title: Chemosensitivity profile assay of circulating cancer cells: prognostic and predictive value in epithelial tumors.
abstract: The prognostic value associated with the detection of circulating tumor cells (CTCs) in metastatic breast cancer by the CellSearch technology raise additional issues regarding the biological value of this information. We postulated that a drug-resistance profile of CTCs may predict response to chemotherapy in cancer patients and therefore could be used for patient selection. One hundred 5 patients with diagnosis of carcinoma were enrolled in a prospective trial. CTCs were isolated from peripheral blood, and positive samples were evaluated for the expression of a panel of genes involved in anticancer drugs resistance. The drug-resistance profile was correlated with disease-free survival (DFS; patients in adjuvant setting) and time to progression (TTP; metastatic patients) in a 24-months follow-up. Objective response correlation was a secondary end point. Fifty-one percent of patients were found positive for CTCs while all blood samples from healthy donors were negative. The drug-resistance profile correlates with DFS and TTP (p < 0.001 in both). Sensitivity of the test: able to predict treatment response in 98% of patients. Specificity of the test: 100%; no sample from healthy subject was positive for the presence of CTCs. Positive and negative predictive values were found to be 96.5 and 100%, respectively. We identified a drug-resistance profile of CTCs, which is predictive of response to chemotherapy, independent of tumor type and stage of disease. This approach may represent a first step toward the individualization of chemotherapy in cancer patients.
authors.affiliation: Dipartimento Medicina Sperimentale, Sapienza Università di Roma, Viale Regina Elena 324, Roma, Italy. paola.gazzaniga@uniroma1.it
authors.forename: Paola
authors.initials: P
authors.lastname: Gazzaniga
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Naso
authors.forename: Angela
authors.initials: A
authors.lastname: Gradilone
authors.forename: Enrico
authors.initials: E
authors.lastname: Cortesi
authors.forename: Orietta
authors.initials: O
authors.lastname: Gandini
authors.forename: Walter
authors.initials: W
authors.lastname: Gianni
authors.forename: Maria Agnese
authors.initials: MA
authors.lastname: Fabbri
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Franco
authors.initials: F
authors.lastname: di Silverio
authors.forename: Luigi
authors.initials: L
authors.lastname: Frati
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Aglianò
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000187:drug effects*; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
chemical_list: D000970:Antineoplastic Agents