Sinusoidal obstruction syndrome and nodular regenerative hyperplasia are frequent oxaliplatin-associated liver lesions and partially prevented by bevacizumab in patients with hepatic colorectal metastasis.
OBJECTIVE
Because of its efficacy, oxaliplatin (OX) is increasingly used as a chemotherapeutic agent in the treatment of colorectal liver metastases (CRLM). Oxaliplatin-associated liver toxicity has been reported and can affect clinical practice, but studies on its prevalence and a full pathological description are lacking. The aims of this study were to fill this gap by providing, from a pathologist's perspective, a detailed assessment of the spectrum of hepatic lesions associated with OX, to suggest a scoring system to quantify them, and to investigate the protective effect of bevacizumab against OX-associated damage.


RESULTS
The spectrum of oxaliplatin-associated liver lesions was investigated in a multi-institutional series of surgically resected CRLM (n = 385). Among 274 patients treated by OX, 54% had moderate/severe sinusoidal obstruction syndrome (SOS). Peliosis, centrilobular perisinusoidal/venular fibrosis and nodular regenerative hyperplasia (NRH) developed in 10.6%, 47% and 24.5%, respectively. The 111 patients treated by surgery alone had no lesions. Hepatic lesions were less severe in patients treated with OX/bevacizumab (n = 70) compared with the group treated by OX alone (n = 204), with an incidence of moderate/severe SOS (31.4% versus 62.2%), peliosis (4.3% versus 14.6%), NRH (11.4% versus 28.9%, respectively) and centrilobular/venular fibrosis (31.4% versus 52%, respectively) (P < 0.001).


CONCLUSIONS
Pathologists should be aware of the distinctive lesions associated with OX and of their high prevalence. OX-related lesions are less frequent in patients treated with bevacizumab, suggesting that this drug has a preventive effect. Uniform criteria for diagnosis and grading of OX-associated lesions should help to include histological data in the optimal multidisciplinary management of CRLM.
Rubbia-Brandt
Laura
L
Division of Pathology, Geneva University Hospital, Geneva, Switzerland. laura.rubbia-brandt@hcuge.ch
Lauwers
Gregory Y
GY
Wang
Huamin
H
Majno
Pietro E
PE
Tanabe
Kenneth
K
Zhu
Andrew X
AX
Brezault
Catherine
C
Soubrane
Olivier
O
Abdalla
Eddie K
EK
Vauthey
Jean-Nicolas
JN
Mentha
Gilles
G
Terris
Benoit
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D006504:Hepatic Veno-Occlusive Disease / Q000188:drug therapy / Q000209:etiology* / Q000601:surgery; D006801:Humans; D006965:Hyperplasia / Q000139:chemically induced / Q000209:etiology / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D000077150:Oxaliplatin; D012189:Retrospective Studies
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab