1. Healthcare

Supplementary appendix
This appendix formed part of the original submission and has been peer reviewed.
We post it as supplied by the authors.
Supplement to: Kunkler IH, Williams LJ, Jack WJL, Cameron DA, Dixon JM,
on behalf of the PRIME II investigators. Breast-conserving surgery with or
without irradiation in women aged 65 years or older with early breast cancer
(PRIME II): a randomised controlled trial. Lancet Oncol 2015; published online Jan 28.
http://dx.doi.org/10.1016/ S1470-2045(14)71221-5.
Breast conserving surgery with or without irradiation in women aged 65 years or older
with early breast cancer: the PRIME II randomised controlled trial (supplementary
web material)
Table 1: Contribution of variables of interest by multivariate analysis
Variable
HR (95% CI)
p-value
Tumour size (ref 0-10mm)
10·1-20mm
20·1-30mm
1
0·53 (0·23, 1·22)
1·17 (0·43, 3·20)
0·14
0·76
Margins (ref >5mm)
<1mm
1-5mm
Re-excision
1
2·11 (0·26, 17·13)
0·97 (0·43, 2·21)
1·14 (0·41, 3·17)
0·49
0·94
0·81
Grade (ref G1)
G2
G3
1
1·24 (0·56, 2·78)
3·64 (0·93, 14·26)
0·60
0·06
Age (ref 65-69)
70+
1
1·99 (0·90, 4·40)
0·09
LVI (ref No)
Yes
1
1·35 (0·31, 5·94)
0·69
ER status (ref High)
Low
1
2·40 (0·97, 5·93)
0·06
Radiotherapy (ref Yes)
No
1
4·87 (1·86, 12·74)
0·0013
Analysis by Cox proportional hazard model. PgR not included due to high levels of missing data.
1
Figure 1: Survival
2
Table 2: Cause of death by trial arm
Cause
No RT (n=668)
RT (n=658)
Total (n=1326)
Breast cancer
BC present but not cause
8
2
Unknown (2)
35
Cardiac (3)
Cerebrovascular (1)
Diabetes mellitus (1)
Renal failure (1)
Respiratory (5)
Septicemia (1)
Suicide (1)
Vascular (3)
Unknown (5)
4
1
Pancreatic cancer (1)
30
Cardiac (6)
Cerebrovascular (0)
Diabetes mellitus (0)
Renal failure (1)
Respiratory (5)
Septicemia (0)
Suicide (0)
Vascular (3)
Unknown (5)
12
3
Secondary cancers:
Ampulla (0)
Bowel (0)
Colon (3)
Endometrial (0)
Liver (1)
Lung (3)
Lymphoma (1)
Melanoma (1)
Ovary (2)
Pancreas (0)
Vulva (1)
Unknown (2)
4
49 (7·3%)
Secondary cancers:
Ampulla (1)
Bowel (2)
Colon (1)
Endometrial (2)
Liver (0)
Lung (4)
Lymphoma (1)
Melanoma (1)
Ovary (1)
Pancreas (1)
Vulva (0)
Unknown (1)
5
40 (6·1%)
No breast cancer
Cause unknown
Total
3
65
9
89 (6·7%)
Table 3: Other trials assessing the role of whole breast irradiation after breast conserving surgery
Study
No of
Patients
Period
of
recruitment
Median
Follow-Up
(years)
Age (years)
Tumor
Size
(cm)
Fisher et al10
1,009
1989-1989
8
Any age
<1
Fyles et al2
Blamey et al3
Potter et al4
Forrest et al8
Winzer et al14
Hughes et al17
18
Tinterri et al
Kunkler et al
Treatment after
surgery
Tamoxifen
RT + tamoxifen
RT + placebo
769
1992-2000
5·6
>50
≤5
Tamoxifen
RT + tamoxifen
1135
1992-2000
13·9
<70
<2
None
RT
Tamoxifen
RT + tamoxifen
869
1996-2004
4·5
Postmenopausal
≤3
Tamoxifen or Al
(mean, 66)
Tamoxifen or Al +RT
585
1985-1991
5·7
<70
≤4
Tamoxifen
RT + tamoxifen
361†
1991-1998
10
45-75
≤2
None
RT
Tamoxifen
RT + tamoxifen
636
1994-1999
10·5
≥70
≤2·0
Tamoxifen
RT + tamoxifen
749
2001-2005
5·0
55-75
<2·5
None
RT
1326
2004-2009
5·0
≥65
≤3
Tamoxifen or AI
RT + Tamoxifen or AI
Abbreviations: LR Local recurrence AI, aromatase inhibitor; RT, radiation therapy; pa, per annum
†347 analyzed
‡ calculated by LW from data in the paper
4
LR (%)
p-value
for RT
vs no
RT
17
3
9
8
1
1·9% pa
0·7% pa
0·8% pa
0% pa
6
2
24·5
5·8
34
10
8
9
9
2
3
1
4·1
1·3
< 0·001
0·001
<0·001
< 0·001
<0·001‡
<0·001
< 0·001
0·07
<0·001
Table 4: Recruiting sites and investigators
Site
Investigators
Aberdeen Royal Infirmary
University Hospital Aintree
Bishop Auckland Hospital
Basildon Hospital
Belfast City Hospital
Serbia Oncology & Radiology Institute,
Belgrade
Bristol Haematology and Oncology Centre
Royal Sussex County Hospital, Brighton
Queen's Hospital, Burton upon Trent
Burnley General Hospital
Blackpool Victoria Hospital
Charing Cross Hospital, London
Christie Hospital, Manchester
North Cumbria Hospitals
Clatterbridge Centre for Oncology
Walsgrave Hospital, Coventry
Conquest Hospital, St Leonards-on-Sea
Derbyshire Royal Infirmary
Dumfries & Galloway Royal Infirmary
Derriford Hospital, Plymouth
Darlington Memorial Hospital
Eastbourne District General Hospital
Essex County Hospital, Colchester
Western General Hospital, Edinburgh
Royal Devon & Exeter NHS Trust
Frenchay Hospital, Bristol
Furness General Hospital
George Eliot Hospital, Nuneaton
Geelong Hospital, Australia
Hope Hospital, Salford
University Hospital of Hartlepool
Wycombe General Hospital
Raigmore Hospital, Inverness
James Cook University Hospital,
Middlesbrough
Kent Oncology Centre
Leicester Royal infirmary
Leighton Hospital, Crewe
Macclesfield General Hospital
Manor Hospital, Walsall
Milton Keynes General Hospital
Maidstone Hospital
Mount Vernon Centre for Cancer Treatment,
Northwood
North Devon District Hospital
University Hospital of North Tees
Dr D Bissett, Dr G Plataniotis, Dr T Sarkar, Dr R Sharma
Dr S O’Reilly, Dr P Schofield
Dr J Hardman, Dr Wadd
Dr C Trask
Dr J Clarke
Dr J Mladenovic, Dr S Šušnjar
Churchill Hospital, Oxford
St Mary's Hospital, Portsmouth
Queen Elizabeth, Gateshead
Queen Margaret Hospital, Dunfermline
Royal Berkshire Hospital, Reading
Queen Mary's Hospital, Roehampton
Royal Lancaster Infirmary
Pennine Acute Hospitals NHS Trust
Royal Shrewsbury Hospital
Sandwell Hospital & City Hospital, West
Bromwich
St Bartholomew's Hospital, London
Southend Hospital
Solihull Hospital
St John's at Howden
Institute of Oncology Sremska Kamenica,
Yugoslavia
Stoke Mandeville Hospital, Aylesbury
Stepping Hill, Stockport
Dr A Bahl, Dr M Beresford, Dr S Goodman, Dr A Kumar
Dr D Bloomfield, Dr A Robinson, Dr R Simcock
Dr P Chakraborti, Dr AD Chetiyawardana, Dr M Persic
Dr W Appel, Dr M Hogg, Dr Young
Dr A Hindley, Dr S Susnerwala
Dr C Lowdell
Dr J Loncaster, Dr Magee, Dr V Misra, Dr Stewart, Dr Welsh
Dr P Dyson
Dr N Thorp, Dr Syndikus
Prof R Grieve, Dr C Irwin, Dr D Jones, Dr A Stockdale
Dr G Sadler
Dr P Chakraborti, Dr Otim-Oyet, Dr Vijayan, Dr P Woodings
Dr T Evans
Dr N Dorey, Dr Dubey, Dr S Kelly, Dr P Macleod, Dr C Tyrrell
Dr J Hardiman
Dr A Robinson, Dr S Westwell
Dr P Murray
Dr T Evans, Prof I Kunkler
Dr A Goodman, Dr A Hong, Dr D Hwang
Mr Cawthorn, Mr Sahu, Dr Shea, Dr M Shere
Dr G Skailes
Dr L Fresco, Prof R Grieve, Dr Reinecke
Dr M Francis, Dr I Porter
Dr Magee, Miss Z Saad
Dr A Rathmell
Dr B Lavery, Dr S Oliveros
Mr I Daltrey, Dr K Kelly, Mr P Walsh
Dr J Hardman, Dr Vandervolt
Dr O Al-Saliki, Dr S Coltart, Dr N Mithal, Dr H Smedley
Dr I Boiangiu, Dr I Peat
Dr P Burt
Dr L Barraclough, Dr R Hunter, Dr Jain, Dr Lee
Dr I Fernando
Prof Eldeeb, Dr A Taylor
Dr C Abson, Dr R Burcombe, Dr R Jyothirmayi, Dr G Sadler, Dr A Visioli
Dr M Ah-See, Dr R Ashford, Dr E Maher, Dr A Makris, Dr D Miles, Dr P
Ostler
Dr A Hong, Dr D Hwang
Dr N Storey
Dr Hill, Dr Jacobs, Dr A Jones, Dr B Lavery, Dr S Oliveros, Dr A Sabharwal,
Dr A Salisbury, Dr K Shah, Dr E Sugden, Dr K Vallis, Dr Yeoh
Dr Dubois, Dr A Suovouri
Dr H Lucraft, Dr Mazdai
Dr V Cowie, Dr T Evans, Mr G Neades, Dr S Peoples, Mr I Young
Dr J Barrett, Dr C Charlton, Mr S Courtney
Dr C Lowdell
Dr A Birtle, Dr G Skailes
Dr J Loncaster, Dr V Misra
Dr R Agrawal
Dr D Spooner
Dr C Cottrill, Dr V Wolstenholme
Dr A Robinson, Dr C Trask
Dr A Stockdale
Dr F Yuille
Dr J Trifunović
Dr C Alcock, Dr A Allcock, Dr E Chadwick, Dr B Lavery, Dr S Oliveros, Dr
A Salisbury
Dr A Chittalia
5
Site
Investigators
Sunderland NHS Trust
St Thomas's Hospital, London
Tameside General Hospital, Ashton under
Lyne
Torbay Hospital, Torquay
Dr S Chatterjee
Dr Ahmad, Dr L Brazil, Dr H Dobbs, Dr Harris, Dr Putt, Dr A Tutt
Dr A Sykes
Taunton & Somerset
University of Patras Medical School
Victoria Infirmary, Glasgow
William Buckland, The Alfred
Whipps Cross University Hospital, London
Weston General Hospital
Western Infirmary, Glasgow
Warwick Hospital
Sheffield and area hospitals
West Suffolk Hospital, Bury St Edmunds
Worthing & Southlands NHS Trust
Dr P Bliss, Dr A Goodman
Dr H Barlow, Dr Barthakur, Dr M Beresford, Dr O Frim, Dr J Graham, Dr A
Robinson
Prof D Kardamakis
Mr D Smith, Miss S Stallard
Dr K Taylor
Dr C Cottrill
Dr M Tomlinson
Dr A Alhasso, Dr P Canney, Dr G Fraser, Dr J Hicks, Dr Kodikara, Dr D
Ritchie, Mr M Rizwanullah
Prof R Grieve, Dr D Jones, Dr Stockdale, Dr Teoh
Dr C Bridgewater, Dr K Dunn, Dr B Foran, Dr M Hatton, Dr I Manifold, Dr
Ram
Dr M Moody, Dr C Woodward
Dr F Castell, Mr A Johri, Dr S Mitra
6