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Leicester Warwick Medical School
Neoplasia IV
Incidence, Prognosis,
Treatment of Cancer
Professor Rosemary A [email protected]
Department of Pathology
INCIDENCE OF CANCER
MALE FEMALE
Lung 21% Breast 27%
Prostate 15% Lung 12%
Colorectal 13% Colorectal 12%
Bladder 8% Ovary 5%
Lymphoma 4% Lymphoma 3%
AGE INCIDENCE
0
10000
20000
30000
40000
50000
60000
70000
<10 10-19 20-29 30-39 40-49 50-59 60-69 70-79 >80
Cancer Registrations per year. UK
Age Range
AGE INCIDENCE
<10 - childhood neoplasms (Wilms, neuroblastoma, retinoblastoma), leukaemia, CNS tumours
10-10 - leukaemia, osteosarcomas
20-29 - leukaemia, teratomas, lymphoma
30-39 - carcinoma, seminoma, lymphoma, sarcoma
40-49 - carcinoma, lymphoma, glioma, sarcoma
50< - carcinoma, sarcoma, lymphoma, leukaemia
CANCER MORTALITY
MALE FEMALE
Lung 28% Breast 18%
Prostate 12% Lung 17%
Colorectal 11% Colorectal 12%
Stomach 6% Ovary 6%
Oesophagus 5% Pancreas 5%
5 YEAR SURVIVAL RATES FROM CANCER
Pancreas 3% Prostate 60%
Lung 12% Breast 65%
Stomach 19% Non-melanoma90%
Ovary 35% NH lymphoma 37%
Colon/rectum 50%
PREDICTING TUMOUR BEHAVIOUR
Size of tumour
Node status
Distant metastasis
Staging
Grade
Receptors/Molecular alterations
35404550556065707580859095
100
0 12 24 36 48 60 72 84
Months
Su
rviv
al %
<2cm
2-4.9cm
>5 cm
35404550556065707580859095
100
12 24 36 48 60 72 84
Months
Su
rviv
al %
No NodalInvolvement
1-3 PositiveNodes
4+ PositiveNodes
STAGING
Dukes staging for neoplasms of rectum
A Not extending through muscularis propria >90% 5 yr survival
B Extending through muscularis propria 70% 5 yr survival
C Lymph nodes involved 30% 5 yr survival
STAGINGTNM
T = tumour N = node M = metastasiseg. breast, lungT1 = <2cm size T2 = 2 - 5 cm T3 = skin and/ or chest wall involvedN0 = no axilliary nodes involvedN1 = mobile nodes involvedM0 = no metastasesM1 = demonstrable metastases
STAGINGHodgkin’s Disease
(Ann Arbor)I one group of nodes involvedII two separate groups, same side of diaphragmIII nodes involved both sides of diaphragm, plus spleenIV bone marrow, lung, other sitesA no symptomsB fever, itching
GRADING
Degree of differentiation e.g. breast
• degree of tubule formation
• extent of nuclear variation
• number of mitoses
Grade 1 Grade 2
Grade 3
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10
Years
Su
rviv
al %
Grade I
Grade II
Grade III
TREATMENT
• Surgery
• Radiotherapy
• Chemotherapy
• Hormone therapy
• Others – cancer specific, vaccines
TREATMENT
Primary
• Depends on of nature of tumour
• Stage
Adjuvant
• Recurrent/metastases
RADIOTHERAPY
Factors
• Type of radiation
• Cumulative dose
• Rate of delivery
• Target tissues
RADIOTHERAPY
Cells and tissues of the body and their
tumours vary in their capacity to sustain
injury
• Phase of cell cycle
• Repair mechanisms
• Oxygenation
RADIOTHERAPY
SENSITIVITY
Normal Tumour
High Lymphoid Lymphoma
Bone marrow Leukaemia
Spermatogonia Seminoma
Fairly high Epidermis SquamousG I mucosa carcinomas
RADIOTHERAPYSENSITIVITY
NORMAL TUMOUR
Medium breast carcinomas of
pancreas breast, pancreas,
bladder bladder, ovary, lung
Low bone, mature sarcomas
cartilage, gliomas
nerves
CHEMOTHERAPY
Drugs used have effects at particular stages of the cell cycle
Effects depend on tumour cells being in cell cycle
Also have an effect on rapidly dividing cells eg. bone marrow
CHEMOTHERAPY
Cyclophosphamide- can act on cells in G1, S phase and mitosis.
Vincristine - can block cells entering cell cycle and act on mitosis
Methotrexate - acts on cells in S phase
PREDICTING RESPONSE
• Hormone TherapyDetection of hormone (oestrogen) receptor
• HerceptinDetection of amplification/overexpression of HER-2
High oestrogen
receptor (ER)
Low ER
Neg ER
c-c-erberbB-2/B-2/neuneu/HER-2/HER-2
• antibodies made and modified for use in humans
• if HER-2 present as detected by Hercep-Test, then can use Herceptin® for treatment
TUMOUR MARKERS
Products liberated from tumour into blood stream
May aid diagnosis and can be used to gauge response to therapy and for follow up.
TUMOUR MARKERS
Alpha fetoprotein - Hepatocellular carcinoma
Germ cell tumours
Human chorionic - Trophoblastic tumours
gonadotrophin
TUMOUR MARKERS
Acid phosphatase - Prostatic carcinoma
Prostate specificantigen
Carcinoembryonic - GI tractantigen
Hormone products - Endocrine tumours
SCREENING
Aims to detect pre-malignant, noninvasive and early invasive cancers to improve prognosis.
• Cervix
• Breast
• Large Intestine
• Prostate
SCREENING
Cervical
Relies on cytological examination of smears to detect “early” changes - dysplasia
Factors include - age range screened- population at risk- adequate smear- cytological examination
SCREENINGBreast
Aims to identify invasive cancers before they can be felt (10-15 mm in size )
Relies on mammography
50-64 (69) years
Factors - frequency of screening - age range - would all lesions progress?
HOW CAN WE IMPROVE PROGNOSIS?
• Identify “at risk” groupsfamilialoccupational
• Detect at an earlier stagecervixbreast
• Prevention
