Skip to main content
Erschienen in: Current Treatment Options in Oncology 9/2016

01.09.2016 | Neuro-oncology (GJ Lesser, Section Editor)

Controversies in the Therapy of Brain Metastases: Shifting Paradigms in an Era of Effective Systemic Therapy and Longer-Term Survivorship

verfasst von: Colette J. Shen, MD, PhD, Michael Lim, MD, Lawrence R. Kleinberg, MD

Erschienen in: Current Treatment Options in Oncology | Ausgabe 9/2016

Einloggen, um Zugang zu erhalten

Opinion statement

With the development of therapies that improve extracranial disease control and increase long-term survival of patients with metastatic cancer, effective treatment of brain metastases while minimizing toxicities is becoming increasingly important. An expanding arsenal that includes surgical resection, whole brain radiation therapy, radiosurgery, and targeted systemic therapy provides multiple treatment options. However, significant controversies still exist surrounding appropriate use of each modality in various clinical scenarios and patient populations in the context of cancer care strategies that control systemic disease for increasingly longer periods of time. While whole brain radiotherapy alone is still a reasonable and standard option for patients with multiple metastases, several randomized trials have now revealed that survival is maintained in patients treated with radiosurgery or surgery alone, without upfront whole brain radiotherapy, for up to four brain metastases. Indeed, recent data even suggest that patients with up to 10 metastases can be treated with radiosurgery alone without a survival detriment. In an era of dramatic advances in targeted and immune therapies that control systemic disease and improve survival but may not penetrate the brain, more consideration should be given to brain metastasis-directed treatments that minimize long-term neurocognitive deficits, while keeping in mind that salvage brain therapies will likely be more frequently required. Less toxic therapies now also allow for concurrent delivery of systemic therapy with radiosurgery to brain metastases, such that treatment of both extracranial and intracranial disease can be expedited, and potential synergies between radiotherapy and agents with central nervous system penetration can be harnessed.
Literatur
1.
Zurück zum Zitat Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004;22(14):2865–72. doi:10.1200/JCO.2004.12.149. CrossRefPubMed Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004;22(14):2865–72. doi:10.​1200/​JCO.​2004.​12.​149.​ CrossRefPubMed
3.
Zurück zum Zitat Schouten LJ, Rutten J, Huveneers HA, Twijnstra A. Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer. 2002;94(10):2698–705.CrossRefPubMed Schouten LJ, Rutten J, Huveneers HA, Twijnstra A. Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer. 2002;94(10):2698–705.CrossRefPubMed
7.
Zurück zum Zitat Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009;10(11):1037–44. doi:10.1016/S1470-2045(09)70263-3. CrossRefPubMed Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009;10(11):1037–44. doi:10.​1016/​S1470-2045(09)70263-3.​ CrossRefPubMed
8••.
Zurück zum Zitat Soffietti R, Kocher M, Abacioglu UM, Villa S, Fauchon F, Baumert BG, et al. A European Organisation for Research and Treatment of Cancer phase III trial of adjuvant whole-brain radiotherapy versus observation in patients with one to three brain metastases from solid tumors after surgical resection or radiosurgery: quality-of-life results. J Clin Oncol. 2013;31(1):65–72. doi:10.1200/JCO.2011.41.0639. This paper reports quality-of-life results for the EORTC 22952-26001 randomized trial evaluating the addition of WBRT to radiosurgery or surgery for brain metastases and suggests better quality of life with omission of WBRT.CrossRefPubMed Soffietti R, Kocher M, Abacioglu UM, Villa S, Fauchon F, Baumert BG, et al. A European Organisation for Research and Treatment of Cancer phase III trial of adjuvant whole-brain radiotherapy versus observation in patients with one to three brain metastases from solid tumors after surgical resection or radiosurgery: quality-of-life results. J Clin Oncol. 2013;31(1):65–72. doi:10.​1200/​JCO.​2011.​41.​0639. This paper reports quality-of-life results for the EORTC 22952-26001 randomized trial evaluating the addition of WBRT to radiosurgery or surgery for brain metastases and suggests better quality of life with omission of WBRT.CrossRefPubMed
10••.
Zurück zum Zitat Johung KL, Yeh N, Desai NB, Williams TM, Lautenschlaeger T, Arvold ND, et al. Extended survival and prognostic factors for patients with ALK-rearranged non-small-cell lung cancer and brain metastasis. J Clin Oncol. 2016;34(2):123–9. doi:10.1200/JCO.2015.62.0138. This multi-institutional study demonstrates that long-term survival is possible in patients with brain metastases from ALK-rearranged NSCLC treated with brain radiotherapy and TKIs.CrossRefPubMed Johung KL, Yeh N, Desai NB, Williams TM, Lautenschlaeger T, Arvold ND, et al. Extended survival and prognostic factors for patients with ALK-rearranged non-small-cell lung cancer and brain metastasis. J Clin Oncol. 2016;34(2):123–9. doi:10.​1200/​JCO.​2015.​62.​0138. This multi-institutional study demonstrates that long-term survival is possible in patients with brain metastases from ALK-rearranged NSCLC treated with brain radiotherapy and TKIs.CrossRefPubMed
11••.
Zurück zum Zitat Shen CJ, Kummerlowe MN, Redmond KJ, Rigamonti D, Lim MK, Kleinberg LR. Stereotactic radiosurgery: treatment of brain metastasis without interruption of systemic therapy. Int J Radiat Oncol Biol Phys. 2016;95(2):735–42. doi:10.1016/j.ijrobp.2016.01.054. This single-institution study suggests that concurrent treatment with brain SRS and systemic therapy is associated with minimal neurologic and hematologic toxicity and is safe for most patients.CrossRefPubMed Shen CJ, Kummerlowe MN, Redmond KJ, Rigamonti D, Lim MK, Kleinberg LR. Stereotactic radiosurgery: treatment of brain metastasis without interruption of systemic therapy. Int J Radiat Oncol Biol Phys. 2016;95(2):735–42. doi:10.​1016/​j.​ijrobp.​2016.​01.​054. This single-institution study suggests that concurrent treatment with brain SRS and systemic therapy is associated with minimal neurologic and hematologic toxicity and is safe for most patients.CrossRefPubMed
12.
Zurück zum Zitat Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, et al. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA. 2006;295(21):2483–91.CrossRefPubMed Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, et al. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA. 2006;295(21):2483–91.CrossRefPubMed
13••.
Zurück zum Zitat Brown PD, Asher AL, Ballman KV, Farace E, Cerhan JH, Anderson SK, et al. NCCTG N0574 (Alliance): a phase III randomized trial of whole brain radiation therapy (WBRT) in addition to radiosurgery (SRS) in patients with 1 to 3 brain metastases. J Clin Oncol. 2015;33 (suppl; abstr LBA4). This randomized, phase III trial (in abstract form) represents one of four large studies evaluating the role of WBRT added to SRS for 1–3 brain metastases and focuses on cognitive function as a primary endpoint. Brown PD, Asher AL, Ballman KV, Farace E, Cerhan JH, Anderson SK, et al. NCCTG N0574 (Alliance): a phase III randomized trial of whole brain radiation therapy (WBRT) in addition to radiosurgery (SRS) in patients with 1 to 3 brain metastases. J Clin Oncol. 2015;33 (suppl; abstr LBA4). This randomized, phase III trial (in abstract form) represents one of four large studies evaluating the role of WBRT added to SRS for 1–3 brain metastases and focuses on cognitive function as a primary endpoint.
14.
Zurück zum Zitat Kocher M, Soffietti R, Abacioglu U, Villa S, Fauchon F, Baumert BG, et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol. 2011;29(2):134–41. doi:10.1200/JCO.2010.30.1655. CrossRefPubMed Kocher M, Soffietti R, Abacioglu U, Villa S, Fauchon F, Baumert BG, et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol. 2011;29(2):134–41. doi:10.​1200/​JCO.​2010.​30.​1655.​ CrossRefPubMed
15••.
Zurück zum Zitat Yamamoto M, Serizawa T, Shuto T, Akabane A, Higuchi Y, Kawagishi J, et al. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol. 2014;15(4):387–95. doi:10.1016/S1470-2045(14)70061-0. This multi-institutional prospective study suggests that treatment with SRS alone may be an appropriate approach for patients with multiple brain metastases, as outcomes were similar for patients with 5–10 brain metastases versus 4 or fewer metastases.CrossRefPubMed Yamamoto M, Serizawa T, Shuto T, Akabane A, Higuchi Y, Kawagishi J, et al. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol. 2014;15(4):387–95. doi:10.​1016/​S1470-2045(14)70061-0. This multi-institutional prospective study suggests that treatment with SRS alone may be an appropriate approach for patients with multiple brain metastases, as outcomes were similar for patients with 5–10 brain metastases versus 4 or fewer metastases.CrossRefPubMed
16.
Zurück zum Zitat Yamanaka K, Iwai Y, Yasui T, Nakajima H, Komiyama M, Nishikawa M, et al. Gamma knife radiosurgery for metastatic brain tumor: the usefulness of repeated gamma knife radiosurgery for recurrent cases. Stereotact Funct Neurosurg. 1999;72(Suppl 1):73–80.CrossRefPubMed Yamanaka K, Iwai Y, Yasui T, Nakajima H, Komiyama M, Nishikawa M, et al. Gamma knife radiosurgery for metastatic brain tumor: the usefulness of repeated gamma knife radiosurgery for recurrent cases. Stereotact Funct Neurosurg. 1999;72(Suppl 1):73–80.CrossRefPubMed
17.
Zurück zum Zitat Chen JC, Petrovich Z, Giannotta SL, Yu C, Apuzzo ML. Radiosurgical salvage therapy for patients presenting with recurrence of metastatic disease to the brain. Neurosurgery. 2000;46(4):860–6. discussion 866-7.PubMed Chen JC, Petrovich Z, Giannotta SL, Yu C, Apuzzo ML. Radiosurgical salvage therapy for patients presenting with recurrence of metastatic disease to the brain. Neurosurgery. 2000;46(4):860–6. discussion 866-7.PubMed
18.
Zurück zum Zitat Kwon KY, Kong DS, Lee JI, Nam DH, Park K, Kim JH. Outcome of repeated radiosurgery for recurrent metastatic brain tumors. Clin Neurol Neurosurg. 2007;109(2):132–7.CrossRefPubMed Kwon KY, Kong DS, Lee JI, Nam DH, Park K, Kim JH. Outcome of repeated radiosurgery for recurrent metastatic brain tumors. Clin Neurol Neurosurg. 2007;109(2):132–7.CrossRefPubMed
19•.
Zurück zum Zitat Shultz DB, Modlin LA, Jayachandran P, Von Eyben R, Gibbs IC, Choi CY, et al. Repeat courses of stereotactic radiosurgery (SRS), deferring whole-brain irradiation, for new brain metastases after initial SRS. Int J Radiat Oncol Biol Phys. 2015;92(5):993–9. doi:10.1016/j.ijrobp.2015.04.036. References 19 and 20 suggest that repeated course of SRS for new brain metastases following initial SRS is a safe and effective approach.CrossRefPubMed Shultz DB, Modlin LA, Jayachandran P, Von Eyben R, Gibbs IC, Choi CY, et al. Repeat courses of stereotactic radiosurgery (SRS), deferring whole-brain irradiation, for new brain metastases after initial SRS. Int J Radiat Oncol Biol Phys. 2015;92(5):993–9. doi:10.​1016/​j.​ijrobp.​2015.​04.​036. References 19 and 20 suggest that repeated course of SRS for new brain metastases following initial SRS is a safe and effective approach.CrossRefPubMed
20•.
Zurück zum Zitat Shen CJ, Rigamonti D, Redmond KJ, Kummerlowe MN, Lim M, Kleinberg LR. The strategy of repeat stereotactic radiosurgery without whole brain radiation treatment for new brain metastases: outcomes and implications for follow-up monitoring. Pract Radiat Oncol. 2016. doi:10.1016/j.prro.2016.04.004. References 19 and 20 suggest that repeated course of SRS for new brain metastases following initial SRS is a safe and effective approach. Shen CJ, Rigamonti D, Redmond KJ, Kummerlowe MN, Lim M, Kleinberg LR. The strategy of repeat stereotactic radiosurgery without whole brain radiation treatment for new brain metastases: outcomes and implications for follow-up monitoring. Pract Radiat Oncol. 2016. doi:10.​1016/​j.​prro.​2016.​04.​004. References 19 and 20 suggest that repeated course of SRS for new brain metastases following initial SRS is a safe and effective approach.
22.
Zurück zum Zitat Borgelt B, Gelber R, Kramer S, Brady LW, Chang CH, Davis LW, et al. The palliation of brain metastases: final results of the first two studies by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys. 1980;6(1):1–9.CrossRefPubMed Borgelt B, Gelber R, Kramer S, Brady LW, Chang CH, Davis LW, et al. The palliation of brain metastases: final results of the first two studies by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys. 1980;6(1):1–9.CrossRefPubMed
23.
Zurück zum Zitat Gondi V, Hermann BP, Mehta MP, Tome WA. Hippocampal dosimetry predicts neurocognitive function impairment after fractionated stereotactic radiotherapy for benign or low-grade adult brain tumors. Int J Radiat Oncol Biol Phys. 2012;83(4):e487–93. doi:10.1016/j.ijrobp.2011.10.021. CrossRefPubMed Gondi V, Hermann BP, Mehta MP, Tome WA. Hippocampal dosimetry predicts neurocognitive function impairment after fractionated stereotactic radiotherapy for benign or low-grade adult brain tumors. Int J Radiat Oncol Biol Phys. 2012;83(4):e487–93. doi:10.​1016/​j.​ijrobp.​2011.​10.​021.​ CrossRefPubMed
24.
Zurück zum Zitat Shibamoto Y, Baba F, Oda K, Hayashi S, Kokubo M, Ishihara S, et al. Incidence of brain atrophy and decline in mini-mental state examination score after whole-brain radiotherapy in patients with brain metastases: a prospective study. Int J Radiat Oncol Biol Phys. 2008;72(4):1168–73. doi:10.1016/j.ijrobp.2008.02.054. CrossRefPubMed Shibamoto Y, Baba F, Oda K, Hayashi S, Kokubo M, Ishihara S, et al. Incidence of brain atrophy and decline in mini-mental state examination score after whole-brain radiotherapy in patients with brain metastases: a prospective study. Int J Radiat Oncol Biol Phys. 2008;72(4):1168–73. doi:10.​1016/​j.​ijrobp.​2008.​02.​054.​ CrossRefPubMed
25.
Zurück zum Zitat Borgelt B, Gelber R, Larson M, Hendrickson F, Griffin T, Roth R. Ultra-rapid high dose irradiation schedules for the palliation of brain metastases: final results of the first two studies by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys. 1981;7(12):1633–8.CrossRefPubMed Borgelt B, Gelber R, Larson M, Hendrickson F, Griffin T, Roth R. Ultra-rapid high dose irradiation schedules for the palliation of brain metastases: final results of the first two studies by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys. 1981;7(12):1633–8.CrossRefPubMed
26.
Zurück zum Zitat Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, 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. 2004;363(9422):1665–72. doi:10.1016/S0140-6736(04)16250-8. CrossRefPubMed Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, 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. 2004;363(9422):1665–72. doi:10.​1016/​S0140-6736(04)16250-8.​ CrossRefPubMed
27.
Zurück zum Zitat DeAngelis LM, Delattre JY, Posner JB. Radiation-induced dementia in patients cured of brain metastases. Neurology. 1989;39(6):789–96.CrossRefPubMed DeAngelis LM, Delattre JY, Posner JB. Radiation-induced dementia in patients cured of brain metastases. Neurology. 1989;39(6):789–96.CrossRefPubMed
28.
Zurück zum Zitat Roman DD, Sperduto PW. Neuropsychological effects of cranial radiation: current knowledge and future directions. Int J Radiat Oncol Biol Phys. 1995;31(4):983–98.CrossRefPubMed Roman DD, Sperduto PW. Neuropsychological effects of cranial radiation: current knowledge and future directions. Int J Radiat Oncol Biol Phys. 1995;31(4):983–98.CrossRefPubMed
29.
Zurück zum Zitat Aoyama H, Tago M, Kato N, Toyoda T, Kenjyo M, Hirota S, 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. 2007;68(5):1388–95.CrossRefPubMed Aoyama H, Tago M, Kato N, Toyoda T, Kenjyo M, Hirota S, 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. 2007;68(5):1388–95.CrossRefPubMed
30.
Zurück zum Zitat Li J, Bentzen SM, Renschler M, Mehta MP. Regression after whole-brain radiation therapy for brain metastases correlates with survival and improved neurocognitive function. J Clin Oncol. 2007;25(10):1260–6.CrossRefPubMed Li J, Bentzen SM, Renschler M, Mehta MP. Regression after whole-brain radiation therapy for brain metastases correlates with survival and improved neurocognitive function. J Clin Oncol. 2007;25(10):1260–6.CrossRefPubMed
31.
Zurück zum Zitat Regine WF, Huhn JL, Patchell RA, St Clair WH, Strottmann J, Meigooni A, et al. Risk of symptomatic brain tumor recurrence and neurologic deficit after radiosurgery alone in patients with newly diagnosed brain metastases: results and implications. Int J Radiat Oncol Biol Phys. 2002;52(2):333–8.CrossRefPubMed Regine WF, Huhn JL, Patchell RA, St Clair WH, Strottmann J, Meigooni A, et al. Risk of symptomatic brain tumor recurrence and neurologic deficit after radiosurgery alone in patients with newly diagnosed brain metastases: results and implications. Int J Radiat Oncol Biol Phys. 2002;52(2):333–8.CrossRefPubMed
32.
Zurück zum Zitat Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, et al. Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol. 2012;30(4):419–25. doi:10.1200/JCO.2011.38.0527. CrossRefPubMed Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, et al. Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol. 2012;30(4):419–25. doi:10.​1200/​JCO.​2011.​38.​0527.​ CrossRefPubMed
33•.
Zurück zum Zitat Aoyama H, Tago M, Shirato H, Japanese Radiation Oncology Study Group 99-1 (JROSG 99-1) Investigators. Stereotactic radiosurgery with or without whole-brain radiotherapy for brain metastases: secondary analysis of the JROSG 99-1 randomized clinical trial. JAMA Oncol. 2015;1(4):457–64. doi:10.1001/jamaoncol.2015.1145. This secondary analysis of the JROSG 99-1 randomized trial suggests that certain subgroups of patients with favorable prognosis based on diagnosis-specific graded prognostic assessment (DS-GPA) may benefit from addition of WBRT to SRS.CrossRefPubMed Aoyama H, Tago M, Shirato H, Japanese Radiation Oncology Study Group 99-1 (JROSG 99-1) Investigators. Stereotactic radiosurgery with or without whole-brain radiotherapy for brain metastases: secondary analysis of the JROSG 99-1 randomized clinical trial. JAMA Oncol. 2015;1(4):457–64. doi:10.​1001/​jamaoncol.​2015.​1145. This secondary analysis of the JROSG 99-1 randomized trial suggests that certain subgroups of patients with favorable prognosis based on diagnosis-specific graded prognostic assessment (DS-GPA) may benefit from addition of WBRT to SRS.CrossRefPubMed
34•.
Zurück zum Zitat Sahgal A, Aoyama H, Kocher M, Neupane B, Collette S, Tago M, et al. Phase 3 trials of stereotactic radiosurgery with or without whole-brain radiation therapy for 1 to 4 brain metastases: individual patient data meta-analysis. Int J Radiat Oncol Biol Phys. 2015;91(4):710–7. doi:10.1016/j.ijrobp.2014.10.024. This meta-analysis of phase 3 trials of SRS with or without WBRT suggests improved survival with SRS alone for patients age 50 or younger.CrossRefPubMed Sahgal A, Aoyama H, Kocher M, Neupane B, Collette S, Tago M, et al. Phase 3 trials of stereotactic radiosurgery with or without whole-brain radiation therapy for 1 to 4 brain metastases: individual patient data meta-analysis. Int J Radiat Oncol Biol Phys. 2015;91(4):710–7. doi:10.​1016/​j.​ijrobp.​2014.​10.​024. This meta-analysis of phase 3 trials of SRS with or without WBRT suggests improved survival with SRS alone for patients age 50 or younger.CrossRefPubMed
35.
Zurück zum Zitat Varlotto JM, Flickinger JC, Niranjan A, Bhatnagar A, Kondziolka D, Lunsford LD. The impact of whole-brain radiation therapy on the long-term control and morbidity of patients surviving more than one year after gamma knife radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys. 2005;62(4):1125–32.CrossRefPubMed Varlotto JM, Flickinger JC, Niranjan A, Bhatnagar A, Kondziolka D, Lunsford LD. The impact of whole-brain radiation therapy on the long-term control and morbidity of patients surviving more than one year after gamma knife radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys. 2005;62(4):1125–32.CrossRefPubMed
36.
Zurück zum Zitat Shaw E, Scott C, Souhami L, Dinapoli R, Kline R, Loeffler J, et al. Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys. 2000;47(2):291–8.CrossRefPubMed Shaw E, Scott C, Souhami L, Dinapoli R, Kline R, Loeffler J, et al. Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys. 2000;47(2):291–8.CrossRefPubMed
38•.
Zurück zum Zitat Gondi V, Pugh SL, Tome WA, Caine C, Corn B, Kanner A, et al. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial. J Clin Oncol. 2014;32(34):3810–6. doi:10.1200/JCO.2014.57.2909. This phase II trial suggests an approach to minimize memory loss with WBRT through hippocampal sparing.CrossRefPubMedPubMedCentral Gondi V, Pugh SL, Tome WA, Caine C, Corn B, Kanner A, et al. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial. J Clin Oncol. 2014;32(34):3810–6. doi:10.​1200/​JCO.​2014.​57.​2909. This phase II trial suggests an approach to minimize memory loss with WBRT through hippocampal sparing.CrossRefPubMedPubMedCentral
39.
Zurück zum Zitat Brown PD, Pugh S, Laack NN, Wefel JS, Khuntia D, Meyers C, et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro-Oncology. 2013;15(10):1429–37. doi:10.1093/neuonc/not114. CrossRefPubMedPubMedCentral Brown PD, Pugh S, Laack NN, Wefel JS, Khuntia D, Meyers C, et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro-Oncology. 2013;15(10):1429–37. doi:10.​1093/​neuonc/​not114.​ CrossRefPubMedPubMedCentral
41.
Zurück zum Zitat Shaw EG, Rosdhal R, D’Agostino Jr RB, Lovato J, Naughton MJ, Robbins ME, et al. Phase II study of donepezil in irradiated brain tumor patients: effect on cognitive function, mood, and quality of life. J Clin Oncol. 2006;24(9):1415–20.CrossRefPubMed Shaw EG, Rosdhal R, D’Agostino Jr RB, Lovato J, Naughton MJ, Robbins ME, et al. Phase II study of donepezil in irradiated brain tumor patients: effect on cognitive function, mood, and quality of life. J Clin Oncol. 2006;24(9):1415–20.CrossRefPubMed
42.
Zurück zum Zitat Bhatnagar AK, Flickinger JC, Kondziolka D, Lunsford LD. Stereotactic radiosurgery for four or more intracranial metastases. Int J Radiat Oncol Biol Phys. 2006;64(3):898–903.CrossRefPubMed Bhatnagar AK, Flickinger JC, Kondziolka D, Lunsford LD. Stereotactic radiosurgery for four or more intracranial metastases. Int J Radiat Oncol Biol Phys. 2006;64(3):898–903.CrossRefPubMed
44.
Zurück zum Zitat Mohammadi AM, Recinos PF, Barnett GH, Weil RJ, Vogelbaum MA, Chao ST, et al. Role of gamma knife surgery in patients with 5 or more brain metastases. J Neurosurg. 2012;117(Suppl):5–12. doi:10.3171/2012.8.GKS12983. PubMed Mohammadi AM, Recinos PF, Barnett GH, Weil RJ, Vogelbaum MA, Chao ST, et al. Role of gamma knife surgery in patients with 5 or more brain metastases. J Neurosurg. 2012;117(Suppl):5–12. doi:10.​3171/​2012.​8.​GKS12983.​ PubMed
46.
Zurück zum Zitat Muacevic A, Kreth FW, Horstmann GA, Schmid-Elsaesser R, Wowra B, Steiger HJ, et al. Surgery and radiotherapy compared with gamma knife radiosurgery in the treatment of solitary cerebral metastases of small diameter. J Neurosurg. 1999;91(1):35–43. doi:10.3171/jns.1999.91.1.0035. CrossRefPubMed Muacevic A, Kreth FW, Horstmann GA, Schmid-Elsaesser R, Wowra B, Steiger HJ, et al. Surgery and radiotherapy compared with gamma knife radiosurgery in the treatment of solitary cerebral metastases of small diameter. J Neurosurg. 1999;91(1):35–43. doi:10.​3171/​jns.​1999.​91.​1.​0035.​ CrossRefPubMed
47.
Zurück zum Zitat O’Neill BP, Iturria NJ, Link MJ, Pollock BE, Ballman KV, O’Fallon JR. A comparison of surgical resection and stereotactic radiosurgery in the treatment of solitary brain metastases. Int J Radiat Oncol Biol Phys. 2003;55(5):1169–76.CrossRefPubMed O’Neill BP, Iturria NJ, Link MJ, Pollock BE, Ballman KV, O’Fallon JR. A comparison of surgical resection and stereotactic radiosurgery in the treatment of solitary brain metastases. Int J Radiat Oncol Biol Phys. 2003;55(5):1169–76.CrossRefPubMed
48.
Zurück zum Zitat Ahluwalia MS, Vogelbaum MV, Chao ST, Mehta MM. Brain metastasis and treatment. F1000Prime Rep. 2014;6:114–114. eCollection 2014. doi: 10.12703/P6-114. Ahluwalia MS, Vogelbaum MV, Chao ST, Mehta MM. Brain metastasis and treatment. F1000Prime Rep. 2014;6:114–114. eCollection 2014. doi: 10.​12703/​P6-114.​
49.
Zurück zum Zitat Kalkanis SN, Kondziolka D, Gaspar LE, Burri SH, Asher AL, Cobbs CS, 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 Neuro-Oncol. 2010;96(1):33–43. doi:10.1007/s11060-009-0061-8. CrossRef Kalkanis SN, Kondziolka D, Gaspar LE, Burri SH, Asher AL, Cobbs CS, 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 Neuro-Oncol. 2010;96(1):33–43. doi:10.​1007/​s11060-009-0061-8.​ CrossRef
50.
Zurück zum Zitat Patchell RA, Tibbs PA, Regine WF, Dempsey RJ, Mohiuddin M, Kryscio RJ, et al. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA. 1998;280(17):1485–9.CrossRefPubMed Patchell RA, Tibbs PA, Regine WF, Dempsey RJ, Mohiuddin M, Kryscio RJ, et al. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA. 1998;280(17):1485–9.CrossRefPubMed
51•.
Zurück zum Zitat Brennan C, Yang TJ, Hilden P, Zhang Z, Chan K, Yamada Y, et al. A phase 2 trial of stereotactic radiosurgery boost after surgical resection for brain metastases. Int J Radiat Oncol Biol Phys. 2014;88(1):130–6. doi:10.1016/j.ijrobp.2013.09.051. This is the first prospective study of SRS boost of resected brain metastases and demonstrates excellent local control and maintained survival compared to historical standards.CrossRefPubMed Brennan C, Yang TJ, Hilden P, Zhang Z, Chan K, Yamada Y, et al. A phase 2 trial of stereotactic radiosurgery boost after surgical resection for brain metastases. Int J Radiat Oncol Biol Phys. 2014;88(1):130–6. doi:10.​1016/​j.​ijrobp.​2013.​09.​051. This is the first prospective study of SRS boost of resected brain metastases and demonstrates excellent local control and maintained survival compared to historical standards.CrossRefPubMed
52.
Zurück zum Zitat Hwang SW, Abozed MM, Hale A, Eisenberg RL, Dvorak T, Yao K, et al. Adjuvant gamma knife radiosurgery following surgical resection of brain metastases: a 9-year retrospective cohort study. J Neuro-Oncol. 2010;98(1):77–82. doi:10.1007/s11060-009-0051-x. CrossRef Hwang SW, Abozed MM, Hale A, Eisenberg RL, Dvorak T, Yao K, et al. Adjuvant gamma knife radiosurgery following surgical resection of brain metastases: a 9-year retrospective cohort study. J Neuro-Oncol. 2010;98(1):77–82. doi:10.​1007/​s11060-009-0051-x.​ CrossRef
54.
Zurück zum Zitat Prabhu R, Shu HK, Hadjipanayis C, Dhabaan A, Hall W, Raore B, et al. Current dosing paradigm for stereotactic radiosurgery alone after surgical resection of brain metastases needs to be optimized for improved local control. Int J Radiat Oncol Biol Phys. 2012;83(1):e61–6. doi:10.1016/j.ijrobp.2011.12.017. CrossRefPubMed Prabhu R, Shu HK, Hadjipanayis C, Dhabaan A, Hall W, Raore B, et al. Current dosing paradigm for stereotactic radiosurgery alone after surgical resection of brain metastases needs to be optimized for improved local control. Int J Radiat Oncol Biol Phys. 2012;83(1):e61–6. doi:10.​1016/​j.​ijrobp.​2011.​12.​017.​ CrossRefPubMed
55.
Zurück zum Zitat Minniti G, Esposito V, Clarke E, Scaringi C, Lanzetta G, Salvati M, et al. Multidose stereotactic radiosurgery (9 Gy x 3) of the postoperative resection cavity for treatment of large brain metastases. Int J Radiat Oncol Biol Phys. 2013;86(4):623–9. doi:10.1016/j.ijrobp.2013.03.037. CrossRefPubMed Minniti G, Esposito V, Clarke E, Scaringi C, Lanzetta G, Salvati M, et al. Multidose stereotactic radiosurgery (9 Gy x 3) of the postoperative resection cavity for treatment of large brain metastases. Int J Radiat Oncol Biol Phys. 2013;86(4):623–9. doi:10.​1016/​j.​ijrobp.​2013.​03.​037.​ CrossRefPubMed
56•.
Zurück zum Zitat Atalar B, Modlin LA, Choi CY, Adler JR, Gibbs IC, Chang SD, et al. Risk of leptomeningeal disease in patients treated with stereotactic radiosurgery targeting the postoperative resection cavity for brain metastases. Int J Radiat Oncol Biol Phys. 2013;87(4):713–8. doi:10.1016/j.ijrobp.2013.07.034. References 56 and 57 represent a large, single-institution experience with SRS to the post-operative resection cavity and suggest higher risk of leptomeningeal disease with breast cancer histology, as well as improved local control with a 2-mm SRS margin around the resection cavity.CrossRefPubMed Atalar B, Modlin LA, Choi CY, Adler JR, Gibbs IC, Chang SD, et al. Risk of leptomeningeal disease in patients treated with stereotactic radiosurgery targeting the postoperative resection cavity for brain metastases. Int J Radiat Oncol Biol Phys. 2013;87(4):713–8. doi:10.​1016/​j.​ijrobp.​2013.​07.​034. References 56 and 57 represent a large, single-institution experience with SRS to the post-operative resection cavity and suggest higher risk of leptomeningeal disease with breast cancer histology, as well as improved local control with a 2-mm SRS margin around the resection cavity.CrossRefPubMed
57•.
Zurück zum Zitat Choi CY, Chang SD, Gibbs IC, Adler JR, Harsh IV GR, Lieberson RE, et al. Stereotactic radiosurgery of the postoperative resection cavity for brain metastases: prospective evaluation of target margin on tumor control. Int J Radiat Oncol Biol Phys. 2012;84(2):336–42. doi:10.1016/j.ijrobp.2011.12.009. References 56 and 57 represent a large, single-institution experience with SRS to the post-operative resection cavity and suggest higher risk of leptomeningeal disease with breast cancer histology, as well as improved local control with a 2-mm SRS margin around the resection cavity.CrossRefPubMed Choi CY, Chang SD, Gibbs IC, Adler JR, Harsh IV GR, Lieberson RE, et al. Stereotactic radiosurgery of the postoperative resection cavity for brain metastases: prospective evaluation of target margin on tumor control. Int J Radiat Oncol Biol Phys. 2012;84(2):336–42. doi:10.​1016/​j.​ijrobp.​2011.​12.​009. References 56 and 57 represent a large, single-institution experience with SRS to the post-operative resection cavity and suggest higher risk of leptomeningeal disease with breast cancer histology, as well as improved local control with a 2-mm SRS margin around the resection cavity.CrossRefPubMed
58.
Zurück zum Zitat Ojerholm E, Lee JY, Thawani JP, Miller D, O’Rourke DM, Dorsey JF, et al. Stereotactic radiosurgery to the resection bed for intracranial metastases and risk of leptomeningeal carcinomatosis. J Neurosurg. 2014;121(Suppl):75–83. doi:10.3171/2014.6.GKS14708. PubMed Ojerholm E, Lee JY, Thawani JP, Miller D, O’Rourke DM, Dorsey JF, et al. Stereotactic radiosurgery to the resection bed for intracranial metastases and risk of leptomeningeal carcinomatosis. J Neurosurg. 2014;121(Suppl):75–83. doi:10.​3171/​2014.​6.​GKS14708.​ PubMed
60.
Zurück zum Zitat Gaspar LE, Mehta MP, Patchell RA, Burri SH, Robinson PD, Morris RE, 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 Neuro-Oncol. 2010;96(1):17–32. doi:10.1007/s11060-009-0060-9. CrossRef Gaspar LE, Mehta MP, Patchell RA, Burri SH, Robinson PD, Morris RE, 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 Neuro-Oncol. 2010;96(1):17–32. doi:10.​1007/​s11060-009-0060-9.​ CrossRef
63.
Zurück zum Zitat Ammirati M, Cobbs CS, Linskey ME, Paleologos NA, Ryken TC, Burri SH, et al. The role of retreatment in the management of recurrent/progressive brain metastases: a systematic review and evidence-based clinical practice guideline. J Neuro-Oncol. 2010;96(1):85–96. doi:10.1007/s11060-009-0055-6. CrossRef Ammirati M, Cobbs CS, Linskey ME, Paleologos NA, Ryken TC, Burri SH, et al. The role of retreatment in the management of recurrent/progressive brain metastases: a systematic review and evidence-based clinical practice guideline. J Neuro-Oncol. 2010;96(1):85–96. doi:10.​1007/​s11060-009-0055-6.​ CrossRef
64.
Zurück zum Zitat Sundaresan N, Sachdev VP, DiGiacinto GV, Hughes JE. Reoperation for brain metastases. J Clin Oncol. 1988;6(10):1625–9.PubMed Sundaresan N, Sachdev VP, DiGiacinto GV, Hughes JE. Reoperation for brain metastases. J Clin Oncol. 1988;6(10):1625–9.PubMed
68.
Zurück zum Zitat Sadikov E, Bezjak A, Yi QL, Wells W, Dawson L, Millar BA, et al. Value of whole brain re-irradiation for brain metastases—single centre experience. Clin Oncol (R Coll Radiol). 2007;19(7):532–8.CrossRef Sadikov E, Bezjak A, Yi QL, Wells W, Dawson L, Millar BA, et al. Value of whole brain re-irradiation for brain metastases—single centre experience. Clin Oncol (R Coll Radiol). 2007;19(7):532–8.CrossRef
70.
Zurück zum Zitat Wong WW, Schild SE, Sawyer TE, Shaw EG. Analysis of outcome in patients reirradiated for brain metastases. Int J Radiat Oncol Biol Phys. 1996;34(3):585–90.CrossRefPubMed Wong WW, Schild SE, Sawyer TE, Shaw EG. Analysis of outcome in patients reirradiated for brain metastases. Int J Radiat Oncol Biol Phys. 1996;34(3):585–90.CrossRefPubMed
71.
Zurück zum Zitat Caballero JA, Sneed PK, Lamborn KR, Ma L, Denduluri S, Nakamura JL, et al. Prognostic factors for survival in patients treated with stereotactic radiosurgery for recurrent brain metastases after prior whole brain radiotherapy. Int J Radiat Oncol Biol Phys. 2012;83(1):303–9. doi:10.1016/j.ijrobp.2011.06.1987. CrossRefPubMed Caballero JA, Sneed PK, Lamborn KR, Ma L, Denduluri S, Nakamura JL, et al. Prognostic factors for survival in patients treated with stereotactic radiosurgery for recurrent brain metastases after prior whole brain radiotherapy. Int J Radiat Oncol Biol Phys. 2012;83(1):303–9. doi:10.​1016/​j.​ijrobp.​2011.​06.​1987.​ CrossRefPubMed
72.
Zurück zum Zitat Chao ST, Barnett GH, Vogelbaum MA, Angelov L, Weil RJ, Neyman G, et al. Salvage stereotactic radiosurgery effectively treats recurrences from whole-brain radiation therapy. Cancer. 2008;113(8):2198–204. doi:10.1002/cncr.23821. CrossRefPubMed Chao ST, Barnett GH, Vogelbaum MA, Angelov L, Weil RJ, Neyman G, et al. Salvage stereotactic radiosurgery effectively treats recurrences from whole-brain radiation therapy. Cancer. 2008;113(8):2198–204. doi:10.​1002/​cncr.​23821.​ CrossRefPubMed
74•.
Zurück zum Zitat Lucas Jr JT, Colmer IV HG, White L, Fitzgerald N, Isom S, Bourland JD, et al. Competing risk analysis of neurologic vs. non-neurologic death in patients undergoing radiosurgical salvage following whole brain radiotherapy failure (WBRT): who actually dies of their brain metastases? Int J Radiat Oncol Biol Phys. 2015;92(5):1008–15. doi:10.1016/j.ijrobp.2015.04.032. This study provides a nomogram to estimate risk of neurologic death following salvage SRS for patients who have failed prior WBRT for brain metastases.CrossRefPubMedPubMedCentral Lucas Jr JT, Colmer IV HG, White L, Fitzgerald N, Isom S, Bourland JD, et al. Competing risk analysis of neurologic vs. non-neurologic death in patients undergoing radiosurgical salvage following whole brain radiotherapy failure (WBRT): who actually dies of their brain metastases? Int J Radiat Oncol Biol Phys. 2015;92(5):1008–15. doi:10.​1016/​j.​ijrobp.​2015.​04.​032. This study provides a nomogram to estimate risk of neurologic death following salvage SRS for patients who have failed prior WBRT for brain metastases.CrossRefPubMedPubMedCentral
76.
Zurück zum Zitat Antonadou D, Paraskevaidis M, Sarris G, Coliarakis N, Economou I, Karageorgis P, et al. Phase II randomized trial of temozolomide and concurrent radiotherapy in patients with brain metastases. J Clin Oncol. 2002;20(17):3644–50.CrossRefPubMed Antonadou D, Paraskevaidis M, Sarris G, Coliarakis N, Economou I, Karageorgis P, et al. Phase II randomized trial of temozolomide and concurrent radiotherapy in patients with brain metastases. J Clin Oncol. 2002;20(17):3644–50.CrossRefPubMed
78.
Zurück zum Zitat Cao KI, Lebas N, Gerber S, Levy C, Le Scodan R, Bourgier C, et al. Phase II randomized study of whole-brain radiation therapy with or without concurrent temozolomide for brain metastases from breast cancer. Ann Oncol. 2015;26(1):89–94. doi:10.1093/annonc/mdu488. CrossRefPubMed Cao KI, Lebas N, Gerber S, Levy C, Le Scodan R, Bourgier C, et al. Phase II randomized study of whole-brain radiation therapy with or without concurrent temozolomide for brain metastases from breast cancer. Ann Oncol. 2015;26(1):89–94. doi:10.​1093/​annonc/​mdu488.​ CrossRefPubMed
79.
Zurück zum Zitat Keime-Guibert F, Napolitano M, Delattre JY. Neurological complications of radiotherapy and chemotherapy. J Neurol. 1998;245(11):695–708.CrossRefPubMed Keime-Guibert F, Napolitano M, Delattre JY. Neurological complications of radiotherapy and chemotherapy. J Neurol. 1998;245(11):695–708.CrossRefPubMed
80.
Zurück zum Zitat Verger E, Gil M, Yaya R, Vinolas N, Villa S, Pujol T, et al. Temozolomide and concomitant whole brain radiotherapy in patients with brain metastases: a phase II randomized trial. Int J Radiat Oncol Biol Phys. 2005;61(1):185–91.CrossRefPubMed Verger E, Gil M, Yaya R, Vinolas N, Villa S, Pujol T, et al. Temozolomide and concomitant whole brain radiotherapy in patients with brain metastases: a phase II randomized trial. Int J Radiat Oncol Biol Phys. 2005;61(1):185–91.CrossRefPubMed
81.
Zurück zum Zitat Yovino S, Kleinberg L, Grossman SA, Narayanan M, Ford E. The etiology of treatment-related lymphopenia in patients with malignant gliomas: modeling radiation dose to circulating lymphocytes explains clinical observations and suggests methods of modifying the impact of radiation on immune cells. Cancer Investig. 2013;31(2):140–4. doi:10.3109/07357907.2012.762780. CrossRef Yovino S, Kleinberg L, Grossman SA, Narayanan M, Ford E. The etiology of treatment-related lymphopenia in patients with malignant gliomas: modeling radiation dose to circulating lymphocytes explains clinical observations and suggests methods of modifying the impact of radiation on immune cells. Cancer Investig. 2013;31(2):140–4. doi:10.​3109/​07357907.​2012.​762780.​ CrossRef
82.
Zurück zum Zitat Kleinberg L, Grossman SA, Piantadosi S, Zeltzman M, Wharam M. The effects of sequential versus concurrent chemotherapy and radiotherapy on survival and toxicity in patients with newly diagnosed high-grade astrocytoma. Int J Radiat Oncol Biol Phys. 1999;44(3):535–43.CrossRefPubMed Kleinberg L, Grossman SA, Piantadosi S, Zeltzman M, Wharam M. The effects of sequential versus concurrent chemotherapy and radiotherapy on survival and toxicity in patients with newly diagnosed high-grade astrocytoma. Int J Radiat Oncol Biol Phys. 1999;44(3):535–43.CrossRefPubMed
83•.
Zurück zum Zitat Welsh JW, Komaki R, Amini A, Munsell MF, Unger W, Allen PK, et al. Phase II trial of erlotinib plus concurrent whole-brain radiation therapy for patients with brain metastases from non-small-cell lung cancer. J Clin Oncol. 2013;31(7):895–902. doi:10.1200/JCO.2011.40.1174. This phase II trial demonstrates the safety of concurrent erlotinib with WBRT for patients with brain metastases from NSCLC.CrossRefPubMedPubMedCentral Welsh JW, Komaki R, Amini A, Munsell MF, Unger W, Allen PK, et al. Phase II trial of erlotinib plus concurrent whole-brain radiation therapy for patients with brain metastases from non-small-cell lung cancer. J Clin Oncol. 2013;31(7):895–902. doi:10.​1200/​JCO.​2011.​40.​1174. This phase II trial demonstrates the safety of concurrent erlotinib with WBRT for patients with brain metastases from NSCLC.CrossRefPubMedPubMedCentral
84.
Zurück zum Zitat Gaudy-Marqueste C, Carron R, Delsanti C, Loundou A, Monestier S, Archier E, et al. On demand gamma-knife strategy can be safely combined with BRAF inhibitors for the treatment of melanoma brain metastases. Ann Oncol. 2014;25(10):2086–91. doi:10.1093/annonc/mdu266. CrossRefPubMed Gaudy-Marqueste C, Carron R, Delsanti C, Loundou A, Monestier S, Archier E, et al. On demand gamma-knife strategy can be safely combined with BRAF inhibitors for the treatment of melanoma brain metastases. Ann Oncol. 2014;25(10):2086–91. doi:10.​1093/​annonc/​mdu266.​ CrossRefPubMed
85.
Zurück zum Zitat Ahmed KA, Freilich JM, Sloot S, Figura N, Gibney GT, Weber JS, et al. LINAC-based stereotactic radiosurgery to the brain with concurrent vemurafenib for melanoma metastases. J Neuro-Oncol. 2015;122(1):121–6. doi:10.1007/s11060-014-1685-x. CrossRef Ahmed KA, Freilich JM, Sloot S, Figura N, Gibney GT, Weber JS, et al. LINAC-based stereotactic radiosurgery to the brain with concurrent vemurafenib for melanoma metastases. J Neuro-Oncol. 2015;122(1):121–6. doi:10.​1007/​s11060-014-1685-x.​ CrossRef
86.
Zurück zum Zitat Hecht M, Zimmer L, Loquai C, Weishaupt C, Gutzmer R, Schuster B, et al. Radiosensitization by BRAF inhibitor therapy-mechanism and frequency of toxicity in melanoma patients. Ann Oncol. 2015;26(6):1238–44. doi:10.1093/annonc/mdv139. CrossRefPubMed Hecht M, Zimmer L, Loquai C, Weishaupt C, Gutzmer R, Schuster B, et al. Radiosensitization by BRAF inhibitor therapy-mechanism and frequency of toxicity in melanoma patients. Ann Oncol. 2015;26(6):1238–44. doi:10.​1093/​annonc/​mdv139.​ CrossRefPubMed
89.
Zurück zum Zitat Sharabi AB, Nirschl CJ, Kochel CM, Nirschl TR, Francica BJ, Velarde E, et al. Stereotactic radiation therapy augments antigen-specific PD-1-mediated antitumor immune responses via cross-presentation of tumor antigen. Cancer Immunol Res. 2015;3(4):345–55. doi:10.1158/2326-6066.CIR-14-0196. CrossRefPubMed Sharabi AB, Nirschl CJ, Kochel CM, Nirschl TR, Francica BJ, Velarde E, et al. Stereotactic radiation therapy augments antigen-specific PD-1-mediated antitumor immune responses via cross-presentation of tumor antigen. Cancer Immunol Res. 2015;3(4):345–55. doi:10.​1158/​2326-6066.​CIR-14-0196.​ CrossRefPubMed
90•.
Zurück zum Zitat Kiess AP, Wolchok JD, Barker CA, Postow MA, Tabar V, Huse JT, et al. Stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab: safety profile and efficacy of combined treatment. Int J Radiat Oncol Biol Phys. 2015;92(2):368–75. doi:10.1016/j.ijrobp.2015.01.004. References 90–92 suggest that combination immune therapy and brain SRS is well-tolerated and associated with favorable local control and survival in patients with melanoma brain metastases.CrossRefPubMedPubMedCentral Kiess AP, Wolchok JD, Barker CA, Postow MA, Tabar V, Huse JT, et al. Stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab: safety profile and efficacy of combined treatment. Int J Radiat Oncol Biol Phys. 2015;92(2):368–75. doi:10.​1016/​j.​ijrobp.​2015.​01.​004. References 90–92 suggest that combination immune therapy and brain SRS is well-tolerated and associated with favorable local control and survival in patients with melanoma brain metastases.CrossRefPubMedPubMedCentral
91•.
Zurück zum Zitat Knisely JP, Yu JB, Flanigan J, Sznol M, Kluger HM, Chiang VL. Radiosurgery for melanoma brain metastases in the ipilimumab era and the possibility of longer survival. J Neurosurg. 2012;117(2):227–33. doi:10.3171/2012.5.JNS111929. References 90–92 suggest that combination immune therapy and brain SRS is well-tolerated and associated with favorable local control and survival in patients with melanoma brain metastases.CrossRefPubMed Knisely JP, Yu JB, Flanigan J, Sznol M, Kluger HM, Chiang VL. Radiosurgery for melanoma brain metastases in the ipilimumab era and the possibility of longer survival. J Neurosurg. 2012;117(2):227–33. doi:10.​3171/​2012.​5.​JNS111929. References 90–92 suggest that combination immune therapy and brain SRS is well-tolerated and associated with favorable local control and survival in patients with melanoma brain metastases.CrossRefPubMed
92•.
Zurück zum Zitat Ahmed KA, Stallworth DG, Kim Y, Johnstone PA, Harrison LB, Caudell JJ, et al. Clinical outcomes of melanoma brain metastases treated with stereotactic radiation and anti-PD-1 therapy. Ann Oncol. 2016;27(3):434–41. doi:10.1093/annonc/mdv622. References 90–92 suggest that combination immune therapy and brain SRS is well-tolerated and associated with favorable local control and survival in patients with melanoma brain metastases.CrossRefPubMed Ahmed KA, Stallworth DG, Kim Y, Johnstone PA, Harrison LB, Caudell JJ, et al. Clinical outcomes of melanoma brain metastases treated with stereotactic radiation and anti-PD-1 therapy. Ann Oncol. 2016;27(3):434–41. doi:10.​1093/​annonc/​mdv622. References 90–92 suggest that combination immune therapy and brain SRS is well-tolerated and associated with favorable local control and survival in patients with melanoma brain metastases.CrossRefPubMed
Metadaten
Titel
Controversies in the Therapy of Brain Metastases: Shifting Paradigms in an Era of Effective Systemic Therapy and Longer-Term Survivorship
verfasst von
Colette J. Shen, MD, PhD
Michael Lim, MD
Lawrence R. Kleinberg, MD
Publikationsdatum
01.09.2016
Verlag
Springer US
Erschienen in
Current Treatment Options in Oncology / Ausgabe 9/2016
Print ISSN: 1527-2729
Elektronische ISSN: 1534-6277
DOI
https://doi.org/10.1007/s11864-016-0423-3

Weitere Artikel der Ausgabe 9/2016

Current Treatment Options in Oncology 9/2016 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.