Influence of Urethra Sparing on Tumor Control Probability and Normal Tissue Complication Probability in Focal Dose Escalated Hypofractionated Radiotherapy: A Planning Study Based on Histopathology Reference

Abstract

PurposeMultiparametric magnetic resonance tomography (mpMRI) and prostate specific membrane antigen positron emission tomography (PSMA-PET/CT) are used to guide focal radiotherapy (RT) dose escalation concepts. Besides improvements of treatment effectiveness, maintenance of a good quality of life is essential. Therefore, this planning study investigates whether urethral sparing in moderately hypofractionated RT with focal RT dose escalation influences tumour control probability (TCP) and normal tissue complication probability (NTCP).Patients and Methods10 patients with primary prostate cancer (PCa), who underwent 68Ga PSMA-PET/CT and mpMRI followed by radical prostatectomy were enrolled. Intraprostatic tumour volumes (gross tumor volume, GTV) based on both imaging techniques (GTV-MRI and -PET) were contoured manually using validated contouring techniques and GTV-Union was created by summing both. For each patient three IMRT plans were generated with 60 Gy to the whole prostate and a simultaneous integrated boost up to 70 Gy to GTV-Union in 20 fractions by (Plan 1) not respecting and (Plan 2) respecting dose constraints for urethra as well as (Plan 3) respecting dose constraints for planning organ at risk volume for urethra (PRV = urethra + 2mm expansion). NTCP for urethra was calculated applying a Lyman-Kutcher-Burman model. TCP-Histo was calculated based on PCa distribution in co-registered histology (GTV-Histo). Complication free tumour control probability (P+) was calculated. Furthermore, the intrafractional movement was considered.ResultsMedian overlap of GTV-Union and PRV-Urethra was 1.6% (IQR 0-7%). Median minimum distance of GTV-Histo to urethra was 3.6 mm (IQR 2 – 7 mm) and of GTV-Union to urethra was 1.8 mm (IQR 0.0 – 5.0 mm). The respective prescription doses and dose constraints were reached in all plans. Urethra-sparing in Plans 2 and 3 reached significantly lower NTCP-Urethra (p = 0.002) without significantly affecting TCP-GTV-Histo (p = p > 0.28), NTCP-Bladder (p > 0.85) or NTCP-Rectum (p = 0.85), resulting in better P+ (p = 0.006). Simulation of intrafractional movement yielded even higher P+ values for Plans 2 and 3 compared to Plan 1.ConclusionUrethral sparing may increase the therapeutic ratio and should be implemented in focal RT dose escalation concepts.

A Novel Radiotherapeutic Approach to Treat Bulky Metastases Even From Cutaneous Squamous Cell Carcinoma: Its Rationale and a Look at the Reliability of the Linear-Quadratic Model to Explain Its Radiobiological Effects

“…TCP was calculated based on the LQ Poisson’s model ( 21 , 22 ) through the use of the pyradiobiology software ( 23 , 24 ). The values of the parameters TCD50 and γ are those for head and neck squamous cells, at 51.77 Gy and 2.28, respectively ( 25 ).…”

Feasibility, pitfalls and results of a structured concept-development phase for a randomized controlled phase III trial on radiotherapy in primary prostate cancer patients

“…Results of RM planning study were published elsewhere [ 18 ]. Summarized prescriptions doses and constraints were reached in all plans, even when sparing of planning organ at risk volume for urethra (PRV-Urethra) was performed.…”

“…These models allow consequently the prediction of the potential tumor control and occurring toxicities of new RT regimen before being applied in cancer patients. The NTCP was calculated in dependence of the RT dose distribution in the organs at risk: bladder, rectum and urethra according to our previous publications [ 17 , 18 ]. Additionally, the TCP was calculated under consideration of the dose distribution in the intraprostatic tumor mass in co-registered histopathology reference ( 19 , 20 ).…”

“…: 469/14) and written informed consent was obtained from every patient. Please see our previous publication [ 18 ] for methodological details.…”

PSMA-PET/MRI-Based Focal Dose Escalation in Patients with Primary Prostate Cancer Treated with Stereotactic Body Radiation Therapy (HypoFocal-SBRT): Study Protocol of a Randomized, Multicentric Phase III Trial

“…Two RCTs reported good safety profile with doses of 6.1–7.25 Gy per fraction [ 7 , 8 ]. Additionally, for primary PCa a dose–response relationship with improved tumor control rates at higher doses has been demonstrated [ 9 , 10 , 11 ]. Overcoming the issue of limited possibilities for dose escalation to the whole prostate, concepts of focal RT dose escalation have been implemented in RT practice, enabling the macroscopic intraprostatic tumor mass (ITM) to be irradiated under maintenance of dose constraints to adjacent organs at risk (OAR).…”