general oncology from devita presentation

1. Dr. Chanchal

2. Definition-
 It is a process by which peoples who have no symptoms were
undergone a test or procedure at regular intervals up to particular limit
of life.
 Screening is offered in apparently normal individuals.
 Cancer screening is a secondary form of cancer prevention.
 Fixed group of tests as per guidelines have been done.
 Usually theses tests are not confirmatory for cancer but indicate that a
cancer may be present.

3. Goal of cancer screening:
 To detect cancer at early stage to prevent death & suffering from the
disease.
 Treatment by using minimum therapeutic intervention.
At least four requirements must be met for screening to be
efficacious:
1. The disease burden must be significant.
2. The natural history of the disease must have a detectable preclinical
phase.
3. An acceptable screening test must be available for early detection of
cancers.
4. Treatment started earlier due to screening test must results in an
improvement in outcome.

4. Abnormal Normal

6. Screening Surveillance
People who have no symptoms were
undergo test usually at regular intervals at
certain times in person’s life.
It is continuous, systematic collection and
analysis of particular health problem in
particular risk group of patients.
Fixed – tests as well as time of initiation
of screening
Flexible – tests as well as
Time of initiation of surveillance may
vary.
Employed on general population of that
area.
Employed on particular high risk group
of patients.
Basic goal is early detection of a
subclinical condition.
Basic goal is prevention and control of
particular condition consequences.
Ex. Screening tests applied in general
population group.
Ex. Surveillance of breast cancer in BRCA
+ve case (high risk).

7. Principles of screening [Wilson & Junger, WHO Report 1968]-
 The condition must be an important health problem.
 There should be existence of a suitable diagnostic test.
 The test should be acceptable by general population.
 Facilities for that acceptable diagnostic test should be available.
 The natural history of disease or time line of disease must be clearly understood.
 There should be a recognized latent or pre clinical phase.
 There should be acceptable and recommended treatment guidelines for that
particular disease.
 The cost of case finding should be economically balanced.

8. PROGRAMMATIC / ORGANISED
SCREENING
OPPORTUNISTIC SCREENING
Screening offered to groups of people through a
well coordinated program.
Happens when an individual asks the doctor/
health professional for a test.
OR
Test is offered by a health professional
Screening services has been monitored &
evaluated.
No monitoring or evaluation done.
All subjects are offered with same services,
information & support
Different subject may be offered with different
services.
Large number of people are invited to take part Subjects make their own appointment for test
or undergo test during medical visit for other
reasons
More Useful to the community Less useful to the community

9. 9
Screening benefits
Improved outcome for those with
+ve screening tests
Less radical Rx needed
for cure in early stages
Assurance and decrease
in anxiety for those with
–ve test results
Others -
•Early stage of diagnosis.
•Less chances of systemic spread.
•Higher chance of curative intent of treatment.

10. 10
Screening - risks
Longer morbidity for
peoples whose prognosis
remains unaltered
Overtreatment of
questionable abnormalities
False assurance for
those with false – ve
results
High anxiety & morbidity
for those with false +ve
results
Hazard of screening
e.g., radiation
exposure,
invasiveness due to
test.

11. Short term outcomes-
 No. of individuals in the target population who were offered screening.
 No. of individuals in the target population who received screening.
 Proportion of target population who were examined by multiple screening
tests.
 Proportion of abnormal screened individuals comes out to have definite
diagnosis of cancer.
 Monetary cost per cancer detected patient.
 Sensitivity & Specificity of screening test.
 PPV & NPV of screening test.

12. Long term outcome-
 Stage wise distribution of detected cancer.
 Case fatality rate.
 Cause specific cancer mortality rate.
 Total monitory costs of programme.

15. There must be balance between cost & benefits of screening test.
Basic models for the evaluation of costs & outcomes:
 COST BENEFIT ANALYSIS-
◦ Expressed in terms of monetary benefit.
◦ Difficult & arbitrary.
 COST EFFECTIVENESS ANALYSIS-
◦ Expressed in terms of health outcomes benefit.
◦ Cost to detect one cancer case, prevent one cancer related mortality, addition of a
year of life , improvement in QOL etc.
 MARGINAL COST PER YEAR OF LIFE SAVED[MCYLS]-
◦ Most appropriate estimate of cost effectiveness of cancer screening at the most
basic level.
◦ Marginal costs= Cost of screening program- Cost of case detection &
management without screening
◦ Marginal effectiveness= Years gained by screening- years expected without
◦ MCYLS= Marginal cost/Marginal effectiveness

16. •The point in the natural history of disease before which therapy is most effective is
termed as critical point.
•Screening tests are only effective if the condition or disease has a critical point.
•Treatment provided before the critical point is more efficacious than treatment
provided later.

17. 17
Screening program –
evaluation bias
Lead time bias Length time bias
Over diagnosis Self - selection

18. Lead time:
 The duration of time between a cancer detected by screening test
minus cancer detected due to development of symptoms is termed as
lead time.
Lead time bias:
 If there is earlier detection of disease due to screening but still death
occurs at the same time as it would occur in the absence of screening,
then there will be a false appearance of increase in survival due to
screening. This is referred to as lead-time bias.
 Lead time bias occurs when the natural history of disease is not
affected by screening.

19. Lead time bias:

20. Length time bias:
 Screening was usually found to be effective in detecting slow
growing & less aggressive disease because of long pre-clinical phase.
 Less successful at detecting more aggressive, faster growing disease
because of very short pre-clinical phase available for detection of
disease with screening.
 Biological behavior of disease affects the results from screening test.
 Length time bias will create the impression that screening is more
effective & improve survival more than it actually do.
 But this improvement in survival is actually due to less aggressiveness
of disease & good prognosis.

21. Length time bias:
Slow progressive / indolent disease-
•Longer preclinical phase
•Less chance of death due to disease.
•This improvement in survival is not due to screening but due to less aggressive
biological behavior of disease

22. Over diagnosis bias:
 Form of length time bias.
 When the screening test will able to detect the disease in early course of
time but that disease will not going to harm the patient in whole life.
 Disease may remain subclinical through out life.
 Ex. Ca prostate diagnosed at 70 yrs of age patient.

23. Stage shift-
 Cancer detection at an earlier stage may be possible by screening test
but still patient will not going to benefit as patient may show stage
shift later in life (Develop metastasis later).
 Both lead time bias and length bias contribute to this phenomenon.
 Ex. – Men undergo screening test and diagnosed as localized ca
prostate. Patient underwent radical prostatectomy but later he develop
relapse due to unrecognized micromets.

24. Self selection bias-
 Also k/a healthy volunteer effect.
 Due to people who voluntarily participate in a clinical trials.
 They must be more health conscious, more likely to control risk
factors & more alert to s/s of disease.
 Misinterpretation of better survival & recovery statistics.
 Adequately controlled for by randomization procedures (RCT).

25.  The U.S. Preventive Services Task Force (USPSTF) and the American
Cancer Society (ACS) are two organizations that issue widely used
cancer guidelines.
 Both use methods that comply with National Academy of Medicine
standards.
 Cancers for which screening is recommended for average risk
population-
◦ Breast cancer.
◦ Cervical cancer.
◦ Prostate cancer.
 Cancers for which screening is recommended for high risk population
only-
◦ Colorectal cancer.
◦ Lung cancer.
◦ Liver cancer.
◦ ovary cancer.

27. Breast is perfect organ for screening because-
 Leading cause of premature mortality.
 Slow progressive disease, hence having sufficient preclinical phase.
 Availability of acceptable screening tools.
 Screening is associated with reduced breast cancer morbidity and
mortality (30-40%).
 Availability of acceptable treatment guidelines.

28.  Clinical encounter-
• Medical history –r/o any co-morbidity, estimate life expectancy.
• Family history- if positive consider for genetic testing.
• Risk assessment-using Gail, Claus, BRCAPRO etc.
• CBE-r/o cases of ca breast.
• Women should be counselled regarding potential benefits, risks and limitations of breast
screening.
 Upper age limit for screening in breast still not established as per NCCN-2019.
◦ ACS- till life expectancy is >10 yrs.
◦ USPSTF- 75 Yrs.
 For women with dense breast explain the need of supplementary screening test
◦ Low sensitivity of mammogram.
◦ High risk of breast cancer (2 fold ).
 3D-Mammograms appears to be helpful in young women and women with dense
breast.

29.  Multiple studies shows that tomosynthesis can improve the cancer detection
rate and decrease the call back rate.
◦ More radiation exposure, more expensive and more time consuming procedure so still
not recommended as first choice.
 USG breast also shown to improve the cancer detection rate.
◦ Operator dependent.
◦ Increase in call back rate.
◦ Increase benign breast biopsy rates.
 FDA approved role of MRI only in screening of high risk cases.
 No role of molecular imaging in breast cancer screening-
◦ Breast specific gamma imaging.
◦ PET –CT scan.
 No role of thermography or ductal lavage as a part of screening procedures.

30. Breast cancer screening tools-
• Breast self examination (BSE)
• Clinical breast examination (CBE)
• Mammography.
• Tomosynthesis.
• Ultrasonography.
• Magnetic resonance imaging

31. Breast self examination (BSE)-
 It is the integral part of breast awareness and education.
 Local health provider educate the female about normal breast.
 Provide training for BSE.
 BSE should be done 2-3 days after menstruation.
 Educate her about the signs and symptoms of malignancy.
 Counsel the female about the risks and benefits of screening.

32. Step – 1
 Begins by looking at breasts in the mirror with shoulder straight and
arms on hips.
Step – 2
 Now, raise arms look for any warning signals in armpits.
Step – 3
 Next, feel the breast in lying down position with flat fingers in up &
down, circular and wedges.
Step - 4
 Feel for the breasts in standing or sitting.
Step - 5
 Check for any nipple discharge in last.

34. 2 large trials
St Petersburg, Russia (122,471
women)
Shanghai, China (266,064
women)
• Women in experimental group were meticulously trained in proper BSE technique
and had reinforcement sessions.
• Follow up period was 9-11 years.
• Result :
• No decrease in breast cancer mortality.
• No improvement in the number or stage of cancers detected.
• There were e/o harm –
• Nearby 2 fold increase in false +ve results, physician visits, and Bx for
benign diseases.

35.  It is the physical examination of breast done by a trained clinician.
 Between 20 – 39 years, CBE is recommended every 3 years in this
age group.
 At 40 years, it should be done annually, ideally near or prior to the
time of annual mammography.
 It includes systematic physical examination of breast by inspection,
palpation breast, axilla and supra-clavicular fossa.
 Sensitivity= 54%, specificity=94%
 No RCT for CBE alone has been done as a screening modality.

36. Mammography
Types of mammogram
 Baseline mammogram-
◦ Ist mammogram of female.
 Screening mammogram-
◦ Done on an asymptomatic female.
◦ Only two specific views were taken for each breast.
◦ No need of radiologist supervision.
 Diagnostic mammogram-
◦ Done on a symptomatic female.
◦ Additional views may be taken for each breast.
◦ Need radiologist supervision.

39. 3D- Mammography
 Also k/a Tomosynthesis.
 Can be considered for dense breast
and in high risk cases if MRI is not
available (NCCN-2019).
 60 consecutive films were taken for
interpretation.
 Computerized system has been used
for reconstruction of 3D images of
breast.
 Advantages-
◦ Overlapping of tissue is avoided so, less
chances of artifacts as well as missing of
lesion.
 Disadvantages-
◦ More time consuming.
◦ More radiation exposure.
◦ Requires huge storage capacity.

43.  Since 2015, recommended age to start screening with mammography
in an average risk women is 40 years.
 Since 1963 till 1991 nine RCT’s have included 40-49 years age
group. Women (>2,00,000) participants.
 Two trials, the CNBSS-1 and CNBSS-2, showed no benefit for this
age group even with longer follow-up.
 Meta-analysis of other eight trials suggest a benefit (risk reduction
15%-40%) if we start mammographic screening at age of 40 years.
 Benefits –
◦ Mortality reduction.
◦ Less aggressive treatment required.
◦ More range of treatment options.

45.  Evaluation of CISNET model of benefits of screening women between 40-
49 yrs by using annual breast mammography (Engel et al-2015)
◦ Saves 30% more lives as compared to biennial screening.
◦ Saves 34% more life years as compared to biennial screening.
◦ Reduces breast cancer specific mortality rate-
 0.6/1000 deaths in 40-45 yr age group.
 0.7/1000 deaths in 45-49 yr age group.
 Breast cancer screening if done annually-
◦ Decrease in breast cancer mortality.
◦ Better patient management.
◦ Early detection of DCIS before conversion to invasive cancer.
CISNET- cancer intervention and surveillance modeling network.

47.  Radiation dose= .1-.2 cgy.
 Radiation dose delivered by MMG is
equivalent to 5 CXR-P/A view.
 It has been estimated that annual
mammography will cause up to one
breast cancer per 1,000 women
screened from age 40 to 80 years.
 Women with BRCA1 or BRCA2
mutations are at increased risk for
radiation-induced oncogenesis,
because of impaired DNA repair
mechanisms .

48.  USG as screening test is not recommended as 1st line investigation in breast.
 Can be considered in females with dense breast.
 Used in conjunction with mammography in young females.
 Features of malignancy on USG breast-
◦ Spiculation.
◦ Angular ill-defined margins.
◦ Heterogenicity.
◦ Hypervascularity.
◦ Extension of lesion into duct.
 Disadvantages-
◦ Operator dependence
◦ High false positivity rate.
◦ Increased breast biopsy rate leading to increase in patient anxiety.
◦ Increase rate of follow-up imaging.
◦ Increase in recall rate.

49. Senstivity=80-85% specificity= 65-70%

50.  Recommended only for the high risk group.
 Annual MRI begins 10 yrs after RT but not prior to 25 yrs.
 Preferably be performed on day 7-15 of menstrual cycle.
 Limitations-
◦ Requires a dedicated breast coil.
◦ Requires an expert radiologist and ability to perform guided biopsy if required
◦ Availability issues.
◦ Expensive and more time consuming.
 Higher sensitivity (71-100%) but low specificity (37-97%) as compared to
Mammography hence having high false positivity rate.
 Micro calcifications are not detectable on MRI.
 No RCT for impact of screening MRI on survival in breast screening.

51. Evidence based recommendations of MRI screening-
 First degree relatives of BRCA carriers who are untested.
 Life time risk of ≥ 20% as defined by models that largely depend on
family history ex. Claus, BRCAPRO, BORDICEA and Tyrer-cuzick
models.
 5 yr risk of invasive breast cancer ≥ 1.7% in women ≥ 35 yrs
(modified Gail model).
Expert based recommendations of MRI screening-
 RT to chest wall b/w 10-30 yr of age.
 Life time risk of breast cancer is ≥ 20% based on previous H/O LCIS
and ADH/ALH
Indications of Breast screening with MRI

52. No sufficient evidence for or against MRI screening-
 Life time risk of 15-20% as defined by models that largely depend on
family history ex. Claus, BRCAPRO, BORDICEA and Tyrer-cuzick
models.
 Extremely dense breast on mammogram.
 Females with personal h/o breast cancer including DCIS.
No recommendations of MRI screening-
 Women with ≤ 15% life time risk.

53. Contraindications to performing
breast MRI-
 Patient's inability to lie prone.
 Marked spine abnormality like -
kyphosis or Scoliosis.
 Marked obesity.
 Extremely large breasts.
 Severe claustrophobia.
 History of allergy to contrast media.
 Pacemaker, Cochlear implant or any
other metallic implant inside body.

54. Breast MRI enhancement curves-
 Following administration of Gadolinium there were three
possible enhancement kinetic curves for a lesion on breast MRI.
 Kuhl’s enhancement curves-
◦ Type I curve: Progressive enhancement pattern
 Continuous increase in signal intensity throughout time .
 Usually considered benign with only a small proportion of (~6%) of malignant lesions
having this pattern
◦ Type II curve: Plateau pattern
 Initial uptake followed by the plateau in enhancement pattern.
 Considered for risk of malignancy (7-28% risk of cancer)
◦ Type III curve: Washout pattern
 Relatively rapid uptake followed by rapid wash out.
 Strongly suggestive of malignancy (>29% risk of cancer)

56. Average risk group High risk group
Those women who do not have –
•Personal H/O breast cancer.
•Family H/O breast cancer.
•Genetic mutation related to breast cancer.
•H/O RT to chest wall at age< 30 yrs.
•Risk of breast cancer in this group is same
as that of general population of that area.
Those women who have -
•Women with personal h/o breast cancer .
•Women with pedigree suggestive of genetic
mutations ex. BRCA mutation.
•Life time risk of ≥ 20% as defined by
models that largely depend on family history.
•5 yr risk of invasive breast cancer ≥ 1.7% in
women ≥ 35 yrs (modified Gail model).
•Life time risk of breast cancer is ≥ 20%
based on previous H/O LCIS and
ADH/ALH
•H/O RT to chest wall b/w age-10 to 30 yrs

58. Score ≥ 1.7% in female ≥ 35 yrs is considered as high risk

59. Screening test Average risk group High risk group
BSE •Breast awareness.
•Start at ≥ 20 yrs of age.
•2-3 days after
menstruation.
•Every month.
Same as average risk
group.
CBE •Start at ≥ 20-39 yrs of age
every 3 yearly.
•At ≥ 40 yrs of age-
annually.
Every 6 monthly.

60. Screening test Average risk group High risk group
Mammography •Started at 40 yrs of age till
75 yrs or till pt have good
health.
•Done annually.
•10 yrs prior to youngest
family member diagnosed
with disease but not before
30 yrs.
•Start at ≥ 30 yrs of age.
•Done annually. ( alternate
with MRI every 6 monthly)
MRI •Not recommended •10 yrs prior to youngest
family member diagnosed
with disease but not before
25 yrs.
•Start at ≥ 25 yrs of age.
•Done annually (alternate
with MMG every 6

61. Clinical encounter-
•Medical history.
•Family history.
•Risk assessment.
•CBE.
Breast awareness-
•Education provided by local health provider about normal breast.
• About Signs and symptoms of malignancy.
•About how to do BSE.
•Counsel the female about the risks and benefits of screening.

64. Screening test BRCA +ve
women
BSE •Breast awareness.
•start at 18 yrs of age.
•2-3 days after menstruation.
•Every month.
CBE •Start at 25 yrs of age every 6 monthly.
Mammography •Start at 30-75 yrs of age annually.
•Consider for tomosynthesis.
MRI with contrast •Start at 25-75 yrs of age annually.
Discuss risk reducing options with patient

65. Screening test BRCA +ve
women
BSE •Breast awareness .
•start at 35 yrs of age.
•Every month.
CBE •Start at 35 yrs of age annually.
Mammography •Not routinely done
•Only when pt had gynecomastia or any
other abnormality in breast.
MRI with contrast •Start at 40 yrs of age annually.
Start prostate cancer screening at 45 yr of age.

66.  Counsel the patient for risk reduction
strategies.
◦ RRM.
◦ RRSO.
◦ Chemoprevention.
 Educate pt for BRCA related cancers.
 Start ovarian screening at age of 35 yrs.
 Start prostate screening at age of 45 yrs.
 Rule out pancreatic malignancy with
investigational protocol.
 Full body skin and eye examination for
melanoma.
 Need of genetic counselling for relatives at
risk.

73. Study Compliance % reduction in breast cancer
deaths
95% CI
Years of follow-up Reduction
HIP 65% 10 29% 11 to 44
Malmo
MMST-1
74% 9 4% 35 to 32
Swedish study 89% 16 29% 17 to 43
Edinburgh 61% 7 17% 18 to 42
Stockholm 81% 7 24% 16 to 50

75. 75
Programmatic / Organized
screening
•Screening program done in a well
defined & co-ordinated manner.
•Monitored and evaluated.
• offered to large group of people
Follow specific screening
cascade. Epidemiologist
reaches to population
Opportunistic screening
•Not defined & co-ordination
•No monitoring and evaluation.
•Offered to particular individual
Done often when a person presents to
the health system
Actively offered by a
health professional
It is requested
by an individual
OR
Screening
Follow specific screening
cascade