Table 1.

Eligibility criteria for randomized controlled studies.

Study	Inclusion criteria	Exclusion criteria
Price [5]	•Painful bone metastases •Cytological or histological evidence of malignancy	•Prognosis less than 6 weeks •incapable of completing the pain chart •Pathological fracture of long bone •Previous radiotherapy •Change in systemic therapy within 6 weeks
Cole [6]	•Metastatic bone pain •Life expectancy of at least 3 months	•Spinal cord or peripheral nerve compression syndrome •Actual or threatened pathological fracture •Previous radiotherapy
Kagei [7]	•Painful bone metastases	•Treated with chemotherapy on same day as radiotherapy •Fracture which was not vertebral compression fracture caused by bone metastases
Gaze [8]	•Histologically or cytologically proven cancer, and demonstrated by plain radiography or skeletal scintigraphy •Could be re-entered into the trial if separate, previously untreated, painful areas •Maximum field size of 150 cm2 was allowed where spinal cord or bowel was included in the field, or 200 cm2 for more peripheral sites	•Prior irradiation •New concurrent systemic treatment •Serious inter-current illness or life expectancy of <4 weeks •Spinal cord compression, vertebral collapse above the level of L2, impending or established pathological fracture, or prior surgical fixation •Widespread disease requiring large-field or hemi-body irradiation
Nielsen [9]	•Painful bone metastases localized to a single region that previous radiotherapy to the region concerned could be encompassed within a single radiation field •Histopathologically or cytologically confirmed malignancy and metastases were radiologically verified •Able to complete a pain evaluation form •Life expectancy more than 6 weeks	•Pathological fractures except compression fractures of the vertebral spinal column •Spinal cord compression
Foro [10]	•Painful bony metastases •Any primary tumor	•Pathological fractures •Risk of fractures •Medulla compression •Requiring hemi-body irradiation
Koswig [11]	•Histologically proven breast, lung, prostate and kidney carcinoma •Radiologically solitary osteolysis with or without fracture risk and with pain •Osteolytic lesion had to be suitable for bone density measurements via CT	•Prior irradiation •New systematic therapies in the last two weeks
BPTWP [12]	•Histological or cytological diagnosis of cancer •Age over 18 years •pain •Willingness to complete pain questionnaires for 12 months	•Pathological fracture of a long bone •Previous radiotherapy •Earlier entry into the same trial
Kirkbride [13]	•Painful bone metastases from any primary tumour site and the estimated survival was >4 months	Not available
Ozsaran [14]	•Solitary or multiple bone metastases •Cytological or histological evidence of malignancy •Karnofsky performance status greater or equal to 50 •Allowed to re-enter the trial if they previously untreated painful bone metastases	•Previous radiotherapy •Prior surgical treatment for pathologic fracture or cord compression
Sarkar [15]	•Patient able to determine subjectively the amount of pain. •Cytologically or histologically proven malignant disease with painful bone metastases	•previous radiotherapy •concurrent chemotherapy or hormone therapy •chemotherapy within the last 4 weeks or hormone therapy within the last 8 weeks •Pathological fracture
Altundag [16]	•Histological or pathological malignancy •Painful bone metastases •pain can be assessed/quantified	•prior radiation therapy •surgical intervention •Symptoms of spinal cord compression •Pathological breaks
Badzio [17]	•Cytological or histopathological evidence of cancer •Confirmed by X-ray	•Pathological fracture or previous irradiation to the metastatic sites
van der Linden [18]	•Painful bone metastases •solid tumors •Pain score minimum 2 on 11-point scale (0=no pain to 10=worst imaginable pain) •Metastases treatable in one radiotherapy target volume	•Pathologic fracture or impending fracture needing surgical fixation •Spinal cord compression •Renal cell carcinoma or melanoma •cervical spine •Previous radiotherapy
Roos [19]	•Pathologically confirmed malignancy •Plain X-ray or bone scan evidence of bone metastasis •Pain or dysaesthesia predominantly of a neuropathic nature •Life expectancy at least six weeks. •Able to complete the pain assessments	•Metastasis within the distribution of the neuropathic pain (e.g. shaft of femur metastasis with L2 neuropathic pain) •Prior radiotherapy to the index site •Clinical or radiological evidence of compression of the spinal cord or cauda equina •Pathological fracture of long bone(s) at index site •Change in systemic therapy within 6 weeks before, or anticipated within 4 weeks after commencing radiotherapy •Neuropathic pain due primarily to extra-skeletal tumor
Hartsell [20]	•Age of 18 years or older •Histologically proven malignancy of breast and prostate •Radiographic evidence of bone metastasis •Painful bone metastasis •A Karnofsky performance status of at least 40 •Life expectancy of at least 3 months •Pain assessed with the Worst Pain Score from the Brief Pain Inventory, requiring a score of at least 5 on a scale of 10 (or a score of less than 5 but taking narcotic medications with a daily oral morphine equivalent dose of at least 60 mg) •Patient with up to 3 separate sites of painful metastases •Patient receiving biphosphonates or systemic therapy (hormonal therapy, chemotherapy, immunotherapy, or systemic radioisotope therapy) as long as no introduction of any systemic therapy within the 30 days before entry into the study	•Pathologic fracture or impending fracture of the treatment site •Planned surgical fixation of the bone •Clinical or radiographic evidence of spinal cord or cauda equina compression and/or effacement
El-Shenshawy [21]	•Painful bone metastases from a solid tumor •Radiologically verified bony metastases •Histopathologically or cytologically confirmed malignancy	•Previous radiotherapy •Pathological fractures except compression fractures of the vertebral spinal column and suspicion of spinal cord compression •Chemotherapy and/or hormonal treatment was allowed but not during radiotherapy, and all changes related to such treatment were carefully registered •New concurrent treatment
Hamouda [22]	•Localized bone metastases •Histological or cytological evidence of malignancy •Radiographic evidence of bone metastasis •No change in chemotherapy or hormonal therapy within 30 days	•Pathological fractures •Previous radiotherapy
Safwat [23]	•18 years or older •Known malignancy metastatic to bone causing neuropathic pain •Life expectancy of at least 3 months	•Clinical or radiological evidence of cord or cauda equina compression •irradiation or hormonal treatment, biphosphonates or chemotherapy within 10 weeks prior to the study
Amouzegar-Hashemi [24]	•Adult with painful uncomplicated bone metastases	•Cord compression or existing or impending pathologic fracture
Foro Arnalot [25]	•Age of 18 years or older •Estimated life expectancy of at least 1 month	•Reported pain due to a pathological fracture or •impending fracture following Mirels׳ criteria; patients with a score of 9 were referred for prophylactic surgical fixation •Clinical or radiographic evidence of spinal cord compression •Pain at more than one site •Prior radiotherapy •Pain could not be assessed either because of an overall poor state of health or due to difficulties in applying the ordinal pain scale (OS)
Steenland [26]	•Painful bone metastases from solid tumor •Pain score of at least 2 on 11-point scale at time of admission •Bone metastases treatable in one target volume •Karnofsky index of 60% or more	•previously irradiated •Pathological fracture needing surgical fixation •Spinal cord compression •Melanoma or renal cell carcinoma •Cervical spine
Sande [27]	•Biopsy- or cytology-proven malignancy and bone metastasis verified either by bone X-ray, bone scan, CT or MRI •Karnofsky performance status above 40 •Painful bone metastases	•Previous irradiation •Spinal cord compression •Need of bone surgery •unable to complete the QOL assessment tools •Life expectancy less than 6 weeks
Kaasa [28]	•Painful bone metastases •Biopsy-or cytology-proven malignancy, bone metastasis verified by bone X-ray, bone scan, CT or MRI •Karnofsky performance status above 40	•Previous irradiation •spinal cord compression •Need of bone surgery •Unable to complete the QOL assessment tools •Life expectancy less than 6 weeks
Haddad [29]	•Adult with painful uncomplicated bone metastases	•Cord compression or existing or impending pathologic fracture