Treatment modalities

This section provides an overview of the primary treatment modalities (types of treatment) for children and young people with cancer.

Four primary modalities are used:

  • Cytotoxic chemotherapy
  • Surgery
  • Radiotherapy (including proton beam radiotherapy)
  • Biological therapies (eg immunotherapy)

Combinations of these modalities are often used in treatment.

Cytotoxic chemotherapy

Chemotherapy is also known as Systemic Anti-Cancer Therapy (SACT). Cytotoxic chemotherapy may be used in several ways:

  1. Adjuvant therapy: Chemotherapy is used in conjunction with another treatment, such as surgery or radiotherapy, to treat disease
  2. Neo-Adjuvant: Chemotherapy is used to shrink a tumour before it is removed surgically.
  3. Curative Therapy: Chemotherapy is given with the aim of cure
  4. Concurrent: Chemotherapy is given alongside other types of treatment such as with radiotherapy to increase the sensitivity of the cancer cells to radiation.
  5. Palliative: Cure may not be possible but chemotherapy can be given to slow tumour growth and help relieve symptoms.

Normal cell growth is a controlled process whereas the growth of cancer cells is not. Cancer cells have damaged DNA that means they continue to multiply when normal cells would stop. The cell cycle describes the stages a cell goes through when it multiplies. Cytotoxic chemotherapy drugs attack cells at various stages in the cell cycle. They are not targeted therapy; they destroy all rapidly dividing cells indiscriminately. This means a large proportion of cancerous cells are affected but unfortunately so are healthy cells[1]. The effects on the healthy cells are the cause of most chemotherapy side-effects, for example, on hair, bone marrow, gastrointestinal tract and epithelial cells. 

Cytotoxic drugs are classified by both their action on the cell and their chemical group. When drugs are classified by their activity on the cell they are split into two groups, those that are cell cycle specific and those that are cell cycle non- specific.

Chemical groups of drugs are split into:

  • Alkylating agents
  • Antimetabolites
  • Vinca alkaloids
  • Anti tumour antibiotics
  • Miscellaneous (this group covers all drugs that cannot be categorised. This might be due to lack of knowledge on the drug and its actions or to the drug having more than one action)

Combinations of drugs that work in slightly different ways are usually used to treat cancer so that more cancer cells are likely to be killed and the cancer cells are less likely to become resistant to these drugs [2]. 

Cytotoxic chemotherapy drugs can be delivered via various routes:

  • Intravenous: This is the most commonly used route for cancers in children and young people. The majority of patients will have a central venous access device for their treatment.
  • Oral: Some chemotherapy drugs can be given by mouth (or via a nasogastric tube or gastrostomy). Oral chemotherapy is commonly used as part of the treatment for acute lymphoblastic leukaemia (ALL) and some types of brain tumours.
  • Intramuscular: Some drugs can only be given by injection into a muscle. This method is used commonly as part of treatment for ALL.
  • Intrathecal: As chemotherapy in the bloodstream may not reach the fluid around the brain and spine, chemotherapy may need to be given via this route. This is most often used in the treatment of ALL and non-Hodgkin’s lymphoma.
  • Sub-cutaneous
  • Intravesicular: directly into bladder or other organ
  • Intra-arterial: directly into a tumour

Surgery

Depending on the diagnosis, surgery may be required for childhood and adolescent tumours. This may be the first part of treatment and include a biopsy, or may be undertaken after initial chemotherapy that will hopefully have shrunk the tumour. For some tumour types surgery will be the only treatment required.

The aim of surgery is to remove the tumour entirely, ideally with clear disease-free margins. However, this is not possible for brain tumours and therefore a scan soon after surgery is very important to determine if the entire tumour has been removed. The tumour is sent for pathology to confirm the diagnosis. If chemotherapy has been given before surgery then the percentage of necrosis (dead cells) can be determined. This may guide subsequent treatment.

The size and location of a tumour will influence how complicated surgery and subsequent recovery is. The surgeon and the oncologist discuss the optimum timing of surgery, to allow only the minimum interruption possible between chemotherapy cycles.

Limb sparing surgery 

Radiotherapy

Radiotherapy is the treatment of disease using ionizing radiation. The radiation is transmitted in a beam to the area of the body that requires treatment. The aim is to destroy cancer cells and do as little harm as possible to healthy tissues. Radiotherapy is used for the following reasons:

  1. Curative: To destroy the tumour
  2. Neo-adjuvant: To reduce the size of the tumour before surgery
  3. Adjuvant: To ensure all the cancer cells are destroyed after surgery
  4. Palliative: To slow down the progress of the tumour, relieve pain or other symptoms 

Treatment must be carefully planned in advance and this can take considerable time. For patients receiving radiotherapy to the head a mould or mask (Picture 1) is sometimes required to keep the head still during treatment. Often a mark will be tattooed onto the body to ensure the treatment is given accurately to the right place each time. This is also helpful should the patient require treatment in the future near to the original site [3]. It is essential that the patient keeps completely still during radiotherapy. Young children (under the age of 6) or those with learning difficulties or problems with pain may require general anaesthesia, although with good Play Specialist support some children as young as 2 years can achieve this without anaesthetic. Radiotherapy is usually given once a day from Monday to Friday over a period of a few weeks. Occasionally radiotherapy is given twice a day.

The amount and duration of radiotherapy depends on the type of cancer, its location in the body and the treatment protocol the patient is on.

The side-effects of radiotherapy can be split into two categories, early or acute effects and late or delayed effects. Severity of side-effects is dependant on site, length and treatment dose of radiotherapy and often any adjuvant therapies such as chemotherapy.

Side-effects include:

  • Tiredness/fatigue
  • Skin reactions (erythema, dry skin or peeling/flaking skin that may reveal the moist dermal layer)
  • Hair loss
  • Oral (dry mouth, mucositis)
  • Nausea and vomiting
  • Diarrhoea
  • Myelosuppression

Some children or young people having a stem cell or bone marrow transplant may have total body irradiation (TBI). The purpose of TBI is to remove the immune system and destroy any remaining disease in the body. TBI is usually given 3-4 weeks before the stem cell transplant and is delivered over 1-8 sessions, with two sessions often being given in one day. Some side-effects of TBI occur during treatment but others may occur months or years afterwards.[4].

CCLG Total body irradiation factsheet 

Proton beam radiotherapy

Proton beam radiotherapy (also called proton radiotherapy or proton beam therapy) is an alternative form of radiation cancer treatment that may target some tumours more precisely because the radiation beam travels into the body in a different way. It can be programmed to stop at a measured point (the tumour site), thus reducing the effects caused by the exit beam. This precision may cause less damage to surrounding healthy tissue and therefore patients may experience less side-effects, particularly in the long term. As children and young people’s bodies are still growing, they are more sensitive to the damage to healthy tissue caused by radiation.

Because of this proton radiotherapy has generated increasing interest over recent years. However, at present there is no suitable facility to treat children and young people with proton radiotherapy in the UK. Two sites are planned, in Manchester and London, but will not be operational until 2018/9 at the earliest. However, patients who may benefit from this approach can be referred to centres overseas. Since 2008 the NHS has funded access to this treatment for specific tumours. Patients who may be suitable are referred to the Clinical Reference Panel of the NHS Proton Overseas Programme. This panel reviews individual cases and decide purely on clinical grounds, whether the case is suitable for proton radiotherapy. If accepted the patient can then be referred to a suitable proton centre overseas, usually in the USA, and will be funded by the NHS.

Biological therapy (also called immunotherapy)

Biotherapy is the therapeutic use of biological materials or biological response modifiers. Biotherapies are a relatively new development in cancer and are becoming increasingly used for childhood and adolescent cancer. These drugs work differently to chemotherapy drugs and are often referred to as targeted therapy as they target specific cells rather than destroying all rapidly dividing cells.[5]

Types of biological therapies:

  • Angiogenesis inhibitors: Interfere with the development of blood vessels, meaning the cancer is unable to receive the oxygen and nutrients it requires to survive. e.g. Thalidomide.
  • Cancer growth inhibitors: Interfere with the chemical signals that cancer cells use to grow and divide, e.g. Imatinib
  • Cancer vaccines: Still currently being developed, with the aim of stimulating the immune system to identify cancer cells as abnormal and destroy them.
  • Gene therapy: Very new and still being developed, with the aim of putting genes into cancer cells to make them more sensitive to chemotherapy [6]
  • Interleukin and Interferon: Given to stimulate the body’s own immune system to fight some kinds of cancer, encouraging the body’s immune system to kill cancer cells
  • Monoclonal antibodies: Work by recognising the protein on the surface of the cancer cell and then locking onto it. This triggers the body’s immune system to attack the cancer cell causing the cell to kill itself.

Why do we use biotherapies? [2]

  1. To provide a cure as primary or, more commonly, adjuvant therapy
  2. Improve overall response or improve survival when used in conjunction with usual therapies
  3. Maintain and enhance a child or young person’s quality of life when treatment is no longer curative- Palliative
  4. Also can be used to decrease the severity of toxicities caused by chemotherapy, for example GCSF.(link GCSF to glossary & ? adjunctive therapies & drug sheets)

As with other cancer treatment modalities biotherapies cause a varied amount of side-effects. Again this variation is due to the type of therapy that is used and often the individual patient. Some of the common side-effects are:

  • Flu-like symptoms
  • Fatigue
  • Joint pain
  • Muscle pain
  • Rigors
  • Nausea
  • Vomiting
  • Rashes
  • Hypotension
  • Capillary leak syndrome

References

[1] Chordas, C and Graham, K., (2010) ‘Chemotherapy’, in Tomlinson, D and Kline, N. (ed.) Paediatric Oncology Nursing, New York: Springer

[2] Haematology/Oncology Service (2010) Cytotoxic Certification Course Resource Book for Registered Nurses, Canterbury District Health Board: Author

[3] Loch, I and Khorrami, J. (2010) ‘Radiotherapy’ in Tomlinson, D and Kline, N. (ed.) Paediatric Oncology Nursing, New York: Springer

[4] Childrens Cancer and Leukaemia Group (CCLG) (2013) Total Body Irradiation – Information for young people and families factsheet www.cclg.org.uk

[5] Gianer, L. (2010) ’Biological and Targeted Therapies’ in Tomlinson, D and Kline, N. (ed.) Paediatric Oncology Nursing, New York: Springer

[6] Cancer Research UK http://www.cancerresearchuk.org