lung cancer screening

1. LUNG CANCER SCREENING
Dr. Lokesh Lalwani

2. LungCancer Epidemiology
Worldwide – predicted in 2018
• Incidence - 2.1 million newcases
• Mortality - 1.8 milliondeaths
MC cancer in India after
India – predicted in 2018
• Incidence - 67,795 new cases (4th
breast, oral cavity andcervix)
• Mortality – 63,475 deaths (3rd MCcancer related deaths after
breast and oral cavity)
CACancer JClin.2018;68(6):394-424

3. Stage at presentation
Localized, 16%
Regional, 22%
Distant, 57%
Unknown, 5%
SEERCancerStatistics Review, 2009-2015

4. 5-YearRelative Survival
56.3%
29.7%
7.8%
60.00%
50.00%
40.00%
30.00%
20.00%
10.00%
0.00%
Localized Unknown
4.7%
Regional Distant
5-year survival rate
Percent surviving 5 years –18.6%
SEERCancerStatistics Review, 1975-2015

5. LungCancerScreening- CXR
1951-1975: 10 prospective studies, of which 4 are RCT
s–
• TheMemorial-Sloan Kettering LungProject (MSKLP) (sputum
+CXR)
• TheJohnHopkins lung project (JHLP)(Sputum +CXR)
• TheMayo Lungproject (MLP)
• TheCzechoslovakian study (CS)

6. 2013

9. CT scan v/s Chest X-ray
Median delay in diagnosis wasfound to be >1year with cxr.
Themiss-rate for lesions
• ≤ 10mm was 70%
• 10-20mm was30%
• 21-30mm was25%
• The overall accuracy of interpretation for lung cancer – 61%for
CXR,Sensitivity – 23%, Specificity – 96%, when compared to CT
scan
Chest.1999 Mar;115(3):720-4

10. Low DoseCTscan
• Non contrast study
• Multi detector, helical CTscan
• High resolution imagereconstruction
• Estimated effective dose –1.4mSv
• 7-8mSvfor CECTchest, 0.1mSvfor CXR
AJRAm JRoentgenol.2011;197(5):1165

11. a- non solid nodule, b- partially solid nodule, c- solid nodule

13. Solid nodule on
initial screening
≤5 mm
Annual screening until patient is no longer
a candidate for definitive treatment
6-7 mm LDCT in 6 months
8-14
mm
LDCT in 3 months or consider PET/CT
≥ 15
mm
Chest CT ±
contrast and/or
PET/CT
Low
suspicion of
lung cancer
LDCT in 3 months
High
suspicion of
malignancy
Biopsy or
surgical
excision
No cancer
Annual
screening
Cancer
confirmed

14. Part solid
nodule on
initial
screening
≤5 mm
Annual screening until patient is no
longer a candidate for definitive
treatment
≥6 mm with
solid
component ≤5
mm
LDCT in 6 months
≥6 mm with solid
component 6-7
mm
LDCT in 3 months or consider PET/CT
Solid
component ≥ 8
mm
Chest CT ±
contrast
and/or PET/CT
Low
suspicion
of lung
cancer
LDCT in 3 months
High
suspicion of
malignancy
Biopsy or
surgical
excision
No cancer
Annual
screening
Cancer
confirmed

15. Non solid nodule on
initial screening LDCT
≤ 19 mm
Annual screening LDCT
until patient is no
longer candidate for
definitive treatment
≥ 20 mm LDCT in 6 months

16. National LungScreeningTrial
• Multicenter, RCT
,USA
• 53,454 participants were enrolled between 2002 –2004
• LDCT(26,722) vsCXR(26,732)
• 3 screenings –T0(at randomization), T1and T2at 1-year
intervals
Inclusion Criteria :
• Age- 55 - 74 years
• Cigarette smoking of at least 30 packyears
• If former smokers - must have quit within the previous 15
years
NEnglJMed 2011;365:395-409.

17. Positive test – “suspicious for” lungcancer
• Any non calcified nodule measuring at least 4 mm in any
diameter
• Adenopathy
• Effusion
Minor abnormalities–
• Clinically significant conditions other than lungcancer
• After the third round of screening (T2), abnormalities
suspicious for lung cancer that were stable across the three
rounds
NEnglJMed 2011;365:395-409.

18. NEnglJMed 2011;365:395-409.

19. NEnglJMed 2011;365:395-409.

20. Lungcancer specific mortality
• 356 (LDCT)vs443 (CXR)deaths from lungcancer
• 20.0% (95% CI, 6.8 to 26.7; P= 0.004) reduction in rate of
death from lungcancer
• total of 320 individuals with high risk factors needed to
screen to prevent one death from lungcancer
Overall mortality
• 1877 (LDCT)vs 2000 (CXR)deaths
• 6.7%reduction (95%CI,1.2 to 13.6; P=0.02) in the rate of
death from anycause
NEnglJMed 2011;365:395-409.

21. NLST
NEnglJMed 2011;365:395-409.

22. NELSONtrial
Dutch-Belgian RandomizedLung
CancerScreening Trial
Hypothesis :
• Lung cancer screening by LDCT will reduce 10-year lung
cancer mortality by 25% in high-risk (ex-)smokers between 50
and 75 years of age.
Inclusion Criteria :
• Men aged50-75 years
• Smokedcigarettes - >15/day for >25 years or >10/day for >30
years
• Ifquit smoking then <10 years.
CancerImaging (2011) 11, S79-S84

23. NELSONtrial
• LDCTscreening at baseline (round 1), after 1 year (round2),
after 3 years (round 3) and after 5.5 years after baseline
(round 4)
• 15,822 participants randomized in 1:1 ratio to screening LDCT
(7915) vsno screening (7909)
Thorax2017;72:48–56.

24. NELSONtrial
CancerImaging (2011) 11, S79S84

25. NELSONtrial
• Management wasdetermined based on the highest nodule
category found
• Growth was defined aschange in volume of at least25%
between scans
• NODCA
T3 - indeterminate test result which required arepeat
scan3-4 months later to assessgrowth
CancerImaging (2011) 11, S79S84

26. NELSON
Thorax2017;72:48–56.

27. Factors NLST NELSON
Screening design LDCTvsCXR LDCTvsno screening
Screening rounds 3 4
Length of screening
interval (years)
1 1, 2 and 2.5
Yearof initiation 2002 2003
Enrolled participants 53,454 15,822
Positive result Maximum axial diameter
≥4mm
Volume >500mm3 or
Volume 50-500mm3 andVDT
<400 days
Negative result Maximal axial diameter <4mm Volume <50mm3
Entry criteria
Age(yrs) 55-75 50-75
Smokingstatus Current and former smokers Current and former smokers
Smokingcessation <15 years <10years
Smokinghistory ≥30 pack years ≥15 per day for 25 yearsor
≥10 per day for 30years
J.Compar.Effect. Res.(2013) 2(5)

28. Cumulativedata NLST NELSON
Positive screening result 24.2% 1.9%
Falsepositive rate after
positive screening result
96.4% 59.4%
Lungcancer detection rate 2.4% 3.2%
%of StageI cancers
detected
61.6% 69.4%
LDCTsensitivity for LC 93.8% 94.6%
LDCTspecificity for LC 73.4% 98.3%
J.Compar.Effect. Res.(2013) 2(5)
Thorax2017;72:48–56.
• 26%reduction in lung cancerdeaths at 10yearsofstudy follow-up

29. Am JRespir Crit CareMed Vol 187, Iss.8, pp 848–854,Apr 15, 2013

30. Preventive Medicine 89 (2016) 301–314

31. Preventive Medicine 89 (2016) 301–314

32. Other benefits of L
Cscreening
• Improved QOL
• Reduction in disease relatedmorbidity
• Reduction in treatment relatedmorbidity
• Reduction in anxiety and psychosocialburden
• Increased smoking cessation rates
• Other occult diseases: thyroid nodule, renal
tumour, aortic aneurysm, breast cancer etc.

33. Risksof L
Cscreening
• Falsepositive results
• Rangefrom 10-43%
• Cumulative risk is 33%for aperson undergoing LCscreening
with 2 sequential annualscans
• Benign intrapulmonary LNand non calcified granulomas

34. Risksof L
Cscreening
Br JRadiol;91:20170460

35. • V
olumetric analysis in NELSON trial – decreases the false
positives
Lung-RADS(Lung Imaging Reporting and Data System)
• Increased sizethreshold from 4 mm greatesttransverse
diameter to 6 mm transverse bi-dimensionalaverage
• 20 mm for nonsolidnodules
• Growth for preexisting nodules (>1.5mm)

36. Category No:
Name
Findings Management Probability
of
malignancy
Negative 1 Nonodules
Nodules with complete/central/popcorncalcification
Fatcontaining nodules
AnnualLDCT <1%
Benign 2 SN:<6mm, New - <4mm AnnualLDCT <1%
PSN:<6mm in baseline
NSN:<20mm or
≥20 mm andunchanged
Probably
benign
3 SN:≥6 to <8mm at baselineor
New – 4 mm to <6mm
6 monthLDCT 1-2%
PSN:≥6 mm with solid component <6mmor
New <6mm
NSN:≥20 mm on baseline CTornew
Suspicious 4A SN:≥8 to <15mm at baselineor
Growing <8 mmor
New 6 to <8mm
PSN:≥6 mm with solid component ≥6 mm to <8mm or
new or growing <4mm solidcomponent
Endobronchial nodule
3 month LDCT;
PET/CTmaybe
usedwhen
there is a≥8mm
solid
component
5-15%
4B SN:≥15 mm or
New or growing, and ≥8 mm
PSN:asolid component ≥8 mm or
New or growing ≥4 mm solidcomponent
CECTChest±
PET/CTand
tissue sampling.
PET/CTmaybe
usedwhen
there is a≥8mm
>15%
4X Category 3 or 4 nodules with additional findings thatincreasethe
suspicion of malignancy

37. Application of Lung-RADSto NLST
Lung-RADS at
baseline
NLSTat
baseline
Lung-RADS
after baseline
NLSTafter
baseline
Sensitivity 84.9% 93.5% 78.6% 93.8%
Falsepositive
result rate
12.8% 27.3% 5.3% 21.8%
PPV 6.9% 3.8% 11.0% 3.5%
NPV 99.81% 99.9% 99.81% 99.93%
Ann Intern Med.2015;162:485-491

38. BRELT1:First Brazilian L
CscreeningTrial
• Single center study
• Jan2013 to July2014
• Inclusion criteria similar toNLST
• 790 participants were enrolled
• Positive scans– pulmonary nodules >4mm (similar to
NLST)
Ann ThoracSurg 2016;101:481–8

39. BREL
T1Protocol

40. BREL
T1Results

41. China
• Multicenter, RCT
,1:1 randomization
• LDCT(3512) vsstandard care(3145)
• Nov 2013 to Nov2014
Inclusion criteria :
• Age- 45-70 years and at least one riskfactor
• ≥20 pack year history
• H/o any cancer in close family members
• Prior h/o any cancer in theparticipant
• Occupational exposure to carcinogens
• Longh/o passivesmoking (>2 hr every day for at least 10years)
• Longterm exposure to cooking oilfumes
LungCancer117 (2018) 20–26

42. • Positive results – 22.9%(804/3512)
• Lungcancer detection rate was1.5%(51/3512)
• Falsepositive rate – 21.8%(753/3461)

43. SouthKorea
• August 1999 – Sept 2003
• Single center, observational study
• Age≥45 years and either ≥20 pack years (high risk group)or
<20pack year smoking or non smokers (low riskgroup)
• 6406 participants underwent LDCT
JKoreanMed Sci2005; 20: 402-8

44. • For solid nodule and >10 mm – immediate intervention(tissue
diagnosis) was done
• For solid nodule <10 mm – follow up scan6 monthslater
• For GGO>10 mm - immediate intervention (tissue diagnosis)
was done
• For GGO <10 mm – f/u scan after 2 months, then after 6
months and annually thereafter

45. • 35%(2,255 of 6,406) of screened subjects had at least one ormore
non-calcified nodules (n=4,037)
• 2,085 subjects had 3,783 solid nodules (mean- 1.8 nodulesper
subject)
• 170 subjects had 254 GGOnodules (mean- 1.5 nodules per subject)
23 lung cancerswere detected with an overall detection rateof
• 0.36%(23 of 6,406)
• 0.57%(23 of 4,037) of non calcifiednodules

47. PET/CT
• Retrospective study from India
• 191 patients with solitarypulmonary nodule undergoing FDG-
PET/CT
• Thefinal pathological diagnosis wasmalignancy in 75.3%
(144/191) of nodules
Indian JCancer2017;54:271-5.

50. • 24.7%(47/191) were benign
• 64%(30/47) had afalse positive PET-CTat aSUVcut-off of 2.5

51. Solid nodule >8mm in diameter
Determine pretest clinical probability of malignancy
Low(<5%) Moderate (5-60%) High(>60%)
Serial CT
surveillance
Non SurgicalBiopsy
SurgicalResection
ClearGrowth ?
negative
yes
no
suspicious
SurgicalBiopsy
positive
PETscan
Hypermetabolic ?
intense
CHESTrecommendations for SN-Asia
CHEST2016; 150(4):877-893

52. • The expert panel recommends that regardless of whether
clinical judgment or a calculation model is used, clinicians
must decide if the clinical probability suggests further imaging
studies, biopsy, and/or resection areneeded
For benign nodules (low probability of malignancy), an accurate
diagnosis is required in
• TBor other infections requiring specifictreatment
• Patients who are on high-doseimmunosuppression

53. Solid, indeterminate nodule >8 mm in diameter with moderate
(5-60%) probability of malignancy (when - discordance between
the clinical and radiologicfeatures)
characterize the nodule before surgical resection
• Consider functional imaging, preferably with PET, to
or
continued radiological surveillance
limitations:
• False-positive (e.g., TB,fungal and parasitic disease) and
• False-negative slow-growing tumors (eg, adenocarcinoma in
situ)

54. • In an individual with a solid, indeterminate nodule >8 mm in
diameter with high (>60%) probability of malignancy,
functional imaging has a greater role in preoperative staging
than in characterizing thenodule
• T
o rule out previously undetected metastases before surgical
intervention

55. Smokers were less likely to agree that early-stage survival is good (43% vs.
53%; OR: 0.64,0.46–0.88) or be willing to have surgery for an early stage,
screen-detected cancer (84% vs. 94%; OR: 0.38, 0.21–0.68), compared with
former smokers.

56. Liquid biopsies include circulating
nucleic acids, circulating proteins and circulating
tumour cells (CTCs)

57. Sensitivity of LCS according to
adherence

58. Conclusion
 L
Cscreening by LDCTscanreduces mortality (lungcancer specificandall cause
mortality)
 Application of Lung-RAD
Sandvolumetric analysis reduces falsepositive rates
 In amoderate risk patient, useof PET/CTscanislessreliable andemphasisshould beon
non surgicalbiopsy
 Newermodilitiesarerequiredtodiagnoselungcancerwithlesssideeffects.