• Around 60–70% of patients with painful bone metastases experience pain relief after conventional radiotherapy.
• When studying pain response after radiotherapy for bone metastases, leaving out the patients who are lost to follow-up results in response rates that are more favorable.
• Pain scores are lowest at 6 weeks after radiotherapy, after which mean pain scores increase again but are still lower compared to baseline.
Radiotherapy is the standard local treatment for patients with painful bone metastases, but effectiveness has primarily been evaluated in trial populations. The aim of this study was to study pain response to palliative radiotherapy in a prospective cohort of unselected patients with bone metastases.
Patients with painful bone metastases referred to the UMC Utrecht for radiotherapy and enrolled in the PRESENT cohort were included in this study. For all patients, pain response to radiotherapy was assessed, and responders were defined as patients with a complete or partial pain response. Patients with stable pain scores, pain increase, or undetermined response were regarded non-responders. Pain scores obtained at baseline and after 2, 4, 6, 8, and 12 weeks following radiotherapy were obtained. Pain response rates of the total treated population, as well as response rates of the assessable patients, were calculated. To measure the percentage of the remaining time spent with pain relief, the net pain relief (NPR) was calculated by dividing the period of pain relief by the period of survival.
Of the 432 patients enrolled in this study, 262 patients (61%) experienced a complete or partial response. In the 390 assessable patients, this percentage was 67%. Median time to response was 4 weeks (range 1–15 weeks), and the NPR was 64%.
Compared to randomized trial populations, palliative radiotherapy in our unselected patients with bone metastases showed similar pain response rates (61%), with a reasonable duration of this effect.
Kirkbride P, Tannock IF (2008) Trials in palliative treatment--have the goal posts been moved? Lancet Oncol 9:186–187 CrossRef
Westhoff PG, de Graeff A, Monninkhof EM, Pomp J, van Vulpen M, Leer JW et al (2015) Quality of life in relation to pain response to radiation therapy for painful bone metastases. Int J Radiat Oncol Biol Phys 93:694–701 CrossRef
Sze WM, Shelley M, Held I, Mason M (2004) Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy - a systematic review of the randomised trials. Cochrane Database Syst Rev 2:CD004721
Rich SE, Chow R, Raman S, Liang Zeng K, Lutz S, Silva MF et al (2018) Update of the systematic review of palliative radiation therapy fractionation for bone metastases. Radiother Oncol 126:547–557 CrossRef
Van Spall HG, Toren A, Kiss A, Fowler RA (2007) Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review. JAMA 297:1233–1240 CrossRef
Bennette CS, Ramsey SD, McDermott CL, Carlson JJ, Basu A, Veenstra DL (2016) Predicting low accrual in the National Cancer Institute’s Cooperative Group Clinical Trials. J Natl Cancer Inst 108(2):djv324 CrossRef
Chow E, Wong R, Hruby G, Connolly R, Franssen E, Fung KW, Andersson L, Schueller T, Stefaniuk K, Szumacher E, Hayter C, Pope J, Holden L, Loblaw A, Finkelstein J, Danjoux C (2001) Prospective patient-based assessment of effectiveness of palliative radiotherapy for bone metastases. Radiother Oncol 61:77–82 CrossRef
Bartlett C, Doyal L, Ebrahim S, Davey P, Bachmann M, Egger M et al (2005) The causes and effects of socio-demographic exclusions from clinical trials. Health Technol Assess 9:iii–iiv ix-x, 1–152 CrossRef
Relton C, Torgerson D, O’Cathain A, Nicholl J (2010) Rethinking pragmatic randomised controlled trials: introducing the “cohort multiple randomised controlled trial” design. BMJ 340:c1066 CrossRef
Young-Afat DA, Verkooijen HM, Van Gils CH, Van der Velden JM, Burbach J, Elias SG et al (2016) Staged-informed consent in the cohort multiple randomized controlled trial design. Epidemiology 27:389–392 CrossRef
Cleeland CS, Ryan KM (1994) Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap 23:129–138
Groenvold M, Petersen MA, Aaronson NK, Arraras JI, Blazeby JM, Bottomley A, EORTC Quality of Life Group et al (2006) The development of the EORTC QLQ-C15-PAL: a shortened questionnaire for cancer patients in palliative care. Eur J Cancer 42:55–64 CrossRef
Zeng L, Chow E, Bedard G, Zhang L, Fairchild A, Vassiliou V, Alm el-Din MA, Jesus-Garcia R, Kumar A, Forges F, Tseng LM, Hou MF, Chie WC, Bottomley A (2012) Quality of life after palliative radiation therapy for patients with painful bone metastases: results of an international study validating the EORTC QLQ-BM22. Int J Radiat Oncol Biol Phys 84:e337–e342 CrossRef
Devlin NJ, Krabbe PFM (2013) The development of new research methods for the validation of EQ-5D-5L. Eur J Health Econ 14:1–3 CrossRef
Chow E, Hoskin P, Mitera G, Zeng L, Lutz S, Roos D, Hahn C, van der Linden Y, Hartsell W, Kumar E, International Bone Metastases Consensus Working Party (2012) Update of the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases. Int J Radiat Oncol Biol Phys 82:1730–1737 CrossRef
Vermorken JB, Schrijvers DLAL, Weyler L, Carp L, Parizel PM (2005) Diagnostiek in de oncologie. In: Van de Velde, CJH, van Krieken, JHJM, de Mulder, PHM, Vermorken, JB (eds) Oncologie, 7th edn. Bohn Stafleu van Loghum, Houten, p 84
Salazar OM, Rubin P, Hendrickson FR, Komaki R, Poulter C, Newall J, Asbell SO, Mohiuddin M, van Ess J (1986) Single-dose half-body irradiation for palliation of multiple bone metastases from solid tumors—Final Radiation Therapy Oncology Group report. Cancer 58:29–36 CrossRef
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, STROBE Initiative (2007) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 370:1453–1457 CrossRef
van der Linden YM, Dijkstra SP, Vonk EJ, Marijnen CA, Leer JW, Dutch Bone Metastasis Study Group (2005) Prediction of survival in patients with metastases in the spinal column: results based on a randomized trial of radiotherapy. Cancer 103:320–328 CrossRef
Howell DD, James JL, Hartsell WF, Suntharalingam M, Machtay M, Suh JH et al (2013) Single-fraction radiotherapy versus multifraction radiotherapy for palliation of painful vertebral bone metastases-equivalent efficacy, less toxicity, more convenient: a subset analysis of Radiation Therapy Oncology Group trial 97-14. Cancer 11:888–896 CrossRef
Zeng L, Chow E, Zhang L, Culleton S, Holden L, Jon F, Khan L, Tsao M, Barnes E, Danjoux C, Sahgal A (2012) Comparison of pain response and functional interference outcomes between spinal and non-spinal bone metastases treated with palliative radiotherapy. Support Care Cancer 20:633–639 CrossRef
van der Linden YM, Lok JJ, Steenland E, Martijn H, van Houwelingen H, Marijnen CA et al (2004) Single fraction radiotherapy is efficacious: a further analysis of the Dutch Bone Metastasis Study controlling for the influence of retreatment. Int J Radiat Oncol Biol Phys 59:528–5237 CrossRef
Foro Arnalot P, Fontanals AV, Galcerán JC, Lynd F, Latiesas XS, de Dios NR, Castillejo AR, Bassols ML, Galán JL, Conejo IM, López MA (2008) Randomized clinical trial with two palliative radiotherapy regimens in painful bone metastases: 30 Gy in 10 fractions compared with 8 Gy in single fraction. Radiother Oncol 89:150–155 CrossRef
Steenland E, Leer JW, van Houwelingen H, Post WJ, van den Hout WB, Kievit J, de Haes H, Martijn H, Oei B, Vonk E, van der Steen-Banasik E, Wiggenraad RGJ, Hoogenhout J, Wárlám-Rodenhuis C, van Tienhoven G, Wanders R, Pomp J, van Reijn M, van Mierlo T, Rutten E (1999) 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 52:101–109 CrossRef
van der Velden JM, Peters M, Verlaan JJ, Versteeg AL, Zhang L, Tsao M, Danjoux C, Barnes E, van Vulpen M, Chow E, Verkooijen HM (2017) Development and internal validation of a clinical risk score to predict pain response after palliative radiation therapy in patients with bone metastases. Int J Radiat Oncol Biol Phys 99:859–866 CrossRef
Wang XS, Rhines LD, Shiu AS, Yang JN, Selek U, Gning I, Liu P, Allen PK, Azeem SS, Brown PD, Sharp HJ, Weksberg DC, Cleeland CS, Chang EL (2012) Stereotactic body radiation therapy for management of spinal metastases in patients without spinal cord compression: a phase 1-2 trial. Lancet Oncol 13:395–402 CrossRef
Westhoff PG, Verdam MGE, Oort FJ, Jobsen JJ, van Vulpen M, Leer JWH, Marijnen CAM, de Graeff A, van der Linden YM (2016) Course of quality of life after radiation therapy for painful bone metastases: a detailed analysis from the Dutch Bone Metastasis Study. Int J Radiat Oncol Biol Phys 95:1391–1398 CrossRef
Lussier D, Huskey AG, Portenoy RK (2004) Adjuvant analgesics in cancer pain management. Oncologist 9:571–591 CrossRef
Li KK, Hadi S, Kirou-Mauro A, Chow E (2008) When should we define the response rates in the treatment of bone metastases by palliative radiotherapy? Clin Oncol (R Coll Radiol) 20:83–89 CrossRef
- Evaluation of effectiveness of palliative radiotherapy for bone metastases: a prospective cohort study
Joanne M. van der Velden
Yvette M. van der Linden
Anne L. Versteeg
A. Sophie Gerlich
Bart J. Pielkenrood
Helena M. Verkooijen
- Springer Berlin Heidelberg
Journal of Radiation Oncology
Print ISSN: 1948-7894
Elektronische ISSN: 1948-7908
Neu im Fachgebiet Onkologie
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