bartholomew's Hospital (P.W.), and Patient and Public Representative (D.P.), London, the Mount Vernon Cancer Centre, Northwood (P.O.), the James Cook University Hospital, Middlesbrough (H.V.), University Hospitals Birmingham, Birmingham (D.F.), the Clatterbridge Cancer Centre, Birkenhead (S.T.), Queen's University Belfast, Belfast (S.J.), Churchill Hospital, Oxford (P.C.), University Hospitals of Leicester, Leicester (K.K.), Freeman Hospital, Newcastle (J.F.), University Hospitals Coventry and Warwickshire, Coventry (A.C.), Velindre Cancer Centre, Cardiff (J.S.), and Cambridge University Hospitals NHS Foundation Trust, Cambridge (A.M.) - all in the United Kingdom; Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (A.L., W.C.), and the Department of Oncology, McMaster University, Hamilton, ON (I.D.) - both in Canada; and Cancer Trials Ireland and St. Luke's Radiation Oncology Network, St. Luke's Hospital - both in Dublin (J.A.).

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Classifications MeSH

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