Pseudoprogression of malignant glioma in Chinese patients receiving concomitant chemoradiotherapy.
OBJECTIVE
To investigate the frequency of pseudoprogression of glioblastoma in Chinese patients receiving concomitant chemoradiotherapy and investigate its association with pseudoprogression and tumour molecular marker O(6)-methylguanine-DNA methyltransferase promoter methylation status.


METHODS
Case series with internal comparisons.


METHODS
University teaching hospital, Hong Kong.


METHODS
Patients with glioblastoma treated with concomitant chemoradiotherapy during April 2005 to June 2010 were reviewed. Magnetic resonance imaging brain scans, pre- and post-concomitant chemoradiotherapy and 3-monthly thereafter were reviewed by an independent neuroradiologist according to Macdonald's criteria. Relevant patient information (clinical condition, performance score, development of new neurological deficits, use of steroids, and survival) was retrieved. For each patient, O(6)-methylguanine-DNA methyltransferase methylation status was investigated with genomic DNA from formalin-fixed or paraffin-embedded sections of tumour tissues by methylation-specific polymerase chain reaction.


RESULTS
During the study period, 28 primary glioblastoma patients underwent concomitant chemoradiotherapy. The mean age of the patients was 48 (range, 16-71) years. Thirteen patients (13/28, 46%) developed early radiological progression of the tumour after completion of concomitant chemoradiotherapy, of whom five (39%) were subsequently found to have had pseudoprogression. Patients with pseudoprogression showed a trend towards longer survival (22 months in pseudoprogression vs 17 months in all others vs 11 months in those with genuine progression). Among the 27 patients tested for O(6)-methylguanine-DNA methyltransferase promoter status, 12 (44%) were methylated. Two (2/12, 17%) in the methylated group had pseudoprogression, while three (3/15, 20%) in the unmethylated group had pseudoprogression.


CONCLUSIONS
Nearly half of all patients (46%) developed early radiological progression (within 3 months of completing concomitant chemoradiotherapy). Moreover, about one in three of such patients had pseudoprogression. Pseudoprogression is an important clinical condition to be aware of to prevent premature termination of an effective treatment.
The CUHK Brain Tumour Centre, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong.
Danny T M
DT
Chan
Rebecca Y T
RY
Ng
Deyond Y W
DY
Siu
Peggy
P
Tang
Michael K M
MK
Kam
Brigette B Y
BB
Ma
George K C
GK
Wong
Stephanie C P
SC
Ng
Jesse C S
JC
Pang
Claire K Y
CK
Lau
X L
XL
Zhu
H K
HK
Ng
W S
WS
Poon
D000293:Adolescent; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000235:genetics / Q000628:therapy*; D059248:Chemoradiotherapy; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D018450:Disease Progression; D005909:Glioblastoma / Q000235:genetics / Q000628:therapy*; D005910:Glioma / Q000235:genetics / Q000628:therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D015254:DNA Modification Methylases; D019853:O(6)-Methylguanine-DNA Methyltransferase