GENERAL PRINCIPLES OF ONCOLOGY

DR. BENJAMIN S P EARNEST

CANCER BIOLOGY

 Most human neoplasms are clonal in origin, i.e. they arise from a single
population of precursor or cancer stem cells.
 Cancer is increasingly common the older we get and can be related to a
time dependent accumulation of DNA damage that is not repaired by the
normal mechanisms of genome maintenance, damage tolerance and
checkpoint pathways.
 Malignant transformation may result from a gain in function as cellular
proto-oncogenes
 Alternatively, there may be a loss of function of tumour suppressor genes
COMMON GENETIC ABNORMALITIES IN CANCER
GOMPERTZIAN TUMOR GROWTH
TUMOUR IMMUNOLOGY

 Tumour cells are usually not recognized and killed by the immune system.

 There are two main reasons.

 The first is failure to express molecules such as HLA and co-stimulatory B7 molecules that are required for
activation of cytotoxic, or ‘killer’, T lymphocytes.
 Second, tumours may also actively secrete immunosuppressive cytokines and cause a generalized
immunosuppression.
SIX
BIOLOGICAL
CAPABILITIES
OF A
CANCER CELL
 ASYMPTOMATIC DETECTION THROUGH SCREENING
 The aim of screening programmes is to improve individual and/or population survival by
detecting cancer at its very early stages when the patient is asymptomatic.
EXAMPLES OF CANCER SCREENING

 Cervical smear for carcinoma of the cervix

 Mammography for carcinoma of the breast

 PSA for carcinoma of the prostate

 CA125 for carcinoma of the ovaries

 Endoscopy for carcinoma of the colon

SVC OBSTRUCTION

 Superior vena cava obstruction (SVCO) is a common complication of cancer that can occur
through extrinsic compression or intravascular blockage.
 The most common causes of extrinsic compression are lung cancer, lymphoma and
metastatic tumours.
 Patients with cancer can also develop SVCO due to intravascular blockage in association
with a central catheter or thrombophilia secondary to the tumour.
 HYPERCALCAEMIA
 Hypercalcaemia is the most common metabolic disorder in patients with cancer and has a
prevalence of 15–20 cases per 100 000 persons.
 The incidence is highest in myeloma and breast cancer (approximately 40%), intermediate
in non-small cell lung cancer, and uncommon in colon, prostate and small cell lung
carcinomas.
 It is most commonly due to over-production of PTHrP.
 The symptoms of hypercalcaemia include drowsiness, confusion, nausea and vomiting,
constipation, polyuria, polydipsia and dehydration.
NEUTROPENIC FEVER

 Neutropenic fever is defined as a pyrexia of 38°C for over 1 hour in a patient with a neutrophil count
< 1.0 × 109/L.
 Neutropenic fever is an emergency in cancer patients as, if left untreated, it can result in septicaemia
with a high mortality rate.
 It is usually secondary to chemotherapy but may occur with radiotherapy if large amounts of bone
marrow are irradiated; it may also be a component of pancytopenia due to malignant infiltration of the
bone marrow
 Blood cultures should be done along with high dose IV empirical antibiotics. Typical first-line empirical
therapy consists of an anti-pseudomonal β-lactam (ceftazidime, cefotaxime or meropenem), or a
combination of an aminoglycoside and a broad-spectrum penicillin with anti-pseudomonal activity
(gentamicin and piperacillin). Metronidazole should be added if anaerobic infection is suspected, and
flucloxacillin or vancomycin or teicoplanin where Gram-positive infection is suspected
BIOPSY AND HISTOLOGICAL EXAMINATION

 The diagnosis of cancer may be suspected by both patient and doctor but advice about
treatment can usually only be given based on a tissue diagnosis.
 Malignant lesions can be distinguished morphologically from benign ones by the
pleiomorphic nature of the cells, increased numbers of mitoses, nuclear abnormalities of
size, chromatin pattern and nucleolar organization and evidence of invasion into
surrounding tissues, lymphatics or vessels.
 More differentiated tumours have a better prognosis than poorly-differentiated ones.
FROZEN SECTION

 In some tumours where the surgical procedure will vary depending on the presence of
malignancy, an intraoperative histological opinion can be rapidly obtained using a tissue
sample processed using ‘frozen section’ techniques, which requires the availability of a
histopathologist.
IMMUNOCYTOCHEMISTRY

 Immunocytochemistry, using monoclonal antibodies against tumour antigens, is very

helpful in differentiating between lymphoid and epithelial tumours and between some
subsets of these, for example T- and B-cell lymphomas, germ cell tumours, prostatic
tumours, neuroendocrine tumours, melanomas and sarcomas.
MOLECULAR MARKERS OF GENETIC ABNORMALITIES

 Fluorescent in situ hybridization (FISH) can be used to look for characteristic chromosomal
translocations, e.g. in lymphoma and leukaemia, as well as deletions or amplifications, e.g. in
breast cancer
 Tissue microarrays can identify patterns of multiple genomic alterations and single nucleotide
polymorphisms (SNPs), e.g. in breast cancer and lymphoma
 RNA assays with RT-PCR can be used to identify tissue of origin with prognostic and predictive
relevance.
 Genomics and proteomics are being investigated in order to target new (and expensive)
therapies, e.g. imatinib in CML and GIST, trastuzumab and lapatinib in breast cancer and
erlotinib in lung cancer.
CANCER TREATMENT
CURATIVE TREATMENT

 For most solid tumours local control is necessary, but not sufficient, for cure because of the
presence of systemic (microscopic) disease, while haematological cancers are usually
disseminated from the outset
 For most common solid tumours such as lung, breast and colorectal cancer, there is no
current cure of bulky (clinically detectable) metastases, but micrometastatic disease
treated by adjuvant systemic therapy after surgery can be cured in 10–20% of patients.
 A few rare cancers are so chemosensitive that even bulky metastases can be cured, e.g.
leukaemia, lymphoma, gonadal germ cell tumours and choriocarcinoma.
ADJUVANT VS. NEO-ADJUVANT THERAPY

Adjuvant therapy Neo-adjuvant therapy

 This is defined as treatment given, in  Treatment given before primary surgery,

the absence of macroscopic evidence of to both shrink the tumour to improve
metastases, to patients at risk of the local excision and treat any
recurrence from micrometastases, micrometastases as soon as possible.
following treatment given for the
primary lesion.
PALLIATIVE TREATMENT

 When cure is no longer possible, palliation, i.e. relief of tumour symptoms, preservation of
quality of life and prolongation of life, is possible in many cancers in proportion to their
drug and radiation sensitivity.
STAGING INVESTIGATIONS

 Careful history and physical examination are the most important staging procedures

 Ultrasonogram, radiography, CT scan, MRI, PET scan, radionuclide bone scan (SPECT imaging)

 Serum calcium, LFT, RFT

 Bronchoscopy, mediastinoscopy, VATS, GI endoscopy, laparoscopy

 Staging surgery
RESPONSE
EVALUATION
CRITERIA IN
SOLID
TUMORS
SURGERY
BIOPSY

 In the vast majority of cases, a histological or cytological diagnosis of cancer is necessary,

and tissue will also provide important information such as tumour type and differentiation,
to assist subsequent management.
EXCISION

 The main curative management of most solid cancers is surgical excision.

 There is increasing evidence that outcome is related to surgical expertise, and most
multidisciplinary teams include surgeons experienced in the management of a particular
cancer.
PALLIATION

 Examples include the treatment of

 faecal incontinence with a defunctioning colostomy;
 fixation of pathological fractures
 decompression of spinal cord compression
 treatment of fungating skin lesions by ‘toilet’ surgery.
CHEMOTHERAPY
CELL CYCLE
B
D

E
A, C
COMBINATION THERAPY

 Chemotherapeutic agents are not specific for cancer cells, however, and the side-effects of
treatment are a result of their anti-proliferative actions in normal tissues such as the bone
marrow, skin and gut.
 In order to overcome drug resistance and to limit the side-effects of different drugs,
chemotherapy is most commonly given as a combination of agents.
 Drugs are conventionally given by intravenous injection every 3–4 weeks, allowing enough time
for the patient to recover from short-term toxic effects before the next dose.
MODE OF ADMINISTRATION

 Chemotherapy should be administered into a vein in which the infusion is free-flowing to

minimise the risk of extravasation as many are vesicant or locally irritant.
 Chemotherapy is potentially dangerous to the person giving the therapy, because cytotoxics are
carcinogenic and teratogenic.
 Policies must be in place for the use of gloves and aprons and for the safe disposal of syringes
containing cytotoxics.
HICKMAN CATHETER
–TUNNELED CENTRAL VENOUS CATHETER
RADIATION THERAPY (RADIOTHERAPY)
RADIATION THERAPY (RADIOTHERAPY)

 Ionising radiation can be delivered by radiation emitted from the decay of radioactive isotopes
or by high-energy radiation beams, usually X-rays.
 Teletherapy: application from a distance by a linear accelerator.
 Brachytherapy: direct application of a radioactive source on to or into a tumour.

 Intravenous injection of a radioisotope: such as iodine for cancer of the thyroid and
131

89
strontium for the treatment of bone metastases from prostate cancer.
RADIATION FIELD MARKINGS WITH INDIA INK
AND RADIATION BURNS ON THE CHEST
Adverse effects of
chemotherapy
and
radiotherapy
HORMONE THERAPY
HORMONE THERAPY

Breast cancer Prostate cancer

 Breast tumours that are positive for  In prostate cancer, hormonal therapy
expression of the oestrogen receptor (ER) aimed at reducing androgen levels can
respond well to anti-oestrogen therapy and provide good long-term control of
assessment of ER status is now standard in advanced disease
the diagnosis of breast cancer.
IMMUNOTHERAPY
IMMUNOTHERAPY

 Interferons are active in melanoma and lymphoma, and there is evidence that they are
beneficial as adjuvants (after surgery and chemotherapy respectively) to delay recurrence.
 The most striking example of successful immunotherapy is that with rituximab, an antibody
against the common B-cell antigen CD20.
 It increases complete response rates and improves survival in diffuse large cell non-Hodgkin’s lymphoma when
combined with chemotherapy
BIOLOGICAL THERAPIES
BIOLOGICAL THERAPIES

 Gefitinib/erlotinib:
 These agents inhibit the activity of the epidermal growth factor receptor

 Imatinib:
 Developed to inhibit the BCR-ABL gene product, tyrosine kinase

 Bevacizumab:
 This is a monoclonal antibody that inhibits vascular endothelial growth factor A (VEGF-A)

 Trastuzumab
 Trastuzumab (herceptin) targets the HER2 receptor, an oncogene
LOG RANK TEST
KAPLAN MEYER CURVE
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