2.5 Metastatic Disease and Palliative care Cheat Sheet (DRAFT) by Molly

Cancer metastasis is the process by which a cancer cell leaves the primary tumour, travels to a distant site by way of the blood and lymphatic circul­atory channels, and establ­ishes a second tumor in this new site.

In these patients some 70-75% will develop bone metastases at some stage of their illness and indeed post mortem findings seem to suggest that the figure may actually be higher.

Bone metastases can cause consid­erable morbidity – pain, pathol­ogical fracture, vertebral collapse (and associated spinal cord compre­ssion) and hyper-­cal­caemia. In advanced cases such as these, the role of radiation therapy is in palliation of symptoms.

The distri­bution of bone metastases tends to mirror the distri­bution of red bone marrow – i.e. they are more likely to arise in: spine; ribs; pelvis; proximal append­icular skeleton

The most common mechanism by which cancer affects bone is by haemat­olo­gical spread.

Malignant cells enter the bone marrow space and appear to be attracted to the bone forming surfaces by chemot­actic agents (most likely collagen fibres).

The vertebrae are thirty­-three in number, and are grouped under the names cervical, thoracic, lumbar, sacral, and coccygeal, according to the regions they occupy. There are seven in the cervical region, twelve in the thoracic, five in the lumbar, five in the sacral, and four in the coccygeal. The vertebra are regularly referred to in radiation therapy for land marking, treatment and image recogn­ition.

In addition it is also essential to determine: pain and mobility; analgesic requir­ements

The radioi­sotopes are injected intrav­enously and taken up by areas of increased osteoblast activity.

If the patient has presented with a pathol­ogical fracture then internal fixation is always indicated prior to external beam radiot­herapy (assuming that the patient can undergo surgery).

Endocrine therapy (hormonal interv­ention)

In premen­opausal women surgical or radiation induced oophor­erctomy or a LHRH-r­ele­asing hormone or tamoxifen may be indicated. In postme­nop­ausal women tamoxifen, or aromatase inhibitors are used.

In prostate cancer orchid­ectomy (one or both testicles are removed) or preferably the use of goserelin acetate (Zoladex) is an option.

Chemot­herapy may be of use in cases of advanced breast cancer and myeloma where bone metastases may be diffuse making radiot­herapy imprac­tical.

It should be noted that the tolerance of patients’ bone marrow is likely to be signif­icantly reduced, either as a result of destru­ction by the tumour itself or as a conseq­uence of previous radiot­herapy (including radioi­sot­opes).

Bispho­sph­onates play an important role in the management of osteolytic metastases (e.g. from breast cancer) and can promote healing and lessen pain thus reducing the incidence of pathol­ogical fractures and spinal cord compre­ssions.

These drugs are well tolerated and side effects are minimal. Biphos­pho­nates also play an important associated role in the management of tumour­-in­duced hyperc­alc­aemia.

Relief of pain is partic­ularly important in the management of bone metastases and analgesic drugs are almost always used in sympto­matic patients.

Medical management of metastatic bony disease pain typically begins with parace­tamol or nonste­roidal anti-i­nfl­amm­atory drugs or cycloo­yge­nase-2 inhibitors that are aimed at allevi­ating inflam­matory states associated with bone pain.

This will severely impact on the patient’s mobility.

The first decision to make is whether the patient can lie prone or supine.

One thing to remember though regardless of technique is that the upper level and lower level of the field should cover full vertebrae and should not be part way through a vertebra.

Since the aim of radiation therapy is to deliver a tumorc­idial dose and minimise the dose to the surrou­nding healthy struct­ures, this technique is less than ideal.

It is unlikely that these patients will be prone. Sometimes the patient will be simulated supine in a stabil­isation cast/shell for ease of set up and reprod­uci­bility.

For this reason a multi field technique is often employed. Wedged posterior obliques with either a direct posterior, or anterior, field is normally indicated for treating these patients.

the spinal column is located poster­iorly. Multi field techniques are commonly used in the thoracic region.

Multi field techniques are used in the lumbar region, either opposing anterior and posterior photon fields or a 3 field technique. The 3 field technique may use either posterior oblique fields or laterals to achieve the desired dose distri­bution to the required depth.

Just below the last Thoracic (T12) and first Lumbar (L1) vertebra the spinal cord ends at the Conus Medull­aris. From this point the spinal nerves, resembling a horse’s tail, become known as the Cauda Equina, and extend to the coccyx. These nerves are suspended in spinal fluid.

To include the lumbar and sacral region, the typical radiation field will resemble a spade, larger inferiorly to cover the nerves as they spread out in the sacral region, and then shielding either side of the vertebral column at the level of the lumbar spine region. Once again, current practice would be to use a multi field approach.

This will severely impact on the patient’s mobility.

The first decision to make is whether the patient can lie prone or supine.

One thing to remember though regardless of technique is that the upper level and lower level of the field should cover full vertebrae and should not be part way through a vertebra.

Since the aim of radiation therapy is to deliver a tumorc­idial dose and minimise the dose to the surrou­nding healthy struct­ures, this technique is less than ideal.

It is unlikely that these patients will be prone. Sometimes the patient will be simulated supine in a stabil­isation cast/shell for ease of set up and reprod­uci­bility.

For this reason a multi field technique is often employed. Wedged posterior obliques with either a direct posterior, or anterior, field is normally indicated for treating these patients.

the spinal column is located poster­iorly. Multi field techniques are commonly used in the thoracic region.

Multi field techniques are used in the lumbar region, either opposing anterior and posterior photon fields or a 3 field technique. The 3 field technique may use either posterior oblique fields or laterals to achieve the desired dose distri­bution to the required depth.

Just below the last Thoracic (T12) and first Lumbar (L1) vertebra the spinal cord ends at the Conus Medull­aris. From this point the spinal nerves, resembling a horse’s tail, become known as the Cauda Equina, and extend to the coccyx. These nerves are suspended in spinal fluid.

To include the lumbar and sacral region, the typical radiation field will resemble a spade, larger inferiorly to cover the nerves as they spread out in the sacral region, and then shielding either side of the vertebral column at the level of the lumbar spine region. Once again, current practice would be to use a multi field approach.

As the treatment is palliative intent, the daily fraction size is usually large at the start (up to 3-4 Gy) to get the dose in quickly to attempt a quick response. After a few of these larger fractions the radiation oncologist may then prescribe a more normal fracti­onation of 2-3 Gy per day up to a dose of between 20 and 30 Gy.

As the treatment is palliative intent, the daily fraction size is usually large at the start (up to 3-4 Gy) to get the dose in quickly to attempt a quick response. After a few of these larger fractions the radiation oncologist may then prescribe a more normal fracti­onation of 2-3 Gy per day up to a dose of between 20 and 30 Gy.

As the treatment is palliative intent, the daily fraction size is usually large at the start (up to 3-4 Gy) to get the dose in quickly to attempt a quick response. After a few of these larger fractions the radiation oncologist may then prescribe a more normal fracti­onation of 2-3 Gy per day up to a dose of between 20 and 30 Gy.

As the treatment is palliative intent, the daily fraction size is usually large at the start (up to 3-4 Gy) to get the dose in quickly to attempt a quick response. After a few of these larger fractions the radiation oncologist may then prescribe a more normal fracti­onation of 2-3 Gy per day up to a dose of between 20 and 30 Gy.

The junction of the upper and lower fields is usually at the level of the iliac crests. A single dose of 6 Gy to the upper body and 8 Gy to the lower body is prescr­ibed. The treatment is usually given with the patient as an in-patient due to the expected signif­icant side effects of delivering radiation to such a large volume within the patient.

For a sternum treatment, with the patient flat on their back, the treatment area is usually flat enough. On some occasions you may see the patient is on an incline plane to achieve the flat area.

For lateral ribs, the patient will often have to be lying on their contra­lateral side. If this happens, the patient will be fairly unstable, so at simulation make sure that you have taken all measures to ensure that the patient is comfor­table and stable.

The role of chemot­herapy in circum­stances where little or no survival benefit is antici­pated remains contro­ver­sial.

Palliative cytotoxic chemot­herapy is less widely used than radiation therapy as the toxicities associated with chemot­herapy are more common and more difficult to justify according to the criteria for good pallia­tion.

This will severely impact on the patient’s mobility.

The first decision to make is whether the patient can lie prone or supine.

One thing to remember though regardless of technique is that the upper level and lower level of the field should cover full vertebrae and should not be part way through a vertebra.

Since the aim of radiation therapy is to deliver a tumorc­idial dose and minimise the dose to the surrou­nding healthy struct­ures, this technique is less than ideal.

It is unlikely that these patients will be prone. Sometimes the patient will be simulated supine in a stabil­isation cast/shell for ease of set up and reprod­uci­bility.

For this reason a multi field technique is often employed. Wedged posterior obliques with either a direct posterior, or anterior, field is normally indicated for treating these patients.

the spinal column is located poster­iorly. Multi field techniques are commonly used in the thoracic region.

Multi field techniques are used in the lumbar region, either opposing anterior and posterior photon fields or a 3 field technique. The 3 field technique may use either posterior oblique fields or laterals to achieve the desired dose distri­bution to the required depth.

Just below the last Thoracic (T12) and first Lumbar (L1) vertebra the spinal cord ends at the Conus Medull­aris. From this point the spinal nerves, resembling a horse’s tail, become known as the Cauda Equina, and extend to the coccyx. These nerves are suspended in spinal fluid.

To include the lumbar and sacral region, the typical radiation field will resemble a spade, larger inferiorly to cover the nerves as they spread out in the sacral region, and then shielding either side of the vertebral column at the level of the lumbar spine region. Once again, current practice would be to use a multi field approach.

This is because the patients need prompt treatment as they are at risk of permanent, irreve­rsible damage. To minimise risks and discomfort for these patients, they are treated immedi­ately following the planning procedure.

The first is for spinal cord compre­ssion - where the tumour is impinging on the cord itself, or a nerve, with the potential to leave the patient a paraplegic or a quadri­plegic if left untreated.

A lymphatic strip will also be required for drainage, i.e. sparing a strip of skin on the medial edge of the arm.

A consid­eration for these patients, and/or if you are treating their forearm, is missing the side rails of the bed with the posterior field.

The SN/tip of shoulder measur­ement is required to reproduce the shoulder position.

The tip of elbow to chest wall measur­ement will control the arm position, ensuring that the treatment area is correct.

A reference line will be required, possibly from mid-se­par­ation elbow through to mid- separation wrist. Other anatomical references are epicon­dyles on the wrist. A series of tattoo­s/skin marks will be required to ensure the same RL is obtained on each day of treatment.

If not, the metastases and a margin around the lesion will be treated: Shielding may be positioned superi­or-­med­ially to minimise bowel and bladder toxicity. Diarrhoea and cystitis may be experi­enced if included within the pelvic region of the fields.

A strip of skin also needs to be spared from the radiation field. If the entire circum­ference of the leg is treated, the lymphatic drainage will be impaired, resulting in severe swelling of the limb (lymph­oed­ema). This is often called ‘ring barking’. This scenario is unacce­ptable from a patient’s quality of life perspe­ctive, and should be avoided at all costs.

Patients are positioned supine, with a bolster under their knees and some form of foot separation device to maintain the leg position.

UBP/ML (upper border pubis/­mid­line) and location from anterior commissure (Ant Comm.) or Base of Penis (BOP); and

When a full femur is being treated, the length of the field is often longer than can be achieved with the standard jaw setting (espec­ially when the hemi-p­elvis is also encomp­assed in the field).

To achieve this, the SSD is typically set (known as fixed SSD) to 120 or 130 cm. (Compare this to having an isocentric technique with 100 at the isocentre and an SSD of approx­imately 90 cm.

When deciding on the dose to be prescribed to a patient the following points are some to be considered by the radiation oncolo­gist:

Overlap of the area to be treated with previous areas of irradi­ation is of concern for any patient.

This will help to establish if the patient can safely receive further treatment, partic­ularly with metastases to vertebral bodies where the underlying critical structure is the spinal cord.

Patients rarely experience erythema due to the lower doses being below skin tolerance. Most patients will experience tiredness. However, it is difficult to distin­guish between radiation induced symptoms and those associated with the disease itself.

Radiation Therapy for metastatic disease covers many anatomical sites. However, there are some underlying principles that can be applied to all sites. To meet patient positi­oning principles it is important that the patient is as comfor­table as possible.

-patient position including: vertical baselines (VBL); reference lines (RL)
-stretches (the distance between two anatomical landma­rks);
-CT slice at 'zero' location or imaging centre, referenced to an anatomical landmark;
-position of tattoos or skin marks

The baselines and reference lines selected should be perpen­dicular to each other and any measur­ements from those lines to CT reference points or isocentre should be perpen­dicular also.

-prompt relief of symptoms
-minimal toxicity from treatment
-simple treatment technique
-minimal number of treatment fractions

Pain is the most important symptom of patients with metastatic cancer, as pain interferes with mobility, sleep and psycho­logical issues.

Patients with metastatic disease may experience pain crises, charac­terised by acute onset of a new pain quality. This may be due to a pathol­ogical fracture, spinal cord compre­ssion, intestinal obstru­ction or perfor­ation, vascular compli­cation, other compli­cations or acute breakt­hrough of pre-ex­isting constant pain.

This differ­ent­iation may aid selection of adequate analge­sics, comedi­cation, and help assessment of the underlying cause and the most approp­riate treatment options.

1. The tumour: the site, size, spread, operab­ility, radios­ens­iti­vity, chemo-­sen­sit­ivity, and histology all need to be consid­ered.

3. The resources available: Most oncolo­gical treatments require technical expertise, experience and specialist equipment. The availa­bility of these resource requir­ements may influence treatment management options when patients are unable to travel, or are living in rural or regional areas where specialist treatment may not be available.

Primary tumours that commonly spread to the lungs include: breast, colore­ctal, lung, testic­ular, pancre­atic, oesoph­ageal, stomach, ovarian, renal cell and prostate carcin­omas, osteogenic and soft tissue sarcomas, and melanoma.

Pulmonary haemat­ogenous spread occurs most commonly from tumours that have direct venous drainage into the lungs, such as head and neck, kidney, testis, melanoma, and osteos­arc­oma’s.

Tumour emboli may become trapped in an individual lymph node, or may bypass certain nodes and become establ­ished in distant nodal sites called "­ski­p" metastasis.

Diagnostic invest­iga­tions for metastatic lung cancer may include: chest x-ray; CT; bronch­oscopy; sputum cytology (examines a sample of sputum (mucus) under a micros­cope); CT guided needle biopsy; thorac­oscopy; medias­tin­oscopy

Palliative laser therapy can provide rapid relief for dyspnea and haemop­tysis if due to disease in the trachea or main bronchi.

Treatment with chemot­herapy and/or biological agents is used when a patient is not an optimal surgical patient or when surgery would be ineffe­ctive in removing all the cancer, such as in instances of medias­tinal, lympha­ngitic, or pleural metast­asis.

Generally radiation therapy is used infreq­uently to treat pulmonary metast­asis, except in lung cancer, and is reserved for palliation for cough, haemop­tysis, or pain.

Surgery
Chemotherapy – limited use
Corticosteroids

If the patient is terminally ill, relief of intrac­ranial pressure by steroids alone (dexam­eth­osone 4mg orally) may be all that is approp­riate.

Depending on the patient’s condition, the radiation oncologist will prescribe either 20 Gy in five fractions or 30 Gy in 10 fractions prescribed to midplane.

The intent of the treatment is palliative to relieve the patient of their neurol­ogical symptoms. Their prognosis remains poor.

An oncologist may prescribe a boost when the patient has demons­trated a good response and there is a solitary metast­asis. This boost may be treated with external beam, or the other option is stereo­tactic radiation therapy.

If this baseline is not achievable the jaws can be rotated so the inferior beam edge remains the same, or an alternate baseline can be chosen and MLC collim­ation employed to shield the eyes and oral cavity.

These patients have a limited prognosis, but if they live long enough to develop cataracts, their quality of life will usually be poor.

If the isocentre is on the vertical baseline (VBL), ATN and ML, asymmetric collim­ation can be used to achieve this. Two opposing lateral fields ensure that an even dose is delivered throughout the skull. If the patient has metastases in the cerebe­llum, the lower level of the field needs to be increased by a few centim­etres, which would then irradiate the eyes and some of the nasal cavity. If this is the case, the eyes will need to be shielded.

Brain metastases may be detected at the same time the primary tumour is diagnosed (synchr­onous presen­tation) or as is the case for over 80% of cases, the brain metastases develop after the primary is diagnosed (metach­ronous presen­tation).

Intrac­ranial metastases may occur in the meninges, brain or the skull. 80% of brain metastases occur in the cerebral hemisp­heres and 16% in the cerebe­llum. Rarely deposits may occur in the basal ganglia, brainstem, pituitary gland and the choroid plexus.

physical examin­ation testing reflexes; a neurol­ogical examin­ation; CT; Contrast enhanced MRI; Arteri­ography (radio­graphy of an artery); Biopsy