
"Local radiotherapy plays an important and responsible role in the management of bone metastases according to the different treatment objectives in the sense of pain relief, remineralization and cord decompression. Radiotherapy schedules, aimed at the relief of pain, need to take into consideration life expectancy. Patients with a reduced life expectancy could have a good high chance of achieving pain relief with a single dose of 8 Gy. Patients with a solitary metastasis, patients with a longer life expectancy and patients with a pathological fracture should be treated with 'curative' irradiation doses, aimed at killing the maximum number of tumor cells. [134]

In addition to pain relief, remineralization is also an important treatment goal. Conventional radiotherapy with doses of 40-50 Gy resulted in pain relief in 70-100% and in remineralization in 60-80% of the patients. Remineralization could not be accelerated by short-course fractionation courses, but resulted in faster pain relief. Short-course fractionation schedules are not indicated as a 'standard' treatment in the vertebral column. Surgery is the treatment of choice for immediate cord decompression and stabilization of a pathological vertebral fracture. Radiotherapy alone could decrease neurological impairment and is suitable for patients with gradual onset and progression of symptoms, no spinal instability and lesions of the cauda equina." [134]

Intensity and severity of radiation-induced nausea and emesis depend on a number of factors including irradiation site, irradiation dose, treatment field (width and length), and age of the patients. Although less intensive than that induced by chemotherapy, during protracted courses of fractionated radiotherapy discomfort can be substantial. As early as 1953, Court-Brown [2] described characteristic symptoms after single-fraction radiotherapy as "acute irradiation syndrome": irradiation was followed by asymptomatic period of 40-90 minutes, after that the patient experienced an acute episode of emesis, usually without preceding nausea. After a period of relative stabilization, additional episodes of emesis occurred for six hours after irradiation, decreasing its intensity with time. Danjoux et al. [5] noted a higher incidence of radiation-induced emesis after the upper half-body irradiation (UHBI) than after the lower half-body irradiation (LHBI), lack of efficacy of antiemetics administered, and similar response to emesis after the lower or the upper half-body irradiation. These results suggested that critical area was the upper abdomen. [117]

Targeting of radiotherapy can be based on improving physical dose distribution of radiation delivered or on utilization of specific biological processes for targeting. Tools for physical targeting include Brach therapy, hadron therapy, conformal radiotherapy, stereotactic radiotherapy, stereotactically guided conformal fractionated radiotherapy, and intensity-modulated radiotherapy. Biological targeting can be based on specific metabolic pathways such as uptake of iodine-131 by thyroid cancer cells, difference in substrate uptake between cancer cells and normal cells (e.g. boronophenylalanine in boron neutron capture therapy), targeting of radioactive isotopes by specific carrier molecules (radioimmunotherapy, labeled hormone derivatives or bone-seeking phosphonates), or on the distribution of elements in the body (therapy of bone metastases with a calcium analog strontium-89 or phosphorus-32). [29]

Painful bone metastases are common in oncologic practice. The role of surgery should be limited to patients with neurologic compression or severe mechanical instability. [102]  Ninety percent of patients with symptomatic bone metastases obtain some pain relief with a low dose, brief course of palliative radiotherapy. One half of the responding patients may experience complete pain relief. A single dose of 800 cGy in the setting of painful bone metastasis may provide pain control comparable to more protracted treatment at a higher dose of radiation. [80] There seem to be no significant differences in pain relief between the different fractionation schedules. A palliation is ensured in 75% of all cases with a partial response of 42% and complete response of 33%. With regard to pain response these results do not justify a recommendation for a standard fractionation schedule. Current fractionation schedules such as 10 x 3 Gy for 2 weeks or 5 x 4 Gy for 1 week should probably be used.[53]   In one study, two short courses of radiation for bone pain were compared: 20 Gy in one week (daily dose 4 Gy), and 30 Gy in 3 weeks (daily dose 2 Gy).  There was a light trend favoring 30 Gy in frequency of pain relief and recalcification. [78] However, it is not known whether these short radiation schedules are adequate for patients with longer prognoses, or what the optimal fractionation schedule is for maintaining the structural integrity of the bone.

For patients with symptomatic widespread bone metastases, options include bisphosphonates or radiotherapy.  There are two forms of systemic radiotherapy available: hemibody irradiation and intravenous injection of radionuclides. Studies have shown the combination of either focal irradiation and hemibody irradiation or focal irradiation and the injection of strontium-89 prolongs the pain-free duration of the patients. [80,100,125]   HBI is a powerful palliative treatment in patients with multiple symptomatic bone metastases.  Analysis of one study of 78 procedures on 71 patients, treated with 6 Gy (upper half-body) or 8 Gy (lower half-body) HBI in single fraction: Complete (37.5%) or partial responses were observed in 72/78 (92.3%) procedures, 80% appearing during the first 72 hours. A mean response duration of 101 days over a mean overall survival of 141 days implies coverage of 70% of patient's life span.  [72]

A slower development of motor deficits before beginning of radiotherapy means a better therapeutic effect and a more favorable functional outcome after treatment. The prognosis is extraordinarily poor if severe deterioration of motor function occurs within 48 hours before radiotherapy.  [54]

A meta-analysis of the literature on Radiotherapy for Skeletal Metastases was done in 1996. It was based on 171 scientific articles involving over 13,000 patients, and states:   <b>"Radiotherapy has been well documented as a method for alleviating pain, but the mechanisms underlying this effect are largely unknown. When used for pain palliation, radiotherapy achieves freedom from pain, or substantial alleviation of pain in nearly all cases, with few side effects.</b> Half-body irradiation is effective in treating multiple metastatic sites and should be considered for use more frequently. However, this increases the requirements on equipment, dosimetry, and hospital beds. Systemic radiotherapy with radionuclides may be indicated for generalized skeletal pain. The role of radiotherapy in preventing or healing fractures is not fully evaluated. Optimum dose levels and fractionation schedules have not been established. Early radiotherapy for spinal cord compression may prevent symptoms from worsening, but the effects on existing paralysis are modest." [55] 

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compiled/written by doctordee
with thanks to Lynette and Laura 
June 2002 
updated December 2003
