title: DNA flow cytometry and the outcome of chemoimmunotherapy in metastatic melanoma.
abstract: DNA ploidy and S-phase fraction (SPF) were measured by flow cytometry on tumours from 80 patients with disseminated malignant melanoma. All patients received a four-drug chemotherapy regimen (dacarbazine, vincristine, bleomycin and lomustine) plus interferon. Specimens were taken for analysis from the latest metastases biopsied before the start of the treatment. In 13 patients we also analysed sequential samples taken after the treatment at the time of progression. DNA aneuploidy was observed in 65% of the patients. Among the 40 responders there were 26 with aneuploid tumours (65%). Aneuploidy did not reach statistical significance as a prognostic sign in the unstratified study population, but when stratified by response groups, DNA aneuploidy was a significant prognostic factor for a better response (P = 0.04). SPF could be calculated in 76 tumours. Out of 40 responding patients (complete or partial response), 23 had tumours with an SPF higher than the median. Accordingly, patients with a high SPF survived longer than those with a low SPF, with median survival times of 9.8 months and 8.7 months, respectively (P = 0.18). We conclude that DNA aneuploidy and a high SPF are associated with longer survival in patients with disseminated melanoma treated with a chemoimmunotherapy regimen. Based on our findings we claim that, among patients receiving chemoimmunotherapy, high SPF and aneuploidy are not signs of unfavourable prognosis, which is in contrast to previous observations in melanoma patients receiving heterogeneous therapy.
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Hahka-Kemppinen
authors.forename: T
authors.initials: T
authors.lastname: Muhonen
authors.forename: S
authors.initials: S
authors.lastname: Nordling
authors.forename: S
authors.initials: S
authors.lastname: Pyrhönen
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics*; D003606:Dacarbazine / Q000008:administration & dosage; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy; D007372:Interferons / Q000627:therapeutic use*; D008130:Lomustine / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D011003:Ploidies; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D004273:DNA, Neoplasm; D001761:Bleomycin; D014750:Vincristine; D008130:Lomustine; D003606:Dacarbazine; D007372:Interferons