Radiotherapy in Palliative Medicine
ABSTRACT
Family doctors should know the indications of palliative radiotherapy in order to refer appropriately. They have to answer questions about side effects and to manage them when the patient is in the community. In palliative care, radiotherapy can curtail grow or even shrink the tumour temporarily bringing about relief of pain and other symptoms. It is indicated for spinal cord compression, cerebral metastases, superior vena cava obstruction, bone metastases and pathological fracture; control of haemorrhage, fungation and ulceration as well as relief of obstructions of ducts, hollow viscera, blood and lymphatic vessels. Management of the common acute side effects are discussed. The patients usually do not live long enough for the late side effects to occur.
Radiotherapy plays an important role in palliative medicine. Its aim is to control local symptoms with minimum associated acute radiation reaction.1 It can reduce or abolish symptoms, restrains growth of tumour, preserves function and body image, prevents bony fractures and prevents erosion or compression of blood vessels. Palliative radiotherapy is usually delivered in relatively low doses in a single treatment or a short course over one to two weeks. By reducing the total doses, acute reactions are kept to the minimum.1
Family doctors who are looking after terminal cancer patients should know the indications of radiotherapy so that the patients can be referred at an appropriate time for maximum benefit from its use. We have to answer their questions about the possible side effects. With more patients staying in the community, the family doctor should also know how to manage the side-effects of radiotherapy which may occur after the patient is discharged from the hospital. Because of the severity of some of the side-effects, the patients need reassurance and support from their family doctors. They want to know when the side effects will resolve following completion of radiotherapy.
Because of the relatively faster multiplication of cancer cells, radiation has a more damaging effect on cancer cells than normal cells. In palliative care patients, although radiotherapy cannot cure the patient, it can help curtailing growth or even shrink the tumour temporarily bringing about relief of symptoms or slowing deterioration of symptoms.
After irradiation, inflammation can occur in and around the tumour, causing a temporary enlargement of the tumour with its deleterious effects. It has to be cautious if the tumour is large and is within or adjacent to critical organs, e.g. in intracranial metastases and vertebral column metastases. This is particularly so if the cancer is relatively radio-resistant. Patients of intracranial tumour or trachea compression can be given high dose of steroid before radiotherapy. Important tubes adjacent to cancers to be radiated can be intubated beforehand.
It takes a couple of weeks for the cancer to shrink. The patients who have been on dexamethasone, orally or parenterally, to control the inflammation should continue it until there is clinical improvement and then taper the dose slowly to a low maintenance dose within a few weeks.
Radiotherapy is very effective in relieving pain caused by bone metastasis. The effect is independent of the histology of the primary tumour.4 Some degree of pain relief occurs in 80 percent of patients, half of them occurs within the first two weeks. Pain relief is seen up to 4 weeks from the start of treatment.4 If pain returns to a previously irradiated site, retreatment may be feasible particularly after single dose treatment.5 In some patients, there may be an acute exacerbation of pain within a few hours after single fraction palliative radiotherapy.
Radioactive Strontium is selectively taken up at sites of osteoblastic activity in bone metastases.7 It can cause effective pain relief in 80 percent of patients and can reduce the number of new painful sites. It can be given as a single intravenous injection and can be repeated at three-monthly interval if appropriate to manage pain from multiple metastases.8
Neuropathic pain caused by direct tumour compression and infiltration of brachial plexus from apical lung tumours and at the lumbosacral plexus from pelvic tumours of the bowel, bladder, ovary or uterus respond very well to palliative doses of radiotherapy with significant pain relief in up to 80 percents of patients.9,10,11
Internal fixation is the preferred management of fracture in long bones. However, radiotherapy is indicated in vertebral collapse, fracture of ribs and girdle bones, where surgery is not feasible or when the patient has poor performance status. Palliative radiotherapy can lead to pain relief and enable bone healing.
After internal fixation, radiotherapy can be given to control progression of the metastatic tumour and enabling healing of bone around the prosthesis.
It plays a great role in the management of spinal cord compression. The outcome of treatment depends primarily upon the speed of diagnosis and neurological status at initiation of treatment. Early radiotherapy can prevent disastrous consequences of cord compression such as urinary retention and paraplegia which can cause rapid deterioration of the quality of life of the patient.
Growth of cancers or enlarging lymph nodes close to important ducts and tracts such as oesophagus,17 upper airway, rectum, ureter, or bile duct can cause obstruction with serious adverse consequences such as dysphagia, dyspnoea, intestinal obstruction, uraemia and pain. Obstruction of lymphatic channels or blood vessels can cause lymphoedema, ischaemia and the life threatening superior vena cava obstruction.18 Radiotherapy can help relieve impending or actual obstruction with improvement of quality of life.
Radiotherapy is a well established effective treatment of cerebral metastases, reducing raised intracranial pressure, improving symptoms and preventing progressive neurological deficits. Eighty percent of patients have reduced headache, motor and sensory loss, and confusion with a complete response rate of between 35 and 55 percents.2
A new stereotactic technique can focus an x-ray beam on a small spheroidal volume around a solitary metastasis with a good response rate.3
Radiotherapy is effective in controlling vaginal and colorectal bleeding,12 haematuria,13 haemoptysis14,15,16 and bleeding from nasopharyngeal or superficial ulcerating cancers.
Local irradiation is most valuable in the prevention of fungation when the overlying skin is still intact. Radiotherapy can palliatively retard the progress or temporarily improve fungation and ulceration of superficial cancers such as those in the head and neck, breast and skin cancers with cosmetic benefits.
In emergency, arrange urgent consultation with radiotherapist over the phone. In patients who have an impending serious consequence, such as spinal cord compression, increased intracranial pressure, superior vena cava obstruction or other duct obstruction, give a large dose of dexamethasone intravenously while waiting.
Palliative radiotherapy is usually delivered as a single or a small number of large-dose fractions in minimal number of hospital visits, in contrast with a large number of small doses in curative radiotherapy.14 Late side effects depend on the dose per fraction. It is of little significance in patients who are receiving radiotherapy for palliation. They usually do not live long enough to suffer from the late side effects.
Radiotherapy can cause acute side effects which peak at about one to two weeks after treatment. They generally resolve completely three to four weeks later. Worsening of symptoms can occur before improvement because of tumor oedema. Prophylactic intubation of ducts or tubes may be indicated before irradiation, and high dose steroid has to be started in certain situations and continued for a couple of weeks. Because of lack of controlled studies, many of the suggested management described here are empirical.
The severity depends on total dose and duration of treatment. For palliative radiotherapy, because of the lower dose in a shorter duration than in curative radiotherapy, the acute side effect is usually minimal.
Rapid cellular turnover of the gastrointestinal tract makes it particularly vulnerable to the damaging effect of radiotherapy.
Virtually all patients who receive radiotherapy to the head and neck develop oral side effects.19 Dry mouth from reduced saliva production can be troublesome. This can be helped with small frequent sips of ice drinks or semifrozen fruit juice. Artificial saliva has to be used several times per hours to be helpful.20 Oral pilocarpine 5mg tds is safe and effective.21 Glycerin can dehydrate the mucosa and lemon juice can exhaust the salivary gland. These have to be avoided. Dry or sore lip can be soothed with soft yellow paraffin.
Together with dry mouth, it can cause mucositis with painful ulceration, diffuse erythrema, pseudomembrane formation, altered taste and dysphagia. These usually develop about two weeks after initiation of radiotherapy and heal by about two to three weeks after the end of radiotherapy.22 Cool, soft and low salt food can be tolerated better than hot dry food. The patient needs good mouth care and should avoid smoking, alcohol spicy and acidic foods.23 Rinse and gargle with normal saline and clean the teeth thoroughly with a soft brush after each meal. Frequent rinsing with dilute sodium bicarbonate solution is soothing and prevents infection. Regular thymol or chlorhexidine mouthwashes can also prevent infection but some patients do not like the taste.
In the presence of multiple painful ulcers, gargle with benzydamine (Difflam) mouthwash, which has an anti-inflammatory and mild local anaesthetic action, (15ml 3-6 hourly) or soluble aspirin solution (300mg in 5ml water) half an hour before food can make oral feeding less painful.20 Sucralfate suspension, made from crushed tablet or sachets of powder (1 gm), given before meals protects the ulcers by coating raw mucosa.24 The suspension can be held in the mouth for a few minutes and be swallowed in the case of oesophagitis. Mucaine, a combination of antacid and local analgesic (10mls), can be given in the same manner,20 but is less effective. Gargle with tetracycline solution four times a day after food can promote healing of aphthous ulcer and prevent bacterial infection of ulceration.
If the pain is severe, the patient may swish 10ml of xylocaine viscous in the mouth for thirty seconds and spit out.22 It can be swallowed if there is painful oesophagitis. Avoid taking food or drinking within one hour post-application for fear of choking. Severe oral pain may require systemic analgesic such as morphine.25 Some patients may need nasogastric feeding for a few days to maintain nutrition.
Secondary oral thrush can be treated with nystatin oral suspension (1ml) or micronazole (Daktarin) oral gel (1 teaspoon) four times daily after food. If the patient has reduced saliva production and in the presence of painful ulcers, sucking of amphotericin lozenges is less appropriate. In severe stomatitis or oesophagitis, the patient needs oral fluconazole 100mg daily for two to three weeks. Oral anti-viral agents are indicated for activation of herpes stomatitis.
It can persist for several days even though antiemetics are given before radiotherapy. It is worsened by anxiety, so reassurance is important. It may first appear two days after radiotherapy when the patient is at home under the care of the family doctor. The new 5HT3 receptor antagonists, such as ondansetron (8mg twice daily) and tropisetron etc, are very effective, but are very expensive. The dopamine receptor antagonists, such as haloperidol (1-1.5mg bd) and metoclopramide (10-20mg tds), are also effective in a dose higher than in general use. If the patients cannot tolerate oral medication, they need initial control with subcutaneous or intravenous injection followed by oral maintenance dose. Dexamethasone (4mg daily), orally or parenterally, or prednisolone (10-30mg daily) is a very good adjuvant.
It is caused by mucositis and release of prostaglandin. It begins in the second week of radiotherapy and lasts 1-2 weeks after completion. Sometimes, it may be so severe that the patient needs electrolyte and fluid replacement. Most patients can tolerate a low fibre diet. It can be controlled with Lomotil, loperamide (maximum 16mg/day) or codeine (30-60mg two to three times daily) if the patient is not already receiving a stronger opioid. In severe cases, steroid or non-steroidal anti-inflammatory drugs (NSAIDs) are indicated to reduce inflammation of the gut and hence diarrhoea.
The skin responds to radiotherapy quite similarly to a sunburnt, but differs in extent and duration.26 Moist regions with opposed skin surfaces, such as the perineum or inframamary fold, are particularly affected. Reaction usually develops in one to two weeks and lasts for two to three weeks. During this period, avoid sun exposure, hot baths and protect from further trauma such as friction from tight clothing, straps, etc. Wash with warm water and pat dry with a soft towel. Avoid cosmetics, deodorants, adhesive plasters, perfumed soap or creams. Mild skin reactions require no active treatment. Do not apply fentanyl patch on irradiated skin area.
Erythema Emollient like aqueous cream has a soothing effect. One percent hydrocortisone cream can reduce pain and inflammation, but avoid it in the genital area. Oral analgesic and even steroid are indicated for more severe pain.
Dry peeling follows erythema. Emollients containing soft liquid paraffin or sorbolene with 10% glycerine can be applied. Some preparations with benzalkonium have an additional antiseptic effect.
Weeping is most common in moist skin folds and can last for weeks in severe cases. Topical gentian violet can promote drying, ease pain and prevent infection, but has a staining problem. Silver sulphadiazine cream may be helpful. Starch powder in baby powders help keep the skin dry and comfortable. However, talcum powder and any cream containing metal salts, such as zinc oxide cream, should be avoided during treatment because these may enhance the reaction. In severe cases, short term use of normal saline, in the form of wet compress, promotes epithelisation. The dressing has to be changed when it becomes dry. Frequent change can also prevent infection. Infection needs oral antibiotic treatment.
Hair starts to fall off within a few days of cranial irradiation. Complete alopecia is usually unavoidable.27 Wearing a wig can have psychological benefit. Generally, hair will regrow in two to three months if the patient does not die before that.
Pneumonitis presenting as dry cough and dyspnoea may be seen up to 4 months after radiotherapy which has included the lungs. It can be managed with oral steroid such as dexamethasone 4mg daily or prednisone 50mg daily tailing off in 2 to 3 weeks. Antibiotics are required if there is secondary infection.
After infection is excluded, frequency and dysuria of radiation cystitis can be managed by alkalinising urine with potassium citrate 1-2 sachet three to four times a day. Pyridium 1-2 tablets tds is also effective. If they are not effective, systemic analgesics may be of value. The patient should increase fluid intake.
Alteration of circadian rhythm, headache, tiredness, nausea, confusion, somnolence or insomnia can occur after brain irradiation. Haloperidol (0.5-1.5mg bd) can be prescribed for nausea, insomnia and confusion. These usually improve within one to two weeks. The patient should be reassured of their transient nature. If the clinical features deteriorate after the first few doses of radiotherapy, consistent with increased cerebral oedema, a high dose of dexamethasone should be started or increased, maintained for two weeks before tapering off to a lower maintenance dose. If the patient is on anti-epileptic agents for convulsion caused by the brain secondaries, it is preferable not to reduce it.
Late side effects arise months to years after completion of treatment. Patients who received radiotherapy for palliative purpose usually have died before these occur.
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1. Radiotherapy is a very effective tool for palliation of symptoms of terminal cancer patients.
2. The common indications are spinal cord compression, superior vena cava obstruction, bone metastases, pathological fracture, cerebral metastases, control of haemorrhage, fungation and ulceration as well as relief of obstructions of ducts, hollow viscera, blood and lymphatic vessels.
3. For most of the indications, radiotherapy is most beneficial if it is used early when the performance status of the patient is still good.
4. Acute side effects generally peak at 1-2 weeks from the start of treatment and resolve completely in three to four weeks after completion of treatment.
5. Symptoms may deteriorate before improvement occurs because of swelling of the irradiated tumour. Prophylactic intubation or high dose of dexamethasone may be necessary.