screening

1. Breast Cancer And Lung
Cancer Screening

2. • Cancer screening refers to a test or examination
performed on an asymptomatic individual.

3. BREAST CANCER
SCREENING

4. Components Of A Breast Screening
Evaluation :
I. Breast awareness (ie, patient familiarity with her breasts),
II. Physical examination (by a health-care provider )
III. Screening mammography
IV. Screening breast magnetic resonance imaging (MRI).
Although there is preliminary evidence that breast ultrasonography
can be a useful screening adjunct to mammography in the evaluation
of high-risk women with dense breasts, its use as a screening test is
not recommended at this time.

5. I. Breast Self examination

6. IMPACT
• To date, no study has shown that BSEs decrease mortality.
• The UK Trialists study, a nonrandomized study with 16 years
of follow-up, showed no significant difference in breast cancer
mortality between the BSE and control groups
• BSEs have been studied in two large randomized trials

7. Cochrane review---no reduction of breast cancer
mortality and high chance of benign breast biopsy
RUSSIAN : CHINESE/SHANGHAI:
• 124,000
• monthly BSEs versus no
BSEs
• There was no difference in
mortality rates, despite the
BSE group having a higher
proportion of early stage
tumors and a significant
increase in the proportion of
cancer patients surviving 15
years after diagnosis.
• 266,000
• 10 years of follow-up
• there was no difference in
mortality, but the
intervention arm had a
significantly higher
incidence of benign breast
lesions diagnosed and breast
biopsies preformed.

8. BSE guidelines :
• No screening organization now recommends routine
instruction of women in BSE
• The ACS, the NCCN, and ACOG all promote teaching patients
about breast self-awareness, the concept that a woman should
be familiar with her own breasts and bring any changes to the
attention of her health provider
• Breast Cancer Detection Demonstration Project : the
estimated overall sensitivity of breast self-examination in
detecting breast cancer was 26%

9. II . Clinical Breast Examination :
• A clinical breast exam (CBE) is systemic palpation and visual
inspection of entire breast by a health professional such as a
doctor, nurse practitioner, nurse, or physician assistant.(ACS)
• National breast and cervical cancer early detection program
(UK) :
sensitivity –58.8%
specificity—93.4%

11. Guidelines For CBE :
• ACS - Every 3 y from ages 20 to 39, then annually
• ACOG
every 1-3yrs from ages 30-39yrs ,then annually
• NCCN
• USPSTF – insufficient evidence
• CANADIAN TASK FORCE - Every 1–2 y starting at age 40

12. III . Screening Mammography :
• Mammography is the process of using low-energy X-rays to
examine the human breast, which is used as a
diagnostic and screening
tool.
• goal –
Early detection of
breast cancer.
• Only screening modality to
have shown decrease in mortality.

13. • Screening mammography has resulted in a shift in both the
Incidence & stage of patients presenting with breast cancer.
• Advantages—
low cost
low radiation Dose
high sensitivity
• Poor performance - women younger than 50 years
due to lower breast cancer incidence, faster-growing
tumors, and reduced mammographic sensitivity caused by breast
density

14. Interpretation :
• Fatty – lease dense, appear dark on image
• Glandular tissue – dense, appear bright on image
• Pectoral muscle, axillary lymph nodes, calcifications (calcium
deposits), fluid filled cysts, tumors – dense, appear bright on
image

16. Mediolateral Oblique View
• Pectoral shadow seen down
to level of nipple or lower
• Inframammary fold well
seen
• Nipple in profile
• Length of posterior nipple
line (pnl) within one 1cm
in size c.F PNL on CC
• Images symmetric

17. Craniocaudal View
• All glandular tissue identified
• Nipple in profile
• Nipple in midline of image
• Length of posterior nipple line
(pnl) within one 1cm in size
c.F PNL on MLO
• Images symmetric

18. Mammographic Features Characteristic Of
Breast Cancer :
Mass with spiculated
margins
Microcalcification Architectural distortion

20. Impact Of Mammographic Screening
• First advocated in the 1950s.
• The Health Insurance Plan (HIP) Study –1963- 61,000 women
• MMG + CBE vs. no screening
• Mammography reduced breast cancer mortality by 30% at
about 10 years after study entry.
• 18 years FU - 25% lower breast cancer mortality rate in
screening arm.

21. 9 PROSPECTIVE RANDOMISED TRIALS :

22. • Screening women 40 to 75 years of age does reduce the relative
risk of breast cancer death by 10% to 25%.
• The 10 studies demonstrate that the risk–benefit ratio is more
favorable for women aged 60-69 yrs versus those aged 50 – 59
years of age .
• The Canadian screening trial suggests mammographies and
clinical breast examinations do not decrease risk of death for
woman aged 40 to 49 and that mammographies add nothing to
CBEs for women age 50 to 59 years
• the Kopparberg Sweden study suggests that mammographies are
associated with a 32% reduction in the risk of death for women
aged 40 to 74 years

23. Guidelines - screening
mammography:
• ACOG
• ACS
Annually beginning at age 40
• NCCN
• ACR
• CANADIAN TASK FORCE - Annually for women ages 50 to
74
• USPSTF - Every 2 y for women ages 50 to 74

24. USG Breast
• It is primarily used in the diagnostic evaluation of a breast
mass identified by palpation or mammography.
• There is little evidence to support the use of ultrasound as an
initial screening test.

25. ACRIN 666 trial
• Breast ultrasound was offered to women with increased
mammographic breast density and, if either test was positive,
they were referred for a breast biopsy.
• The radiologists performing the ultrasounds were not aware of
the mammographic findings.
• Mammography detected 7.6 cancers per 1,000 women screened
• Ultrasound increased the cancer detection rate to 11.8 per
1,000.
• Additional cancers were identified in 0.42% of women, but
sonography disproportionately increased the number of
biopsies

26. IV . SCREENING MRI
• The sensitivity of MRI for breast cancer detection is estimated at
71% to 100%
• Breast MRI vs mammography
sensitivity >mammography
specificity <mammography
resulting in a higher rate of false-positive findings
• Micro calcifications are not detectable with MRI

27. • MRI of the breast is not a replacement for mammography or
ultrasound imaging but rather a supplemental tool.
• Breast MRI has never been directly compared with
mammography in the general population,

28. Indications :
Annual MRI as an adjunct to mammography starting at age 30 is
recommended for women:
• With a known BRCA mutation.
• Who are untested but have a first-degree relative with a BRCA
mutation.
• Li Fraumeni syndrome
• Cowden syndrome
• Who had been treated with radiation to the chest for Hodgkin
disease

29. NCCN :
• MRI is more sensitive but less specific than mammography,
leading to a high FP rate and more unnecessary biopsies,
especially among young women.
• The impact of MRI breast screening on breast cancer mortality
has not yet been determined.

30. Newer techniques
• Newer technologies may improve screening accuracy for
women with dense breasts.

31. Full field digital mammography
(FFDM)
• Full field digital mammography (FFDM) produces a flat 2
dimensional image.
• It uses a special detector capable of transforming x-ray images into
electronic digital image.
• Advantages Of Digital :
less false positives
no film processing
faster image acquisition
less call backs (due to ability to manage image digitally)
• ACRIN trial—digital = screen film mammography overall
superior in young women and those with dense
breasts.

32. Digital Breast Tomosynthesis (DBT)
• It uses x-rays and a digital detector to generate cross-sectional
images of the breasts.
• Data are limited, but compared to mammograms, DBT appears
to offer increased sensitivity and a reduction in the recall rates.

33. The tomosynthesis mammographic imaging screening trial –NCI
sponsored screening trial comparing the diagnostic accuracy of
screening for breast cancer with 3 D DBT plus two dimensional
FFDM versus FFDM alone

34. Molecular Breast MRI
• Approved by US FDA
• Uses intravenous 99mTc-sestamibi and gamma camers to image
the breast
• Adjunct to mammography

35. Abbreviated (Fast) MRI
• Takes 3-5 mins to image the breast
• More feasible, less costly and more accessible than conventional
MRI
Ultrafast breast MRI :
• It is developed to capture the inflow of contrast in breast lesions
and hence enable dynamic analysis of contrast wash-in rather than
contrast wash-out.
• The technique analyzes the pharmacokinetic characteristics of
breast cancer vasculature, which was shown to allow good
separation between benign and malignant breast lesions

36. SCREENING
RECOMMENDATIONS

37. Screening Women Age 40 to 49
Mammography, like all screening tests, is more efficient in
populations with higher disease prevalence.
• Mammography is, therefore, a better test in women age 50 to
59 years than it is among women age 40 to 49 years because
the risk of breast cancer increases with age.
• Younger women have lower incidence of disease
• A larger proportion have increased breast density, which can
obscure lesions (lower sensitivity).
• Younger women are more likely to develop aggressive, fast-
growing breast cancers that are diagnosed due to symptoms
between regular screening visits.

38. • In a HIP randomised trial,women aged 40-49yrs had mortality
benefit at 18yrs of follow up.
• The Canadian screening trial suggests mammographies and
clinical breast examinations do not decrease risk of death for
woman aged 40 to 49 and that mammographies add nothing to
CBEs for women age 50 to 59 years
• The Kopparberg Sweden study suggests that mammographies
are associated with a 32% reduction in the risk of death for
women aged 40 to 74 years

39. • The USPSTF meta-analysis of eight large randomized trials --
15% relative reduction in mortality (relative risk [RR], 0.85;
95% confidence interval [CI], 0.75 to 0.96) from
mammography screening for women aged 40 to 49 years after
11 to 20 years of follow-up.
• This is equivalent to number needing to invite 1,904 women
over 10 years to prevent one breast cancer death.
• Decision should include—
Benefits
Harms- Over diagnosis, false positive, false negative tests and
radiation induced breast cancer

40. Biennial Vs Annual Screening
• In an effort to decrease FP rates, some have suggested
screening every 2 years rather than yearly.
• The CISNET Model consistently shows that biennial screening
of women ages 40 to 70 only marginally decreases the number
of lives saved while halving the false positive rate.
• Notably, the Swedish two-county trial, which had a planned
24-month screening interval (the actual interval was 33
months) reported one of the greatest reductions in breast
cancer mortality among the RCTs conducted to date.

41. • False negative tests delay diagnosis and provide false
reassurance
• They are common in younger women and those with dense
breasts
• Mucinous and lobular breast tumors also tend to blend in with
the normal breast

42. Risk Assessment
Risk factors for breast cancer include the following:
• 2 fold increase risk : Extremely dense breasts on
mammography or a first-degree relative with breast cancer
• 1.5 - 2 fold increase risk : Prior benign breast biopsy, second-
degree relatives with breast cancer, or heterogeneously dense
breasts.
• 1-1.5 fold increase risk : Current oral contraceptive use,
nulliparity, and age at first birth 30 years and older

44. Average Risk
According to ACS : Average risk women are those without a
• Personal history of breast cancer,
• Suspected or confirmed genetic mutation known to increase
risk of breast cancer (eg, BRCA),
• History of previous radiotherapy to the chest at a young age.

45. ACS-Guidelines
• Women should undergo regular screening mammography
starting at age 45yrs
• Women aged 45 to 54 years should be screened annually
• Women should have the opportunity to begin annual screening
between ages 40-44 yrs
• Women 55 years and older should transition to biennial
screening or have the opportunity to continue screening
annually.
• Women should continue screening mammography as long as
their overall health is good and they have a life expectancy of 10
years or longer.
ACS do no recommend CBE or BSE

46. Others
• The USPSTF, the American College of Physicians, and the
Canadian Task Force on the Periodic Health Examination
recommend routine screening beginning at age 50 years
• NCCN –
 For women between ages 25 and under 40 years, recommends
CBE every 1 to 3 years and breast awareness encouraged.
 For women aged 40 years and older,
-- annual CBE and screening mammography, and
encourages breast awareness.

47. Screening Women at High Risk
High Risk women are those :
• With a known BRCA mutation
• Who are untested but have a first-degree relative with a BRCA
mutation
• Who had been treated with radiation to the chest for Hodgkin
disease
• Who have an approximately 20% to 25% or greater lifetime risk
of breast cancer based on specialized breast cancer risk
estimation models.

48. 5-year Risk Of Invasive Breast Cancer ≥1.7% In
Women≥35 Yrs ( As Per GAIL Model ) :
MODIFIED GAIL model …
• Current age
• Age at menarche
• Age at first live birth or nulliparity
• Number of first-degree relatives with breast cancer
• Number of previous benign breast biopsies
• Atypical hyperplasia in a previous breast biopsy
• Race*
The Gail model is intended for women who have never had a diagnosis
of breast cancer, ductal carcinoma in situ (DCIS), or lobular carcinoma
in situ (LCIS) and who do not have a strong family history suggesting
inherited breast cancer.

49. Women with a Lifetime Risk of Breast
Cancer >20% based on models largely
dependent on family history:
• MODELS – Claus, Tyrer-Cuzick, and other models.
• BRCA risk patients -- BRCAPRO and Breast and Ovarian
Analysis of Disease Incidence and Carrier Estimation
Algorithm (BOADICEA)
• Ontario Family History Risk Assessment Tool
• Manchester scoring system
• Referral Screening Tool
• Pedigree Assessment Tool
• Family History Screen (FHS-7)

50. High risk :
Prior history of breast cancer
• History and physical examination 1-4 times per year as
clinically appropriate for 5 yrs. and then annually.
• Mammography every 12 months.
• Women on tamoxifen : annual gynecological assessment every
12 months if uterus is present.
• If no clinical symptoms or signs of recurrent disease – no need
of metastasis screening.
• Women on aromatase inhibitor – bone health monitoring.

51. • Annual screening Mammographies and MRIs starting at age 30
is recommended for high risk women
• Genetic testing for BRCA1 and BRCA2 mutations and other
markers of breast cancer risk has identified a group of women at
high risk for breast cancer.
• Mammography is less sensitive at detecting breast cancers in
women carrying BRCA1 and BRCA2 mutations, possibly
because such cancers occur in younger women.
• MRI screening may be more sensitive than mammography in
women at high risk, but specificity is lower.

53. Screening –
Special populations

55. • Breast awareness - >18yrs
• CBE – every 6-12 months starting at age 25yrs
• Breast screening:
25-29yrs – annual MRI or Mammogram
30-75yrs – annual mammogram and breast MRI
>75yrs – individual basis
• Risk reduction mastectectomy and counselling
• Risk reduction salpingo oopherectomy –35 – 40yrs
• If not elected risk reducing salpngo oopherectomy then
Concurrent TVS and CA-125 every 6 months starting at 30yrs
or 5-10yrs before earliest age at first ovarian cancer diagnosis in
family.
• Chemoprevention.

57. Clin Breast Cancer. 2007 Dec;7(11):875-82. doi: 10.3816/CBC.2007.n.053.
Bilateral prophylactic oophorectomy and bilateral prophylactic
mastectomy in a prospective cohort of unaffected BRCA1 and BRCA2
mutation carriers.
Friebel TM1, Domchek SM, Neuhausen SL, Wagner T, Evans DG, Isaacs C, Garber
JE, Daly MB, Eeles R, Matloff E, Tomlinson G, Lynch HT, Tung N, Blum JL, Weitzel
J, Rubinstein WS, Ganz PA, Couch F, Rebbeck TR.

58. BRCA Positive Men :

59. Li Fraumeni Syndrome
• For women with a TP53 mutation who are treated for breast
cancer, screening of remaining breast tissue with annual
mammography and breast MRI should continue.
• Discuss option of risk-reducing mastectomy and counsel
regarding degree of protection, degree of cancer risk, and
reconstruction options.
• Address psychosocial, social, and quality-of-life aspects of
undergoing risk-reducing mastectomy.

60. Cowden Syndrome :
• Breast awareness >18yrs
• CBE every 6-12 months >25yrs or 5-10yrs before
Earliest known breast cancer in family
• Annual mammogram and MRI >30-35yrs
• Endometrial cancer – annual endometrial biopsies and/or USG
>30-35yrs
• Option of risk reducing mastectomy

63. Ductal Carcinoma In Situ
• The incidence of noninvasive ductal carcinoma in situ (DCIS)
has increased more than fivefold since 1970 as a direct
consequence of widespread screening mammographies.
• DCIS is a heterogeneous condition with low- and
intermediate-grade lesions taking a decade or more to
progress.

64. • There is little evidence that the early detection and aggressive
treatment of low- and intermediate- grade DCIS reduces breast
cancer mortality.
• The standard of care for all grades of DCIS is lumpectomy
with radiation or mastectomy, followed by tamoxifen for 5
years.
• Genomic characterization will hopefully lead to the
identification of a subset of noninvasive cancers that can be
treated less aggressively or even observed.

65. BENEFITS
• The primary benefit of screening with mammography is a
decrease in breast cancer mortality.
• In a 2015 systematic review and a 2012 meta-analysis --
screening mammography was estimated to reduce the odds of
dying of breast cancer by approximately 20 percent
• The absolute benefit of screening depends on the patient’s age
and is lower in younger women because they have a lower
baseline risk of cancer.
• A 2016 systematic review analyzed risk reduction by age: with
at least 11 years of follow-up,
Age Relative Risk for mortality
39-49yrs 0.92 (95% CI 0.75-1.02)
50 to 59 years of age 0.86 (0.68-0.97)
60 to 69 years of age 0.67 (0.54-0.83)

67. HARMS
• Overdiagnosis –
 Identification of breast cancer that would not have caused clinical
consequences in a woman's lifetime had it not been detected.
 Estimates for overdiagnosis in breast cancer range from 10 percent or
less to over 50 percent of all women diagnosed with breast cancer.
• False-positive mammogram result
 young age, increased breast density, family or personal history of
breast cancer, prior breast biopsies, current estrogen use, three years
between screenings, lack of comparison to prior mammograms, and an
individual radiologist’s tendency to over-read .

69. • Radiation
– Screening mammogram has 4mSv of radiation
Annual mammograms will cause one breast cancer upto 1000
women screened from age 40-80yrs
• Discomfort – Mammographic screening can be uncomfortable
or painful.
• False negative tests :
 Delay diagnosis and provide false reassurance
 They are common in younger women and those with dense
breasts
 Mucinous and lobular breast tumors also tend to blend in with
the normal breast

71. LUNG CANCER SCREENING

72. 1940’s – Chest x ray and sputum cytology
• Diagnosis of an increased number of cancers
• Increased proportion of early stage cancers
• Larger proportion of screen- diagnosed patients surviving more
than 5 years.
Mass lung cancer screening MLP trial

73. Mayo Lung Project (1971)
• 9,200 male smokers
• randomized to either have sputum cytology collected and CXRs
done every 4 months for 6 years or to have these same tests
performed annually.
At 13 years of follow-up
• more early stage cancers in the intensively screened arm (n = 99)
> control arm (n = 51)
• number of advanced tumors was nearly identical (107 vs 109)
• Despite an increase in 5-year survival (35% versus 15%)
intensive screening was not associated with a reduction in lung
cancer mortality (3.2 versus 3.0 deaths per 1,000 person-years,
respectively)

75. • The impact of screening on cancer incidence persisted through
nearly 20 years of follow-up.
• There were 585 lung cancers diagnosed on the intensive
screening arm versus 500 on the control arm (p = 0.009) and
intensive screening continued to be associated with a
significant increase in disease- specific survival.
• However, a concomitant decrease in lung-cancer mortality did
not emerge with long-term follow-up (4.4 lung cancer deaths
per 1,000 person-years in the intensively screened arm versus
3.9 per 1,000 person-years in the control arm).
• This suggests that some lung cancers diagnosed by screening
would not have resulted in death had they not been detected
(i.e., overdiagnosis)

76. A meta-analysis of the three studies evaluating different screening
schedules using chest x ray and sputum cytology found that more
frequent screening was associated with an increase (albeit not
statistically significant), rather than a decrease, in lung cancer
mortality when compared with less frequent screening

77. PLCO trial
(Prostate, Lung, Colorectal and Ovarian) trial
• 10 sites across the United States
• randomized trial
• 55,000 men and women, aged 55 to 74 years.
• Participants were randomized to receive annual, single-view,
posteroanterior CXRs for 4 years versus routine care.
• With 13 years of follow-up, no significant difference in lung
cancer mortality was observed.

78. Oken, JAMA 2011;306(17):1865-1873
• 3 annual chest X-rays (n=77445) vs usual care (n=77456)
• 55-74 yrs, 45% never smokers
Number of lung cancers
1696
vs 1620

79. Oken, JAMA. 2011;306(17):1865-1873
1213-intervention arm
vs 1230 -control
Deaths from lung cancer

80. Bach, ACCP guidelines, Chest 2007;132:69S-77S
Lung Cancer Screening with CT
Diameter 2
mm
8 mm 40 mm 200mm
Nb of cells 4.106 3.108 33.109 4.1012
Screening « window »

81. Smith-Bindman, N Engl J Med 2010;10.1056
Computed Tomography (CT) of the Chest
938mGy/cm
15.9 mSv
88mGy/cm
1.5 mSv
Routine Low-dose

82. Low-dose computerized tomography
(LDCT)
• It uses an average of 1.5 mSv of radiation to perform a lung scan
in 15 seconds.
• A conventional CT scan uses 8 mSv of radiation and takes
several minutes.
• The LDCT image is not as sharp as the conventional image, but
sensitivity and specificity for the detection of lung lesions are
similar.

83. National Lung Screening Trial
(NLST)
• 53,000 persons
Smokers
Former Smokers
≥ 30 PA
Age 55-74
Stop<15 yrs
3 annual LDCT
Chest x ray
Years
0 1 2

84. Positive - “suspicious for” lung cancer
• CT scans that revealed any noncalcified nodule measuring at
least 4 mm in any diameter.
• Radiographic images that revealed any noncalcified nodule or
mass.

85. • With a median follow-up of 6.5 years,
20% relative reduction in lung
cancer mortality
(95% CI, 6.8 to 26.7; p = 0.004)
13% more lung cancers were
diagnosed

86. • Another important finding from the NLST was a 6.7% (95% CI,
1.2 to 13.6; p = 0.02) decrease in death from any cause in the
LDCT group.
• NLST participants were at high risk for developing lung cancer
based on their smoking history.
• Indeed, 25% of all participant deaths were due to lung cancer.
• A further analysis of the NLST shows that screening prevented the
greatest number of lung cancer deaths among participants who
were at the highest risk but prevented very few deaths among those
at the lowest risk.
• These findings provide empirical support for risk-based screening.

87. Limitations of LDCT
• The risk of a False Positive finding in the first screen was 21%.
• Overall, after three CT scans, 39.1% of participants had at least one
positive screening result.
• Of those who screened positive, the FP rate was 96.4% in the LDCT
group.
• Positive results require additional workup, which can include
conventional CT scans, a needle biopsy, bronchoscopy,
mediastinoscopy, or thoracotomy.
• These diagnostic procedures are associated with anxiety, expense, and
complications (e.g., pneumo- or hemothorax after a lung biopsy).
• In the LDCT study arm, there were 16 deaths within 60 days of an
invasive diagnostic procedure. Of the 16 deaths, 6 ultimately did not
have cancer.
• Radiation side effects

88. Overdiagnosis:
• There is a reservoir of biologically indolent lung cancer and
that a percentage of screen-detected lung cancers represent
overdiagnosis.
• The estimated rate of overdiagnosis in the long-term follow-up
of the Mayo Lung Study and the other CXR studies was 17 to
18.5%.
• 8.5% of the cancers diagnosed on the LDCT arm of the NLST
represented overdiagnosis.
• It is not known whether the widespread adoption of LDCT
lung cancer screening will result in higher complication rates
and a less favorable risk–benefit ratio.
• LDCT lung cancer screening should clearly be considered for
those at high risk of the disease.

89. NELSON TRIAL
(Dutch-Belgian Lung Cancer Screening Trial)
 Automated volumetric measurment for
non-calcified nodules

90. Recommendations
ACS
the American College of Chest Physicians (AACP)
the American Society of Clinical Oncology (ASCO)
National Comprehensive Cancer Network (NCCN)

91. • Discuss the benefits, uncertainties, and harms associated with
screening for lung cancer with LDCT.
• The USPSTF guidelines give LDCT a grade B
recommendation, concluding that there is moderate certainty
that annual screening for lung cancer with LDCT is of
moderate net benefit in asymptomatic persons at high risk for
lung cancer based on age, total cumulative exposure to tobacco
smoke, and years since quitting.
ACS USPSTF

92. Newer Modalities
PET –
• Annual low-dose computed tomography (LDCT) f/b PET with fluorodeoxyglucose
(FDG) for evaluating patients with noncalcified lesions ≥7 mm in diameter
• In one study, FDG-PET correctly diagnosed 19 of 25 indeterminate nodules .
• The sensitivity, specificity, positive predictive value, and negative predictive value of
FDG-PET for the diagnosis of malignancy were 69, 91, 90, and 71 percent,
respectively. When a negative FDG-PET was followed three months later with a
repeat CT, the negative predictive value was 100 percent.
Non Radiographic technologies –
• Identification of molecular and protein-based tumor biomarkers, may also contribute
to the early detection of lung cancer.
• Helps to identify people with significantly higher lung cancer risk in whom the
likelihood that radiographic studies would detect early-stage lung cancer is
increased.

93. Technologies under investigation include:
• Immunostaining or molecular analysis of sputum for tumor
markers. As examples, p16 ink4a promoter hypermethylation
and p53 mutations have been shown to occur in chronic
smokers before there is clinical evidence of neoplasia
• Automated image cytometry of sputum.
• Fluorescence bronchoscopy
• Exhaled breath analysis of volatile organic compounds, which
appear to be more common in patients with lung cancer
• Serum protein microarrays for detecting molecular markers
• Genomic and proteomic analysis of bronchoscopic samples
Potential biosamples for biomarker analysis include airway epithelium (including
buccal mucosa), sputum, exhaled breath, and blood . The National Lung Screening
Trial (NLST) has established a biospecimen repository of blood, sputum, and urine
samples serially collected from over 10,000 NLST participants for future
investigation.

94. ●Assessing tumor growth patterns – The Continuous Observation of
Smoking (COSMOS) study investigated whether estimation of the volume
doubling time (VDT) or growth rate of tumors detected by LDCT scans could be
used to determine which tumors may represent indolent cancers and thus potential
overdiagnosis .
• VDT correlated with lung cancer mortality rates (9.2 percent per year for fast-
growing and 0.9 percent per year for slow-growing or indolent cancers).
• Ten percent of the cancers identified in the COSMOS cohort had a VDT of
600 days or more, and 25 percent had a VDT of 400 or more days and thus
might represent overdiagnosis; such tumors might reasonably be managed
with less aggressive intervention.
VDT TUMOR TYPE
<400 days fast-growing
400 to 599 days slow-growing
>600 days indolent