Skip to main content

Advertisement

SpringerLink
Log in

Bone metastases in gastrointestinal cancer

  • Research Paper
  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

Colorectal (CRC) and gastroesophageal (GEC) cancers unusually spread to the bone. However, bone metastases (BM) are responsible for skeletal-related events (SREs) associated with an altered quality of life. Aiming to describe the characteristics and prognostic influence of BM from gastro-intestinal cancers, we performed a retrospective analysis of prospectively collected data in patients treated in our institution (1996–2006). 189 patients (5.5 %) developed BM: 79 with GEC and 110 with CRC. 57 patients had bone-exclusive metastases. In univariate analyses, the median time to BM occurrence was correlated with the primary tumour (PT) localisation, surgery, histology and TNM staging. However, in multivariate analyses, the occurrence delay was significantly shorter only for patients with GEC (HR 2.1), N1–2 status (HR 1.9), M1 status (HR 2.4), and epidermoid carcinoma (HR 6.0). Pain was the most frequent clinical sign leading to BM diagnosis (77.2 %). SRE occurred in 55 % of patients. Median overall survivals (OSs) of patients with CRC and GEC were 9.4 months [95 % confidence interval (95 % CI) 6.4–11.1] and 3.4 months (95 % CI 2.5–9.0), respectively. In univariate analyses, OS was correlated with PT surgery and NM staging, and the number of BM. In multivariate analyses, only the PT surgery and the number of BM remained correlated with OS. Our results suggest that there may be a subset of patients associated with a quicker development of BM. Given their higher risk of SRE, they could benefit from an early screening, calling for further prospective studies encompassing patients with and without BM.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Notes

  1. IFL (irinotecan, 5-fluorouracile and leucovorin).

  2. IROX (irinotecan and oxaliplatin).

  3. FOLFOX (5-fluorouracile, oxaliplatin and leucovorin).

References

  1. Milosavljevic T, Kostic-Milosavljevic M, Jovanovic I, Krstic M (2010) Gastrointestinal and liver tumours and public health in Europe. Eur Rev Med Pharmacol Sci 14:259–262

    CAS  PubMed  Google Scholar 

  2. Coleman RE (2004) Bisphosphonates: clinical experience. Oncologist 9:14–27. doi:10.1634/theoncologist.9-90004-14

    Article  CAS  PubMed  Google Scholar 

  3. Mundy GR (2002) Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2:584–593. doi:10.1038/nrc867

    Article  CAS  PubMed  Google Scholar 

  4. Clamp A, Danson S, Nguyen H et al (2004) Assessment of therapeutic response in patients with metastatic bone disease. Lancet Oncol 5:607–616. doi:10.1016/S1470-2045(04)01596-7

    Article  PubMed  Google Scholar 

  5. Sundermeyer ML, Meropol NJ, Rogatko A et al (2005) Changing patterns of bone and brain metastases in patients with colorectal cancer. Clin Colorectal Cancer 5:108–113

    Article  PubMed  Google Scholar 

  6. Nordlinger B, Sorbye H, Glimelius B et al (2008) Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet 371:1007–1016. doi:10.1016/S0140-6736(08)60455-9

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Adam R, Wicherts DA, de Haas RJ et al (2009) Patients with initially unresectable colorectal liver metastases: is there a possibility of cure? J Clin Oncol 27:1829–1835. doi:10.1200/JCO.2008.19.9273

    Article  PubMed  Google Scholar 

  8. Olivier T, Gastaud L, Maschi C et al (2014) Metastasis to unusual sites. Bull Cancer (Paris). doi:10.1684/bdc.2014.1889

    Google Scholar 

  9. Saad F, Lipton A, Cook R et al (2007) Pathologic fractures correlate with reduced survival in patients with malignant bone disease. Cancer 110:1860–1867. doi:10.1002/cncr.22991

    Article  PubMed  Google Scholar 

  10. Saad F, Gleason DM, Murray R et al (2002) A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 94:1458–1468. doi:10.1093/jnci/94.19.1458

    Article  CAS  PubMed  Google Scholar 

  11. Hortobagyi GN, Theriault RL, Porter L et al (1996) Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases. N Engl J Med 335:1785–1792. doi:10.1056/NEJM199612123352401

    Article  CAS  PubMed  Google Scholar 

  12. Silvestris N, Pantano F, Ibrahim T et al (2013) Natural history of malignant bone disease in gastric cancer: final results of a multicenter bone metastasis survey. PLoS ONE 8:e74402. doi:10.1371/journal.pone.0074402

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Coleman RE (1997) Skeletal complications of malignancy. Cancer 80:1588–1594

    Article  CAS  PubMed  Google Scholar 

  14. Roth ES, Fetzer DT, Barron BJ et al (2009) Does colon cancer ever metastasize to bone first? A temporal analysis of colorectal cancer progression. BMC Cancer 9:274. doi:10.1186/1471-2407-9-274

    Article  PubMed Central  PubMed  Google Scholar 

  15. Santini D, Tampellini M, Vincenzi B et al (2012) Natural history of bone metastasis in colorectal cancer: final results of a large Italian bone metastases study. Ann Oncol 23:2072–2077. doi:10.1093/annonc/mdr572

    Article  CAS  PubMed  Google Scholar 

  16. Besbeas S, Stearns MW Jr (1978) Osseous metastases from carcinomas of the colon and rectum. Dis Colon Rectum 21:266–268

    Article  CAS  PubMed  Google Scholar 

  17. Kanthan DR, Loewy J, Kanthan SC (1999) Skeletal metastases in colorectal carcinomas. Dis Colon Rectum 42:1592–1597. doi:10.1007/BF02236213

    Article  CAS  PubMed  Google Scholar 

  18. Katoh M, Unakami M, Hara M, Fukuchi S (1995) Bone metastasis from colorectal cancer in autopsy cases. J Gastroenterol 30:615–618

    Article  CAS  PubMed  Google Scholar 

  19. Welch JP, Donaldson GA (1979) The clinical correlation of an autopsy study of recurrent colorectal cancer. Ann Surg 189:496–502

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Park JM, Song KY, O JH et al (2013) Bone recurrence after curative resection of gastric cancer. Gastric Cancer 16:362–369. doi:10.1007/s10120-012-0193-y

    Article  PubMed  Google Scholar 

  21. Park HS, Rha SY, Kim HS et al (2011) A prognostic model to predict clinical outcome in gastric cancer patients with bone metastasis. Oncology 80:142–150. doi:10.1159/000328507

    Article  PubMed  Google Scholar 

  22. Dennis K, Wong K, Zhang L et al (2011) Palliative radiotherapy for bone metastases in the last 3 months of life: worthwhile or futile? Clin Oncol 23:709–715. doi:10.1016/j.clon.2011.05.004

    Article  CAS  Google Scholar 

  23. Pavlakis N, Schmidt R, Stockler M (2005) Bisphosphonates for breast cancer. Cochrane Database Syst Rev Online CD003474. doi:10.1002/14651858.CD003474.pub2

  24. Stopeck AT, Lipton A, Body J-J et al (2010) Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol 28:5132–5139. doi:10.1200/JCO.2010.29.7101

    Article  CAS  PubMed  Google Scholar 

  25. Saad F, Gleason DM, Murray R et al (2004) Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 96:879–882

    Article  CAS  PubMed  Google Scholar 

  26. Rosen LS, Gordon D, Tchekmedyian NS et al (2004) Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: a randomized, Phase III, double-blind, placebo-controlled trial. Cancer 100:2613–2621. doi:10.1002/cncr.20308

    Article  CAS  PubMed  Google Scholar 

  27. Patel LR, Camacho DF, Shiozawa Y et al (2011) Mechanisms of cancer cell metastasis to the bone: a multistep process. Future Oncol Lond Engl 7:1285–1297. doi:10.2217/fon.11.112

    Article  CAS  Google Scholar 

  28. Janni W, Vogl FD, Wiedswang G et al (2011) Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse—a European pooled analysis. Clin Cancer Res 17:2967–2976. doi:10.1158/1078-0432.CCR-10-2515

    Article  PubMed  Google Scholar 

  29. Morgan TM, Lange PH, Porter MP et al (2009) Disseminated tumor cells in prostate cancer patients after radical prostatectomy and without evidence of disease predicts biochemical recurrence. Clin Cancer Res 15:677–683. doi:10.1158/1078-0432.CCR-08-1754

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Cunningham D, Starling N, Rao S et al (2008) Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 358:36–46. doi:10.1056/NEJMoa073149

    Article  CAS  PubMed  Google Scholar 

  31. Lee J, Lim T, Uhm JE et al (2007) Prognostic model to predict survival following first-line chemotherapy in patients with metastatic gastric adenocarcinoma. Ann Oncol 18:886–891. doi:10.1093/annonc/mdl501

    Article  CAS  PubMed  Google Scholar 

  32. Hernandez RK, Maegbaek ML, Liede A et al (2014) Bone metastases, skeletal-related events, and survival among children with cancer in Denmark. J Pediatr Hematol Oncol. doi:10.1097/MPH.0000000000000106

    PubMed  Google Scholar 

  33. Peugniez C, Hiret S, Galais M-P et al (2014) Les facteurs prédictifs de contrôle tumoral des carcinomes épidermoïdes métastatiques de l’oesophage traités par chimiothérapie à base de sels de platine: premiers résultats de l’étude E-DIS. In: JFHOD congress, Paris, France, p 108, #CO.87. http://www.snfge.org/sites/default/files/SNFGE/JFHOD/livre-resumes-jfhod-2014-vfinale.pdf

  34. Goldberg RM, Sargent DJ, Morton RF et al (2004) A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 22:23–30. doi:10.1200/JCO.2004.09.046

    Article  CAS  PubMed  Google Scholar 

  35. Henry DH, Costa L, Goldwasser F et al (2011) Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol 29:1125–1132. doi:10.1200/JCO.2010.31.3304

    Article  CAS  PubMed  Google Scholar 

  36. Aapro M, Abrahamsson PA, Body JJ et al (2008) Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel. Ann Oncol 19:420–432. doi:10.1093/annonc/mdm442

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to acknowledge the editorial assistance of Dr. Vanessa Guillaumon and Dr. Julie Courraud.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Digestive Oncology, Institut régional du Cancer de Montpellier (ICM) – Val d’Aurelle, 208 avenue des Apothicaires, 34298, Montpellier Cedex 5, France

    Fabienne Portales, Emmanuelle Samalin, Eric Assenat, Thibault Mazard & Marc Ychou

  2. Biostatistics Unit, Institut régional du Cancer de Montpellier (ICM) – Val d’Aurelle, Montpellier, France

    Simon Thézenas

  3. Medical and Digestive Oncology Unit, Hôpital Saint-Eloi, CHU de Montpellier, Montpellier, France

    Eric Assenat & Thibault Mazard

Authors
  1. Fabienne Portales
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Simon Thézenas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emmanuelle Samalin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eric Assenat
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thibault Mazard
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marc Ychou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fabienne Portales.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Portales, F., Thézenas, S., Samalin, E. et al. Bone metastases in gastrointestinal cancer. Clin Exp Metastasis 32, 7–14 (2015). https://doi.org/10.1007/s10585-014-9686-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10585-014-9686-x

Keywords

Search

Navigation