Michael Ehmann

Quality assurance for clinical studies in regional deep hyperthermia

BackgroundA guideline is provided for the implementation of regional deep hyperthermia treatments under strict rules of quality assurance. The objective is to guarantee a comparable and comprehensible method in the treatment and scientific analysis of hyperthermia. The guideline describes regional deep hyperthermia (RHT) and MR-controlled partial body hyperthermia (PBH) of children, young and adult patients. According to this guideline, hyperthermia treatment is always applied in combination with chemotherapy and/or radiotherapy.MethodsThe guideline is based on practical experience from several hyperthermia centers. The procedure allows applying jointly coordinated standards and quality control in hyperthermia for studies.ResultsThe guideline contains recommendations for hyperthermia treatments, including indication, preparation, treatment, and standardized analysis.HintergrundZur Durchführung von qualitätsgesicherten Tiefenhyperthermiebehandlungen wurde eine Leitlinie erstellt. Ziel war, ein vergleichbares und nachvollziehbares Vorgehen bei der Behandlung und der wissenschaftlichen Auswertung von Hyperthermiebehandlungen zu gewährleisten. Die Leitlinie beschreibt die „Regionale Tiefenhyperthermie“ (RHT) und die „MR-kontrollierte Teilkörperhyperthermie“ (PBH) von Kindern, jugendlichen und erwachsenen Patienten. Hyperthermie im Sinne der Leitlinie wird als Kombinationsbehandlung mit einer Chemo- und/oder Strahlentherapie durchgeführt.MethodikDie Leitlinie basiert auf praktischen Erfahrungen mehrerer Hyperthermiezentren. Dieses Vorgehens erlaubt abgestimmte Standards in der Anwendung und der Qualitätskontrolle in der Hyperthermie für Studien.ErgebnisseDiese Leitlinie enthält Empfehlungen für Hyperthermiebehandlungen mit Indikationsstellung, Vorbereitung, Durchführung und standardisierter Auswertung.

Intrafraction motion of the prostate during an IMRT session: a fiducial-based 3D measurement with Cone-beam CT.

BackgroundImage-guidance systems allow accurate interfractional repositioning of IMRT treatments, however, these may require up to 15 minutes. Therefore intrafraction motion might have an impact on treatment precision. 3D geometric data regarding intrafraction prostate motion are rare; we therefore assessed its magnitude with pre- and post-treatment fiducial-based imaging with cone-beam-CT (CBCT).Methods39 IMRT fractions in 5 prostate cancer patients after 125I-seed implantation were evaluated. Patient position was corrected based on the 125I-seeds after pre-treatment CBCT. Immediately after treatment delivery, a second CBCT was performed. Differences in bone- and fiducial position were measured by seed-based grey-value matching.ResultsFraction time was 13.6 ± 1.6 minutes. Median overall displacement vector length of 125I-seeds was 3 mm (M = 3 mm, Σ = 0.9 mm, σ = 1.7 mm; M: group systematic error, Σ: SD of systematic error, σ: SD of random error). Median displacement vector of bony structures was 1.84 mm (M = 2.9 mm, Σ = 1 mm, σ = 3.2 mm). Median displacement vector length of the prostate relative to bony structures was 1.9 mm (M = 3 mm, Σ = 1.3 mm, σ = 2.6 mm).Conclusiona) Overall displacement vector length during an IMRT session is < 3 mm.b) Positioning devices reducing intrafraction bony displacements can further reduce overall intrafraction motion.c) Intrafraction prostate motion relative to bony structures is < 2 mm and may be further reduced by institutional protocols and reduction of IMRT duration.

Flattening-filter-free intensity modulated breath-hold image-guided SABR (Stereotactic ABlative Radiotherapy) can be applied in a 15-min treatment slot

Hypofractionated image-guided stereotactic ablative radiotherapy (igSABR) is effective in small lung/liver lesions. Computer-assisted breath-hold reduces intrafraction motion but, as every gating/triggering strategy, reduces the duty cycle, resulting in long fraction times if combined with intensity-modulated radiotherapy (IMRT). 10 MV flattening-filter-free IMRT reduces daily fraction duration to <10 min for single doses of 5-20 Gy.

Guideline for the clinical application, documentation and analysis of clinical studies for regional deep hyperthermia

ObjectivesThese guidelines contain recommendations for the implementation of quality-assured hyperthermia treatments. The objective is to guarantee an internationally comparable and easily understandable method for hyperthermia treatment and for the subsequent scientific analysis of the treatment results. The guidelines describe “regional deep hyperthermia” (RHT) and MR-controlled “partial body hyperthermia” (PBH) of children, adolescents and adult patients. Hyperthermia in terms of these guidelines is defined as a treatment combining chemotherapy and/or radiation therapy.MethodsThese guidelines are based on practical experience from several hyperthermia centres in Europe. Our collaborative effort has ensured coordinated standards and quality control procedures in regional deep and partial body hyperthermia. The guidelines were developed by the Atzelsberg Research Group of the IAH (http://www.hyperthermie.org) of the German Cancer Society (“Deutsche Krebsgesellschaft”) to specifically ensure that the multi-institutional studies initiated by the Atzelsberg Research Group are executed following a single, uniform level of quality.ResultsThe guidelines contain recommendations for procedural methods for treatment using hyperthermia. They commence with diagnosis, which is followed by preparation and treatment and concludes with standardised analysis for the reporting of results.ZusammenfassungHintergrundDiese Leitlinie enthält Empfehlungen zur Durchführung von qualitätsgesicherten Hyperthermiebehandlungen. Ziel ist, ein vergleichbares und nachvollziehbares Vorgehen bei der Behandlung und der wissenschaftlichen Auswertung der Hyperthermie zu gewährleisten. Die Leitlinie beschreibt die „Regionale Tiefenhyperthermie“ (RHT) und die „MR-kontrollierte Teilkörperhyperthermie“ (PBH) von Kindern, Jugendlichen und erwachsenen Patienten. Die Hyperthermie im Sinne dieser Leitlinie wird als Kombinationsbehandlung mit einer Chemo- und/oder Strahlentherapie durchgeführt.MethodikDie vorgestellte Leitlinie basiert auf praktischen Erfahrungen von mehreren Hyperthermiezentren. Dieses Vorgehens erlaubt gemeinsam abgestimmte Standards in der Anwendung und der Qualitätskontrolle in der Hyperthermie für Studien, die im Rahmen des Atzelsberger Arbeitskreises in der Interdisziplinären Arbeitsgruppe Hyperthermie (http://www.hyperthermie.org) in der Deutschen Krebsgesellschaft und dem Technischen Komitee der „European Society for Hyperthermic Oncology“ (ESHO) entwickelt wurden, um sicher zu stellen, dass multizentrische Studien, die vom Atzelsberger Arbeitskreis entwickelt wurden, nach einem standardisierten, einheitlichen Qualitätsmaßstab durchgeführt werden.ErgebnisseDiese Leitlinie enthält Empfehlungen für das Vorgehen bei Hyperthermiebehandlungen von der Indikationsstellung, der Vorbereitung, der Durchführung bis zur standardisierten Auswertung.Die deutschsprachige Version des Beitrags ist auf SpringerLink unter „Supplemental“ zu finden.

Arc therapy for total body irradiation--a robust novel treatment technique for standard treatment rooms.

BACKGROUND AND PURPOSE We developed a simple and robust total body irradiation (TBI) method for standard treatment rooms that obviates the need for patient translation devices. METHODS AND MATERIALS Two generic arcs with rectangular segments for a patient thickness of 16 and 20 cm (arc16/arc20) were generated. An analytical fit was performed to determine the weights of the arc segments depending on patient thickness and gantry angle. Stability and absolute dose for both arcs were measured using EBT3 films in a range of solid water slab phantom thicknesses. Additionally ionization chamber measurements were performed every 10 cm at a source surface distance (SSD) of ∼ 200 cm. RESULTS The measured standard deviation for arc16 is ± 3% with a flatness ⩽ 9.0%. Arc20 had a standard deviation of ± 3% with a flatness ⩽ 7.3% for all measured thicknesses. The theoretical curves proved to be accurate for the prediction of the segment weightings for the two arcs. In vivo measurements for the first 22 clinical patients showed a dose deviation of less than 3%. CONCLUSIONS Arc therapy is a convenient and stable method for TBI. This cost-effective approach has been introduced clinically, obviating the need for field patches and to physically move the patient.

Quality assurance guidelines for superficial hyperthermia clinical trials: I. Clinical requirements

Abstract Quality assurance guidelines are essential to provide uniform execution of clinical trials and treatment in the application of hyperthermia. This document provides definitions for a good hyperthermia treatment and identifies the clinical conditions where a certain hyperthermia system can or cannot adequately heat the tumour volume. It also provides brief description of the characteristics and performance of the current electromagnetic (radiative and capacitive), ultrasound and infra-red heating techniques. This information helps to select the appropriate heating technique for the specific tumour location and size, and appropriate settings of the water bolus and thermometry. Finally, requirements of staff training and documentation are provided. The guidelines in this document focus on the clinical application and are complemented with a second, more technical quality assurance document providing instructions and procedure to determine essential parameters that describe heating properties of the applicator for superficial hyperthermia. Both sets of guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.

Phase I/II trial of combined kyphoplasty and intraoperative radiotherapy in spinal metastases

BACKGROUND CONTEXT Spinal metastases occur in 30%-50% of patients with systemic cancer. The primary goals of palliation are pain control and prevention of local recurrence. PURPOSE This study aimed to test the safety and efficacy of a combined modality approach consisting of kyphoplasty and intraoperative radiotherapy (Kypho-IORT). STUDY DESIGN/SETTING Kyphoplasty and intraoperative radiotherapy was a prospective, single-center phase I/II trial. Patients were enrolled in a classical 3+3 scheme within the initial phase I, where Kypho-IORT was applied using a needle-shaped 50 kV X-ray source at three radiation dose levels (8 Gy in 8-mm, 8 Gy in 11-mm, and 8 Gy in 13-mm depth). Thereafter, cohort expansion was performed as phase II of the trial. The trial is registered with clinicaltrials.gov, number NCT01280032. PATIENT SAMPLE Patients aged 50 years and older with a Karnofsky Performance Status of at least 60% and with one to three painful vertebral metastases confined to the vertebral body were eligible to participate. OUTCOME MEASURES The primary end point was safety as per the occurrence of dose-limiting toxicities. The secondary end points were pain reduction, local progression-free survival (L-PFS), and overall survival (OS). METHODS Pain was measured using the visual analog scale (VAS) and local control was assessed in serial computed tomography or magnetic resonance imaging scans. RESULTS None of the nine patients enrolled in the phase I showed dose-limiting toxicities at any level and thus, 52 patients were subsequently enrolled into a phase II, where Kypho-IORT was performed at various dose levels. The median pain score significantly dropped from 5 preoperatively to 2 at the first postoperative day (p<.001). Of 43 patients who reported a pre-interventional pain level of 3 or more, 30 (69.8%) reported a reduction of ≥3 points on the first postoperative day. A persistent pain reduction beyond the first postoperative day of ≥3 points was seen in 34 (79.1%) patients. The 3, 6, and 12 month L-PFS was excellent with 97.5%, 93.8%, and 93.8%. The 3, 6, and 12 months OS was 76.9%, 64.0%, and 48.4%. CONCLUSION Kyphoplasty and intraoperative radiotherapy is safe and immediately provided sustained pain relief with excellent local control rates in patients with painful vertebral metastases.

Stereotactic ultrasound for target volume definition in a patient with prostate cancer and bilateral total hip replacement

PURPOSE Target-volume definition for prostate cancer in patients with bilateral metal total hip replacements (THRs) is a challenge because of metal artifacts in the planning computed tomography (CT) scans. Magnetic resonance imaging (MRI) can be used for matching and prostate delineation; however, at a spatial and temporal distance from the planning CT, identical rectal and vesical filling is difficult to achieve. In addition, MRI may also be impaired by metal artifacts, even resulting in spatial image distortion. Here, we present a method to define prostate target volumes based on ultrasound images acquired during CT simulation and online-matched to the CT data set directly at the planning CT. METHODS AND MATERIALS A 78-year-old patient with cT2cNxM0 prostate cancer with bilateral metal THRs was referred to external beam radiation therapy. T2-weighted MRI was performed on the day of the planning CT with preparation according to a protocol for reproducible bladder and rectal filling. The planning CT was obtained with the immediate acquisition of a 3-dimensional ultrasound data set with a dedicated stereotactic ultrasound system for online intermodality image matching referenced to the isocenter by ceiling-mounted infrared cameras. MRI (offline) and ultrasound images (online) were thus both matched to the CT images for planning. Daily image guided radiation therapy (IGRT) was performed with transabdominal ultrasound and compared with cone beam CT. RESULTS Because of variations in bladder and rectal filling and metal-induced image distortion in MRI, soft-tissue-based matching of the MRI to CT was not sufficient for unequivocal prostate target definition. Ultrasound-based images could be matched, and prostate, seminal vesicles, and target volumes were reliably defined. Daily IGRT could be successfully completed with transabdominal ultrasound with good accordance between cone beam CT and ultrasound. CONCLUSIONS For prostate cancer patients with bilateral THRs causing artifacts in planning CTs, ultrasound referenced to the isocenter of the CT simulator and acquired with intermodal online coregistration directly at the planning CT is a fast and easy method to reliably delineate the prostate and target volumes and for daily IGRT.

Other Applications of INTRABEAM

Intraoperative radiotherapy (IORT) permits the delivery of a high radiation dose directly to the residual tumour or tumour bed while sparing nearby normal tissues. In most cases, IORT with the INTRABEAM® system is employed as a part of multimodal treatment, with the aim of providing an additional benefit in terms of prevention of local recurrence. IORT is used to treat many tumours, the most common being:

Akuttoxizität nach hypofraktionierter versus konventionell fraktionierter Strahlentherapie bei Patienten mit Prostatakarzinom@@@Acute toxicity after hypofractionated versus conventionally fractionated radiotherapy for patients with prostate cancer

fraktionierung wurde separat für urogenitale und gastrointestinale Akuttoxizität getestet mit der Nullhypothese, dass kumulative Inzidenzen jedes Toxizitätstyps nicht mehr als 8 % höher in der Hypofraktionierungsgruppe als bei Standardfraktionierung sind. Akute urogenitale und gastrointestinale Toxizitäten wurden anhand der RTOGEORTC-Kriterien sowohl mit „Case Report Forms“ als auch mit Fragebögen erhoben. Dies geschah prätherapeutisch, 2-mal während und 3 Monate nach Abschluss der Strahlentherapie. Die Analysen wurden in der Intentionto-Treat-Population durchgeführt. Die Patientenrekrutierung ist abgeschlossen und die Studie registriert (www. controlled-trials.com, Nummer ISRCTN85138529).