Radiotherapy in lung adenocarcinoma with brain metastases: effects of activating epidermal growth factor receptor mutations on clinical response
Open accessAbstract
PURPOSE: Whole-brain radiation therapy (WBRT) has been applied to inoperable brain metastases in lung adenocarcinoma. Recently, an in vitro study showed reduced clonogenic survival of mutant epidermal growth factor receptor (EGFR) lung cancer cell lines in response to ionizing radiation compared with that of the wild type. To elucidate the role of EGFR mutations in radiation treatment, we evaluated the clinical response to WBRT and survival of lung adenocarcinoma patients with brain metastases. EXPERIMENTAL DESIGN: This was a retrospective analysis of 63 patients with brain metastases from lung adenocarcinoma who were treated with WBRT. Demographic data, EGFR mutation status, response to WBRT, and survival data were collected. Clinical response was assessed 1 month after the start of WBRT. Univariate and logistic regression models were used to test potential predictive factors associated with clinical response. Log-rank test and Cox regression were analyzed to identify factors that affected survival. RESULTS: Clinical response to WBRT was observed in 29 patients (46%), with 34 nonresponder patients (54%). Patients with EGFR mutations had higher response rates to WBRT compared with those with the wild-type (54% versus 24%; P = 0.045). Both the administration of EGFR tyrosine kinase inhibitor (P = 0.034) and EGFR mutation (P = 0.029) were independently associated with response to WBRT. In Cox regression analysis, WBRT responder (P = 0.010) and absence of extracranial metastases (P = 0.002) were associated with better survival. CONCLUSIONS: Both the EGFR mutations and the administration of EGFR TKI during WBRT were independent predictors of response to WBRT in brain metastases of lung adenocarcinoma.
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Patients with EGFR-mutant NSCLC demonstrate high response rates to whole brain radiation therapy.
“patients with EGFRmutant NSCLC demonstrate high response rates to whole brain radiation therapy (WBRT) 110”
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Cites
Lynch, T. J., Bell, D. W., Sordella, R., Gurubhagavatula, S., Okimoto, R. A., Brannigan, B. W., Harris, P. L., Haserlat, S. M., Supko, J. G., Haluska, F. G., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040938 · Cited by 11,486 · see citing works
<i>EGFR</i> Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy
Paez, J. G., Jänne, P. A., Lee, J. C., Tracy, S., Greulich, H., Gabriel, S., Herman, P., Kaye, F. J., Lindeman, N., Boggon, T. J., et al. (2004) · Science · doi:10.1126/science.1099314 · Cited by 9,368 · see citing works
Radiotherapy plus Cetuximab for Squamous-Cell Carcinoma of the Head and Neck
Bonner, J. A., Harari, P. M., Giralt, J., Azarnia, N., Shin, D. M., Cohen, R. B., Jones, C. U., Sur, R. K., Raben, D., Jassem, J., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa053422 · Cited by 5,109 · see citing works
Pao, W., Miller, V., Zakowski, M., Doherty, J., Politi, K., Sarkaria, I., Singh, B., Heelan, R., Rusch, V., Fulton, L., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405220101 · Cited by 4,338 · see citing works
Gaspar, L. E., Scott, C., Rotman, M., Asbell, S. O., Phillips, T. L., Wasserman, T. H., McKenna, W. G., & Byhardt, R. W. (1997) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/s0360-3016(96)00619-0 · Cited by 2,548 · see citing works
Andrews, D. W., Scott, C., Sperduto, P. W., Flanders, A. E., Gaspar, L. E., Schell, M. C., Werner‐Wasik, M., Demas, W. F., Ryu, J. K., Bahary, J.-P., et al. (2004) · The Lancet · doi:10.1016/s0140-6736(04)16250-8 · Cited by 2,418 · see citing works
Shigematsu, H., Lin, L., Takahashi, T., Nomura, M., Suzuki, M., Wistuba, I. I., Fong, K. M., Lee, H., Toyooka, S., Shimizu, N., et al. (2005) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/dji055 · Cited by 2,377 · see citing works
Mitsudomi, T., Kosaka, T., Endoh, H., Horio, Y., Hida, T., Mori, S., Hatooka, S., Shinoda, M., Takahashi, T., & Yatabe, Y. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.00.992 · Cited by 938 · see citing works
Validation of the RTOG recursive partitioning analysis (RPA) classification for brain metastases
Gaspar, L. E., Scott, C., Murray, K., & Curran, W. J. (2000) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/s0360-3016(00)00547-2 · Cited by 531 · see citing works
Mehta, M. P., Rodrigus, P. T. R., Terhaard, C. H. J., Rao, A. R., Suh, J. H., Roa, W., Souhami, L., Bezjak, A., Leibenhaut, M. H., Komaki, R. U., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.12.122 · Cited by 466 · see citing works
Schmidt‐Ullrich, R., Mikkelsen, R. B., Dent, P., Todd, D. G., Valerie, K. C., Kavanagh, B. D., Contessa, J. N., Rorrer, W. K., & Chen, P. B. (1997) · Oncogene · doi:10.1038/sj.onc.1201275 · Cited by 412 · see citing works
Current Management of Brain Metastases, With a Focus on Systemic Options
Langer, C. J., & Mehta, M. P. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.03.145 · Cited by 377 · see citing works
Gefitinib in patients with brain metastases from non-small-cell lung cancer: a prospective trial
Ceresoli, G. L., Cappuzzo, F., Gregorc, V., Bartolini, S., Crinò, L., & Villa, E. (2004) · Annals of Oncology · doi:10.1093/annonc/mdh276 · Cited by 351 · see citing works
Akimoto, T., Hunter, N. R., Buchmiller, L., et al. (1999) · PubMed · Cited by 350 · see citing works
Mehta, M. P., Tsao, M. N., Whelan, T. J., et al. (2005) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2005.05.023 · Cited by 347 · see citing works
Brain metastases in adenocarcinoma of the lung: frequency, risk groups, and prognosis.
Sørensen, J. B., Hansen, H. H., Hansen, M., & Dombernowsky, P. (1988) · Journal of Clinical Oncology · doi:10.1200/jco.1988.6.9.1474 · Cited by 341 · see citing works
The epidermal growth factor receptor mediates radioresistance
Liang, K., Ang, K. K., Milas, L., Hunter, N. R., & Fan, Z. (2003) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/s0360-3016(03)00511-x · Cited by 292 · see citing works
Patterns of HER-2/neu Amplification and Overexpression in Primary and Metastatic Breast Cancer
Simon, R., Nocito, A., Hubscher, T., et al. (2001) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/93.15.1141 · Cited by 291 · see citing works
Zidan, J., Dashkovsky, I., Stayerman, C., et al. (2005) · British Journal of Cancer · doi:10.1038/sj.bjc.6602738 · Cited by 282 · see citing works
Huang, S. M., Li, J., Armstrong, E. A., & Harari, P. M. (2002) · PubMed · Cited by 263 · see citing works
Das, A. K., Sato, M., Story, M. D., Peyton, M., Graves, R., Redpath, S., Girard, L., Gazdar, A. F., Shay, J. W., Minna, J. D., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-2627 · Cited by 217 · see citing works
Parra, H. J. S., Cavina, R., Latteri, F. S., Zucali, P. A., Campagnoli, E., Morenghi, E., Grimaldi, G. C., Roncalli, M. G., & Santoro, A. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6601923 · Cited by 200 · see citing works
Hotta, K., Kiura, K., Ueoka, H., Tabata, M., Fujiwara, K., Kozuki, T., Okada, T., Hisamoto, A., & Tanimoto, M. (2004) · Lung Cancer · doi:10.1016/j.lungcan.2004.04.036 · Cited by 176 · see citing works
Priestman, T. J., Dunn, J., Brada, M., et al. (1996) · Clinical Oncology · doi:10.1016/s0936-6555(05)80717-4 · Cited by 171 · see citing works
Shih, J., Gow, C., Yu, C., Yang, C., Chang, Y., Tsai, M., Hsu, Y., Chen, K., Su, W., & Yang, P. (2005) · International Journal of Cancer · doi:10.1002/ijc.21458 · Cited by 170 · see citing works
Self-citationNieder, C., Nestle, U., Motaref, B., et al. (2000) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/s0360-3016(99)00416-2 · Cited by 168 · see citing works
Epidermal growth factor receptor and tumor response to radiation: in vivo preclinical studies
Milas, L., Fan, Z., Andratschke, N. H., et al. (2004) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2003.08.035 · Cited by 162 · see citing works
Potential indicators of radiosensitivity in squamous cell carcinoma of the head and neck
Sheridan, M. T., O’Dwyer, T. P., Seymour, C. B., et al. (1997) · Radiation Oncology Investigations · doi:10.1002/(sici)1520-6823(1997)5:4 · Cited by 153 · see citing works
Han, S., Hwang, P. G., Chung, D. H., Kim, D., Im, S., Kim, Y. T., Kim, T., Heo, D. S., Bang, Y., & Kim, N. K. (2004) · International Journal of Cancer · doi:10.1002/ijc.20550 · Cited by 150 · see citing works
Chiu, C., Tsai, C., Chen, Y., et al. (2004) · Lung Cancer · doi:10.1016/j.lungcan.2004.05.014 · Cited by 143 · see citing works
Italiano, A., Burel‐Vandenbos, F., Otto, J., Mouroux, J., Fontaine, D., Marcy, P. Y., Cardot‐Leccia, N., Thyss, A., & Pédeutour, F. (2006) · Annals of Oncology · doi:10.1093/annonc/mdl038 · Cited by 128 · see citing works
HER2gene status in primary breast cancers and matched distant metastases
Tapia, C., Savic, S., Wagner, U., et al. (2007) · Breast Cancer Research · doi:10.1186/bcr1676 · Cited by 124 · see citing works
Epidermal Growth Factor Receptor as a Genetic Therapy Target for Carcinoma Cell Radiosensitization
Lammering, G., Hewit, T. H., Hawkins, W., Contessa, J. N., Reardon, D. B., Lin, P., Valerie, K. C., Dent, P., Mikkelsen, R. B., & Schmidt‐Ullrich, R. (2001) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/93.12.921 · Cited by 95 · see citing works
Shimato, S., Mitsudomi, T., Kosaka, T., et al. (2006) · Neuro-Oncology · doi:10.1215/15228517-2005-002 · Cited by 91 · see citing works
Survival following whole brain radiation treatment for cerebral metastases: an audit of 474 patients
Broadbent, A. M., Hruby, G., Tin, M. M., et al. (2004) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2004.02.019 · Cited by 68 · see citing works
Moscetti, L. I., Nelli, F., Felici, A., et al. (2006) · Cancer · doi:10.1002/cncr.22399 · Cited by 67 · see citing works
Kępka, L., Cieślak, E., Bujko, K., et al. (2005) · Acta Oncologica · doi:10.1080/02841860510029699 · Cited by 58 · see citing works
Yang, C., Shih, J., Chen, K., Yu, C., Yang, T., Lin, C., Su, W., Gow, C., Hsu, C., Chang, G., et al. (2006) · Cancer · doi:10.1002/cncr.22220 · Cited by 54 · see citing works
Self-citationRadiotherapy for brain metastases: defining palliative response
Bezjak, A., Adam, J., Panzarella, T., Levin, W., Barton, R., Kirkbride, P., McLean, M., Mason, W. P., Wong, C. S., & Laperrière, N. (2001) · Radiotherapy and Oncology · doi:10.1016/s0167-8140(01)00426-1 · Cited by 53 · see citing works
HER2 in Brain Metastases: Issues of Concordance, Survival, and Treatment
Fuchs, I. B., Loebbecke, M., Bühler, H., et al. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.04.016 · Cited by 53 · see citing works
Prognostic factors in lung cancer with brain metastasis
Mehmet, S., Demiral, A. N., Çetingöz, R., et al. (1998) · Radiotherapy and Oncology · doi:10.1016/s0167-8140(97)00124-2 · Cited by 52 · see citing works
Current Strategies in Whole-brain Radiation Therapy for Brain Metastases
Mehta, M. P., & Khuntia, D. (2005) · Neurosurgery · doi:10.1227/01.neu.0000182742.40978.e7 · Cited by 50 · see citing works
Effectiveness of whole brain radiotherapy in the treatment of brain metastases: a systematic review
Pease, N. J., Edwards, A., & Moss, L. (2005) · Palliative Medicine · doi:10.1191/0269216305pm1017oa · Cited by 48 · see citing works
Whole brain radiation therapy in management of brain metastasis: results and prognostic factors
Saito, E. Y., Viani, G. A., Ferrigno, R., Nakamura, R. A., Novaes, P. E., Pellizzon, A. C. A., Fogaroli, R. C., Conte, M. A., & Salvajoli, J. V. (2006) · Radiation Oncology · doi:10.1186/1748-717x-1-20 · Cited by 43 · see citing works
Radiation Recall Dermatitis May Represent the Koebner Phenomenon
Camidge, D. R., Price, A., Ortmann, E., et al. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.99.148 · Cited by 23 · see citing works
Effect of gefitinib (ZD1839) on metastatic brain tumour
Takahashi, H., Ohrui, T., Ebihara, S., et al. (2003) · Lung Cancer · doi:10.1016/j.lungcan.2003.09.017 · Cited by 19 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Gaspar L, Scott C, Rotman M, et al. Recursive parti- tioning analysis (RPA) of prognostic factors in three RadiationTherapy Oncology Group (RTOG) brain me- tastases trials. Int J Radiat Oncol Biol Phys 1997;37: 745 ^51.
- Liang K, Ang KK, Milas L, Hunter N, Fan Z. The epi- dermal growth factor receptor mediates radioresist- ance. Int J Radiat Oncol Biol Phys 2003;57:246 ^54.
Cited by
Sorted by citations
Wu, J.-Y., Wu, S.-G., Yang, C.-H., Gow, C.-H., Chang, Y.-L., Yu, C.-J., Shih, J.-Y., & Yang, P.-C. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-5123 · Cited by 319 · see citing works
Self-citationBrain metastases from lung cancer responding to erlotinib: the importance of<i>EGFR</i>mutation
Porta, R., Sánchez-Torres, J. M., Paz-Ares, L., Massutí, B., Reguart, N., Mayo, C., Lianes, P., Queralt, C., Guillem, V., Salinas, P., et al. (2011) · European Respiratory Journal · doi:10.1183/09031936.00195609 · Cited by 316 · see citing works
Tan, D. S. W., Yom, S. S., Tsao, M. S., Pass, H. I., Kelly, K., Peled, N., Yung, R. C., Wistuba, I. I., Yatabe, Y., Unger, M., et al. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2016.05.008 · Cited by 201 · see citing works
Soon, Y. Y., Leong, C. N., Koh, W. Y., & Tham, I. W. K. (2015) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2014.12.011 · Cited by 110 · see citing works
Gerber, N. K., Yamada, Y., Rimner, A., Shi, W., Riely, G. J., Beal, K., Yu, H. A., Chan, T. A., Zhang, Z., & Wu, A. J. (2014) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2014.02.022 · Cited by 96 · see citing works
- Authors
- Gow, C.-H., Chien, C.-R., Chang, Y.-L., Chiu, Y.-H., Kuo, S.-H., Shih, J.-Y., Chang, Y.-C., Yu, C.-J., Yang, C.-H., & Yang, P.-C.
- Affiliations
- Luodong Poh-Ai Hospital (TW)
- 2Division of Radiation Oncology, Department of Oncology,
- 3Department of Pathology,
- National Taiwan University (TW)
- National Taiwan University Hospital (TW)
- 1Department of Internal Medicine,
- 4Department of Medical Imaging, and
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2008-01-01
- Volume
- 14
- Issue
- 1
- Pages
- 162-168
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2119831956
- Cited by
- 146
- References
- 46
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 6 · 2022: 3 · 2021: 2 · 2020: 5 · 2019: 7 · 2018: 7 · 2017: 18 · 2016: 18 · 2015: 16 · 2014: 16 · 2013: 13 · 2012: 7
- FWCI
- 7.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Council (NSC-95-2314-B-002-113-MY3)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Brain Metastases and Treatment
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Keywords
- lung adenocarcinoma, brain metastases, whole brain radiotherapy, EGFR mutation, EGFR tyrosine kinase inhibitors, radiosensitivity, predictors of treatment response, survival, extracranial metastases
- MeSH terms
- Adenocarcinoma, Adult, Age Factors, Aged, Aged, 80 and over, Brain Neoplasms, Combined Modality Therapy, Enzyme Inhibitors, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Protein-Tyrosine Kinases, Radiation Tolerance, Retrospective Studies, Smoking, ErbB Receptors
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