Therapy and prophylaxis of brain metastases

Expert Review of Anticancer Therapy

Volumn 10, Issue 11, 2010, Pages 1763-1777

  Kienast, Yvonne ^a   Winkler, Frank ^b  

^a ROCHE DIAGNOSTICS GMBH   (Germany)

^b UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

Author keywords

angiogenesis; brain; CNS; dormancy; metastases; molecular targeted therapy; prophylaxis; radiosurgery; surgery; therapy

Indexed keywords

ANGIOGENESIS INHIBITOR; ANTICONVULSIVE AGENT; ANTINEOPLASTIC AGENT; BEVACIZUMAB; CHEMOKINE; CHEMOKINE RECEPTOR CXCR4; CORTICOSTEROID; DEXAMETHASONE; EFAPROXIRAL; EPIDERMAL GROWTH FACTOR; EPIDERMAL GROWTH FACTOR RECEPTOR; ERLOTINIB; GADOLINIUM; GEFITINIB; LAPATINIB; MONOCLONAL ANTIBODY; PROTEIN TYROSINE KINASE INHIBITOR; RADIOSENSITIZING AGENT; SORAFENIB; SUNITINIB; TEMOZOLOMIDE; THALIDOMIDE; TOPOTECAN; TRASTUZUMAB; VARDENAFIL; VASCULOTROPIN A;

ALGORITHM; BLOOD BRAIN BARRIER; BRAIN EDEMA; BRAIN METASTASIS; CANCER CELL; CANCER CONTROL; CANCER RADIOTHERAPY; CANCER SURGERY; CLINICAL PRACTICE; COMPUTER ASSISTED TOMOGRAPHY; DISTANT METASTASIS; DRUG EFFICACY; DRUG SAFETY; DRUG SUBSTITUTION; DRUG WITHDRAWAL; HUMAN; LOW DRUG DOSE; MOLECULARLY TARGETED THERAPY; MULTIMODALITY CANCER THERAPY; NEUROSURGERY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PRACTICE GUIDELINE; PRIMARY TUMOR; PROGNOSIS; RADIOSURGERY; REVIEW; SEIZURE; STEREOTACTIC RADIOSURGERY; SURVIVAL RATE; SURVIVAL TIME; TREATMENT INDICATION; TREATMENT OUTCOME; UNSPECIFIED SIDE EFFECT; WHOLE BRAIN RADIATION THERAPY;

BRAIN NEOPLASMS; HUMANS;

EID: 78649264510     PISSN: 14737140     EISSN: 17448328     Source Type: Journal    
DOI: 10.1586/era.10.165     Document Type: Review

References (150)

1. Gavrilovic IT, Posner JB. Brain metastases: epidemiology and pathophysiology. J. Neurooncol. 75(1), 5-14 (2005).
2. Fidler IJ, Yano S, Zhang RD, Fujimaki T, Bucana CD. The seed and soil hypothesis: vascularisation and brain metastases. Lancet Oncol. 3(1), 53-57 (2002).
3. Bos PD, Zhang XH, Nadal C et al. Genes that mediate breast cancer metastasis to the brain. Nature 459(7249), 1005-1009 (2009).
4. Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nat. Rev. Cancer 2(8), 563-572 (2002). • Excellent overview detailing the metastatic cascade.
5. Kienast Y, von Baumgarten L, Fuhrmann M et al. Real-time imaging reveals the single steps of brain metastasis formation. Nat. Med. 16(1), 116-122 (2010). • First study to monitor the single steps of brain metastasis in real time.
6. Hwang TL, Close TP, Grego JM, Brannon WL, Gonzales F. Predilection of brain metastasis in gray and white matter junction and vascular border zones. Cancer 77(8), 1551-1555 (1996).
7. Delattre JY, Krol G, Thaler HT, Posner JB. Distribution of brain metastases. Arch. Neurol. 45(7), 741-744 (1988).
8. Chamberlain MC. Anticancer therapies and CNS relapse: overcoming blood-brain and blood-cerebrospinal fuid barrier impermeability. Expert Rev. Neurother. 10(4), 547-561 (2010).
9. Takeshima H, Kuratsu J, Nishi T, Ushio Y. Prognostic factors in patients who survived more than 10 years after undergoing surgery for metastatic brain tumors: report of 5 cases and review of the literature. Surg. Neurol. 58(2), 118-123 (2002).
10. Patch ell RA, Tibbs PA, Walsh JW et al A randomized trial of surgery in the treatment of single metastases to the brain. N. Engl. J. Med. 322(8), 494-500 (1990). • Study to establish surgical resection in addition to whole-brain radiation therapy (WBRT) as standard treatment for a single brain metastasis.
11. Patel RR, Mehta MP. Targeted therapy for brain metastases: improving the therapeutic ratio. Clin. Cancer Res. 13(6), 1675-1683 (2007).
12. Chamberlain MC. Brain metastases: a medical neuro-oncology perspective. Expert Rev. Neurother. 10(4), 563-573 (2010).
13. Johnson JD, Young B. Demographics of brain metastasis. Neurosurg Clin. N. Am. 7(3), 337-344 (1996).
14. Sundermeyer M, Meropol N, Rogatko A et al. Changing patterns of colorectal metastasis: a 10-year retrospective review. J. Clin. Oncol. 22 (Suppl. 14) (2004) (Abstract 3548).
15. Shmueli E, Wigler N, Inbar M. Central nervous system progression among patients with metastatic breast cancer responding to trastuzumab treatment. Eur. J. Cancer 40(3), 379-382 (2004).
16. Omuro AM, Kris MG, Miller VA et al High incidence of disease recurrence in the brain and leptomeninges in patients with nonsmall cell lung carcinoma after response to geftinib. Cancer 103(11), 2344-2348 (2005).
17. Palmieri D, Chambers AF, Felding-Habermann B, Huang S, Steeg PS. The biology of metastasis to a sanctuary site. Clin. Cancer Res. 13(6), 1656-1662 (2007). • Review of brain metastases and the brain as a pharmacological sanctuary site.
18. Gaspar L, Scott C, Rotman M et al Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int. J. Radiat. Oncol. Biol Phys. 37(4), 745-751 (1997).
19. Sperduto PW, Berkey B, Gaspar LE, Mehta M, Curran W. A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1, 960 patients in the RTOG database. Int. J. Radiat. Oncol. Biol. Phys. 70(2), 510-514 (2008). • A new prognostic score, adding the number of brain metastases to the already known prognostic factors.
20. Lagerwaard FJ, Levendag PC. Prognostic factors in patients with brain metastases. Forum (Genova) 11(1), 27-46 (2001).
21. Altundag K, Bondy ML, Mirza NQ et al Clinicopathologic characteristics and prognostic factors in 420 metastatic breast cancer patients with central nervous system metastasis. Cancer 110(12), 2640-2647 (2007). • Large retrospective study analyzing prognostic factors among patients with breast cancer and brain metastases.
22. Grinberg-Rashi H, Ofek E, Perelman M et al. The expression of three genes in primary non-small cell lung cancer is associated with metastatic spread to the brain. Clin. Cancer Res. 15(5), 1755-1761 (2009).
23. Gabos Z, Sinha R, Hanson J et al Prognostic significance of human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer. J. Clin. Oncol. 24(36), 5658-5663 (2006).
24. Pestalozzi BC, Zahrieh D, Price KN et al. Identifying breast cancer patients at risk for central nervous system (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG). Ann. Oncol. 17(6), 935-944 (2006).
25. Lin NU, Claus E, Sohl J, Razzak AR, Arnaout A, Winer EP. Sites of distant recurrence and clinical outcomes in patients with metastatic triple-negative breast cancer: high incidence of central nervous system metastases. Cancer 113(10), 2638-2645 (2008).
26. Lorger M, Krueger JS, O'Neal M, Staflin K, Felding-Habermann B. Activation of tumor cell integrin a v b3 controls angiogenesis and metastatic growth in the brain. Proc. Natl Acad. Sci. USA 106(26), 10666-10671 (2009).
27. Muller A, Homey B, Soto H et al Involvement of chemokine receptors in breast cancer metastasis. Nature 410(6824), 50-56 (2001).
28. Zlotnik A. Chemokines in neoplastic progression. Semin. Cancer Biol. 14(3), 181-185 (2004).
29. Chamberlain MC. Anticancer therapies and CNS relapse: overcoming blood-brain and blood-cerebrospinal fuid barrier impermeability. Expert Rev. Neurother. 10(4), 547-561 (2010).
30. Khuntia D, Brown P, Li J, Mehta MP. Whole-brain radiotherapy in the management of brain metastasis. J. Clin. Oncol. 24(8), 1295-1304 (2006). • Current state of the art of the role of WBRT brain metastasis treatment.
31. Patchell RA. The management of brain metastases. Cancer Treat. Rev. 29(6), 533-540 (2003).
32. Kurtz JM, Gelber R, Brady LW, Carella RJ, Cooper JS. The palliation of brain metastases in a favorable patient population: a randomized clinical trial by the Radiation Therapy Oncology Group. Int. J. Radiat. Oncol. Biol. Phys. 7(7), 891-895 (1981).
33. Murray KJ, Scott C, Greenberg HM et al. A randomized Phase III study of accelerated hyper fractionation versus standard in patients with unresected brain metastases: a report of the Radiation Therapy Oncology Group (RTOG) 9104. Int. J. Radiat. Oncol. Biol. Phys. 39(3), 571-574 (1997). • Phase III trial of WBRT in brain metastases.
34. Chatani M, Matayoshi Y, Masaki N, Inoue T. Radiation therapy for brain metastases from lung carcinoma. Prospective randomized trial according to the level of lactate dehydrogenase. Strahlenther. Onkol. 170(3), 155-161 (1994).
35. Gaspar LE, Mehta MP, Patchell RA et al. The role of whole brain radiation therapy in the management of newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline. J. Neurooncol. 96(1), 17-32 (2010).
36. Nieder C, Berberich W, Schnabel K. Tumor-related prognostic factors for remission of brain metastases after radiotherapy Int. J. Radiat. Oncol. Biol Phys. 39(1), 25-30 (1997).
37. Bentzen SM, Trotti A. Evaluation of early and late toxicities in chemoradiation trials. J. Clin. Oncol. 25(26), 4096-4103 (2007).
38. Scott C, Suh J, Stea B, Nabid A, Hackman J. Improved survival, quality of life, and quality-adjusted survival in breast cancer patients treated with efaproxiral (Efaproxyn) plus whole-brain radiation therapy for brain metastases. Am. J. Clin. Oncol. 30(6), 580-587 (2007).
39. Mehta MP, Rodrigus P, Terhaard CH et al Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases. J. Clin. Oncol. 21(13), 2529-2536 (2003). • Large randomized prospective Phase III study of WBRT with or without motexafn gadolinium (a radiosensitizer).
40. Hedde JP, Neuhaus T, Schuller H et al A Phase I/II trial of topotecan and radiation therapy for brain metastases in patients with solid tumors. Int. J. Radiat. Oncol. Biol. Phys. 68(3), 839-844 (2007). • Trial preliminarily suggesting a potential efficacy of topotecan as a radiosensitizer in brain metastases.
41. Mikkelsen T, Paleologos NA, Robinson PD et al. The role of prophylactic anticonvulsants in the management of brain metastases: a systematic review and evidence-based clinical practice guideline. J. Neurooncol. 96(1), 97-102 (2010).
42. Bromfeld EB. Epilepsy in patients with brain tumors and other cancers. Rev. Neurol. Dis. 1 (Suppl. 1), S27-S33 (2004).
43. Ranjan T, Abrey LE. Current management of metastatic brain disease. Neurotherapeutics 6(3), 598-603 (2009).
44. Noordijk EM, Vecht CJ, Haaxma-Reiche H et al. The choice of treatment of single brain metastasis should be based on extracranial tumor activity and age. Int. J. Radiat. Oncol. Biol. Phys. 29(4), 711-717 (1994). • Study reflecting the importance of control of extracranial metastasis prior to successful management of brain metastasis.
45. Al Shamy G, Sawaya R. Management of brain metastases: the indispensable role of surgery J. Neurooncol. 92(3), 275-282 (2009).
46. Kalkanis SN, Kondziolka D, Gaspar LE et al. The role of surgical resection in the management of newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline. J. Neurooncol. 96(1), 33-43 (2010).
47. Manon R, O'Neill A, Knisely J et al. Phase II trial of radiosurgery for one to three newly diagnosed brain metastases from renal cell carcinoma, melanoma, and sarcoma: an Eastern Cooperative Oncology Group study (E 6397). J. Clin. Oncol. 23(34), 8870-8876 (2005).
48. Wronski M, Maor MH, Davis BJ, Sawaya R, Levin VA. External radiation of brain metastases from renal carcinoma: a retrospective study of 119 patients from the M. D. Anderson Cancer Center. Int. J. Radiat. Oncol. Biol. Phys. 37(4), 753-759 (1997).
49. Mori Y, Kondziolka D, Flickinger JC, Kirkwood JM, Agarwala S, Lunsford LD. Stereotactic radiosurgery for cerebral metastatic melanoma: factors affecting local disease control and survival. Int. J. Radiat. Oncol. Biol. Phys. 42(3), 581-589 (1998).
50. Mori Y, Kondziolka D, Flickinger JC, Logan T, Lunsford LD. Stereotactic radiosurgery for brain metastasis from renal cell carcinoma. Cancer 83(2), 344-353 (1998).
51. Hart MG, Grant R, Walker M, Dickinson H. Surgical resection and whole brain radiation therapy versus whole brain radiation therapy alone for single brain metastases. Cochrane Database Syst. Rev. 1, CD003292 (2005).
52. Vecht CJ, Haaxma-Reiche H, Noordijk EM et al. Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery? Ann. Neurol. 33(6), 583-590 (1993).
53. Mintz AH, Kestle J, Rathbone MP et al. A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis. Cancer 78(7), 1470-1476 (1996).
54. Bindal RK, Sawaya R, Leavens ME, Lee JJ. Surgical treatment of multiple brain metastases. J. Neurosurg. 79(2), 210-216 (1993).
55. Swinson BM, Friedman WA. Linear accelerator stereotactic radiosurgery for metastatic brain tumors: 17 years of experience at the University of Florida. Neurosurgery 62(5), 1018-1031 (2008). • Large and robust prospective data analysis involving stereotactic radiosurgery for brain metastases.
56. Suh JH. Stereotactic radiosurgery for the management of brain metastases. N Engl J. Med. 362(12), 1119-1127 (2010).
57. Maldaun MV, Aguiar PH, Lang F, Suki D, Wildrick D, Sawaya R. Radiosurgery in the treatment of brain metastases: critical review regarding complications. Neurosurg Rev. 31(1), 1-8 (2008).
58. Muacevic A, Wowra B, Siefert A, Tonn JC, Steiger HJ, Kreth FW Microsurgery plus whole brain irradiation versus gamma knife surgery alone for treatment of single metastases to the brain: a randomized controlled multicentre Phase III trial. J. Neurooncol. 87(3), 299-307 (2008).
59. Bindal AK, Bindal RK, Hess KR et al. Surgery versus radiosurgery in the treatment of brain metastasis. J. Neurosurg 84(5), 748-754 (1996).
60. Andrews DW, Scott CB, Sperduto PW et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: Phase III results of the RTOG 9508 randomised trial. Lancet 363(9422), 1665-1672 (2004). • Established the role of a stereotactic boost after WBRT for patients with one to three brain metastases.
61. Kondziolka D, Patel A, Lunsford LD, Kassam A, Flickinger JC. Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int. J. Radiat. Oncol. Biol. Phys. 45(2), 427-434 (1999).
62. Chougule PB, Burton-Williams M, Saris S et al. Randomized treatment of brain metastasis with gamma knife radiosurgery, whole brain radiotherapy or both. Int. J. Radiat. Oncol. Biol. Phys. 48 (Suppl. 3), 114(2000).
63. O'Neill BP, Iturria NJ, Link MJ, Pollock BE, Ballman K V, O'Fallon JR. A comparison of surgical resection and stereotactic radiosurgery in the treatment of solitary brain metastases. Int. J. Radiat. Oncol. Biol. Phys. 55(5), 1169-1176 (2003).
64. Rades D, Kueter JD, Veninga T, Gliemroth J, Schild SE. Whole brain radiotherapy plus stereotactic radiosurgery (WBRT+SRS) versus surgery plus whole brain radiotherapy (OP+WBRT) for 1-3 brain metastases: results of a matched pair analysis. Eur. J. Cancer 45(3), 400-404 (2009).
65. Suh JH. Stereotactic radiosurgery for the management of brain metastases. N. Engl. J. Med. 362(12), 1119-1127 (2010).
66. Roberge D, Petrecca K, El Refae M, Souhami L. Whole-brain radiotherapy and tumor bed radiosurgery following resection of solitary brain metastases. J. Neurooncol. 95(1), 95-99 (2009).
67. Kim PK, Ellis TL, Stieber VW et al. Gamma knife surgery targeting the resection cavity of brain metastasis that has progressed after whole-brain radiotherapy. J. Neurosurg. 105 (Suppl.), 75-78 (2006).
68. Iwai Y, Yamanaka K, Yasui T. Boost radiosurgery for treatment of brain metastases after surgical resections. Surg. Neurol. 69(2), 181-186 (2008).
69. Soltys SG, Adler JR, Lipani JD et al. Stereotactic radiosurgery of the postoperative resection cavity for brain metastases. Int. J. Radiat. Oncol. Biol. Phys 70(1), 187-193 (2008).
70. Mathieu D, Kondziolka D, Flickinger JC et al. Tumor bed radiosurgery after resection of cerebral metastases. Neurosurgery 62(4), 817-823 (2008).
71. Do L, Pezner R, Radany E, Liu A, Staud C, Badie B. Resection followed by stereotactic radiosurgery to resection cavity for intracranial metastases. Int. J. Radiat. Oncol. Biol. Phys. 73(2), 486-491 (2009).
72. Limbrick DD Jr, Lusis EA, Chicoine MR et al. Combined surgical resection and stereotactic radiosurgery for treatment of cerebral metastases. Surg. Neurol. 71(3), 280-288 (2009).
73. Patchell RA, Tibbs PA, Regine WF et al. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA 280(17), 1485-1489 (1998). • Randomized study that established the role of adjuvant WBRT for brain metastases.
74. Aoyama H, Shirato H, Tago M et al. Stereotactic radiosurgery plus wholebrain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA 295(21), 2483-2491 (2006).
75. Chang EL, Wefel JS, Hess KR et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 10(11), 1037-1044 (2009). • First study analyzing neurocognitive function in patients with brain metastases and WBRT treatment.
76. Meyers CA, Smith JA, Bezjak A et al. Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafn gadolinium: results of a randomized Phase III trial. J. Clin. Oncol. 22(1), 157-165 (2004).
77. Aoyama H, Tago M, Kato N et al. Neurocognitive function of patients with brain metastasis who received either whole brain radiotherapy plus stereotactic radiosurgery or radiosurgery alone. Int. J. Radiat. Oncol. Biol. Phys. 68(5), 1388-1395 (2007).
78. Regine WF, Huhn JL, Patchell RA et al. Risk of symptomatic brain tumor recurrence and neurologic defcit after radiosurgery alone in patients with newly diagnosed brain metastases: results and implications. Int. J. Radiat. Oncol. Biol. Phys. 52(2), 333-338 (2002).
79. Mueller RP, Soffetti R, Abacioglu MU et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of 1-3 cerebral metastases: results of the EORTC 22952-26001 study. Presented at: 2009 ASCO Annual Meeting. FL, USA, 29 May-2 June 2009. • Prospective results on the combination of WBRT with local treatment (surgery or stereotactic radiosurgery), including their impact on local control, neurologic symptoms and survival.
80. Mehta MP, Paleologos NA, Mikkelsen T et al. The role of chemotherapy in the management of newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline. J. Neurooncol. 96(1), 71-83 (2010).
81. Peereboom DM. Chemotherapy in brain metastases. Neurosurgery 57 (5 Suppl.), S54-S65 (2005).
82. Knisely JP, Berkey B, Chakravarti A et al. A Phase III study of conventional radiation therapy plus thalidomide versus conventional radiation therapy for multiple brain metastases (RTOG 0118). Int. J. Radiat. Oncol. Biol. Phys. 71(1), 79-86 (2008).
83. Quantin X, Bozonnat MC, Pujol JL. Recursive Partitioning Analysis Groups II-III brain metastases of non-small cell lung cancer: a Phase II randomized study comparing two concurrent chemoradiotherapy regimens. J. Thorac. Oncol. 5(6), 846-851 (2010).
84. Gerstner ER, Fine RL. Increased permeability of the blood-brain barrier to chemotherapy in metastatic brain tumors: establishing a treatment paradigm. J. Clin. Oncol. 25(16), 2306-2312 (2007). • Critical review analyzing the problem of permeability of the blood-brain barrier to different antineoplastic drugs.
85. Weller M, Steinbach JP, Wick W Temozolomide: a milestone in the pharmacotherapy of brain tumors. Future Oncol. 1(6), 747-754 (2005).
86. Antonadou D, Paraskevaidis M, Sarris G et al. Phase II randomized trial of temozolomide and concurrent radiotherapy in patients with brain metastases. J. Clin. Oncol. 20(17), 3644-3650 (2002).
87. Chua D, Krzakowski M, Chouaid C et al. Whole-brain radiation therapy plus concomitant temozolomide for the treatment of brain metastases from non-small-cell lung cancer: a randomized, open-label Phase II study. Clin. Lung Cancer 11(3), 176-181 (2010).
88. Mikkelsen T, Anderson J, Doyle TJ et al. Phase I/II dose escalation trial of concurrent temozolomide and whole brain radiation therapy for multiple brain metastasis. J. Neurooncol. DOI: 10.1007/s11060-010-0187-8 (2010) (Epub ahead of print). • Highlights the emerging role of targeted therapy in the treatment of brain metastases.
89. Schild SE, Behl D, Markovic SN et al. Brain metastases from melanoma: is there a role for concurrent temozolomide in addition to whole brain radiation therapy? Am. J. Clin. Oncol. DOI: 10.1097/COC.0b013e3181c4c54b (2009) (Epub ahead of print).
90. Olson JJ, Paleologos NA, Gaspar LE et al. The role of emerging and investigational therapies for metastatic brain tumors: a systematic review and evidence-based clinical practice guideline of selected topics. J. Neurooncol. 96(1), 115-142 (2010).
91. Ferber D. Bridging the blood-brain barrier: new methods improve the odds of getting drugs to the brain cells that need them. PLoS Biol. 5(6), e169 (2007).
92. Aguirre-Ghiso JA. Models, mechanisms and clinical evidence for cancer dormancy. Nat. Rev. Cancer 7(11), 834-846 (2007).
93. Lin NU, Winer EP. Brain metastases: the HER2 paradigm. Clin. Cancer Res. 13(6), 1648-1655 (2007). • Excellent overview detailing the HER2 paradigm, with implications for clinical practice and future research.
94. Lin NU, Carey LA, Liu MC et al. Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer. J. Clin. Oncol. 26(12), 1993-1999 (2008).
95. Slamon DJ, Leyland-Jones B, Shak S et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med. 344(11), 783-792 (2001).
96. Romond EH, Perez EA, Bryant J et al Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N. Engl. J. Med. 353(16), 1673-1684 (2005).
97. Leyland-Jones B. Human epidermal growth factor receptor 2-positive breast cancer and central nervous system metastases. J. Clin. Oncol. 27(31), 5278-5286 (2009).
98. Hu J, Ljubimova JY, Inoue S et al. Phosphodiesterase type 5 inhibitors increase Herceptin transport and treatment efficacy in mouse metastatic brain tumor models. PLoS ONE 5(4), e10108 (2010).
99. Krop IE, Beeram M, Modi S et al. Phase I study of trastuzumab-DM1, an HER2 antibody-drug conjugate, given every 3 weeks to patients with HER2-positive metastatic breast cancer. J. Clin. Oncol 28(16), 2698-2704 (2010).
100. Polli JW, Olson KL, Chism JP et al An unexpected synergist role of P-glycoprotein and breast cancer resistance protein on the central nervous system penetration of the tyrosine kinase inhibitor lapatinib (N-{3-chloro-4-[(3-fluorobenzyl) oxy]phenyl}-6-[5-({[2-(methylsulfonyl) ethyl]amino }methyl)-2-furyl]-4-quinazolinamine; GW572016). Drug Metab. Dispos. 37(2), 439-442 (2009).
101. Cameron D, Casey M, Press M et al. A Phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res. Treat. 112(3), 533-543 (2008).
102. Geyer CE, Forster J, Lindquist D et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N. Engl. J. Med. 355(26), 2733-2743 (2006).
103. Gril B, Palmieri D, Bronder JL et al. Effect of lapatinib on the outgrowth of metastatic breast cancer cells to the brain. J. Natl Cancer Inst. 100(15), 1092-1103 (2008).
104. Fukuoka M, Yano S, Giaccone G et al. Multi-institutional randomized Phase II trial of geftinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected]. J. Clin. Oncol. 21(12), 2237-2246 (2003).
105. Kris MG, Natale RB, Herbst RS et al. Efficacy of geftinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA 290(16), 2149-2158 (2003).
106. Ceresoli GL, Cappuzzo F, Gregorc V, Bartolini S, Crino L, Villa E. Gefitinib in patients with brain metastases from non-small-cell lung cancer: a prospective trial. Ann. Oncol. 15(7), 1042-1047 (2004).
107. Chiu CH, Tsai CM, Chen YM, Chiang SC, Liou JL, Perng R P. Gefitinib is active in patients with brain metastases from non-small cell lung cancer and response is related to skin toxicity. Lung Cancer 47(1), 129-138 (2005).
108. Wu C, Li YL, Wang ZM, Li Z, Zhang TX, Wei Z. Gefitinib as palliative therapy for lung adenocarcinoma metastatic to the brain. Lung Cancer 57(3), 359-364 (2007).
109. Shimato S, Mitsudomi T, Kosaka T et al. EGFR mutations in patients with brain metastases from lung cancer: association with the efficacy of geftinib. Neuro. Oncol. 8(2), 137-144 (2006).
110. Hirsch FR, Herbst RS, Olsen C et al. Increased EGFR gene copy number detected by fluorescent in situ hybridization predicts outcome in non-small-cell lung cancer patients treated with cetuximab and chemotherapy J. Clin. Oncol. 26(20), 3351-3357 (2008).
111. Katayama T, Shimizu J, Suda K et al. Efficacy of erlotinib for brain and leptomeningeal metastases in patients with lung adenocarcinoma who showed initial good response to geftinib. J. Thorac. Oncol 4(11), 1415-1419 (2009). • Report on the effectiveness of erlotinib for the treatment of CNS lesions after geftinib failure.
112. Yano S, Shinohara H, Herbst RS et al. Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis. Cancer Res. 60(17), 4959-4967 (2000).
113. Hurwitz H, Fehrenbacher L, Novotny W et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N. Engl. J. Med. 350(23), 2335-2342 (2004).
114. Escudier B, Pluzanska A, Koralewski P et al. Bevacizumab plus interferon a-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind Phase III trial. Lancet 370(9605), 2103-2111 (2007).
115. Miller K, Wang M, Gralow J et al Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N. Engl. J. Med. 357(26), 2666-2676 (2007).
116. Sandler A, Gray R, Perry MC et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N. Engl. J. Med. 355(24), 2542-2550 (2006).
117. Johnson DH, Fehrenbacher L, Novotny WF et al. Randomized Phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-smallcell lung cancer. J. Clin. Oncol. 22(11), 2184-2191 (2004).
118. Van Meir EG, Hadjipanayis CG, Norden AD, Shu HK, Wen PY, Olson JJ. Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA Cancer J. Clin. 60(3), 166-193 (2010).
119. Gordon MS, Margolin K, Talpaz M et al Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J. Clin. Oncol. 19(3), 843-850 (2001).
120. Socinski MA, Langer CJ, Huang JE et al. Safety of bevacizumab in patients with non-small-cell lung cancer and brain metastases. J. Clin. Oncol. 27(31), 5255-5261 (2009).
121. Besse B, Lasserre SF, Compton P, Huang J, Augustus S, Rohr UP. Bevacizumab safety in patients with central nervous system metastases. Clin. Cancer Res. 16(1), 269-278 (2010).
122. Labidi SI, Bachelot T, Ray-Coquard I et al Bevacizumab and paclitaxel for breast cancer patients with central nervous system metastases: a case series. Clin. Breast Cancer. 9(2), 118-121 (2009).
123. Novello O, Abrey LE, Grossi F. Administration of sunitinib to patients with nonsmall cell lung cancer and irradiated brain metastases: a Phase II trial. J. Clin. Oncol. 27 (15 Suppl.) (2009) (Abstract 8077). • Trial using sunitinib, which was shown to have activity in brain metastases and was well tolerated.
124. Gendron RL. A plasticity for blood vessel remodeling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF. Surv. Ophthalmol. 44(2), 184-185 (1999).
125. Hellberg C, Ostman A, Heldin CH. PDGF and vessel maturation. Recent Results Cancer Res. 180, 103-114 (2010).
126. Shikada Y, Yonemitsu Y, Koga T et al Platelet-derived growth factor-AA is an essential and autocrine regulator of vascular endothelial growth factor expression in non-small cell lung carcinomas. Cancer Res. 65(16), 7241-7248 (2005).
127. Potapova O, Laird AD, Nannini MA et al Contribution of individual targets to the antitumor efficacy of the multitargeted receptor tyrosine kinase inhibitor SU11248. Mol Cancer Ther. 5(5), 1280-1289 (2006).
128. Hasumi Y, Klosowska-Wardega A, Furuhashi M, Ostman A, Heldin CH, Hellberg C. Identification of a subset of pericytes that respond to combination therapy targeting PDGF and VEGF signaling. Int. J. Cancer 121(12), 2606-2614 (2007).
129. Bergers G, Song S, Meyer-Morse N, Bergsland E, Hanahan D. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J. Clin. Invest. 111(9), 1287-1295 (2003).
130. Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307(5706), 58-62 (2005).
131. Bergers G, Hanahan D. Modes of resistance to anti-angiogenic therapy. Nat. Rev. Cancer 8(8), 592-603 (2008). • Excellent review describing modes of resistance to antiangiogenic therapies.
132. Ebos JM, Lee CR, Cruz-Munoz W, Bjarnason GA, Christensen JG, Kerbel RS. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 15(3), 232-239 (2009).
133. Paez-Ribes M, Allen E, Hudock J et al Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 15(3), 220-231 (2009).
134. Massard C, Zonierek J, Gross-Goupil M, Fizazi K, Szczylik C, Escudier B. Incidence of brain metastases in renal cell carcinoma treated with sorafenib. Ann. Oncol. 21(5), 1027-1031 (2010).
135. Lamszus K, Brockmann MA, Eckerich C et al. Inhibition of glioblastoma angiogenesis and invasion by combined treatments directed against vascular endothelial growth factor receptor-2, epidermal growth factor receptor, and vascular endothelial-cadherin. Clin. Cancer Res. 11(13), 4934-4940 (2005).
136. Slotman B, Faivre-Finn C, Kramer G et al Prophylactic cranial irradiation in extensive small-cell lung cancer. N. Engl. J. Med. 357(7), 664-672 (2007).
137. Blanchard P, Le Pechoux C. Prophylactic cranial irradiation in lung cancer. Curr. Opin. Oncol. 22(2), 94-101 (2010).
138. Auperin A, Arriagada R, Pignon JP et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N. Engl. J. Med. 341(7), 476-484 (1999). • Meta-analysis demonstrating a survival advantage to prophylactic cranial irradiation in patients with small-cell lung cancer that have achieved a complete remission.
139. Laplanche A, Monnet I, Santos-Miranda JA et al. Controlled clinical trial of prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Lung Cancer 21(3), 193-201 (1998).
140. Arriagada R, Le Chevalier T, Borie F et al Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. J. Natl Cancer Inst. 87(3), 183-190 (1995). • Prospective randomized controlled trial of prophylactic cranial irradiation demonstrating that after 2 years no decline in neuropsychologic function could be observed.
141. Le Pechoux C, Dunant A, Senan S et al. Standard-dose versus higherdose prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer in complete remission after chemotherapy and thoracic radiotherapy (PCI 99-01, EORTC 22003-08004, RTOG 0212, and IFCT 99-01): a randomised clinical trial. Lancet Oncol. 10(5), 467-474 (2009). • Dose and fractionation randomized study for prophylactic cranial irradiation: 25 Gy remains the standard of care.
142. Topkan E, Yildirim BA, Selek U, Yavuz MN. Cranial prophylactic irradiation in locally advanced non-small cell lung carcinoma: current status and future perspectives. Oncology 76(3), 220-228 (2009).
143. Huang F, Alrefae M, Langleben A, Roberge D. Prophylactic cranial irradiation in advanced breast cancer: a case for caution. Int. J. Radiat. Oncol. Biol. Phys. 73(3), 752-758 (2009).
144. Slotman BJ, Mauer ME, Bottomley A et al. Prophylactic cranial irradiation in extensive disease small-cell lung cancer: short-term health-related quality of life and patient reported symptoms: results of an international Phase III randomized controlled trial by the EORTC Radiation Oncology and Lung Cancer Groups. J. Clin. Oncol. 27(1), 78-84 (2009). • Evaluation of quality of life and the role of prophylactic cranial irradiation in patients with extensive disease small-cell lung cancer responding to chemotherapy.
145. Winkler F, Kozin SV, Tong RT et al Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell 6(6), 553-563 (2004). • First study to provide preclinical proof of the normalization concept.
146. Therasse P, Eisenhauer EA, Verweij J. RECIST revisited: a review of validation studies on tumour assessment. Eur. J. Cancer 42(8), 1031-1039 (2006).
147. van't Veer LJ, Dai H, van de Vijver MJ et al. Gene expression profling predicts clinical outcome of breast cancer. Nature 415(6871), 530-536 (2002).
148. Sneed PK, Suh JH, Goetsch SJ et al. A multi-institutional review of radiosurgery alone vs. radiosurgery with whole brain radiotherapy as the initial management of brain metastases. Int. J. Radiat. Oncol. Biol. Phys. 53(3), 519-526 (2002).
149. Agboola O, Benoit B, Cross P et al. Prognostic factors derived from recursive partition analysis (RPA) of Radiation Therapy Oncology Group (RTOG) brain metastases trials applied to surgically resected and irradiated brain metastatic cases. Int. J. Radiat. Oncol. Biol. Phys. 42(1), 155-159 (1998).
150. Diener H, Putzki N. Leitlinien für Diagnostik und Therapie in der Neurologie. Georg Thieme Verlag, Stuttgart, Germany, 654 ff (2008).