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UME_HemOnc_CancerInstruction for resident 21112022.pptx
1. Introduction of Cancer
Assoc.prof. Yi Hyeon Gyu, MD.PhD.
Dept. Oncology and Hematology
Vinmec International Hospital
College of Health Sciences, VinUniversity
3. MAJOR CAUSES OF DEATH IN VIETNAM
Source: Institute for Health Metrics and Evaluation (http://www.healthdata.org/Vietnam)
4. CANCER STATISTICS IN VIETNAM
• New cancer cases in
2018: 165,000
• Cancer deaths in
2018: 115,000
• 300,000 people
currently living with
cancer
Cancer Control. (2019). Cancers in Vietnam-Burden and Control Efforts: A Narrative Scoping Review.
5. CANCER INCIDENCE IN THE UNITED STATES: 2021
Source: CA: A Cancer Journal for Clinicians, 2021
6. CANCER DEATHS IN THE UNITED STATES: 2021
Source: CA: A Cancer Journal for Clinicians, 2021
7. INCIDENCE OF SPECIFIC CANCERS OVER TIME
Source: CA: A Cancer Journal for Clinicians, 2021
12. WHAT IS CANCER?
• Cancer is a disease in which cells bearing
mutations in critical genes proliferate and survive
in an uncontrolled manner
• Genetic changes/mutations ⇒ loss of
homeostatic control ⇒ unregulated growth
• The cells lose their normal appearance and
behavior and are able to invade surrounding
tissues and metastasize
Seminars in Cancer Biology. (2012). Figure 4.
13. NOMENCLATURE
• Neoplasm = tumor: Abnormal growth or mass of tissue (“neo” = new; “plasma”
= formation); includes both benign and malignant growths
• Malignant = cancer: Has ability to invade tissues and metastasize
• Benign: localized: Does not invade tissues or metastasize
• Cancers are classified according to the cell type from which they arise
• Carcinomas (85% of cancers): From epithelial cells (lung, breast, prostate, colon,
pancreas, oral cavity, skin). Subtype is adenocarcinoma, which arises from
glandular epithelial cells, or squamous cell carcinoma from skin
• Leukemias and lymphomas (8%): From white blood cells
• Sarcomas (1%): From bone, connective tissue, other soft tissues
• Other (6%): Central nervous system, melanoma, germ cell, etc.
14. NEOPLASTIC VS. NON-NEOPLASTIC GROWTH
Increased Increased
Cell number
Clonal Polyclonal
Clonality
Genetic
alterations
Response to
injury/stimulus
Mechanism
Irreversible Reversible
Reversibility
Neoplasia Hyperplasia
Process
15. CANCER SPECTRUM
• Cancer is not just one disease;
there are more than 100
different types of cancer
(cancers of different organs;
cancers due to different
mutations)
• However, the different types
of cancer do have common
properties
Lung
Breast
Colon
Bladder
Prostate
Some common
carcinomas
Leukemia (blood cells)
Lymphoma
(lymph nodes)
Some common
sarcomas
Liposarcoma (fat)
Osteosarcoma (bone)
Myosarcoma (muscle)
16. FEATURES OF CANCER CELLS
• Limitless replicative potential
• Resistance to cell death (apoptosis) ⇒ increased
survival
• Loss of normal cellular differentiation
• Unresponsiveness to regulatory signals
• Recruitment of blood supply (angiogenesis)
• Genetic instability
• Cell spread to unrelated tissues (metastasis)
17. MALIGNANCY EVENTUALLY RESULTS IN INVASION
AND METASTASIS
• Operational definition: Benign tumors are
neither highly invasive nor metastatic, can
be cured surgically
• Malignancies are typically invasive and
metastatic
• “Cancer” implies malignancy, and usually
the potential for metastasis
• Surgery often used in early stages, when
metastasis not present
• Chemotherapy/radiation used when
metastasis present
• Newer forms of therapy: Immunotherapy,
drugs designed to affect specific molecular
targets
Invasion
Metastasis: Melanoma in lung
Penn Collection
19. CANCER METASTASIS
Metastatic melanoma Metastatic prostate cancer
• Cancer often metastasizes first to local draining lymph nodes, then to distant
sites
• Specific cancers often have a predilection for distant site(s) of metastasis
(e.g., GI tumors to liver; lung cancer to brain, bone, liver, adrenals)
Penn Collection
20. EXAMPLE OF CANCER CONSEQUENCES: LUNG
CANCER
• Local symptoms/complications
• Hemoptysis (spitting up blood)
• Obstruction of an airway leading to collapse of lung supplied by the airway and/or
infection distal to the obstruction (post-obstructive pneumonia)
• Direct invasion of adjacent structures
• Pleura and chest wall
• Mediastinum (pericardium, phrenic nerve, recurrent laryngeal nerve)
• Paraneoplastic syndromes (distant effects not due to metastasis)
• Metastasis
• Lymph nodes (hilar, mediastinal)
• Distant sites (bone, brain, liver, adrenals)
• From treatment (surgery, radiation, chemotherapy)
21. CAUSES OF DEATH IN PATIENTS WITH CANCER
• Obstruction/destruction of critical organs ⇒ Loss of normal function
• Infection due to impaired immune responses
• Wasting (cachexia)
• Hemorrhage
22. • In some cancers, can see progressive changes over time leading from
mild dysplasia to full-blown disease. As disease becomes more advanced,
cells look less and less “normal”: Progressively less differentiated
• Changes correlate to gradual, multistep loss of homeostatic controls
CIN = Cervical intraepithelial neoplasia
CANCER EVOLUTION
Normal CIN I CIN II CIN III
23. IMPORTANT TERMS IN CANCER EVOLUTION
• Metaplasia (chuyển sản): Replacement of one cell type with related type (e.g.,
columnar vs. stratified epithelial cell)
• Dysplasia (loạn sản – tiền ung): Slightly abnormal looking cells, disorganized
architecture (e.g., precursor to malignancy)
• Anaplasia (thiểu sản): Undifferentiated features, normal architecture lost, tissue of
origin often unclear
Modified from Wilentz et al. (2000) Cancer Res. 60: 2002
24. COMPOSITION OF SOLID TUMORS
• All tumors consist of two basic cellular components
• Neoplastic cells
• Usually resemble cell type from which they arose
• Major determinant of biologic behavior
• Stroma
• Connective tissue and blood vessels
• Provides support and nutrient supply
26. OVERVIEW OF CANCER STAGING
• Definition: Cancer staging is a description of the extent of cancer involvement
• Takes into account such factors as local size, invasiveness, spread to lymph nodes,
and distant metastasis
• Part of the diagnostic evaluation of any cancer is determination of its stage
• Stage of a cancer affects its prognosis
• Stage of a cancer is a critical determinant of optimal therapy
27. TNM SYSTEM AND TUMOR STAGING
• TNM system is internationally accepted for tumor staging
• Records primary and regional nodal extent or tumor and presence of absence of
metastases
• Categories
• T: Description of primary tumor site
• N: Description of regional lymph node involvement
• M: Description of presence or absence of metastatic spread
• A number is assigned to each TNM category
• The combination of TNM numbers determines the stage
28. STAGE 1
• Stage 1: (T1,N0,M0) Primary tumor limited to organ of origin, no evidence of
lymph or vascular spread. Usually amenable to surgical resection. Long-term
(5 year) survival: 75% to 90%
29. STAGE 2
• Stage 2: (T2,N1,M0) Primary tumor spread into surrounding tissue and
lymph nodes immediately draining tumor region (“sentinel” nodes).
Surgically resectable, but not always entirely. 5-year survival: 45% to 55%
30. STAGE 3
• Stage 3: (T3,N2, M0) Primary tumor large, with fixation to deeper structures
(invasive). Sentinel lymph nodes involved, may be enlarged and fixed to
underlying tissues. Tumor often not fully resectable. 5-year survival: 15% to 25%
31. STAGE 4
• Stage 4: (T4,N4,M+) Extensive primary tumor (may be more than 10 cm in
diameter), has invaded underlying or surrounding tissues. Extensive lymph
node involvement, and evidence of distant metastases. 5-year survival <10%
32. EXAMPLES OF STAGING IN LUNG CANCER
Example Stage*
Solitary 2 cm pulmonary nodule representing cancer; no other
tumor involvement
I
Lung cancer with ipsilateral hilar lymph node involvement II
Lung cancer with contralateral hilar lymph node involvement III
Lung cancer with distant metastases to brain IV
* The staging system is actually more detailed, with subdivisions of each stage
33. CANCER PRESENTATION IN VIETNAM BY STAGE
Note: Data are from 2009. Screening program for cervical, breast, oral,
and colorectal cancer implemented in 2008 with support of the National
Cancer Control Programme.
http://www.cancercontrol.info/cc2016/cancer-control-in-vietnam-where-we-are/
36. EXAMPLE OF TUMOR GRADING: PROSTATE CANCER
• The score is determined
from 2 areas (primary
pattern and secondary
pattern). The 2 scores
are added together to
give a final score
(maximum of 10)
Wikimedia Commons, Creative Commons License. 2019. User Mikael Häggström.
40. RELEVANCE OF TUMOR MARKERS TO TREATMENT
• Endocrine therapy used in management of hormone receptor-positive
breast cancer
• Depleting estrogen with an aromatase inhibitor, which inhibits conversion of
estrogen precursors to estrogen (e.g., anastrozole)
• Targeting the estrogen receptor with a selective estrogen receptor modulator
(SERM) (e.g., tamoxifen)
• Monoclonal antibody to HER2 used in HER2+ tumors (e.g., trastuzumab)
42. WHAT IS CANCER SCREENING?
• Definition: Cancer screening refers to a test or examination performed on an
individual without any symptoms or findings suggesting a cancer is present
• Goal: Detect a cancer in order to provide early therapeutic intervention that
will improve outcomes and prevent death
• Underlying scientific assumption and rationale for screening: Cancer starts
with a small, localized tumor that progresses in size, spreads regionally, and
metastasizes to distant sites
• Early detection can identify a localized, asymptomatic primary tumor and prevent
progression and spread
43. POTENTIAL HARMS OF CANCER SCREENING
• Anxiety regarding identification of a finding that may not be important
• Identification of a false positive (positive test but no cancer present)
• Identification of a cancer that may not be clinically important
• Cost of screening and subsequent testing
• Radiation exposure (when screening involves X-rays)
• Complications from invasive diagnostic or therapeutic procedures
44. PERFORMANCE CHARACTERISTICS OF A
SCREENING TEST
Characteristic Description Formula
Sensitivity
Proportion of individuals with a positive
screening test among all individuals with
the disease
TP/(TP + FN)
Specificity
Proportion of individuals with a negative
screening test among all individuals
without the disease
TN/(TN + FP)
Positive predictive value (PPV)
Proportion of individuals with a positive
screening test who have the disease
TP/(TP + FP)
Negative predictive value (NPV)
Proportion of individuals with a negative
screening test who do not have the
disease
TN/(TN + FN)
TP = true positives, TN = true negatives, FP = false positives, FN = false negatives
45. ADDITIONAL FACTORS REGARDING SCREENING
• As sensitivity of a screening test increases (i.e., greater likelihood of detecting
a cancer), the specificity decreases (i.e., greater likelihood of picking up a
false positive)
• Some screening tests (e.g., mammogram, chest CT scan) are subjective and
operator dependent (i.e., dependent upon the skill of the radiologist)
• Positive predictive value (PPV) and negative predictive value (NPV) depend
upon disease prevalence
46. IMPORTANT CHARACTERISTICS FAVORING
SCREENING
• Characteristics of the screening test
• High sensitivity and specificity
• Acceptable to the patient
• Relatively inexpensive when applied to
large numbers of individuals
• Characteristics of the disease
• Relatively high prevalence in the
population
• Available, effective treatment
• Demonstrable effect of early
intervention on outcomes
47. CAUTIONS: BENEFITS OF A SCREENING TEST
• Lead time bias
• Screening results in earlier diagnosis than would have occurred in absence of
screening
• Survival is time measured from detection until death: Will appear prolonged with
earlier detection, even when course of disease is unchanged
• Mortality is deaths at a given interval after screening vs. no screening: Is not
affected by lead time bias
• Overdiagnosis
• Detection of tumors that are not biologically destined to harm the patient
• Detection of tumors that will not cause harm in the lifespan of the specific patient
48. LEAD TIME BIAS
Lead time makes survival longer, but mortality has not
improved and screening was not beneficial
Mortality also improved and screening (with
treatment) was beneficial
Course of disease without screening
Source: Cancer: Principles and Practice of Oncology, 10th ed. Wolters Kluwer, 2015.
49. SCREENING FOR SPECIFIC CANCERS
• Screening recommendations
available
• Breast
• Colon
• Cervix
• Lung
• Prostate
• No definite screening
recommendations
• Ovary
• Uterine (endometrial)
• Skin
• Esophageal
• Gastric
• Pancreatic
• Liver
50. SCREENING FOR BREAST CANCER
• Screening with mammography in women 40 to 75 years old reduces
relative risk of breast cancer death by 10% to 25%
• Risk–benefit ratio seen particularly in women over age 50
• Studies vary regarding benefit in women between 40 and 49
• Breast self-examination has not been shown to reduce mortality
• Current guidelines in United States vary by society
• Definite: Mammography screening ages 50 to 74
• Debate: Start at age 40 vs. individual decision between ages 40 and 49
• Debate: Screen annually vs. every two years
• More intensive screening recommended for patients at higher risk
51. SCREENING FOR COLORECTAL CANCER
• Earlier tests used for colorectal cancer screening: Rigid sigmoidoscopy, flexible
sigmoidoscopy, fecal occult blood testing, barium enema
• Rationale for current preferred method: Colonoscopy
• Can detect early cancers throughout entire colon
• Can detect and remove precancerous polyps
• Screening reduces incidence and mortality of cancer by 20% to 30%
• Current guidelines in United States for individuals at average risk
• Preferred: Start screening at age 50 (until age 75) with colonoscopy every 10 years
• Other options: Flexible sigmoidoscopy every 5 years; annual high sensitivity fecal
occult blood testing, barium enema every 5 years
• More intensive screening for individuals at high risk
52. SCREENING FOR CERVICAL CANCER
• Pap smear of cervix with cytologic examination traditionally used to detect pre-
malignant and malignant cells from the cervix
• More recent: HPV testing on the cervical smear, often done in addition to
cytologic examination
• Current guidelines in United States
• Women ages 21 to 29: Screening with cervical cytology every three years
• Women ages 30 to 65: Screening every five years with both HPV testing and
cytology (or every three years with cytology alone)
53. SCREENING FOR LUNG CANCER
• Screening with chest X-ray or sputum cytology has not definitely been shown to
reduce mortality
• Screening with low-dose chest CT scan reduces mortality by 20%
• Concern with screening: >90% of abnormalities detected on screening are benign
• Screening is done only in high-risk individuals: Smokers or ex-smokers (who have
quit within the past 15 years) with more than 30-pack-year history of smoking
• Age to start screening: 55 years old
• Age to discontinue screening: 74 to 80 years old (recommendations vary)
• Recommendation for shared decision-making between patient and doctor, with
patient informed about benefits and risks
54. SCREENING FOR PROSTATE CANCER
• Screening done by measurement of serum prostate-specific antigen (PSA)
• PSA is glycoprotein produced by prostate gland
• Not specific for cancer: May be elevated with benign prostatic hypertrophy (BPH),
prostate inflammation, prostate trauma
• Controversy about screening: Lead time bias and overdiagnosis
• Many men die with prostate cancer, not from prostate cancer
• Risks of overdiagnosis: Anxiety, complications from biopsy and treatment
• Recommendations in United States have varied over time
• Shared decision-making discussion with men about benefits and risks
• If decision to screen, start at age 50, screen every one to two years, up to age 70
55. CANCER SCREENING IN VIETNAM
• Viet/American cervical cancer prevention project: Pap screening program
starting in 1996
• Decrease in cervical cancer incidence from 29.2 per 100,000 in 1998 to 16 in
100,000 in 2003
• No national screening program in place
• Survey data: 25% of women between 18 and 69 years old ever had cervical cancer
screening (32% between ages 30 and 49)
• Pilot programs for cancer screening in Vietnam from 2008 to 2015
• Cervical cancer screening using Pap smears
• Breast cancer screening with breast examination
• Oral cancer screening with visual inspection
• Colorectal cancer screening with fecal occult blood testing
• Pilot programs have only reached 2% of target population
Cancer Control. (2019). Cancers in Vietnam-Burden and Control Efforts: A Narrative Scoping Review.
