Management of Radiation-Induced Brachial Plexus Neuropathy

ABSTRACT: This report was prepared by a special committee of the Royal College of Radiologists. It provides a British perspective on how to manage this potential complication of breast irradiation. Portions of the report are summarized or, where indicated, reproduced in their entirety, with the permission of the College. [ONCOLOGY 10(5):685-700, 1996]

Introduction

Patients treated for breast cancer may suffer a range of upper limb problems, from mild edema and changes in inner arm sensation related to surgery, to the rare, but severely disabling brachial plexus neuropathy associated with radiation damage. Public attention focused on the latter problem by a group of British patients, the Radiation Action Group Exposure (RAGE), led to a House of Lords debate (May 1994). As a result of that debate, a multidisciplinary committee was set up in July 1994, under the auspices of the Royal College of Radiologists, to consider how women with axillary tunnel damage associated with radiation should be managed. The 14-member committee, which was chaired by Dr. E.J. Maher, Consultant Oncologist, Mount Vernon Centre for Cancer Treatment, included patients as well as oncology professionals. The committee's report was presented to the Board of the Faculty of Clinical Oncology of the Royal College of Radiologists on February 3, 1995.

The committee had the following objectives:

1. To assess the optimum management of women who have suffered axillary tunnel damage following radio therapy for breast cancer and the current availability of specialist services for such management.

2. To make recommendations on how services for this group of women can best be organized.

3. To report through the Faculty Board of the Royal College of Radiologists, the Joint Council of Clinical Oncology, and then to the Chief Medical Officer. The report would then be submitted to the Clinical Outcomes Group of the Department of Health.

What is Axillary Tunnel Damage?

For their report, the committee members used the term "axillary tunnel damage" to describe the spectrum of problems associated with damage to tissues adjacent to the clavicle and under the armpit due to treatment with ionizing radiation. The most serious complication is generally acknowledged to be damage to the nerve cords, ie, radiation-induced brachial plexopathy (RIBP).

The committee based its assessment of optimal management of axillary tunnel damage and current availability of specialist services on three sources of information: (1) consultation with RAGE (including results of a survey conducted by that organization), (2) a literature review, and (3) consultation with individual experts and organizations.

The committee found no completely unambiguous guidelines on the diagnosis or management of RIBP and associated problems in the literature. Also, most studies were based on small selected series of cases considered retrospectively rather than large prospective randomized trials. Thus, there is no solid research base. The committee took the view that, despite these acknowledged limitations, the views of sufferers, as represented by RAGE, should be paramount in recommendation of services and was guided by the priorities identified by the RAGE members.

Assessment of Need and Available Services

The chief problems reported were unrelieved pain, characteristically neuropathic in character, and paralysis of the hand and then of the whole arm. Further complications included bone pain and necrosis, lung damage, severe fibrosis, and lymphoedema.

For RAGE members one of the worst deficiencies was denial of the problem, which compounded the real anger they felt at not being warned of the possible dangers of radiotherapy.

Patients reported difficulties in obtaining a diagnosis or even information about the condition. There appeared to be no structured management plan, with problems in gaining access to expert help at the different stages of progression of the condition, in particular, pain management and access to occupational therapy, including aids to daily living. There was also a failure to provide psychological support.

The RAGE survey reported some good practice. In particular, pools of expertise were found in cancer treatment units, palliative care units, and pain clinics, but there was poor communication among them, no clear protocols, and difficulties in patient access. Based on perceived shortfalls, information was collated on the following topics:

• Organization of a coordinated professional network
• Role of neurologist in diagnosis
• Role of neurophysiologist in diagnosis
• Role of breast care nurse
• Management of neuropathic pain
• Role of occupational therapies
• Management of lymphoedema interest group
• Role of specialist surgical intervention
• Role of pain clinic

These papers were used to inform the work of the committee. Draft guidelines, completed on December 31, 1994, were widely circulated before presentation to the Board of the Faculty of Clinical Oncology of the Royal College of Radiologists on February 3, 1995.

Radiation-Induced Brachial Plexopathy (RIBP)

The following is the full text of this portion of the Royal College report. It is reproduced, with permission, from Management of Adverse Effects Following Breast Radiotherapy. London, The Royal College of Radiologists, 1995. The full texts of this report and the complementary report by Thelma Bates and R.G.B. Evans, Brachial Plexus Neuropathy Following Radiotherapy for Breast Carcinoma (London: RCR, 1995. ISBN 1 872599 18 4) are available from: http://www.rcr.ac.uk/Enquiries.

The committee recognizes that there is a difficult balance to be struck between the benefits of postoperative radiotherapy in reducing the risks of recurrence and death and the risks of serious morbidity. A relatively high dose of radiation is necessary to sterilize microscopic deposits of breast cancer. Survival may be prolonged by postoperative radiotherapy in selected patients. However, at these levels of dose, there is a relatively steep increase in the risk of complications. The price of reducing dose in order to reduce the risk of major morbidity is an increase in the risk of loco-regional recurrence and possibly an increase in cancer related plexopathy.

It is anticipated that the peak incidence of RIBP in the UK has been reached, possibly related to changes in technique over the late 70s and early 80s, but this is only conjecture and will be examined by the formal audit being conducted by Dr. Bates and Dr. Evans for the Royal College of Radiologists; however, it is also possible that the trend away from supraclavicular fossa and axillary radiotherapy could lead to more cancer related plexopathy. In view of the uncertainty as to which patients benefit from nodal radiotherapy, it is essential that treatment options are discussed carefully with appropriate specialists.

How Is it Caused?

In a minority of patients, supraclavicular and/or axillary irradiation may cause edema and fibrous tissue to constrict the brachial plexus. Substantial loss of myelin occurs with disappearance of the axis cylinders. The neurolemmal sheath itself undergoes varying degrees of fibrous thickening. Hyalinization and obliteration of blood vessels causes further ischemia of nerve fibers. The precise mechanisms of damage are still incompletely understood.

Genetic Factors

More recently it has become recognized that individual variations in radiosensitivity to the same total dose and fractionation may be, in part, genetically determined. It has been estimated that up to 20% of patients may be heterozygous for the ataxia-telangiectasia gene which confers substantial enhancement in radiation reactions. This may account for the abnormally intense axillary fibrosis following post operative radiotherapy in some patients. However, at the time of writing this report, there is no reliable test to determine whether an individual is heterozygous for the ataxia-telangiectasia gene or not and other genes may be equally important. While this is a promising area of research, there is no evidence that genetic factors are responsible for the injuries reported by RAGE.

How Frequent is RIBP?

Reports of the incidence of RIBP among women who have undergone postoperative axillary irradiation vary widely. This probably reflects differing criteria for the diagnosis of RIBP and the range of dose and fractionation schedules described in the literature. However, it is a rare complication probably affecting less than 1% of treated patients. Its rarity means that a general practitioner is unlikely to see a single case during his or her professional lifetime. Similarly, many health care professionals involved in the treatment of breast cancer may be unfamiliar with the clinical features of RIBP.

How Does RIBP Present?

The most common presenting symptoms of RIBP are:

• Tingling and numbness of the thumb and forefinger.
• Wasting and weakness of the small muscles of the hand.
• Persistent pain in the shoulder region.

These symptoms appear from 6 months to over 20 years after treatment with the most commonly reported incidence between the 2nd and the 5th year after radiotherapy. It should be emphasised that such symptoms may be caused by a variety of unrelated conditions and, if related to cancer and its treatment, are more likely to be due to recurrent cancer than RIBP.

How Does RIBP Evolve?

Typically, a patient will present with numbness of the fingers. Wasting of the small muscles of the hand will follow within months or years. Pain will follow a variable course: characteristically it follows the distribution of nerves supplied by C5 and C6, although it may involve the whole brachial plexus; the features of the pain vary not only in different individuals but also within the same individuals at different times. Such neuropathic pain is notoriously difficult to manage. Between one third and two thirds of patients with RIBP will develop progressive loss of function of the hand and arm over a period of months or years. In a minority, progression may arrest without significant loss of function. As paralysis becomes complete the severity of pain may recede but in other cases persistent causalgic pain remains.

There is a variable incidence of other associated problems including bone necrosis/fracture, lymphoedema and circulation problems. Persistent pain and increasing disability may result in clinical depression and non-specific stress-related illness.

How is RIBP Diagnosed?

Diagnosis may involve the following and their teams:

• Consultant oncologist.
• Neurologist.
• Breast care nurse.
• Neurophysiologist.
• Radiologist.
• Breast surgeon.

RIBP is a diagnosis of exclusion based on the demonstration of a brachial plexopathy in an irradiated site in the absence of other causes, in particular recurrent cancer.

At the time of presenting symptoms and signs it is usually (but not always) possible to confirm a brachial plexopathy, but there are no completely reliable criteria for distinguishing the cause to be radiation rather than recurrent cancer.

Diagnosis rests on:

• Recognition of the significance of the common presenting symptoms
• Competent history and physical examination to identify a neurological deficit and to detect obvious recurrent cancer. This may require assessment by a neurologist as well as clinical oncologist.
• Investigations:

-Chest x-ray, cervical spine x-ray.
-CT/MRI axilla SCF and cervical spine.
-Biopsy of suspicious areas (preferably under CT control).
-Neurophysiological tests: nerveconduction and needle studies toidentify a lesion in the brachialplexus.
-Screen for metastatic disease: liver ultrasound, bone scan.

The committee proposes the consultant oncologist as best placed to recognize the significance of symptoms and coordinate diagnosis. There was, however, debate among the members of the committee and outside experts consulted as to the appropriate sequence of investigation. Some recommended CT and MRI before neurophysiological tests; others that referral to a neurologist was essential before proceeding to either MRI or neurophysiological studies; others that it would be within the competence of a clinical oncologist to coordinate all these investigations. Much depends on local expertise and the committee recommends that a local coordinating clinician makes appropriate recommendations; however, this committee would expect that, in the face of persistent symptoms (more than 3 months) and/ or objective signs suggesting a brachial plexus neuropathy, patients should have at least:

• CT/MRI scan axilla, supraclavicular fossa (with biopsy under CT control of suspicious areas).
• Neurophysiological studies (nerve conduction and needle studies).

A diagnosis of cancer related plexopathy is suggested by:

• Rapid progression of weakness (particularly involving muscles supplied by lower plexus).
• Abnormal supraclavicular/axillary nodes.
• Evidence of metastatic disease elsewhere.
• Horner's syndrome.

Initial absence of these does not exclude the possibility of tumor, as demonstrable cancer has been reported many years after initial symptoms. Abnormal masses should be biopsied, ideally under local anaesthetic, but open exploration may be required. Even then negative findings do not completely exclude cancer.

Plexopathy related to cancer may respond to systemic chemotherapy and/ or a second course of radiotherapy; in the presence of rapidly progressive weakness and a negative biopsy patients may consider a trial of chemotherapy in combination with high dose steroids.

Is There Treatment for RIBP?

Surgery-Operations have been described to decompress the brachial plexus and revascularize nerves and surrounding tissues, but there is no treatment which will reliably reverse or change the natural history of RIBP. In general, the most successful results will be obtained with a team of a surgeon with skills in the management of brachial plexus injury (generally an orthopaedic or neurosurgeon) and a vascular and/or reconstructive surgeon used to placing vascularized flaps within heavily irradiated tissues.

The success rates vary both in the literature and amongst reports from individual RAGE members who have undergone surgery. Some have noted improvement of motor function and others improvement of pain; however, others have reported deterioration as a result of such surgery. It is possible such surgery may delay vascular insufficiency and avoid progression to complete loss of motor function in selected cases. In general, most value is obtained within 12 months of presenting symptoms. Patients with severe vascular problems have eventually required amputation. It should be noted that this is not an effective measure to relieve pain.

Mr R Birch was consulted by this committee and comments that operations are hazardous and difficult and should not be attempted by the occasional surgeon, but that teams with appropriate skills are available in several parts of the UK. The committee feels that further research is required before producing recommendation for the use of such surgery. Mr Birch, who is prepared to be consulted by health care professionals managing cases, feels there is a need for significant investment in those centers dealing with brachial plexus injury of all sorts, if more surgery and/or research is to go forward.

Medication-Thyroxine and salicylates, eg, phentoxyphylene have been proposed to inhibit development of radiation fibrosis in selected cases. Recently, the antioxidant agent Cu/Zn superoxide dismutase (Lipsod) has been successfully used to reduce fibrosis, in a French study (Delanian et al 1994). Again more research is required before recommendations can be made.

How Should Patients With RIBP Be Managed?

The key to effective management is a collaborative multidisciplinary approach with honest explanation and communication with the patient, as well as all health care professionals involved. It must be acknowledged that RIBP is essentially an incurable condition, as unrealistic expectations reduce the chances of producing useful improvements in quality of life.

In the absence of definitive treatment, management should be directed towards optimizing symptom control and function to maintain as good a quality of life as possible. This should be combined with careful surveillance to detect and treat recurrent cancer, particularly in the first 2 years after presentation.

The committee considered various health care professionals to coordinate the management of patients with RIBP but concluded that a clinical oncologist is the best placed to recognize the condition, to give an honest explanation both of uncertainties and possible prognosis, and to recognize and treat recurrent cancer.

The committee would expect a coordinating consultant oncologist in each center to liaise with the following health care professionals and teams in the management of such patients:

• Anesthetist and psychologist/psychiatrist, as part of pain clinic.
• Breast Care Nurse.
• GP and District Nurse.
• Lymphoedema clinic.
• Occupational therapist.
• Palliative care clinic.
• Physiotherapist.

In addition, a range of complementary therapists (aromatherapists, masseurs, acupuncturists, reflexologists) have been helpful to RAGE members, particularly for those who have been recognized late and have had little or no psychological support. The committee feels more research is needed both in the contribution of complementary therapies and the management of those patients with multiple problems related to axillary tunnel damage, but is not able to make specific recommendations at present.

The key elements of management include:

• Information and explanation to empower patients to help themselves to cope with the condition.
• Systematic management of pain. In view of the emphasis placed by RAGE on this detailed guidelines are included in [the Appendix].
• Assistance with the functions of daily living, in particular access to the recommended aids listed in [the Appendix].
• Psychological support including access to a nurse counselor, information on voluntary organizations and self help groups and regular evaluation for clinical depression.• Regular surveillance to detect and treat recurrent cancer, particularly in the first 2 years.

The committee recommends that one oncologist in every cancer unit and cancer center is responsible for identifying and briefing each member of the team to allow coordinated care, following the guidelines in pain management documented in the Appendices, Symptomatic Management of Neuropathic Pain, and Occupational Aids.

The committee has identified a provisional list of named oncologists in every radiotherapy treatment center in the UK. Ninety percent of these have access to occupational therapy, physiotherapy, pain clinic, breast care nurse, lymphoedema clinic, palliative care clinic and complementary therapy.

The committee proposes that the audit of breast cancer treatment includes key symptoms suspicious of brachial plexopathy in order to facilitate future follow up and management of such cases.

Surveillance

The committee recommends that all those patients with a provisional diagnosis of RIBP are followed by a clinical oncologist at least 3-monthly for 2 years to evaluate:

• Symptoms.
• Function.
• Evidence of recurrent cancer.
• Evidence of clinical depression.
• Other complications, eg, lymphoedema; pathological fractures; vascular insufficiency.

Thereafter they should be seen 6-12 monthly indefinitely depending on their symptoms.

If problems arise in between, the GP is an important point of contact; however, given the rarity of RIBP it is not a condition that they would readily recognize and patients should also be able to have access to a key nurse, ideally a breast care nurse, but failing that, an identified community Macmillan (palliative care) nurse to facilitate speedy referral for re-evaluation.

Safety Net

The committee recognizes that, in some cases involving suspected iatrogenic damage, relationships break down with the treating oncologist, in which case it proposes that the breast care nurse should act as key worker to facilitate discussion with the treating oncologist and allow referral to an alternative oncologist in the same center or the identified regional specialist.

The committee has identified a directory of oncologists in each cancer center and cancer unit...and the services to which they have access. It proposes that this information be made available to all breast care nurses through their regional coordinators and, ideally, also to voluntary groups.

The committee proposes that further education of breast care nurses in identification and management of RIBP and associated problems is included in their training, possibly with the addition of regional seminars under the auspices of CRMF. If a patient has no breast care nurse, advice should be available from regional breast care nurse coordinators. The committee has identified a list of these....

The committee recognizes that many health care professionals will not have seen a case of RIBP. It has not been possible within the time frame and resources of this committee to identify all those with expertise in, each discipline but, as a step in the right direction, a group of specialists, including an experienced occupational therapist, physiotherapist, anesthetist, neurologist, specialist surgeon, neurosurgeon, orthopedic surgeon, radiologist, palliative care doctor, all of whom have advised the committee, have indicated that they are willing to act in an advisory capacity to their colleagues faced with such cases.... A more expanded directory will be prepared, if funds become available.

An unacceptable burden is currently falling on RAGE committee members and the committee proposes that written information for patients is produced by a collaboration between BACUP, CancerLink and Breast Cancer Care and a more extended directory of advisory services made available.

In addition the Committee has liaised with BACUP and CancerLink to facilitate formal counseling and help to RAGE committee members in their work in supporting patients. This committee feels that the supportive as well as the campaigning role of RAGE should be acknowledged.

Summary of Guidelines

Following is the full text of this portion of the Royal College report. It is reproduced, with permission, from Management of Adverse Effects Following Breast Radiotherapy. London, The Royal College of Radiologists, 1995.

While the chance of axillary tunnel damage is small, all those who have received radiotherapy to the supraclavicular fossa and/or axilla should be given information to allow them to recognize and report significant symptoms to obtain rapid expert assessment and management.

When patients complete radiotherapy symptoms to watch for should be given to both patients and GP. Included in this should be the information that persistent tingling of the fingers, particularly associated with shoulder pain or weakness of the hand, should result in urgent assessment by the treating oncologist, as it could rarely be an early symptom of recurrent cancer, or a complication related to surgery or radiotherapy.

Diagnosis

Diagnosis of RIBP rests on demonstrating brachial plexopathy in an irradiated site in the absence of other causes, particularly recurrent cancer. Even in the absence of a negative biopsy, recurrent cancer cannot be absolutely excluded particularly over the first 2 years from presentation. Key elements of diagnosis include:

• Recognition of presenting symptoms.
• Physical examination
• X-ray chest and cervical spine
• CT /MRI scan of supraclavicular fossa, axilla and cervical spine
• Biopsy of suspicious lesions
• Electrophysiological studies (including both nerve conduction studies and needle studies) to localize lesion in the brachial plexus.

Surveillance

Patients with a provisional diagnosis of RIBP should be followed three-monthly for 2 years and thereafter 6-12 monthly depending on symptoms.

Management

Management involves a multidisciplinary team coordinated by a clinical oncologist designated in every cancer center and cancer unit. The coordinating consultant oncologist is responsible for liaising with the following to make sure they are aware of protocols:

• Breast care nurse.
• Breast surgeon.
• GP and District Nurse.
• Occupational therapist.
• Pain clinic (anesthetist, psychologist psychiatrist).
• Palliative care clinic.
• Physiotherapist. and, if possible,
• Complementary therapists.

Key elements of management include:

• Information and explanation to empower patients to help themselves.
• Systematic management of pain.
• Assistance with functions of daily living.
• Psychological support including access to voluntary groups.
• Regular surveillance to detect and treat cancer.

Safety Net

Where patients have problems either in gaining access to a diagnosis or treatment, a breast care nurse should be able to facilitate this. Information and advice as to management contained in a fact sheet and directory of services is proposed to be circulated to all breast care nurses and voluntary organizations. This information will be available to patients although experts will only be able to give advice to fellow health care professionals.

Appendix: Symptomatic Management of Neuropathic Pain

This portion of the Royal College report is reproduced in full from Managment of Adverse Effects Following Breast Radiotherapy. London, The Royal College of Radiologists, 1995. It was prepared by Dr. Carol Davis, Senior Lecturer in Palliative Medicine, Countess Mountbatten House, Southampton.

Radiotherapy for breast cancer can cause immediate effects such as desquamation of skin and acute neuropathic pain which are usually self-limiting. Post-breast surgery and mastectomy syndromes are common in up to 15% of patients, some of whom also present with neurological damage, particularly to the patient's intercostal brachial nerve.

Classical long-term sequelae of radiotherapy can develop between 6 months and over 20 years from treatment. They are caused by damage to the brachial plexus, lymphatics, vasculature and bones and are characterized by progressive functional loss with or without pain and lymphoedema. Tumor recurrence can also account for progressive brachial plexus damage but is more common in the lower nerve roots C8 to Tl, which are relatively protected from radiation damage by the clavicle, in contrast to radiation damage which is most common in the upper roots C5/6.

Clinical Features and General Approach to Management

Neuropathic pain implies pain in the distribution of a nerve, secondary to functional or pathological change in the nerve. In the context of post-radiation pain in patients treated for breast cancer, it is caused by damage to the brachial plexus (brachial plexopathy). Neuropathic pain is recognized as a difficult pain to treat. Ideally, the first step in symptomatic management is to establish the diagnosis but this is not necessarily clearcut in patients with brachial plexopathy and cancer (Kori et al 1981).

The features of the pain vary not only in different individuals but also within the same individual at different times: the pain may be constant or intermittent and occurs in the distribution of affected nerves.

Common descriptors of neuropathic pain: burning, shooting, pins and needles, tingling, toothache, numbness, cramp, stiffness, frostbite, tightness.

The key to diagnosis lies in a thorough clinical history and examination which may need to be supplemented by appropriate investigations such as CT scan and MRI. Investigations must be directed at establishing whether the symptom is a sign of treatment-related nerve damage or recurrent disease.

Symptomatic treatment should not be delayed and can be commenced whilst investigations are underway. Unless active tumor is demonstrated, management should be aimed at optimizing symptom control and function, thus maintaining a good quality of life as possible. A collaborative and multi-disciplinary approach is required. Open and honest explanation is essential as is good communication with all involved. Appropriate information must be available for both patients and health care professionals. Many patients will have been cured of breast cancer and the aim of treatment should be pain relief that is as complete and long-lasting as possible. It is important that side-effects of the treatment are kept to a minimum and that they do not increase the patient's disability. The least toxic treatments should be tried first.

Symptomatic Management

This includes:

1. Pharmacological and non-pharmacological strategies.
2. Psychological approaches.
3. Help with activities of daily living.
4. Interventional techniques.

Pharmacological and Non-Pharmacological Strategies

Neuropathic pain is relatively insensitive to conventional analgesics including non-steroidal anti-inflammatory drugs (NSAIDs) and both weak and strong opioids. Radiotherapy-induced neuropathic pain in the upper limb may co-exist with other pains including bone pain and visceral/soft tissue pain which are usually sensitive to these agents. Pharmacological treatment must therefore be directed at each component of the pain.

Adjuvant Analgesics-Tricyclic anti-depressants...should be used as first-line pharmacological therapy. Amitriptyline is the most likely to cause side-effects but is, like the others, very effective treatment for neuropathic pain. The dose should be slowly tirated upwards. The sedative effects of some anti-depressants can be utilised to improve sleep. Pain relief is independent of the effects of the drug on depression but, if the patient is clinically depressed, there is no doubt that relief of depression will improve the patient's perception of the pain.

Anti-convulsants are usually as second-line pharmacology treatment and can be particularly useful in cases with paroxysmal, shooting pain. Some clinicians replace anti-depressants with one of this class of drugs whilst others use them together. These strategies have not been compared in a clinical trial in patients with neuropathic pain of any etiology. Carbamazepine and sodium valpoate are most commonly used; if one anti-convulsant does not work even after dose-escalation, then there is possibly less likelihood of success with another.

Refractory pain can be treated with anti-arrhythmic drugs (flecainide or mexilitine) but caution is necessary in patients in whom cardiac status may be compromised by previous radiotherapy or ischemic heart disease. Some centers only prescribe such treatment after a successful intravenous lignocaine challenge.

The use of adjuvant analgesics is well reviewed elsewhere (Charlton 1993, Portenoy 1993).

Baclofen can be helpful, particularly if the pain is of mixed etiology and there is a post-surgical element to the pain, for example intercostal-brachial nerve damage.

Corticosteroids can be useful in the management of neuropathic pain, but should be used in the setting of radiotherapy induced neuropathic pain with extreme caution because of long-term toxicity.

There is some evidence that the application of topical NSAID's, local anesthetics and capsaicin can relieve neuropathic pain through a direct effect on cutaneous, sensory nerve endings.

There is increasing clinical and laboratory evidence that NMDA receptor antagonists, such as ketamine, can relieve neuropathic pain but toxicity can be severe and dose-limiting. Agents available to date have to be administered parenterally and are currently undergoing further evaluation. Others are being developed.

Conventional Analgesics-The insensitivity of neuropathic pain to conventional analgesics, particularly opioids, is the subject of considerable debate. There is little doubt that this type of pain is relatively insensitive to opioids but some believe that high doses of morphine or standard doses of alternative opioid analgesics such as methadone can bring about symptom relief. A short trial of dihydrocodeine, morphine or methadone is justified in patients who have failed to respond to other pharmacological strategies, since long term benefit can be obtained in a proportion of such patients.

Non-pharmacological Strategies-The local application of heat or cold is often helpful though cumbersome. Neuropathic pain is sometimes eased by gentle rubbing and massage with or without essential oils which should not be used if the skin is broken. Benefit from these strategies is a useful predictor of success with TENS or acupuncture.

Transcutaneous electrical nerve stimulation (TENS) is a simple non-invasive technique which can be particularly helpful for neuropathic pain (Thompson and Filshie 1993). It should be used early in the course of treatment either before or alongside a tricyclic anti-depressant. Electrodes are frequently sited paravertebrally alongside affected segments (eg C5 and 6) with or without peripheral placement either proximal to the painful areas or on trigger points. It is usually necessary to adjust repeatedly the stimulation sites before optimal pain relief is achieved and this technique should not be abandoned before this has been tried. A minimum trial of 3 weeks duration, trying sequential placement sites and varying other parameters including the machine so that continuous, burst and modulated outputs are tried, has been found helpful in patients with avulsion neurological injuries and is recommended.

The physiotherapist is often the best person to advise on the use of pain relieving techniques such as heat, ice, TENS and massage as well as to give advice on mobility and functional adaptation. Careful assessment, advice on positioning, skin care, splinting, supportive aids (eg, slings) and muscle re-education may be necessary where brachial plexus damage has occurred. Progressive graded exercises, including mobilisation and soft tissue stretching exercises may be appropriate to maintain and improve range of movement and minimize the effects of muscle fibrosis following radiotherapy.

Instruction in self-management is important as is prophylactic advice to prevent further complication due to sensation loss and to alert the patient to the signs of early lymphoedema.

Acupuncture can provide relief of neuropathic pain (Thompson and Filshie 1993). It appears to have a sympatholytic effect and can improve functional ability. Symptom relief, if achieved, is cumulative and after three treatments at weekly intervals, the treatment intervals can be increased (Filshie, personal communication).

The role of complementary therapies in the management of patients with brachial plexopathy requires medical evaluation. It is essential that the practitioner is aware of the nature and cause of the symptoms. Healing, gentle massage and aromatherapy may be comforting and are unlikely to cause harm.

Psychological Approaches

Chronic pain of any cause is often associated with psychological morbidity. A wide range of emotions including anger and bitterness are normal reactions to this situation and are often more intense if the problem has been induced by treatment. These emotions can become pathological and contribute to anxiety and depression.

There is evidence that a variety of strategies can be employed to prevent psychological morbidity; these include giving appropriate information and advice, acknowledging distress and openly discussing the likely cause of the pain and the possible treatment options. Some strategies can be used to limit pre-existing psychological morbidity. A proportion of patients with radiotherapy-induced brachial plexopathy will require specialist psychological and/or psychiatric support.

Activities of Daily Living

The patient should have early access to a hospital-based or a community-based occupational therapy service. An individual and full physical, functional, psychological and social assessment is essential. Following this, advice on appropriate coping strategies and the use of practical equipment, if necessary, can be given. Adaptations to the home and car may be required. The patient's needs may change with time and so follow-up visits should be arranged as necessary.

Interventional Techniques

Nerve Blocks-The plasticity of the nervous system is such that so-called "permanent" nerve blocks may only last for days, weeks or months but side-effects may be permanent and unacceptable for some patients. Such blocks should be reserved for highly selected patients treated in specialized centers. Regional guanethidine and stellate ganglion blocks are the most commonly performed.

Neurosurgical Procedures-In a small proportion of patients, neurosurgical intervention will be required. The most appropriate procedure is determined not only by the patient's symptoms but also by the results of investigations delineating the degree of nerve damage and the chances of long-term success. Dorsal root entry zone ablation (DREZ) is one such operation; M. Powell at the National Hospital will offer advice on this.

Organizational Issues

Each patient will have individual needs but patients should have access, through their general practitioner to a clinical oncologist (see the Summary of the Guidelines). Good communication is essential both between team members and between the team, the patient and their family.

Research and Training Issues

Good clinical practice should be research-based whenever possible. There is an urgent need for clinical trials and relevant laboratory studies addressing the management of patients with brachial plexopathy after radiotherapy. In addition, within the core curricular for students and systems of continuing education for trained personnel, it is essential that certain issues are covered in detail, ie communication skills, including listening skills, assessment of pain, management of pain, holistic approach to patient care.

Conclusions

The management of patients with radiotherapy-induced brachial plexopathy requires an open-minded, multidisciplinary, patient centered approach. A combination of pharmacological and non-pharmacological strategies will be required and should be used logically. Adequate therapeutic trials are essential. First-line treatment should comprise TENS with or without a tricyclic antidepressant. Early access to physiotherapy and occupational therapy services and to psychological support when necessary is vital. The aim of management should always be optimisation of symptom control and function so that the patient can enjoy as good a quality of life as possible.

References:

Charlton E: Neuropathic pain. Prescribers' Journal 33:244-249,1993

Kori SH, Foley KM, Posner JB: Brachial plexus lesions in patientswith cancer: 100 cases. Neurology 31:45-50, 1981.

Maguire P: ABC of breast diseases: psychological aspects. Br MedJ 309: 1649-1652, 1994.

Portenoy R: Adjuvant analgesics in pain management, in Doyle D,Hanks GWC, Macdonald N (eds): Oxford Textbook of Palliative Medicine,pp 187-203. Oxford Medical Publications, 1993

Thompson JW, Filshie J: Transcutaneous electrical nerve stimulation(TENS) and acupuncture, in Doyle D, Hanks GWC, Macdonald N (eds)Oxford Textbook of Palliative Medicine, pp 229-244. Oxford MedicalPublications, 1993.