[F-18]-fluorodeoxyglucose positron emission tomography for targeting radiation dose escalation for patients with glioblastoma multiforme: clinical outcomes and patterns of failure.

PURPOSE [F-18]-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging for brain tumors has been shown to identify areas of active disease. Radiation dose escalation in the treatment of glioblastoma multiforme may lead to improved disease control. Based on these premises, we initiated a prospective study of FDG-PET for the treatment planning of radiation dose escalation for the treatment of glioblastoma multiforme. METHODS AND MATERIALS Forty patients were enrolled. Patients were treated with standard conformal fractionated radiotherapy with volumes defined by MRI imaging. When patients reached a dose of 45-50.4 Gy, they underwent FDG-PET imaging for boost target delineation, for an additional 20 Gy (2 Gy per fraction) to a total dose of 79.4 Gy (n = 30). RESULTS The estimated 1-year and 2-year overall survival (OS) for the entire group was 70% and 17%, respectively, with a median overall survival of 70 weeks. The estimated 1-year and 2-year progression-free survival (PFS) was 18% and 3%, respectively, with a median of 24 weeks. No significant improvements in OS or PFS were observed for the study group in comparison to institutional historical controls. CONCLUSIONS Radiation dose escalation to 79.4 Gy based on FDG-PET imaging demonstrated no improvement in OS or PFS. This study establishes the feasibility of integrating PET metabolic imaging into radiotherapy treatment planning.

[1]  T. Wiggers,et al.  Effects on functional outcome after IORT-containing multimodality treatment for locally advanced primary and locally recurrent rectal cancer. , 2002, International journal of radiation oncology, biology, physics.

[2]  David A Mankoff,et al.  Volumetric analysis of 18F-FDG PET in glioblastoma multiforme: prognostic information and possible role in definition of target volumes in radiation dose escalation. , 2002, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[3]  M. Berger,et al.  Corpus callosum involvement as a prognostic factor for patients with high-grade astrocytoma. , 1997, International journal of radiation oncology, biology, physics.

[4]  G Di Chiro,et al.  Prediction of survival in glioma patients by means of positron emission tomography. , 1985, Journal of neurosurgery.

[5]  R. Weichselbaum,et al.  Glioblastoma cells block radiation‐induced programmed cell death of endothelial cells , 2004, FEBS letters.

[6]  D. Hwang,et al.  Prediction of Pathology and Survival by FDG PET in Gliomas , 2003, Journal of Neuro-Oncology.

[7]  E. Papadimitriou,et al.  Irradiated C6 glioma cells induce angiogenesis in vivo and activate endothelial cells in vitro , 2004, International journal of cancer.

[8]  D F Nelson,et al.  Combined modality approach to treatment of malignant gliomas--re-evaluation of RTOG 7401/ECOG 1374 with long-term follow-up: a joint study of the Radiation Therapy Oncology Group and the Eastern Cooperative Oncology Group. , 1988, NCI monographs : a publication of the National Cancer Institute.

[9]  J. Knisely,et al.  Importance of hypoxia in the biology and treatment of brain tumors. , 2002, Neuroimaging clinics of North America.

[10]  T. Nose,et al.  Reduction of nitroxides and radioprotective ability in glioblastoma cells , 2006, Brain Tumor Pathology.

[11]  J. Contessa,et al.  ERBB receptor tyrosine kinases and cellular radiation responses , 2003, Oncogene.

[12]  A. Chakravarti,et al.  Survivin enhances radiation resistance in primary human glioblastoma cells via caspase-independent mechanisms , 2004, Oncogene.

[13]  R. Mirimanoff,et al.  MGMT gene silencing and benefit from temozolomide in glioblastoma. , 2005, The New England journal of medicine.

[14]  Reto Meuli,et al.  Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  Alona Muzikansky,et al.  The prognostic significance of phosphatidylinositol 3-kinase pathway activation in human gliomas. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  Benedick A Fraass,et al.  Survival and failure patterns of high-grade gliomas after three-dimensional conformal radiotherapy. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  S. Goldman,et al.  Regional glucose metabolism and histopathology of gliomas: A study based on positron emission tomography‐guided stereotactic biopsy , 1996, Cancer.

[18]  A. Giese.  Glioma invasion--pattern of dissemination by mechanisms of invasion and surgical intervention, pattern of gene expression and its regulatory control by tumorsuppressor p53 and proto-oncogene ETS-1. , 2003, Acta neurochirurgica. Supplement.

[19]  R. Maciunas,et al.  Optimal cutoff levels of F-18 fluorodeoxyglucose uptake in the differentiation of low-grade from high-grade brain tumors with PET. , 1995, Radiology.

[20]  Susan M. Chang,et al.  18‐fluorodeoxyglucose uptake and survival of patients with suspected recurrent malignant glioma , 1997, Cancer.

[21]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[22]  D. Nelson,et al.  Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials. , 1993, Journal of the National Cancer Institute.

[23]  R. Mirimanoff,et al.  Concomitant and adjuvant temozolomide (TMZ) and radiotherapy (RT) for newly diagnosed glioblastoma multiforme (GBM). Conclusive results of a randomized phase III trial by the EORTC Brain & RT Groups and NCIC Clinical Trials Group , 2004 .

[24]  Adam Dicker,et al.  The contribution of epidermal growth factor receptor (EGFR) signaling pathway to radioresistance in human gliomas: a review of preclinical and correlative clinical data. , 2004, International journal of radiation oncology, biology, physics.

[25]  Thomas L. Ellis,et al.  A Phase I dose escalating study of intensity modulated radiation therapy (IMRT) for the treatment of glioblastoma multiforme (GBM) , 2004 .