Predictive assay of neoadjuvant chemotherapy in management of oral cancer

Predictive assay of neoadjuvant chemotherapy in management of oral cancer
Accepted 12 October 2006
T. Tsuji13, M. Noguchi2, Y. Kido1, H. Kubota1, K. Takemura1, K. Nakamori1, H. Hiratsuka1
International Journal of Oral & Maxillofacial Surgery

Abstract
Neoadjuvant chemotherapy (NAC) for oral squamous cell carcinoma has a positive impact on organ preservation and/or survival only in patients who achieve an excellent anti-tumour effect with this therapy. Predictive assay for NAC can play an important role in establishing tailor-made treatments for oral squamous cell carcinoma. In this retrospective study, the anti-tumour effects of cisplatin-based NAC in 70 patients with oral squamous cell carcinoma were reviewed in relation to biological markers of tumour cell proliferation activity: tumour grade, cellular DNA content, mitotic index, apoptotic index, ki-67 positive rate, and p53 and Bax expression. Tumour grade, Bax expression, apoptotic index and cellular DNA content were significantly correlated with the anti-tumour effects of NAC in univariate analysis. Tumour grade, Bax expression and apoptotic index were selected as independent predictive factors by means of multiple logistic analysis. Using the regression equation from these results, the prediction rate for anti-tumour effects was 70%. For patients in whom NAC is predicted to be ineffective, it may be necessary to choose another treatment option in order to improve their survival and quality of life.

Key words: predictive assay, neoadjuvant chemotherapy, oral squamous cell carcinoma, the effects of preoperative chemotherapy, multiple logistic, regression analysis
Article Outline
Ô Abstract

Ô Materials and methods

Ô Patients and specimens

Ô Measurement of DNA content

Ô Immunohistochemistry

Ô Identification of apoptotic cells

Ô Assessment of effects of preoperative chemotherapy

Ô Statistical analysis

Ô Results

Ô Histopathological response to preoperative chemotherapy

Ô Pathological findings from resection specimens

Ô Histopathological response to preoperative chemotherapy and clinical outcomes

Ô Logistic regression analysis

Ô Discussion

Ô References

Ô Copyright

Carcinoma of the head and neck region shows a high sensitivity to anticancer drugs. Since the 1980s, multiple drug therapies, including cisplatin (CDDP), have been incorporated into multidisciplinary treatments to eradicate micrometastatic foci and reduce tumour size. This treatment is used as a preoperative therapy for radical surgical operations of advanced cancer of the head and neck region in the hope of improving the permanent cure rate6, 14. Although this treatment has been shown to contribute to functional preservation in cancer of the hypopharynx and larynx, no convincing evidence has been obtained of a contribution to a better prognosis for survival13, 24.

It was shown that the tumours that were sensitive to preoperative chemotherapy exhibited a good response to radiation therapy and had a good prognosis for survival5. These results clearly indicate that the effects of preoperative chemotherapy reflect the properties of the treated tumours. If these effects could be predicted with high accuracy, it would also be possible to predict their contribution to organ preservation and prognosis for survival in the limited group of patients who show good responses to preoperative chemotherapy.

There are various in vivo and in vitro tests available to predict the sensitivity of cancer cells to chemotherapeutic drugs. These tests are not used clinically because the results obtained from them in solid cancers are not necessarily in accord with the clinical effects. This discrepancy occurs because the effects of chemotherapeutic drugs on individual tumours depend on multiple factors, including not only sensitivity of the cancer cells but also clinical and histological factors as well as a number of cellular properties7.

The aim of this study was to determine the correlation of various factors related to proliferation and differentiation of oral squamous cell carcinoma with the effects of preoperative chemotherapy, and thus to predict the effects of preoperative chemotherapy.

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