Top

Published in:

Open Access 01-12-2015 | Research

Increased survival with the combination of stereotactic radiosurgery and gefitinib for non-small cell lung cancer brain metastasis patients: a nationwide study in Taiwan

Published in: Radiation Oncology | Issue 1/2015

Abstract

Purpose

Whole brain irradiation (WBRT) either with or without resection has historically been the treatment for brain metastases from non-small cell lung cancer (NSCLC). The effect of gamma knife (GK) radiosurgery, chemotherapy, or the combination remains incompletely defined. In this study, we assessed the outcome of brain metastases from non-small cell lung cancer treated by WBRT followed by GK, gefitinib, or the combination of GK and gefitinib.

Material and methods

We retrieved the records of NSCLC patients with brain metastases from the National Health Insurance Research Database (NHIRD) of Taiwan from 2004 to 2010. WBRT either with or without resection was the first line treatment for nearly all patients. The decision to add GK and/or gefitinib treatment was at the discretion of the treating physician and based upon a patient’s medical records and imaging data. These patients were classified into four groups including WBRT, WBRT + gefitinib, WBRT + GK, WBRT + gefitinib + GK. These data was evaluated for difference in survival and factors that portended an extended survival from the time of brain metastasis diagnosis.

Results

Of the 60194 patients with newly diagnosed NSCLC, 23874 (39.6 %) developed brain metastases. The distribution of patients for the groups was WBRT for 20241, WBRT + gefitinib for 3379, WBRT + GK for 155, and WBRT+ gefitinib + GK for 99 patients. The median survival for the time of brain metastasis diagnosis for WBRT, WBRT+ gefitinib, WBRT+ GK, WBRT+ gefitinib + GK groups was 0.53, 1.01, 1.46, and 2.25 years, respectively (p < 0.0001). The hazard ratio (95 % CI) for survival was 1, 0.56, 0.43, and 0.40, respectively (p < 0.001). The adjusted hazard ratio (95 % CI) by age, sex and Charlson comorbidity index (CCI) was 1, 0.73, 0.49, and 0.42, respectively (p < 0.001).

Conclusion

Patients with brain metastases from NSCLC receiving GK or gefitinib demonstrated extended survival. The improved survival seen with GK and gefitinib suggests a survival benefit in selected patients receiving the combined treatment. Further Phase II study should be conducted to assessment these influence.

Rizzi A, Tondini M, Rocco G, Rossi G, Robustellini M, Radaelli F, et al. Lung cancer with a single brain metastasis: therapeutic options. Tumori. 1990;76(6):579–81.PubMed

Sperduto PW, Chao ST, Sneed PK, Luo X, Suh J, Roberge D, et al. Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4,259 patients. Int J Radiat Oncol Biol Phys. 2010;77(3):655–61.PubMedCrossRef

Pan HC, Sheehan J, Stroila M, Steiner M, Steiner L. Gamma knife surgery for brain metastases from lung cancer. J Neurosurg. 2005;102(Suppl):128–33.PubMedCrossRef

Chen JC, Petrovich Z, O’Day S, Morton D, Essner R, Giannotta SL, et al. Stereotactic radiosurgery in the treatment of metastatic disease to the brain. Neurosurgery. 2000;47(2):268–79.PubMedCrossRef

Kim YS, Kondziolka D, Flickinger JC, Lunsford LD. Stereotactic radiosurgery for patients with nonsmall cell lung carcinoma metastatic to the brain. Cancer. 1997;80(11):2075–83.PubMedCrossRef

Nakagawa K, Tago M, Terahara A, Aoki Y, Sasaki T, Kurita H, et al. A single institutional outcome analysis of Gamma Knife radiosurgery for single or multiple brain metastases. Clin Neurol Neurosurg. 2000;102(4):227–32.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCentralPubMedCrossRef

10.

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.PubMedCrossRef

11.

Salomon DS, Brandt R, Ciardiello F, Normanno N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol. 1995;19(3):183–232.PubMedCrossRef

12.

Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard JY, et al. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected]. J Clin Oncol. 2003;21(12):2237–46.PubMedCrossRef

13.

Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304(5676):1497–500.PubMedCrossRef

14.

Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350(21):2129–39.PubMedCrossRef

15.

Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, et al. EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A. 2004;101(36):13306–11.PubMedCentralPubMedCrossRef

16.

Huang SF, Liu HP, Li LH, Ku YC, Fu YN, Tsai HY, et al. High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan. Clin Cancer Res. 2004;10(24):8195–203.PubMedCrossRef

17.

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. 2004;15(7):1042–7.PubMedCrossRef

18.

Cappuzzo F, Ardizzoni A, Soto-Parra H, Gridelli C, Maione P, Tiseo M, et al. Epidermal growth factor receptor targeted therapy by ZD 1839 (Iressa) in patients with brain metastases from non-small cell lung cancer (NSCLC). Lung Cancer. 2003;41(2):227–31.PubMedCrossRef

19.

Chiu CH, Tsai CM, Chen YM, Chiang SC, Liou JL, Perng RP. Gefitinib is active in patients with brain metastases from non-small cell lung cancer and response is related to skin toxicity. Lung Cancer. 2005;47(1):129–38.PubMedCrossRef

20.

Lai CS, Boshoff C, Falzon M, Lee SM. Complete response to erlotinib treatment in brain metastases from recurrent NSCLC. Thorax. 2006;61(1):91.PubMedCentralPubMedCrossRef

21.

Popat S, Hughes S, Papadopoulos P, Wilkins A, Moore S, Priest K, et al. Recurrent responses to non-small cell lung cancer brain metastases with erlotinib. Lung Cancer. 2007;56(1):135–7.PubMedCrossRef

22.

Shimato S, Mitsudomi T, Kosaka T, Yatabe Y, Wakabayashi T, Mizuno M, et al. EGFR mutations in patients with brain metastases from lung cancer: association with the efficacy of gefitinib. Neuro Oncol. 2006;8(2):137–44.PubMedCentralPubMedCrossRef

23.

Chinnaiyan P, Huang S, Vallabhaneni G, Armstrong E, Varambally S, Tomlins SA, et al. Mechanisms of enhanced radiation response following epidermal growth factor receptor signaling inhibition by erlotinib (Tarceva). Cancer Res. 2005;65(8):3328–35.PubMed

24.

Ochs JS. Rationale and clinical basis for combining gefitinib (IRESSA, ZD1839) with radiation therapy for solid tumors. Int J Radiat Oncol Biol Phys. 2004;58(3):941–9.PubMedCrossRef

25.

Ma S, Xu Y, Deng Q, Yu X. Treatment of brain metastasis from non-small cell lung cancer with whole brain radiotherapy and Gefitinib in a Chinese population. Lung Cancer. 2009;65(2):198–203.PubMedCrossRef

26.

Law A, Karp DD, Dipetrillo T, Daly BT. Emergence of increased cerebral metastasis after high-dose preoperative radiotherapy with chemotherapy in patients with locally advanced nonsmall cell lung carcinoma. Cancer. 2001;92(1):160–4.PubMedCrossRef

27.

Xu Z, Schlesinger D, Toulmin S, Rich T, Sheehan J. Impact of triple-negative phenotype on prognosis of patients with breast cancer brain metastases. Int J Radiat Oncol Biol Phys. 2012;84(3):612–8.PubMedCrossRef

28.

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.PubMedCrossRef

29.

Thatcher N, Chang A, Parikh P, Rodrigues PJ, Ciuleanu T, von PJ, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet. 2005;366(9496):1527–37.PubMedCrossRef

30.

Maruyama R, Nishiwaki Y, Tamura T, Yamamoto N, Tsuboi M, Nakagawa K, et al. Phase III study, V-15-32, of gefitinib versus docetaxel in previously treated Japanese patients with non-small-cell lung cancer. J Clin Oncol. 2008;26(26):4244–52.PubMedCrossRef

31.

Kim ES, Hirsh V, Mok T, Socinski MA, Gervais R, Wu YL, et al. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet. 2008;372(9652):1809–18.PubMedCrossRef

32.

Cufer T, Vrdoljak E, Gaafar R, Erensoy I, Pemberton K. Phase II, open-label, randomized study (SIGN) of single-agent gefitinib (IRESSA) or docetaxel as second-line therapy in patients with advanced (stage IIIb or IV) non-small-cell lung cancer. Anticancer Drugs. 2006;17(4):401–9.PubMedCrossRef

33.

Asahina H, Yamazaki K, Kinoshita I, Sukoh N, Harada M, Yokouchi H, et al. A phase II trial of gefitinib as first-line therapy for advanced non-small cell lung cancer with epidermal growth factor receptor mutations. Br J Cancer. 2006;95(8):998–1004.PubMedCentralPubMedCrossRef

34.

Inoue A, Suzuki T, Fukuhara T, Maemondo M, Kimura Y, Morikawa N, et al. Prospective phase II study of gefitinib for chemotherapy-naive patients with advanced non-small-cell lung cancer with epidermal growth factor receptor gene mutations. J Clin Oncol. 2006;24(21):3340–6.PubMedCrossRef

35.

Sutani A, Nagai Y, Udagawa K, Uchida Y, Koyama N, Murayama Y, et al. Gefitinib for non-small-cell lung cancer patients with epidermal growth factor receptor gene mutations screened by peptide nucleic acid-locked nucleic acid PCR clamp. Br J Cancer. 2006;95(11):1483–9.PubMedCentralPubMedCrossRef

36.

Tamura K, Okamoto I, Kashii T, Negoro S, Hirashima T, Kudoh S, et al. Multicentre prospective phase II trial of gefitinib for advanced non-small cell lung cancer with epidermal growth factor receptor mutations: results of the West Japan Thoracic Oncology Group trial (WJTOG0403). Br J Cancer. 2008;98(5):907–14.PubMedCentralPubMedCrossRef

37.

Sequist LV, Martins RG, Spigel D, Grunberg SM, Spira A, Janne PA, et al. First-line gefitinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutations. J Clin Oncol. 2008;26(15):2442–9.PubMedCrossRef

38.

Lee DH, Han JY, Yu SY, Kim HY, Nam BH, Hong EK, et al. The role of gefitinib treatment for Korean never-smokers with advanced or metastatic adenocarcinoma of the lung: a prospective study. J Thorac Oncol. 2006;1(9):965–71.PubMedCrossRef

39.

Cappuzzo F, Ligorio C, Janne PA, Toschi L, Rossi E, Trisolini R, et al. Prospective study of gefitinib in epidermal growth factor receptor fluorescence in situ hybridization-positive/phospho-Akt-positive or never smoker patients with advanced non-small-cell lung cancer: the ONCOBELL trial. J Clin Oncol. 2007;25(16):2248–55.PubMedCrossRef

40.

Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.PubMedCrossRef

41.

Birim O, Kappetein AP, Bogers AJ. Charlson comorbidity index as a predictor of long-term outcome after surgery for nonsmall cell lung cancer. Eur J Cardiothorac Surg. 2005;28(5):759–62.PubMedCrossRef

42.

Wang CY, Lin YS, Tzao C, Lee HC, Huang MH, Hsu WH, et al. Comparison of Charlson comorbidity index and Kaplan-Feinstein index in patients with stage I lung cancer after surgical resection. Eur J Cardiothorac Surg. 2007;32(6):877–81.PubMedCrossRef

43.

Ganti AK, Siedlik E, Marr AS, Loberiza Jr FR, Kessinger A. Predictive ability of Charlson comorbidity index on outcomes from lung cancer. Am J Clin Oncol. 2011;34(6):593–6.PubMedCrossRef

44.

Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med. 1990;322(8):494–500.PubMedCrossRef

45.

McKillop D, Hutchison M, Partridge EA, Bushby N, Cooper CM, Clarkson-Jones JA, et al. Metabolic disposition of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in rat, dog and man. Xenobiotica. 2004;34(10):917–34.PubMedCrossRef

46.

Heimberger AB, Learn CA, Archer GE, McLendon RE, Chewning TA, Tuck FL, et al. Brain tumors in mice are susceptible to blockade of epidermal growth factor receptor (EGFR) with the oral, specific, EGFR-tyrosine kinase inhibitor ZD1839 (iressa). Clin Cancer Res. 2002;8(11):3496–502.PubMed

47.

Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354(6):567–78.PubMedCrossRef

48.

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.PubMedCentralPubMedCrossRef

49.

Sperduto PW, Hall WA. Radiosurgery, cost-effectiveness, gold standards, the scientific method, cavalier cowboys, and the cost of hope. Int J Radiat Oncol Biol Phys. 1996;36(2):511–3.PubMedCrossRef

50.

Sperduto PW, Wang M, Robins HI, Schell MC, Werner-Wasik M, Komaki R, et al. 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. Int J Radiat Oncol Biol Phys. 2013;85(5):1312–8.PubMedCentralPubMedCrossRef

Title: Increased survival with the combination of stereotactic radiosurgery and gefitinib for non-small cell lung cancer brain metastasis patients: a nationwide study in Taiwan
Publication date: 01-12-2015
Published in: Radiation Oncology / Issue 1/2015
Electronic ISSN: 1748-717X
DOI: https://doi.org/10.1186/s13014-015-0431-7

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Increased survival with the combination of stereotactic radiosurgery and gefitinib for non-small cell lung cancer brain metastasis patients: a nationwide study in Taiwan

Abstract

Purpose

Material and methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Material and methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2015

Dosimetric evaluation of synthetic CT relative to bulk density assignment-based magnetic resonance-only approaches for prostate radiotherapy

Integration of BOLD-fMRI and DTI into radiation treatment planning for high-grade gliomas located near the primary motor cortexes and corticospinal tracts

Miliary pattern of brain metastases – a case report of a hyperacute onset in a patient with malignant melanoma documented by magnetic resonance imaging

Dose calculation of Acuros XB and Anisotropic Analytical Algorithm in lung stereotactic body radiotherapy treatment with flattening filter free beams and the potential role of calculation grid size

Prospective study of cetuximab and gemcitabine in combination with radiation therapy: feasibility and efficacy in locally advanced pancreatic head cancer

Regional hyperthermia of the abdomen, a pilot study towards the treatment of peritoneal carcinomatosis