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Hypofractionated Intensity-Modulated Radiotherapy (IMRT) for Prostate Cancer Using Patient-Specific Cancer Biology

E Her1 , A Haworth2 , A Kennedy3 , H Reynolds4 , Y Sun5 , M Bangert6 , S Williams7 , M Ebert8*, (1) University of Western Australia, Perth, Western Australia, (2) University of Sydney, Sydney, New South Wales, (3) Sir Charles Gairdner Hospital, Perth, 6009, (4) Peter MacCallum Cancer Centre, Melbourne, Victoria, (5) University of Sydney, Sydney, New South Wales, (6) German Cancer Research Centre, Heidelberg, Heidelberg, (7) Peter MacCallum Cancer Centre, Melbourne, Victoria, (8) The University of Western Australia, Nedlands,


(Tuesday, 7/31/2018) 11:00 AM - 12:15 PM

Room: Karl Dean Ballroom A1

Purpose: To compare radiotherapy treatment plans for prostate cancer, biologically-optimised using patient-specific tumour cell distributions obtained from multi-parametric MRI, generated for conventional and hypofractionated schedules.

Methods: Five prostate cancer patients that underwent radical prostatectomy were selected as part of a program to develop bio-focussed prostate radiotherapy (BiRT). The proposed biological optimisation involves using tumour control probability (TCP) to guide inverse-planned intensity-modulated radiotherapy (IMRT) and to determine a patient-specific prescription dose. Patient-specific clonogen distribution maps were derived from multiparametric MRI using machine learning methods based on ground-truth histology and used to inform the TCP model. Biologically-optimised plans with equal TCP, generated for a conventional schedule (78 Gy/39 fractions) and hypofractionated schedules (60 Gy/20 fractions, 36.25 Gy/5 fractions), were compared for each patient using dose-volume and dose distribution metrics for specific normal tissues. A single-fraction schedule was also examined using linear-quadratic and linear-quadratic-linear survival models.

Results: Biologically-optimised hypofractionated plans demonstrated a statistically significant reduction in rectal and bladder dose in comparison with conventionally-fractionated plans. The tissue sparing effect was more pronounced with extreme hypofractionation. Single-fraction prostate IMRT was feasible for both survival models in the single case investigated, though the two models predicted widely-differing estimates for optimal dose prescription.

Conclusion: This study indicates potential for significant reduction in dose to the rectum and bladder for hypofractionated treatment of prostate cancer, with the benefit enhanced if a biologically-driven dose painting approach is utilised, based on patient-level information of the clonogenic cell distribution. Results of this study supports further clinical investigations into the use of extreme hypofractionation.

Funding Support, Disclosures, and Conflict of Interest: This work was supported by the Australian National Health and Medical Research Council (APP1126955).


Inverse Planning, MRI, Prostate Therapy


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