Hilke Vorwerk

Radiotherapy of malignant gliomas: Comparison of volumetric single arc technique (RapidArc), dynamic intensity-modulated technique and 3D conformal technique

PURPOSE The analysis was designed to identify the optimal radiation technique for patients with malignant glioma. METHODS A volumetric-modulated radiation treatment technique (RapidArc), an IMRT technique and a 3D conformal technique were calculated on computed tomograms of 14 consecutive patients with malignant glioma. The treatment plans were compared with each other using dose-volume histograms. RESULTS The 3D conformal technique showed a good PTV coverage, if PTV was distant to organs at risk (OAR). If PTV was nearby OAR, the 3D technique revealed a poor PTV coverage in contrast to both intensity-modulated techniques. The conventional IMRT technique showed a slightly better PTV coverage than RapidArc. The advantages of RapidArc were a shorter treatment time, less monitor units and a small V(107%). CONCLUSIONS If PTV is distant to OAR, the use of 3D conformal technique is sufficient. Otherwise an intensity-modulated technique should be used. RapidArc was faster than conventional IMRT and should be preferred if PTV coverage is adequate.

Conformal radiotherapy planning of cervix carcinoma: differences in the delineation of the clinical target volume. A comparison between gynaecologic and radiation oncologists.

PURPOSE To assess uncertainties in the definition of the clinical target volume (CTV) for patients scheduled for primary radiotherapy of cervix carcinoma. METHODS AND MATERIALS Seven physicians (five radiation oncologists and two gynaecologists) independently contoured the CTVs for three patients. All observers were provided with the same clinical information. CTVs were entered directly in the treatment planning system. Differences were analysed qualitatively and quantitatively. RESULTS The qualitative analysis revealed a good agreement by all observers on anatomical structures identified to be at risk for tumour spread. Quantitatively, however, a large interobserver variability was found. The ratio between largest and smallest volumes ranged between 3.6 and 4.9 for all observers (3.6-4.9 for the radiation oncologists, 1.3-2.8 for the gynaecologists). The median three-dimensional difference in gravity centres ranged between 10.9 and 26.3mm for the respective patients. The ratio of common volumes to encompassing volumes ranged between 0.11 and 0.13 for the radiation oncologists, and between 0.30 and 0.57 for the gynaecologists. CONCLUSIONS Although there was a good consistency in outlined anatomical structures, for the radiation therapy of carcinomas of the uterine cervix a large interobserver variability in CTV delineation concerning the magnitude and relative location of volumes was observed. Compared to other factors, e.g. set-up and organ motion, interobserver variability in CTV definition seems to have the highest impact on the geometrical accuracy in the radiotherapy of this tumour entity.

The delineation of target volumes for radiotherapy of lung cancer patients.

PURPOSE Differences in the delineation of the gross target volume (GTV) and planning target volume (PTV) in patients with non-small-cell lung cancer are considerable. The focus of this work is on the analysis of observer-related reasons while controlling for other variables. METHODS In three consecutive patients, eighteen physicians from fourteen different departments delineated the GTV and PTV in CT-slices using a detailed instruction for target delineation. Differences in the volumes, the delineated anatomic lymph node compartments and differences in every delineated pixel of the contoured volumes in the CT-slices (pixel-by-pixel-analysis) were evaluated for different groups: ten radiation oncologists from ten departments (ROs), four haematologic oncologists and chest physicians from four departments (HOs) and five radiation oncologists from one department (RO1D). RESULTS Agreement (overlap > or = 70% of the contoured pixels) for the GTV and PTV delineation was found in 16.3% and 23.7% (ROs), 30.4% and 38.6% (HOs) and 32.8% and 35.9% (RO1D), respectively. CONCLUSION A large interobserver variability in the PTV and much more in the GTV delineation were observed in spite of a detailed instruction for delineation. The variability was smallest for group ROID where due to repeated discussions and uniform teaching a better agreement was achieved.

Interfractional and intrafractional accuracy during radiotherapy of gynecologic carcinomas: a comprehensive evaluation using the ExacTrac system

PURPOSE To evaluate positioning uncertainties with an infrared body marker-based positioning system (ExacTrac) compared with conventional laser positioning in patients treated for gynecologic carcinomas, and to investigate patient movement during therapy. MATERIALS AND METHODS Ten patients were positioned both with a conventional laser system and with the ExacTrac system. Positioning accuracy was evaluated using repeated electronic portal images. Average displacements and overall, systematic, and random errors were calculated and compared for the two positioning methods. Further, inter- and intrafractional patient movement including time trends in positioning displacements, respiratory amplitudes, and breathing frequencies were analyzed by online documentation of body marker movement with the ExacTrac system. RESULTS Average displacements ranged between -3.6 and 6.7 mm for the three coordinates. Mean systematic and random errors ranged from 1.6 to 3.7 mm and 2.2 to 3.7 mm, respectively, with no significant differences between conventional and ExacTrac positioning (p > 0.07). The main breathing direction was from dorsocaudal to anterocranial in 9 of 10 patients. The mean 3D breathing amplitude in the pelvis was 2.4 mm (0.49-6.96 mm). Significant interfractional and intrafractional time trends were observed concerning breathing amplitudes and positioning displacements. CONCLUSIONS The observed displacements did not vary significantly between the two evaluated positioning systems. The analysis of registered body marker positions revealed a wide variation in respiratory frequencies, breathing amplitudes, and patient displacements with interfractional and intrafractional time trends. Systems that allow the measurement of each patients motion characteristics are a necessary requirement for all efforts at individually tailored radiation therapy.

Organ function and quality of life after transoral laser microsurgery and adjuvant radiotherapy for locally advanced laryngeal cancer.

Background and Purpose:Transoral laser microsurgery (TLM) and adjuvant radiotherapy are an established therapy regimen for locally advanced laryngeal cancer at our institution. Aim of the present study was to assess value of quality of life (QoL) data with special regard to organ function under consideration of treatment efficacy in patients with locally advanced laryngeal cancer treated with larynx-preserving TLM and adjuvant radiotherapy.Patients and Methods:From 1994 to 2006, 39 patients (ten UICC stage III, 29 UICC stage IVA/B) with locally advanced laryngeal carcinomas were treated with TLM and adjuvant radiotherapy. Data concerning treatment efficacy, QoL (using the VHI [Voice Handicap Index], the EORTC QLQ-C30 and QLQ-H&N35 questionnaires) and organ function (respiration, deglutition, voice quality) were obtained for ten patients still alive after long-term follow-up. Correlations were determined using the Spearman rank test.Results:After a median follow-up of 80.8 months, the 5-year overall survival rate was 46.8% and the locoregional control rate 76.5%, respectively. The larynx preservation rate was 89.7% for all patients and 100% for patients still alive after follow-up. Despite some verifiable problems in respiration, speech and swallowing, patients showed a subjectively good QoL.Conclusion:TLM and adjuvant radiotherapy is a curative option for patients with locally advanced laryngeal cancer and an alternative to radical surgery. Even if functional deficits are unavoidable in the treatment of locally advanced laryngeal carcinomas, larynx preservation is associated with a subjectively good QoL.Hintergrund und Ziel:Lasermikrochirurgie und adjuvante Strahlentherapie sind in der Klinik der Autoren etablierte Behandlungsmethoden lokal fortgeschrittener Larynxkarzinome mit guten onkologischen Ergebnissen und einer hohe Rate an Organerhalt. Bei organerhaltender Therapie sind funktionelle Einschränkungen oft unvermeidbar. Neben den onkologischen Ergebnissen sollten in dieser Studie das objektive Ausmaß solcher Einschränkungen und deren subjektive Wertung durch die Patienten untersucht werden.Patienten und Methodik:Von 1994 bis 2006 wurden 39 Patienten (zehn UICC-Stadium III, 29 UICC-Stadium IVA/B) mit lokal fortgeschrittenen Larynxkarzinomen mittels Lasermikrochirurgie und adjuvanter Strahlentherapie behandelt. Bei zehn Patienten erfolgte im Rahmen der Nachsorge in den Jahren 2006/2007 eine Erhebung von Lebensqualitätsdaten. Die Schluckfunktion wurde flexibel endoskopisch überprüft, die Atmung durch eine Bodyplethysmographie. Die Objektivierung der Stimmqualität erfolgte durch das Göttinger Heiserkeitsdiagramm.Ergebnisse:Nach einer medianen Beobachtungsdauer von 80,8 Monaten betrugen die 5-Jahres-Überlebensrate 46,8% und die lokoregionale Kontrollrate 76,5%. Eine Salvage-Laryngektomie bei Lokalrezidiv erhielten vier Patienten, so dass im Verlauf eine 89,7%ige Rate an Larynxerhalt erreicht werden konnte. Bei der objektiven Untersuchung der Funktionseinschränkungen zeigte sich bei fünf Patienten eine gelegentliche Aspiration bei kräftigem Hustenreflex. Die übrigen fünf Patienten wiesen keine Schluckstörung auf. Eine Normalstimme lag bei keinem Patienten vor. Es bestand jedoch keine signifikante Korrelation der objektivierten Funktionsstörungen mit den Lebensqualitätsfunktionsskalen: Subjektiv schätzen die Patienten ihre Lebensqualität als gut ein.Schlussfolgerung:Lasermikrochirurgie und adjuvante Strahlentherapie sind eine Therapieoption für lokal fortgeschrittene Larynxkarzinome, die neben guten onkologischen Ergebnissen eine hohe Rate an Organerhalt ermöglicht. Die Patienten schätzen ihre Lebensqualität im weiteren Verlauf subjektiv als gut ein. Die tatsächlichen funktionellen Einschränkungen werden durch die Lebensqualitätsdaten allerdings nicht sicher abgebildet. Daher ist zur objektiven Beurteilung posttherapeutischer Funktionsergebnisse die klinische Erhebung funktioneller Befunde erforderlich.

Single fraction radiosurgery using Rapid Arc for treatment of intracranial targets

BackgroundStereotactic-Radio-Surgery (SRS) using Conformal-Arc-Therapy (CAT) is a well established irradiation technique for treatment of intracranial targets. Although small safety margins are required because of very high accuracy of patient positioning and exact online localisation, there are still disadvantages like long treatment time, high number of monitor units (MU) and covering of noncircular targets. This planning study analysed whether Rapid Arc (RA) with stereotactic localisation for single-fraction SRS can solve these problems.MethodsTen consecutive patients were treated with Linac-based SRS. Eight patients had one or more brain metastases. The other patients presented a symptomatic vestibularis schwannoma and an atypic meningeoma. For all patients, two plans (CAT/RA) were calculated and analysed.ResultsConformity was higher for RA with additional larger low-dose areas. Furthermore, RA reduced the number of MU and the treatment time for all patients. Dose to organs at risk were equal or slightly higher using RA in comparison to CAT.ConclusionsRA provides a new alternative for single-fraction SRS irradiation combining advantages of short treatment time with lower number of MU and better conformity in addition to accuracy of stereotactic localisation in selected cases with uncomplicated clinical realization.

Apoptosis induction by inhibitors of Ser/Thr phosphatases 1 and 2A is associated with transglutaminase activation in two different human epithelial tumour lines

Two epithelial tumour lines, HeLa and KB, were treated with okadaic acid and calyculin A, specific inhibitors of Ser/Thr phosphatases (PP), esp. PP1 and PP2A. Morphological criteria, analysis of DNA fragmentation and studies of membrane integrity revealed that both agents concentration‐ and time‐dependently induced apoptosis at nanomolar concentrations which in these cells was associated with the stimulation of a transglutaminase activity. Since a non‐functional derivative of okadaic acid did not affect cell viability apoptosis was apparently related to the inhibition of PP1 and PP2A. Membrane damage marker activity was delayed by at least 24 h when compared to nuclear alterations.

The impact of varying volumes in rectal balloons on rectal dose sparing in conformal radiation therapy of prostate cancer. A prospective three-dimensional analysis.

Background and Purpose:The use of a rectal balloon leads to a protection of the posterior rectal wall in irradiation of prostate cancer. The purpose of this analysis was to quantitatively assess the optimal volume in rectal balloons concerning rectal dose sparing in different clinical target volumes (CTVs) in prostate cancer irradiation.Patients and Methods:14 patients with localized prostate cancer undergoing external beam radiotherapy were investigated. The prostate, the entire and the proximal seminal vesicles were delineated as CTV. Treatment plans without a rectal balloon and with a rectal balloon inflated with 40 ml (six patients) or 60 ml air (eight patients) were generated for each CTV and compared concerning rectal dose volume histograms.Results:The use of a rectal balloon filled with 40 ml air led to no significant advantage in radiation exposure of the rectal wall in all CTVs. The use of a rectal balloon filled with 60 ml air resulted in a significant decrease of the exposed rectal wall volume in all CTVs with a reduced estimated risk for chronic toxicity in case of inclusion of the proximal or entire seminal vesicles into the CTV.Conclusion:The use of a rectal balloon filled with 60 ml air led to a significantly decreased proportion of the irradiated rectal wall for all CTVs. This volume filled in rectal balloons is therefore recommended for use. In case of irradiation of the prostate without the seminal vesicles, the use of a rectal balloon should be considered carefully concerning the patients’ imaginable discomfort using a rectal balloon and a questionable advantage concerning the estimated risk for chronic toxicity.Hintergrund und Ziel:Der Einsatz eines rektal applizierten Ballons führt zu einem Schutz der Rektumhinterwand bei der Bestrahlung des Prostatakarzinoms. Das Ziel der vorliegenden Analyse war, das optimale Volumen in rektalen Ballons bezüglich Darmschonung bei verschiedenen klinischen Zielvolumina (CTVs) bei Bestrahlung von Patienten mit Prostatakarzinom quantitativ zu erfassen.Patienten und Methodik:14 Patienten mit Prostatakarzinom, die eine Radiotherapie erhielten, wurden untersucht. Die Prostata und proximale/ganze Samenblasen wurden als CTV definiert. Pläne mit und ohne Ballon, gefüllt mit 40 ml (sechs Patienten) oder 60 ml Luft (acht Patienten), wurden für jedes CTV erstellt und die Dosis-Volumen-Histogramme des Darms miteinander verglichen.Ergebnisse:Der Einsatz eines mit 40 ml Luft gefüllten Ballons führte zu keiner signifikanten Reduktion der Darmwandbelastung bei allen CTVs (Tabelle 1). Der Einsatz eines mit 60 ml Luft gefüllten Ballons führte zu einer signifikanten Reduktion der Darmwandbelastung bei allen CTVs (Tabelle 2 und Abbildungen 4 bis 6). Dadurch konnte im Fall einer Einbeziehung der proximalen und ganzen Samenblasen in das CTV das geschätzte Risiko für Spättoxizität reduziert werden (Tabelle 3).Schlussfolgerung:Der Einsatz eines mit 60 ml Luft gefüllten Ballons führte zu einer signifikanten Reduktion der Darmwandbelastung bei allen CTVs. Dieses Volumen wird daher beim Einsatz rektaler Ballons empfohlen. Im Fall einer Bestrahlung nur der Prostata sollte der Einsatz eines rektalen Ballons sorgfältig geprüft werden, da er den Patienten Unbehagen verursachen kann und der Nutzen bezüglich einer geschätzten Reduktion der Spättoxizität fraglich ist.

Guidelines for delineation of lymphatic clinical target volumes for high conformal radiotherapy: head and neck region

The success of radiotherapy depends on the accurate delineation of the clinical target volume. The delineation of the lymph node regions has most impact, especially for tumors in the head and neck region. The purpose of this article was the development an atlas for the delineation of the clinical target volume for patients, who should receive radiotherapy for a tumor of the head and neck region. Literature was reviewed for localisations of the adjacent lymph node regions and their lymph drain in dependence of the tumor entity. On this basis the lymph node regions were contoured on transversal CT slices. The probability for involvement was reviewed and a recommendation for the delineation of the CTV was generated.

Two years experience with quality assurance protocol for patient related Rapid Arc treatment plan verification using a two dimensional ionization chamber array.

PurposeTo verify the dose distribution and number of monitor units (MU) for dynamic treatment techniques like volumetric modulated single arc radiation therapy - Rapid Arc - each patient treatment plan has to be verified prior to the first treatment. The purpose of this study was to develop a patient related treatment plan verification protocol using a two dimensional ionization chamber array (MatriXX, IBA, Schwarzenbruck, Germany).MethodMeasurements were done to determine the dependence between response of 2D ionization chamber array, beam direction, and field size. Also the reproducibility of the measurements was checked. For the patient related verifications the original patient Rapid Arc treatment plan was projected on CT dataset of the MatriXX and the dose distribution was calculated. After irradiation of the Rapid Arc verification plans measured and calculated 2D dose distributions were compared using the gamma evaluation method implemented in the measuring software OmniPro (version 1.5, IBA, Schwarzenbruck, Germany).ResultsThe dependence between response of 2D ionization chamber array, field size and beam direction has shown a passing rate of 99% for field sizes between 7 cm × 7 cm and 24 cm × 24 cm for measurements of single arc. For smaller and larger field sizes than 7 cm × 7 cm and 24 cm × 24 cm the passing rate was less than 99%. The reproducibility was within a passing rate of 99% and 100%. The accuracy of the whole process including the uncertainty of the measuring system, treatment planning system, linear accelerator and isocentric laser system in the treatment room was acceptable for treatment plan verification using gamma criteria of 3% and 3 mm, 2D global gamma index.ConclusionIt was possible to verify the 2D dose distribution and MU of Rapid Arc treatment plans using the MatriXX. The use of the MatriXX for Rapid Arc treatment plan verification in clinical routine is reasonable. The passing rate should be 99% than the verification protocol is able to detect clinically significant errors.