Effectiveness of reirradiation for painful bone metastases: a systematic review and meta-analysis.

PURPOSE Reirradiation of painful bone metastases in nonresponders or patients with recurrent pain after initial response is performed in up to 42% of patients initially treated with radiotherapy. Literature on the effect of reirradiation for pain control in those patients is scarce. In this systematic review and meta-analysis, we quantify the effectiveness of reirradiation for achieving pain control in patients with painful bone metastases. METHODS AND MATERIALS A free text search was performed to identify eligible studies using the MEDLINE, EMBASE, and the Cochrane Collaboration library electronic databases. After study selection and quality assessment, a pooled estimate was calculated for overall pain response for reirradiation of metastatic bone pain. RESULTS Our literature search identified 707 titles, of which 10 articles were selected for systematic review and seven entered the meta-analysis. Overall study quality was mediocre. Of the 2,694 patients initially treated for metastatic bone pain, 527 (20%) patients underwent reirradiation. Overall, a pain response after reirradiation was achieved in 58% of patients (pooled overall response rate 0.58, 95% confidence interval = 0.49-0.67). There was a substantial between-study heterogeneity (I² = 63.3%, p = 0.01) because of clinical and methodological differences between studies. CONCLUSIONS Reirradiation of painful bone metastases is effective in terms of pain relief for a small majority of patients; approximately 40% of patients do not benefit from reirradiation. Although the validity of results is limited, this meta-analysis provides a comprehensive overview and the most quantitative estimate of reirradiation effectiveness to date.

[1]  P. Hoskin,et al.  Palliation of bone metastases. , 1991, European journal of cancer.

[2]  Ehud Mendel,et al.  Palliative radiotherapy for bone metastases: an ASTRO evidence-based guideline. , 2011, International journal of radiation oncology, biology, physics.

[3]  T. Wilt,et al.  Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy--a systematic review of randomised trials. , 2002, Clinical oncology (Royal College of Radiologists (Great Britain)).

[4]  Douglas G Altman,et al.  [The Strengthening the Reporting of Observational Studies in Epidemiology [STROBE] statement: guidelines for reporting observational studies]. , 2007, Gaceta sanitaria.

[5]  J. Yarnold 8 Gy single fraction radiotherapy for the treatment of metastatic skeletal pain: randomised comparison with a multifraction schedule over 12 months of patient follow-upOn behalf of the Bone Pain Trial Working Party , 1999 .

[6]  W. Curran,et al.  Economic Analysis of Radiation Therapy Oncology Group 97-14: Multiple Versus Single Fraction Radiation Treatment of Patients With Bone Metastases , 2009, American journal of clinical oncology.

[7]  H. V. van Houwelingen,et al.  Single fraction radiotherapy is efficacious: a further analysis of the Dutch Bone Metastasis Study controlling for the influence of retreatment. , 2004, International journal of radiation oncology, biology, physics.

[8]  J. Waxman,et al.  Bone metastasis in prostate cancer: emerging therapeutic strategies , 2011, Nature Reviews Clinical Oncology.

[9]  T. Pajak,et al.  Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) , 1995, International journal of radiation oncology, biology, physics.

[10]  S. Pocock,et al.  The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. , 2008, Journal of clinical epidemiology.

[11]  B. Jeremic,et al.  Second single 4 Gy reirradiation for painful bone metastasis. , 2002, Journal of pain and symptom management.

[12]  B. Ferrell,et al.  The management of cancer pain , 2011, CA: a cancer journal for clinicians.

[13]  S. L. Wanders,et al.  Single-dose radiotherapy (6 Gy): palliation in painful bone metastases. , 1995, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[14]  B. Jeremic,et al.  Single 4 Gy re-irradiation for painful bone metastasis following single fraction radiotherapy. , 1999, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[15]  Wolfgang Viechtbauer,et al.  Conducting Meta-Analyses in R with the metafor Package , 2010 .

[16]  D. Cole A randomized trial of a single treatment versus conventional fractionation in the palliative radiotherapy of painful bone metastases. , 1989, Clinical oncology (Royal College of Radiologists (Great Britain)).

[17]  J Kievit,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. , 1999, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[18]  J. Waxman,et al.  Bone metastasis in prostate cancer: emerging therapeutic strategies , 2011, Nature Reviews Clinical Oncology.

[19]  J. Yarnold,et al.  Low dose single fraction radiotherapy in the treatment of metastatic bone pain: a pilot study. , 1988, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[20]  M. Callstrom,et al.  Ablation of skeletal metastases: current status. , 2010, Journal of vascular and interventional radiology : JVIR.

[21]  Arthur C. Lucas,et al.  Principles and Practice of Radiation Oncology, 4th Edition , 2005 .

[22]  J. Yarnold,et al.  A prospective randomised trial of 4 Gy or 8 Gy single doses in the treatment of metastatic bone pain. , 1992, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[23]  P. Hoskin,et al.  International consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases. , 2002, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[24]  P. Hoskin,et al.  Retreatment with radiotherapy for painful bone metastases. , 1994, International journal of radiation oncology, biology, physics.

[25]  J. de Haes,et al.  Measuring psychological and physical distress in cancer patients: structure and application of the Rotterdam Symptom Checklist. , 1990, British Journal of Cancer.

[26]  Y. M. van der Linden,et al.  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. , 2006, Clinical oncology (Royal College of Radiologists (Great Britain)).

[27]  C. Cleeland Undertreatment of cancer pain in elderly patients. , 1998, JAMA.

[28]  J. Kievit,et al.  Single- versus multiple-fraction radiotherapy in patients with painful bone metastases: cost-utility analysis based on a randomized trial. , 2003, Journal of the National Cancer Institute.

[29]  C. Perez,et al.  Principles and Practice of Radiation Oncology , 1987 .

[30]  H. Hoshi,et al.  Reirradiation with local-field radiotherapy for painful bone metastases. , 2002, Radiation medicine.

[31]  W. Sze,et al.  Palliative radiotherapy trials for bone metastases: a systematic review. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[32]  Y. M. van der Linden,et al.  Update of the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases. , 2012, International journal of radiation oncology, biology, physics.