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Which factors can aid clinicians to identify a risk of pain during the following month in patients with bone metastases? A longitudinal analyses

Abstract

Purpose

Explore clinical factors associated with higher pain intensity and future pain in patients with bone metastases to identify patients who can benefit from closer follow-up or pain-modifying interventions.

Methods

This is a secondary analysis of 606 patients with bone metastases included in a multicenter longitudinal study. The dependent variables were “average pain” and “worst pain” in the last 24 h (0–10 NRS). Twenty independent variables with potential association to pain intensity were selected based on previous literature. Cross-sectional analyses were performed with multiple linear regression to explore factors associated with pain intensity at baseline. Longitudinal data were analyzed with a generalized equation models to explore current factors associated with pain intensity at the next visit in 1 month.

Results

Current pain intensity (p < 0.001), sleep disturbances (p 0.01 and 0.006), drowsiness (p 0.003 and 0.033) and male gender (p 0.045 and 0.001) were associated with higher average and worst pain intensity in 1 month. In addition, breakthrough pain was related to higher worst pain intensity (p 0.003) in 1 month. The same variables were also associated with higher average pain intensity at baseline.

Conclusion

Higher current pain intensity, sleep disturbances, drowsiness, male gender, and breakthrough pain are factors associated with higher pain intensity in patients with bone metastases at the next follow-up in 1 month. These factors should be assessed in clinical practice and may aid clinicians in identifying patients that can benefit from closer follow-up or interventions to prevent lack of future pain control.

Trial registration in clinicaltrials.gov

NCT01362816.

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References

  1. Bruera E, Kuehn N, Miller MJ, Selmser P, Macmillan K (1991) The Edmonton symptom assessment system (ESAS): a simple method for the assessment of palliative care patients. J Palliat Care 7:6–9

    PubMed  CAS  Article  Google Scholar 

  2. Chow E, Zeng L, Salvo N, Dennis K, Tsao M, Lutz S (2012) Update on the systematic review of palliative radiotherapy trials for bone metastases. Clin Oncol 24:112–124

    Article  CAS  Google Scholar 

  3. Clare C, Royle D, Saharia K, Pearse H, Oxberry S, Oakley K, Allsopp L, Rigby AS, Johnson MJ (2005) Painful bone metastases: a prospective observational cohort study. Palliat Med 19:521–525

    Article  PubMed  Google Scholar 

  4. Cleeland CS (2006) The measurement of pain from metastatic bone disease: capturing the patient’s experience. Clin Cancer Res 12:6236s–6242s

    Article  PubMed  Google Scholar 

  5. Coleman RE (2006) Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 12:6243s–6249s

    Article  PubMed  Google Scholar 

  6. Delaney A, Fleetwood-Walker SM, Colvin LA, Fallon M (2008) Translational medicine: cancer pain mechanisms and management. Br J Anaesth 101:87–94

    Article  PubMed  CAS  Google Scholar 

  7. Delgado-Guay M, Yennurajalingam S, Parsons H, Palmer JL, Bruera E (2011) Association between self-reported sleep disturbance and other symptoms in patients with advanced cancer. J Pain Symptom Manag 41:819–827

    Article  Google Scholar 

  8. Evans C, McCarthy M (1985) Prognostic uncertainty in terminal care: can the Karnofsky index help? Lancet 1:1204–1206

    Article  PubMed  CAS  Google Scholar 

  9. Fainsinger RL, Fairchild A, Nekolaichuk C, Lawlor P, Lowe S, Hanson J (2009) Is pain intensity a predictor of the complexity of cancer pain management? J Clin Oncol 27:585–590

    Article  PubMed  Google Scholar 

  10. Fayers PM, Hjermstad MJ, Ranhoff AH, Kaasa S, Skogstad L, Klepstad P, Loge JH (2005) Which mini-mental state exam items can be used to screen for delirium and cognitive impairment? J Pain Symptom Manag 30:41–50

    Article  Google Scholar 

  11. Groenvold M, Petersen MA, Aaronson NK, Arraras JI, Blazeby JM, Bottomley A, Fayers PM, de Graeff A, Hammerlid E, Kaasa S, Sprangers MA, Bjorner JB, Group EQoL (2006) The development of the EORTC QLQ-C15-PAL: a shortened questionnaire for cancer patients in palliative care. Eur J Cancer 42:55–64

    Article  PubMed  Google Scholar 

  12. Hagen NA, Stiles C, Nekolaichuk C, Biondo P, Carlson LE, Fisher K, Fainsinger R (2008) The Alberta Breakthrough Pain Assessment Tool for cancer patients: a validation study using a delphi process and patient think-aloud interviews. J Pain Symptom Manag 35:136–152

    Article  Google Scholar 

  13. Hjermstad MJ, Aass N, Aielli F, Bennett M, Brunelli C, Caraceni A, Cavanna L, Fassbender K, Feio M, Haugen DF, Jakobsen G, Laird B, Lohre ET, Martinez M, Nabal M, Noguera-Tejedor A, Pardon K, Pigni A, Piva L, Porta-Sales J, Rizzi F, Rondini E, Sjogren P, Strasser F, Turriziani A, Kaasa S, European Palliative Care Cancer Symptoms (2016) Characteristics of the case mix, organisation and delivery in cancer palliative care: a challenge for good-quality research BMJ Support Palliat Care

  14. Holtan A, Aass N, Nordoy T, Haugen DF, Kaasa S, Mohr W, Kongsgaard UE (2007) Prevalence of pain in hospitalised cancer patients in Norway: a national survey. Palliat Med 21:7–13

    Article  PubMed  Google Scholar 

  15. Im EO, Chee W (2006) Evaluation of the decision support computer program for cancer pain management. Oncol Nurs Forum 33:977–982

    Article  PubMed  Google Scholar 

  16. Kane CM, Hoskin P, Bennett MI (2015) Cancer induced bone pain. BMJ 350:h315

    Article  PubMed  Google Scholar 

  17. Kerba M, Wu JS, Duan Q, Hagen NA, Bennett MI (2010) Neuropathic pain features in patients with bone metastases referred for palliative radiotherapy. J Clin Oncol 28:4892–4897

    Article  PubMed  Google Scholar 

  18. Kinnane N (2007) Burden of bone disease. Eur J Oncol Nurs 11(Suppl 2):S28–S31

    Article  PubMed  Google Scholar 

  19. Knudsen AK, Brunelli C, Klepstad P, Aass N, Apolone G, Corli O, Montanari M, Caraceni A, Kaasa S (2012) Which domains should be included in a cancer pain classification system? Analyses of longitudinal data. Pain 153:696–703

    Article  PubMed  Google Scholar 

  20. Knudsen AK, Brunelli C, Kaasa S, Apolone G, Corli O, Montanari M, Fainsinger R, Aass N, Fayers P, Caraceni A, Klepstad P, European Palliative Care Research C, European Pharmacogenetic S (2011) Which variables are associated with pain intensity and treatment response in advanced cancer patients?—Implications for a future classification system for cancer pain. Eur J Pain 15:320–327

    Article  PubMed  Google Scholar 

  21. Laird BJ, Walley J, Murray GD, Clausen E, Colvin LA, Fallon MT (2011) Characterization of cancer-induced bone pain: an exploratory study. Support Care Cancer 19:1393–1401

    Article  PubMed  Google Scholar 

  22. Lechner B, Chow S, Chow R, Zhang L, Tsao M, Danjoux C, Barnes E, DeAngelis C, Vuong S, Ganesh V, Chow E (2016) The incidence of neuropathic pain in bone metastases patients referred for palliative radiotherapy. Radiother Oncol 118:557–561

    Article  PubMed  Google Scholar 

  23. Lozano-Ondoua AN, Symons-Liguori AM, Vanderah TW (2013) Cancer-induced bone pain: mechanisms and models. Neurosci Lett 557(Pt A):52–59

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Lynch ME, Fischbach C (2014) Biomechanical forces in the skeleton and their relevance to bone metastasis: biology and engineering considerations. Adv Drug Deliv Rev 79-80:119–134

    Article  PubMed  CAS  Google Scholar 

  25. Mantyh PW (2014) Bone cancer pain: from mechanism to therapy. Curr Opin Support Palliat Care 8:83–90

    Article  PubMed  PubMed Central  Google Scholar 

  26. Mercadante S (1997) Malignant bone pain: pathophysiology and treatment. Pain 69:1–18

    Article  PubMed  CAS  Google Scholar 

  27. Mercadante S, Adile C, Ferrera P, Masedu F, Valenti M, Aielli F (2017) Sleep disturbances in advanced cancer patients admitted to a supportive/palliative care unit. Support Care Cancer 25:1301–1306

    Article  PubMed  Google Scholar 

  28. Mercadante S, Portenoy RK (2016) Breakthrough cancer pain: twenty-five years of study. Pain 157:2657–2663

    Article  PubMed  CAS  Google Scholar 

  29. Meuser T, Pietruck C, Radbruch L, Stute P, Lehmann KA, Grond S (2001) Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology. Pain 93:247–257

    Article  PubMed  CAS  Google Scholar 

  30. Miaskowski C (2004) Gender differences in pain, fatigue, and depression in patients with cancer. J Natl Cancer Inst Monogr 2004:139–143

    Article  Google Scholar 

  31. Middlemiss T, Laird BJ, Fallon MT (2011) Mechanisms of cancer-induced bone pain. Clin Oncol 23:387–392

    Article  CAS  Google Scholar 

  32. Nekolaichuk CL, Fainsinger RL, Lawlor PG (2005) A validation study of a pain classification system for advanced cancer patients using content experts: the Edmonton Classification System for Cancer Pain. Palliat Med 19:466–476

    Article  PubMed  Google Scholar 

  33. Nekolaichuk CL, Fainsinger RL, Aass N, Hjermstad MJ, Knudsen AK, Klepstad P, Currow DC, Kaasa S, European Palliative Care Research C (2013) The Edmonton Classification System for Cancer Pain: comparison of pain classification features and pain intensity across diverse palliative care settings in eight countries. J Palliat Med 16:516–523

    Article  PubMed  Google Scholar 

  34. Oh SY, Shin SW, Koh SJ, Bae SB, Chang H, Kim JH, Kim HJ, Hong YS, Park KU, Park J, Lee KH, Lee NR, Lee JL, Jang JS, Hong DS, Lee SS, Baek SK, Choi DR, Chung J, Oh SC, Han HS, Yun HJ, Sym SJ, Yoon SY, Choi IS, Shim BY, Kang SY, Kim SR, Kim HJ (2017) Multicenter, cross-sectional observational study of the impact of neuropathic pain on quality of life in cancer patients. Support Care Cancer 25(12):3759–3767

    Article  PubMed  PubMed Central  Google Scholar 

  35. Pan W (2001) Akaike’s information criterion in generalized estimating equations. Biometrics 57:120–125

    Article  PubMed  CAS  Google Scholar 

  36. Pina P, Sabri E, Lawlor PG (2015) Characteristics and associations of pain intensity in patients referred to a specialist cancer pain clinic. Pain Res Manag 20:249–254

    Article  PubMed  PubMed Central  Google Scholar 

  37. Roodman GD (2012) Genes associate with abnormal bone cell activity in bone metastasis. Cancer Metastasis Rev 31:569–578

    Article  PubMed  CAS  Google Scholar 

  38. Scarpi E, Calistri D, Klepstad P, Kaasa S, Skorpen F, Habberstad R, Nanni O, Amadori D, Maltoni M (2014) Clinical and genetic factors related to cancer-induced bone pain and bone pain relief. Oncologist 19:1276–1283

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. van den Beuken-van Everdingen MH, Hochstenbach LM, Joosten EA, Tjan-Heijnen VC, Janssen DJ (2016) Update on prevalence of pain in patients with cancer: systematic review and meta-analysis. J Pain Symptom Manag 51(1070–1090):e1079

    Google Scholar 

  40. van der Vliet QM, Paulino Pereira NR, Janssen SJ, Hornicek FJ, Ferrone ML, Bramer JA, van Dijk CN, Schwab JH (2017) What factors are associated with quality of life, pain interference, anxiety, and depression in patients with metastatic bone disease? Clin Orthop Relat Res 475:498–507

    Article  PubMed  Google Scholar 

  41. von Moos R, Costa L, Ripamonti CI, Niepel D, Santini D (2017) Improving quality of life in patients with advanced cancer: targeting metastatic bone pain. Eur J Cancer 71:80–94

    Article  Google Scholar 

  42. Winters-Stone KM, Schwartz A, Nail LM (2010) A review of exercise interventions to improve bone health in adult cancer survivors. J Cancer Surviv 4:187–201

    Article  PubMed  Google Scholar 

  43. Wu JS, Beaton D, Smith PM, Hagen NA (2010) Patterns of pain and interference in patients with painful bone metastases: a brief pain inventory validation study. J Pain Symptom Manag 39:230–240

    Article  Google Scholar 

  44. Wu JS, Wong R, Johnston M, Bezjak A, Whelan T, Cancer Care Ontario Practice Guidelines Initiative Supportive Care G (2003) Meta-analysis of dose-fractionation radiotherapy trials for the palliation of painful bone metastases. Int J Radiat Oncol Biol Phys 55:594–605

    Article  PubMed  Google Scholar 

  45. Zeger SL, Liang KY (1986) Longitudinal data analysis for discrete and continuous outcomes. Biometrics 42:121–130

    Article  PubMed  CAS  Google Scholar 

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Funding

This work was supported by the Central Norway Regional Health Authority (grant no. 46055100), the Cancer Foundation St Olavs Hospital, Trondheim University Hospital (grant no. 6070), the Liaison Committee for Education, Research and Innovation in Central Norway, and an unrestricted grant from the Helsinn Group, Switzerland.

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Correspondence to Ragnhild Habberstad.

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Conflicts of interest

Kaasa S. hold stocks in EIR Solutions A/S. The other authors have no conflicts of interest.

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Habberstad, R., Hjermstad, M.J., Brunelli, C. et al. Which factors can aid clinicians to identify a risk of pain during the following month in patients with bone metastases? A longitudinal analyses. Support Care Cancer 27, 1335–1343 (2019). https://doi.org/10.1007/s00520-018-4405-9

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  • DOI: https://doi.org/10.1007/s00520-018-4405-9

Keywords

  • Cancer
  • Pain
  • Bone metastases
  • Cancer-induced bone pain
  • Associations