Neurosurgical management and postoperative whole-brain radiotherapy for colorectal cancer patients with symptomatic brain metastases

  • Giuseppe Aprile
  • Elisa Zanon
  • Francesco Tuniz
  • Emiliana Iaiza
  • Federica De Pauli
  • Nicoletta Pella
  • Stefano Pizzolitto
  • Alberto Buffoli
  • Andrea Piga
  • Miran Skrap
  • Gianpiero Fasola
Original Paper

Abstract

Background

New systemic treatments for advanced colorectal cancer have conferred a survival advantage, allowing patients to reach a median survival of almost 2 years. Due to this remarkable life extension, the incidence of brain metastases, though still low, is progressively increasing over time. There is little reported data on the optimal strategy to manage brain lesions from colorectal cancer.

Methods

To explore the role of an aggressive approach to colorectal cancer brain metastases, we retrospectively collected and analyzed data from 30 patients who underwent neurosurgical resection + whole-brain radiotherapy between March 1998 and December 2006. Univariate (logrank) and multivariate (Cox’s model) analyses were used to identify prognostic factors.

Results

Median age at the time of surgery was 66 years, median ECOG PS was 1, most patients (87%) had concomitant lung and/or liver metastases. Median number of previous chemotherapies was two, with half of the patients being exposed both to oxaliplatin and irinotecan. A median of 27 Gy of radiotherapy were administered to 16 patients after resection. At the time of the analysis, 29 out of 30 patients had died, with a median survival time after brain metastasectomy of 167 days (8–682). Only one patient died within a month from surgery. Median survival was significantly longer in patients who received postsurgical radiotherapy (7.6 vs. 4.7 months, P = 0.014).

Conclusions

Neurosurgical management of symptomatic brain metastases from colorectal cancer is feasible, relatively safe, and offers a chance of prolonged survival. Patients who received radiotherapy after resection experienced a better outcome.

Keywords

Colorectal cancer Brain metastases Radiotherapy Neurosurgery 

References

  1. Adam R, Delvart V, Pascal G, Valenau A, Castaign D, Azoulay D et al (2004) Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg 240:644–657. doi: 10.1097/01.sla.0000145964.08365.01 PubMedCrossRefGoogle Scholar
  2. Amichetti M, Lat G, Dessì M, Orrù S, Farigu R, Orrù P et al (2005) Results of whole brain radiation therapy in patients with brain metastases from colorectal carcinoma. Tumori 91:163–167PubMedGoogle Scholar
  3. Arbit E, Wronsky M, Burt M, Galicich JH (1995) The treatment of patients with recurrent brain metastases. A retrospective analysis of 109 patients with non-small cell lung cancer. Cancer 76:765–773. doi:10.1002/1097-0142(19950901)76:5<765::AID-CNCR2820760509>3.0.CO;2-EPubMedCrossRefGoogle Scholar
  4. Cascino TL, Leavengood JM, Kemeny N, Posner JB (1983) Brain metastases from colorectal carcinoma. J Neurooncol 1:203–209. doi: 10.1007/BF00165604 PubMedCrossRefGoogle Scholar
  5. Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A et al (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351:337–345. doi: 10.1056/NEJMoa033025 PubMedCrossRefGoogle Scholar
  6. Eichler AF, Loeffler JS (2007) Multidisciplinary management of brain metastases. Oncologist 12:884–898. doi: 10.1634/theoncologist.12-7-884 PubMedCrossRefGoogle Scholar
  7. Garden OJ, Rees M, Poston GJ, Mirza D, Saunders M, Ledermann J, Primrose JN, Parks RW (2006) Guidelines for resection of colorectal cancer liver metastases. Gut 55(S3:iii):1–8Google Scholar
  8. Gaspar LE, Scott C, Murray K, Curran W (2000) Validation of the RTOG recursive partitioning analysis (RPA) classification for brain metastases. Int J Radiat Oncol Biol Phys 47:1001–1006. doi: 10.1016/S0360-3016(00)00547-2 PubMedGoogle Scholar
  9. Giantonio BJ, Catalano PJ, Meropol NJ, O’Dwyer PJ, Mitchell EP, Alberts SR et al (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 25:1539–1544. doi: 10.1200/JCO.2006.09.6305 PubMedCrossRefGoogle Scholar
  10. Girard P, Ducreux M, Baldeyrou P, Rougier P, Le Chevalier T, Bougaran J et al (1996) Surgery for lung metastases from colorectal cancer: analysis of prognostic factors. J Clin Oncol 14:2047–2053PubMedGoogle Scholar
  11. Grothey A, Sargent D (2004) Overall survival of patients with advanced colorectal cancer correlates with availability of fluorouracil, irinotecan, and oxaliplatin regardless of whether doublet or single-agent therapy is used in first line. J Clin Oncol 22:1209–1214. doi: 10.1200/JCO.2004.11.037 PubMedCrossRefGoogle Scholar
  12. Grothey A, Sugrue M, Hedrick E, Purdie D, Yi J, Dong W et al (2007) Association between exposure to bevacizumab (BV) beyond first progression (BBP) and overall survival (OS) in patients (pts) with metastatic colorectal cancer (cCRC): results from a large observational study (BRiTE). ASCO Annual meeting proceedings part I. J Clin Oncol 25:4036Google Scholar
  13. Hammoud MA, McCutcehon KM, Elsouki R, Schoppa D, Patt YZ (1996) Colorectal carcinoma and brain metastases: distribution, treatment, and survival. Ann Surg Oncol 3:453–463. doi: 10.1007/BF02305763 PubMedCrossRefGoogle Scholar
  14. Hurwitz H, Fehrebacher L, Novotny W, Cartwright T, Hainsworth J, Heim W et al (2004) Bevacizumab plus irinotecan, fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342. doi: 10.1056/NEJMoa032691 PubMedCrossRefGoogle Scholar
  15. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ (2007) Cancer statistics, 2007. CA Cancer J Clin 57:30–42PubMedCrossRefGoogle Scholar
  16. Jonker DJ, O’Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ et al (2007) Cetuximab for the treatment of colorectal cancer. N Engl J Med 357:2040–2048. doi: 10.1056/NEJMoa071834 PubMedCrossRefGoogle Scholar
  17. Kaal ECA, Niel CGJH, Vecht CJ (2005) Therapeutic management of brain metastases. Lancet Neurol 4:289–298. doi: 10.1016/S1474-4422(05)70072-7 PubMedCrossRefGoogle Scholar
  18. Kelly H, Goldberg R (2005) Systemic therapy for metastatic colorectal cancer: current options, current evidence. J Clin Oncol 20:4553–4560. doi: 10.1200/JCO.2005.17.749 CrossRefGoogle Scholar
  19. Kruser TJ, Chao ST, Elson P, Barnett GH, Vogelbaum MA, Angelov L et al (2008) Multidisciplinary management of colorectal brain metastases: a retrospective study. Cancer 113:158–165. doi: 10.1002/cncr.23531 PubMedCrossRefGoogle Scholar
  20. Mintz A, Perry J, Spithoff K, Chambers A, Laperriere N (2007) Management of single brain metastasis: a practice guideline. Curr Oncol 14:131–143. doi: 10.3747/co.2007.129 PubMedCrossRefGoogle Scholar
  21. Nathoo N, Chahlavi A, Barnett GH, Tomas SA (2005) Pathobiology of brain metastases. J Clin Pathol 58:237–242. doi: 10.1136/jcp.2003.013623 PubMedCrossRefGoogle Scholar
  22. Noordijk EM, Vecht CJ, Haaxma-Reiche H, Padberg GW, Voormolen JH, Hoekstra FH et al (1994) The choice of treatment of single brain metastases should be based on extracranial tumor activity and age. Int J Radiat Oncol Biol Phys 29:711–717PubMedGoogle Scholar
  23. Onodera H, Nagayama S, Tachibana T, Fujimoto A, Imamura M (2005) Brain metastasis from colorectal cancer. Int J Colorectal Dis 20:57–61. doi: 10.1007/s00384-004-0631-3 PubMedCrossRefGoogle Scholar
  24. Patchell RA, Tibbs PA, Regine WF, Dempsey RJ, Mohiuddin M, Kryscio RJ et al (1998) Postoperative radiotherapy in the treatment of single metastasis to the brain: a randomized trial. JAMA 280:1485–1489. doi: 10.1001/jama.280.17.1485 PubMedCrossRefGoogle Scholar
  25. Patchell RA, Regine WF, Loeffler JS, Sawaya R, Andrews DW, Chin LS (2006) Radiosurgery plus whole-brain radiation therapy for brain metastases. JAMA 296:2089–2090. doi: 10.1001/jama.296.17.2089 PubMedCrossRefGoogle Scholar
  26. Pfannschmidt J, Dienemann H, Hoffmann H (2007) Surgical resection of pulmonary metastases from colorectal cancer: a systematic review of published series. Ann Thorac Surg 84:324–328. doi: 10.1016/j.athoracsur.2007.02.093 PubMedCrossRefGoogle Scholar
  27. Soffietti R, Cornu P, Delattre JY, Grant R, Graus F, Grisold W et al (2006) EFNS Guidelines on diagnosis and treatment of brain metastases: report of an EFNS Task Force. Eur J Neurol 13:674–681. doi: 10.1111/j.1468-1331.2006.01506.x PubMedCrossRefGoogle Scholar
  28. Taillibert S, Delattre JY (2005) Palliative care in patients with brain metastases. Curr Opin Oncol 17:588–592. doi: 10.1097/01.cco.0000183673.15133.e2 PubMedCrossRefGoogle Scholar
  29. Van Cutsem E, Nowacki M, Lang I, Cascinu S, Shchepotin I, Maruel J et al (2007a) Randomized phase III trial of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer: the CRYSTAL trial. ASCO Annual meeting proceedings part I. J Clin Oncol 25:4000Google Scholar
  30. Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B et al (2007b) Open-label phase II trial of panitumumav plus best supportive care compared with best supportive care alone in patients with cohemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25:1658–1664. doi: 10.1200/JCO.2006.08.1620 PubMedCrossRefGoogle Scholar
  31. Weinberg JS, Suki D, Hanbali F, Cohen ZR, Lenzi R, Sawaya R (2003) Metastasis of esophageal carcinoma to the brain. Cancer 98:1925–1933. doi: 10.1002/cncr.11737 PubMedCrossRefGoogle Scholar
  32. Weiss L, Grundmann E, Torhorst J, Hartveit F, Moberg I, Eder M et al (1986) Hematogenous metastatic patterns in colonic carcinoma: an analysis of 1541 necroscopies. J Pathol 150:195–203. doi: 10.1002/path.1711500308 PubMedCrossRefGoogle Scholar
  33. Wronski M, Arbit E (1999) Resection of brain metastases from colorectal carcinoma in 73 patients. Cancer 85:1677–1685. doi:10.1002/(SICI)1097-0142(19990415)85:8<1677::AID-CNCR6>3.0.CO;2-CPubMedCrossRefGoogle Scholar
  34. York JE, Striger J, Ajani JA, Wildrick DM, Gokaslan ZL (1999) Gastric cancer and metastasis to the brain. Ann Surg Oncol 6:771–776. doi: 10.1007/s10434-999-0771-3 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Giuseppe Aprile
    • 1
  • Elisa Zanon
    • 1
  • Francesco Tuniz
    • 1
  • Emiliana Iaiza
    • 1
  • Federica De Pauli
    • 1
  • Nicoletta Pella
    • 1
  • Stefano Pizzolitto
    • 1
  • Alberto Buffoli
    • 1
  • Andrea Piga
    • 1
  • Miran Skrap
    • 1
  • Gianpiero Fasola
    • 1
  1. 1.University Hospital of UdineUdineItaly

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