Abstract
Treatment options for inoperable glioblastoma are limited. Low-dose-rate stereotactic iodine-125 brachytherapy (SBT) has been reported as an effective and low-risk treatment option for circumscribed low-grade gliomas and brain metastases. The present study evaluates this treatment approach for patients with inoperable glioblastoma. Between 1990 and 2012, 201 patients with histologically proven glioblastoma were treated with SBT (iodine-125 seeds; median cumulative surface dose, 60 Gy; median dose-rate, 6 cGy/h; median gross-tumor-volume, 17 ml) either as primary treatment (n = 103) or at recurrence (n = 98). In addition to SBT, 90.3 % of patients in the primary treatment group received external boost radiotherapy (median dose, 25.2 Gy). Adjuvant chemotherapy was added for 30.8 % of patients following SBT and consisted of temozolomide for the majority of cases (88.7 %). Procedure-related complications, clinical outcome, progression-free and overall survival (PFS, OS) were evaluated. Median follow-up was 9.8 months. The procedure-related mortality was zero. During follow-up, transient and permanent procedure-related morbidity was observed in 7.5 and 2.0 %, respectively. Calculated from the time of SBT, median OS and PFS rates were 10.5 and 6.2 months, with no significant differences among primary and recurrent tumors (11.1 vs.10.4 months for OS and 6.2 vs. 5.9 months for PFS). For OS, multivariate analysis revealed Karnofsky performance score, age, and adjuvant chemotherapy as independent prognostic factors (all p < 0.01). Low-dose-rate SBT is a relatively safe and potentially effective local treatment option for patients with circumscribed inoperable glioblastoma initially or at recurrence. It deserves prospective validation since it may improve the outcome for a subset of patients with inoperable GBM.
Similar content being viewed by others
References
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996. doi:10.1056/NEJMoa043330
Beauchesne P, Bernier V, Carnin C, Taillandier L, Djabri M, Martin L, Michel X, Maire JP, Khalil T, Kerr C, Gorlia T, Stupp R, Pedeux R (2010) Prolonged survival for patients with newly diagnosed, inoperable glioblastoma with 3-times daily ultrafractionated radiation therapy. Neuro Oncol 12:595–602. doi:10.1093/neuonc/noq008
Chamberlain MC (2011) Bevacizumab for the treatment of recurrent glioblastoma. Clin Med Insights Oncol 5:117–129. doi:10.4137/CMO.S7232
Weller M, Cloughesy T, Perry JR, Wick W (2013) Standards of care for treatment of recurrent glioblastoma—are we there yet? Neuro Oncol 15:4–27. doi:10.1093/neuonc/nos273
Selker RG, Shapiro WR, Burger P, Blackwood, Arena VC, Gilder JC, Malkin MG, Mealey JJ, Jr, Neal JH, Olson J, Robertson JT, Barnett GH, Bloomfield S, Albright R, Hochberg FH, Hiesiger E, Green S (2002) The brain tumor cooperative group nih trial 87-01: a randomized comparison of surgery, external radiotherapy, and carmustine versus surgery, interstitial radiotherapy boost, external radiation therapy, and carmustine. Neurosurgery 51:343–355 discussion 355–347
Laperriere NJ, Leung PM, McKenzie S, Milosevic M, Wong S, Glen J, Pintilie M, Bernstein M (1998) Randomized study of brachytherapy in the initial management of patients with malignant astrocytoma. Int J Radiat Oncol Biol Phys 41:1005–1011
Scharfen CO, Sneed PK, Wara WM, Larson DA, Phillips TL, Prados MD, Weaver KA, Malec M, Acord P, Lamborn KR et al (1992) High activity iodine-125 interstitial implant for gliomas. Int J Radiat Oncol Biol Phys 24:583–591
Zamorano L, Yakar D, Dujovny M, Sheehan M, Kim J (1992) Permanent i-125 implant and external beam radiation-therapy for the treatment of malignant brain-tumors. Stereotact Funct Neurosurg 59:183–192
Prados M, Gutin P, Phillips T, Wara W, Sneed P, Larson D, Lamb S, Ham B, Malec M, Wilson C (1992) Interstitial brachytherapy for newly diagnosed patients with malignant gliomas—the ucsf experience. Int J Radiat Oncol Biol Phys 24:593–597
Sneed PK, Stauffer PR, McDermott MW, Diederich CJ, Lamborn KR, Prados MD, Chang S, Weaver KA, Spry L, Malec MK, Lamb SA, Voss B, Davis RL, Wara WM, Larson DA, Phillips TL, Gutin PH (1998) Survival benefit of hyperthermia in a prospective randomized trial of brachytherapy boost ± hyperthermia for glioblastoma multiforme. Int J Radiat Oncol Biol Phys 40:287–295
Gutin P, Prados M, Phillips T, Wara W, Larson D, Leibel S, Sneed P, Levin V, Weaver K, Silver P (1991) External irradiation followed by an interstitial high-activity i-125 implant boost in the initial treatment of malignant gliomas—NCOG study 6g-82-2. Int J Radiat Oncol Biol Phys 21:601–606
Gaspar L, Zamorano L, Shamsa F, Fontanesi J, Ezzell G, Yakar D (1999) Permanent (125)iodine implants for recurrent malignant gliomas. Int J Radiat Oncol Biol Phys 43:977–982
Fernandez PM, Zamorano L, Yakar D, Gaspar L, Warmelink C (1995) Permanent iodine-125 implants in the up-front treatment of malignant gliomas. Neurosurgery 36:467–473
Chamberlain MC, Barba D, Kormanik P, Berson AM, Saunders WM, Shea MC (1995) Concurrent cisplatin therapy and iodine 125 brachytherapy for recurrent malignant brain tumors. Arch Neurol 52:162–167
Bernstein M, Laperriere N, Glen J (1995) Stereotactic high-activity brachytherapy for malignant intra-axial brain tumors. Status report as of March, 1995. Stereotact Funct Neurosurg 65:167–170
Malkin MG (1994) Interstitial brachytherapy of malignant gliomas: the memorial sloan-kettering cancer center experience. Recent Results Cancer Res 135:117–125
Gutin PH, Phillips TL, Wara WM, Leibel SA, Hosobuchi Y, Levin VA, Weaver KA, Lamb S (1984) Brachytherapy of recurrent malignant brain tumors with removable high-activity iodine-125 sources. J Neurosurg 60:61–68. doi:10.3171/jns.1984.60.1.0061
Koot R, Maarouf M, Hulshof M, Voges J, Treuer H, Koedooder C, Sturm V, Bosch D (2000) Brachytherapy - Results of two different therapy strategies for patients with primary glioblastoma multiforme. Cancer 88:2796–2802
Zamorano L, Yakar D, Dujovny M, Sheehan M, Kim J (1992) Permanent iodine-125 implant and external beam radiation therapy for the treatment of malignant brain tumors. Stereotact Funct Neurosurg 59:183–192
Ruge MI, Kickingereder P, Simon T, Treuer H, Sturm V (2012) Stereotactic iodine-125 brachytherapy for treatment of inoperable focal brainstem gliomas of WHO grades I and II: feasibility and long-term outcome. J Neurooncol 109:273–283. doi:10.1007/s11060-012-0889-1
Ruge MI, Simon T, Suchorska B, Lehrke R, Hamisch C, Koerber F, Maarouf M, Treuer H, Berthold F, Sturm V, Voges J (2011) Stereotactic brachytherapy with iodine-125 seeds for the treatment of inoperable low-grade gliomas in children: long-term outcome. J of clin oncol : off j Am Soc Clin Oncol 29:4151–4159. doi:10.1200/JCO.2011.37.3381
Voges J, Treuer H, Schlegel W, Pastyr O, Sturm V (1993) Interstitial irradiation of cerebral gliomas with stereotactically implanted iodine-125 seeds. Acta Neurochir Suppl (Wien) 58:108–111
Kreth F, Faist M, Rossner R, Birg W, Volk B, Ostertag C (1997) The risk of interstitial radiotherapy of low-grade gliomas. Radiother Oncol 43:253–260
Ruge MI, Suchorska B, Maarouf M, Runge M, Treuer H, Voges J, Sturm V (2011) Stereotactic 125iodine brachytherapy for the treatment of singular brain metastases: closing a gap? Neurosurgery 68: 1209-1218; discussion 1218–1209 doi:10.1227/NEU.0b013e31820b526a
Suchorska B, Ruge M, Treuer H, Sturm V, Voges J (2011) Stereotactic brachytherapy of low-grade cerebral glioma after tumor resection. Neuro Oncol 13:1133–1142. doi:10.1093/neuonc/nor100
Ruge MI, Kickingereder P, Grau S, Dorn F, Galldiks N, Treuer H, Sturm V (2013) Stereotactic iodine-125 brachytherapy for the treatment of WHO grades II and III gliomas located in the central sulcus region. Neuro Oncol 15:1721–1731. doi:10.1093/neuonc/not126
Treuer H, Klein D, Maarouf M, Lehrke R, Voges J, Sturm V (2005) Accuracy and conformity of stereotactically guided interstitial brain tumour therapy using I-125 seeds. Radiother Oncol 77:202–209. doi:10.1016/j.radonc.2005.08.006
Ruge M, Suchorska B, Maarouf M, Runge M, Treuer H, Voges J, Sturm V (2011) Stereotactic (125)iodine brachytherapy for the treatment of singular brain metastases: closing a gap? Neurosurgery 68:1209–1218
Ruge MI, Kickingereder P, Simon T, Treuer H, Sturm V (2012) Stereotactic iodine-125 brachytherapy for treatment of inoperable focal brainstem gliomas of WHO grades I and II: feasibility and long-term outcome. J Neurooncol. doi:10.1007/s11060-012-0889-1
Hochberg FH, Pruitt A (1980) Assumptions in the radiotherapy of glioblastoma. Neurology 30:907–911
Ruge M, Simon T, Suchorska B, Lehrke R, Hamisch C, Koerber F, Maarouf M, Treuer H, Berthold F, Sturm V (2011) Stereotactic brachytherapy with iodine-125 seeds for the treatment of inoperable low-grade gliomas in children: long-term outcome. J Clin Oncol 29:4151–4159
Korinthenberg R, Neuburger D, Trippel M, Ostertag C, Nikkhah G (2011) Long-term results of brachytherapy with temporary iodine-125 seeds in children with low-grade gliomas. Int J Radiat Oncol Biol Phys 79:1131–1138. doi:10.1016/j.ijrobp.2009.12.040
Kreth F, Faist M, Grau S, Ostertag C (2006) Interstitial 125I radiosurgery of supratentorial de novo WHO Grade 2 astrocytoma and oligoastrocytoma in adults: long-term results and prognostic factors. Cancer 106:1372–1381
Kreth F, Thon N, Siefert A, Tonn J (2010) The place of interstitial brachytherapy and radiosurgery for low-grade gliomas. Adv Tech Stand Neurosurg 35:183–212
Vitaz T, Warnke P, Tabar V, Gutin P (2005) Brachytherapy for brain tumors. J Neurooncol 73:71–86
Kreth FW, Thon N, Simon M, Westphal M, Schackert G, Nikkhah G, Hentschel B, Reifenberger G, Pietsch T, Weller M, Tonn JC (2013) Gross total but not incomplete resection of glioblastoma prolongs survival in the era of radiochemotherapy. Ann Oncol 24:3117–3123. doi:10.1093/annonc/mdt388
Capdevila L, Cros S, Ramirez JL, Sanz C, Carrato C, Romeo M, Etxaniz O, Hostalot C, Massuet A, Cuadra JL, Villa S, Balana C (2014) Neoadjuvant cisplatin plus temozolomide versus standard treatment in patients with unresectable glioblastoma or anaplastic astrocytoma: a differential effect of MGMT methylation. J Neurooncol. doi:10.1007/s11060-013-1352-7
Amichetti M, Amelio D (2011) A review of the role of re-irradiation in recurrent high-grade glioma (hgg). Cancers 3:4061–4089. doi:10.3390/cancers3044061
Fogh SE, Andrews DW, Glass J, Curran W, Glass C, Champ C, Evans JJ, Hyslop T, Pequignot E, Downes B, Comber E, Maltenfort M, Dicker AP, Werner-Wasik M (2010) Hypofractionated stereotactic radiation therapy: an effective therapy for recurrent high-grade gliomas. J Clin Oncol 28:3048–3053. doi:10.1200/JCO.2009.25.6941
Combs SE, Thilmann C, Edler L, Debus J, Schulz-Ertner D (2005) Efficacy of fractionated stereotactic reirradiation in recurrent gliomas: long-term results in 172 patients treated in a single institution. J Clin Oncol 23:8863–8869. doi:10.1200/JCO.2005.03.4157
Combs SE, Widmer V, Thilmann C, Hof H, Debus J, Schulz-Ertner D (2005) Stereotactic radiosurgery (SRS): treatment option for recurrent glioblastoma multiforme (GBM). Cancer 104:2168–2173. doi:10.1002/cncr.21429
Shaw E, Scott C, Souhami L, Dinapoli R, Kline R, Loeffler J, Farnan N (2000) 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 47:291–298
Grosu AL, Weber WA, Franz M, Stark S, Piert M, Thamm R, Gumprecht H, Schwaiger M, Molls M, Nieder C (2005) Reirradiation of recurrent high-grade gliomas using amino acid PET (SPECT)/CT/MRI image fusion to determine gross tumor volume for stereotactic fractionated radiotherapy. Int J Radiat Oncol Biol Phys 63:511–519. doi:10.1016/j.ijrobp.2005.01.056
Vordermark D, Kolbl O, Ruprecht K, Vince GH, Bratengeier K, Flentje M (2005) Hypofractionated stereotactic re-irradiation: treatment option in recurrent malignant glioma. BMC Cancer 5:55. doi:10.1186/1471-2407-5-55
Patel M, Siddiqui F, Jin JY, Mikkelsen T, Rosenblum M, Movsas B, Ryu S (2009) Salvage reirradiation for recurrent glioblastoma with radiosurgery: radiographic response and improved survival. J Neurooncol 92:185–191. doi:10.1007/s11060-008-9752-9
Viola A, Major T, Julow J (2006) Comparison of (125)I stereotactic brachytherapy and LINAC radiosurgery modalities based on physical dose distribution and radiobiological efficacy. Radiat Res 165:695–702. doi:10.1667/RR3529.1
Acknowledgments
We would like to thank Volker Sturm for establishing the prospective treatment protocol and for treating numerous patients together with Ralph Lehrke and. Mohammad Maarouf.
Conflict of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
Philipp Kickingereder, Christina Hamisch have contributed equally to this article.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Kickingereder, P., Hamisch, C., Suchorska, B. et al. Low-dose rate stereotactic iodine-125 brachytherapy for the treatment of inoperable primary and recurrent glioblastoma: single-center experience with 201 cases. J Neurooncol 120, 615–623 (2014). https://doi.org/10.1007/s11060-014-1595-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11060-014-1595-y