Hypofractionated stereotactic radiotherapy of limited brain metastases: a single-centre individualized treatment approach

BMC Cancer

Diana Steinmann¹  Michael Bremer¹  Hans Christiansen¹  Jörg Frühauf¹  Martin Werner¹  Stefan Janssen¹  Bettina Märtens¹ 

[1]Radiation Oncology, Medical School Hannover, Carl-Neuberg-Str. 1, Hannover, 30625, Germany

关键词: Fractionation;    SRS;    hfSRT;    Brain tumours;   

Others  :  1080113
DOI  :  10.1186/1471-2407-12-497

 received in 2012-07-27, accepted in 2012-10-23,  发布年份 2012

【 摘 要 】

Background

We retrospectively report treatment results of our single-centre experience with hypofractionated stereotactic radiotherapy (hfSRT) of limited brain metastases in primary and recurrence disease situations. Our aim was to find the most effective and safe dose concept.

Methods

From 04/2006 to 12/2010, 75 patients, with 108 intracranial metastases, were treated with hfSRT.52 newly diagnosed metastases (48%), without up-front whole brain radiotherapy (WBRT), received hfSRT as a primary treatment. 56 metastases (52%) received a prior WBRT and were treated in this study in a recurrence situation. Main fractionation concepts used for primary hfSRT were 6-7x5 Gy (61.5%) and 5x6 Gy (19.2%), for recurrent hfSRT 7-10x4 Gy (33.9%) and 5-6x5 Gy (33.9%).

Results

Median overall survival (OS) of all patients summed up to 9.1 months, actuarial 6-and 12-month-OS was 59% and 35%, respectively. Median local brain control (LC) was 11.9 months, median distant brain control (DC) 3.9 months and intracranial control (IC) 3.4 months, respectively. Variables with significant influence on OS were Gross Tumour Volume (GTV) (p = 0.019), the biological eqivalent dose (calculated on a 2 Gy single dose, EQD2, α/β = 10) < and ≥ median of 39 Gy (p = 0.012), extracerebral activity of the primary tumour (p < 0.001) and the steroid uptake during hfSRT (p = 0.03). LC was significantly influenced by the EQD2, ≤ and > 35 Gy (p = 0.004) in bothuni- and multivariate Cox regression analysis. Median LC was 14.9 months for EQD2 >35 Gy and 3.4 months for doses ≤35 Gy, respectively. Early treatment related side effects were usually mild. Nevertheless, patients with a EQD2 >35 Gy had higher rates of toxicity (31%) than ≤35 Gy (8.3%, p=0.026).

Conclusion

Comparing different dose concepts in hfSRT, a cumulative EQD2 of ≥35 Gy seems to be the most effective concept in patients with primary or recurrent limited brain metastases. Despite higher rates of only mild toxicity, this concept represents a safe treatment option.

【 授权许可】

   
2012 Märtens et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Soffietti R, Ruda R, Mutani R: Management of brain metastases. J Neurol 2002, 249(10):1357-1369.
• [2]Gavrilovic IT, Posner JB: Brain metastases: epidemiology and pathophysiology. J Neurooncol 2005, 75(1):5-14.
• [3]Jenkinson MD, Haylock B, Shenoy A, Husband D, Javadpour M: Management of cerebral metastasis: evidence-based approach for surgery, stereotactic radiosurgery and radiotherapy. Eur J Cancer 2011, 47(5):649-655.
• [4]Borgelt B, Gelber R, Kramer S, Brady LW, Chang CH, Davis LW, Perez CA, Hendrickson FR: 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.
• [5]Feyer P, Sautter-Bihl ML, Budach W, Dunst J, Haase W, Harms W, Sedlmayer F, Souchon R, Wenz F, Sauer R, Breast Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO): DEGRO Practical Guidelines for palliative radiotherapy of breast cancer patients: brain metastases and leptomeningeal carcinomatosis. Strahlenther Onkol 2010, 186(2):63-69.
• [6]Asai A, Matsutani M, Kohno T, Nakamura O, Tanaka H, Fujimaki T, Funada N, Matsuda T, Nagata K, Takakura K: Subacute brain atrophy after radiation therapy for malignant brain tumor. Cancer 1989, 63(10):1962-1974.
• [7]Murray KJ, Scott C, Zachariah B, Michalski JM, Demas W, Vora NL, Whitton A, Movsas B: Importance of the mini-mental status examination in the treatment of patients with brain metastases: a report from the Radiation Therapy Oncology Group protocol 91–04. Int J Radiat Oncol Biol Phys 2000, 48(1):59-64.
• [8]Steinmann D, Schafer C, van Oorschot B, Wypior HJ, Bruns F, Bolling T, Sehlen S, Hagg J, Bayerl A, Geinitz H, Hipp M, Vordermark D: Effects of radiotherapy for brain metastases on quality of life (QoL). Prospective pilot study of the DEGRO QoL working party. Strahlenther Onkol 2009, 185(3):190-197.
• [9]DeAngelis LM, Delattre JY, Posner JB: Radiation-induced dementia in patients cured of brain metastases. Neurology 1989, 39(6):789-796.
• [10]Welzel G, Fleckenstein K, Schaefer J, Hermann B, Kraus-Tiefenbacher U, Mai SK, Wenz F: Memory function before and after whole brain radiotherapy in patients with and without brain metastases. Int J Radiat Oncol Biol Phys 2008, 72(5):1311-1318.
• [11]Al-Shamy G, Sawaya R: Management of brain metastases: the indispensable role of surgery. J Neurooncol 2009, 92(3):275-282.
• [12]Blonigen BJ, Steinmetz RD, Levin L, Lamba MA, Warnick RE, Breneman JC: Irradiated volume as a predictor of brain radionecrosis after linear accelerator stereotactic radiosurgery. Int J Radiat Oncol Biol Phys 2010, 77(4):996-1001.
• [13]Shiau CY, Sneed PK, Shu HK, Lamborn KR, McDermott MW, Chang S, Nowak P, Petti PL, Smith V, Verhey LJ, Ho M, Park E, Wara WM, Gutin PH, Larson DA: Radiosurgery for brain metastases: relationship of dose and pattern of enhancement to local control. Int J Radiat Oncol Biol Phys 1997, 37(2):375-383.
• [14]Levegrun S, Hof H, Essig M, Schlegel W, Debus J: Radiation-induced changes of brain tissue after radiosurgery in patients with arteriovenous malformations: dose/volume-response relations. Strahlenther Onkol 2004, 180(12):758-767.
• [15]Voges J, Treuer H, Sturm V, Buchner C, Lehrke R, Kocher M, Staar S, Kuchta J, Muller RP: Risk analysis of linear accelerator radiosurgery. Int J Radiat Oncol Biol Phys 1996, 36(5):1055-1063.
• [16]Aoki M, Abe Y, Hatayama Y, Kondo H, Basaki K: Clinical outcome of hypofractionated conventional conformation radiotherapy for patients with single and no more than three metastatic brain tumors, with noninvasive fixation of the skull without whole brain irradiation. Int J Radiat Oncol Biol Phys 2006, 64(2):414-418.
• [17]Ernst-Stecken A, Ganslandt O, Lambrecht U, Sauer R, Grabenbauer G: Phase II trial of hypofractionated stereotactic radiotherapy for brain metastases: results and toxicity. Radiother Oncol 2006, 81(1):18-24.
• [18]Hall EJ, Brenner DJ: The radiobiology of radiosurgery: rationale for different treatment regimes for AVMs and malignancies. Int J Radiat Oncol Biol Phys 1993, 25(2):381-385.
• [19]Lindvall P, Bergstrom P, Lofroth PO, Henriksson R, Bergenheim AT: Hypofractionated conformal stereotactic radiotherapy alone or in combination with whole-brain radiotherapy in patients with cerebral metastases. Int J Radiat Oncol Biol Phys 2005, 61(5):1460-1466.
• [20]Lindvall P, Bergstrom P, Lofroth PO, Tommy Bergenheim A: A comparison between surgical resection in combination with WBRT or hypofractionated stereotactic irradiation in the treatment of solitary brain metastases. Acta Neurochir (Wien) 2009, 151(9):1053-1059.
• [21]Kellerer AM, Rossi HH: The biophysical properties of 3.9-GeV nitrogen ions. VI. Interpretation of results. Radiat Res 1973, 55(3):447-456.
• [22]Marchetti M, Milanesi I, Falcone C, De Santis M, Fumagalli L, Brait L, Bianchi L, Fariselli L: Hypofractionated stereotactic radiotherapy for oligometastases in the brain: a single-institution experience. Neurol Sci 2011, 32(3):393-399.
• [23]Meisner J, Meyer A, Polivka B, Karstens JH, Bremer M: Outcome of moderately dosed radiosurgery for limited brain metastases. Report of a single-center experience. Strahlenther Onkol 2010, 186(2):76-81.
• [24]Rades D, Bohlen G, Pluemer A, Veninga T, Hanssens P, Dunst J, Schild SE: Stereotactic radiosurgery alone versus resection plus whole-brain radiotherapy for 1 or 2 brain metastases in recursive partitioning analysis class 1 and 2 patients. Cancer 2007, 109(12):2515-2521.
• [25]Nakagawa K, Tago M, Terahara A, Aoki Y, Sasaki T, Kurita H, Shin M, Kawamoto S, Kirino T, Otomo K: A single institutional outcome analysis of Gamma Knife radiosurgery for single or multiple brain metastases. Clin Neurol Neurosurg 2000, 102(4):227-232.
• [26]Shirato H, Takamura A, Tomita M, Suzuki K, Nishioka T, Isu T, Kato T, Sawamura Y, Miyamachi K, Abe H, Miyasaka K: Stereotactic irradiation without whole-brain irradiation for single brain metastasis. Int J Radiat Oncol Biol Phys 1997, 37(2):385-391.
• [27]Sneed PK, Lamborn KR, Forstner JM, McDermott MW, Chang S, Park E, Gutin PH, Phillips TL, Wara WM, Larson DA: Radiosurgery for brain metastases: is whole brain radiotherapy necessary? Int J Radiat Oncol Biol Phys 1999, 43(3):549-558.
• [28]Fahrig A, Ganslandt O, Lambrecht U, Grabenbauer G, Kleinert G, Sauer R, Hamm K: Hypofractionated stereotactic radiotherapy for brain metastases–results from three different dose concepts. Strahlenther Onkol 2007, 183(11):625-630.
• [29]Aoyama H, Shirato H, Onimaru R, Kagei K, Ikeda J, Ishii N, Sawamura Y, Miyasaka K: Hypofractionated stereotactic radiotherapy alone without whole-brain irradiation for patients with solitary and oligo brain metastasis using noninvasive fixation of the skull. Int J Radiat Oncol Biol Phys 2003, 56(3):793-800.
• [30]Vogelbaum MA, Angelov L, Lee SY, Li L, Barnett GH, Suh JH: Local control of brain metastases by stereotactic radiosurgery in relation to dose to the tumor margin. J Neurosurg 2006, 104(6):907-912.
• [31]Shaw E, Scott C, Souhami L, Dinapoli R, Kline R, Loeffler J, Farnan N: 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):291-298.
• [32]Shehata MK, Young B, Reid B, Patchell RA, St Clair W, Sims J, Sanders M, Meigooni A, Mohiuddin M, Regine WF: Stereotatic radiosurgery of 468 brain metastases < or =2 cm: implications for SRS dose and whole brain radiation therapy. Int J Radiat Oncol Biol Phys 2004, 59(1):87-93.
• [33]Rades D, Hornung D, Veninga T, Schild SE, Gliemroth J: Single brain metastasis: radiosurgery alone compared with radiosurgery plus up-front whole-brain radiotherapy. Cancer 2011, 118(11):2980-2985.
• [34]Hasegawa T, Kondziolka D, Flickinger JC, Germanwala A, Lunsford LD: Brain metastases treated with radiosurgery alone: an alternative to whole brain radiotherapy? Neurosurgery 2003, 52(6):1318-1326. discussion 1326.
• [35]Sneed PK, Suh JH, Goetsch SJ, Sanghavi SN, Chappell R, Buatti JM, Regine WF, Weltman E, King VJ, Breneman JC, Sperduto PW, Mehta MP: A multi-institutional review of radiosurgery alone vs. radiosurgery with whole brain radiotherapy as the initial management of brain metastases. Int J Radiat Oncol Biol Phys 2002, 53(3):519-526.
• [36]De Potter B, De Meerleer G, De Neve W, Boterberg T, Speleers B, Ost P: Hypofractionated frameless stereotactic intensity-modulated radiotherapy with whole brain radiotherapy for the treatment of 1–3 brain metastases. Neurol Sci 2012. Epub ahead of print.
• [37]Narayana A, Chang J, Yenice K, Chan K, Lymberis S, Brennan C, Gutin PH: Hypofractionated stereotactic radiotherapy using intensity-modulated radiotherapy in patients with one or two brain metastases. Stereotact Funct Neurosurg 2007, 85(2–3):82-87.