Prognostic analysis of clinicopathologic factors in 49 patients with diffuse malignant peritoneal mesothelioma treated with cytoreductive surgery and intraperitoneal hyperthermic perfusion.
BACKGROUND
Diffuse malignant peritoneal mesothelioma (DMPM) is a subset of peritoneal mesothelioma with a poor clinical outcome. We performed a prognostic analysis in a cohort of DMPM patients treated homogeneously by cytoreductive surgery and intraperitoneal hyperthermic perfusion (IPHP).


METHODS
Forty-nine DMPM patients who underwent 52 consecutive procedures were enrolled onto the study. Cytoreductive surgery was performed according to the peritonectomy technique, and the IPHP was performed with cisplatin plus doxorubicin or cisplatin plus mitomycin C. We assessed the correlation of the clinicopathologic variables (previous surgical score, age, sex, performance status, previous systemic chemotherapy, carcinomatosis extension, completeness of cytoreduction, IPHP drug schedule, mitotic count [MC], nuclear grade, and biological markers [epidermal growth factor receptor, p16, matrix metalloproteinase 2 and matrix metalloproteinase 9]) with overall and progression-free survival.


RESULTS
The mean age was 52 years (range, 22-74 years). The mean follow-up was 20.3 months (range, 1-89 months). Regarding the biological markers, the rates of immunoreactivity of epidermal growth factor receptor, p16, matrix metalloproteinase 2, and matrix metalloproteinase 9 were 94%, 60%, 100%, and 85%, respectively. The strongest factors influencing overall survival were completeness of cytoreduction and MC, whereas those for progression-free survival were performance status and MC. No biological markers were shown to be of prognostic value.


CONCLUSIONS
Completeness of cytoreduction, performance status, and MC seem to be the best determinants of outcome. These data warrant confirmation by a further prospective formal trial. No biological markers presented a significant correlation with the outcome. The overexpression of epidermal growth factor receptor, matrix metalloproteinase 2, and matrix metalloproteinase 9 and absent or reduced expression of p16 might be related to the underlining tumor kinetics of DMPM and warrant further investigation with other methods.
Deraco
Marcello
M
Department of Surgery, National Cancer Institute, Via Venezian, 1, 20133, Milan, Italy. marcello.deraco@istitutotumori.mi.it
Nonaka
Daisuke
D
Baratti
Dario
D
Casali
Paolo
P
Rosai
Juan
J
Younan
Rami
R
Salvatore
Andreola
A
Cabras Ad
Antonello D
AD
Kusamura
Shigeki
S
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D015415:Biomarkers; D010478:Chemotherapy, Cancer, Regional Perfusion; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D007150:Immunohistochemistry; D008297:Male; D008654:Mesothelioma / Q000401:mortality / Q000473:pathology* / Q000601:surgery / Q000628:therapy*; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D010534:Peritoneal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery / Q000628:therapy*; D011379:Prognosis; D015996:Survival Rate
D015415:Biomarkers; D016685:Mitomycin; D004317:Doxorubicin; D002945:Cisplatin