Brodin, N. Patrik5; Vogelius, Ivan R.6; Bjork-Eriksson, Thomas4; af Rosenschold, Per Munck4; Maraldo, Maja V.4; Aznar, Marianne C.7; Specht, Lena7; Bentzen, Soren M.4
1 Biocomplexity, The Niels Bohr Institute, Faculty of Science, Københavns Universitet2 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet3 Graduate School of Health and Medical Sciences, Graduate School of Health and Medical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet4 unknown5 Biocomplexity, The Niels Bohr Institute, Faculty of Science, Københavns Universitet6 Graduate School of Health and Medical Sciences, Graduate School of Health and Medical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet7 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
Minimizing the life years lost attributable to failure to control the disease and late complication risk
Background. A mathematical framework is presented for simultaneously quantifying and evaluating the trade-off between tumor control and late complications for risk-based radiation therapy (RT) decision-support. To demonstrate this, we estimate life years lost (LYL) attributable to tumor recurrence, late cardiac toxicity and secondary cancers for standard-risk pediatric medulloblastoma (MB) patients and compare the effect of dose re-distribution on a common scale. Methods. Total LYL were derived, based on the LYL attributable to radiation-induced late complications and the LYL from not controlling the primary disease. We compared the estimated LYL for three different treatments in 10 patients: 1) standard 3D conformal RT; 2) proton therapy; 3) risk-adaptive photon treatment lowering the dose to part of the craniospinal (CS) target volume situated close to critical risk organs. Results. Late toxicity is important, with 0.75 LYL (95% CI 0.60-7.2 years) for standard uniform 24 Gy CS irradiation. However, recurrence risk dominates the total LYL with 14.2 years (95% CI 13.4-16.6 years). Compared to standard treatment, a risk-adapted strategy prescribing 12 Gy to the spinal volume encompassing the 1st-10th thoracic vertebrae (Th1-Th10), and 36 Gy to the remaining CS volume, estimated a LYL reduction of 0.90 years (95% CI -0.18-2.41 years). Proton therapy with 36 Gy to the whole CS volume was associated with significantly fewer LYL compared to the risk-adapted photon strategies, with a mean LYL difference of 0.50 years (95% CI 0.25-2.60 years). Conclusions. Optimization of RT prescription strategies considering both late complications and the risk of recurrence, an all-cause mortality dose painting approach, was demonstrated. The risk-adapted techniques compared favorably to the standard, and although in this context, the gain is small compared to estimated uncertainty, this study demonstrates a framework for all-cause mortality risk estimation, rather than evaluates direct clinical applicability of risk-adapted strategies.
Acta Oncologica, 2014, Vol 53, Issue 4, p. 462-470