Abstract
Radiotherapy is involved in 50% of all cancer treatments and 40% of cancer cures. Most of these treatments are delivered in fractions of equal doses of radiation (Fractional Equivalent Dosing (FED)) in days to weeks. This treatment paradigm has remained unchanged in the past century and does not account for the development of radioresistance during treatment. Even if under-optimized, deviating from a century of successful therapy delivered in FED can be difficult. One way of exploring the infinite space of fraction size and scheduling to identify optimal fractionation schedules is through mathematical oncology simulations that allow for in silico evaluation. This review article explores the evidence that current fractionation promotes the development of radioresistance, summarizes mathematical solutions to account for radioresistance, both in the curative and non-curative setting, and reviews current clinical data investigating non-FED fractionated radiotherapy.
Highlights
Received: 21 December 2021Radiotherapy is involved in 50% of all cancer treatments and 40% of cancer cures today [1]
In addition to fractional equivalent dosing (FED), current radiotherapy is delivered in a short-predefined time period (Rule Two) at maximum tolerable dose aiming for tumor eradication
Biological mechanisms to confer resistance vary amongst these studies, all radioresistant clones were evolved through fractionated radiotherapy and displayed increased survival after radiation compared to the parental lines
Summary
Nima Ghaderi 1,† , Joseph Jung 1,† , Sarah C.
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