Abstract
A second course of whole brain radiation therapy (WBRT) has been employed in selected patients with progressive brain metastases providing favorable symptomatic palliation with acceptable toxicity, although its efficacy and safety remain matter of debate. In the present study we have evaluated the outcomes in patients with progressive intracranial disease treated with WBRT reirradiation and concurrent temozolomide between October 2010 and May 2013. Data were obtained from a prospectively maintained database including patients with brain tumors treated with radiotherapy at Sant’Andrea Hospital. We identified 27 patients (10 males and 17 females) with a median age of 54 years who received WBRT reirradiation at a dose of 25 Gy in ten fractions plus concomitant daily temozolomide administered orally at a dose of 75 mg/m2. At the time of repeat WBRT all patients had a KPS ≥ 60. The primary disease sites were lung (n = 18) and breast (n = 9). The median overall survival after the second course of WBRT was 6.2 months and the median time to progression was 5.5 months. Eight patients experienced complete resolution of symptoms, 9 patients had a significant improvement, and 6 patients had no change in their neurologic function. Four patients had further deterioration after reirradiation. Overall, 85 % of patients improved or maintained their neurologic status. No severe acute toxicity during or after the second course of WBRT reirradiation was observed. On multivariate analysis with the Cox proportional hazards model, stable or absent extracranial metastases (p = 0.005) and response to treatment (p = 0.01) were independent favorable prognostic factors for survival. The median and 12-month survival rates were 12 months and 50 % in patients with stable or absent extracranial disease and 4.6 months and 7 % in those with progressive extracranial disease (p = 0.001). In conclusion, in the respect to the small number of treated patients, repeat WBRT plus concomitant temozolomide may be a treatment option in selected patients with multiple brain metastases to improve or maintain neurological conditions and quality of life with acceptable toxicity. The favorable effects of concomitant temozolomide on survival remain unclear.
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Norden AD, Wen PY, Kesari S (2005) Brain metastases. Curr Opin Neurol 18:654–661
Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, Kenjyo M, Oya N, Hirota S, Shioura H, Kunieda E, Inomata T, Hayakawa K, Katoh N, Kobashi G (2006) Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA 295:2483–2491
Kocher M, Soffietti R, Abacioglu U, Villà S, Fauchon F, Baumert BG, Fariselli L, Tzuk-Shina T, Kortmann RD, Carrie C, Hassel MB, Kouri M, Valeinis E, van den Berge D, Collette S, Collette L, Mueller RP (2011) 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 29:134–141
Scoccianti S, Ricardi U (2012) Treatment of brain metastases: review of phase III randomized controlled trials. Radiother Oncol 102:168–179
Ammirati M, Cobbs CS, Linskey ME, Paleologos NA, Ryken TC, Burri SH, Asher AL, Loeffler JS, Robinson PD, Andrews DW, Gaspar LE, Kondziolka D, McDermott M, Mehta MP, Mikkelsen T, Olson JJ, Patchell RA, Kalkanis SN (2010) The role of retreatment in the management of recurrent/progressive brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol 96:85–96
Shehata WM, Hendrickson FR, Hindo WA (1974) Rapid fractionation technique and re-treatment of cerebral metastases by irradiation. Cancer 34:257–261
Kurup P, Reddy S, Hendrickson FR (1980) Results of re-irradiation for cerebral metastases. Cancer 46:2587–2589
Hazuka MB, Kinzie JJ (1988) Brain metastases: results and effects of re-irradiation. Int J Radiat Oncol Biol Phys 15:433–437
Cooper JS, Steinfeld AD, Lerch IA (1990) Cerebral metastases: value of reirradiation in selected patients. Radiology 174:883–885
Wong WW, Schild SE, Sawyer TE, Shaw EG (1996) Analysis of outcome in patients reirradiated for brain metastases. Int J Radiat Oncol Biol Phys 34:585–590
Abdel-Wahab MM, Wolfson AH, Raub W, Landy H, Feun L, Sridhar K, Brandon AH, Mahmood S, Markoe AM (1997) The role of hyperfractionated re-irradiation in metastatic brain disease: a single institutional trial. Am J Clin Oncol 20:158–160
Sadikov E, Bezjak A, Yi QL, Wells W, Dawson L, Millar BA, Laperriere N (2007) Value of whole brain re-irradiation for brain metastases—single centre experience. Clin Oncol (R Coll Radiol) 19:532–538
Akiba T, Kunieda E, Kogawa A, Komatsu T, Tamai Y, Ohizumi Y (2012) Re-irradiation for metastatic brain tumors with whole-brain radiotherapy. Jpn J Clin Oncol 42:264–269
Son CH, Jimenez R, Niemierko A, Loeffler JS, Oh KS, Shih HA (2012) Outcomes after whole brain reirradiation in patients with brain metastases. Int J Radiat Oncol Biol Phys 82:167–172
Ozgen Z, Atasoy BM, Ucuncu Kefeli A, Seker A, Dane F, Abacioglu U (2013) The benefit of whole brain reirradiation in patients with multiple brain metastases. Radiat Oncol 8:186
Mehta MP, Paleologos NA, Mikkelsen T, Robinson PD, Ammirati M, Andrews DW, Asher AL, Burri SH, Cobbs CS, Gaspar LE, Kondziolka D, Linskey ME, Loeffler JS, McDermott M, Olson JJ, Patchell RA, Ryken TC, Kalkanis SN (2010) The role of chemotherapy in the management of newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol 96:71–83
Antonadou D, Paraskevaidis M, Sarris G, Coliarakis N, Economou I, Karageorgis P, Throuvalas N (2002) Phase II randomized trial of temozolomide and concurrent radiotherapy in patients with brain metastases. J Clin Oncol 20:3644–3650
Verger E, Gil M, Yaya R, Viñolas N, Villà S, Pujol T, Quintó L, Graus F (2005) Temozolomide and concomitant whole brain radiotherapy in patients with brain metastases: a phase II randomized trial. Int J Radiat Oncol Biol Phys 61:185–191
Chua D, Krzakowski M, Chouaid C, Pallotta MG, Martinez JI, Gottfried M, Curran W, Throuvalas N (2010) Whole-brain radiation therapy plus concomitant temozolomide for the treatment of brain metastases from non-small-cell lung cancer: a randomized, open-label phase II study. Clin Lung Cancer 11:176–181
Gamboa-Vignolle C, Ferrari-Carballo T, Arrieta Ó, Mohar A (2012) Whole-brain irradiation with concomitant daily fixed-dose temozolomide for brain metastases treatment: a randomised phase II trial. Radiother Oncol 102:187–191
Chang JE, Khuntia D, Robins HI, Mehta MP (2007) Radiotherapy and radiosensitizers in the treatment of glioblastoma multiforme. Clin Adv Hematol Oncol 5:894–902
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Minniti, G., Scaringi, C., Lanzetta, G. et al. Whole brain reirradiation and concurrent temozolomide in patients with brain metastases. J Neurooncol 118, 329–334 (2014). https://doi.org/10.1007/s11060-014-1435-0
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DOI: https://doi.org/10.1007/s11060-014-1435-0