Radiofrequency ablation of osseous metastases for the palliation of pain

A number of different methods have been proposed for pain relief in cancer patients with bone metastases, each with different indications, contraindications and complications (systemic analgesics, bisphosphonates, antitumor chemotherapy, radiotherapy, systemic radio-isotopes, local surgery and vertebroplasty). The ideal treatment has to be fast, safe, effective and tolerable for the patient. CT-guided radiofrequency (RF) ablation may fulfill these criteria. Our experience in the treatment of 30 patients (34 lesions) with painful bone metastases using RF ablation was assessed. There was a significant decrease in the mean past-24-h Brief Pain Inventory (BPI) score for worst pain, for average pain and for pain interference during daily life (4.7, 4.8 and 5.3 units respectively) 4 and 8 weeks after treatment. There was a marked decrease (3 out of 30 patients 4 and 8 weeks after treatment) in the use of analgesics. CT-guided RF ablation appears to be effective for treatment of painful bone metastases.     

Considerations in the selection of radiopharmaceuticals for palliation of bone pain from metastatic osseous lesions.

Bone pain is a common complication for terminal patients with bone metastases from prostate, lung, breast, and other malignancies. A multidisciplinary approach in treating bone pain is generally required, 1 which includes a combination of analgesic drug therapy, radiation therapy, hormonal therapy, and chemotherapy. Over the years, treatment of bone pain using bone-seeking radiopharmaceuticals has been explored extensively. Pharmaceuticals labeled with energetic 1-particle emitters such as 32p, 89Sr, 153Sm, and 186Re, in addition to the low-energy electron emitter 117mSn, have been studied for this purpose. Bone-marrow toxicity as a consequence of chronic irradiation by the energetic , particles is a general problem associated with this form of treatment. It is therefore desirable to identify radiochemicals that minimize the dose to the bone marrow and at the same time deliver therapeutic doses to the bone. Methods: New S values (mean absorbed dose per unit cumulated activity) for target regions of human bone and marrow were used to ascertain the capacity of various radiochemicals to deliver a high bone dose while minimizing the marrow dose. The relative dosimetric advantage of a given radiopharmaceutical compared with a reference radiochemical was quantitated as a dosimetric relative advantage factor (RAF). Several radionuclides that emit energetic 1 particles (32p, 89Sr, 153Sm, 186Re, and 177Lu) and radionuclides that emit low-energy electrons or beta particles (169Er, 117mSn, and 33p) were evaluated. For these calculations, ratios of the cumulated activity in the bone relative to cumulated activity in the marrow alpha equal to 10 and 100 were used. Results: When the radiopharmaceutical was assumed to be uniformly distributed in the endosteum and alpha was taken as 100 for both the reference and test radiochemicals, the RAF values compared with the reference radionuclide 32p were 1.0, 1.2, 1.4, 1.6, 1.7, 1.9, and 2.0 for 89Sr, 186Re, 153Sm, 177Lu, 169Er, 117mSn, and 33P, respectively. In contrast, when the radiopharmaceutical is assumed to be uniformly distributed in the bone volume, the RAF values for these 7 radionuclides were 1.1, 1.5, 2.4, 3.2, 4.5, 5.1, and 6.5, respectively. CONCLUSION: These results suggest that low-energy electron emitters such as 117mSn and 33P are more likely to deliver a therapeutic dose to the bone while sparing the bone marrow than are energetic beta emitters such as 32p and 89Sr. Therefore, radiochemicals tagged with low-energy electron or beta emitters are the radiopharmaceuticals of choice for treatment of painful metastatic disease in bone.     

153Sm-EDTMP for bone pain palliation in skeletal metastases

153Sm-ethylene diamine tetramethylene phosphonate (EDTMP) is a widely available and extensively tested radiopharmaceutical for systemic radionuclide therapy in patients with symptomatic multiple skeletal metastases. Its use is approved for any secondary bone lesion which has been shown to accumulate (99m)Tc-methylene diphosphonate, including breast carcinoma. The molecule is stable in vitro and upon injection more than 50% of the dose is avidly fixed by lesional and non-lesional bone, with the rest being rapidly eliminated unchanged via the urine. The short half-life (46.3 h), the relatively low-energy beta emissions (E(ave)=233 keV) and the gamma emission (103 keV) make (153)Sm a very attractive radionuclide, allowing therapeutic delivery of short-range electrons at relatively high dose rates with external imaging to corroborate biodistribution and possible dosimetric estimates. For a standard dose of 2,590 MBq/70 kg, the estimated radiation dose to metastases is 86.5 Gy. Critical organs are the bladder wall (2.5 Gy/2,590 MBq) and red marrow (4 Gy/2,590 MBq), with the latter being the critical factor in clinical practice as the dose-limiting factor is marrow radiotoxicity. The therapy has, however, proved safe provided that the platelet count exceeds 100 x 10(9)/l and the white blood cell count exceeds 3.5 x 10(9)/l. Clinical data obtained in fewer than 250 patients, within several studies, lead to the following conclusions: a dose of 37 MBq/kg has a better therapeutic ratio than a dose of 18.5 MBq/kg; the mean pain palliation rate after a single treatment in breast cancer is about 80%; toxicity is generally mild and transitory; and re-treatments are effective and safe provided that haematological values have fully recovered.     

Strontium-89 therapy for the pain of osseous metastases

A Phase I and II study has been conducted of the safety and efficacy of 89Sr (injected i.v. as the chloride) to alleviate bone pain due to osseous metastatic disease. Potential attendant hematologic toxicity was also examined. Strontium-90 impurities were always less than 1.5%, employing a new quality control technique which detects the 90Y "daughter". Thirty-eight patients with pain due to osseous metastases requiring regular narcotic more than twice a day, documented by an abnormal bone scan and radiography, received 45 doses (1-4.5 mCi, 16-70 microCi/kg) of 89Sr after informed consent. The performance status (Karnofsky scale) ranged from 20-80%. One patient had complete pain relief while 22 other doses yielded at least a 25% reduction in narcotic requirement lasting at least 1 mo and/or 20% improvement in Karnofsky scale rating. Two patients had marked to complete relief in tumor sites which were not fractured, with no change in fracture pain. Twenty-two did not respond. Response was independent of narcotic requirements, tumor type, or Karnofsky status. No hematologic toxicity occurred. Strontium-89 may be useful as adjuvant therapy for diffuse bone pain, but a double-blind study comparing it to other nonnarcotic modalities is required.     

Multiple daily fractions of radiation in the palliation of pain from bone metastases

Twenty consecutive patients have been treated for palliation of pain from bony metastases with radiotherapy using a regime of multiple daily fractions. Patients received up to three treatments daily with 3-4 hour intervals between fractions. Pain was relieved in all cases and pain relief took place earlier in the treatment than with conventional daily regimes. Nausea was mild in most cases. Some factors in its aetiology are discussed. Acute skin reactions were minimal. The total dosage required and the advantages and disadvantages of the method are discussed.     

Multi-fractionated wide-field radiation therapy for palliation of multiple symptomatic bone metastases from solid tumors

PURPOSE: This was a pilot study to explore the toxicity and response of multi-fractionated wide-field radiation therapy (MF-WFRT) in patients with multiple symptomatic osseous metastases. PATIENTS AND METHODS: From February 1997 to April 1998, a total of nine patients (5 lung cancer, 3 breast cancer, 1 prostate cancer) were treated with MF-WFRT. The patients received 1.5 Gy per fraction (twice a day) to a total dose of 7 Gy in 3 days for the upper body and a total dose of 9 Gy in 3 days for the lower body. Ten treatments in nine patients were carried out with this technique (2 upper half-body, 5 lower half-body, 3 mid-body; one patient had both upper mid-body and lower-half body treatments). RESULTS: Pain relief was complete in two patients (20%) and eight (80%) achieved better than 50% pain relief. Seventy-five percent of pain responders achieved pain relief within one week of MF-WFRT. The pain relief was long-lasting and continued without need of reirradiation for 45% of the remainder of the patients' lives. The incidence of gastrointestinal complications was low, basically Grade 1-2 toxicity. Four patients (40%) experienced Grade 3-4 hematological toxicity. Hematological toxicity was treated with blood transfusion or G-CSF. General tolerance was excellent, and no pneumonitis or radiation-related deaths occurred. CONCLUSION: This treatment modality appears to be well tolerated and effective. The optimal indications, dose, and fractionation for MF-WFRT should be further explored in randomized studies.     

89Sr治疗老年患者前列腺癌骨转移骨痛的临床观察

目的 评价89^SrCl2对老年患者前列腺癌骨转移伴骨痛的临床疗效及不良反应.方法 对外科去势治疗术后的老年患者前列腺癌骨转移伴有不同程度骨痛患者48例,使用89^SrCl2静脉注射治疗,观察其镇痛效果、骨转移灶的变化、前列腺特异性抗原（PSA）及不良反应等.结果 48例患者接受89^Sr治疗后,止痛的总有效率达89.6%,无效10.4%,骨转移灶有明显减少.对PSA有不同程度的下降.所有治疗者均未发现严重的不良反应和毒副作用.结论 89^SrCl2对去势治疗术后的老年患者前列腺癌骨转移骨痛的临床止痛疗效明显,特别是对多发骨转移癌伴骨痛患者是一种有效的治疗方法.     

A practical guide to targeted therapy for bone pain palliation

Targeted radionuclide therapy is an effective and cost efficient treatment for multi-site metastatic bone pain. This paper discusses the physical characteristics of the licensed radiopharmaceuticals (153)Sm ethylenediamine-N,N,N',N'-tetrakis(methylene phosphonic acid) ((153)Sm-EDTMP), (186)Re 1,1-hydroxyethylidenediphosphonate ((186)Re-HEDP) and (89)SrCl(2) and considers the factors influencing treatment choice in specific clinical settings. The advantages and practical limitations of this approach are discussed, with emphasis on defining criteria for patient selection and response monitoring. Opportunities for future research and development are outlined.     

Bone pain palliation with strontium-89 in cancer patients with bone metastases.

Strontium-89 is a pure beta-emitting radioisotope, a chemical analogue of calcium, and it is therefore avidly concentrated by areas of high osteoblastic activity. Selective uptake and prolonged retention at sites of increased bone mineral turnover provide precise bone lesions targeting. 89Sr chloride (commercialised as Metastron) is typically administered in a single 150 MBq parenteral dose. Its radioactive emission poses very little radioprotection concerns. Overall, studies show pain relief in up to 80% of patients, of which 10 to 40% became effectively pain free. The mean duration of palliation was 3-4 months. The mechanism of pain relief is controversial ; it is probably, but not only, related to the absorbed dose in the tumour and bone. There is no clear dose-response relationship. The only reported toxicity is temporary myelosuppression. WBC and platelets should be monitored at least on a weekly basis until they return to baseline. It seems that only patients with a reasonably good general condition stand to benefit from this treatment. In conclusion, systemic radionuclide therapy using 89Sr represents a feasible, safe, effective, well tolerated and cost-effective palliative treatment in patients with refractory bone pain.     

Strontium-89 for palliation of pain from bone metastases in patients with prostate and breast cancer

We have used strontium-89 chloride (⁸⁹Sr) for the palliative treatment of metastatic bone pain. Seventy-six patients (50 males with prostate carcinoma and 26 females with breast cancer) were treated with 148 MBq of ⁸⁹Sr. Sixteen patients were retreated, receiving two or three doses; the total number of injected doses was consequently 95. The Karnofsky performance status was assessed and pain and analgesia were scored on scales of 9 and 5 points, respectively. The efficacy of ⁸⁹Sr was evaluated at 3 months of treament. Three levels of response were considered: good – when there was an increase in the Karnofsky status and a decrease in the pain score (equal to or higher than 4) or analgesic score (equal to or higher than 1); partial – when there was an increase in the Karnofsky status and a decrease in the pain score (2 or 3 points) without significant changes in the analgesic score; no response – if no variation or deterioration in these parameters was observed. In prostate cancer patients, the response was good in 64% of cases and partial in 25%, and there was no response in the remaining 11%. In breast cancer patients, the response was good in 62% of cases and partial in 31%, and there was no response in the remaining 8%. Duration of the response ranged from 3 to 12 months (mean 6 months). In the patients who were retreated the effectiveness was as good as after the first dose of ⁸⁹Sr. A decrease in the initial leucocyte and platelet counts was observed after the 1st month of treatment, with a gradual partial to complete recovery within 6 months. It is concluded that ⁸⁹Sr is an effective agent in palliative therapy for metastatic bone pain in patients with prostate or breast carcinoma. If required, retreatment can be administered safely and with the same efficacy as is achieved by the first dose. Received 13 March and in revised form 6 June 1997     

Half body irradiation for the palliation of bone metastases.

Half body irradiation using single large doses of photons has been reported as an effective modality for the palliation of symptoms due to widespread metastatic bone malignancy. Over a 7 year period (1982-1988) sixteen patients with disseminated malignancy were given half body irradiation at Auckland Hospital. Treatment consisted of a single dose of radiation of between 5 and 8 Gray. Either 6 or 8 MV photon beams were used. Twelve patients received treatment to the lower half body, three patients to the upper half body and one patient to both upper and lower half body. Significant pain relief occurred in fifteen patients and two patients experienced improvement with hypercalcaemia. All patients tolerated the treatment well and toxicity was minimal.     

用于骨痛治疗的放射性核素

介绍了用于骨疼痛治疗的放射性核素89Sr、153Sm、186Re、188Re和117Snm,评述了这些核素的生产以及在骨疼痛治疗中的应用,并对每个核素的优缺点进行了讨论。     

肿瘤骨转移疼痛患者对188Re-HEDP的耐受性研究

Objective To study the tolerance to 188Re-1-hydroxy-1 ,1-ethylidene disodium phosphonate(HEDP) in patients with bone pain caused by osseous metastases. Methods Thirty-one patients(10with prostate cancer, 9 with breast cancer, 3 with lung cancer, 5 with liver cancer, 2 with rectal cancer, 1with esophageal cancer and 1 with renal cancer) received a single injection dose of 188Re-HEDP. The patients were divided into four groups according to the injection dose: 20 MBq/kg (6 patients), 30 MBq/kg(6 patients), 40 MBq/kg (9 patients), and 50 MBq/kg (10 patients). Haematological toxicity (WHO grading) of grade Ⅲ- Ⅳ was considered unacceptable. Vital signs and adverse effects after injection were recorded for 8 weeks. Blood counts were measured weekly during a period of 8 weeks. Biochemical parameters and electrocardiogram were assayed at week 4 and 8. Statistical analysis was performed for per-protocol (pp) population (t-test). Results Twenty-seven patients belonged to PP population with 5 in the group of 20 MBq/kg, 5 in the group of 30 MBq/kg, 8 in the group of 40 MBq/kg and 9 in the group of 50 MBq/kg.No obvious adverse effects and no significant change of vital signs, electrocardiogram, liver and renal function were found after injection. Alkaline phosphatase was slightly higher than baseline at week 4 and 8 after therapy, but the difference was not statistically significant. In the 20 MBq/kg group, reversible grade Ⅰ leucopenia was noted in 1 patient. In the 30 MBq/kg group, 2 patients showed reversible grade Ⅰ leucopenia including 1 alone with reversible grade Ⅲ thrombopenia. In the 40 MBq/kg group, reversible grade Ⅰ leucopenia and thrombopenia was observed in 1 patient and reversible grade Ⅱ leucopenia and thrombopenia in another patient. In the .50 MBq/kg group, 3 patients showed reversible grade Ⅱ leucopenia. The lowest level of thrombopenia was at week 4(143.5 × 109/L), leucopenia at week 6 (5.4 × 109/L) and anaemia at week 8(t = 3.1325, 3.3156, 3.4917, all P ＜ 0. 05 compared with baseline). At week 8, the mean level of platelet and leucocyte recovered to baseline. "Bounce pain" was found in 2 of 27 patients (7.41%).Conclusions The dose of 20 MBq/kg, 30 MBq/kg, 40 MBq/kg or 50 MBq/kg of 188Re-HEDP do not cause significant side effects on cancer patients with bone metastases, though there is a tendency that the haematological toxicity may increase as the dose of 188Re-HEDP increases.     

肿瘤骨转移疼痛患者对^188Re-HEDP的耐受性研究

目的 评价^188Re-1-羟基-1,1-二膦酸钠乙烷（即依替膦酸盐,HEDP）治疗肿瘤骨转移疼痛患者的安全性.方法 符合入选标准的31例患者（前列腺癌10例,乳腺癌9例,肺癌3例,肝癌5例,直肠癌2例,食管癌1例,肾癌1例,均随时间顺序人选）知情同意后接受了按体质量肘静脉单次注射^188ReHEDP,据药物递增剂量分为4个组：20 MBq/kg组6例、30 MBq/kg组6例、40 MBq/kg组9例、50 MBq/kg组10例.低剂量组安全性分析结束并显示安全后,才开始下一剂量组试验.如果患者出现由于用药引起的不可耐受的、WHO公布的Ⅲ或Ⅳ级骨髓毒性,即终止剂量递增,并认为前一组剂量为最大可接受剂量.观察指标包括给药前及给药后8周内每例患者的生命体征（用药后1,6,12,24,48,72 h和1,2,3,4,6,8周）,血细胞计数（用药后1,2,3,4,6和8周）,心电图,肝、肾功能,ALP（用药后4,8周）,＂反跳痛＂以及不良反应等.统计分析主要针对符合方案集（PP）人群,包括统计描述和统计推断（t检验）.结果 31例患者中有27例属于PP人群：20 MBq/kg组5例、30 MBq/kg组5例、40 MBq/kg组8例、50 MBq/kg组9例.在受试剂量范围内,没有观察到188Re-HEDP对患者生命体征、心电图、肝肾功能和ALP的不良影响.20 MBq/kg组的5例患者中仅1例自细胞出现WHO Ⅰ级毒性;30 MBq/kg组5例患者中2例白细胞出现WHO Ⅰ级毒性,其中1例合并血小板Ⅲ级毒性,但给药后8周白细胞和血小板均恢复正常;40 MBq/kg组8例患者中2例白细胞和血小板同时出现毒性反应,分别为WHO Ⅰ级和Ⅱ级,表现为白细胞和血小板同时、同级减低;50 MBq/kg组9例患者中3例白细胞出现WHOⅡ级毒性.全部患者的血小板均在给药后4周达最低水平,平均为143.5×109/L;白细胞均在给药后6周达最低水平,平均为5.4×109/L（两者与给药前基线值比较,t值分别为3.1325和3.3156,P均＜0.05）,给药后8周自细胞和血小板均恢复到基线水平;而血红蛋白在给药后8周最低（与基线值比较,t值为3.4917,P＜0.05）.PP人群27例中有2例出现＂反跳痛＂,发生率7.41%（2/27）.结论 按体质量注射188Re-HEDP 20,30,40和50 MBq/kg对肿瘤骨转移患者均无明显毒性及不良反应,且随着用药剂量增加,188Re-HEDP对骨髓的抑制有增加趋势.     

Bone pain palliation with strontium-89 in breast cancer patients with bone metastases and refractory bone pain

Fifteen patients with breast cancer and skeletal metastases who had bone pain refractory to opioid analgesics and who were not eligible for or had not responded to local field radiotherapy, were treated with strontium-89. All patients had received previous treatment with chemotherapy and radiotherapy for bone metastases. Severity of bone pain, sleeping pattern, mobility and dependency on analgesics were evaluated before and 4, 8 and 12 weeks after⁸⁹Sr administration. Patients received 2 MBq/kg (118–148 MBq) of⁸⁹Sr by i.v. injection. Pain relief and a reduction in analgesic requirements were observed in 7 of the 15 (47%) patients, with a reduction in the severity score from 34% to 71%. Duration of the response varied from 3 to 7 months. A decrease in peripheral blood cell count was observed in 11 patients: a 15%–66% reduction in white cell count and a 14%–75% reduction in platelet count were detected at 12 weeks after treatment in these patients. We conclude that⁸⁹Sr is effective (47% response rate) for bone pain palliation in patients with bone metastases from breast cancer. Dependency on opioid analgesics may be reduced in patients with refractory bone pain.     

An individual dosimetric approach to 153Sm-EDTMP therapy for pain palliation in bone metastases in correlation with clinical results

BACKGROUND: The clinical results of therapy using 153Sm ethylenediamine-N,N,N'N'-tetrakis(methylene phosphonic acid) (153Sm-EDTMP) were correlated with radiation dose indices in metastases, with the intention of improving the therapeutic efficacy. METHODS: Fifty-six patients with disseminated bone metastases were treated. Prior to therapy, whole-body scans and single photon emission computed tomography (SPECT) of the trunk were performed. Whole-body retention of 99mTc labelled phosphonates was compared with 153Sm-EDTMP retention after therapy. Estimations of the volumes of bone lesions were done by SPECT. Assuming a solid tumour but a thin metabolically active boundary zone between tumour and healthy bone that absorbed the beta radiation, we estimated an 'irradiated volume' by using a spherical shell model of 6 mm thickness. Local tracer uptake in lesions was assessed by regions of interest techniques on conjugated views of whole-body scans with homogeneous attenuation correction. Calculation of the dose index by applying the Medical Internal Radiation Dosimetry (MIRD) scheme was done retrospectively in 10 patients and prospectively in 22 cases. Depending on changes in pain/mobility scores, results were classified as 'very good', 'good' and 'no response'. RESULTS: A mean dose index > or =10 per lesion was estimated under the condition of a homogeneous uptake within the idealized, spherical, tumour volume. Assuming that the uptake of the radiopharmaceutical occurs mostly within an outer shell of the tumour, dose indices to this 'irradiated volume' can increase to more than twice that value. CONCLUSION: Very good clinical results for bone pain palliation by using 153Sm-EDTMP therapy could be found in patients receiving a dose index >15 per lesion. Even this approximate dosimetric approach, considering the individual differences in tumour spread and the varying intensity of 153Sm uptake, could improve the impact of 153Sm-EDTMP for pain control in cancer patients.     

The effect of repeated strontium-89 chloride therapy on bone pain palliation in patients with skeletal cancer metastases

One hundred and eighteen patients with painful skeletal metastases of malignant diseases (predominantly prostate, breast and lung cancer) were treated with 150 MBq of strontium-89 chloride (Metastron, Amersham, UK) intravenously. The results were evaluated according to a score considering pain relief, mobility, analgesic intake and general feeling. In only five patients (4.2%) was no improvement observed; mild improvement was noted in 48 (40.7%), and substantial or complete improvement in 56 (47.5%) and 9 (7.6%), respectively. The mean painless period after a single ⁸⁹SrCl dose was 3.3±2.28 months (in patients with prostate, lung, breast and other types of cancer it was 3.65±2.11, 3.29±1.27, 3.08±0.48 and 3.44±1.36 months, respectively). During a 3-year study, ⁸⁹SrCl treatment was successively repeated up to 5 times in some patients (total number of Metastron applications was 256) who benefited from the first Metastron administration and did not show signs of myelosuppression. Even after repeated treatment, relief was consistent and the duration of the period without pain increased (in particular in patients with breast cancer, in whom the period of relief was prolonged from 3.08±0.48 months after the first dose to 5.33±2.36 months after the fifth ⁸⁹SrCl administration). The increased painless period was not observed after repeated treatment in the patient group comprising miscellaneous types of cancer, and the degree of improvement was less apparent. During the course of successive ⁸⁹SrCl treatments, transient signs of myelosuppression indicated by a decrease in white cell and thrombocyte counts of at least 25% were observed 10 times after Metastron administration (twice in two patients), i.e. in 3.9% of all ⁸⁹SrCl administrations; these transient haematological changes of moderate grade were closely connected with Metastron administration. Palliative treatment of metastatic skeletal pain with ⁸⁹SrCl improves the quality of life in most patients suffering from prostate, lung and breast cancer and may be safely repeated with the same benefit and without significant myelosuppression. The beneficial effect of ⁸⁹SrCl treatment seems to be less pronounced in other types of cancer with painful skeletal metastases. Received 9 February and in revised form 20 May 1998     

Labelling of Re-ABP with 188Re for bone pain palliation.

Etidronate and medronate have been labelled with technetium-99m (99mTc-HEDP, 99mTc-MDP) for bone scanning and, with rhenium-188 (188Re-HEDP) to palliate the pain resulting from bone metastases. The objective of this study was to label alendronate, ABP, a new bisphosphonate, with SnF2-reduced-188Re. The reagents for the 5 mg ABP kit were SnF2, KReO4 and gentisic acid at acid pH. The chemical, spectroscopic and microscopic characteristics, quality control, rat bone uptake of [188Re]Re-ABP and similarities with 99mTc-ABP are presented. We conclude that this is a promising new radiopharmaceutical for bone metastases pain palliation.     

Bone pain palliation with 85Sr therapy.

The aim of this retrospective study was to evaluate the efficacy of 85Sr in the palliation of metastatic bone pain. 85Sr decays by electron capture with a gamma emission of 514 keV and associated x-ray emissions of 10-15 keV; physical half-life is 64 d. METHODS: Between 1977 and 1992, 119 doses of 85Sr chloride (mean activity 335 MBq [9 mCi]) were intravenously administered to 108 patients with hyperalgic generalized bone metastases from prostatic carcinoma (52 patients), breast carcinoma (41) or other cancers (15). Pain, performance status, blood and urinary excretion values were investigated during follow-up, and survival time was recorded. Strontium bone scans were obtained up to 8 wk after injection to document isotope biodistribution and to estimate absorbed doses. RESULTS: At 12 wk, 72.2% of patients showed significant benefit from treatment, i.e., enhanced quality of life and pain relief; 49.1% became free of pain. These beneficial effects lasted from 1 to 36 mo (mean 4.3 mo). The best symptomatic improvement was seen in patients treated at an early stage of metastatic skeletal disease and in prostate cancer patients. No evidence of a significant dose-response relationship was found in the data analysis. The mean absorbed dose ratio of metastases to marrow was estimated at 8.2. We found no evidence that hematological toxicity was a major problem; however, all patients experienced a reduction in blood counts, especially in platelets. CONCLUSION: Systemic radionuclide therapy using 85Sr is a feasible, effective and well-tolerated palliative treatment in patients with refractory bone pain. We attained at least the same response rate as that reported with bone-seeking beta-emitting radionuclides such as 89Sr. The patients who benefited the most from 85Sr treatment were in an early stage of metastatic disease or had prostate cancer. Our clinical findings could not be linked to either the total injected activity of 85Sr or the estimated absorbed dose delivered to metastases.