Radiotherapy is a key component of both radical (curative) and palliative treatment for cancer. Most patients are treated using a high energy beam of X-rays delivered to a precise area, using a linear accelerator. Radiotherapy can be given either as external radiotherapy from outside the body or from within the body as internal radiotherapy.

The dose of radiation is defined as irradiation absorbed by each kilogram of tissue expressed as Grays (Gy) - 1 Gy = 1 J/kg of tissue. The dose is usually given in a number of daily fractions with the total dose determined by tumour sensitivity and normal tissue tolerance. Cells start to recover within 6 hours of radiation. Therefore if fractions are too close together then normal tissues would suffer excessive toxicity, but too far apart and sublethal damage to cancerous tissue could be repaired.

Treatment is planned by a multidisciplinary team on the basis of a combination of physical findings, diagnostic imaging information, anatomy, pathology and natural history of the tumour involved.

The efficacy of radiotherapy in treating malignant cells varies widely between different malignancies. Radiation therapy should not be administered during any trimester of pregnancy.¹

Uses of radiotherapy¹

• When used alone in the early stages of certain cancers, radiotherapy can be curative, e.g. Hodgkin's disease, non-Hodgkin's lymphoma, carcinoma of the larynx, prostate or cervix, and some tumours of the central nervous system, e.g. medulloblastoma.
• Compared with surgery, radiation often offers improved or equivalent tumour control with less morbidity. Radiation and surgery treatments require individual patient assessment and discussion of the patient's condition and preferences.
• Patients medically unfit for surgery, e.g. cardiovascular, respiratory or other chronic diseases.
• Anatomically unresectable cancers.
• Close proximity to critical structures, e.g. blood vessels, central nervous system, peripheral nerves.
• Preoperative, e.g. to shrink the tumour, facilitating subsequent surgical resection.
• Postoperative, e.g. to decrease the risk of local or regional tumour recurrence.
• Palliative, e.g. to relieve bone pain, reduce spinal cord compression, control bleeding or relieve airway or gastrointestinal obstruction.

How radiotherapy works

• The exact mechanisms of action of radiation's antimitotic properties are still being elucidated. It is largely thought to function through the generation of free radicals that break double-stranded DNA and cause irreversible loss of a cell's reproductive capacity, leading to its death.
• Since cancer cells tend to have a reduced ability to repair this damage compared with normal cells, they are selectively harmed by the radiation. It is also thought that radiation influences the cell cycle, interfering with the normal processes of growth, senescence and 'programmed' cell death (apoptosis).
• Another factor in sparing normal tissues is the precision with which radiotherapy beams are 'aimed' to take account of any anatomical distinction between normal and cancerous tissues.
• The toxic effects of radiation require the presence of oxygen, so hypoxic tissues are less sensitive to radiotherapy. Resection of a large, poorly vascularised tumour can improve outcome from irradiation.

Treatment planning and delivery of radiation

• Radiation is usually delivered either by external beam irradiation or brachytherapy, where a radiation device is placed within or nearby the target tumour. This latter technique is used successfully in treatment of cancers affecting the head and neck, cervix and endometrium.
• Radioactive I₁₃₁ can be taken orally to treat thyrotoxicosis and thyroid cancers.
• The delivery of radiotherapy is carefully planned using CT or MRI scans to localise target tissues. Contemporary treatment-planning computers allow 3D anatomical data to be used to design the irradiation beams and fields. This maximises the dose to the required target but spares adjacent normal tissue as much as possible.
• Patients are very carefully immobilised and thermoplastic masks or other similar positioning devices are often used. Treatment technique and volume are tried on a radiation simulator which duplicates the treatment plan using only superficial radiation for imaging and accessing accurately the location of the radiation beam.
• Tattoos are placed on the patient to ensure that treatments are delivered to the same tumour volume each time. Blocks are often used to shield normal tissues such as the heart and lungs.
• A common technique is to use maximum tolerated dose to the total treatment volume plus a boost delivered directly to the tumour.

Radiotherapy modalities¹

External beam radiation therapy

• Three-dimensional conformal radiation therapy: CT or MRI is used to target tumours while minimising radiation exposure of healthy tissues.
• Four-dimensional radiation therapy: computer-assisted tracking or gating of CT images of moving targets, for tumours that are susceptible to movement, e.g. lung, liver, pancreas or breast.
• Intensity-modulated radiation therapy: the radiation beam is divided into components, which permits sparing of normal tissues.
• Stereotactic radiosurgery (e.g. gamma knife): Multiple radiation beams converge on the tumour, delivering high-dose radiation to the tumour but little to surrounding tissues.
• Stereotactic body radiation therapy (e.g. CyberKnife®): high-dose radiation delivered using robotic guidance.

Internal radiation therapy

• Temporary brachytherapy implant: a radiation source is placed within or near the tumour target and is later removed.
• Permanent brachytherapy implant: a low-dose rate (i.e. long half-life) radiation source is placed within or near the tumour target.
• Systemic radiation therapy: systemically administered radioisotopes target tumour cells.

Acute complications of radiotherapy

• Acute effects are defined as occurring during the treatment and within 2-3 weeks after its completion.
• Acute effects can be distressing but tend to resolve.
• General fatigue is the most common acute adverse effect.
• Rapidly proliferating tissues, e.g. skin, mucosa and bone marrow are most sensitive to the toxic affects of radiotherapy.
• Skin:
  • Erythema, dry and moist desquamation, skin tanning (starts in hair follicles), hair loss and sweat/sebaceous gland dysfunction.
  • The use of high-energy radiographs has vastly reduced the severity of skin reactions to radiotherapy.
  • When a need for skin irradiation exists, e.g. skin involvement by tumour or skin as the target for basal cell cancers, the technique is altered to produce a brisk skin reaction.
  • Where the skin is denuded (moist desquamation), it must be kept scrupulously clean to avoid superinfection.
  • Skin heals from the outer margins inwards by about 3 weeks.
  • Hair loss occurs in the treatment field but is usually temporary, regrowing within a few weeks of ceasing treatment.
  • Chemotherapeutic agents can enhance skin sensitivity.
  • Topical aloe vera gel has been claimed as a useful prophylactic agent for skin burns in radiotherapy, particularly at high doses,^2,3 but some randomised trials have not demonstrated a significant effect.⁴
  • Aqueous cream can be used to soothe the symptoms of dry desquamation.⁴
• Gastrointestinal tract:
  • Loss of taste, salivary dysfunction, oral mucositis, diarrhoea, nausea and vomiting.
  • Severe, painful mucositis may be complicated by yeast or bacterial superinfection and antimicrobials should be considered.
• Bone marrow:
  • Patients may develop cytopenias.
  • In whole body irradiation, white cell count falls with immune suppression.
  • When bone marrow reactions are severe enough, repeat treatments may need to be delayed to allow normal tissues to repair.
• Lungs:
  • Irradiation of the lung can cause pneumonitis with fevers, cough, dyspnoea and pulmonary infiltrates that may require steroids.⁵

Long-term complications

Long-term complications are specific to tissues involved and usually occur if normal tissue tolerance is exceeded. Needs careful dosimetry and planning to avoid this, e.g. >45 Gy to the spinal cord causes myelitis and >20 Gy to the kidney can cause renal impairment.

• Neck: high dose can lead to fibrosis and decreased movement with a woody texture, especially after surgery.⁶
• Jaw muscles: fibrosis impairing mastication. Postoperative jaw exercises may reduce this complication.⁶
• Lymphatic system: lymphoedema, intermittent erysipelas.
• Infertility.
• Wounds: delayed healing.
• Skin:
  • Telangiectasis can occur as a late complication.
  • Ulceration over bone with exposure and possible osteoradionecrosis is fortunately rare and requires a long-term approach that may involve antibiotics, hyperbaric oxygen and surgery.
• Salivary function:
  • Loss of salivary flow with xerostomia is a common complication after head/neck irradiation and particularly likely if the parotids have been irradiated.
  • Pilocarpine may help to increase salivary flow, and artificial saliva or frequent sipping of water may be useful.⁶
  • Intravenous amifostine given during treatment has been shown to reduce the severity and duration of radiotherapy-related xerostomia without effects on survival.⁷ However, it is expensive, needs to be injected daily, and can cause nausea and vomiting, so it may not be widely accepted.⁶
  • Close attention should be paid to oral hygiene during head and neck radiotherapy to reduce the risk of oral disease.
  • Oral and gingival tissue may undergo atrophy and telangiectasis as a late complication.
• Central nervous system:
  • Spinal cord irradiation may cause transverse myelitis and Lhermitte's symptom (electric shock-like sensation in upper limbs on neck flexion).
  • Full transverse myelitis with Brown-Séquard syndrome is fortunately rare and a complication that should be carefully avoided at all costs.
• Endocrine: hypothyroidism directly or through hypothalamopituitary axis.
• Eye: cataracts, dry eye syndrome, retinitis.
• Ears: otitis or sensorineural hearing loss.
• Increased risk of subsequent malignancy:
  • Can cause development of secondary tumours.
  • Not a problem where radiotherapy is palliative but where used curatively, e.g. in Hodgkin's disease, tumours such as sarcomas and cancers of the lung, oesophagus and breast can prove fatal.

Document references

1. Gerber DE, Chan TA; Recent advances in radiation therapy. Am Fam Physician. 2008 Dec 1;78(11):1254-62. [abstract]
2. Olsen DL, Raub W Jr, Bradley C, et al; The effect of aloe vera gel/mild soap versus mild soap alone in preventing skin reactions in patients undergoing radiation therapy. Oncol Nurs Forum. 2001 Apr;28(3):543-7. [abstract]
3. Maddocks-Jennings W, Wilkinson JM, Shillington D; Novel approaches to radiotherapy-induced skin reactions: a literature review. Complement Ther Clin Pract. 2005 Nov;11(4):224-31. [abstract]
4. Heggie S, Bryant GP, Tripcony L, et al; A Phase III study on the efficacy of topical aloe vera gel on irradiated breast tissue. Cancer Nurs. 2002 Dec;25(6):442-51. [abstract]
5. Jenkins P, D'Amico K, Benstead K, et al; Radiation pneumonitis following treatment of non-small-cell lung cancer with continuous hyperfractionated accelerated radiotherapy (CHART). Int J Radiat Oncol Biol Phys. 2003 Jun 1;56(2):360-6. [abstract]
6. Schreiber GJ; Radiation Therapy, General Principles, Medscape, Jan 2010
7. Wasserman TH, Brizel DM, Henke M, et al; Influence of intravenous amifostine on xerostomia, tumor control, and survival after radiotherapy for head-and- neck cancer: 2-year follow-up of a prospective, randomized, phase III trial. Int J Radiat Oncol Biol Phys. 2005 Nov 15;63(4):985-90. [abstract]

Internet and further reading

• Schneck MJ; Radiation Necrosis; eMedicine, February 2010.

Acknowledgements