This is the current release of the guideline.

Advanced cancer with:

• Brain metastases
• Malignant epidural spinal cord compression
• Malignant superior vena cava obstruction
• Bone metastases
• Upper aero-digestive tract obstruction, compression, or invasion
• Malignancy-associated urogenital or gastrointestinal bleeding, or hemoptysis

To provide recommended palliative radiotherapy strategies for adult patients with advanced cancer

Adult patients with:

• Single or multiple brain metastases arising from cancer of any histology other than germ cell tumours or hematologic malignancies
• Impending or established malignant epidural spinal cord compression
• Malignant superior vena cava obstruction
• Complicated or uncomplicated bone metastases
• Upper aero-digestive tract obstruction, compression, or invasion
• Malignancy-associated urogenital or gastrointestinal bleeding, or hemoptysis

Brain Metastases

1. Neurosurgical opinion
2. Post-operative whole brain radiotherapy (WBRT)
3. Stereotactic radiosurgery (SRS)
4. WBRT alone
5. WBRT with SRS boost
6. Salvage SRS in selected cases
7. Repeat WBRT on a case-by-case basis

Note: Altered fractionation, partial brain dose escalation, and chemotherapy post-WBRT were considered but not recommended. Use of radiosensitizers was not recommended outside of a clinical trial setting.

Spinal Cord Compression

1. Short-course multi-fraction radiotherapy
2. Consultation with spinal service for a surgical opinion for overt or established spinal cord compression

Superior Vena Cava Obstruction

1. Chemotherapy and/or radiotherapy
2. Stent insertion

Note: Steroids and concurrent radiotherapy and chemotherapy were considered but not recommended.

Bone Metastases

1. Single-fraction or fractionated external beam radiation
2. Dexamethasone (participation in a clinical trial is encouraged)
3. Hemibody irradiation with premedication
4. Radioisotope selection (strontium-89, samarium-153)
5. Surgery
6. Postoperative radiation
7. Percutaneous vertebroplasty and kyphoplasty

Airway Obstruction or Compression

1. Radiotherapy
2. Endobronchial brachytherapy
3. Photodynamic therapy
4. Neodymium-doped yttrium-aluminum-garnet (Nd-YAG) laser
5. Stenting

Note: Radiotherapy for patients with incurable disease but minimal to no symptoms and concurrent chemoradiotherapy as standard of care in patients with non-small cell lung cancer (NSCLC) were considered but not recommended.

Gastrointestinal Obstruction or Compression

1. External beam radiotherapy
2. Stent placement or brachytherapy
3. Surgical bypass

Note: Concurrent chemoradiotherapy was considered but not recommended outside of a clinical trial.

Urogenital Bleeding

External beam radiotherapy

Gastrointestinal Bleeding

Radiotherapy either alone or with chemotherapy

Hemoptysis

1. Endoluminal brachytherapy
2. External beam radiotherapy

Research Questions

Specific research questions to be addressed by the guideline document were formulated by the guideline lead(s) and Knowledge Management (KM) Specialist using the PICO question format (patient or population, intervention, comparisons, outcomes).

Guideline Questions

What are the recommended strategies for the management and treatment of adult patients with:

• A newly diagnosed solitary brain metastasis?
• Newly diagnosed multiple brain metastases?
• Progressive or recurrent brain metastases?
• Impending or established malignant spinal cord compression?
• Superior vena cava obstruction?
• Uncomplicated bone metastases, including the role of hemibody irradiation, radioisotopes, and surgery?
• Complicated bone metastases, including the role of re-treatment?
• Malignant airway compression or obstruction?
• Malignant gastrointestinal compression or obstruction?
• Malignancy-associated urogenital or gastrointestinal bleeding?
• Malignancy-associated hemoptysis?

Search Strategy

For the 2010 guideline update, the following electronic databases were searched (January 2008 to March 2010): Medline, EMBASE, CINAHL, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Registry, and PubMed. The search strategy involved a combination of medical subject heading (MeSH) terms and text words. The specific search terms used for the Medline search are provided in Appendix A in the original guideline document; this search strategy was modified, as appropriate, and repeated for each of the other databases searched. Articles were excluded from the review if they: had a non-English abstract, were not available through the library system, were case studies involving less than 10 patients, involved pediatric patients, or were published prior to the year 2008. To identify additional articles, the references of articles identified through the formal searches were scanned for additional sources, and an environmental scan of the literature was also performed. All retrieved articles were graded and assigned a level of evidence (see the "Rating Scheme for the Strength of the Evidence" field).

A search for new or updated clinical practice guidelines published from January 2004 to March 2010 was also conducted, and yielded published guidelines by the following organizations: American College of Chest Physicians, American College of Radiology, American Society for Radiation Oncology (ASTRO), Australian Cancer Network, British Columbia Cancer Agency (BCCA), Cancer Care Ontario (CCO), International RadioSurgery Association (IRSA), National Cancer Institute (NCI), National Comprehensive Cancer Network (NCCN), National Institute for Health and Clinical Excellence (NICE), and Scottish Intercollegiate Guidelines Network (SIGN).

Not stated

For the 2010 update, evidence was selected and reviewed by a working group comprised of radiation oncologists from Alberta Health Services – Cancer Care and a Knowledge Management (KM) Specialist from the Guideline Utilization Resource Unit (GURU). A detailed description of the methodology followed during the guideline development process can be found in the Guideline Utilization Resource Unit Handbook  (see the "Availability of Companion Documents" field).

Evidence Tables

Evidence tables containing the first author, year of publication, patient group/stage of disease, methodology, and main outcomes of interest are assembled using the studies identified in the literature search. Existing guidelines on the topic are assessed by the KM Specialist using portions of the AGREE II instrument (http://www.agreetrust.org ) and those meeting the minimum requirements are included in the evidence document. Due to limited resources, GURU does not regularly employ the use of multiple reviewers to rank the level of evidence; rather, the methodology portion of the evidence table contains the pertinent information required for the reader to judge for himself the quality of the studies.

The working group members formulated the guideline recommendations based on the evidence synthesized by the Knowledge Management (KM) Specialist during the planning process, blended with expert clinical interpretation of the evidence. As detailed in the Guideline Utilization Resource Unit Handbook  (see the "Availability of Companion Documents" field), the working group members may decide to adopt the recommendations of another institution without any revisions, adapt the recommendations of another institution or institutions to better reflect local practices, or develop their own set of recommendations by adapting some, but not all, recommendations from different guidelines.

The degree to which a recommendation is based on expert opinion of the working group and/or the Provincial Tumour Team members is explicitly stated in the guideline recommendations. Similar to the American Society of Clinical Oncology (ASCO) methodology for formulating guideline recommendations, the Guideline Utilization Resource Unit (GURU) does not use formal rating schemes for describing the strength of the recommendations, but rather describes, in conventional and explicit language, the type and quality of the research and existing guidelines that were taken into consideration when formulating the recommendations.

Not applicable

There is some evidence that strontium is cost-effective compared to local external beam radiotherapy alone.

When the draft guideline document was completed, revised, and reviewed by the Knowledge Management (KM) Specialist and the working group members, it was sent to all members of the Provincial Tumour Team for review and comment. The working group members then made final revisions to the document based on the received feedback, as appropriate. Once the guideline was finalized, it was officially endorsed by the Provincial Tumour Team Lead and the Director of Provincial Clinical Teams.

Brain Metastases

Recommendations for a Solitary Brain Metastasis

1. A neurosurgical opinion is strongly recommended for excision of a single brain metastasis in patients with a good performance status (PS) and minimal, no, or controlled extra-cranial disease, especially where there is no previous pathologic confirmation of malignancy. Surgical resection followed by post-operative whole brain radiotherapy (WBRT) is associated with a survival benefit over WBRT alone. Post-operative WBRT reduces the risk of recurrence, increases the duration of functional independence, and decreases the likelihood of death secondary to neurological causes.
2. In patients not eligible for surgery, stereotactic radiosurgery (SRS) should be considered in patients with one brain metastasis (smaller than 4 cm), good PS, and limited or controlled extra-cranial disease. The addition of SRS to WBRT improves local control and may improve survival in patients with a solitary brain metastasis. Detailed information regarding quality of life (QoL) measures for patients treated with SRS is limited at the present time. SRS alone is not routinely considered standard of care, but in certain clinical situations where surveillance and salvage therapy are readily accessible, treatment with SRS alone may be an option.
3. In patients not eligible for surgery or SRS, WBRT alone is associated with an improvement in median survival compared to no treatment or steroids.
4. No strong evidence supports a specific WBRT dose fractionation schedule, with generally equivalent symptomatic improvement, median time to progression, and median survival for all regimens. A dose of 30Gy/10 fractions may be associated with less late neuromorbidity in select long-term survivors however, and should be considered in the setting of planned SRS boost.
5. Altered fractionation and partial brain dose escalation have not proved clinically useful to date.
6. Although studies investigating chemotherapy following WBRT suggest an improved in-brain response, they also generally report increased toxicity and no statistically significant survival benefit, and are therefore not currently recommended outside of a clinical trial setting.
7. The use of radiosensitizers is not recommended outside of a clinical trial setting.

Recommendations for Multiple Brain Metastases

8. For patients with up to four newly diagnosed brain metastases smaller than 4 cm in size, there is strong evidence from two large randomized controlled trials and several systematic reviews and meta-analyses that SRS boost after WBRT significantly improves local control and PS compared with WBRT alone. There may also be a survival advantage for certain subgroups of patients, although the evidence is limited.
9. WBRT alone is associated with an improvement in median survival compared to steroids alone. No strong evidence supports a specific dose fractionation schedule, with generally equivalent symptomatic improvement, median time to progression, and median survival reported for all regimens.
10. A WBRT dose of 30 Gy/10 fractions may be associated with less late neuromorbidity in select long term survivors, and should be considered in the setting of planned SRS boost.
11. Altered fractionation and partial brain dose escalation has not proved clinically useful to date.
12. SRS alone is not routinely considered standard of care, but in certain clinical situations where surveillance and salvage therapy are readily accessible, treatment with SRS alone may be an option.
13. There is limited evidence to suggest that chemotherapy in combination with WBRT is associated with improved in-brain responses and increased time to neurological progression, particularly for patients with non-small cell lung cancer (NSCLC) or breast cancer. However, several studies also report increased toxicity and no statistically significant survival benefit; therefore chemotherapy in combination with WBRT is not currently recommended for patients with multiple brain metastases outside of a clinical trial setting.
14. The use of radiosensitizers is not recommended outside of a clinical trial setting at the present time.

Recommendations for Recurrent or Progressive Brain Metastases

15. Although there is a lack of evidence for the use of SRS in the salvage setting, SRS as salvage may be an option for select patients with one to four recurrent or progressive brain metastases, good PS, and minimal, no, or controlled extra-cranial disease.
16. Repeat WBRT may be considered on a case-by-case basis. Patients who may benefit most from repeat WBRT include those with: a survival greater than six to nine months after initial WBRT, new neurological symptoms, and good PS.

Spinal Cord Compression (SCC)

Recommendations for Impending Spinal Cord Compression

1. Retrospective data suggests that radiotherapy may preserve neurologic function in patients with radiological impending SCC (i.e., no neurologic deficits, and back pain as the only symptom). There is insufficient evidence at present, however, to guide practice on the optimal dose fractionation schedule, as well as the most appropriate role for surgery in patients with impending SCC.

Recommendations for Overt or Established Spinal Cord Compression

2. It is strongly recommended that a spinal service be consulted for a surgical opinion.
3. In patients who are not candidates for surgery, radiotherapy alone is the recommended treatment, although the optimal dose and fractionation schedule is not known.

Superior Vena Cava Obstruction (SVCO)

Recommendations

1. For patients with lung cancer, chemotherapy and/or radiotherapy are effective in relieving SVCO in the majority of patients. While there is insufficient evidence to guide practice on radiotherapy dose fractionation, a retrospective review of SVCO due to any histology reported that an initial dose greater than or equal to 3 Gy/fraction yielded a higher rate of symptomatic relief in less than two weeks than a conventional dose of 2 Gy/fraction.
2. Stent insertion appears to provide rapid relief of associated symptoms, particularly for patients who fail to respond to chemotherapy or radiotherapy, patients with relapsed SVCO after chemotherapy or radiotherapy, and patients with NSCLC. The optimal timing of stent insertion is currently uncertain, and the role of radiotherapy post-insertion has not been defined. The need for long-term anticoagulation therapy to prevent stent occlusion also remains unclear.
3. There is a lack of evidence to support the use of steroids in the management of patients with SVCO.
4. Concurrent radiotherapy and chemotherapy have not been shown to improve response rates, symptomatic relief or survival in patients with SVCO.

Bone Metastases

Recommendations for External Beam Radiation

1. Uncomplicated bone metastases. A single 8 Gy treatment is recommended as the standard therapy for uncomplicated bone metastases. There is insufficient evidence to recommend a specific dose fractionation schedule for treatment indications other than pain relief, such as long-term disease control for patients with a solitary bone metastasis.
2. Complicated bone metastases. For bone metastases causing neuropathic pain, either 8 Gy in a single fraction or 20 Gy/5 fractions may be considered standard. Although there is no consensus, most guideline authors recommend fractionated radiotherapy in a patient with an impending or established fracture who is not a candidate for surgical intervention. There is also insufficient evidence to recommend a specific dose fractionation schedule for treatment of soft tissue masses associated with bony disease or other complicated bone metastases.
3. Dexamethasone may be an effective prophylactic agent for the prevention of pain flare after palliative radiotherapy for bone metastases. Whenever possible, participation in a clinical trial, such as the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) SC.23 trial, which is soon opening for enrollment in Canada, is encouraged.

Recommendations for Re-treatment

4. Re-treatment of bone metastases is effective in providing pain relief. Enrollment in a clinical trial, such as the NCIC CTG SC.20 trial in Canada, is strongly encouraged. Pending the results of this ongoing trial, re-treatment with a single 8 Gy fraction or 20 Gy/5 fractions (20 Gy/8 fractions for spine and whole pelvis) are reasonable alternatives depending on the previous dose and treatment volume.

Recommendations for Hemibody Irradiation (HBI)

5. HBI is an effective palliative treatment for symptoms associated with widespread bony metastases.
6. Either a single fraction or a fractionated course of HBI may be considered for the palliation of pain. Single fraction HBI is effective in providing pain relief often within 24 to 48 hours, with some evidence to suggest a decreased need for subsequent local radiotherapy. HBI may be delivered either to the upper half (base of skull to iliac crest; 6 Gy/1 fraction) or lower half of the body (iliac crest to ankles; 8 Gy/1 fraction).
7. HBI treatment is associated with transitory but potentially severe hematopoietic and gastrointestinal tract toxicity. Patients should be premedicated with intravenous fluids, antiemetics and corticosteroids, and provided with analgesics in the event of pain flare. Sequential treatment of both the upper and lower body requires a four to six week gap for interval recovery of myelosuppression.

Recommendations for Radioisotopes

8. Strontium-89 and samarium-153 are both effective in providing pain relief, and work equally well in various cancers without evidence of a dose response. Symptom response can take two to three weeks, with complete relief in up to 20 percent of patients and a mean duration of pain relief of up to six months. Flare reaction occurs in approximately ten percent of patients. Myelosuppression is usually grade two or less, and is self-limited, with recovery in eight to 12 weeks. Strontium may be particularly useful in hormone refractory metastatic prostate cancer when painful bone metastases are poorly controlled by opioid analgesics and patients are not candidates for multiple local radiotherapy fields or HBI.
9. There is some evidence that strontium is cost-effective compared to local external beam radiotherapy alone. Patient eligibility criteria are strict however (i.e., minimum PS and laboratory values, painful sites of disease on both sides of the diaphragm), and radioisotopes should not be used in the presence of pathologic fracture, spinal cord compression, or nerve root compression.
10. The evidence for alternating a radioisotope after a lack of response to a different one is poorly defined. The role of strontium as an adjunct to palliative external beam radiotherapy remains uncertain.
11. Radioisotopes may preclude further systemic chemotherapy or eligibility for clinical trials of systemic therapy. Further research is needed to examine the use of radioisotopes in combination with systemic therapies.

Recommendations for Surgery

12. Impending fracture. An impending fracture is defined as a bony metastasis that, if not addressed, has a significant likelihood of fracture under normal physiological stresses. Depending on individual and disease factors, patients with an impending fracture may benefit from surgery, radiotherapy or both. If the patient is inoperable due to a co-morbidity or deteriorating condition, palliative radiotherapy (20 Gy/5 fractions) is reasonable to reduce pain.
13. Post-operative radiotherapy. Postoperative radiotherapy, delivered at a dose of 20 Gy/5 fractions or 30 Gy/10 fractions, suppresses tumour growth and prevents destabilization of a prosthesis by maintaining the structural integrity of the bone in which it is fixed. Post-operative radiotherapy decreases pain, increases the frequency of normal use of the extremity, decreases the likelihood of revision procedures/implant failure, minimizes the risk of disease progression, and reduces the risk of refracture.
14. Percutaneous vertebroplasty and kyphoplasty. Percutaneous vertebroplasty and kyphoplasty are minimally invasive surgical techniques that are alternatives to open surgery for restoring stability to bone metastases, most commonly in the spine and pelvis. These are both potential treatment options for patients who are not suitable for invasive spinal surgery due to medical comorbidities, multilevel disease, or profound neurologic deficits. The combination of percutaneous vertebroplasty or kyphoplasty with external beam radiotherapy remains undefined at the present time.

Upper Aero-Digestive Tract Obstruction

Recommendations for Airway Obstruction or Compression

1. There is no evidence to support delivery of immediate thoracic radiotherapy in patients with minimal to no symptoms secondary to incurable disease. Radiotherapy could be deferred until symptoms warrant, unless a patient is at risk of a serious adverse outcome with disease progression, such as airway compromise.
2. When indicated to palliate intrathoracic symptoms such as airway compromise, short course multi-fraction radiotherapy is preferred over single fraction treatment.
3. There is no evidence to support concurrent chemoradiotherapy as standard of care for symptom relief in patients with NSCLC.
4. Endobronchial brachytherapy may be considered in patients with obstructing proximal airway tumours.
5. Endobronchial brachytherapy may also be considered in select patients with NSCLC previously treated with external beam radiotherapy who become obstructed due to recurrent or progressive disease.
6. Photodynamic therapy, neodymium-doped yttrium-aluminum-garnet (Nd-YAG) laser, and stenting may also be considered as alternatives for symptom control.

Recommendations for Gastrointestinal Obstruction or Compression

7. For palliation of dysphagia secondary to advanced esophageal cancer, external beam radiotherapy with 30 Gy/10 fractions or 35 Gy/15 fractions is a reasonable choice.
8. Stent placement or brachytherapy are also options in appropriately selected patients.
9. Surgical bypass may be considered in select patients with malignancy-associated gastrointestinal obstruction or compression, favourable disease, and no metastases, who are not amenable to other palliative methods.
10. Outside of a clinical trial, concurrent chemoradiotherapy is not considered standard of care.

Bleeding

Recommendations for Urogenital Bleeding

1. External beam radiotherapy has been shown to control hematuria in up to 60 percent of patients with advanced bladder cancer; and control rates of 80 percent at six weeks have recently been reported in patients with advanced prostate cancer. In patients with a life expectancy less than six months, external beam radiotherapy treatment with 8 Gy/1 fraction could be considered. Otherwise, a short course multi-fraction schedule could be considered.
2. In patients with vaginal bleeding who are unsuitable for radical treatment, radiotherapy is effective in resolving bleeding secondary to endometrial or cervical cancer. There is insufficient evidence to recommend an ideal dose and fractionation schedule. Radiotherapy may also be used to control bleeding and palliate pain and mass effect in advanced ovarian cancer.

Recommendations for Gastrointestinal Bleeding

3. Palliative radiotherapy either alone or with chemotherapy provides reasonable control of bleeding, dysphagia, and pain associated with gastrointestinal malignancies. Insufficient information exists to recommend a specific fractionation schedule, although one recent retrospective analysis noted a response rate of 68 percent in patients with unresectable gastric cancer treated with a median total dose of 40 Gy.

Recommendations for Hemoptysis

4. When indicated to palliate intrathoracic symptoms, including hemoptysis, similar symptom control and QoL outcomes have been reported regardless of dose fractionation, although there may be a survival advantage with 20 Gy/5 fractions over 10 Gy/1 fraction.
5. Endoluminal brachytherapy is an option for managing bleeding in patients who are not eligible for more aggressive treatment, where facilities and expertise exist.

None provided

The type of evidence supporting the recommendations is not specifically stated.

Appropriate use of palliative radiotherapy to improve outcomes in patients with advanced cancer

Toxicity of therapy

Radioisotopes should not be used in the presence of pathologic fracture, spinal cord compression, or nerve root compression.

The recommendations contained in this guideline are a consensus of currently accepted approaches to management, derived from a review of relevant scientific literature. Clinicians applying these guidelines should, in consultation with the patient, use independent medical judgment in the context of individual clinical circumstances to direct care.

Not applicable: The guideline was not adapted from another source.

Alberta Health Services, Cancer Care

Palliative Radiotherapy Working Group

Not stated

Participation of members of the Palliative Care Tumour Team in the development of this guideline has been voluntary and the authors have not been remunerated for their contributions. There was no direct industry involvement in the development or dissemination of this guideline. Alberta Health Services – Cancer Care recognizes that although industry support of research, education and other areas is necessary in order to advance patient care, such support may lead to potential conflicts of interest. Some members of the Palliative Care Tumour Team are involved in research funded by industry or have other such potential conflicts of interest. However, the developers of this guideline are satisfied it was developed in an unbiased manner.

This is the current release of the guideline.

Electronic copies: Available in Portable Document Format (PDF) from the Alberta Health Services Web site .

The following is available:

• Guideline utilization resource unit handbook. Edmonton (Alberta): Alberta Health Services, Cancer Care; 2011 Dec. 5 p. Electronic copies: Available in Portable Document Format (PDF) from the Alberta Health Services Web site .

None available

This NGC summary was completed by ECRI Institute on February 10, 2012. The information was verified by the guideline developer on March 30, 2012.

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.