RESUMEN
Recent results indicate that the adjusted DNA Index (aDI), a measure of nuclear DNA content, is a significant prognostic factor for patients with advanced laryngeal cancer treated with surgery and radiation therapy. Because DNA aneuploidy is an indirect measure of the proliferative activity of a cell population, a study was conducted to examine differences in tumor response to induction chemotherapy based on aDI values. Pretreatment tumor specimens were obtained from 50 patients with stage III and IV laryngeal squamous cell carcinoma who underwent induction chemotherapy (cisplatin/5-FU). With the use of computerized cytomorphometry, DNA content and nuclear area were measured and associations with tumor site, stage, chemotherapy response, tumor recurrence, and survival were examined. An elevated aDI was more frequent in patients with a chemotherapeutic response (p = 0.08), and mean aDI was higher among the complete responders. There were no complete responders among patients with a low aDI value (< 0.024). Neither aDI nor nuclear area correlated significantly with organ preservation or patient survival. Our results indicate that a complete response is more likely for patients with tumors with an elevated aDI and that pretreatment aDI may be useful in selecting high-risk patients who might benefit from chemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , ADN de Neoplasias/análisis , Neoplasias Laríngeas/tratamiento farmacológico , Neoplasias Laríngeas/genética , Anciano , Aneuploidia , Carcinoma de Células Escamosas/mortalidad , Cisplatino/administración & dosificación , Fluorouracilo/administración & dosificación , Humanos , Neoplasias Laríngeas/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pronóstico , Tasa de SupervivenciaRESUMEN
BACKGROUND: Alterations in DNA content, nuclear morphologic characteristics, and histologic grading have been associated with prognosis in several types of solid malignant neoplasms. METHODS: To determine the potential usefulness of these factors in predicting tumor behavior in patients with laryngeal squamous cell carcinoma, tumor specimens from 88 previously untreated patients with Stage III or IV cancers were studied. The DNA content and nuclear area (NA) were measured for individual nuclei of each tumor with the use of Azure A-stained frozen sections. An adjusted DNA index (aDI) for each patient was calculated from the slope of the linear regression analysis of nuclear DNA index on NA. Hematoxylin and eosinstained sections were examined and graded systematically for histologic growth pattern. All patients were enrolled in a prospective clinical trial and had laryngectomy and postoperative radiation therapy. RESULTS: The disease-free survival length was longer and the relapse rates were lower in patients with a low aDI (P less than 0.005) and with tumors exhibiting low-grade growth patterns (P less than 0.001). CONCLUSIONS: These parameters were independent of staging variables and were better predictors of tumor relapse than traditional clinical staging classifications.