Principles of Cancer Care

1
Principles of Cancer Care

• Introduction
• Overall cancer incidence rising
• breast, colon, lung, prostate,lymphoma
• Some cancers have reduced incidence
• cervix, stomach, endometrial
• Second highest cause of mortality

2
Principles of Cancer Care

• Terminology
• Neoplasia - new growth
• malignant - uncontrolled growth and dissemination
• Hyperplasia - increased cell number
• Metaplasia - mature cell type replacement
• Dysplasia - altered epithelial cell size, shape
  and orientation. CIS most severe form

3
Principles of Cancer Care

• Causes of Neoplasia
• Immunodefficiency - transplant tumours, Kaposi
• Familial - Breast cancer, MEN, Lynch, FAP,
• Physical carcinogenesis
• foreign body - asbestos
• ionizing radiation
• Chemical carcinogenesis
• Viruses

4
Biology of Cancer

• Clonality
• Most tumours arise from a single altered cell
• Most transformed cells die or are destroyed
• Surviving cell
• heritability
• escape from normal control

5
Biology of Cancer

• Tumour volume doubling
• Single cell - 30 doublings ? 1 cm3
• Lethal at 40 doublings - 1 kg
• Tumour growth is initially fast - followed by
  growth deceleration
• Clinically doubling in tumour size over 2-3 months

6
Tumour With Hypoxic Cells
7
Biology of Metastasis

• Tumour acquires blood supply even before they are
  palpable Þ early metastatic potential
• Cure of cancer must include
• attempt to eradicate primary completely
• attempt to eradicate metastasis

8
Biology of Metastasis

• Active or passive dissemination of neoplastic
  disease from primary to distant site
• change enables cells to enter circulation
• adherence to endothelial walls
• extravasation
• invasion of stroma

9
Biology of Metastasis

• Haematogenous spread
• most tumour cell in bloodstream are rapidly
  destroyed
• lt 0.1 of cells survive to invade
• surviving cells are selected resistant
  subpopulation of primary tumour
• Subpopulation characteristics for metastasis
• destruction of basement membrane to enter vessel
• survival of blood turbulence
• appropriate ligand for cell adhesion molecule
• motility ability
• degradative enzymes - collengenase type IV

10
Biology of Metastasis

• Subpopulation characteristics for metastasis
• successful tumours can grow to 1-2 mm
• further growth requires acquisition of blood
  supply
• angiogenesis is active process requiring tumour
  angiogenic factors

Highly vascular tumours have increased potential
for metastasis - more likely that suitable cell
will eventually enter blood stream
11
Biology of Metastasis

• Lymphatic spread
• Host invasion causes lymphatic vessel penetration
• Tumour emboli may get trapped in first node or
  bypass to more distant node - skip lesion
• Lymph nodes react to tumour and enlarge
• Are nodes a barrier/filter ?
• Lymphatic /vascular anastomosis exist
• nodal enlargement is a marker for dissemination

12
(No Transcript)
13
Blood Supply of the Colon
14
Biology of Cancer

• Mortality from cancer
• Local tumour effect
• Metastatic disease
• Systemic effects
• malnutrition
• depression of immunocompetence
• cytolkine/other compound release
• Understanding each tumour natural history is
  essential for therapy planning
• e.g. difference in breast Ca and head/neck Ca

15
(No Transcript)
16
Biology of Cancer

• Mortality from cancer
• Local tumour effect
• Metastatic disease
• Systemic effects
• malnutrition
• depression of immunocompetence
• cytolkine/other compound release
• Understanding each tumour natural history is
  essential for therapy planning
• e.g. difference in breast Ca and head/neck Ca

17
Importance of Early Detection of Tumours

• Too early for mutation to cells that can spread
  - eradicated before metastasis
• Treatment may reduce tumour bulk enough for
  immune system to manage
• Too early to acquire resistance to chemotherapy

18
Screening for Tumours

• High incidence population
• Population at risk
• Hep B carriers - HCC
• APC gene and FAP
• racial - Japanese and stomach cancer
• Familial breast cancer
• Sensitive, cheap non invasive tests
• pap smear, faecal occult blood, mammogram
• Early stage of tumour - treatment makes a
  difference

19
Screening for Tumours

• Lead Time Bias
• diagnosis made earlier, prognosis not made better
• Length Bias
• slow growing tumours, longer preclinical stage
• Self Selection Bias
• persons who present themselves for screening cf.
  The general population

20
Surgical Principles

• Diagnosis
• Staging
• Fitness for surgery / treatment
• Surgery and or other treatment

21
Surgical Principles

• Methods of Diagnosis
• Fine needle aspiration
• Histology
• incision
• excision
• luminal
• percutaneous wide bore needle - guided by
  imaging
• Tumour markers

22
Window for FNA
23
(No Transcript)
24
(No Transcript)
25
Laparoscopic Biopsy
26
Lap Biopsy of Liver Lesion
27
Surgical Principles

• Staging - UICC normenclature
• T -tumour
• N- nodal status
• M - metastasis
• The T,N,M is transcribed to a stage group I,
  II, III, IV

28
Pericolic perirectal tissue
29
(No Transcript)
30
Surgical Principles

• Stage Groups
• I - early treatable
• II - early treatable (nodes ve)
• III - locally advanced
• IV - Metastatic

Stage I II early - curative approach Stage
III locally advanced - potential for cure Stage
IV systemic - palliation
31
Surgical Principles

• Staging
• Clinical
• Imaging
• Intraoperative
• Pathological - pTMN

32
Surgical Principles

• Fitness for surgery/treatment
• CVS, Renal, endocrine, Resp., haematopoetic
• Additional test if warranted e.g. 2D ECHO
• Specific situations -
• Liver - Childs grade
• Thorax - spirometry, blood gases

33
(No Transcript)
34
(No Transcript)
35
(No Transcript)
36
Major Treatment Modalities

• Surgery
• Ionising radiation - RT - Radiotherapy
• Chemotherapy
• Hormonal Therapy
• Immunotherapy

37
Principles of Surgical Oncology

• Radical surgery alone replaced by multimodality
  approach
• Appreciation of early metastatic potential
• Risk of tumour margins
• Lymph node involvement
• Marker of metastatic disease - phenotype capable
  of producing metastasis is present
• Survival in node positive is disease is half
  node negative disease
• Malignancies dont always spread stepwise
• primary ? lymph nodes ? distant sites

38
Principles of Surgical Oncology

• Survival has improved with
• less radical surgery
• early detection
• treatment modalities for metastasis

39
Surgical Principles

• Surgeon must understand
• natural history
• pattern of mets
• failure patterns
• Decision
• aim of treatment - cure or palliation
• need for other modalities
• timing of different modalities

40
Surgical Principles

• Surgery may be for
• primary disease eradication - radical operation
• secondary eradication or debulking
• palliation such as bypass, palliative resection
• Radical operation
• removal of tumour completely
• removal of wide margin of normal tissue
• removal of primary draining lymphatics
• obey oncological principles

41
Radical Wipple operation
42
Operative specimen - Wipple Operation
43
Gastrojejunostomy for Palliation
44
Radiotherapy

• Ionizing radiation - photons and electrons
• higher energy deeper penetration
• destroys important molecules e.g. DNA,
• reaction with water produces free radicals
  damage of DNA and other molecules
• unit of energy is the gray Gy 100 rad
• delivered by brachytherapy or teletherapy
• In general for local control of neoplasm

45
Ionizing radiation

• Multiplying tumour cells are sensitive
• G0 tumour cells protected
• Cells at centre of solid tumour
• Ischemic cells
• Hypoxic cells
• Multiplying normal tissue at risk
• skin, GI mucosa, bone marrow, germ cells
• Quiescent normal tissue not sensitive
• Bone, liver

46
Tumour With Hypoxic Cells
47
RT- Increasing dose kills more tumour cells as
well as normal tissue
48
RT - Tumour destruction vs organ complications
- probability curves
49
Radiotherapy

• Fractionation
• Total dose given in series of small doses
• Reduces damage to normal tissue
• Maximises tumour killing

50
Radiotherapy

• Fractionation how does it work ?
• Each doses kills sensitive cells but spares G0
  cells
• Reoxygenation of remnant G0 cells makes them
  divide and be susceptible tumour - each fraction
  kills more cells
• Normal tissue is spared due to repair after each
  small sublethal dose minimise complications

51
Radiotherapy With Surgery

• Surgery removes tumour but margins are at risk
  for seeding
• Wider surgery increases complications
• RT excellent for margins (oxygen rich) poor for
  center of tumour (oxygen poor)
• Combination of surgery followed by RT increases
  probability of free margins and reduces local
  recurrence

52
Principles of Chemotherapy

• Tumour mass growth slows as tumour enlarges -
  cells at center die or remain dormant (G0)
  because of blood supply limitation
• Only dividing cells (growth fraction) are killed
• Growth fraction is maximum at 37 of max size
• Each dose of chemotherapy kills a fraction of
  total cells

53
Principles of Chemotherapy

• Concept of log kill
• Suppose a patient has 10 mets of 1 cm3 each (109
  cells) total of 1010 cells.
• One cycle of drugs produces 1-log kill or 90
  eradication
• 6 drug cycles will give 6-log kill or 99.9999
  eradication
• Each met will then have 103 cells left -
  clinically undetectable(complete remission)
  but recurrence is likely

54
Principles of Chemotherapy

• Concept of log kill
• If we start with smaller volume after 6 drug
  cycles we may have 102 cells per met
• Immune system may be able to mop up - actual
  cure

55
Principles of Chemotherapy

• Chemotherapy for solid tumours is most effective
  for small (early) tumours
• Not suitable for solid primaries
• Ideal for early metastasis

In general ChemoRx is for systemic control after
primary treatment
56
Types of Chemotherapy

• Curative - for tumours with 100 growth fraction
  - blood malignancies
• Adjuvant - treatment of micrometastasis after
  curative treatment of primary by other modality
  usually surgery
• Neoadjuvant - given before definitive surgery
• Palliative - control of disseminated disease

57
Administering Chemotherapy

• Select effective drug - consider toxicity
• Calculate dose needed - consider patient
  performance, co morbid conditions
• Suitable intervals to allow normal tissue to
  recover - esp. bone marrow
• Support patient and treat toxicity
• Compassion Quality of Life

58
Administering Chemotherapy

• Plant Alkaloids
• Antibiotics
• Alkylating Agents
• Antimetabolites
• Combination Chemotherapy
• prevents emergence of early resistance
• additively increase in cytotoxic potency

59
Cancer Therapy