Flow-cytophotometric DNA Measurements for Monitoring and Planning Chemotherapy in Anaplastic Thyroid Carcinoma

Abstract

Anaplastic thyroid carcinoma is an aggressive tumour uncontrollable by surgery and/or irradiation, whereas addition of chemotherapy resulted in some long term survivors. In a series of 76 patients with anaplastic thyroid carcinoma treated from 1973–87 at the Institute of Oncology Ljubljana the best survival (median 15 months) was obtained with a combination of chemotherapy, irradiation, followed by surgery. However, only 6 out of 53 patients (11%) with primarily inoperable tumours in whom treatment was started with chemotherapy and irradiation were rendered operable. Since 1988 flow-cytophotometric DNA measurements have been used for immediate evaluation of the effect of chemotherapy and planning of treatment in anaplastic thyroid carcinoma at the Institute of Oncology. The aim of this study was to evaluate whether monitoring of treatment by flow-cytophotometric DNA measurements improved results of treatment in those patients.

From 29 patients with anaplastic thyroid carcinoma treated from 1988–1991 in 20 treatment was started with chemotherapy and irradiation. Sequential flow-cytophotometric DNA measurements for evaluation of chemotherapy were performed in 19 patients. Fine-needle aspiration biopsies were performed before and sequentially after the application of cytostatic drugs. DNA measurements (mercury lamp cytophotometer PAS II PARTEC) and cytomorphological studies were conducted on fine needle aspiration biopsy samples. The results of flow-cytophotometric DNA measurements after single cytostatic drug were used for planning combined chemotherapy or chemotherapy and irradiation. Vinblastine or Cis-Platinum or Adriamycin or Novantron were used for perturbation of the tumour cell cycle. When DNA measurements showed an accumulation of cells in a particular phase of a cell cycle the next drug effective in that phase was used at the most appropriate time. Local tumour control was significantly better in the group of patients monitored with flow-cytophotometric DNA measurements. Of 20 pts in whom treatment was started with chemotherapy and irradiation there were 8 responders (3 CR and 5 PR). In the patients treated from 1973–87 there were only 11% responders to chemotherapy and irradiation in contrast with 8/20 (40%) in the present series (p < 0.05). Six of these patients are alive (6,8,10,22 and 31 months) after treatment. Introduction of sequential flow-cytophotometric DNA measurements and cytomorphological examination of fine-needle aspiration biopsy specimens make possible individually tailored treatment which results in significantly improved locoregional control and may contribute to prolonged survival in patients with anaplastic thyroid carcinoma.