BIOPROP: Biologically Optimised Prostate Cancer Radiotherapy or Dose Painting


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Isabel Syndikus1, Julien Uzan1, Philip Mayles1, Alan Nahum1
1Clatterbridge Centre for Oncology, Bebington, Merseyside, United Kingdom

Background

Patients with localised prostate cancer have better survival after high dose radiotherapy combined with hormone therapy compared to either treatment alone; however, a significant proportion relapse locally. Further conventional dose escalation may improve biochemical control, but at increased toxicity. We propose BIOPROP, a phase-II trial for intermediate- and poor-risk patients: radiobiologically optimised isotoxic intensity-modulated RT, including dose painting of the dominant interprostatic lesions (DILs). A Feasibility Study Application was recently submitted to CTAAC.

Method

We have implemented Radiobiological optimisation via the Pinnacle TPS Research Interface (PRI). The objective is: maximise Tumour Control Probability (TCP – Marsden model [1]) whilst not exceeding fixed Normal Tissue Complication Probability (NTCP – Lyman-Kutcher-Burman model [1]), for different rectal endpoints - bleeding [2] and faecal incontinence [3]. All patients receive adjuvant hormone therapy. Randomisation is between:

ARM 1: UK standard intensity-modulated (IM) treatment – uniform 74 Gy to the PTV in 37 fractions.

ARM 2: IM plan created with the above biological objective plus the physical objectives of maximum 84 Gy in the PTV but only 74 Gy to the urethra.

ARM 3: DILs are identified from template biopsies and diffusion-weighted MRI with higher clonogen density being assigned. The biological and physical objectives are as for Arm 2.  

Results

Six CHHIP [4] patients have been re-planned according to the above criteria. The average TCP in Arm 1 is 71.8% [5]. In Arm 2, the escalated dose distributions in the PTV yield 74.9% and 75.2% for ?/? = 10, 3 respectively, for negligible changes in NTCP.

In Arm 3 mean TCPs are 79.7% and 80.8% respectively, also for negligible toxicity change.

As a feasibility test, one patient has been treated according to Arm 3.  

Conclusion

Radiobiologically-guided dose painting is expected to yield significant TCP gains. Treatments will be delivered with rotational IMRT (RapidArc, SmartArc, VMAT, Tomotherapy) ensuring maximum conformality.