Principles of Oncology

Dr. Murali. U. M.S ; M.B.A.

Prof. of Surgery

D Y Patil Medical College

Mauritius.

Objectives

Biological nature of cancer

Etiology of cancer

Management aspects of cancer

Palliative care – Principles

Historical Perspective

Hippocrates used the Greek words, carcinos and carcinoma to describe tumors, thus calling

cancer “karkinos” tumor.

The world's oldest documented case of cancer hails from ancient Egypt, in 1500 B.C.

Treated by cauterization, a method to destroy tissue with a hot instrument called “fire drill”.

Rudolph Virchow in late 19th century recognized that even cancerous cells were derived

from other cells. ( Abnormal proliferation )

Theodar Boveri (1914) - importance of chromosomes abnormalities – cancer cells.

By 1940, Oswald Avery – DNA genetic material within the chromosomes.

In 1953, Watson & Crick described the structure of DNA – paved the way for the study of

molecular biology of cancer.

Cancer cells - Psychopath

No respect for the rights of other cells.

Violate the democratic principles of normal cellular

organisation.

Theiir proliferation is uncontrolled.

Ability to spread is unbounded.

Their inexorable, relentless progress destroys first

the tissue and then the host.

Malignant Transformation

Self sufficiency in growth

signals.

Insensitivity to growth –

inhibitory signals. [TGF-

β]/[CDKIs]

Evasion of apoptosis.

Limitless replicative

potential.

Malignant transformation

Sustained angiogenesis.

Ability to invade and

metastasize.

Defects in DNA repair.

Escape from immune

attack.

Flowchart depicting a simplified scheme of the molecular basis of cancer

Tumour – Growth

The majority of the growth of a tumour occurs before it is

clinically detectable.

By the time they are detected, tumours have passed the

period of most rapid growth, that period when they might

be most sensitive to anti-proliferative drugs.

There has been plenty of time, before diagnosis, for

individual cells to detach, invade, implant and form distant

metastases.

Cancer cells usually follows “Gompertzian growth” pattern.

Gompertzian Growth

Etiology

Both inheritance and environment are important

determinants of whether or not an individual

develops cancer.

The knowledge we have concerning the causes of

cancer can be used to design appropriate strategies

for prevention or earlier diagnosis.

CAUSES OF CANCER

Management of Cancer

Screening

Diagnosis & classification

Investigation & staging

Therapeutic decision making

Criteria for Screening test

The disease

- Recognisable early stage

- Treatment at an early stage more effective than at a later age

The test

- Sensitive and specific

- Acceptable to the screened population

- Safe & Inexpensive

The programme

- Adequate diagnostic facilities for those with a positive test

- High-quality treatment for screen-detected disease to minimise morbidity and mortality

- Screening repeated at intervals if the disease is of insidious onset

- Benefit must outweigh physical and psychological harm

Diagnosis and Classification

Accurate diagnosis is the key to the successful management of cancer.

Precise diagnosis is crucial to the choice of correct therapy.

Different tumours are classified in different ways: “Gleason system”

Well (G1)

Moderate (G2)

Poorly differentiated (G3)

Staging

It is not sufficient simply to know what a cancer is; it is imperative to know its site and extent.

If it is localised, then locoregional treatments such as surgery and radiation therapy may be curative.

If the disease is widespread, then, although such local interventions may contribute to cure, they will be insufficient,andsystemic treatment, for example with drugs or hormones, will be required.

Staging is the process whereby the extent of disease is mapped out – “Will Rogers phenomenon”

TNM method for Staging of Tumor

T - score: size and extent of invasion of the primary tumor

N - score: number and location of histologically involved regional lymph nodes

M - score: presence or absence of distant metastasis.

Decision making

As the management of cancer becomes more complex, it becomes impossible for any

individual clinician to have the intellectual and technical competence that is necessary to

manage all the patients presenting with a particular type of tumour.

The formation of multidisciplinary teams represents an attempt to make certain that each

and every patient with a particular type of cancer is managed appropriately.

Teams should not only be multidisciplinary, they should be multiprofessional.

Principles of Surgery – Cancer

For most solid tumours, surgery remains the definitive treatment and the only

realistic hope of cure. Role of surgery in cancer treatment include –

Diagnosis & staging

Removal of primary disease

Removal of metastatic disease

Palliation

Surgery in Cancer

Diagnosis & Staging

> Lap Ultrasound & Biopsy

> Sampling Lymph nodes

Removal of primary disease

> Removal of primary tumour + lymph node

Removal of metastatic disease

> Liver metastases - Resection

> Lung metastases – Pulmonary resection

Palliation

> By pass procedures

Principles of Non-surgical Treatment – Cancer

In contrast to surgery, it is possible to construct dose–response relationships for both the

benefits (such as tumour cure rate) and harms (such as tissue damage that is both severe

and permanent) associated with non-surgical interventions.

Principle of selective toxicity : Treatment must be delivered in such a way as to ensure that

the damage done to the tumour is more than the damage done to the normal tissues.

General Strategy : Spatial distribution of therapies / Adjuvant therapy .

Radiotherapy

It is pretentious, but true, to state that radiotherapy is a precisely targeted form of

gene therapy for cancer.

The practicalities of radiation therapy are reasonably straightforward:

> Define the target to treat

> Design the optimal technical set-up to provide uniform irradiation of that target

> Choose that schedule of treatment that delivers radiation to that target in such

a way as to maximise the therapeutic ratio

“5 R’s” – Radiotherapy

Repair of cellular damage

Reoxygenation of the tumour

Redistribution within cell cycle

Repopulation of cells

Radiosensitivity

Chemotherapy

Selective toxicity is the fundamental principle underlying the

use of CT in clinical practice.

CT, by itself rarely sufficient to cure cancer.

Over 95 different drugs - licensed by the FDA for the treatment of cancer.

Of these, over 65% - cytotoxic drugs

15% - hormonal therapies

15% - interact with speciific targets -

“targeted therapies”

Combined Therapy – Principles

Combat drug resistance

Use effective agents

Agents with different modes of action (synergy)

Agents with non-overlapping toxicities

Consider spatial co-operation

Palliative Therapy – Principles

Symptom relief

Psychosocial interventions

Physical & practical support

Information & knowledge

Nutritional support

Social support

Financial support

Spiritual support