Spinal cord response to altered fractionation and re-irradiation: radiobiological considerations and role of bioeffect models.

The aim of radiation oncologist is to implement an uncomplicated loco regional control of cancer by radiation therapy. The bioeffect of a physical dose depends on the nature of the tissue, fractionation scheme, dose rate and treatment time. The transformation of absorbed dose into a bioeffect dose is controlled by treatment variables and the radiobiological characteristics of the relevant tissue. Various bioeffect models have been proposed to predict the biological effect of radiotherapy treatments. Dale has proposed extrapolated response dose (ERD) equations for external beam therapy, intracavitary brachytherapy and interstitial brachytherapy. Within the context of the LQ model, the parameter which quantifies the overall biological effect on a given tissue is the biologically effective dose (BED) which is obtained by applying repopulation correction to ERD (Orton). Thames proposed the total effect (TE) concept based on the incomplete repair LQ model which accounts for the biological effect of a fractionated course of radiotherapy. Spinal cord myelitis limits the dose to tumours in the head and neck, thoracic and upper abdominal regions resulting in reduction of tumour control probability. Radiation myelopathy is one of the most devastating complications of clinical radiotherapy. Treatment techniques that are designed to minimize the risk of spinal cord injury are likely to underdose the tumour consequent failure to control the disease. Since radiation myelopathy results in severe and irreversible morbidity, it is important to establish the tolerance dose of the spinal cord. A number of patients have recently been reported to have developed radiation myelopathy following hyperfractionated accelerated radiotherapy. As the survival rates of patients increase, radiation oncologists are more frequently faced with the problem of treatment of late recurrence or second tumours situated within or close to previously treated site. A rationale for taking a decision in treating in such a condition is even more complex than the original condition and requires knowledge of the kinetics of decay of occult injury of the previous treatment. To test the validity of ERD, clinically reported data of altered fractionation to the spinal cord for 7 patients reported by Wong et al, Saunders et al and Bogaert et al, were analysed, ERD values were calculated and compared with compiled clinical literature data of 3233 patients for the incidence of spinal cord myelitis reported by Cohen and Creditor, Wara et al, Abbatucci et al and Jeremic et al for conventional fractionation. ERD values were estimated with alpha/beta of 2.5 Gy for the conventional and altered fractionation data. To test the validity of TE concept for clinical data of re-irradiation tolerance of the spinal cord, the data of the 22 patients compiled by Nieder et al were used. Clinical data compiled from the literature of Cohen and Creditor, Wara et al, Abbatucci et al and Jeremic et al, were used for comparison.