Contents

Diagnosis

Staging and Prognosis

Treatment

Toxicity and Late Effects

Cancer Research (i) Basic Science

Cancer Research (ii) Clinical Trials and Epidemiology

Diagnosis

Biopsy

This is the removal of a small section of the tumour, the sample will be analysed by a histopathologist in order to establish a precise diagnosis. Surgical procedure. This may be a needle biopsy, where a very fine needle is used to take a tiny sample of the tumour. Occasionally a surgeon may remove the whole tumour prior to diagnosis; a resection biopsy.

Haematology

is the branch of medicine that specialises in the study and treatment of blood and blood tissues (including bone marrow). A blood count is where the various types cells in the blood are measured. This may aid diagnosis and will be used during treatment to monitor toxicity. The Haematologist may also examine samples from a bone marrow aspiration (needle into the bone) and samples of spinal fluid from a lumbar puncture (needle between the vertebra of the spine).

Histopathology

the study of cells relating to the disease. (Histology is the microscopic study of cells and tissues, Pathology is the study of the disease). The histopathologist will determine a precise diagnosis by laboratory tests and microscopic examination of the cells.

Differentiation

is where normal cells go through physical changes in order to form the different specialised tissues of the body. Malignant cells may range from well-differentiated (closely resembling the tissue of origin) or undifferentiated or anaplastic (bearing little similarity to the tissue of origin). In general it is the undifferentiated or anaplastic histologies which are more aggressive.

Tumour Markers

A substance in the body that may indicate the presence of cancer. Markers may be secreted by the tumour itself or produced by the body in response to the cancer. Tumour markers may aid diagnosis or give an indicator of how treatment is progressing. These markers are usually specific to certain types of cancer. For example neuron-specific enolase (NSE) is associated with a number of types of cancers, in particular neuroblastoma. Also alphafetoprotein (AFP) levels are often abnormally high in patients with Germ cell tumours.

Medical Imaging

Types of medical imaging include:

• X-ray Examination of X-ray films may indicate the site and extent of the tumour and aid in the detection of metastatic spread.
• CT Computed tomography (CT or CAT scan) makes a cross-sectional x-ray picture of a "slice" of the body. The machine rotates around the patient taking x-rays from different angles, the images are then processed by a computer.
• MRI Magnetic resonance imaging. This is used to determine if the biochemical activity of a tissue responds normally to magnetic forces, tumours may give an abnormal signal.
• Ultrasound The use of sound waves to image the underlying structures of the body. Ultrasonic waves are reflected differently depending on the type of tissue they pass through, aiding the detection of abnormal tissues.

Staging and Prognosis

Benign

Not spreading, usually a more mild disease.

Malignant

Cancerous, where the tumour grows uncontrollably and may spread.

In-situ / Invasive

Localised

A tumour restricted to a single site.

Metastases

Where the tumour has spread to other parts of the body beyond the primary site. Metastatic sites (secondaries) my be regional or distant from the original tumour.

Staging

Staging is where the disease is categorised as to how far it has spread. The precise staging system used will depend on the type of cancer the patient has. In general low stage patients are those with localised tumours that are easily resectable, whilst high stage patients are those with widespread metastases. The treatment given may largely depend upon which stage the patient is at diagnosis.

Prognosis

is the expected outcome of a disease and it's treatment, this may be influenced by a variety of factors such as stage, age, site etc. depending on the particular type of cancer. For example, in general a patient with localised disease may have a more favourable prognosis compared to a patient with widespread disease which may be less favourable.

Remission

is where the symptoms of cancer are no longer present. There is no longer any evidence of the disease using the available investigations.

Relapse

This is when the disease reoccurs after a period in remission.

Refractory

This is where the cancer is resistant to treatment, patient may nevergo into remission, possibly with stable or progressive disease.

Restaging

This is where the patient is staged again after a period of treatment to access the response to therapy.

Follow-up

When treatment is complete the periodic visits to the physician are needed to monitor the patient and ensure there has been no recurrence of the disease.

Treatment

Curative treatment

treatment to destroy the cancer.

Palliative treatment

treatment which relieves the symptoms and pain.

Surgery

• Pre-operative chemotherapy - drugs given to shrink the tumour before surgery.
• Complete resection this is where all of the tumour has been totally removed during surgery, as opposed to an incomplete resection. The surgical specimen may be examined by a pathologist to determine if it is likely to have removed all of the primary tumour. If there is any tumour left after surgery this may be macroscopic (visible to the eye) or microscopic, in either case radiotherapy may be needed to kill the remaining tumour cells.
• Prosthesis - an artificial replacement e.g. for an amputated limb.
• Endoprosthesis - a prosthesis which fits inside the body e.g. replacing the thigh bone.

Radiotherapy

• External radiotherapy - radioactivity from a source outside the body.
• Internal radiotherapy - placing radioactive source within the body in or near to the tumour to kill the cancer cells (Brachytherapy).
• Fractions - the radiotherapy dose is divided into a number of smaller doses to reduce the risk of side effects. There is normally one fraction per day.
• Hyperfractionated radiotherapy - more than one fraction is given per day.
• Radiotherapy field - the area towards which the radiotherapy was directed.
• Total Body Irradiation (TBI) - radiation to the whole body e.g. to destroy all malignant cells prior to bone marrow transplant (BMT).

Chemotherapy

Since the 1960's the development and use of drugs has dramatically improved the prognosis for many types of cancer. Chemo- means chemicals, for most types of cancer chemotherapy will consist of a number of different drugs, this is known as combination chemotherapy. Chemotherapy may be given in a variety of ways; Intravenously (IV) -into a vein is the most common, Intramuscularly (IM) -injection into a muscle, Orally -by mouth, Subcutaneously (SC) -injection under the skin, Intralesionally (IL) -directly into a cancerous area, Intrathecally (IT)-into the fluid around the spine, Topically -medication will be applied onto the skin.

• Cytotoxic - cytotoxic drugs kill or damage cells. The normal cells of the body grow and die in a controlled way, but cancer cells keep growing and multiplying. Chemotherapy destroys cancer cells by stopping them from growing or multiplying at one or more points during the life cycle of the cell.
• Central line - a thin plastic line into a vein in the chest used for the delivery of chemotherapy e.g. HICKMAN® catheter.
• Drug resistance is where tumour cells become resistant to chemotherapy. Some tumour cells will be chemo-sensitive and are killed by anticancer drugs; the cells that remain are likely to be more resistant. Thus by selection it is the most resistant cells survive and divide, they may be resistant to a particular drug, a class of drugs, or all drugs.

Bone Marrow Transplantation (BMT)

The bone marrow is destroyed by high dose chemotherapy and possibly radiotherapy which has been given to kill malignant cells in the body. Healthy matching marrow is then transplanted into the patient.

• Allogeneic BMT Healthy marrow is taken from a matched donor and used to replace the patients bone marrow which has been destroyed by high dose chemotherapy. The donor may be a relative, if the patient has a twin this may be the best match, otherwise a brother, sister, or another unrelated person may donate marrow.
• Autologous BMT In an autologous bone marrow transplant the marrow is first taken from the patient. The marrow is usually then purged with chemicals to kill any malignant cells in it, and may then be frozen to preserve it. High dose chemotherapy is given to the destroy the patient's remaining marrow. The frozen marrow is then thawed and transplanted back into the patient.
• Peripheral Blood Stem Cell Rescue (PBSC)

New approaches - Gene therapy / Immunotherapy

In the future patients might be immunised against their own cancers by injecting them with their own tumour cells after they have been genetically modified. The gene-modified tumour cells may encourage the patients own immune system to destroy the cancer cells. Tumour necrosis factor (TNF) and interleukin-2 (IL-2) are substances associated with the immune system which encourage anititumour activity.

Toxicity and Late Effects

Acute

Transient. Some side effects may be of short duration. May be sudden or severe.

Chronic

Long lasting. Some side effects may be long lasting e.g. kidney damage.

Immuno-suppressive

Drugs may dampen the immune system making the patient prone to infections.

Neutropenia

reduced levels of white cells in the blood. Febrile neutropenia -with fever.

WHO toxicity gradings

World Health Organisation toxicity grading guidelines. In general these range from grade 0 (none) to grade 4 (life threatening).

Late effects

It is possible that treatment may have delayed effects e.g. on fertility and growth.

Cancer Research (i) Basic Science

Developing new drugs

two general approaches include a) the mass screening of thousands of natural substances to see if they have any anti cancer potential; or b) making new compounds in the laboratory e.g. creating analogues of existing drugs (slightly modified chemical structures) designed to make the drug more potent.

Pre-clinical testing of drugs.

New drugs may be tested on animals to indicate the maximum doses, toxicities and anti cancer potential before they are tested on humans (see phase I trials).

In vitro / in vivo

experiments may be in vitro (in the test tube) or in vivo (in the body). Much laboratory work uses cell cultures (cells grown in the lab); either from established cell lines or from material collected at biopsy/surgery.

Biochemistry.

There is a great deal of research investigating the mechanisms of how drugs are metabolised and absorbed by the body's cells. Growing knowledge in this field provides the foundations for improving the anticancer potential for existing drugs and for developing new 'designer' drugs. Other work includes research into the machanisms of drug resistance.

Tumour biology

cytogenetics. During recent years there has been rapid advances in the understanding of tumour biology at the genetic level. Research into the genes associated with different cancers include the identification of oncogenes, tumour supressor genes. This is a key area of cancer research, providing a basis for the development of new treatments and new diagnostic tools. In the future treatment may be more tailored to the biological features of the cancer rather than the standard clinical features.

Cells, Chromosomes and Genes

There are more than 100 trillion cells in the human body. Every cell (except the red blood cells) contain the entire human genome that is, all the genetic information necessary to build a human being. This information is encoded in the DNA.

Inside the cell's nucleus, DNA is tightly twisted and packed into 23 pairs of chromosomes (one chromosome in each pair comes from each parent).

There are 46 human chromosomes which are estimated to contain about 100,000 individual genes that determine each person's inherited human characteristics. Each gene is a segment of double-stranded DNA which holds the information for making a specific molecule, usually a protein. This information (or code) lies in varying sequences of vast numbers of pairs of the four chemical bases that make up the DNA. A change in the sequence (a mutation), or missing sequences (deletion) of these bases may result in an altered protein that does not work properly, or a failure to produce that protein altogether.

Cancer Research (ii) Clinical Trials and Epidemiology

Types of study

Some Studies are experimental which make in intervention e.g. clinical trials, others are observational in which no medical intervention is made. Studies may also be prospective ie. ongoing into the future, or retrospective ie. looking at historical data. In general studies aim to test a hypothesis (theory) by disproving null hypothesis (the opposite theory) e.g. in a trial of a new drug the null hypothesis might be that the new drug has no effect on survival.

Phase I clinical trials

Tests new types of treatment and aim to define a safe dose that will be used for further studies. This is usually the first testing of a treatment on humans after extensive laboratory work. Recruitment for Phase I trials are usually from patients for whom no other effective therapy is known.

Phase II clinical trials

Test the anti cancer effects of the new treatment, and include very detailed toxicity investigations. If there is effective antitumour activity, it may be incorporated in a future phase III study.

Phase III clinical trials

Compare one or more treatments of proven efficacy. Often patients will be randomised between an established 'standard' treatment and a new 'experimental' treatment - it is not known which is the better treatment.

Randomisation

Treatment is randomly allocated to ensure there is no systematic bias in the results.

Ethical approval

all new trials have to first be approved by an independent ethics committee.

Informed consent

is where patients agree to a treatment / randomisation having a reasonable understanding of it.

Morbidity

Looking at the incidence or prevalence of a disease in a population.

Mortality

Looking at the death rates caused by a disease.

Epidemiology

The study of populations. Regional and National cancer registries record all cancers enabling population based studies in cancer to be carried out. Knowing how many people get a type of cancer out of the overall population provides the information needed to calculate incidence rates.

Longitudanal Studies

are studies where individuals are followed over time. A fixed population (cohort) may be monitored over a number of years.

Cross-sectional Studies

are studies that are carried out at just one point in time.

Case Control Studies

are where cases are compared to controls, in order to avoid bias the controls are matched for factors such as age and sex. The aim is to investigate possible associations between certain factors and risk of disease. For example a study investigating smoking and the risk of lung cancer.

Meta Analysis

is where data from a number of studies are lumped together in order to provide evidence for or against a hypothesis.

This guide by Simon Cotterill

First created 4th March 1996
Last modified: 1st February 2014