Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme

被引:1050
作者
Maier-Hauff, Klaus [1 ]
Ulrich, Frank [2 ]
Nestler, Dirk [1 ]
Niehoff, Hendrik [2 ]
Wust, Peter [3 ]
Thiesen, Burghard [4 ]
Orawa, Helmut [5 ]
Budach, Volker [3 ]
Jordan, Andreas [3 ,4 ]
机构
[1] Bundeswehrkrankenhaus Berlin, Dept Neurosurg, D-10115 Berlin, Germany
[2] Helios Klinikum Krefeld, Clin Neurosurg, Krefeld, Germany
[3] Charite, Dept Radiotherapy, D-13353 Berlin, Germany
[4] MagForce Nanotechnol AG, Berlin, Germany
[5] Charite, Coordinat Ctr Clin Studies KKS, D-13353 Berlin, Germany
关键词
Glioblastoma; Magnetic nanoparticles; Radiotherapy; Recurrence; Thermotherapy; QUALITY-OF-LIFE; MALIGNANT GLIOMA; PHASE-II; SALVAGE THERAPY; PROSTATE-CANCER; STEREOTACTIC RADIOTHERAPY; ADJUVANT TEMOZOLOMIDE; TREATMENT OPTION; CLINICAL-TRIALS; NCIC TRIAL;
D O I
10.1007/s11060-010-0389-0
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Therapy options at the time of recurrence of glioblastoma multiforme are often limited. We investigated whether treatment with a new intratumoral thermotherapy procedure using magnetic nanoparticles improves survival outcome. In a single-arm study in two centers, 66 patients (59 with recurrent glioblastoma) received neuronavigationally controlled intratumoral instillation of an aqueous dispersion of iron-oxide (magnetite) nanoparticles and subsequent heating of the particles in an alternating magnetic field. Treatment was combined with fractionated stereotactic radiotherapy. A median dose of 30 Gy using a fractionation of 5 x 2 Gy/week was applied. The primary study endpoint was overall survival following diagnosis of first tumor recurrence (OS-2), while the secondary endpoint was overall survival after primary tumor diagnosis (OS-1). Survival times were calculated using the Kaplan-Meier method. Analyses were by intention to treat. The median overall survival from diagnosis of the first tumor recurrence among the 59 patients with recurrent glioblastoma was 13.4 months (95% CI: 10.6-16.2 months). Median OS-1 was 23.2 months while the median time interval between primary diagnosis and first tumor recurrence was 8.0 months. Only tumor volume at study entry was significantly correlated with ensuing survival (P < 0.01). No other variables predicting longer survival could be determined. The side effects of the new therapeutic approach were moderate, and no serious complications were observed. Thermotherapy using magnetic nanoparticles in conjunction with a reduced radiation dose is safe and effective and leads to longer OS-2 compared to conventional therapies in the treatment of recurrent glioblastoma.
引用
收藏
页码:317 / 324
页数:8
相关论文
共 41 条
[11]   SAFETY AND EFFICACY OF BEVACIZUMAB WITH HYPOFRACTIONATED STEREOTACTIC IRRADIATION FOR RECURRENT MALIGNANT GLIOMAS [J].
Gutin, Philip H. ;
Iwamoto, Fabio M. ;
Beal, Kathryn ;
Mohile, Nimish A. ;
Karimi, Sasan ;
Hou, Bob L. ;
Lymberis, Stella ;
Yamada, Yoshiya ;
Chang, Jenghwa ;
Abrey, Lauren E. .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2009, 75 (01) :156-163
[12]   ACNU-cisplatin continuous infusion chemotherapy as salvage therapy for recurrent glioblastomas: phase II study [J].
Gwak, HS ;
Youn, SM ;
Kwon, AH ;
Lee, SH ;
Kim, JH ;
Rhee, CH .
JOURNAL OF NEURO-ONCOLOGY, 2005, 75 (02) :173-180
[13]   EGFRvIII Antibody-Conjugated Iron Oxide Nanoparticles for Magnetic Resonance Imaging-Guided Convection-Enhanced Delivery and Targeted Therapy of Glioblastoma [J].
Hadjipanayis, Costas G. ;
Machaidze, Revaz ;
Kaluzova, Milota ;
Wang, Liya ;
Schuette, Albert J. ;
Chen, Hongwei ;
Wu, Xinying ;
Mao, Hui .
CANCER RESEARCH, 2010, 70 (15) :6303-6312
[14]   Salvage therapy in patients with glioblastoma -: Is there any benefit? [J].
Hau, P ;
Baumgart, U ;
Pfeifer, K ;
Bock, A ;
Jauch, T ;
Dietrich, J ;
Fabel, K ;
Grauer, O ;
Wismeth, C ;
Klinkhammer-Schalke, M ;
Allgäuer, M ;
Schuierer, G ;
Koch, H ;
Schlaier, J ;
Brawanski, A ;
Bogdahn, U ;
Steinbrecher, A .
CANCER, 2003, 98 (12) :2678-2686
[15]   A phase I dose escalation study of hypofractionated stereotactic radiotherapy as salvage therapy for persistent or recurrent malignant glioma [J].
Hudes, RS ;
Corn, BW ;
Werner-Wasik, M ;
Andrews, D ;
Rosenstock, J ;
Thoron, L ;
Downes, B ;
Curran, WJ .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 1999, 43 (02) :293-298
[16]   Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study [J].
Issels, Rolf D. ;
Lindner, Lars H. ;
Verweij, Jaap ;
Wust, Peter ;
Reichardt, Peter ;
Schem, Baard-Christian ;
Abdel-Rahman, Sultan ;
Daugaard, Soeren ;
Salat, Christoph ;
Wendtner, Clemens-Martin ;
Vujaskovic, Zeljko ;
Wessalowski, Ruediger ;
Jauch, Karl-Walter ;
Duerr, Hans Roland ;
Ploner, Ferdinand ;
Baur-Melnyk, Andrea ;
Mansmann, Ulrich ;
Hiddemann, Wolfgang ;
Blay, Jean-Yves ;
Hohenberger, Peter .
LANCET ONCOLOGY, 2010, 11 (06) :561-570
[17]   Thermotherapy using magnetic nanoparticles combined with external radiation in an orthotopic rat model of prostate cancer [J].
Johannsen, M ;
Thiesen, B ;
Gneveckow, U ;
Taymoorian, K ;
Waldöfner, N ;
Scholz, R ;
Deger, S ;
Jung, K ;
Loening, SA ;
Jordan, A .
PROSTATE, 2006, 66 (01) :97-104
[18]   Morbidity and quality of life during thermotherapy using magnetic nanoparticles in locally recurrent prostate cancer:: Results of a prospective phase I trial [J].
Johannsen, M. ;
Gneveckow, U. ;
Taymoorian, K. ;
Thiesen, B. ;
Waldoefner, N. ;
Scholz, R. ;
Jung, K. ;
Jordan, A. ;
Wust, P. ;
Loening, S. A. .
INTERNATIONAL JOURNAL OF HYPERTHERMIA, 2007, 23 (03) :315-323
[19]   Thermotherapy of prostate cancer using magnetic nanoparticles: Feasibility, imaging, and three-dimensional temperature distribution [J].
Johannsen, Manfred ;
Gneueckow, Uwe ;
Thiesen, Burghard ;
Taymoorian, Kasra ;
Cho, Chie Hee ;
Waldofner, Norbert ;
Scholz, Regina ;
Jordan, Andreas ;
Loening, Stefan A. ;
Wust, Peter .
EUROPEAN UROLOGY, 2007, 52 (06) :1653-1662
[20]   The effect of thermotherapy using magnetic nanoparticles on rat malignant glioma [J].
Jordan, A ;
Scholz, R ;
Maier-Hauff, K ;
van Landeghem, FKH ;
Waldoefner, N ;
Teichgraeber, U ;
Pinkernelle, J ;
Bruhn, H ;
Neumann, F ;
Thiesen, B ;
von Deimling, A ;
Felix, R .
JOURNAL OF NEURO-ONCOLOGY, 2006, 78 (01) :7-14