Radiation therapy in the management of symptomatic bone metastases: The effect of total dose and histology on pain relief and response duration

Purpose: In order to better define variables and factors that may influence the pain response to radiation, and to look for a radiation regimen that c an assure the highest percentage and the longest duration of pain relief, w e performed a prospective, although not randomized, study on patients with bone metastases from various primary sites. Methods and Materials: From December 1988 to March 1994, 205 patients with a total of 255 solitary or multiple bone metastases from several primary tu mors were treated in our radiotherapy center with palliative intent. Irradi ation fields were treated with three main fractionation schedules: (1) Conv entional fractionation: 40-46 Gy/20-23 fractions in 5-5.5 weeks; (2) Short course: 30-36 Gy/10-12 fractions in 2-2.3 weeks; (3) Fast course: 8-28 Gy/1 -4 consecutive fractions. Pain intensity was self-assessed by patients usin g a visual analogic scale graduated from 0 (no pain) to 10 (the strongest p ain one can experience). Analgesic requirement was assessed by using a five -point scale, scoring both analgesic strength and frequency (0 = no drug or occasional nonopioids; 1 = Nonopioids once daily; 2 Nonopioids more than o nce daily; 3 = Mild opioids (oral codeine, pentazocine, etc.), once daily; 4 = Mild opioids more than once daily; 5 = Strong opioids (morphine, meperi dine, etc.). Complete pain relief meant the achievement of a score less tha n or equal to 2 in the pain scale or 0 in the analgesic requirement scale. Partial pain relief indicated a score of 3 to 4 or of 1 to 2 on the former and latter scale, respectively. Results: Total pain relief(complete + partial) was observed in 195 (76%) si tes, in 158 of which (62%) a complete response was obtained. Metastases fro m NSC lung tumors appeared to be the least responsive among all primary tum ors, with 46% complete pain relief in comparison to 65% and 83% complete re lief in breast (p = 0.04) and in prostate metastases (p = 0.002), respectiv ely. A significant difference in pain relief was detected among the several ranges of total dose delivered to the painful metastases, with 81%, 65%, a nd 46% complete relief rates in the 40-46 Gy, 30-36 Gy (p = 0.03), and 8-28 Gy (p = 0.0001) dose ranges respectively. A straight correlation between t otal dose and complete pain relief was confirmed by the curve calculated by the logistic model which shows that doses of 30 Gy or more are necessary t o achieve complete pain relief in 70% or more of bone metastases. This corr elation holds also for the duration of pain control, as shown by the actuar ial analysis of time to pain progression. Multivariate analyses, with compl ete pain relief and time to pain progression as endpoints show a highly sig nificant effect of radiation dose (p = 0.0007) and performance status (p = 0.003), with lower rates of complete pain relief and shorter time to pain p rogression observed after smaller radiation total doses or higher Eastern C ooperative Oncology Group (ECOG) scores. Conclusion: Although single-dose or short course irradiation is an attracti ve treatment in reducing the number of multiple visits to radiotherapy depa rtments for patients with painful bone metastases, it is nevertheless clear that aggressive protracted treatments seem to offer significant advantages especially for patients in whom the expected life span is not short. (C) 1 998 Elsevier Science Inc.