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Objective Failure rate in randomized controlled trials (RCTs) is > 50%, includes safety-problems, underpowered statistics, lack of efficacy, lack of funding or insufficient patient recruitment and is even more pronounced in oncology trials. We present results of a structured concept-development phase (CDP) for a phase III RCT on personalized radiotherapy (RT) in primary prostate cancer (PCa) patients implementing prostate specific membrane antigen targeting positron emission tomography (PSMA-PET). Materials and methods The 1 yr process of the CDP contained five main working packages: (i) literature search and scoping review, (ii) involvement of individual patients, patients’ representatives and patients’ self-help groups addressing the patients’ willingness to participate in the preparation process and the conduct of RCTs as well as the patient informed consent (PIC), (iii) involvement of national and international experts and expert panels (iv) a phase II pilot study investigating the safety of implementation of PSMA-PET for focal dose escalation RT and (v) in-silico RT planning studies assessing feasibility of envisaged dose regimens and effects of urethral sparing in focal dose escalation. Results (i) Systematic literature searches confirmed the high clinical relevance for more evidence on advanced RT approaches, in particular stereotactic body RT, in high-risk PCa patients. (ii) Involvement of patients, patient representatives and randomly selected males relevantly changed the PIC and initiated a patient empowerment project for training of bladder preparation. (iii) Discussion with national and international experts led to adaptions of inclusion and exclusion criteria. (iv) Fifty patients were treated in the pilot trial and in- and exclusion criteria as well as enrollment calculations were adapted accordingly. Parallel conduction of the pilot trial revealed pitfalls on practicability and broadened the horizon for translational projects. (v) In-silico planning studies confirmed feasibility of envisaged dose prescription. Despite large prostate- and boost-volumes of up to 66% of the prostate, adherence to stringent anorectal dose constraints was feasible. Urethral sparing increased the therapeutic ratio. Conclusion The dynamic framework of interdisciplinary working programs in CDPs enhances robustness of RCT protocols and may be associated with decreased failure rates. Structured recommendations are warranted to further define the process of such CDPs in radiation oncology trials.

A basis for future trials with stereotactic body radiotherapy (SBRT) for tumors of the liver hilum should be established. Thus, dosage concepts, planning processes, and dose constraints as well as technical innovations are summarized in this contribution.On the background of our own data, the current literature was reviewed. The use of SBRT in the most common tumors of the liver hilum (pancreatic cancer and Klatskin tumors) was investigated. Dose constraints were calculated in 2 Gy standard fractionation doses.A total of 8 pilot or phase I/II studies about SBRT in the liver hilum were identified. In recent years, the SBRT technique has developed very quickly from classical stereotactic body frame radiotherapy to IGRT techniques including gating and tracking systems. In the studies using classical body frame technique, patients experienced considerable toxicities (duodenal ulcer/perforation) as compared to tolerable side effects in IGRT studies (10% grade 3 and 4 toxicities). Dose constraints for duodenum, liver, kidneys, colon, and spinal cord were derived from the investigated studies. Survival and local tumor control data are very heterogeneous: median survival in these patients with locally advanced pancreatic or Klatskin tumors ranges between 5 and 32 months. Excellent local tumor control rates of about 80% over 24 months were achieved using SBRT.Despite a few negative results, SBRT seems to be a promising technique in the treatment of tumors of the liver hilum. Highest precision in diagnostics, positioning, and irradiation as well as strict dose constraints should be applied to keep target volumes as small as possible and side effects tolerable.