A Phase III International Randomised Trial Comparing Single with Multiple Fractions for Re-irradiation of Painful Bone Metastases: National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) SC 20
2005; Elsevier BV; Volume: 18; Issue: 2 Linguagem: Inglês
10.1016/j.clon.2005.11.014
ISSN1433-2981
AutoresEdward Chow, Peter Hoskin, J. Wu, Daniel Roos, Yvette M. van der Linden, William F. Hartsell, Reinhold Vieth, C. Wilson, J Pater,
Tópico(s)Cancer Diagnosis and Treatment
ResumoBone metastases are a common manifestation of distant relapse from many types of malignant tumours, especially from cancers of the breast, prostate and lung. Radiotherapy is a well-recognised effective modality in the palliative treatment of painful bone metastases. Various fractionation schedules are used by radiation oncologists, ranging from a single 6 or 8 Gy fraction to multiple fractions, such as 40 Gy in 20 fractions over 4 weeks [1Bone Pain Trial Working Party 8 Gy single fraction radiotherapy for the treatment of metastatic skeletal pain: randomised comparison with a multifraction schedule over 12 months of patient follow-up.Radiother Oncol. 1999; 52: 111-121Abstract Full Text Full Text PDF PubMed Scopus (419) Google Scholar, 2Gaze M.N. Kelly C.G. Kerr G.R. et al.Pain relief and quality of life following radiotherapy for bone metastases: a randomised trial of two fractionation schedules.Radiother Oncol. 1997; 45: 109-116Abstract Full Text PDF PubMed Scopus (246) Google Scholar, 3Jeremic B. Shibamoto Y. Acimovic L. et al.A randomized trial of three single-dose radiation therapy regimens in the treatment of metastatic bone pain.Int J Radiat Oncol Biol Phys. 1998; 42: 161-167Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar, 4Nielsen O.S. Bentzen S.M. Sandberg E. Gadeberg C.C. Timothy A.R. Randomized trial of single dose versus fractionated palliative radiotherapy of bone metastases.Radiother Oncol. 1998; 47: 233-240Abstract Full Text Full Text PDF PubMed Scopus (280) Google Scholar, 5Niewald M. Tkocz H.J. Abel U. et al.Rapid course radiation therapy vs. more standard treatment: a randomized trial for bone metastases.Int J Radiat Oncol Biol Phys. 1996; 36: 1085-1089Abstract Full Text PDF PubMed Scopus (135) Google Scholar, 6Price P. Hoskin P.J. Easton D. Austin D. Palmer S.G. Yarnold J.R. Prospective randomised trial of single and multifraction radiotherapy schedules in the treatment of painful bony metastases.Radiother Oncol. 1986; 6: 247-255Abstract Full Text PDF PubMed Scopus (402) Google Scholar, 7Rasmusson B. Vejborg I. Jensen A.B. et al.Irradiation of bone metastases in breast cancer patients: a randomized study with 1 year follow-up.Radiother Oncol. 1995; 34: 179-184Abstract Full Text PDF PubMed Scopus (119) Google Scholar, 8Steenland E. Leer J.W. van Houwelingen H. et al.The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study.Radiother Oncol. 1999; 52: 101-109Abstract Full Text Full Text PDF PubMed Scopus (584) Google Scholar, 9Tong D. Gillick L. Hendrickson F.R. The palliation of symptomatic osseous metastases: final results of the study by the Radiation Therapy Oncology Group.Cancer. 1982; 50: 893-899Crossref PubMed Scopus (699) Google Scholar, 10Cole D.J. A randomised trial of a single treatment versus conventional fractionation in the palliative radiotherapy of painful bone metastases.Clin Oncol. 1989; 1: 59-62Abstract Full Text PDF PubMed Scopus (199) Google Scholar, 11Madsen E.L. Painful bone metastases: efficacy of radiotherapy assessed by the patients: a randomized trial comparing 4 Gy×6 versus 10 Gy×2.Int J Radiat Oncol Biol Phys. 1983; 9: 1775-1779Abstract Full Text PDF PubMed Scopus (140) Google Scholar, 12Okawa T. Kita M. Goto M. Nishijima H. Miyaji N. Randomized prospective clinical study of small, large and twice a day fraction radiotherapy for painful bone metastases.Radiother Oncol. 1988; 13: 99-104Abstract Full Text PDF PubMed Scopus (95) Google Scholar, 13Koswig S. Budach V. Remineralization and pain relief in bone metastases after different radiotherapy fractions (10 times 3 Gy vs 1 time 8 Gy). A prospective study.Strahlenther Onkol. 1999; 175 ([in German]): 500-508Crossref PubMed Scopus (236) Google Scholar, 14Hirokawa Y. Wadasaki K. Kashiwado K. et al.A multi-institutional prospective randomized study of radiation therapy of bone metastases.Nippon Igaku Hoshasen Gakkai Zasshi. 1988; 48: 1425-1431PubMed Google Scholar, 15Hartsell W. Scott C. Bruner D. et al.Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases.J Natl Cancer Inst. 2005; 97: 798-804Crossref PubMed Scopus (680) Google Scholar]. Randomised trials addressing the optimal radiotherapy dose-fractionation schedule for palliation of uncomplicated painful bone metastases have not suggested convincingly that any one fractionation is superior to another in terms of pain control. In the recent randomised trial for neuropathic pain due to bone metastases, a single 8 Gy fraction was not shown to be as effective as 20 Gy in five fractions, nor was it statistically significantly worse [16Roos D. Turner S. O'Brien P. et al.Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic pain due to bone metastases (Trans-Tasman Radiation Oncology Group, TROG 96.05).Radiother Oncol. 2005; 75: 54-63Abstract Full Text Full Text PDF PubMed Scopus (225) Google Scholar]. Practice continues to embrace both single doses and multifraction schedules [17Haddad P. Wong R.K. Pond G.R. et al.Factors influencing the use of single vs multiple fractions of palliative radiotherapy for bone metastases: a 5-year review.Clin Oncol. 2005; 17: 430-434Abstract Full Text Full Text PDF Scopus (42) Google Scholar]. Effective systemic treatment and better supportive care can result in improved survival, and certain subsets of patients with bone metastases have longer life expectancies than before. An increasing number of patients outlive the duration of the benefits of initial palliative radiotherapy for symptomatic bone metastases, requiring re-irradiation of the previously treated sites. Additionally, some patients fail to respond initially but may benefit from re-irradiation. Among the radiation trials comparing single- with multiple-fractionation schemes, re-irradiation rates varied from 11% to 42% after single-fraction and from 0% to 24% after multiple-fraction regimens (Table 1). However, re-irradiation to the previously radiated sites was at the discretion of the treating radiation oncologists who were not blinded to the initial treatment, and there were no guidelines explaining when, why and what dose of re-irradiation should be given.Table 1Re-irradiation rates reported in randomised trials of dose-fractionation schedulesRandomised studyRe-irradiation rate (%)Low-dose fractionHigh-dose fractionTrials comparing single-fraction against multifraction radiotherapy Bone Pain Trial Working Party 1Bone Pain Trial Working Party 8 Gy single fraction radiotherapy for the treatment of metastatic skeletal pain: randomised comparison with a multifraction schedule over 12 months of patient follow-up.Radiother Oncol. 1999; 52: 111-121Abstract Full Text Full Text PDF PubMed Scopus (419) Google Scholar2310 Steenland et al. 8Steenland E. Leer J.W. van Houwelingen H. et al.The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study.Radiother Oncol. 1999; 52: 101-109Abstract Full Text Full Text PDF PubMed Scopus (584) Google Scholar257 Nielsen et al. 4Nielsen O.S. Bentzen S.M. Sandberg E. Gadeberg C.C. Timothy A.R. Randomized trial of single dose versus fractionated palliative radiotherapy of bone metastases.Radiother Oncol. 1998; 47: 233-240Abstract Full Text Full Text PDF PubMed Scopus (280) Google Scholar2012 Cole 10Cole D.J. A randomised trial of a single treatment versus conventional fractionation in the palliative radiotherapy of painful bone metastases.Clin Oncol. 1989; 1: 59-62Abstract Full Text PDF PubMed Scopus (199) Google Scholar250 Price et al. 6Price P. Hoskin P.J. Easton D. Austin D. Palmer S.G. Yarnold J.R. Prospective randomised trial of single and multifraction radiotherapy schedules in the treatment of painful bony metastases.Radiother Oncol. 1986; 6: 247-255Abstract Full Text PDF PubMed Scopus (402) Google Scholar113 Hartsell et al. 15Hartsell W. Scott C. Bruner D. et al.Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases.J Natl Cancer Inst. 2005; 97: 798-804Crossref PubMed Scopus (680) Google Scholar189 Roos et al. 16Roos D. Turner S. O'Brien P. et al.Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic pain due to bone metastases (Trans-Tasman Radiation Oncology Group, TROG 96.05).Radiother Oncol. 2005; 75: 54-63Abstract Full Text Full Text PDF PubMed Scopus (225) Google Scholar2924Trials comparing single fractions at different doses (4 vs 8 Gy) Jeremic et al. 3Jeremic B. Shibamoto Y. Acimovic L. et al.A randomized trial of three single-dose radiation therapy regimens in the treatment of metastatic bone pain.Int J Radiat Oncol Biol Phys. 1998; 42: 161-167Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar4238 Hoskin et al. 18Hoskin P.J. Price P. Easton D. et al.A prospective randomised trial of 4 Gy or 8 Gy single doses in the treatment of metastatic bone pain.Radiother Oncol. 1992; 23: 74-78Abstract Full Text PDF PubMed Scopus (229) Google Scholar209Trials comparing different multifraction regimens Niewald et al. 5Niewald M. Tkocz H.J. Abel U. et al.Rapid course radiation therapy vs. more standard treatment: a randomized trial for bone metastases.Int J Radiat Oncol Biol Phys. 1996; 36: 1085-1089Abstract Full Text PDF PubMed Scopus (135) Google Scholar22 Tong et al. 9Tong D. Gillick L. Hendrickson F.R. The palliation of symptomatic osseous metastases: final results of the study by the Radiation Therapy Oncology Group.Cancer. 1982; 50: 893-899Crossref PubMed Scopus (699) Google Scholar, 19Gillick L, Goldberg S. Technical Report No. 185R, Final Analysis RTOG Protocol No. 74-02, 1981.Google Scholar (RTOG 7402) Solitary met2411 Multiple mets2312 Open table in a new tab Many patients with relapsed pain or poor response to initial radiation may be lost to follow-up or may not be referred back to the radiation oncologist for consideration of re-irradiation. The response to re-irradiation in the published reports is variable, and no consistent policy for dose fractionation is followed or recommended. Price et al. [20Price P. Hoskin P.J. Easton D. et al.Low dose single fraction radiotherapy in the treatment of metastatic bone pain: a pilot study.Radiother Oncol. 1988; 12: 297-300Abstract Full Text PDF PubMed Scopus (58) Google Scholar] reported on seven patients who, after failure to respond to the initial single 4 Gy fraction, were given repeat radiotherapy within 8 weeks. Four of them received a single 8 Gy, and the other three a fractionated course. No significant pain relief was achieved by the second radiotherapy treatment in these seven patients. Cole [10Cole D.J. A randomised trial of a single treatment versus conventional fractionation in the palliative radiotherapy of painful bone metastases.Clin Oncol. 1989; 1: 59-62Abstract Full Text PDF PubMed Scopus (199) Google Scholar] reported that re-treatment of patients after initial single or multifraction treatment was not successful in all patients, and 50% of the 42 patients requiring re-treatment needed stronger supplementary analgesics. Hoskin et al. [18Hoskin P.J. Price P. Easton D. et al.A prospective randomised trial of 4 Gy or 8 Gy single doses in the treatment of metastatic bone pain.Radiother Oncol. 1992; 23: 74-78Abstract Full Text PDF PubMed Scopus (229) Google Scholar] randomised patients to either 4 or 8 Gy single-dose radiotherapy in the treatment of metastatic bone pain. During the 12-week study period, 28 patients randomised to 4 Gy were re-treated with radiotherapy to the same site compared with 12 randomised to 8 Gy. Twelve out of 17 (71%) evaluable patients responded to re-treatment in the 4 Gy arm and four out of nine (44%) responded in the 8 Gy arm. Uppelschoten et al. [21Uppelschoten J.M. Wanders S.L. de Jong J.M. Single-dose radiotherapy (6 Gy): palliation in painful bone metastases.Radiother Oncol. 1995; 36: 198-202Abstract Full Text PDF PubMed Scopus (55) Google Scholar] reported that, after long intervals from a previous single 6 Gy of radiation, re-irradiation with another 6 Gy was able to reduce pain in 13 out of 18 patients. Mithal et al. [22Mithal N. Needham P. Hoskin P. Retreatment with radiotherapy for painful bone metastases.Int J Radiat Oncol Biol Phys. 1994; 29: 1011-1014Abstract Full Text PDF PubMed Scopus (113) Google Scholar] reported a retrospective analysis of 105 consecutive patients treated with palliative radiotherapy for painful bone metastases. A total of 280 individual treatment sites were identified, of which 57 were re-treated once and eight were re-treated twice. The overall response rate to initial treatment was 84% for pain relief, and, at first re-treatment, this was 87%. Seven out of eight (88%) patients re-treated a second time also achieved pain relief. A total of 17 out of 23 (74%) patients responded (complete response and partial response) to second radiation that used a number of single-fraction regimens, which was not significantly inferior to 31 out of 34 (91%) obtained with more protracted regimens. No relation to radiation dose, primary tumour type or site was seen. Jeremic et al. [23Jeremic B. Shibamoto Y. Igrutinovic I. Single 4 Gy re-irradiation for painful bone metastases following single fraction radiotherapy.Radiother Oncol. 1999; 52: 123-127Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar] investigated the effectiveness of a single fraction of 4 Gy given for re-treatment of bone metastases after previous single-fraction radiotherapy. Of 135 patients re-treated, 109 patients were re-treated because of pain relapsing, whereas 26 patients were re-irradiated after initial non-response. Of the 109 patients who were re-irradiated for pain relapse, 80 (74%) patients responded (complete response=31% and partial response=42%). Among the 26 patients who initially did not respond, there were 12 (46%) responses. The authors concluded that the lack of response to initially single-fraction radiotherapy should not deter repeat irradiation. The same group also reported the efficacy of the second single 4 Gy re-irradiation for painful bone metastases after the previous two single fractions. The overall response rate of the 25 patients (19 responders and six non-responders to the two prior single fractions) was 80%, with both complete response and partial response being 40% [24Jeremic B. Shibamoto Y. Igrutinovic I. Second single 4 Gy reirradiation for painful bone metastasis.J Pain Symptom Manage. 2002; 23: 26-30Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar]. The Dutch Bone Metastases Study Group recently presented the efficacy of re-irradiation of painful bone metastases [25van der Linden Y.M. Lok J.J. et al.Single fraction radiotherapy is efficacious: a further analysis of the Dutch Bone Metastasis Study controlling for the influence of retreatment. Dutch Bone Metastases Study Group.Int J Radiat Oncol Biol Phys. 2004; 59: 528-537Abstract Full Text Full Text PDF PubMed Scopus (260) Google Scholar]. For patients not responding to the initial radiation and who were re-irradiated, 66% of patients who initially received a single 8 Gy responded to the re-treatment compared with 33% of patients who received the initial multifraction regimens. Re-treatment for patients with progression was successful in 70% of patients receiving the single-fraction regimen compared with 57% of patients receiving the multifraction regimen. In general, re-treatment was effective in 63% of all re-treated patients. In summary, available data support the re-irradiation of sites of metastatic bone pain after initial irradiation, particularly where this follows an initial period of response. There is also limited evidence that a proportion of initial non-responders would respond to a re-irradiation. Although the data do support the clinical practice of re-irradiation, the preferred dose fractionation at time of re-irradiation is unknown. Small patient numbers in retrospective and prospective studies, and the prevailing reservation among radiation oncologists to consider re-irradiation clearly emphasise the need for more information on this issue. To date, no prospective randomised study investigating the efficacy of re-irradiation has been published. Whether there is a dose–response phenomenon for re-irradiation is unknown. Although there is no convincing evidence that a dose–response phenomenon exists for the initial radiotherapy for bone metastases [1Bone Pain Trial Working Party 8 Gy single fraction radiotherapy for the treatment of metastatic skeletal pain: randomised comparison with a multifraction schedule over 12 months of patient follow-up.Radiother Oncol. 1999; 52: 111-121Abstract Full Text Full Text PDF PubMed Scopus (419) Google Scholar, 2Gaze M.N. Kelly C.G. Kerr G.R. et al.Pain relief and quality of life following radiotherapy for bone metastases: a randomised trial of two fractionation schedules.Radiother Oncol. 1997; 45: 109-116Abstract Full Text PDF PubMed Scopus (246) Google Scholar, 3Jeremic B. Shibamoto Y. Acimovic L. et al.A randomized trial of three single-dose radiation therapy regimens in the treatment of metastatic bone pain.Int J Radiat Oncol Biol Phys. 1998; 42: 161-167Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar, 4Nielsen O.S. Bentzen S.M. Sandberg E. Gadeberg C.C. Timothy A.R. Randomized trial of single dose versus fractionated palliative radiotherapy of bone metastases.Radiother Oncol. 1998; 47: 233-240Abstract Full Text Full Text PDF PubMed Scopus (280) Google Scholar, 5Niewald M. Tkocz H.J. Abel U. et al.Rapid course radiation therapy vs. more standard treatment: a randomized trial for bone metastases.Int J Radiat Oncol Biol Phys. 1996; 36: 1085-1089Abstract Full Text PDF PubMed Scopus (135) Google Scholar, 6Price P. Hoskin P.J. Easton D. Austin D. Palmer S.G. Yarnold J.R. Prospective randomised trial of single and multifraction radiotherapy schedules in the treatment of painful bony metastases.Radiother Oncol. 1986; 6: 247-255Abstract Full Text PDF PubMed Scopus (402) Google Scholar, 7Rasmusson B. Vejborg I. Jensen A.B. et al.Irradiation of bone metastases in breast cancer patients: a randomized study with 1 year follow-up.Radiother Oncol. 1995; 34: 179-184Abstract Full Text PDF PubMed Scopus (119) Google Scholar, 8Steenland E. Leer J.W. van Houwelingen H. et al.The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study.Radiother Oncol. 1999; 52: 101-109Abstract Full Text Full Text PDF PubMed Scopus (584) Google Scholar, 9Tong D. Gillick L. Hendrickson F.R. The palliation of symptomatic osseous metastases: final results of the study by the Radiation Therapy Oncology Group.Cancer. 1982; 50: 893-899Crossref PubMed Scopus (699) Google Scholar, 10Cole D.J. A randomised trial of a single treatment versus conventional fractionation in the palliative radiotherapy of painful bone metastases.Clin Oncol. 1989; 1: 59-62Abstract Full Text PDF PubMed Scopus (199) Google Scholar, 11Madsen E.L. Painful bone metastases: efficacy of radiotherapy assessed by the patients: a randomized trial comparing 4 Gy×6 versus 10 Gy×2.Int J Radiat Oncol Biol Phys. 1983; 9: 1775-1779Abstract Full Text PDF PubMed Scopus (140) Google Scholar, 12Okawa T. Kita M. Goto M. Nishijima H. Miyaji N. Randomized prospective clinical study of small, large and twice a day fraction radiotherapy for painful bone metastases.Radiother Oncol. 1988; 13: 99-104Abstract Full Text PDF PubMed Scopus (95) Google Scholar, 13Koswig S. Budach V. Remineralization and pain relief in bone metastases after different radiotherapy fractions (10 times 3 Gy vs 1 time 8 Gy). A prospective study.Strahlenther Onkol. 1999; 175 ([in German]): 500-508Crossref PubMed Scopus (236) Google Scholar, 14Hirokawa Y. Wadasaki K. Kashiwado K. et al.A multi-institutional prospective randomized study of radiation therapy of bone metastases.Nippon Igaku Hoshasen Gakkai Zasshi. 1988; 48: 1425-1431PubMed Google Scholar, 15Hartsell W. Scott C. Bruner D. et al.Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases.J Natl Cancer Inst. 2005; 97: 798-804Crossref PubMed Scopus (680) Google Scholar, 16Roos D. Turner S. O'Brien P. et al.Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic pain due to bone metastases (Trans-Tasman Radiation Oncology Group, TROG 96.05).Radiother Oncol. 2005; 75: 54-63Abstract Full Text Full Text PDF PubMed Scopus (225) Google Scholar], patients failing initial palliative radiotherapy may have a different tumour biology that necessitates a higher radiation dose for clinical response. A large, prospective randomised study of re-irradiation with commonly used dose-fractionation schedules will help address these practical questions facing radiation oncologists when providing palliative radiation services. This has been recently launched, as trial SC 20, led by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) and with intergroup collaboration from the Trans-Tasman Radiation Oncology Group (TROG), the National Cancer Research Network of UK (NCRN), a Dutch Collaborative Group and most recently the Radiation Therapy Oncology Group (RTOG) in the USA. Patients with painful bone metastases after previous palliative radiotherapy to the diseased bone will be included in this study. The initial radiation dose to the extremities or ribs can be a single fraction of 6 or 8 Gy, 18 Gy in four fractions, 20 Gy in five fractions, 24 Gy in six fractions or 30 Gy in 10 fractions. The initial radiation dose to the metastases in the spine and pelvis can be a single fraction of 6 or 8 Gy, 18 Gy in four fractions, and 20 Gy in five fractions. Patients given an initial dose of 24 Gy in six fractions, 27 Gy in eight fractions or 30 Gy in 10 fractions to the spine or any part of the pelvis encompassing small or large bowel, rectum, or both, are not eligible for the study. Initial doses of 24 Gy in six fractions, 27 Gy in eight fractions or 30 Gy in 10 fractions to the acetabulum/hip and proximal femur are eligible as long as the medial field border of the initial treatment did not cross midline (pubic symphysis). Randomisation is to either a single dose of 8 Gy or 20 Gy in five daily fractions (eight fractions if over spine or whole pelvis with the initial radiation dose given in multiple fractions). The primary end point is to compare pain relief after re-irradiation [26Daut R. Cleeland C. Flanery R. Development of the Wisconsin Brief Pain questionnaire to assess pain in cancer and other diseases.Pain. 1983; 17: 197-210Abstract Full Text PDF PubMed Scopus (1287) Google Scholar, 27Chow E. Wu J. Hoskins P. et al.International consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases.Radiother Oncol. 2002; 64: 275-280Abstract Full Text Full Text PDF PubMed Scopus (305) Google Scholar]. Secondary objectives also examine side-effects and quality-of-life issues. In addition, the SC 20U companion study will evaluate markers of bone metabolism assayed from urine specimens of patients with bone metastases currently available for clinical investigation. Among the novel markers used to assess bone resorption are products of bone collagen breakdown that include (1) the pyridinium cross-links (PYD), pyridinoline and deoxypyridinoline (DPD); (2) N-telopeptide; and (3) C-telopeptide. These bone resorption markers have largely replaced urinary hydroxyproline as the preferred biochemical markers of bone turnover in the clinical laboratory. In the recent UK Bone Pain Radiotherapy Trial, 22 patients were entered into a supplementary study to establish the effects of local radiotherapy for metastatic bone pain on markers of osteoclast activity, particularly the pyridinium cross-links PYD and DPD, the latter being specific for bone turnover. Urinary pyridinium concentrations were compared with pain response. In the non-responding patients, baseline concentrations of both PYD and DPD were higher than in responders, and rose further after treatment, whereas, in responders, the mean values remained unchanged. This resulted in significant differences between responders and non-responders for both indices after treatment (P=0.027). The authors concluded that radiotherapy-mediated inhibition of bone resorption, and thus osteoclastic activity, could be a predictor for pain response [28Hoskin P.J. Stratford M.R.L. Folkes L.K. et al.Effect of local radiotherapy for bone pain on urinary markers of osteoclast activity.Lancet. 2000; 355: 1428-1429Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar]. Urine samples from a subset of patients in the SC20 trial treated in Canada and the UK will be collected and analysed to correlate the response of re-irradiation to the change of urinary markers of osteoclast activity. At the time of writing, 136 of the actual target of 650 patients have been randomised. The investigators encourage continued support of this clinically relevant intergroup trial. For further information and enrolment, please contact the following:NCIC CTG: Drs E. Chow ([email protected]) and J. Wu ([email protected])TROG: Dr D. Roos ([email protected])NCRN UK: Prof P. Hoskin ([email protected])Dutch Group: Dr Y. van der Linden ([email protected])RTOG: Dr W. Hartsell ([email protected])NCIC CTG office: Dr J. Pater ([email protected]) and Ms C. Wilson ([email protected])SC20 and SC20U protocols can be viewed at the web site: http://www.ctg.queensu.ca/public/Clinical_Trials/public_ph_3_trial_summary.html#SC20
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