Radiotherapy in palliative medicine

V S P Chan 陳瑞波

HK Pract 2002;24:436-443

Summary

Family doctors should know the indications of palliative radiotherapy in order to refer appropriately. They must answer questions about side effects and manage them when the patient is back in the community. In palliative care, radiotherapy can curtail growth 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; for control of haemorrhage, fungation and ulceration as well as relief of obstruction 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 late side effects to occur.

摘要

家庭醫生必須認識紓緩性放療以便做正確的轉 介，並且要解答有關的副作用，而且為治療後出院的病人提供適當的診治。紓緩性放療可以減慢腫瘤的增長，甚至令腫瘤暫時性縮小，從而緩和痛楚及其他徵狀。適應證包括脊髓擠壓、腦轉移、上腔靜脈阻塞、骨骼轉移及病理性骨折；可以控制出血，腫瘤生長及潰瘍，減輕管道，內臟，血管及淋巴腺的阻塞。文中並討論到如何處理常見的急性副作用，長期的副作用則因病情的關係而不常見。

Introduction

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, restrain growth of tumour, preserve function and body image, prevent bony fractures and 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 dose, acute reactions are kept to the minimum.¹

Family doctors who are looking after terminal cancer patients should know the indications for radiotherapy so that their patients can be referred at an appropriate time for maximum benefit. We have to answer patients' 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 hospital. Because of the severity of some 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.

Indications

Although radiotherapy cannot cure the cancer patient, it can help to curtail cancer growth or even shrink the tumour temporarily bringing about relief of symptoms or slowing down deterioration of symptoms. This is because cancer cells multiply relatively faster and radiation has a more damaging effect on cancer cells than on normal cells.

After irradiation, inflammation can occur in and around the tumour, causing a temporary swelling of the tumour with its deleterious effects. We must 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 with intracranial tumour or tracheal compression can be given a high dose of steroid before radiotherapy. Important ducts adjacent to cancers to be radiated can be intubated beforehand.

It takes a couple of weeks for the cancer to shrink. Patients who have been on dexamethasone, orally or parenterally, to control inflammation should continue to do so until there is clinical improvement, tapering off to a low maintenance dose within a few weeks.

Pain relief

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 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 is possible particularly after single dose treatment.⁵ In some patients, there may be an acute exacerbation of pain within the first few hours after single fraction palliative radiotherapy.

Radioactive Strontium is selectively taken up at sites of osteoblastic activity in bone metastases.⁷ It can give 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 be repeated at three-monthly interval if needed 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, responds very well to palliative doses of radiotherapy with significant pain relief in up to 80 percents of patients.^9-11

Pathological fracture

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 enable healing of bone around the prosthesis.

Spinal cord compression

Palliative radiotherapy has a big role to play 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 in turn can cause rapid deterioration in the quality of life of the patient.

Relief of impending or actual obstruction of ducts and hollow viscera

Growth of cancers or enlarging lymph nodes close to important ducts and tracts such as the 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 to quality of life.

Brain metastases

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 percent.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

Control of haemorrhage

Radiotherapy is effective in controlling vaginal and colorectal bleeding,¹² haematuria,¹³ haemoptysis^14-16 and bleeding from nasopharyngeal or superficial ulcerating cancers.

Control of fungation and ulceration

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.

Arrangement of radiotherapy

In an emergency, arrange an urgent consultation with the radiotherapist over the phone. In patients with 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 a minimal number of hospital visits, in contrast to a large number of small doses in curative radiotherapy.¹⁴ Late side effects depend on the dose per fraction which is of little significance in patients who are receiving radiotherapy for palliation. The patients usually do not live long enough to suffer from the late side effects.

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 takes place because of tumour oedema. Prophylactic intubation of ducts or tubes may be indicated before irradiation, and high dose steroid should be started in certain situations and continued for a couple of weeks. Because of a lack of controlled studies, many of the suggested managements described here are empirical.

Acute side effects

The severity of side effects depends on the total dose and the duration of treatment. For palliative radiotherapy, because of the lower dose in a shorter duration than in curative radiotherapy, the acute side effects are usually minimal.

Gastrointestinal (GI) system

Rapid cellular turnover makes the gastrointestinal tract particularly vulnerable to the damaging effect of radiotherapy.

Stomatitis/oesophagitis

Virtually all patients who receive radiotherapy to the head and neck regions 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 given several times per hour 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.

Additionally, radiotherapy can also 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. Patients need good mouth care and should avoid smoking, alcohol spicy and acidic foods.²³ They need to rinse and gargle the mouth 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.

For multiple painful mouth ulcers, gargling 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 (1gm), given before meals can protect the ulcers by coating the 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 However, this is less effective. Gargling with tetracycline solution, four times a day after food, can promote healing of aphthous ulcer and prevent bacterial infection.

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 after 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 (1teaspoon) four times daily after food. If the patient has reduced saliva production and in the presence of painful ulcers, sucking of amphotericin lozenges is not appropriate. In severe stomatitis or oesophagitis, the patient needs oral fluconazole 100mg daily for two to three weeks. Oral anti-viral agents are indicated if there is activation of herpes stomatitis.

Nausea and vomiting

Nausea and vomiting can occur and persist for several days even though antiemetics are given before radiotherapy. They are worsened by anxiety, so reassurance is important. They may first appear a few days after radiotherapy when the patient is already 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 expensive. The dopamine receptor antagonists, such as haloperidol (1-1.5mgbd) and metoclopramide (10-20mg tds), are also effective in a dose higher than in general use. If 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.

Diarrhoea

This is caused by mucositis and the 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.

Proctitis

Proctitis can occur in patients who have radiotherapy to the pelvis. Sitz bath with a table salt solution is soothing. Pain and swelling can be relieved by suppositories or creams used for treating haemorrhoids, which contain a combination of steroid and local analgesics. Avoid preparations which contain zinc oxide, such as Rectinol. In severe conditions, oral steroid or steroid foam retention enema may be used.

Skin

The skin responds to radiotherapy quite similarly to a sunburn, but differs in extent and its duration.26 Moist regions with opposing skin surfaces, such as the perineum or the inframammary folds, are particularly affected. Reaction usually develops in one or two weeks and lasts for two to three weeks. During this period, avoid exposure to the sun or hot baths and protect the skin from further trauma such as friction from tight clothing, straps, etc. Wash the skin 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

Emollients such as aqueous cream have a soothing effect. 1% hydrocortisone cream can reduce pain and inflammation, but should be avoided in the genital area. Oral analgesics and even steroid are indicated for more severe pain.

Dry peeling

Following erythema, there may be peeling of skin. Emollients containing soft liquid paraffin or sorbolene with 10% glycerine can be applied. Some preparations with benzalkonium have an additional antiseptic effect.

Weeping

There can be weeping, 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.

Alopecia

Hair starts to fall out 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.

Respiratory system

Inflammatory reaction presenting as dry cough and dyspnoea may be seen up to 4 months after radiotherapy which has included the lungs. This 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.

Urinary system

After infection is excluded, frequency and dysuria from radiation cystitis can be managed by alkalinising the urine with potassium citrate 1-2 sachet three to four times a day. Pyridium 1-2 tablets tds is also effective. If needed, systemic analgesics may be added and be of value. The patient should increase fluid intake.

Neurological system

Alteration of circadian rhythm, headache, tiredness, nausea, confusion, somnolence or insomnia can occur after brain irradiation. Haloperidol (0.5-1.5mg bd) can be given for nausea, insomnia and confusion. These symptoms usually improve within one to two weeks. The patient should be reassured that the symptoms are of a 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 be increased and maintained for two weeks before tapering off to a lower maintenance dose. If the patient is on anti-epileptic agents for convulsion caused by brain secondaries, it is preferable to continue and not reduce any dosage.

Late side effects

Late side effects arise months to years after completion of treatment. Patients who received radiotherapy for palliative purpose would usually have died before these effects become prominent.