Anticancer Drug Action Assessed by Serial DNA Flow Cytometry during Induction Chemotherapy in Oral Squamous Cell Carcinoma: Impacts on the Development of Individualized Treatment Strategies

Abstract

Biopsy specimens from 53 advanced oral squamous cell carcinomas were taken before and after intra-arterial induction chemotherapy and analyzed by DNA flow cytometry. The 5-year overall survival rate was 90% in patients with diploid carcinomas in contrast to only 18% of those with pretherapeutically aneuploid tumors. A clear decrease of aneuploid cell numbers during chemotherapy indicated that DNA flow cytometry substantially allows monitoring of cytotoxic effects in vivo. Even if the immediate response to chemotherapy was significantly better in carcinomas with a complete disappearance of aneuploid tumor cells during treatment than in cases with persisting aberrant cells, the overall survival rate was nearly identical in both groups.

Chromosomal Composition of Aneuploid Clones with Different DNA Contents in Head and Neck Squamous Cell Carcinomas as Determined by Combined Flow Cytometry and Fluorescence In Situ Hybridization

“…Using this highresolution FCM technique, we recently reported survival rates of more than 80% for patients with flow cytometrically diploid oral carcinomas in contrast to rates of less than 50% for the aneuploid group. This difference was independent of tumour size or differentiation [2,5], of whether the tumours were primaries or recurrences [9] and of whether the patients were treated by surgery alone or with induction chemotherapy [24,25]. This ploidy-specific difference in outcome applied in like manner to tumours accommodating aneuploid clones with minor DNA content aberrations [2,7].…”

“…Despite this general competence for clonal diversification, FCM studies have shown that head and neck carcinomas mostly contain a single aneuploid clone, and no changes of FCM patterns in favour of multiconality has been observed during tumour progression [2]. Although individual tumours develop clones with widely differing DNA contents [2,7], DNA-aneuploid cell populations are characterised by a pronounced stability during metastasis and recurrence development [7,9,20,24,25]. These observations strongly suggest mechanisms that determine the acquisition and maintenance of particular karyotypic patterns.…”

The value of DNA flow cytometry in predicting the development of lymph node metastasis and survival in patients with locally recurrent oral squamous cell carcinoma

“…The current study provides further evidence of this hypothesis. Although the number of patients with diploid recurrence was low, a favorable 87% 5‐year survival rate indicated that the already excellent outcome of radical primary tumor surgery1‐3 could largely be reestablished by a second local intervention, provided that aneuploid tumor cell populations had not emerged during recurrence development. Thus, there was no evidence of a significantly different pattern of host tissue invasion in diploid tumors that recurred compared with those that did not.…”

“…With radical surgery, a 5‐year survival rate of nearly 90% was achieved for patients with diploid primary squamous cell carcinoma, in contrast to a rate of approximately 30% for patients with aneuploid primary tumors. This suggests that prognosis can be improved by local intervention alone before the development of aneuploid tumor cell lines 1‐3. In fact, the risk of recurrence at the primary site has been reported to range between 46% and 71% for surgically resected aneuploid oral carcinomas, compared with between 4% and 9% for diploid tumors 4, 5.…”