Reirradiation treatment effects in the clinic (ReTEC) proposal – proof of concept based on spinal cord dose tolerance for reirradiation with stereotactic body radiotherapy

BACKGROUND: Since the inception of spinal radiosurgery decades ago, the factors influencing spinal cord recovery have remained unclear. Elucidating these factors would aid in reirradiation planning and delivery. We describe modeling reirradiation normal tissue complication probabilities (NTCP) from compiled published data, akin to the collaborative Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) and High Dose per Fraction, Hypofractionated Treatment Effects in the Clinic (HyTEC) projects. PURPOSE: Simple dose-time recovery factors for the spinal cord serve as a basis to propose the Reirradiation Treatment Effects in the Clinic (ReTEC) project. ReTEC aims to define human organ recovery factors to convert the total composite dose to an equivalent physical dose compatible with the de novo therapy dose tolerance limits. Additionally, we present a system for automating analyses as well as clinical implementation of radiation dose-time recovery. METHODS: Published literature was queried for stereotactic voxel-wise composite reirradiation plans involving the spinal cord, but none were found. Hence, minimum reporting criteria were used instead: spinal cord maximum dose (Dmax) of each course, time interval between courses, and number of fractions or biologically effective dose, per patient or in sufficiently homogeneous groups of patients. Recovery factors and logistic model parameters were fitted with maximum likelihood techniques. RESULTS: An NTCP model was derived from 13 papers with data from 282 lesions, including six myelopathy cases. The model suggested spinal cord recovery of more than 50% in less than 1 year, which is faster and more complete than current clinical practice, but with wide confidence intervals (CI) (bootstrap 95% CI: 31%-95% when the time interval was 1 year). CONCLUSION: Due to limited data, we recommend remaining within current standard guidelines until more comprehensive analyses, optimally under the ReTEC initiative, refute or validate these estimates. ReTEC would require composite plans accounting for differing Dmax locations in each course. Nevertheless, this proof-of-concept Dmax model provides insight and serves as a basis to propose ReTEC.