Prognostic value of CD109+ circulating endothelial cells in recurrent glioblastomas treated with bevacizumab and irinotecan.
BACKGROUND
Recent data suggest that circulating endothelial and progenitor cells (CECs and CEPs, respectively) may have predictive potential in cancer patients treated with bevacizumab, the antibody recognizing vascular endothelial growth factor (VEGF). Here we report on CECs and CEPs investigated in 68 patients affected by recurrent glioblastoma (rGBM) treated with bevacizumab and irinotecan and two Independent Datasets of rGBM patients respectively treated with bevacizumab alone (n=32, independent dataset A: IDA) and classical antiblastic chemotherapy (n=14, independent dataset B: IDB).


METHODS
rGBM patients with KPS ≥50 were treated until progression, as defined by MRI with RANO criteria. CECs expressing CD109, a marker of tumor endothelial cells, as well as other CEC and CEP subtypes, were investigated by six-color flow cytometry.


RESULTS
A baseline count of CD109+ CEC higher than 41.1/ml (1(st) quartile) was associated with increased progression free survival (PFS; 20 versus 9 weeks, P=0.008) and overall survival (OS; 32 versus 23 weeks, P=0.03). Longer PFS (25 versus 8 weeks, P=0.02) and OS (27 versus 17 weeks, P=0.03) were also confirmed in IDA with CD109+ CECs higher than 41.1/ml but not in IDB. Patients treated with bevacizumab with or without irinotecan that were free from MRI progression after two months of treatment had significant decrease of CD109+ CECs: median PFS was 19 weeks; median OS 29 weeks. The presence of two non-contiguous lesions (distant disease) at baseline was an independent predictor of shorter PFS and OS (P<0.001).


CONCLUSIONS
Data encourage further studies on the predictive potential of CD109+ CECs in GBM patients treated with bevacizumab.
Department of Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico C, Besta, Milan, Italy.
Lucia
L
Cuppini
Angelica
A
Calleri
Maria Grazia
MG
Bruzzone
Elena
E
Prodi
Elena
E
Anghileri
Serena
S
Pellegatta
Patrizia
P
Mancuso
Paola
P
Porrati
Anna Luisa
AL
Di Stefano
Mauro
M
Ceroni
Francesco
F
Bertolini
Gaetano
G
Finocchiaro
Marica
M
Eoli
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D015703:Antigens, CD / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D016896:Treatment Outcome; D055815:Young Adult
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D000970:Antineoplastic Agents; C120523:CD109 protein, human; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; D000068258:Bevacizumab; D000077146:Irinotecan; D002166:Camptothecin