Cargando…

Concurrent bevacizumab and temozolomide alter the patterns of failure in radiation treatment of glioblastoma multiforme

BACKGROUND: We investigated the pattern of failure in glioblastoma multiforma (GBM) patients treated with concurrent radiation, bevacizumab (BEV), and temozolomide (TMZ). Previous studies demonstrated a predominantly in-field pattern of failure for GBM patients not treated with concurrent BEV. METHO...

Descripción completa

Detalles Bibliográficos
Autores principales: Shields, Lisa BE, Kadner, Robert, Vitaz, Todd W, Spalding, Aaron C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648458/
https://www.ncbi.nlm.nih.gov/pubmed/23618500
http://dx.doi.org/10.1186/1748-717X-8-101
_version_ 1782268847390195712
author Shields, Lisa BE
Kadner, Robert
Vitaz, Todd W
Spalding, Aaron C
author_facet Shields, Lisa BE
Kadner, Robert
Vitaz, Todd W
Spalding, Aaron C
author_sort Shields, Lisa BE
collection PubMed
description BACKGROUND: We investigated the pattern of failure in glioblastoma multiforma (GBM) patients treated with concurrent radiation, bevacizumab (BEV), and temozolomide (TMZ). Previous studies demonstrated a predominantly in-field pattern of failure for GBM patients not treated with concurrent BEV. METHODS: We reviewed the treatment of 23 patients with GBM who received 30 fractions of simultaneous integrated boost IMRT. PTV60 received 2 Gy daily to the tumor bed or residual tumor while PTV54 received 1.8 Gy daily to the surrounding edema. Concurrent TMZ (75 mg/m^2) daily and BEV (10 mg/kg every 2 weeks) were given during radiation therapy. One month after RT completion, adjuvant TMZ (150 mg/m^2 × 5 days) and BEV were delivered monthly until progression or 12 months total. RESULTS: With a median follow-up of 12 months, the median disease-free and overall survival were not reached. Four patients discontinued therapy due to toxicity for the following reasons: bone marrow suppression (2), craniotomy wound infection (1), and pulmonary embolus (1). Five patients had grade 2 or 3 hypertension managed by oral medications. Of the 12 patients with tumor recurrence, 7 suffered distant failure with either subependymal (5/12; 41%) or deep white matter (2/12; 17%) spread detected on T2 FLAIR sequences. Five of 12 patients (41%) with a recurrence demonstrated evidence of GAD enhancement. The patterns of failure did not correlate with extent of resection or number of adjuvant cycles. CONCLUSIONS: Treatment of GBM patients with concurrent radiation, BEV, and TMZ was well tolerated in the current study. The majority of patients experienced an out-of-field pattern of failure with radiation, BEV, and TMZ which has not been previously reported. Further investigation is warranted to determine whether BEV alters the underlying tumor biology to improve survival. These data may indicate that the currently used clinical target volume thought to represent microscopic disease for radiation may not be appropriate in combination with TMZ and BEV.
format Online
Article
Text
id pubmed-3648458
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-36484582013-05-09 Concurrent bevacizumab and temozolomide alter the patterns of failure in radiation treatment of glioblastoma multiforme Shields, Lisa BE Kadner, Robert Vitaz, Todd W Spalding, Aaron C Radiat Oncol Research BACKGROUND: We investigated the pattern of failure in glioblastoma multiforma (GBM) patients treated with concurrent radiation, bevacizumab (BEV), and temozolomide (TMZ). Previous studies demonstrated a predominantly in-field pattern of failure for GBM patients not treated with concurrent BEV. METHODS: We reviewed the treatment of 23 patients with GBM who received 30 fractions of simultaneous integrated boost IMRT. PTV60 received 2 Gy daily to the tumor bed or residual tumor while PTV54 received 1.8 Gy daily to the surrounding edema. Concurrent TMZ (75 mg/m^2) daily and BEV (10 mg/kg every 2 weeks) were given during radiation therapy. One month after RT completion, adjuvant TMZ (150 mg/m^2 × 5 days) and BEV were delivered monthly until progression or 12 months total. RESULTS: With a median follow-up of 12 months, the median disease-free and overall survival were not reached. Four patients discontinued therapy due to toxicity for the following reasons: bone marrow suppression (2), craniotomy wound infection (1), and pulmonary embolus (1). Five patients had grade 2 or 3 hypertension managed by oral medications. Of the 12 patients with tumor recurrence, 7 suffered distant failure with either subependymal (5/12; 41%) or deep white matter (2/12; 17%) spread detected on T2 FLAIR sequences. Five of 12 patients (41%) with a recurrence demonstrated evidence of GAD enhancement. The patterns of failure did not correlate with extent of resection or number of adjuvant cycles. CONCLUSIONS: Treatment of GBM patients with concurrent radiation, BEV, and TMZ was well tolerated in the current study. The majority of patients experienced an out-of-field pattern of failure with radiation, BEV, and TMZ which has not been previously reported. Further investigation is warranted to determine whether BEV alters the underlying tumor biology to improve survival. These data may indicate that the currently used clinical target volume thought to represent microscopic disease for radiation may not be appropriate in combination with TMZ and BEV. BioMed Central 2013-04-25 /pmc/articles/PMC3648458/ /pubmed/23618500 http://dx.doi.org/10.1186/1748-717X-8-101 Text en Copyright © 2013 Shields et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Shields, Lisa BE
Kadner, Robert
Vitaz, Todd W
Spalding, Aaron C
Concurrent bevacizumab and temozolomide alter the patterns of failure in radiation treatment of glioblastoma multiforme
title Concurrent bevacizumab and temozolomide alter the patterns of failure in radiation treatment of glioblastoma multiforme
title_full Concurrent bevacizumab and temozolomide alter the patterns of failure in radiation treatment of glioblastoma multiforme
title_fullStr Concurrent bevacizumab and temozolomide alter the patterns of failure in radiation treatment of glioblastoma multiforme
title_full_unstemmed Concurrent bevacizumab and temozolomide alter the patterns of failure in radiation treatment of glioblastoma multiforme
title_short Concurrent bevacizumab and temozolomide alter the patterns of failure in radiation treatment of glioblastoma multiforme
title_sort concurrent bevacizumab and temozolomide alter the patterns of failure in radiation treatment of glioblastoma multiforme
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648458/
https://www.ncbi.nlm.nih.gov/pubmed/23618500
http://dx.doi.org/10.1186/1748-717X-8-101
work_keys_str_mv AT shieldslisabe concurrentbevacizumabandtemozolomidealterthepatternsoffailureinradiationtreatmentofglioblastomamultiforme
AT kadnerrobert concurrentbevacizumabandtemozolomidealterthepatternsoffailureinradiationtreatmentofglioblastomamultiforme
AT vitaztoddw concurrentbevacizumabandtemozolomidealterthepatternsoffailureinradiationtreatmentofglioblastomamultiforme
AT spaldingaaronc concurrentbevacizumabandtemozolomidealterthepatternsoffailureinradiationtreatmentofglioblastomamultiforme