Histology-Specific Metastasis

  • Michael T. Milano
  • Joseph K. Salama
Part of the Medical Radiology book series (MEDRAD)


For patients with metastases, limited in the number of sites and extent of organ involvement (termed oligometastases), metastasis-directed therapies, including stereotactic body radiotherapy (SBRT) can render some patients free of disease for extended periods of time, and potentially cured. When oligometastatic patients are classified by their underlying histopathologic disease, the impact of metastasis-directed therapy on the natural history of that specific disease state can be better understood for that specific cancer type. To date, there are published outcome studies of SBRT for oligometastases from non-small-cell lung cancer, colorectal cancer, renal cancer, melanoma, sarcoma, and breast cancer, which we review. The available data suggests that SBRT for oligometastases is associated with favorable outcomes, including in patients with cancers generally thought to be radioresistant. Patients treated to all known sites of disease can achieve very long disease-free intervals bordering on cure.


Renal Cell Carcinoma Lung Metastasis Intensity Modulate Radiation Therapy Stereotactic Body Radiotherapy Renal Cell Carcinoma Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Al-Asfoor A, Fedorowicz Z, Lodge M (2008) Resection versus no intervention or other surgical interventions for colorectal cancer liver metastases. Cochrane Database Syst Rev 16:CD006039Google Scholar
  2. Benedict SH, Yenice KM, Followill D, Galvin JM, Hinson W, Kavanagh B, Keall P, Lovelock M, Meeks S et al (2010) Stereotactic body radiation therapy: the report of AAPM task group 101. Med Phys 37:4078–4101PubMedCrossRefGoogle Scholar
  3. Billingsley KG, Burt ME, Jara E, Ginsberg RJ, Woodruff JM, Leung DH, Brennan MF (1999) Pulmonary metastases from soft tissue sarcoma: analysis of patterns of diseases and postmetastasis survival. Ann Surg 229:602–610; discussion 610–602Google Scholar
  4. Blackmon SH, Shah N, Roth JA, Correa AM, Vaporciyan AA, Rice DC, Hofstetter W, Walsh GL, Benjamin R, Pollock R, Swisher SG, Mehran R (2009) Resection of pulmonary and extrapulmonary sarcomatous metastases is associated with long-term survival. Ann Thorac Surg 88:877–884 discussion 884–875PubMedCrossRefGoogle Scholar
  5. Blomgren H, Lax I, Naslund I, Svanstrom R (1995) Stereotactic high dose fraction radiation therapy of extracranial tumors using an accelerator: clinical experience of the first thirty-one patients. Acta Oncol 34:861–870PubMedCrossRefGoogle Scholar
  6. Brown RE, Bower MR, Martin RC (2010) Hepatic resection for colorectal liver metastases. Surg Clin North Am 90:839–852PubMedCrossRefGoogle Scholar
  7. Cheruvu P, Metcalfe SK, Katz AW, Philip A, Okunieff P, Milano MT (2010) Retrospective review of stereotactic body radiotherapy (SBRT) for lung metastases from colorectal cancer (CRC). Int J Radiat Oncol Biol Phys 78:S316CrossRefGoogle Scholar
  8. Cheruvu P, Metcalfe SK, Metcalfe J, Chen Y, Okunieff P, Milano MT (2011) Comparison of outcomes in patients with stage III versus limited stage IV non-small cell lung cancer. Radiat Oncol 6:80PubMedCrossRefGoogle Scholar
  9. Demaria S, Ng B, Devitt ML, Babb JS, Kawashima N, Liebes L, Formenti SC (2004) Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int J Radiat Oncol Biol Phys 58:862–870PubMedCrossRefGoogle Scholar
  10. Dhakal S, Corbin KS, Milano MT, Philip A, Sahasrabudhe D, Jones C, Constine LS (2012) Stereotactic body radiotherapy for pulmonary metastases from soft-tissue sarcomas: excellent local lesion control and improved patient survival. Int J Radiat Oncol Biol Phys (in press)Google Scholar
  11. Elias D, Liberale G, Vernerey D, Pocard M, Ducreux M, Boige V, Malka D, Pignon JP, Lasser P (2005) Hepatic and extrahepatic colorectal metastases: when resectable, their localization does not matter, but their total number has a prognostic effect. Ann Surg Oncol 12:900–909PubMedCrossRefGoogle Scholar
  12. Engels B, Everaert H, Gevaert T, Duchateau M, Neyns B, Sermeus A, Tournel K, Verellen D, Storme G, De Ridder M (2011) Phase II study of helical tomotherapy for oligometastatic colorectal cancer. Ann Oncol 22:362–368PubMedCrossRefGoogle Scholar
  13. Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH (1999) Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 230:309–318 discussion 318–321PubMedCrossRefGoogle Scholar
  14. Formenti SC, Demaria S (2009) Systemic effects of local radiotherapy. Lancet Oncol 10:718–726PubMedCrossRefGoogle Scholar
  15. Formenti S, Friedman K, Chao K, Adams S, Fenton-Kerimian M, Donach ME, Demaria S (2008) Abscopal response in irradiated patients: results of a proof of principle trial. Int J Radiat Oncol Biol Phys 72:S6–S7CrossRefGoogle Scholar
  16. Gerszten PC, Burton SA, Ozhasoglu C, Vogel WJ, Welch WC, Baar J, Friedland DM (2005a) Stereotactic radiosurgery for spinal metastases from renal cell carcinoma. J Neurosurg Spine 3:288–295PubMedCrossRefGoogle Scholar
  17. Gerszten PC, Burton SA, Quinn AE, Agarwala SS, Kirkwood JM (2005b) Radiosurgery for the treatment of spinal melanoma metastases. Stereotact Funct Neurosurg 83:213–221PubMedCrossRefGoogle Scholar
  18. Greco C, Zelefsky MJ, Lovelock M, Fuks Z, Hunt M, Rosenzweig K, Zatcky J, Kim B, Yamada Y (2011) Predictors of local control after single-dose stereotactic image-guided intensity-modulated radiotherapy for extracranial metastases. Int J Radiat Oncol Biol Phys 79:1151–1157PubMedCrossRefGoogle Scholar
  19. Hasselle MD, Haraf DJ, Rusthoven KE, Golden DW, Salgia R, Villaflor VM, Shah N, Hoffman PC, Chmura SJ, Connell PP, Vokes EE, Weichselbaum RR, Salama JK (2012) Hypofractionated image-guided radiation therapy for patients with limited volume metastatic non-small cell lung cancer. J Thorac Oncol (in press)Google Scholar
  20. Hellman S, Weichselbaum RR (1995) Oligometastases. J Clin Oncol 13:8–10PubMedGoogle Scholar
  21. Hoyer M, Roed H, Traberg Hansen A, Ohlhuis L, Petersen J, Nellemann H, Kiil Berthelsen A, Grau C, Aage Engelholm S, Von der Maase H (2006) Phase II study on stereotactic body radiotherapy of colorectal metastases. Acta Oncol 45:823–830PubMedCrossRefGoogle Scholar
  22. Inoue M, Ohta M, Iuchi K, Matsumura A, Ideguchi K, Yasumitsu T, Nakagawa K, Fukuhara K, Maeda H, Takeda S, Minami M, Ohno Y, Matsuda H (2004) Benefits of surgery for patients with pulmonary metastases from colorectal carcinoma. Ann Thorac Surg 78:238–244PubMedCrossRefGoogle Scholar
  23. Kang JK, Kim MS, Kim JH, Yoo SY, Cho CK, Yang KM, Yoo HJ, Seo YS, Lee DH, Kang HJ, Kim YH, Shin US (2010) Oligometastases confined one organ from colorectal cancer treated by SBRT. Clin Exp Metas 27:273–278CrossRefGoogle Scholar
  24. Kao J, Packer S, Vu HL, Schwartz ME, Sung MW, Stock RG, Lo YC, Huang D, Chen SH, Cesaretti JA (2009) Phase 1 study of concurrent sunitinib and image-guided radiotherapy followed by maintenance sunitinib for patients with oligometastases: acute toxicity and preliminary response. Cancer 115:3571–3580PubMedCrossRefGoogle Scholar
  25. Khan AJ, Mehta PS, Zusag TW, Bonomi PD, Penfield Faber L, Shott S, Abrams RA (2006) Long term disease-free survival resulting from combined modality management of patients presenting with oligometastatic, non-small cell lung carcinoma (NSCLC). Radiother Oncol 81:163–167PubMedCrossRefGoogle Scholar
  26. Kim MS, Yoo SY, Cho CK, Yoo HJ, Choi CW, Seo YS, Kang JK, Lee DH, Hwang DY, Moon SM, Kang HJ, Kim YH (2009) Stereotactic body radiation therapy using three fractions for isolated lung recurrence from colorectal cancer. Oncology 76:212–219PubMedCrossRefGoogle Scholar
  27. Kuvshinoff B, Fong Y (2007) Surgical therapy of liver metastases. Semin Oncol 34:177–185PubMedCrossRefGoogle Scholar
  28. Mahmoud N, Bullard Dunn K (2010) Metastasectomy for stage IV colorectal cancer. Dis Colon Rectum 53:1080–1092PubMedCrossRefGoogle Scholar
  29. Mehta N, Mauer AM, Hellman S, Haraf DJ, Cohen EE, Vokes EE, Weichselbaum RR (2004) Analysis of further disease progression in metastatic non-small cell lung cancer: implications for locoregional treatment. Int J Oncol 25:1677–1683PubMedGoogle Scholar
  30. Metcalfe SK, Cheruvu P, Katz AW, Philip A, Okunieff P, Milano MT (2010) Prospective trial of stereotactic body radiation therapy for colorectal oligometastases. In: Proceedings of American Radium Society, vol S059Google Scholar
  31. Milano MT, Constine LS, Okunieff P (2008a) Normal tissue toxicity after small field hypofractionated stereotactic body radiation. Radiat Oncol 3:36PubMedCrossRefGoogle Scholar
  32. Milano MT, Katz AW, Muhs AG, Philip A, Buchholz DJ, Schell MC, Okunieff P (2008b) A prospective pilot study of curative-intent stereotactic body radiation therapy in patients with 5 or fewer oligometastatic lesions. Cancer 112:650–658PubMedCrossRefGoogle Scholar
  33. Milano MT, Katz AW, Schell MC, Philip A, Okunieff P (2008c) Descriptive analysis of oligometastatic lesions treated with curative-intent stereotactic body radiotherapy. Int J Radiat Oncol Biol Phys 72:1516–1522PubMedCrossRefGoogle Scholar
  34. Milano MT, Katz AW, Zhang H, Okunieff P (2012) Oligometastases treated with stereotactic body radiation therapy: long-term follow-up of a prospective study. Int J Radiat Oncol Biol Phys (in press)Google Scholar
  35. Pastorino U, Buyse M, Friedel G et al (1997) Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases: the international registry of lung metastases. J Thorac Cardiovasc Surg 113: 37–49Google Scholar
  36. Ranck MC, Golden DW, Corbin KS, Hasselle MD, Liauw SL, Stadler WM, Hahn OM, Weichselbaum RR, Salama JK (2012) Stereotactic Body Radiotherapy for the Treatment of Oligometastatic Renal Cell Carcinoma. Am J Clin Oncol [Epub ahead of print]Google Scholar
  37. Rusthoven KE, Hammerman SF, Kavanagh BD, Birtwhistle MJ, Stares M, Camidge DR (2009) Is there a role for consolidative stereotactic body radiation therapy following first-line systemic therapy for metastatic lung cancer? a patterns-of-failure analysis. Acta Oncol 48:578–583PubMedCrossRefGoogle Scholar
  38. Salama JK, Chmura SJ, Mehta N, Yenice KM, Stadler WM, Vokes EE, Haraf DJ, Hellman S, Weichselbaum RR (2008) An initial report of a radiation dose-escalation trial in patients with one to five sites of metastatic disease. Clin Cancer Res 14:5255–5259PubMedCrossRefGoogle Scholar
  39. Salama JK, Hasselle MD, Chmura SJ, Malik R, Mehta N, Yenice KM, Villaflor VM, Stadler WM, Hoffman PC, Cohen EEW, Connell PP, Haraf DJ, Vokes EE, Hellman S, Weichselbaum RR (2012) Stereotactic body radiotherapy (SBRT) for multi-site extracranial oligometastases: final report of a dose escalation trial in patients with one to five sites of metastatic disease. Cancer (in press)Google Scholar
  40. Singh D, Yi WS, Brasacchio RA, Muhs AG, Smudzin T, Williams JP, Messing E, Okunieff P (2004) Is there a favorable subset of patients with prostate cancer who develop oligometastases? Int J Radiat Oncol Biol Phys 58:3–10PubMedCrossRefGoogle Scholar
  41. Sternberg DI, Sonett JR (2007) Surgical therapy of lung metastases. Semin Oncol 34:186–196PubMedCrossRefGoogle Scholar
  42. Stinauer MA, Kavanagh BD, Schefter TE, Gonzalez R, Flaig T, Lewis K, Robinson W, Chidel M, Glode M, Raben D (2011) Stereotactic body radiation therapy for melanoma and renal cell carcinoma: impact of single fraction equivalent dose on local control. Radiat Oncol 6:34PubMedCrossRefGoogle Scholar
  43. Teh B, Bloch C, Galli-Guevara M, Doh L, Richardson S, Chiang S, Yeh P, Gonzalez M, Lunn W, Marco R, Jac J, Paulino A, Lu H, Butler E, Amato R (2007) The treatment of primary and metastatic renal cell carcinoma (RCC) with image-guided stereotactic body radiation therapy (SBRT). Biomed Imaging Interv J 3:e6PubMedGoogle Scholar
  44. Timmerman RD (2008) An overview of hypofractionation and introduction to this issue of seminars in radiation oncology. Semin Radiat Oncol 18:215–222PubMedCrossRefGoogle Scholar
  45. Timmerman RD, Bizekis CS, Pass HI, Fong Y, Dupuy DE, Dawson LA, Lu D (2009) Local surgical, ablative, and radiation treatment of metastases. CA Cancer J Clin 59:145–170PubMedCrossRefGoogle Scholar
  46. van der Pool AE, Mendez Romero A, Wunderink W, Heijmen BJ, Levendag PC, Verhoef C, Ijzermans JN (2010) Stereotactic body radiation therapy for colorectal liver metastases. Br J Surg 97:377–382PubMedCrossRefGoogle Scholar
  47. Weichselbaum RR, Hellman S (2011) Oligometastases revisited. Nat Rev Clin Oncol 8:378–382PubMedGoogle Scholar
  48. Wersall PJ, Blomgren H, Lax I, Kalkner KM, Linder C, Lundell G, Nilsson B, Nilsson S, Naslund I, Pisa P, Svedman C (2005) Extracranial stereotactic radiotherapy for primary and metastatic renal cell carcinoma. Radiother Oncol 77:88–95PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Department of Radiation OncologyUniversity of RochesterRochesterUSA
  2. 2.Department of Radiation OncologyDuke UniversityDurhamUSA

Personalised recommendations