Dose Response Relationship of Nuclear Changes with Fractionated Radiotherapy in Assessing Radiosensitivity of Oral Squamous Cell Carcinoma

Radiotherapy is frequently used as treatment for oral cancer either alone or in combination with surgery. Reaction of tumor tissue to radiotherapy often shows marked inter-individual variability making it difficult to assess and predict the treatment outcome for individual patients. Recently attention has been drawn towards the role of radiation induced nuclear changes to assess radiosensitivity. Objectives: To establish the relationship between various nuclear changes with radiation dose and to explore the possibility of utilizing them as an assay to predict tumor response to radiotherapy. Study Design: Study group consisted of 20 patients with histologically proven oral squamous cell carcinoma treated by fractionated radiotherapy, receiving a total of 60 Gy of external beam radiation in 30 fractions of 2 Gy each given daily. Serial scrape smears were collected from the lesion and contralateral normal site before the start of treatment and after 4th, 8th, and 12th fraction. Staining with acridine orange fluorescent dye and May-Grunwald Giemsa stain was done to assess nuclear abnormalities like micronucleation, nuclear budding, binucleation, and multinucleation. These were then correlated with tumor response. Results: Statistically significant dose related increase in all nuclear abnormalities was observed with micronucleation being the most reliable independent parameter for assessing radiation induced damage of cancer cells. Nuclear abnormalities were significantly higher in lesional tissue than normal but did not show statistically significant correlation with tumor response though there was a trend towards higher counts in patients with good tumor response. Conlusion: A direct dose-response relationship exists between the frequencies of various nuclear abnormalities and radiation exists in oral squamous cell carcinoma patients undergoing fractionated radiotherapy. Further studies are required to improve the understanding of the role of these changes in predicting tumor radiosensitivity.