Simon Kirste

Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors: a prospective, randomized, placebo-controlled, double-blind pilot trial.

Patients irradiated for brain tumors often suffer from cerebral edema and are usually treated with dexamethasone, which has various side effects. To investigate the activity of Boswellia serrata (BS) in radiotherapy‐related edema, we conducted a prospective, randomized, placebo‐controlled, double‐blind, pilot trial.

Determination of major boswellic acids in plasma by high-pressure liquid chromatography/mass spectrometry

Until now, dexamethasone is the medication of choice to reduce peritumoral edema associated with primary and secondary brain tumors. Because of the severe side effects accompanying such a treatment the interest in alternative agents that may be co-administered with glucocorticoids and help to reduce the required dose is constantly increasing. Boswellia serrata gum resin extracts (BSE), which have been designated an orphan drug status by the European Medicines Agency (EMA) in 2002 for the treatment of peritumoral edema, may represent a promising supplemental herbal remedy. However, clinical studies on the effect of BSE on brain edema as well as analyzes of serum levels are very scarce. Based on that background a prospective, placebo controlled, and double blind clinical pilot trial was conducted on 14 patients applying for the first time a high dose of 4200 mg BSE per day and 13 patients receiving placebo. For monitoring the serum levels of all major boswellic acids (BAs) a highly sensitive HPLC-MS method has been developed that allows the determination of KBA and AKBA from 5.0 ng/ml to 3000 ng/ml and of αBA, βBA, AαBA and AβBA from 0.5 ng/ml to 12,000 ng/ml. It is the first validated method that covers such a wide concentration range, which makes it suitable to be used as standard method in clinical trials as it compensates for the great pharmacokinetic variability in the plasma levels of BAs observed in clinical practice. Average steady concentrations (ng/ml) in the range of 6.4-247.5 for KBA, 0-15.5 for AKBA, 36.7-4830.1 for αBA, 87.0-11948.5 for βBA, 73.4-2985.8 for AαBA and 131.4-6131.3 for AβBA were determined in the verum group. The here quantified steady state levels suggest βBA to be a possible candidate for the anti-inflammatory and anti-edemateous effects of BSE. In general, the serum level analysis underlines the promising clinical results of BSE on cerebral edema.

3 Tesla multiparametric MRI for GTV-definition of Dominant Intraprostatic Lesions in patients with Prostate Cancer – an interobserver variability study

PurposeTo evaluate the interobserver variability of gross tumor volume (GTV) - delineation of Dominant Intraprostatic Lesions (DIPL) in patients with prostate cancer using published MRI criteria for multiparametric MRI at 3 Tesla by 6 different observers.Material and methods90 GTV-datasets based on 15 multiparametric MRI sequences (T2w, diffusion weighted (DWI) and dynamic contrast enhanced (DCE)) of 5 patients with prostate cancer were generated for GTV-delineation of DIPL by 6 observers. The reference GTV-dataset was contoured by a radiologist with expertise in diagnostic imaging of prostate cancer using MRI. Subsequent GTV-delineation was performed by 5 radiation oncologists who received teaching of MRI-features of primary prostate cancer before starting contouring session. GTV-datasets were contoured using Oncentra Masterplan® and iplan® Net. For purposes of comparison GTV-datasets were imported to the Artiview® platform (Aquilab®), GTV-values and the similarity indices or Kappa indices (KI) were calculated with the postulation that a KI > 0.7 indicates excellent, a KI > 0.6 to < 0.7 substantial and KI > 0.5 to < 0.6 moderate agreement. Additionally all observers rated difficulties of contouring for each MRI-sequence using a 3 point rating scale (1 = easy to delineate, 2 = minor difficulties, 3 = major difficulties).ResultsGTV contouring using T2w (KI-T2w = 0.61) and DCE images (KI-DCE = 0.63) resulted in substantial agreement. GTV contouring using DWI images resulted in moderate agreement (KI-DWI = 0.51). KI-T2w and KI-DCE was significantly higher than KI-DWI (p = 0.01 and p = 0.003). Degree of difficulty in contouring GTV was significantly lower using T2w and DCE compared to DWI-sequences (both p < 0.0001). Analysis of delineation differences revealed inadequate comparison of functional (DWI, DCE) to anatomical sequences (T2w) and lack of awareness of non-specific imaging findings as a source of erroneous delineation.ConclusionsUsing T2w and DCE sequences at 3 Tesla for GTV-definition of DIPL in prostate cancer patients by radiation oncologists with knowledge of MRI features results in substantial agreement compared to an experienced MRI-radiologist, but for radiotherapy purposes higher KI are desirable, strengthen the need for expert surveillance. DWI sequence for GTV delineation was considered as difficult in application.

Xerostomia after radiotherapy in the head & neck area: long-term observations.

To investigate the development of xerostomia more than 5 years after radiotherapy for head and neck cancer, a prospective longitudinal study was done. A xerostomia questionnaire was answered by 42 patients 41 and 90 months after radiotherapy: xerostomia at rest did not change significantly over time whereas the difficulties with speaking improved and the difficulties with eating worsened. Subjective xerostomia does not reach a steady state even more than 5 years after radiotherapy.

Evaluation of intensity modulated radiation therapy dose painting for localized prostate cancer using 68Ga-HBED-CC PSMA-PET/CT: A planning study based on histopathology reference

PURPOSE To demonstrate the feasibility and to evaluate the tumour control probability (TCP) and normal tissue complication probability (NTCP) of IMRT dose painting using 68Ga-HBED-CC PSMA PET/CT for target delineation in prostate cancer (PCa). METHODS AND MATERIALS 10 patients had PSMA PET/CT scans prior to prostatectomy. GTV-PET was generated on the basis of an intraprostatic SUVmax of 30%. Two IMRT plans were generated for each patient: Plan77 which consisted of whole-prostate IMRT to 77Gy, and Plan95 which consisted of whole-prostate IMRT to 77Gy and a simultaneous integrated boost to the GTV-PET up to 95Gy (35 fractions). The feasibility of these plans was judged by their ability to adhere to the FLAME trial protocol. TCP-histo/-PET were calculated on co-registered histology (GTV-histo) and GTV-PET, respectively. NTCPs for rectum and bladder were calculated. RESULTS All plans reached prescription doses whilst adhering to dose constraints. In Plan77 and Plan95 mean doses in GTV-histo were 75.8±0.3Gy and 96.9±1Gy, respectively. Average TCP-histo values for Plan77 and Plan95 were 70% (range: 15-97%), and 96% (range: 78-100%, p<0.0001). Average TCP-PET values for Plan77 and Plan95 were 55% (range: 27-82%), and 100% (range: 99-100%, p<0.0001). There was no significant difference between TCP-PET and TCP-histo in Plan95 (p=0.25). There were no significant differences in rectal (p=0.563) and bladder (p=0.3) NTCPs. CONCLUSIONS IMRT dose painting using PSMA PET/CT was technically feasible and resulted in significantly higher TCPs without higher NTCPs.

Erfassung möglicher Verbesserungen im Ablauf der Strahlentherapie — eine Patientenbefragung

ZusammenfassungEinleitung und HintergrundIm Rahmen der Qualitätssicherung werden an den Ablauf einer Strahlentherapie zunehmend größere Anforderungen gestellt. Die direkt betroffenen Patienten bemerken in der täglichen Therapie jedoch viele Maßnahmen der Qualitätskontrolle, z. B. zusätzliche Sicherheitschecks, nicht. Durch eine gezielte Befragung der Patienten sollten Verbesserungsmöglichkeiten des Behandlungsablaufs aus deren Perspektive identifiziert werden.Patienten und MethodenMittels eines neu entwickelten Fragebogens wurden in einem definierten Erhebungszeitraum von 1 Monat insgesamt 624 Strahlentherapiepatienten (Rücklauf: n = 600, 96,2 %) über verschiedene Aspekte des Therapieablaufs befragt. Weiterhin wurden bei der befragten Stichprobe Auskünfte über ihre spezifischen Bedürfnisse sowie Vorschläge zu konkreten Verbesserungsmöglichkeiten im Kontext einer strahlentherapeutischen Behandlung erhoben.ErgebnisseInsgesamt waren die Patienten mit den Therapieabläufen zufrieden. So gab es z. B. zu der Aussage „Mein erster Kontakt zur Klinik für Strahlenheilkunde verlief so, dass mir sowohl mit Freundlichkeit als auch mit Kompetenz das Gefühl gegeben wurde: Hier werde ich gut betreut“ über 90 % Zustimmung. Bezüglich des Organisationsablaufs legte eine große Mehrheit der Patienten Wert auf einen festgelegten Bestrahlungstermin. Kritikpunkte waren Wartezeiten wegen Wartung oder Ausfall der Bestrahlungsgeräte. Kleinere bzw. kostengünstigere Verbesserungen wie Musik im Bestrahlungsraum sahen die Patienten insgesamt als genauso wichtig an wie teure bauliche Maßnahmen, beispielsweise Tageslicht im Bestrahlungsraum. Positiv hervorgehoben wurde die freundliche Betreuung der Patienten durch das Personal.SchlussfolgerungenDie Situation der Strahlentherapiepatienten war insgesamt zufriedenstellend. Weitere Verbesserungen für die Zukunft sind vor allem aus einer reibungslosen Organisation der Planung und Therapie zu erwarten, wie sie durch elektronische Betriebsablaufsysteme zu erreichen ist. Die Ergebnisse der Befragung konnten in der eigenen Klinik bereits in vielen Bereichen umgesetzt werden. Die Strahlentherapie mit ihren komplexen Abläufen kann hier als Vorbild für andere Bereiche genutzt werden.AbstractIntroduction and BackgroundIn the context of quality assurance, increasing demands are placed on the whole radiotherapy treatment process. The patients directly concerned generally do not realize most aspects of the quality assurance program (e.g., additional safety checks) during their daily therapy. It was the aim of this study to systematically ask patients about potential improvements during the course of radiotherapy treatment from their own perspective.Patients and MethodsIn the defined time span (1 month), 624 radiotherapy patients (600 questionnaires were returned, 96.2%) were interviewed using a questionnaire newly developed to inquire about several aspects of their treatment. Furthermore, they were asked for their specific needs and suggestions for improvements that could be made during the course of radiotherapy treatment.ResultsOverall, the patients were satisfied with the course of their radiotherapy treatment and with patient care. As an example, about 90% agreed with the statement: “My first contact with the radiation oncology unit proceeded with kindness and competence so that I was given the impression that I will be well cared for in this clinic.” Considering the organization of the course of radiotherapy, a large majority of patients attached great value to set appointments for the therapy fractions. A main point of criticism was waiting times or delays caused by servicing or machine failures. Small, low cost improvements as music in the therapy room were considered as important as expensive measures (e.g., daylight in the therapy room). The patients emphasized the importance of staff friendliness.ConclusionThe situation of radiotherapy patients was, in general, satisfactory. Future improvements can be mainly expected from smooth organisation of both planning and treatment which can be achieved by electronic scheduling systems. Many results of the survey could be easily implemented in daily practice. In matters of organization radiation oncology with its complex procedures can be used as a model for other clinical departments.

[Survey of potential improvements during the course of the radiotherapy treatment--a patient questionnaire].

ZusammenfassungEinleitung und HintergrundIm Rahmen der Qualitätssicherung werden an den Ablauf einer Strahlentherapie zunehmend größere Anforderungen gestellt. Die direkt betroffenen Patienten bemerken in der täglichen Therapie jedoch viele Maßnahmen der Qualitätskontrolle, z. B. zusätzliche Sicherheitschecks, nicht. Durch eine gezielte Befragung der Patienten sollten Verbesserungsmöglichkeiten des Behandlungsablaufs aus deren Perspektive identifiziert werden.Patienten und MethodenMittels eines neu entwickelten Fragebogens wurden in einem definierten Erhebungszeitraum von 1 Monat insgesamt 624 Strahlentherapiepatienten (Rücklauf: n = 600, 96,2 %) über verschiedene Aspekte des Therapieablaufs befragt. Weiterhin wurden bei der befragten Stichprobe Auskünfte über ihre spezifischen Bedürfnisse sowie Vorschläge zu konkreten Verbesserungsmöglichkeiten im Kontext einer strahlentherapeutischen Behandlung erhoben.ErgebnisseInsgesamt waren die Patienten mit den Therapieabläufen zufrieden. So gab es z. B. zu der Aussage „Mein erster Kontakt zur Klinik für Strahlenheilkunde verlief so, dass mir sowohl mit Freundlichkeit als auch mit Kompetenz das Gefühl gegeben wurde: Hier werde ich gut betreut“ über 90 % Zustimmung. Bezüglich des Organisationsablaufs legte eine große Mehrheit der Patienten Wert auf einen festgelegten Bestrahlungstermin. Kritikpunkte waren Wartezeiten wegen Wartung oder Ausfall der Bestrahlungsgeräte. Kleinere bzw. kostengünstigere Verbesserungen wie Musik im Bestrahlungsraum sahen die Patienten insgesamt als genauso wichtig an wie teure bauliche Maßnahmen, beispielsweise Tageslicht im Bestrahlungsraum. Positiv hervorgehoben wurde die freundliche Betreuung der Patienten durch das Personal.SchlussfolgerungenDie Situation der Strahlentherapiepatienten war insgesamt zufriedenstellend. Weitere Verbesserungen für die Zukunft sind vor allem aus einer reibungslosen Organisation der Planung und Therapie zu erwarten, wie sie durch elektronische Betriebsablaufsysteme zu erreichen ist. Die Ergebnisse der Befragung konnten in der eigenen Klinik bereits in vielen Bereichen umgesetzt werden. Die Strahlentherapie mit ihren komplexen Abläufen kann hier als Vorbild für andere Bereiche genutzt werden.AbstractIntroduction and BackgroundIn the context of quality assurance, increasing demands are placed on the whole radiotherapy treatment process. The patients directly concerned generally do not realize most aspects of the quality assurance program (e.g., additional safety checks) during their daily therapy. It was the aim of this study to systematically ask patients about potential improvements during the course of radiotherapy treatment from their own perspective.Patients and MethodsIn the defined time span (1 month), 624 radiotherapy patients (600 questionnaires were returned, 96.2%) were interviewed using a questionnaire newly developed to inquire about several aspects of their treatment. Furthermore, they were asked for their specific needs and suggestions for improvements that could be made during the course of radiotherapy treatment.ResultsOverall, the patients were satisfied with the course of their radiotherapy treatment and with patient care. As an example, about 90% agreed with the statement: “My first contact with the radiation oncology unit proceeded with kindness and competence so that I was given the impression that I will be well cared for in this clinic.” Considering the organization of the course of radiotherapy, a large majority of patients attached great value to set appointments for the therapy fractions. A main point of criticism was waiting times or delays caused by servicing or machine failures. Small, low cost improvements as music in the therapy room were considered as important as expensive measures (e.g., daylight in the therapy room). The patients emphasized the importance of staff friendliness.ConclusionThe situation of radiotherapy patients was, in general, satisfactory. Future improvements can be mainly expected from smooth organisation of both planning and treatment which can be achieved by electronic scheduling systems. Many results of the survey could be easily implemented in daily practice. In matters of organization radiation oncology with its complex procedures can be used as a model for other clinical departments.

Outcome after PSMA PET/CT based salvage radiotherapy in patients with biochemical recurrence after radical prostatectomy: a bi-institutional retrospective analysis

Prostate-specific membrane antigen (PSMA) PET/CT detects prostate cancer recurrence at low levels of prostate-specific antigen (PSA). Radiotherapy with dose escalation to the former prostate bed has been associated with improved biochemical recurrence-free survival (BRFS). Thus, we hypothesized that PSMA PET/CT-guided salvage radiotherapy leads to improved BRFS. Methods: In total, 204 consecutive patients were referred for salvage radiotherapy after radical prostatectomy. PSMA PET/CT scans were performed, and patients with PSA persistence (109 patients) or evidence of distant metastases (5 patients) were excluded from this analysis. Thus, the following analysis is based on a total of 90 patients who underwent PSMA PET/CT before radiotherapy due to biochemical recurrence and received salvage radiotherapy. In cases of PET-positive findings, antiandrogen therapy was commenced before initiation of radiotherapy. BRFS (PSA ≤ 0.2 ng/mL) was defined as the study endpoint. Results: PET-positive lesions were detected in 42 of 90 (47%) patients, 24 of 42 (27%) being fossa recurrence only, 12 of 42 (13%) pelvic lymph node only, and 6 of 42 (7%) both fossa and pelvic lymph node. The median PSA before radiotherapy was 0.44 ng/mL (range, 0.11–6.24 ng/mL). Cumulatively, a total dose of 70.0 Gy (range, 67.2–72 Gy) was delivered to local macroscopic tumor, 66 Gy (range, 59.4–70.2 Gy) to the prostatic fossa, 60.8 Gy (range, 54–66 Gy) to PET-positive lymph nodes, and 50.4 Gy (range, 45–50.4 Gy) to the lymphatic pathways. After a median follow-up of 23 mo, BRFS was 78%. Antiandrogen therapy was ongoing in 4 patients at the last follow-up. No significant difference in BRFS between PET-positive patients (74%) and PET-negative patients (82%; P > 0.05) was observed at the last follow-up. Two patients had late genitourinary toxicity, grade 3, and no patient had gastrointestinal toxicity of grade 3 or higher (National Cancer Institute common terminology criteria for adverse events, version 4.03). Conclusion: PSMA PET/CT-guided salvage radiotherapy is an effective and safe local treatment option. No difference in BRFS between PET-positive and PET-negative patients was observed, indicating effective targeting of PET-positive lesions. PSMA PET/CT when readily available should be offered to patients with PSA recurrence for treatment individualization.

Abdominal Stereotactic Body Radiotherapy: Local Control and Correlationto Biologically Equivalent Dose

Aim: We conducted a retrospective study to report on the outcome and toxicity of stereotactic body radiotherapy (SBRT) and to analyze the correlation of local control (LC) and biological equivalent dose (BED) of patients treated with SBRT for upper abdominal lesions. Methods: Patients who completed stereotactic radiotherapy treatment between 05/2007 and 03/2012 were enrolled into the analysis. Different fractionation regimens depending on the dose to organs at risk (OAR) were given. The primary endpoint was LC determined on imaging studies. Toxicities were classified according to CTCAE v4. Physical dose was converted into BED (α / β = 10 Gy) and a tumor control probability model (TCP) was used for dose-response relationship. For outcome analyses the Kaplan-Meier method and log rank tests were used. Results: Forty-two patients were treated with SBRT. Thirty-three patients with 39 lesions were evaluable for further analysis with a median follow-up of 15.2 months. Lesions were located in liver (n = 28), hepatic hilum (n = 8), nodal (n = 2), adrenal (n = 2) and pancreatic head (n = 1). Local failure was observed in 7 lesions at a mean time of 7.3 months (range, 1.5 - 17.9) resulting in a LC rate of 83% at one year and 63% at two years. No significant difference for intra- vs extrahepatic lesions was observed. Lesions treated with a BED ≥ 59.5 Gy had a better LC vs. lesions treated with a BED < 59.5 Gy (88% vs. 68%, p = 0.027). Median overall survival was 14.5 months (2 - 32.5). Observed toxicities were mild (grade 2 in 4 patients, grade 3 in 1 patient). Conclusion: Upper abdominal SBRT is well tolerated and results in excellent local control if BED is ≥ 59.5 Gy. We therefore propose to aim for doses at or above this BED.

Biological imaging for individualized therapy in radiation oncology: part I physical and technical aspects

Recently, there has been an increase in the imaging modalities available for radiotherapy planning and radiotherapy prognostic outcome: dual energy computed tomography (CT), dynamic contrast enhanced CT, dynamic contrast enhanced magnetic resonance imaging (MRI), diffusion-weighted MRI, positron emission tomography-CT, dynamic contrast enhanced ultrasound, MR spectroscopy and positron emission tomography-MR. These techniques enable more precise gross tumor volume definition than CT alone and moreover allow subvolumes within the gross tumor volume to be defined which may be given a boost dose or an individual voxelized dose prescription may be derived. With increased plan complexity care must be taken to immobilize the patient in an accurate and reproducible manner. Moreover the physical and technical limitations of the entire treatment planning chain need to be well characterized and understood, interdisciplinary collaboration ameliorated (physicians and physicists within nuclear medicine, radiology and radiotherapy) and image protocols standardized.