Radiation Therapy for Brain Metastases

Project Summary Title and Description

Title
Radiation Therapy for Brain Metastases
Description
Objective. This evidence report synthesizes the available evidence on radiation therapy for brain metastases. Data sources. We searched PubMed®, Embase®, Web of Science, Scopus, CINAHL®, clinicaltrials.gov, and published guidelines in July 2020; assessed independently submitted data; consulted with experts; and contacted authors. Review methods. The protocol was informed by Key Informants. The systematic review was supported by a Technical Expert Panel and is registered in PROSPERO (CRD42020168260). Two reviewers independently screened citations; data were abstracted by one reviewer and checked by an experienced reviewer. We included randomized controlled trials (RCTs) and large observational studies (for safety assessments), evaluating whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) alone or in combination, as initial or postoperative treatment, with or without systemic therapy for adults with brain metastases due to non-small cell lung cancer, breast cancer, or melanoma. Results. In total, 97 studies, reported in 190 publications, were identified, but the number of analyses was limited due to different intervention and comparator combinations as well as insufficient reporting of outcome data. Risk of bias varied; 25 trials were terminated early, predominantly due to poor accrual. Most studies evaluated WBRT, alone or in combination with SRS, as initial treatment; 10 RCTs reported on post-surgical interventions. The combination treatment SRS plus WBRT compared to SRS alone or WBRT alone showed no statistically significant difference in overall survival (hazard ratio [HR], 1.09; confidence interval [CI], 0.69 to 1.73; 4 RCTs; low strength of evidence [SoE]) or death due to brain metastases (relative risk [RR], 0.93; CI, 0.48 to 1.81; 3 RCTs; low SoE). Radiation therapy after surgery did not improve overall survival compared with surgery alone (HR, 0.98; CI, 0.76 to 1.26; 5 RCTs; moderate SoE). Data for quality of life, functional status, and cognitive effects were insufficient to determine effects of WBRT, SRS, or post-surgical interventions. We did not find systematic differences across interventions in serious adverse events radiation necrosis, fatigue, or seizures (all low or moderate SoE). WBRT plus systemic therapy (RR, 1.44; CI, 1.03 to 2.00; 14 studies; moderate SoE) was associated with increased risks for vomiting compared to WBRT alone. Conclusion. Despite the substantial research literature on radiation therapy, comparative effectiveness information is limited. There is a need for more data on patient-relevant outcomes such as quality of life, functional status, and cognitive effects.
Attribution
N/A
Authors of Report
N/A
Methodology description
Systematic Review
PROSPERO
CRD42020168260
DOI
N/A
Notes
Report can be found here: https://pubmed.ncbi.nlm.nih.gov/34152714/ and https://effectivehealthcare.ahrq.gov/products/radiation-therapy-brain-metastases/research Data was entered into this project prospectively
Funding Source
Agency for Healthcare Research and Quality and Patient-Centered Outcomes Research Institute

Key Questions

1. Key Question 1. What is the effectiveness of WBRT, alone or in combination with SRS or systemic therapies, as initial treatment in patients with brain metastases on patient-relevant outcomes, such as overall survival and quality of life?
2. Key Question 2. What is the effectiveness of SRS/fractionated stereotactic radiation as initial treatment in patients with brain metastases on patient-relevant outcomes, such as overall survival and quality of life?
3. Key Question 3. What is the effectiveness (or comparative effectiveness) of postoperative SRS compared to WBRT, observation, or preoperative SRS in patients with brain metastases on patient-relevant outcomes, such as overall survival and quality of life?
4. Key Question 4. What are the adverse effects (i.e., serious harms) of WBRT, SRS, and systemic therapies for patients with brain metastases (either alone or in combination)?

Associated Extraction Forms

Type
Standard

Associated Studies (each link opens a new tab)

Title Authors Year
Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial P. Mulvenna, M. Nankivell, R. Barton, C. Faivre-Finn, P. Wilson, E. McColl, B. Moore, I. Brisbane, D. Ardron, T. Holt, S. Morgan, C. Lee, K. Waite, N. Bayman, C. Pugh, B. Sydes, R. Stephens, M. K. Parmar, R. E. Langley 2016
Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial H. Aoyama, H. Shirato, M. Tago, K. Nakagawa, T. Toyoda, K. Hatano, M. Kenjyo, N. Oya, S. Hirota, H. Shioura, E. Kunieda, T. Inomata, K. Hayakawa, N. Katoh, G. Kobashi 2006
Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study M. Kocher, R. Soffietti, U. Abacioglu, S. Villa, F. Fauchon, B. G. Baumert, L. Fariselli, T. Tzuk-Shina, R. D. Kortmann, C. Carrie, M. Ben Hassel, M. Kouri, E. Valeinis, D. van den Berge, S. Collette, L. Collette, R. P. Mueller 2011
Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial E. L. Chang, J. S. Wefel, K. R. Hess, P. K. Allen, F. F. Lang, D. G. Kornguth, R. B. Arbuckle, J. M. Swint, A. S. Shiu, M. H. Maor, C. A. Meyers 2009
Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer R. F. Yang, B. Yu, R. Q. Zhang, X. H. Wang, C. Li, P. Wang, Y. Zhang, B. Han, X. X. Gao, L. Zhang, Z. M. Jiang 2017
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 D. W. Andrews, C. B. Scott, P. W. Sperduto, A. E. Flanders, L. E. Gaspar, M. C. Schell, M. Werner-Wasik, W. Demas, J. Ryu, J. P. Bahary, L. Souhami, M. Rotman, M. P. Mehta, W. J. Curran 2004
Veliparib in combination with whole-brain radiation therapy for patients with brain metastases from non-small cell lung cancer: results of a randomized, global, placebo-controlled study P. Chabot, T. C. Hsia, J. S. Ryu, V. Gorbunova, C. Belda-Iniesta, D. Ball, E. Kio, M. Mehta, K. Papp, Q. Qin, J. Qian, K. D. Holen, V. Giranda, J. H. Suh 2017
Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial A. Mahajan, S. Ahmed, M. F. McAleer, J. S. Weinberg, J. Li, P. Brown, S. Settle, S. S. Prabhu, F. F. Lang, N. Levine, S. McGovern, E. Sulman, I. E. McCutcheon, S. Azeem, D. Cahill, C. Tatsui, A. B. Heimberger, S. Ferguson, A. Ghia, F. Demonte, S. Raza, N. Guha-Thakurta, J. Yang, R. Sawaya, K. R. Hess, G. Rao 2017
Radiation-enhancing effect of sodium glycididazole in patients suffering from non-small cell lung cancer with multiple brain metastases: A randomized, placebo-controlled study Y. C. Zeng, R. Wu, R. Xing, F. Chi, S. L. Wang, X. D. Chen, Y. Xuan, L. N. Wu, Q. Y. Duan, M. Y. Tang, N. Niu, Y. N. Sun, G. L. Fan, H. M. Wang 2016
A Randomized Controlled Open-Label Pilot Study of Simvastatin Addition to Whole-Brain Radiation Therapy in Patients With Brain Metastases M. El-Hamamsy, H. Elwakil, A. S. Saad, M. A. Shawki 2016
A phase 3 trial of whole brain radiation therapy and stereotactic radiosurgery alone versus WBRT and SRS with temozolomide or erlotinib for non-small cell lung cancer and 1 to 3 brain metastases: Radiation Therapy Oncology Group 0320 P. W. Sperduto, M. Wang, H. I. Robins, M. C. Schell, M. Werner-Wasik, R. Komaki, L. Souhami, M. K. Buyyounouski, D. Khuntia, W. Demas, S. A. Shah, L. A. Nedzi, G. Perry, J. H. Suh, M. P. Mehta 2013
Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC.3): a multicentre, randomised, controlled, phase 3 trial P. D. Brown, K. V. Ballman, J. H. Cerhan, S. K. Anderson, X. W. Carrero, A. C. Whitton, J. Greenspoon, I. F. Parney, N. N. I. Laack, J. B. Ashman, J. P. Bahary, C. G. Hadjipanayis, J. J. Urbanic, F. G. Barker, E. Farace, D. Khuntia, C. Giannini, J. C. Buckner, E. Galanis, D. Roberge 2017
Efficacy and safety of temozolomide plus whole-brain radiotherapy in the treatment of intracranial metastases H. P. Liu, K. B. Zheng, J. W. Wang 2017
RADVAN: a randomised phase 2 trial of WBRT plus vandetanib for melanoma brain metastases - results and lessons learnt A. Gupta, C. Roberts, F. Tysoe, M. Goff, J. Nobes, J. Lester, E. Marshall, C. Corner, V. Wolstenholme, C. Kelly, A. Wise, L. Collins, S. Love, M. Woodward, A. Salisbury, M. R. Middleton 2016
Defining the optimal planning target volume in image-guided stereotactic radiosurgery of brain metastases: results of a randomized trial J. P. Kirkpatrick, Z. Wang, J. H. Sampson, F. McSherry, J. E. Herndon, K. J. Allen, E. Duffy, J. K. Hoang, Z. Chang, D. S. Yoo, C. R. Kelsey, F. F. Yin 2015
Phase II randomized study of whole-brain radiation therapy with or without concurrent temozolomide for brain metastases from breast cancer K. I. Cao, N. Lebas, S. Gerber, C. Levy, R. Le Scodan, C. Bourgier, J. Y. Pierga, A. Gobillion, A. Savignoni, Y. M. Kirova 2015
Phase III study of efaproxiral as an adjunct to whole-brain radiation therapy for brain metastases J. H. Suh, B. Stea, A. Nabid, J. J. Kresl, A. Fortin, J. P. Mercier, N. Senzer, E. L. Chang, A. P. Boyd, P. J. Cagnoni, E. Shaw 2006
Radiation sensitization with sodium nitrite in patients with brain metastases: a pilot randomized controlled trial S. M. Hosseini, S. Arvandi, S. Razmjoo, H. Shahbazian, F. Rahim, T. Rafie, M. Barahman, A. Bagheri 2015
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 D. Chua, M. Krzakowski, C. Chouaid, M. G. Pallotta, J. I. Martinez, M. Gottfried, W. Curran, N. Throuvalas 2010
Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases D. Kondziolka, A. Patel, L. D. Lunsford, A. Kassam, J. C. Flickinger 1999
Temozolomide added to whole brain radiotherapy in patients with multiple brain metastases of non-small-cell lung cancer: a multicentric Austrian phase II study M. R. Hassler, W. Pfeifer, T. H. Knocke-Abulesz, K. Geissler, G. Altorjai, K. Dieckmann, C. Marosi 2013
Management of brain metastases with stereotactic radiosurgery alone versus whole brain irradiation alone versus both M. M. El Gantery, H. M. Abd El Baky, H. A. El Hossieny, M. Mahmoud, O. Youssef 2014
Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases M. P. Mehta, P. Rodrigus, C. H. Terhaard, A. Rao, J. Suh, W. Roa, L. Souhami, A. Bezjak, M. Leibenhaut, R. Komaki, C. Schultz, R. Timmerman, W. Curran, J. Smith, S. C. Phan, R. A. Miller, M. F. Renschler 2003
Study on lung cancer cells expressing VEGFR2 and the impact on the effect of RHES combined with radiotherapy in the treatment of brain metastases X. D. Jiang, M. H. Ding, Y. Qiao, Y. Liu, L. Liu 2014
Phase II randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases L. L. Rojas-Puentes, M. Gonzalez-Pinedo, A. Crismatt, A. Ortega-Gomez, C. Gamboa-Vignolle, R. Nunez-Gomez, Y. Dorantes-Gallareta, C. Arce-Salinas, O. Arrieta 2013
Whole brain irradiation following surgery or radiosurgery for solitary brain metastases: mature results of a prematurely closed randomized Trans-Tasman Radiation Oncology Group trial (TROG 98.05) D. E. Roos, A. Wirth, B. H. Burmeister, N. A. Spry, K. J. Drummond, J. A. Beresford, B. E. McClure 2006
A placebo-controlled, randomized phase II study of maintenance enzastaurin following whole brain radiation therapy in the treatment of brain metastases from lung cancer B. H. Gronberg, T. Ciuleanu, O. Flotten, A. Knuuttila, E. Abel, S. W. Langer, K. Krejcy, A. M. Liepa, M. Munoz, M. Hahka-Kemppinen, S. Sundstrom 2012
Recursive partitioning analysis classifications I and II: applicability evaluated in a randomized trial for resected single brain metastases W. F. Regine, A. Rogozinska, R. J. Kryscio, P. A. Tibbs, A. B. Young, R. A. Patchell 2004
Whole-brain irradiation with concomitant daily fixed-dose temozolomide for brain metastases treatment: a randomised phase II trial C. Gamboa-Vignolle, T. Ferrari-Carballo, O. Arrieta, A. Mohar 2012
Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial P. D. Brown, S. Pugh, N. N. Laack, J. S. Wefel, D. Khuntia, C. Meyers, A. Choucair, S. Fox, J. H. Suh, D. Roberge, V. Kavadi, S. M. Bentzen, M. P. Mehta, D. Watkins-Bruner 2013
Randomized phase II trial of high-dose melatonin and radiation therapy for RPA class 2 patients with brain metastases (RTOG 0119) L. Berk, B. Berkey, T. Rich, W. Hrushesky, D. Blask, M. Gallagher, M. Kudrimoti, R. C. McGarry, J. Suh, M. Mehta 2007
A phase III study of conventional radiation therapy plus thalidomide versus conventional radiation therapy for multiple brain metastases (RTOG 0118) J. P. Knisely, B. Berkey, A. Chakravarti, A. W. Yung, W. J. Curran, H. I. Robins, B. Movsas, D. G. Brachman, R. H. Henderson, M. P. Mehta 2008
Radiosurgery versus surgery, both with adjuvant whole brain radiotherapy, for solitary brain metastases: a randomised controlled trial D. E. Roos, J. G. Smith, S. W. Stephens 2011
Outcome, quality of life and cognitive function of patients with brain metastases from non-small cell lung cancer treated with whole brain radiotherapy combined with gefitinib or temozolomide. A randomised phase II trial of the Swiss Group for Clinical Cancer Research (SAKK 70/03) G. A. Pesce, D. Klingbiel, K. Ribi, A. Zouhair, R. von Moos, M. Schlaeppi, C. B. Caspar, N. Fischer, S. Anchisi, S. Peters, R. Cathomas, J. Bernhard, N. M. Kotrubczik, G. D'Addario, C. Pilop, D. C. Weber, S. Bodis, M. Pless, M. Mayer, R. Stupp 2012
Phase II randomized trial of temozolomide and concurrent radiotherapy in patients with brain metastases D. Antonadou, M. Paraskevaidis, G. Sarris, N. Coliarakis, I. Economou, P. Karageorgis, N. Throuvalas 2002
A randomised phase III study of palliative radiation with concomitant carboplatin for brain metastases from non-small cell carcinoma of the lung M. Guerrieri, K. Wong, G. Ryan, M. Millward, G. Quong, D. L. Ball 2004
Radiation therapy for brain metastases from lung carcinoma. Prospective randomized trial according to the level of lactate dehydrogenase M. Chatani, Y. Matayoshi, N. Masaki, T. Inoue 1994
A randomized phase III study of accelerated hyperfractionation versus standard in patients with unresected brain metastases: a report of the Radiation Therapy Oncology Group (RTOG) 9104 K. J. Murray, C. Scott, H. M. Greenberg, B. Emami, M. Seider, N. L. Vora, C. Olson, A. Whitton, B. Movsas, W. Curran 1997
Results of a randomized comparison of radiotherapy and bromodeoxyuridine with radiotherapy alone for brain metastases: report of RTOG trial 89-05 T. L. Phillips, C. B. Scott, S. A. Leibel, M. Rotman, I. J. Weigensberg 1995
A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis A. H. Mintz, J. Kestle, M. P. Rathbone, L. Gaspar, H. Hugenholtz, B. Fisher, G. Duncan, P. Skingley, G. Foster, M. Levine 1996
A phase III study of accelerated versus conventional hypofractionated whole brain irradiation in patients of good performance status with brain metastases not suitable for surgical excision P. Davey, D. Hoegler, M. Ennis, J. Smith 2008
Randomized comparison of whole brain radiotherapy, 20 Gy in four daily fractions versus 40 Gy in 20 twice-daily fractions, for brain metastases P. H. Graham, J. Bucci, L. Browne 2010
Efficacy of platinum-based chemotherapy after cranial radiation in patients with brain metastasis from non-small cell lung cancer D. Y. Kim, K. W. Lee, T. Yun, D. W. Kim, T. Y. Kim, D. S. Heo, Y. J. Bang, N. K. Kim 2005
The choice of treatment of single brain metastasis should be based on extracranial tumor activity and age E. M. Noordijk, C. J. Vecht, H. Haaxma-Reiche, G. W. Padberg, J. H. Voormolen, F. H. Hoekstra, J. T. Tans, N. Lambooij, J. A. Metsaars, A. R. Wattendorff, et al. 1994
Results of a phase III study of early versus delayed whole brain radiotherapy with concurrent cisplatin and vinorelbine combination in inoperable brain metastasis of non-small-cell lung cancer: Groupe Francais de Pneumo-Cancerologie (GFPC) Protocol 95-1 G. Robinet, P. Thomas, J. L. Breton, H. Lena, S. Gouva, G. Dabouis, J. Bennouna, P. J. Souquet, P. Balmes, L. Thiberville, P. Fournel, E. Quoix, R. Riou, P. Rebattu, M. Perol, D. Paillotin, F. Mornex 2001
Recursive Partitioning Analysis Groups II-III brain metastases of non-small cell lung cancer: a phase II randomized study comparing two concurrent chemoradiotherapy regimens X. Quantin, M. C. Bozonnat, J. L. Pujol 2010
Final results of the Royal College of Radiologists' trial comparing two different radiotherapy schedules in the treatment of cerebral metastases T. J. Priestman, J. Dunn, M. Brada, R. Rampling, P. G. Baker 1996
The role of steroids in the management of metastatic carcinoma to the brain. A pilot prospective trial A. H. Wolfson, S. M. Snodgrass, J. G. Schwade, A. M. Markoe, H. Landy, L. G. Feun, K. S. Sridhar, A. H. Brandon, M. Rodriguez, P. V. Houdek 1994
Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial P. D. Brown, K. Jaeckle, K. V. Ballman, E. Farace, J. H. Cerhan, S. K. Anderson, X. W. Carrero, F. G. Barker, R. Deming, S. H. Burri, C. Menard, C. Chung, V. W. Stieber, B. E. Pollock, E. Galanis, J. C. Buckner, A. L. Asher 2016
Association of Neurosurgical Resection With Development of Pachymeningeal Seeding in Patients With Brain Metastases D. N. Cagney, N. Lamba, S. Sinha, P. J. Catalano, W. L. Bi, B. M. Alexander, A. A. Aizer 2019
Concurrent Immune Checkpoint Inhibitors and Stereotactic Radiosurgery for Brain Metastases in Non-Small Cell Lung Cancer, Melanoma, and Renal Cell Carcinoma L. Chen, J. Douglass, L. Kleinberg, X. Ye, A. E. Marciscano, P. M. Forde, J. Brahmer, E. Lipson, W. Sharfman, H. Hammers, J. Naidoo, C. Bettegowda, M. Lim, K. J. Redmond 2018
Icotinib versus whole-brain irradiation in patients with EGFR-mutant non-small-cell lung cancer and multiple brain metastases (BRAIN): a multicentre, phase 3, open-label, parallel, randomised controlled trial J. J. Yang, C. Zhou, Y. Huang, J. Feng, S. Lu, Y. Song, C. Huang, G. Wu, L. Zhang, Y. Cheng, C. Hu, G. Chen, L. Zhang, X. Liu, H. H. Yan, F. L. Tan, W. Zhong, Y. L. Wu 2017
The efficacy and roles of combining temozolomide with whole brain radiotherapy in protection neurocognitive function and improvement quality of life of non-small-cell lung cancer patients with brain metastases X. Deng, Z. Zheng, B. Lin, H. Su, H. Chen, S. Fei, Z. Fei, L. Zhao, X. Jin, C. Y. Xie 2017
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A randomized phase III trial of stereotactic radiosurgery (SRS) versus observation for patients with asymptomatic cerebral oligo-metastases in non-small-cell lung cancer S. H. Lim, J. Y. Lee, M. Y. Lee, H. S. Kim, J. Lee, J. M. Sun, J. S. Ahn, S. W. Um, H. Kim, B. S. Kim, S. T. Kim, D. L. Na, J. Y. Sun, S. H. Jung, K. Park, O. J. Kwon, J. I. Lee, M. J. Ahn 2015
Comparison of Gefitinib versus VMP in the combination with radiotherapy for multiple brain metastases from non-small cell lung cancer F. Wang, F. Ning, C. Liu, Y. Hao, L. Li, Z. Yu, S. Chen, B. Li 2015
Randomized trial of erlotinib plus whole-brain radiotherapy for NSCLC patients with multiple brain metastases S. M. Lee, C. R. Lewanski, N. Counsell, C. Ottensmeier, A. Bates, N. Patel, C. Wadsworth, Y. Ngai, A. Hackshaw, C. Faivre-Finn 2014
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Motexafin gadolinium combined with prompt whole brain radiotherapy prolongs time to neurologic progression in non-small-cell lung cancer patients with brain metastases: results of a phase III trial M. P. Mehta, W. R. Shapiro, S. C. Phan, R. Gervais, C. Carrie, P. Chabot, R. A. Patchell, M. J. Glantz, L. Recht, C. Langer, R. K. Sur, W. H. Roa, M. A. Mahe, A. Fortin, C. Nieder, C. A. Meyers, J. A. Smith, R. A. Miller, M. F. Renschler 2009
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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 A. Muacevic, B. Wowra, A. Siefert, J. C. Tonn, H. J. Steiger, F. W. Kreth 2008
Temozolomide and concomitant whole brain radiotherapy in patients with brain metastases: a phase II randomized trial E. Verger, M. Gil, R. Yaya, N. Vinolas, S. Villa, T. Pujol, L. Quinto, F. Graus 2005
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Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery? C. J. Vecht, H. Haaxma-Reiche, E. M. Noordijk, G. W. Padberg, J. H. Voormolen, F. H. Hoekstra, J. T. Tans, N. Lambooij, J. A. Metsaars, A. R. Wattendorff, et al. 1993
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Whole-brain helical tomotherapy with integrated boost for brain metastases in patients with malignant melanoma - final results of the BRAINRT trial H. Hauswald, D. Bernhardt, D. Krug, S. Katayama, G. Habl, J. L. Bermejo, J. Debus, F. Sterzing 2019
Effects of surgery with salvage stereotactic radiosurgery versus surgery with whole-brain radiation therapy in patients with one to four brain metastases (JCOG0504): A Phase III, noninferiority, randomized controlled trial T. Kayama, S. Sato, K. Sakurada, J. Mizusawa, R. Nishikawa, Y. Narita, M. Sumi, Y. Miyakita, T. Kumabe, Y. Sonoda, Y. Arakawa, S. Miyamoto, T. Beppu, K. Sugiyama, H. Nakamura, M. Nagane, Y. Nakasu, N. Hashimoto, M. Terasaki, A. Matsumura, E. Ishikawa, T. Wakabayashi, Y. Iwadate, S. Ohue, H. Kobayashi, M. Kinoshita, K. Asano, A. Mukasa, K. Tanaka, A. Asai, H. Nakamura, T. Abe, Y. Muragaki, K. Iwasaki, T. Aoki, T. Watanabe, H. Sasaki, S. Izumoto, M. Mizoguchi, T. Matsuo, H. Takeshima, M. Hayashi, H. Jokura, T. Mizowaki, E. Shimizu, H. Shirato, M. Tago, H. Katayama, H. Fukuda, S. Shibui 2018
Management of brain metastases in tyrosine kinase inhibitor-Nave epidermal growth factor receptor-mutant non-small-cell lung cancer: A retrospective multi-institutional analysis W. J. Magnuson, N. H. Lester-Coll, A. J. Wu, T. J. Yang, N. A. Lockney, N. K. Gerber, K. Beal, A. Amini, T. Patil, B. D. Kavanagh, D. R. Camidge, S. E. Braunstein, L. C. Boreta, S. K. Balasubramanian, M. S. Ahluwalia, N. G. Rana, A. Attia, S. N. Gettinger, J. N. Contessa, J. B. Yu, V. L. Chiang 2017
Treatment outcomes in patients with multiple brain metastases: A prospective randomized study A. Saha, S. K. Ghosh, C. Roy, P. Kayal 2014
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A Single Blind Randomized Controlled Trial of Hippocampal Avoidance on Neurocognitive Outcomes after Conformal Whole Brain Radiotherapy for Brain Metastases: An Initial Analysis W. C. Yang, F. M. Hsu, Y. F. Chen, C. C. Yang, J. L. Y. Chen, S. H. Kuo, J. C. H. Cheng 2019
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Whole Brain Radiotherapy Versus Stereotactic Radiosurgery in Poor-Prognosis Patients with One to 10 Brain Metastases: A Randomised Feasibility Study Raman, S., Mou, B., Hsu, F., Valev, B., Cheung, A., Vallieres, I., Ma, R., McKenzie, M., Beaton, L., Rackley, T., Gondara, L., Nichol, A. 2020
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Impact of radiation, systemic therapy and treatment sequencing on survival of patients with melanoma brain metastases Rauschenberg, R., Bruns, J., Brtting, J., Daubner, D., Lohaus, F., Zimmer, L., Forschner, A., Zips, D., Hassel, J. C., Berking, C., Kaehler, K. C., Utikal, J., Gutzmer, R., Terheyden, P., Meiss, F., Rafei-Shamsabadi, D., Kiecker, F., Debus, D., Dabrowski, E., Arnold, A., Garzarolli, M., Kuske, M., Beissert, S., Lck, S., Linn, J., Troost, E. G. C., Meier, F. 2019
Tyrosine Kinase Inhibitor Resistance Increased the Risk of Cerebral Radiation Necrosis After Stereotactic Radiosurgery in Brain Metastases of Non-small-Cell Lung Cancer: A Multi-Institutional Retrospective Case-Control Study Zhuang, H., Tao, L., Wang, X., Shi, S., Yuan, Z., Wang, E., Chang, J. Y. 2020
Immunotherapy is associated with improved survival and decreased neurologic death after SRS for brain metastases from lung and melanoma primaries Lanier, C. M., Hughes, R., Ahmed, T., LeCompte, M., Masters, A. H., Petty, W. J., Ruiz, J., Triozzi, P., Su, J., O'Neill, S., Watabe, K., Cramer, C. K., Laxton, A. W., Tatter, S. B., Wang, G., Whitlow, C., Chan, M. D. 2019

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