Post on 16-Dec-2014
description
JOURNAL CLUBRanjita Pallavi MD and Josef Bautista MD
Critical Appraisal of a Guideline
THE AMERICAN ASSOCIATION FOR THORACIC SURGERY
Guidelines for Lung Cancer Screening using Low-dose
Computed Tomography Scans for Lung Cancer Survivors and other
High-risk groups
Lung Cancer Screening
• Nine million US adults should get a yearly low-dose CT yearly until age 79
• This translates to $ 27 billion dollars of yearly healthcare cost for lung cancer screening alone
The AATS Guideline
The AATS Guideline was developed by a 14-member task force and was based from the result of the NSLT trial and the current NCCN guidelines.
OVERVIEW
• The potential benefits of a guideline are only as good as the quality of the guidelines themselves
• The quality of guidelines can be extremely variable and some often fall short of basic standards
• The AGREE instrument was developed to address the variability in guideline quality
THE AGREE II INSTRUMENT
The AGREE II Instrument
GUIDELINE CONTENT
NOMENCLATURE AND DESCRIPTION FOR RATING GUIDELINE RECOMMENDATIONS
STRENGTH OF RECOMMENDATIONS AND LEVEL OF EVIDENCE FOR THE CLINICAL PRACTICE GUIDELINE
TIER 1 GUIDELINE recommendations
• Guideline for Highest Risk Population
• Annual screening beginning age 55 for smokers and former smokers with 30-pack-year history (1a)
• Annual Screening may continue until age 79 (1a)
• Low-dose CT is the screening technology to be used (1a)
• CXR alone should not be used (1a)
• Exclusion: individuals who cannot be offered adequate treatment based on comorbidity or functional status, regardless of age (not graded)
Tier 1 AlgorithmA
ge 5
5-7
9 a
nd
> 3
0
pack y
ear
No lung nodule
Annual LDCT up to
age 79
Solid nodule See Figure 3
Ground glass
opacity
See Figure 4
TIER 2 GUIDELINE recommendations
• Guidelines for lung cancer survivors and patients with combined risk
• Annual screening for those treated for a primary lung Ca + completed 4 years of radiographic surveillance without evidence for recurrence (2b), or
• patients aged 50-79 years with a 20-pack-year smoking history + cumulative risk of developing lung Ca > 5% over the following 5 years (3)
Tier 2 Algorithm
Lu
ng
Ca S
urv
ivor;
Ag
e >
50
an
d >
20 p
ack y
ears
an
d
Ad
ded
ris
k >
5%
of
develo
pin
g C
a w
ith
in 5
years
.
No lung nodule Annual LDCT up to age 79
Solid nodule See Figure 3
Ground glass nodule See Figure 4
Management of LDCT Findings
Solid nodule
<4 mm
Annual LDCT screening to age
79
4-6 mm
LDCT in 6 mo
>6-8 mm
LDCT in 3 mo
No increase
LDCT in 6 mo
No increase
Annual LDCT
Increase
Referral to specialists
Increase
Surgery
>8 mm
Cosider PET-CT
Low suspicion High suspicion
Surgery
Solid Endobronchial
Bronchoscopy
Management of LDCT FindingsGround Glass
Nodule
< 5 mm
Stable
Annual LDCT until age 79
5-10 mm
LDCT in 6 mo
Stable
Annual LDCT until age 79
Suspicious change
Surgical excision
No lung cancer
Lung cancer
> 10 mm
LDCT in 3-6 mo
Suspicious change
Stable
LDCT 6-12 mo or Biopsy or Surgery
Management of LDCT FindingsNew nodule at
annual or followup LDCT
No suspected infection or
inflammation
Solid nodule
Ground glass nodule
Suspected infection or
inflammation
LDCT in 1-2 mo
Resolving
Radiographic follow-up to resolution
Resolved
Annual LDCT until 79
Persistent or enlarging
PET/CT
Suspicious of Ca
Surgical excision
No lung Ca
Annual LDCT until 79
Lung Ca
Biopsy
No lung Ca
Annual LDCT until 79
Lung Ca
Low suspicion
LDCT in 3 mo
APPRAISAL OF THE GUIDELINEACCORDING TO THE AGREE II
TOOL
Scope and Purpose
• Is there a utility for the use of low-dose CT scan as a lung cancer screening strategy for:
• high risk individuals defined as > 55 yo with > 30 pack years of smoking history
• lung cancer survivors
• 50-79 years with a 20 pack year smoking history and other factors producing a cumulative risk of developing lung cancer that is 5% or more over the following 5 years.
Scope and purpose
Rating: 80%
• The scope and the purpose were clearly stated
• The target population was clearly identified
• However, the expected benefits for the target population were not explicitly stated in a measureable way
• No specified way to measure cumulative smoking risk
Stakeholder Involvement• The guideline was developed by a 14-member committee.
• The task force was composed of thoracic radiologists, oncologists, thoracic surgeons, medical oncologists, a pulmonologist, an epidemiologist and a pathologist.
• The guideline mainly evolved from a well-designed single national trial, which was carried out according to a rigid protocol, without seeking views and opinions from the target population
Stakeholder Involvement
Rating: 30%
• There was no mention of the institutions where the task force members came from, and the geographical location that developed the guideline.
• No involvement of the primary care physician in the development guideline
• No participation of the target group in the development of the guideline
Rigour of Development
• The guideline was based on the NLST and the current NCCN guideline
• It referenced 16 articles
Rigour of DevelopmentRating: 50%
• No other relevant literature was presented
• There is no explicit link between the recommendations and the evidence.
• There was no statement regarding the harm of the procedure or the financial aspect of it
• No sufficient description of the external validation of the guideline
• No statement on possible update of the guideline was present
Clarity of Presentation
Rating: 81%
• The recommendations are specific and unambiguous
• Other options for management were not directly considered
• Specific algorithms for different CT findings were defined
ApplicabilityRating: 35%
• Specific algorithm on different lung findings were presented
• The guideline did not identify barriers or facilitators of the implementation process
• No potential resource implications were considered
• There were no monitoring or auditing criteria defined
Editorial Independence
Rating: 63%
• Funding body was clearly stated
• No description of competing interests
GLOBAL APPRAISAL
• The overall quality of the guideline was moderate.
DISCUSSION
Basis of Tier 1 Recommendations
The National Lung Cancer Screening Trial
Main Objective
• NLST compared two ways of detecting lung cancer: low-dose helical computed tomography (CT) and standard chest X-ray, to see if CT screening could reduce lung cancer specific mortality relative to chest X-ray.
Design• Participants were randomized to 3 annual screens with either low-dose
helical CT or single-view chest X-ray
• Multicenter, parallel-group, randomized, control trial
• N = 53,454 adults at high risk for lung Ca
• LDCT n = 26,722
• CXR n = 26732
• Setting: 33 centers in the US
• Enrollment: 2002-2004
• Analysis: Intention-to-treat
• Follow-up: Median 6.5 ( 3.5 year no-intervention followup)
Inclusion and Exclusion Criteria• Inclusion:
• 55 to 74 years of age
• Cigarette smoking history of at least 30 pack-years
• Former smokers must have quit within the past 15 years.
• Exclusion:
• Lung Cancer
• Chest CT in prior 18 months
• Hemoptysis
• Unexplained weight loss of > 15 lbs in prior year
Population• Age: Race:
• 55-59: 42.8% White 90.9%
• 60-64: 30.6% Black: 4.5%
• 65-69: 17.8% Hispanic: 1.8%
• 70-74: 8.8%
• > 74: <0.1%
• Sex: Smoking Status:• Males: 59% Current 48.1%
• Females 41% Former: 51.9%
Outcomes• Primary Outcomes:
• Lung cancer deaths: 247 vs 309 per 100,000 person-years (RR 0.80; 95% CI 0.73-0.93; p=0.004)
• Secondary Outcomes:
• All-cause mortality: 1877 vs 2000 deaths (RR 93.3; 95% CI 1.2-13.6; p=0.02)
• Lung cancer incidence: 645 vs 572 per 100,000 person-years (RR 1.13; 95% CI 1.03-1.23)
Outcomes
• Positive result: Not cancer: Cancer diagnosis:
T0 27.3% vs. 9.2% 10.2% vs. 3% 3.8% vs. 5.7%
T1 27.9% vs. 6.2% 6.1% vs. 1.8% 2.4% vs. 4.4%
T2 16.8% vs. 5.0% 5.8% vs. 1.5% 5.2% vs. 5.5%
Outcomes
Adverse Events
• Complications following any invasive diagnostic interventions where lung cancer confirmed:
• Any complication: 28.4% vs 23.3%
• Complications following any invasive diagnostic interventions where lung cancer NOT confirmed:
• Any complication 0.4% vs 0.3%
Discussion• Number needed to screen with LDCT is 320 to prevent 1
cancer death
• Good overall internal validity:
• Baseline characteristics were similar for both study groups
• Mixed external validity:
• The LDCT were read by highly trained radiologists
• Population screened was younger and had higher education
• High false-positive rate:
• Problem with overdiagnosis:
• In theory there should be the same number of lung cancers in both arms after followup. But the LDCT group had a persistent gap of 120 excress lung cancers
High Risk Population
Why 79 years?
•Peak incidence of lung cancer :70 years in US
•Average life expectancy currently at 78.6 years
•Age alone is a risk factor: Incidence increases linearly with age
Age > 79 years with good functional status
Why annual screening beyond 3 years?
Lung cancer survivors
• Patients treated for primary bronchogenic carcinoma+4 years of radiographic surveillance+No recurrence(level 3)
• HRCT obtained for 4 yrs after resection of stages IA to IIIA NSCLC foll. By annual LDCT screening starting in 5th yr.
• LDCT screening continue lifelong(funcional status+ pulmonary reserve present)
• These pts have continuing 3% risk of lung cancer diagnosis each year.
Patients with combined risk
• 50-79 yrs with 20 pack-year smoking history+cumulative risk of > 5% over 5 years(similar to NCCN)(level 2)
a) COPD (FEV1<70%)
b) Environmental/Occupational exposure: Asbestosis, Silicosis, Radon
c) Prior cancer/Thoracic Radiation therapy(Radiation risks are linear with dose, risk begins after 2 decades)
d) Genetic/Family history
• Risk calculators: To help with self assessment of risk
a) Liverpool Lung Project Model for individual absolute 5 year risk
b) Prostate,Lung,Colorectal and Ovarian Screening trial: 9 yr probability
LLP Model
PLCO Model
CONCLUSION• The guideline aimed to extend the use of NSLT results to
age 79 as extrapolated from the results of the study
• Based on our assessment using the AGREE tool, the guideline is modest in quality
• The guideline recommendations are clearly stated and specific
• There is lack of emphasis on the potential risks of the uncontrolled screening strategy in the general population.
• The rate of false positives and over-diagnosis must be addressed in subsequent updates.
• We feel that the screening strategy be offered with utmost care and only to high-risk individuals