1. The following material is intended for MSKCC internal medicine housestaff teaching
purposes only. The slides were updated for the LibGuide in 2012-2013.

2. Cancer Epidemiology

3. Overall U.S. Cancer Stats
 The U.S. population:
 SEER database (Surveillance, Epidemiology and End
Results):
 National Cancer Institute database tabulating cancer
incidence and mortality figures from 17 sites around the
country

4. Overall U.S. Cancer Stats
 Based on SEER database (Surveillance,
Epidemiology and End Results)
 How many NEW cancer cases in the U.S. expected
for 2010?
*not including CIS except bladder and basal cell and squamous cell skin cancers
 1.6 million American Cancer Society, Cancer Facts and Figures, 2012
 How many cancer deaths in the U.S. expected for
2010?
 577,190 (about 1,500/day; 1 in 4 deaths) American Cancer Society,
Cancer Facts and Figures, 2012

5. Who is at “risk”?
 Everyone
 Most significant risk factor: AGE
 78% all cancers > 55 years
 Lifetime risk
 Men: ~ 1 in 2 (45% risk)
 Women: ~ 1 in 3 (37% risk)
 Relative Risk (RR)
 lung CA in male smokers – RR is 23
 Breast CA in women w 1st degree relative – RR is 2
 What is the Cost?
 NIH estimates: Total $ 263.8 billion in 2010

6. Cancer Epidemiology
 Name the four most common cancers in the
overall U.S. population
 1. PROSTATE
 2. BREAST
 3. LUNG
 4. COLON
 Name the four leading cancers with the
highest mortality in the overall U.S. population
 1. LUNG
 2. COLON
 3. BREAST
 4. PANCREAS

7. 2012: Cancer Incidence &
Mortality
American Cancer Society, Cancer Facts & Figures 2012

8. American Cancer Society, Cancer Facts & Figures 2012

9. American Cancer Society, Cancer Facts & Figures 2012

10. American Cancer Society, Cancer Facts & Figures 2012

11. Cancer Death Rates by
Race/Ethnicity (2003-2008)
American Cancer Society, Cancer Facts & Figures 2012

12. Cancer Deaths Avoided in Men
and Women from 1991-2008
American Cancer Society, Cancer Facts & Figures 2012

13. Global Cancer Stats
Source: Globocan 2008, IARC
 7.6 million deaths in 2008
 What Types of Cancer Cause the Greatest
Number of Deaths Worldwide?
1. Lung cancer: 1.4 million deaths
2. Gastric cancer: 740,000 deaths
3. Liver cancer: 700,000 deaths
4. Colorectal cancer: 610,000 deaths
5. Breast cancer: 460,000 deaths

14. Tumorigenesis &
Classification of Cancers

15. Normal Progression of
Neoplasia

16. What makes a tumor
malignant?
Hanahan & Weinberg. Cell, Vol. 100, 57–70, January 7, 2000
Multiple cumulative mutational events are required for
the progression from normal to malignant phenotype.
At each successive step, mutated cells gain a growth
advantage.

17. Hanahan & Weinberg. Cell, Vol. 144, 646-74, March 4, 2011

18. Loss of Normal Growth
Inhibition

19. Definitions
 Oncogene: a gene which, upon being
activated through gain-of-function
mutation or over-expression, promotes
replication or tissue invasion
 Growth factors
 Transcription factors
 Receptor tyrosine kinases
 Proteins involved in cell cycle

20. Definitions
 Tumor Suppressor
Gene:
 a gene which, upon being
inactivated through loss-
of-function mutation or
under-expression, leads to
cell growth
 Proteins which restrict cell
growth
 Proteins which promote
apoptosis

21. Genetic mutations and
chromosomal abnormalities
 Point mutations
 Insertions / deletions
 Microsatellite instability
 Epigenetic changes (e.g. methylation)
 Telomere lengthening
 Loss of DNA repair genes accelerate the
above changes

22. Tumor Classifications
 Essentially, any cell type in the body can
become cancerous.
 Depending on lineage, a malignant cell
will have certain morphology, staining
characteristics on
immunohistochemistry, and will be
classified accordingly.

23. Cellular Origins of Tumors
Neoplasm
Epithelium
Columnar
Squamous
Germ Cell
Connective
Tissue, Bone,
Muscle
Hematopoietic
Tissue
Melanocytes
Neuroendocrine
Cells
CARCINOMA SARCOMA
LEUKEMIA
LYMPHOMA
MELANOMA
NEUROENDOCRINE
ADENOCARCINOMA
SQUAMOUS CELL CARCINOMA
GERM CELL TUMORS

24. Tissue and cellular analysis:
Immunohistochemistry of
tumors
Carcinoma Sarcoma Leukemia &
Lymphoma
Melanoma Neuroendocrine
Keratins + - - - -
Vimentin &
Desmin - + - - -
CD 45, CD19/20,
CD 3/4/5/8 - - + - -
S-100 - + - + -
HMB-45 - - - + -
Chromogranin,
Synaptophysin,
Silver stains
- - - - +
Stains that are specific for certain carcinomas: PSA, thyroglobulin

25. Concepts in Diagnosis

26. Getting a biopsy sample
Types
 FNA
 Often insufficient;
○ No tissue architecture
○ Limited sample size
 Core biopsy
 Incisional/Excisional biopsy
 Choose your site wisely
 Sampling the lymph node or presumed metastatic site can
give both diagnosis and staging information at the same
time
 Safety, accessibility are always key concerns

27. How we analyze the biopsy
 Tissue level:
 architecture; invasion
 Cellular level:
 histology / morphology
 Immunohistochemistry
○ Expression of
proteins, receptors,
etc.
 surface (CD) markers
(flow cytometry)
 Chromosomal level:
 Karyotyping
 Translocations (FISH)
 Genetic level:
 PCR

28. Karyotyping
 Performed during metaphase, when chromosomes are easily
seen
 Used often in lymphomas and leukemias
www.pathology.washington.edu

29. Fluorescence in situ
Hybridization (FISH)
http://en.wikipedia.org/wiki/Fluorescence_in_situ_hybridization
http://www.kreatech.com

30. Immunohistochemistry
 Lymphoma: BCL2, Ki-67
 Breast: Her2, hormone receptor testing
http://en.wikipedia.org/wiki/Immunohistochemistry
http://www.springerimages.com

31. Flow Cytometry
How Flow Cytometry Works
 Lymphomas are
classified by cell
differentiation
markers (CD)
○ CD 2, 3, 4, 7, 8:
T-Cells
○ CD 19/20: B-cells
○ CD 34: Stem
Cells

32. Polymerase Chain Reaction
(PCR)
 Analyze for specific mutations
 May have prognostic implications
○ AML: FLT3, NMP1
 May identify therapeutic targets
○ NSCLC: EGFR

33. Microarray
 Used for Oncotype Dx
 Level of fluorescence denotes level of
expression compared to control sample http://www.eye-research.org
Adapted from Universitäts-Augenklinik Mainz, Experimentelle Ophthalmologie, Leitung: PD Dr. Dr. F. Grus

34. Concepts in Staging

35. Concepts in Staging: Solid
tumors
 Solid tumors primarily use a TNM system
 T = Tumor size and invasion into nearby structures
 N = Lymph node involvement
 M = Presence of metastasis
 There are variations on this system
 Some use tumor markers (serum markers) as part of
staging
○ Testicular cancer
○ Melanoma

36. Concepts in Staging
 cT1N2M0
 pT1N2M0
 yT1N0M0
c: stage given by clinical
examination of a patient.
p: stage given by pathologic
examination of a surgical
specimen.
y: stage assessed after
neoadjuvant therapy.

37. Prognosticating Cancers
 Staging (T,N,M)
 Prognostic Tools
 IPI for diffuse large B-cell lymphoma
 Adjuvant! Online for breast cancer
 Performance Status

38. Prognosticating Cancers

39. Prognostic or Predictive
 Prognostic Biomarkers:
 Predictive Biomarkers:
Stratifies patients based on risk of an outcome
(recurrence, overall survival) independent of
treatment
• e.g. abnormal LDH in lymphoma
Stratifies patients based on response to specific
treatment regimen
• e.g. Hormone receptor profiling in Breast Cancer

40. Ann Arbor Staging System for
Hodgkin's Disease and Non-
Hodgkin's Lymphoma
Stage I Stage II Stage III Stage IV
• A: Absences of symptoms
• B: B symptoms
• E: Extranodal extension
Adapted from Skarin. Dana-Farber Cancer
Institute Atlas of Diagnostic Oncology. 1991;
with permission.

41. IPI and DLBCL
Sehn L H et al. Blood 2007;109:1857-1861
For diffuse large B cell lymphoma treated
with CHOP:
0, 1 factor = low risk: 35% of cases; 5-
year survival, 73%
2 factors = low-intermediate risk: 27% of cases; 5-
year survival, 51%
3 factors = high-intermediate risk: 22% of cases; 5-
year survival, 43%
4, 5 factors = high risk: 16% of cases; 5-
year survival, 26%
For diffuse large B cell lymphoma treated
with R-CHOP:
0 factor = very good: 10% of cases; 5-
year survival, 94%
1, 2 factors = good: 45% of cases; 5-
year survival, 79%
3, 4, 5 factors = poor: 45% of cases; 5-
year survival, 55%
•Age >60
•Elevated LDH
•ECOG ≥2
•Ann Arbor stage III
or IV
• >1 site of
extranodal
involvement

42. Concepts in Treatment

43. Types of Treatment
 Surgery
 e.g. Lumpectomy
 Radiation (brachytherapy vs. XRT)
 Chemotherapy
 Adriamycin, Cytoxan, Taxol
 Molecularly Targeted Therapies
 Trastuzumab (herceptin)
 Hormonal Therapy
 Immunologic Therapy
 Interferon, ipilimumab
Local Therapy
Systemic Therapy

44. Adjuvant vs. Neoadjuvant
 Adjuvant Therapy:
 Additional cancer treatment given after the
primary treatment to lower the risk that the
cancer will come back.
○ Goal is often to treat micrometastatic disease
for curative intent
 Neoadjuvant therapy:
 Treatment given as a first step to shrink a
tumor before the main treatment, which is
usually surgery, is given.

45. Salvage and Palliative Therapy
 Salvage:
 Treatment that is given after the cancer has
not responded to other treatments.
 Palliative:
 Treatment given to relieve the symptoms
and reduce the suffering caused by cancer
and other life-threatening diseases.

46. Targeted Therapy
Cataldo VD et al. N Engl J Med 2011;364:947-955.

47. Human Epidermal Receptor
Hudis C. NEJM, 2007; 357:39-51

48. RAS/RAF/MEK/ERK
Hudis C. NEJM, 2007; 357:39-51
Cichowski, Nature 2010

49. PI3K/AKT
Hudis C. NEJM, 2007; 357:39-51

50. VEGF
Hudis C. NEJM, 2007; 357:39-51
Croce C. NEJM, 2008; 358:502-511

51. Concepts in Determining
Responses

52. RECIST- Response Evaluation
Criteria in Solid Tumors
 Complete Response (CR)
 No radiographic and no pathologic evidence of disease
 Partial Response (PR)
 30% decrease in sums of longest diameters of lesions
(unidimensional)
 Progression of Disease (POD)
 20% increase in sum of diameters of target lesions and an
absolute increase of at least 5 mm.
○ Note: the appearance of one or more new lesions is also
considered progression
 Stable Disease (SD)
 any tumor shrinkage or growth that does NOT meet above criteria
 Note: Hematologic Malignancies have own scales

53. Understanding Clinical
Research: Survival Outcomes
 Progression-free survival (PFS): length of
time during and after treatment in which a
patient with cancer does not get worse
 Disease-free survival (DFS): length of time
during and after treatment in which a
patient survives without evidence of
disease
 Overall survival (OS)

54. Dr. Bosl’s Four Principles of
Oncology
1. It’s not cancer until proven to be cancer.
2. It’s curable until proven otherwise.
3. It’s treatable until proven otherwise.
4. Even if the cancer isn’t treatable, the patient
is always treatable.