ONCOLOGY

Athira Rameshan
 CANCER

• The International Union Against Cancer has defined cancer as a disturbance of

growth characterized primarily by excessive proliferation of cells without apparent
relation to the physiological demands of the organs involved.
• Oncology deals with the prevention, diagnosis, treatment, and research aspects of
cancer.
• Cancer is a leading cause of death all over the world, 7 million deaths occurred during
2001.
• Among these 2/3 are men and 1/3 are women.
• Healthy normal cells are programmed to know what to do and when to do but
cancerous cells are not programmed like that and so it grow and replicate out of
control
• In normal tissue, the rate of new cell growth and old cell death are in balance but
in case of cancerous cell it is disrupted
 CLASSIFICATION

It can be classified according to:

1. Primary site of origin
2. Histological or tissue type
3. Classification by grade or by stage
CLASSIFICATION BY SITE OF ORIGIN

• By primary sit of origin, cancer can be of specific types like breast cancer, lung
cancer, prostate cancer, renal cell carcinoma, oral cancer etc.
CLASSIFICATION BY TISSUE TYPES

Based on ICD 0-3

Based on tissue types cancer can be classified into 6 major types
• Carcinoma
• Sarcoma
• Myeloma
• Leukemia
• Lymphoma
• Mixed types
Carcinoma

• It originates from the epithelial layer cells of that form the external part of body or
internal covering of organs
• It accounts for 80-90% of cancer because epithelial cells are found abundantly in
body
• Carcinomas usually effect organs or glands capable or secretions like breast, lungs,
bladder, colon and prostate
• It is of two types
• Adenocarcinoma – it develops in organ and rapidly spreading cancers
• Squamous cell carcinoma – appears in squamous epithelium
Sarcoma

• It originates in connecting and supportive tissues including muscles, bones, cartilage

and fat
• Sarcoma appears like the tissue in which they grow
• Bone cancer is the common type, and it is called osteosarcoma
• Other types
• Chondrosarcoma – of cartilage
• Leiomyosoma – of smooth muscles
• Rhabdomyosoma – of skeletal muscles
• Mesothelial sarcoma – membraneous lining of body cavities
• Fibrosarcoma – of fibrous tissue
• Liposarcoma – of fats
Myeloma

• Originates in plasma cells of bone marrow

• It’s a type of blood cancer
Leukemia

• It is a group of cancer that is grouped within blood cancer

• This effects the bone marrow, which produces blood cells
• When cancerous, bone marrow produces excessive immature white blood cells
which fail to perform their functions and patient is prone to infection
• Types of leukemia
• Acute lymphocytic leukemia (ALL)
• Acute myeloid leukemia (AML)
• Chronic lymphocytic leukemia (CLL)
• Chronic myelogenous leukemia
Lymphoma

• It is the cancer in lymphatic system

• Lymphomas can affect any portion of the lymphatic system, including:
• bone marrow
• thymus
• spleen
• tonsils
• lymph nodes

Two types

• Hodgkin’s lymphoma – contains Reed-Sternberg (RS) cells

• Non-Hodgkin’s lymphoma
 STAGING OF CANCER

Types of staging systems

• There are 2 main types of staging systems for cancer.
• These are the TNM system and the number system.

1. The TNM staging system

The TNM staging system stands for Tumour, Node, Metastasis.
• T describes the size of the tumour
• N describes whether there are any cancer cells in the lymph nodes
• M describes whether the cancer has spread to a different part of the body
2. Number staging systems

Stage 1 usually means that a cancer is small and contained within the organ it
started in
Stage 2 usually means that the tumour is larger than in stage 1 but the cancer
hasn't started to spread into the surrounding tissues. Sometimes stage 2 means
that cancer cells have spread into lymph nodes close to the tumour. This depends
on the particular type of cancer
Stage 3 usually means the cancer is larger. It may have started to spread into
surrounding tissues and there are cancer cells in the lymph nodes nearby.
Stage 4 means the cancer has spread from where it started to another body
organ. For example to the liver or lung. This is also called secondary or metastatic
cancer
 Frequency of cancer

MALES FEMALES

Oral cavity 16.3% Breast 24.8%

Lung 12.6% Uterine cervix 16.3%
Lymphoma 6.8 % Oral cavity 9.5%
Pharynx 6.2% Thyroid 9%
Esophagus 6% Ovary 7%
Leukemia 5.9% Leukemia 4.2%
Larynx 5.8% Lymphoma 3.5%
Stomach 3.8% Brain 2.1%
Brain 2.7% Esophagus 1.9%
Liver 2.6% Body of uterine 1.8%
 ETIOLOGY

• Several factors operate to bring about carcinogenesis

• These are genetic, hormonal, metabolic, physical, chemical and other
environmental factors.
• During the course of cell division malignant mutants may be formed which
proliferate to form tumours.
• Carcinogens increase the rate of mutation and thereby the possibility of
malignancy is also increased. Cancer is more frequent in old age, since the
occurrence of aberrant mutation is increased.
• Many mutants are destroyed by immunological mechanisms of the body,
but in case of cancer this is disrupted.
CHEMICAL CARCINOGENS:
• These act cumulatively to bring about carcinogenesis. Food additives, coloring agents
• Aflatoxins and n-nitroso compounds are common carcinogens
• Cancer may be produced:
(a)at the site of exposure to the carcinogen, e.g., skin cancers in tar workers and
buccal cancer in tobacco chewers;
(b)at the site of metabolism, e.g. liver cancer in aflatoxicosis; or
(c)at the site of elimination, e.g., bladder cancer in workers using aromatic amines.

DIET :
• Some dietary factors or aspects of life-styles are significantly associated with certain
malignancies.
• Salt-cured and smoked foods are related with cancer of esophagus and stomach; high
fat diet with cancer of breast and colon.
INITIATION AND PROGRESSION:
• It is postulated that a carcinogen produces a mutation, but it remains dormant unless
acted upon by a promoter
VIRUSES:
• Several viruses have been implicated in many cancers.
PHYSICAL AGENTS:
• Ionizing radiation cause a marked increase in cancer incidence in later life. Exposure
to X-rays in fetal life increases the risk of developing leukemia in later life
GENETIC FACTORS:
• Many neoplasms show evidence of genetic predisposition.
• Retinoblastoma, multiple polyposis of the colon, and carcinoma breast run in
families. Mongolism is associated with a ten-fold increase in the risk of leukemia.
• Blood group A is associated with a higher risk of gastric carcinoma, compared to
blood group B and O.
• Hodgkin’s disease is more frequent in subjects with HLA B 18
ONCOGENES:
• These are altered forms of normal genes called proto-oncogenes. More than 80
human proto-oncogenes are known
TUMOUR MARKERS:
• Tumour markers or tumour index substances are factors released from the tumour
cells; these could be detected in blood and therefore indicate the presence of the
tumour.
• They are useful
(A) For follow up of cancer and to monitor the effectiveness of the therapy
(B) To detect the recurrence of the tumour
(C) For prognosis; serum level of tumour marker usually indicates roughly the
tumour load, which in turn indicates whether the disease is advanced or not
(D) To facilitate detection of cancer.
 FUNCTIONAL ANATOMY AND PATHOPHYSIOLOGY

• Cancer cells possess unique characteristics , in that their proliferation is unregulated

and in that they have the capacity to invade surrounding tissues
• Oncogenesis is a multistage process which often begins with somatic mutation in
single cell , resulting in a growth advantage
• Subsequently further mutations occur, selecting a subset of cells for more rapid
growth which is mediated by increased growth production, constitutive activation of
signaling pathways that stimulate cell divisions
 IMPORTANT FACTORS IN THE PATHOPHYSIOLOGY OF CANCER

 Cell cycle
• Proliferation of normal cell cycle and cancer cells consist of four phases
Two functional phase – S phase and M phase
Two preparatory phase - G₁ phase and G₂ phase

 Regulation of cancer cell growth

• Activation of cell growth - Many cancer cells produce their own proliferation
by a positive feedback loop, a process known as autocrine stimulation
• Inhibition of tumor suppressor genes – in normal cells proteins inhibit cell
growth but these may be inactivated by loss of function or their levels reduced
by diverse mechanism
• Avoidance of apoptosis – evasion of apoptosis is a common finding in cancer. It
can occur through altered activity or loss of function of molecules that take
part in the apoptotic process
 • Maintenance of telomeres – when normal cells replicate there is progressive
shortening of telomeres; eventually this prevents from dividing further. Cancer
cells can replicate an infinite number of times and this is associated with
maintenance of telomere length

 Angiogenesis
• Malignant tumor need to acquire a network of blood vessels for continued
growth. This process is called angiogenesis
• And this is dependent on the production of angiogenic growth factors by the
tumor
• The requirement of tumors to produce angiogenesis has been therapeutically
exploited in the development of agents that target angiogenic molecules or
their receptors
 Immune surveillance
• One of the hallmark of cancer is; cancer cells escape from immune surveillance
• These escape from immune control through three reasons
• Failure of antigen recognition by immune cells
• Tumor escape from the activity of cytotoxic lymphocytes
• Tumor induced immune dysfunction
 Invasion and metastasis
• In cancer cells; cell adhesion molecules (CAM) are absent or dysfunctional
allowing the cells to detach from primary cells and to replicate.
 Anatomical spread of tumors
• tumors can spread both by local invasion and by migration to distant sites
 SYMPTOMS

Local features
• Hemorrhage
• Lump
• Bone pain or fracture
• Skin abnormality
• Ulcer
• Dysphagia
• Increased constipation or abdominal discomfort
• Airway obstruction
• Odynophagia, vomiting
• Abdominal swelling
Non metastatic manifestation

• Weight loss and anorexia

• Fatigue
• Hypercalcemia
• Prothrombotic tendency
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• Lambert- Eaton myasthenia like syndrome
• Subacute cerebellar degeneration
• Acanthosis nigricans
• Dermatomyositis
 Other important features

• Palpable mass
• Weight loss and fever
• Finger clubbing
• Ectopic hormone production
• Neurological paraneoplastic syndromes
Emergency complications

• Spinal cord compression

• Superior vena cava obstruction
• Hypercalcemia
 INVESTIGATION

 Histology
• Light microscopy
• Immunohistochemistry
• Electron microscopy
• Cytogenic analysis
 Imaging
• Radiography
• Ultrasound
• CT
• MRI
• Positron emission tomography
 Biochemical markers
 TREATMENT

• The aim of therapy is to reduce the tumour mass within the shortest possible time
and to destroy the remaining cells and prevent them from multiplying and
disseminating.
• This ideal is possibly achieved only in the case of very few cancers but in the majority
of cases this is not possible due to:
(1)late diagnosis
(2) presence of secondaries early in the disease,
(3) surgical risk
(4) toxic effects of radiation and chemotherapeutic agents.
• Surgery and radiotherapy are most effective to reduce the initial tumour load. These
are the prime modalities of treatment in solid tumours.
• In the case of disseminated neoplasms like leukemia and myeloma and in the case of
some rapidly growing tumours like trophoblastic tumours, chemotherapy has to be
employed as the first line of treatment.
RADIOTHERAPY

• Tumour cells are more radiosensitive as they proliferate faster than normal cells.
• Radiotherapy may be given as the only modality of treatment or combined with
surgery and chemotherapy.
• With the advent of highly sophisticated equipment such as the linear accelerator,
large doses may be focused on deep seated tumours with only minimal injury to
adjacent tissues. Therapeutic efficacy of radiation is enhanced by exposure to
hyperbaric oxygen and radiosensitizing drugs such as metronidazole
• Radiation produces ionization in its path. This causes physical and/or chemical
changes. The nucleic acid in the cell is damaged, so as to arrest the next cell division.
• Radiotherapy mainly affects cells in the dividing phase.
• Depending on the sources of radiation, the radiotherapy may be
(a)unsealed sources - Unsealed sources are radioactive substances kept in liquid
form. The beta rays are the main effective radiation in these sources. For
treating primary and metastatic thyroid cancer

(b)sealed sources or brachytherapy - The radioactive source is covered by platinum

alloy to absorb alpha and beta radiation, so that only gamma rays are allowed to
penetrate into the tissue.

(c)Teletherapy - Here the source of radiation is kept at a distance from the patient.
The high penetration power of the gamma rays has an advantage. Maximum
dose is received not on the skin, but on the underlying tissues, which reduces
unwanted skin reactions. Gamma rays from Caesium or Cobalt are used for
teletherapy
ADVERSE EFFECTS:
The adverse effects of radiotherapy are due to the damage caused to normal tissues;
some degree of which is inevitable
• Skin Epilation, damage to sweat glands, erythema and blisters.
• Mucous membranes - Mucosal surface cells are replenished very rapidly, about a
third being formed everyday. Since radiation damages the dividing cells most,
gastrointestinal problems are very common during radiotherapy
• Blood cells - Bone marrow and lymphoid tissues are highly radiosensitive because
of the higher rate of cell division in the organs.
• Reproductive organs - Complete sterility may result if 1000 rads are given over the
pelvic region
CHEMOTHERAPY

• Chemotherapy is the sheet anchor of therapy in leukemias, advanced lymphomas,

choriocarcinoma and other widely disseminated malignancies.
• The effectiveness of cytotoxic drugs is directly proportional to the doubling time of
the tumours, and is inversely proportional to the number of cancer cells. Prior
reduction of tumour mass by surgery or radiotherapy augments the effectiveness of
chemotherapy.
• Cytotoxic drugs are nonselective and affect all cells which are in certain phases of
their proliferative activity
 SURGERY
Different types of surgery

• Curative Surgery - This type of surgery for cancer involves the removal of cancerous
tissues from the body. It is also called tumor removal surgery.
• Preventive Surgery - It is also known as prophylactic surgery. The surgeons perform
preventive surgery to remove the tissues that have the potential to develop into
cancerous masses, such as the removal of colon polyps to prevent colon cancer.
• Diagnostic Surgery and Staging Surgery - During diagnostic surgery, the surgeon
collects the abnormal tissues and sends them to the laboratory to detect cancer. The
surgeon also determines the tumor size, and if the cancer has spread to other body
parts.
• Debulking Surgery - This tumor removal surgery removes a portion of the cancerous
tissues, as removing the complete tumor may damage the surrounding organs. The
patients undergo chemotherapy and/or radiation therapy to damage the remaining
cancerous tissues.
• Palliative Surgery - Palliative surgery is a surgical intervention that relieves the side
effects of cancerous tissues. It enhances the quality of life in advanced cancer. It is
done to relieve the pressure on the nerves, remove gastrointestinal obstruction, and
prevent bleeding.