Second round results from the Manchester ‘Lung Health Check’ community-based targeted lung cancer screening pilot

Abstract

We report results from the second annual screening round (T1) of Manchester’s ‘Lung Health Check’ pilot of community-based lung cancer screening in deprived areas (undertaken June to August 2017). Screening adherence was 90% (n=1194/1323): 92% of CT scans were classified negative, 6% indeterminate and 2.5% positive; there were no interval cancers. Lung cancer incidence was 1.6% (n=19), 79% stage I, treatments included surgery (42%, n=9), stereotactic ablative radiotherapy (26%, n=5) and radical radiotherapy (5%, n=1). False-positive rate was 34.5% (n=10/29), representing 0.8% of T1 participants (n=10/1194). Targeted community-based lung cancer screening promotes high screening adherence and detects high rates of early stage lung cancer.

Full text

Second round results from the Manchester ‘Lung
Health Check’ community-based targeted lung cancer
screeningpilot
Phil A Crosbie,1,2 Haval Balata,1 Matthew Evison,1 Melanie Atack,3
Val Bayliss-Brideaux,3 Denis Colligan,3,4 Rebecca Duerden,1 Josephine Eaglesfield,3
Timothy Edwards,1 Peter Elton,5 Julie Foster,6 Melanie Greaves,1 Graham Hayler,3
Coral Higgins,4 John Howells,7 Klaus Irion,8 Devinda Karunaratne,8 Jodie Kelly,1
Zoe King,3 Judith Lyons,1 Sarah Manson,1 Stuart Mellor,9 Donna Miller,10
Amanda Myerscough,3 Tom Newton,9 Michelle O’Leary,11 Rachel Pearson,3,4
Julie Pickford,6 Richard Sawyer,1 Nick J Screaton,12 Anna Sharman,1 Maggi Simmons,3
Elaine Smith,1 Ben Taylor,13 Sarah Taylor,3,4 Anna Walsham,14 Angela Watts,1
James Whittaker,15 Laura Yarnell,3,4 Anthony Threlfall,3 Phil V Barber,1 Janet Tonge,3,4
Richard Booton1
Brief communication
To cite: CrosbiePA,
BalataH, EvisonM, etal.
Thorax Epub ahead of print:
[please include Day Month
Year]. doi:10.1136/
thoraxjnl-2018-212547
For numbered affiliations see
end of article.
Correspondence to
DrPhil ACrosbie, Manchester
Thoracic Oncology Centre, North
West Lung Centre, Manchester
University NHS Foundation Trust,
Wythenshawe, M23 9LT, UK;
philip. crosbie@ manchester.
ac. uk
Received 30 August 2018
Revised 12 October 2018
Accepted 22 October 2018
© Author(s) (or their
employer(s)) 2018. Re-use
permitted under CC BY.
Published by BMJ.
ABSTRACT
We report results from the second annual screening
round (T1) of Manchester’s ’Lung Health Check’ pilot of
community-based lung cancer screening in deprived areas
(undertaken June to August 2017). Screening adherence
was 90% (n=1194/1323): 92% of CT scans were classified
negative, 6% indeterminate and 2.5% positive; there
were no interval cancers. Lung cancer incidence was 1.6%
(n=19), 79% stage I, treatments included surgery (42%,
n=9), stereotactic ablative radiotherapy (26%, n=5) and
radical radiotherapy (5%, n=1). False-positive rate was
34.5% (n=10/29), representing 0.8% of T1 participants
(n=10/1194). Targeted community-based lung cancer
screening promotes high screening adherence and detects
high rates of early stage lung cancer.
INTRODUCTION
The National Lung Screening Trial (NLST) demon-
strated a 20% reduction in lung cancer–specific
mortality with annual low-dose CT (LDCT) screening
of high-risk ever smokers compared with chest X-ray.1
A key requirement for screening implementation is
to ensure services are accessible to those at greatest
risk. In Manchester, we developed a community-based
‘Lung Health Check’ (LHC) approach to target high-
risk smokers in deprived areas. LHCs were nurse-led
and included calculation of lung cancer risk using
the PLCOM2012 risk model. Those at higher risk were
eligible for annual LDCT screening over two screening
rounds. There was a high prevalence of lung cancer
detection at baseline (T0; undertaken June to August
2016) (3%); most cancers were early stage (80%) and
therefore radically treatable.2 Here, we report the
results of the second screening round (T1; undertaken
June to August 2017).
METHODS
A description of the screening pilot has previously
been published.2 In brief, ever smokers aged 55–74
at participating general practices (n=14) were
invited to a LHC; this consisted of 6-year lung cancer
risk calculation (PLCOM2012),3 symptom assessment,
smoking cessation advice and spirometry. Individ-
uals at higher risk (defined as ≥1.51% over 6 years)
were offered annual LDCT screening. All LDCT
scans (Optima 660; GE Healthcare) were reported
by National Health Service (NHS) consultant radi-
ologists with an interest in thoracic radiology and
classified as either negative, indeterminate or posi-
tive. Pulmonary nodules were managed in accord-
ance with British Thoracic Society (BTS) guidelines
adapted for an annual screening programme.4 Inde-
terminate scans required surveillance imaging at
3 months and positive scans had findings concerning
for lung cancer requiring immediate assessment
in the rapid access lung cancer clinic based in a
specialist centre. A false positive was any screened
individual referred to the lung cancer clinic who
was not diagnosed with lung cancer. An interval
cancer was defined as any lung cancer diagnosed
outside of screening before the second-round scan
(T1). Volume doubling times (VDTs) were calcu-
lated in accordance with BTS guidelines.4 VDT
was estimated in those without a nodule at baseline
(T0) by assuming the nodule appeared the day after
the CT scan was performed and measured 1 mm.
Lung cancers were managed in accordance with
national guidelines.5 The seventh edition of TNM
lung cancer staging manual was used.6 In this paper,
the first screening round is referred to as T0 and
the second screening round 12 months later as T1.
Individuals with an indeterminate scan at T1 had a
further LDCT scan 3 months later, which we refer
to as the ‘3-month surveillance’ scan.
RESULTS
Ninety per cent of those eligible had a T1 scan
(June to August 2017) (n=1194/1323). Non-at-
tendees were significantly more likely to be
current smokers (63.6% vs 50.6%, p=0.005), but
there was no difference according to deprivation
1CrosbiePA, etal. Thorax 2018;0:1–5. doi:10.1136/thoraxjnl-2018-212547
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Brief communication
(p=0.79) (table 1). The majority of T1 scans were ‘negative’
(92%, n=1099) (figure 1); 71 were ‘indeterminate’ of which
84.1% (n=58/71) were for nodule surveillance. The 3-month
surveillance imaging rate was significantly lower than T0 (6%
vs 13.7%; p=0.0001); six individuals were reclassified positive
after 3-month scans. Overall, 30 scans were ‘positive’ (2.5%,
n=30/1194)—one patient declined assessment. Of 29 individ-
uals seen, 19 were diagnosed with lung cancer and 10 were not.
The false-positive rate was 34.5% (n=10/29), which represents
0.8% of T1 participants (n=10/1,194). This false-positive rate
was significantly lower (p=0.0001) than T0 (corresponding
values 48.1% and 2.8%) and over both screening rounds it was
44.5% and 3.5%, respectively. There were no interval cancers
between T0 and T1.
The incidence of lung cancer in T1 was 1.6% (n=19/1,194),
79% were stage I (n=15), 10.5% stage III (n=2) and 10.5%
stage IV (n=2) (table 2). Pathological subtypes included adeno-
carcinoma (32%, n=6), squamous cell (21%, n=4), small cell
(16%, n=3) and non-small cell lung cancer not otherwise spec-
ified (10.5%, n=2). A clinical diagnosis was confirmed by the
multidisciplinary team in four cases without pathological confir-
mation (21%). Cancer treatments included surgery (42%, n=9),
stereotactic ablative radiotherapy (26%, n=5) and radical radio-
therapy (n=1) (table 2). One individual had surgery for a benign
lesion (granulomatous disease). There were no deaths within 90
days of surgery.
Thirteen individuals with a negative baseline scan (T0)
were diagnosed with lung cancer in the second round; after
Table 1 Comparison of attendees and non-attendees of the second (T1) screening round
Variable
T1 Screening round
P valuesAttendees Non- attendees
No of attendees (%) 1194 129 –
Mean age (years±SD) 64.7 (5.4) 64.2 (5.6) 0.34
Sex M/F (F%) 587/607 (50.8) 65/64 (49.6) 0.79
Median IMD rank (IQR) 2848 (3615) 2908 (4195) 0.79
BMI (±SD) 28.5 (5.4) 28.3 (5.7) 0.73
Lung cancer risk (PLCOM2012±SD) 4.8 (3.8) 5.4 (4.7) 0.13
Education(%) Less than ‘O’ level 822 (68.8) 93 (72.1) 0.58
‘O’ level 213 (17.8) 24 (18.6)
‘A’ level 44 (3.7) 3 (2.3)
University/college 77 (6.4) 5 (3.9)
University degree 26 (2.2) 4 (3.1)
Postgraduate/professional 12 (1.0) 0
Smoking status(%) Current 604 (50.6) 82 (63.6) 0.005
Former 590 (49.4) 47 (36.4)
Smoking exposure(mean±SD) Duration (years) 43.4 (8.3) 45.4 (7.0) 0.008
Cigarettes/day 24.1 (12.8) 23.9 (12.5) 0.83
Pack-years 51.2 (25.9) 53.4 (28.6) 0.37
Spirometry(mean±SD) FEV12.16 (0.7) 2.08 (0.7) 0.26
% predicted FEV184.9 (24.5) 81.0 (21.6) 0.09
FVC 3.17 (1.0) 3.10 (1.0) 0.44
% predicted FVC 100.4 (24.6) 96.3 (23.7) 0.07
FEV1:FVC ratio 67.9 (10.7) 67.6 (12.3) 0.75
Airflow obstruction Yes (%) 588 (49.6) 63 (53.1) 0.45
COPD/emphysema Yes (%) 386 (32.2) 37 (28.7) 0.40
FH lung cancer Yes (%) 326 (27.3) 32 (24.8) 0.54
MRC Dyspnoea Score (%) 1 781 (65.4) 72 (55.8) 0.13
2 261 (21.9) 32 (24.8)
3 98 (8.2) 14 (10.9)
4 53 (4.4) 11 (8.5)
5 1 (0.1) 0
Performance status (%) 0 655 (54.9) 60 (46.5) 0.12
1 403 (33.8) 46 (35.7)
2 116 (9.7) 19 (14.7)
3 20 (1.7) 4 (3.1)
4 0 0
BMI, Body Mass Index;FH, family history;IMD, Index of Multiple Deprivation; MRC, Medical Research Council.
2CrosbiePA, etal. Thorax 2018;0:1–5. doi:10.1136/thoraxjnl-2018-212547
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Brief communication
retrospective review, five were visible at baseline as sub-5 mm
nodules and all were stage I at diagnosis (table 2). The T0
false-negative rate was therefore 0.4% (n=5/1337), negative
predictive value 99.6%, sensitivity 89.4% and specificity 97.1%.
The benign surgical resection rate over both rounds was 2.5%
(n=1/40). Tumour VDT was highest in those with a true nega-
tive baseline scan (average 49±26 days), followed by false-neg-
ative (99±50 days) and indeterminate scans (297±215 days;
p=0.009) (table 2).
DISCUSSION
In this paper, we report results from the second round of the
Manchester ‘Lung Health Check’ pilot, a targeted lung cancer
screening service based in deprived areas of Manchester.
Screening adherence was high (90%) despite most participants
being from the lowest decile of deprivation in England, empha-
sising the benefit of accessible community-based services. The
incidence of lung cancer was 1.6% (n=19), most cancers were
stage I (79%) and 89% of individuals with screen detected cancer
were offered curative-intent treatment. Over both screening
rounds, 4.4% of the cohort were diagnosed with lung cancer,
equivalent to one cancer detected for every 23 people screened.
This is high when compared with other studies and more than
2.5 times that seen in NLST (T0: 1.0%, T1: 0.7%) and NELSON
(T0: 0.9%, T1: 0.7%).1 7 Our benign surgical resection rate was
low at 2.5%, 10-fold lower than NLST and NELSON.1 7 The
pathological confirmation rate and surgical resection rate are
lower than reported in other trials. The exact reason for this
is unclear but may be a consequence of higher deprivation and
increased comorbidity in our population.
When reviewed retrospectively, five cancers diagnosed in the
second screening round were present on baseline CT, and all
were sub-5 mm solid nodules and therefore appropriately clas-
sified as negative in accordance with BTS guidelines .4 In all five
cases, the cancers were stage I when detected, although with
VDTs ranging from 51 to 163 days, there may have been a stage
shift if we had adopted biennial rather than annual screening.
This was also true for cancers that developed in individuals with
true negative baseline scans; the estimated mean VDT of 49 days
in this cohort suggests a more aggressive phenotype.
Figure 1 Diagram showing flow of participants through the screening service.LDCT,low-dose CT scan; MDT, multidisciplinary team.
3CrosbiePA, etal. Thorax 2018;0:1–5. doi:10.1136/thoraxjnl-2018-212547
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Brief communication
It is noteworthy that the proportion of attendees classified as
false positive was three times lower in the second round than
the first; the 3-month surveillance imaging rate was also 30%
lower. This may be a consequence of having the baseline CT as
a comparator; a similar finding was reported by the ITALUNG
study investigators and suggests that the risk of screen-related
harm may be greatest in the first round.8 Over both screening
rounds, the false-positive rate was higher than NELSON but
lower than other studies.1 8–10 In terms of baseline (T0) screening
performance, the service had a sensitivity of 89.4% and speci-
ficity 97.1%. This represents a slightly lower sensitivity (93.8%)
than NLST but a much improved specificity (73.4%).1
In conclusion, we have demonstrated that a targeted commu-
nity-based lung cancer screening programme, delivered within
the NHS, can engage those most at risk and detect a high propor-
tion of curable early stage lung cancers.
Author affiliations
1Manchester Thoracic Oncology Centre, Wythenshawe Hospital, Manchester
University NHS Foundation Trust, Manchester, UK
2Division of Molecular and Clinical Cancer Sciences, Faculty of Biology, Medicine and
Health, University of Manchester, Manchester, UK
3Manchester Clinical Commissioning Group, Macmillan Cancer Improvement
Partnership, Manchester, UK
4Manchester Health and Care Commissioning, Manchester, UK
5Greater Manchester, Lancashire, South Cumbria Strategic Clinical Network,
Manchester, UK
6Manchester City Council, Manchester, UK
7Department of Radiology, Royal Preston Hospital, Preston, UK
8Department of Radiology, Manchester Royal Infirmary, Manchester University NHS
Foundation Trust, Manchester, UK
9Department of Radiology, Royal Blackburn Hospital, Blackburn, UK
10The Black Health Agency, Manchester, UK
11Macmillan Cancer Support, Manchester, UK
12Department of Radiology, Papworth Hospital, Cambridge, UK
13Department of Radiology, Christie NHS Foundation Trust, Manchester, UK
14Department of Radiology, Salford Royal NHS Foundation Trust, Salford, UK
15Department of Radiology, Stockport NHS Foundation Trust, Stockport, UK
Acknowledgements The Macmillan Cancer Improvement Partnership facilitated
the design and development of the pilot. The service was delivered by the lung
cancer team at Wythenshawe Hospital, Manchester University NHS Foundation Trust,
in partnership with Alliance Medical. LDCT reporting was performed by a consortium
of NHS consultant radiologists with subspecialty interest in thoracic medicine. The
pilot service was commissioned by South Manchester Clinical Commissioning Group
on behalf of the three Manchester Clinical Commissioning Groups. Community
engagement was delivered by multiple members of the team and was led by MCIP
and the Manchester CCGs in conjunction with Manchester City Council, Macmillan
Cancer Support and BHA for Equality. This work was supported by the NIHR
Manchester Biomedical Research Centre.
Contributors Service concept: RB, PAC, PVB, AT, JT. Service development by
members of the Macmillan Cancer Improvement Partnership: JT, ZK, GH, CH, PVB,
MA, VB-B, JE, DM, JF, MS, AM, MO’L, RP, JP, LY, AT, PE, DC, ST, RB, PAC, ES, DK, BT, DC,
Table 2 Clinical details of screen detected lung cancers
T0 outcome Stage
VDT
(days) Final stage
Pathology
(subtype) Treatment
Indeterminate pT1a N0 369 IA Adenocarcinoma
(acinar)
Surgery
Indeterminate pT1a N0 148 IA Adenocarcinoma
(acinar)
Surgery
Indeterminate pT1a N0 89 IA Squamous Surgery
Indeterminate pT1a N0 687* IA Adenocarcinoma
(acinar 50%, solid 20%,
lepidic 30%)
Surgery
Indeterminate pT1a N0 206 IA Squamous Surgery
Indeterminate pT1a N0 285 IA Adenocarcinoma
(micropapillary 50%,
papillary 10%, lepidic 40%)
Surgery
Negative† pT1a N0 142 IA Adenocarcinoma
(solid 80%, acinar 20%)
Surgery
Negative cT1a N0 29‡ IA Clinical SABR
Negative† cT1a N0 163 IA Clinical SABR
Negative† cT1a N0 51 IA NSCLC (NOS) SABR
Negative cT1a N0 71§ IA Squamous SABR
Negative cT1a N0 67§ IA Clinical No treatment¶
Negative† cT1b N0 65 IA Clinical Radical radiotherapy
Negative pT2a N0 – IB Adenocarcinoma
(solid 80%, lepidic 20%)
Surgery
Negative† cT2a N0 72 IB NSCLC (NOS) SABR
Negative cT1a N2 37‡ IIIA Squamous Chemoradiotherapy(S)
Negative pT1a N2 86§ IIIA Small cell Surgery/chemotherapy(A)
Negative cT4 N2 M1a 34‡ IV Small cell Chemoradiotherapy(S)
Negative cT3 N3 M1b 16‡ IV Small cell Chemoradiotherapy(S)
*Morphology of nodule changed with increasing density despite low VDT.
†False negative, (S)sequential treatment, (A)adjuvant chemotherapy.
‡Estimated VDT.
§VDT calculated between T1 and T1+3-month surveillance scans.
¶Hadchemoradiotherapy for oesophageal cancer.
NOS, not otherwise specified; NSCLC, non-small cell lung cancer; SABR, stereotactic ablative radiotherapy; VDT, volume doubling time.
4CrosbiePA, etal. Thorax 2018;0:1–5. doi:10.1136/thoraxjnl-2018-212547
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Brief communication
ST. Service operation and delivery by the Manchester University NHS Foundation Trust
lung cancer team: HB, ME, JL, TE, JK, SMan, AWal, RD, MG, RS, AS, ES, PVB, PAC, RB.
Radiology reporting by the radiology consortium: RD, MG, JH, KI, DK, SMel, TN, RS,
NJS, AS, ES, BT, AWat, JW. Analysis of data and drafting of manuscript: PAC, HB, ME,
JT, RB and guarantors of overall content: PAC, RB. Review, revision and agreement of
final manuscript: all authors.
Funding The pilot was supported by funding from Macmillan Cancer Support.
Competing interests None declared.
Patient consent Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Open access This is an open access article distributed in accordance with the
Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits
others to copy, redistribute, remix, transform and build upon this work for any
purpose, provided the original work is properly cited, a link to the licence is given,
and indication of whether changes were made. See: https:// creativecommons. org/
licenses/ by/ 4. 0/.
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