Neuroprotection in radiotherapy of brain metastases: A pattern-of-care analysis in Germany, Austria and Switzerland by the German Society for radiation Oncology - working group Neuro-Radio-Oncology (DEGRO AG-NRO).

Background and purpose: Many patients with solid tumors develop brain metastases (BM). With more patients surviving long-term, preservation of neurocognitive function gains importance. In recent years, several methods to delay cognitive deterioration have been tested in clinical trials. However, knowledge on the extent to which these neuroprotective strategies have been implemented in clinical practice is missing. Materials and methods: We performed an online survey regarding treatment patterns of BM in German-speaking countries, focused on the use of neuroprotective approaches. The survey was distributed among radiation oncologists (ROs) registered within the database of the German Society for Radiation Oncology (DEGRO). Results: Physicians of 78 centers participated in the survey. Whole brain radiotherapy (WBRT) is still preferred by 70 % of ROs over stereotactic radiotherapy (SRT) in patients with 6-10 BM. For 4-5 BM WBRT is preferred by 23 % of ROs. The fraction of ROs using hippocampal sparing (HS) in WBRT has increased to 89 %, although the technique is used on a regular basis only by a minority (26 %). The drug memantine is not widely prescribed (14% of ROs). A trend was observed for university hospitals to implement neuroprotective approaches more frequently. Conclusion: There is considerable heterogeneity regarding the treatment of BM in German-speaking countries and a general standard of care is lacking. Neuroprotective strategies are not yet standard approaches in daily clinical routine, although usage is increasing. Further clinical trials, as well as improvement of technical opportunities and reimbursement, might further shift the treatment landscape towards neuroprotective radiation treatments in the future.

Evaluating the impact of a rigid and a deformable registration method of pre-treatment images for hypoxia-based dose painting.

PURPOSE: To assess the impact of rigid and deformable image registration methods (RIR, DIR) on the outcome of a hypoxia-based dose painting strategy. MATERIALS AND METHODS: Thirty head and neck cancer patients were imaged with [18F]FMISO-PET/CT before radiotherapy. [18F]FMISO-PET/CT images were registered to the planning-CT by RIR or DIR. The [18F]FMISO uptake was converted into oxygen partial pressure (pO2) maps. Hypoxic Target Volumes were contoured on pO2 maps for the deformed (HTVdef) and non-deformed (HTV) cases. A dose escalation strategy by contours, aiming at 95 % tumour control probability (TCP), was applied. HTVs were characterised based on geometry-related metrics, the underlying pO2 distribution, and the dose boost level. A dosimetric and radiobiological evaluation of selected treatment plans made considering RIR and DIR was performed. Moreover, the TCP of the RIR dose distribution was evaluated when considering the deformed [18F]FMISO-PET image as an indicator of the actual target radiosensitivity to determine the potential impact of an unalignment. RESULTS: Statistically significant differences were found between HTV and HTVdef for volume-based metrics and underlying pO2 distribution. Eight out of nine treatment plans for HTV and HTVdef showed differences on the level 10 %/3 mm on a gamma analysis. The TCP difference, however, between RIR and the case when the RIR dose distribution was used with the deformed radiosensitivity map was below 2 pp. CONCLUSIONS: Although the choice of the CTplan-to-PET registration method pre-treatment impacts the HTV localisation and morphology and the corresponding dose distribution, it negligibly affects the TCP in the proposed dose escalation strategy by contours.

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

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.

[De-escalation concepts for chemoradiotherapy of HPV-positive oropharyngeal carcinomas: pros and cons]. / Deeskalationsstrategien für die Radiochemotherapie HPV-positiver Oropharynxkarzinome: Pro und Kontra.

BACKGROUND: In contrast to alcohol- and nicotine-induced head and neck tumors, human papillomavirus (HPV)-positive oropharyngeal carcinoma rather affects younger patients, and the incidence of this entity is continuously increasing. Due to the significantly better prognosis of HPV-positive oropharyngeal carcinoma, various treatment de-escalation strategies are currently being investigated, with the aim of reducing toxicity without affecting the good survival rates of these patients. OBJECTIVE: This study aims to evaluate the evidence for treatment de-escalation in HPV-positive oropharyngeal carcinoma. MATERIALS AND METHODS: A literature search was performed and relevant studies are critically discussed. RESULTS: De-escalation strategies for HPV-associated oropharyngeal carcinoma using induction chemotherapy or radiation dose reduction have demonstrated good oncological results in phase II trials, with lower toxicity rates compared to historical controls. However, both of the first published phase III trials investigating de-escalation of concomitant chemotherapy regimens demonstrated inferior outcomes for the deescalated treatment strategies without improvements in treatment-associated toxicities. Additional phase-III trials investigating other de-escalation strategies have not yet been published. CONCLUSION: Treatment de-escalation should be performed exclusively in prospective studies and can currently not be recommended in clinical routine.

Simple Wound Irrigation in the Postoperative Treatment for Surgically Drained Spontaneous Soft Tissue Abscesses: A Prospective, Randomized Controlled Trial.

BACKGROUND: Soft tissue abscesses are among the most frequently encountered medical problems treated by different surgeons. Standard therapy remains incision and drainage with sterile saline irrigation during postoperative wound healing period. Aim of this prospective randomized controlled trial was to compare sterile irrigation versus nonsterile irrigation. STUDY DESIGN: A single center randomized controlled trial was performed to investigate postoperative wound irrigation. The control group used sterile irrigation, and the intervention group used nonsterile irrigation. Primary endpoints were reinfection and reintervention rates, assessed during follow-up controls for up to 2 years. Secondary endpoints were the duration of wound healing, inability to work, pain and quality of life. RESULTS: Between 04/2016 and 05/2017, 118 patients were randomized into two groups, with 61 allocated to the control- and 57 to the intervention group. Reinfection occurred in a total of 4 cases (6.6%) in the sterile protocol and 4 (7%) in the nonsterile protocol. Quality of life and pain values were comparable during the wound healing period, and patients treated according to the nonsterile irrigation protocol used significantly fewer wound care service teams. Despite equal wound persistence rates, a substantially shorter amount of time off from work was reported in the nonsterile protocol group (p value 0.086). CONCLUSION: This prospective, randomized trial indicates that a nonsterile irrigation protocol for patients operated on for soft tissue abscesses is not inferior to the standard sterile protocol. Moreover, a nonsterile irrigation protocol leads to a shorter period of inability to work with comparable pain and quality of life scores during the wound healing period.

[Quality of indications in bariatric surgery]. / Indikationsqualität in der Adipositaschirurgie.

Bariatric and metabolic surgery is increasingly being utilized in Germany and also worldwide. Due to the increased perioperative risk compared to non-obese patients, a detailed and accurate preoperative assessment of the patient is pivotal to improve postoperative and long-term outcomes. The indications for bariatric surgery have shifted in recent years from a certain body mass index (BMI) to comorbidity-based indications. In 2018 the German S3 guidelines for metabolic surgery defined the indications for bariatric surgery as well as the preoperative assessment. The indications for bariatric metabolic operations should be assessed by an interdisciplinary team consisting of surgeons, internists, diabetologists, psychologists and dietitians. It is paramount that surgeon and patient define realistic goals of these operations. Also, the different types of bariatric operation and their long-term consequences should be discussed. Additionally, a thorough endocrinological assessment by an internist or diabetologist with respect to relevant comorbidities of obesity as well as the adjustment of existing therapies are important. An assessment by a mental health professional is also mandatory; however, psychological comorbidities are not a contraindication as long as the patient is being treated and the disease is controlled. A preoperative short-term high-protein and low-carbohydrate fluid nutrition helps to reduce the risk of postoperative complications, especially for patients with a high BMI. A preoperative weight loss in the sense of a mandatory loss of a defined proportion of the body weight is not useful.

[Normal tissue: radiosensitivity, toxicity, consequences for planning]. / Normalgewebe: Strahlenempfindlichkeit, Toxizität, Konsequenzen für die Planung.

Along with chemotherapy, surgery and immunotherapy, radiotherapy is a mainstay of cancer treatment. Considering the improving survival rates for various malignancies during the past decades, the importance of radiation-induced late normal tissue response is increasing. Quality of life is becoming an important issue in modern cancer treatment and is correlated with acute and late normal tissue response after radiotherapy. A profound understanding of radiation-induced normal tissue response is necessary to sufficiently diagnose and treat radiation-induced side effects and thereby increase the patients' quality of life. Here, the various normal tissue responses in consideration of the radiation biology are specified and prospective options to attenuate radiation-induced side effects are discussed.

One- vs 4-week stent placement after laparoscopic and robot-assisted pyeloplasty: results of a prospective randomised single-centre study.

OBJECTIVES: To determine whether 1-week stenting of the pelvi-ureteric anastomosis of laparoscopic or robot-assisted pyeloplasty is as effective as 4-week stenting, based on their respective success rates. PATIENTS AND METHODS: A total of 100 patients with pelvi-ureteric junction obstruction were treated by Anderson-Hynes pyeloplasty and the anastomosis was stented using a 6-F JJ catheter for either 1 week (1W series) or 4 weeks (4W series), based on a randomisation protocol. Postoperative follow-up was performed at 3 months using intravenous urography (IVU), at 6 months using diuretic renography and at 1, 3 and 5 years using ultrasonography. Statistical analysis was performed using a one-sided Z-test, Pearsons's chi-squared test and a Wilcoxon rank sum test. RESULTS: The primary outcome measure, success rate, which was defined as no obstruction on IVU and diuretic renography, was 100% in the 1W series and not inferior to the success rate of 98% in the 4W series (P = 0.006). The following secondary outcome measures were not significantly different between the 1W and the 4W series with regard to residual symptoms (10 vs 6%; P = 0.48), rate of complications (4 vs 6%; P = 0.65), need for synchronous robot-assisted pyelolithotomy (4 vs 8%; P = 0.47), improvement in split renal function (1 vs 0%; P = 0.59) and duration of surgery (200 vs 192 min; P = 0.87). Only length of hospital stay was significantly different; this was shorter in the 1W series (5 vs 6 days; P = 0.01). CONCLUSIONS: Stenting of the pelvi-ureteric anastomosis after laparoscopic or robot-assisted pyeloplasty for 1 week is as effective as stenting for 4 weeks. Both procedures, laparoscopic or robot-assisted pyeloplasty have an excellent success rate.