Introduction Adaptive Radiotherapy (ART) is already widely used in most large centers in daily clinical routine. However, high-quality data on this topic are scarce and only very few prospective trials have been conducted so far.
Methods The literature and the available evidence have been carefully reviewed, presented and discussed here
Results The broad implementation of image-guided radiotherapy (IGRT) over the last decades led to the advent of adaptive treatments for several indications, with head and neck cancer, prostate cancer and tumors of the upper abdomen being the most prominent examples. Especially recent developments, both in terms of improved imaging and software, allow for more frequent, quicker and even online plan adaptations. For example, hybrid platforms combining a linear accelerator with MRI-imaging, revolutionized "on-board" imaging with improved quality and soft-tissue contrast and machine-learning methods simplified delineation, re-planning and plan quality assurance. Nevertheless, even a generally accepted definition of the term "adaptive radiotherapy" is lacking ,as well as established guidelines of the methods to follow and purposes to pursue. So, the term "adaptive radiotherapy" summarizes very different approaches like either preservation of the original plan despite anatomic changes or maximizing organ sparing, up to more experimental regimens such as spatio-temporal fractionation and different dose-escalation or de-escalation strategies based on response assessment. Every one of these approaches requires different methods and until the procedures and the reporting has been standardized both conducting clinical trials and reproducing clinical results remains a great challenge. Moreover, only very recently investigators started conducting prospective trials evaluating possible benefits of ART. Up to this day, only few results have been published mainly in the indications of head and neck, prostate cancer and upper abdominal tumors, most of them showing clear dosimetric benefits. However, it remains largely unknown if these dosimetric benefits can be translated to improvement in any clinically relevant endpoint. A recent randomized phase iii trial in prostate cancer (MIRAGE) could demonstrate decreased toxicity of MR-guided adaptive stereotactic radiotherapy compared to standard CT-guided approach. Yet, as different platforms and imaging and different target volume margins were used in the two arms, it remains questionable if the differences observed can be attributed to the ART-approach. In contrast to that, the only randomized trial in head and neck cancer examining the possible benefits of ART in reducing xerostomia (ARTIX) failed to meet its primary endpoint. Finally, some promising results from biologically and/or response-based ART for head and neck cancer originate from small phase I-II trials with low patient numbers and short follow up.
Conclusion Although different forms of adaptive radiotherapy are already implemented in most large radiotherapy centers, there are many questions to be answered before this modality becomes standard of care. First of all, there is an urgent and unmet need for international guidelines on performing and reporting ART, depending on the techniques used and the goals pursued. This will allow for more and high-quality prospective randomized trials demonstrating not only obvious dosimetric benefits, but also improvement in clinical endpoints.