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Oligometastases revisited

Abstract

We previously proposed a clinical state of metastasis termed 'oligometastases' that refers to restricted tumor metastatic capacity. The implication of this concept is that local cancer treatments are curative in a proportion of patients with metastases. Here we review clinical and laboratory data that support the hypothesis that oligometastasis is a distinct clinical entity. Investigations of the prevalence, mechanism of occurrence, and position in the metastatic cascade, as well as the determination of molecular markers to distinguish oligometastatic from polymetastatic disease, are ongoing.

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Figure 1: Survival of patients undergoing pulmonary resection of metastatic tumors.

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References

  1. Edge, S. B. et al. (Eds) AJCC Cancer Staging Manual 7th edn (Springer, New York, 2010).

    Google Scholar 

  2. Hellman, S. & Weichselbaum, R. R. Oligometastases. J. Clin. Oncol. 13, 8–10 (1995).

    Article  CAS  PubMed  Google Scholar 

  3. Hughes, K. S. et al. Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of patterns of recurrence. Surgery 100, 278–284 (1986).

    CAS  PubMed  Google Scholar 

  4. Nordlinger, B. et al. Surgical resection of colorectal carcinoma metastases to the liver. A prognostic scoring system to improve case selection, based on 1568 patients. Association Française de Chirurgie. Cancer 77, 1254–1262 (1996).

    Article  CAS  PubMed  Google Scholar 

  5. Fong, Y., Fortner, J., Sun, R. L., Brennan, M. F. & Blumgart, L. H. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann. Surg. 230, 309–318 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Pawlik, T. M. et al. Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases. Ann. Surg. 241, 715–722 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Pastorino, U. et al. Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. The International Registry of Lung Metastases. J. Thorac. Cardiovasc. Surg. 113, 37–49 (1997).

    Article  CAS  PubMed  Google Scholar 

  8. Strong, V. E. et al. Laparoscopic adrenalectomy for isolated adrenal metastasis. Ann. Surg. Oncol. 14, 3392–3400 (2007).

    Article  PubMed  Google Scholar 

  9. Ben-Josef, E. & Lawrence, T. S. Using a bigger hammer: the role of stereotactic body radiotherapy in the management of oligometastases. J. Clin. Oncol. 27, 1537–1539 (2009).

    Article  PubMed  Google Scholar 

  10. Salama, J. K. et al. An initial report of a radiation dose-escalation trial in patients with one to five sites of metastatic disease. Clin. Cancer Res. 14, 5255–5259 (2008).

    Article  CAS  PubMed  Google Scholar 

  11. Rusthoven, K. E. et al. Multi-institutional phase I/II trial of stereotactic body radiation therapy for lung metastases. J. Clin. Oncol. 27, 1579–1584 (2009).

    Article  PubMed  Google Scholar 

  12. Lee, M. T. et al. Phase I study of individualized stereotactic body radiotherapy of liver metastases. J. Clin. Oncol. 27, 1585–1591 (2009).

    Article  PubMed  Google Scholar 

  13. Macdermed, D. M., Weichselbaum, R. R. & Salama, J. K. A rationale for the targeted treatment of oligometastases with radiotherapy. J. Surg. Oncol. 98, 202–206 (2008).

    Article  PubMed  Google Scholar 

  14. Fakiris, A. J. et al. Stereotactic body radiation therapy for early-stage non-small-cell lung carcinoma: four-year results of a prospectice phase II study. Int. J. Radiat. Oncol. Biol. Phys. 75, 677–682 (2009).

    Article  PubMed  Google Scholar 

  15. Minn, A. J. et al. Genes that mediate breast cancer metastasis to lung. Nature 436, 518–524 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Minn, A. J. et al. Lung metastasis genes couple breast tumor size and metastatic spread. Proc. Natl Acad. Sci. USA 104, 6740–6745 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kaplan, R. N., Psaila, B. & Lyden, D. Bone marrow cells in the 'pre-metastatic niche': within bone and beyond. Cancer Metastasis Rev. 25, 521–529 (2006).

    Article  PubMed  Google Scholar 

  18. Erler, J. T. et al. Lysyl oxidase is essential for hypoxia-induced metastasis. Nature 440, 1222–1226 (2006).

    Article  CAS  PubMed  Google Scholar 

  19. Giacchetti, S. et al. Long-term survival of patients with unresectable colorectal cancer liver metastases following infusional chemotherapy with 5-fluorouracil, leucovorin, oxaliplatin and surgery. Ann. Oncol. 10, 663–669 (1999).

    Article  CAS  PubMed  Google Scholar 

  20. Lévi, F. et al. Cetuximab and circadian chronomodulated chemotherapy as salvage treatment for metastatic colorectal cancer (mCRC): safety, efficacy and improved secondary surgical resectability. Cancer Chemother. Pharmacol. 67, 339–348 (2011).

    Article  PubMed  Google Scholar 

  21. Paget, S. The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev. 8, 98–101 (1989).

    CAS  PubMed  Google Scholar 

  22. Deng, C. X. BRCA1: cell cycle checkpoint, genetic instability, DNA damage response and cancer evolution. Nucleic Acids Res. 34, 1416–1426 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Rajagopalan, H. & Lengauer, C. Aneuploidy and cancer. Nature 432, 338–341 (2004).

    Article  CAS  PubMed  Google Scholar 

  24. Gupta, G. P. & Massagué, J. Cancer metastasis: building a framework. Cell 127, 679–695 (2006).

    Article  CAS  PubMed  Google Scholar 

  25. Aguirre-Ghiso, J. A. Models, mechanisms and clinical evidence for cancer dormancy. Nat. Rev. Cancer 7, 834–846 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Fokas, E., Engenhart-Cabillic, R., Daniilidis, K., Rose, F. & An, H. X. Metastasis: the seed and soil theory gains identity. Cancer Metastasis Rev. 26, 705–715 (2007).

    Article  PubMed  Google Scholar 

  27. Uhr, J. W., Scheuermann, R. H, Street, N. E. & Vitetta, E. S. Cancer dormancy: opportunities for new therapeutic approaches. Nat. Med. 3, 505–509 (1997).

    Article  CAS  PubMed  Google Scholar 

  28. Goss, P. E. & Chambers, A. F. Does tumour dormancy offer a therapeutic target? Nat. Rev. Cancer 10, 871–877 (2010).

    Article  CAS  PubMed  Google Scholar 

  29. Dunn, G. P., Koebel, C. M. & Schreiber, R. D. Interferons, immunity and cancer immunoediting. Nat. Rev. Immunol. 6, 836–848 (2006).

    Article  CAS  PubMed  Google Scholar 

  30. Fidler, I. J. & Kripke, M. L. Metastasis results from preexisting variant cells within a malignant tumor. Science 197, 893–895 (1977).

    Article  CAS  PubMed  Google Scholar 

  31. Chambers, A. F, Hill, R. P. & Ling, V. Tumor heterogeneity and stability of the metastatic phenotype of mouse KHT sarcoma cells. Cancer Res. 41, 1368–1372 (1981).

    CAS  PubMed  Google Scholar 

  32. Harris, J. F., Chambers, A. F., Hill, R. P. & Ling, V. Metastatic variants are generated spontaneously at a high rate in mouse KHT tumor. Proc. Natl Acad. Sci. USA 79, 5547–5551 (1982).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cillo, C., Dick, J. E., Ling, V. & Hill, R. P. Generation of drug-resistant variants in metastatic B16 mouse melanoma cell lines. Cancer Res. 47, 2604–2608 (1987).

    CAS  PubMed  Google Scholar 

  34. Khodarev, N. N. et al. STAT1 pathway mediates amplification of metastatic potential and resistance to therapy. PLoS ONE 4, e5821 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Khodarev, N. N. et al. STAT1 is overexpressed in tumors selected for radioresistance and confers protection from radiation in transduced sensitive cells. Proc. Natl Acad. Sci. USA 101, 1714–1719 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Weichselbaum, R. R. et al. An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer. Proc. Natl Acad. Sci. USA 105, 18490–18495 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Wuttig, D. et al. Gene signatures of pulmonary metastases of renal cell carcinoma reflect the disease-free interval and the number of metastases per patient. Int. J. Cancer 125, 474–482 (2009).

    Article  CAS  PubMed  Google Scholar 

  38. Jones, J. et al. Gene signatures of progression and metastasis in renal cell cancer. Clin. Cancer Res. 11, 5730–5739 (2005).

    Article  CAS  PubMed  Google Scholar 

  39. Campbell, P. J. et al. The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature 467, 1109–1113 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Yachida, S. et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467, 1114–1117 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors are supported by grants from the Ludwig Foundation for Cancer Research, the Lung Cancer Research Foundation, and a generous gift from the Foglia Foundation.

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Both authors contributed to researching data for the article, discussion of the content, and writing and editing the manuscript.

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Correspondence to Ralph R. Weichselbaum.

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Competing interests

R. R. Weichselbaum is a stock-holder or Director with the following companies: GenVec, Catherex, and Reflexion. S. Hellman is a stock-holder or Director at InSightec.

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Weichselbaum, R., Hellman, S. Oligometastases revisited. Nat Rev Clin Oncol 8, 378–382 (2011). https://doi.org/10.1038/nrclinonc.2011.44

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