Feasibility of preference-driven dose plan optimization to support shared decision making in anal cancer radiotherapy

Heidi S Rønde M.Sc. (1) ,Leonard Wee Ph.D. (2,3), John Pløen M.D. (3,4), Ane L Appelt Ph.D. (3,5).

1) Department of Medical Physics, Vejle Hospital, Denmark. 2) MAASTRO Clinic, School of Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands. 3) Danish Colorectal Cancer Centre South, Vejle Hospital, and Institute of Regional Health Research, University of Southern Denmark, Denmark. 4) Department of Oncology, Vejle Hospital, Denmark. 5) Leeds Institute of Cancer and Pathology, University of Leeds, and Leeds Cancer Centre, St. James’ University Hospital, Leeds, United Kingdom 

Background
Chemo-radiotherapy is an established primary curative treatment for anal cancer, but clinically equal rationale for different target doses exists. Joint preferences (physician and patient) can be used to determine acceptable trade-offs inherent during radiotherapy treatment planning. If so, it is essential to compare multiple simultaneously optimal plans. We have quantified the degree to which different toxicity priorities might be incorporated into treatment plan selection, to elucidate the feasible decision space for shared decision making in anal cancer radiotherapy.

Materials and methods
Retrospective IMRT plans were generated for 22 representative anal cancer patients. Multi-criteria optimisation handles dynamically changing priorities between clinical objectives while meeting fixed clinical constraints. Four unique dose distributions were designed to represent a wide span of clinically relevant objectives: high dose preference (60.2Gy tumour boost and 50.4Gy to elective nodes with physician-defined order of priorities), low dose preference (53.75Gy tumour boost, 45Gy to elective nodes, physician-defined priorities), bowel sparing preference (lower dose levels and priority for bowel avoidance) and bladder sparing preference (lower dose levels and priority for bladder avoidance). Dose metrics for bowel and bladder were compared for the different planning regimens using descriptive statistics and paired Wilcoxon signed rank tests. 

Results
All plans satisfied constraints for target coverage. A senior radiation oncologist approved a random subset of plans for quality assurance. Compared to a high dose preference, bowel sparing was clinically meaningful at the lower prescribed dose (median change in V45Gy : 234 cm3; inter-quartile range [66;247]; p<0.01) and for a bowel sparing preference (median change in V45Gy : 281 cm3; [73;488]; p<0.01). Compared to a high dose preference, bladder sparing was clinically meaningful at the lower prescribed dose (median change in V35Gy : 13.7%-points; [0.3;30.6]; p<0.01) and for a bladder sparing preference (median change in V35Gy : 30.3%-points; [12.4;43.1]; p<0.01).

Conclusion
There is space available in anal cancer radiotherapy planning to incorporate preferences, though trade-offs are highly patient-dependent. The dominant trade-off in these plans involved the bowel and the bladder, where significant dose-redistribution was possible. Preference-informed dose planning is feasible for clinical studies utilising shared decision making. Further work on tumour control and toxicity modelling is required.