Reinhart A. Sweeney

Potential of image-guidance, gating and real-time tracking to improve accuracy in pulmonary stereotactic body radiotherapy

PURPOSE To evaluate the potential of image-guidance, gating and real-time tumor tracking to improve accuracy in pulmonary stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS Safety margins for compensation of inter- and intra-fractional uncertainties of the target position were calculated based on SBRT treatments of 43 patients with pre- and post-treatment cone-beam CT imaging. Safety margins for compensation of breathing motion were evaluated for 17 pulmonary tumors using respiratory correlated CT, model-based segmentation of 4D-CT images and voxel-based dose accumulation; the target in the mid-ventilation position was the reference. RESULTS Because of large inter-fractional base-line shifts of the tumor, stereotactic patient positioning and image-guidance based on the bony anatomy required safety margins of 12 mm and 9 mm, respectively. Four-dimensional image-guidance targeting the tumor itself and intra-fractional tumor tracking reduced margins to <5 mm and <3 mm, respectively. Additional safety margins are required to compensate for breathing motion. A quadratic relationship between tumor motion and margins for motion compensation was observed: safety margins of 2.4mm and 6mm were calculated for compensation of 10 mm and 20 mm motion amplitudes in cranio-caudal direction, respectively. CONCLUSION Four-dimensional image-guidance with pre-treatment verification of the target position and online correction of errors reduced safety margins most effectively in pulmonary SBRT.

Toxicity after Intensity-Modulated, Image-Guided Radiotherapy for Prostate Cancer

Purpose:To evaluate toxicity after dose-escalated radiotherapy for prostate cancer using intensity-modulated treatment planning (IMRT) and image-guided treatment (IGRT) delivery.Patients and Methods:100 patients were treated with simultaneous integrated boost (SIB) IMRT for prostate cancer: doses of 76.23 Gy and 60 Gy in 33 fractions were prescribed to the prostate and the seminal vesicles, respectively, for intermediate- and high-risk patients (n = 74). The total dose was 73.91 Gy in 32 fractions for low-risk patients and after transurethral resection of the prostate (n = 26). The pelvic lymphatics were treated with 46 Gy in 25 fractions in patients with high risk of lymph node metastases using an SIB to the prostate (n = 25). IGRT was practiced with cone-beam computed tomography. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity was evaluated prospectively (CTCAE v3.0).Results:Treatment was completed as planned by all patients. Acute GI and GU toxicity grade ≥ 2 was observed in 12% and 42% of the patients, respectively, with 4% suffering from GU toxicity grade 3. 6 weeks after treatment, the incidence of acute toxicity grade ≥ 2 had decreased to 12%. With a median follow-up of 26 months, late GI and GU toxicity grade ≥ 2 was seen in 1.5% and 7.7% of the patients at 24 months. Four patients developed late toxicity grade 3 (GI n = 1; GU n = 3). Presence of acute GI and GU toxicity was significantly associated with late GI (p = 0.0007) and GU toxicity (p = 0.006).Conclusion:High-dose radiotherapy for prostate cancer using IMRT and IGRT resulted in low rates of acute toxicity and preliminary results of late toxicity are promising.ZusammenfassungZiel:Erfassung der Toxizität nach intensitätsmodulierter (IMRT), bildgeführter Strahlentherapie (IGRT) des Prostatakarzinoms.Patienten und Methodik:100 Patienten wurden wegen eines Prostatakarzinoms mittels IMRT und simultanen integrierten Boosts (SIB) primar bestrahlt: Gesamtdosen von 76,23 Gy bzw. 60 Gy in 33 Fraktionen wurden im Boostzielvolumen und in den Samenblasen geplant, falls ein hohes oder intermediares Risikoprofil vorlag (n = 74). Bei niedrigem Risiko und Zustand nach transurethraler Prostataresektion wurde eine Gesamtdosis von 73,91 Gy in 32 Fraktionen angewendet (n = 26). Das pelvine Lymphabflussgebiet wurde bei hohem Risiko eines Lymphknotenbefalls mit 46 Gy in 25 Fraktionen behandelt (n = 25), ebenfalls mit einem SIB auf die Prostata. IGRT wurde mittels Cone-Beam-Computertomographie praktiziert. Die akute und chronische gastrointestinale (GI) und urogenitale (GU) Toxizitat wurde prospektiv nach CTCAE v3.0 erfasst.Ergebnisse:Die Behandlung wurde bei allen Patienten planmäßig beendet. Akute GI- und GU-Toxizitat ≥ Grad 2 wurde bei 12% bzw. 42% der Patienten beobachtet; 4% entwickelten eine GU-Toxizitat Grad 3. 6 Wochen nach Therapie war die Inzidenz einer Toxizität ≥ Grad 2 auf 12% zurückgegangen. Nach einer medianen Nachbeobachtungszeit von 26 Monaten wurde eine 2-Jahres-GI-bzw. -GU-Toxizitat ≥ Grad 2 bei 1,5% bzw. 7,7% der Patienten beobachtet. Vier Patienten entwickelten eine Spätnebenwirkung Grad 3 (GI n = 1; GU n = 3). Das Vorhandensein von akuter GI- und GU-Toxizität war mit einer signifikant höheren Inzidenz an späten GI- (p = 0,0007) und GU-Nebenwirkungen (p = 0,006) assoziiert.Schlussfolgerung:Radiotherapie mit hohen Bestrahlungsdosen resultierte in geringer Akuttoxizitat bei Anwendung von IMRT und IGRT; vorläufige Daten zur chronischen Toxizität sind vielversprechend.

Repositioning Accuracy: Comparison of a Noninvasive Head Holder with Thermoplastic Mask for Fractionated Radiotherapy and a Case Report

PURPOSE To compare accuracy, clinical feasibility, and subjective patient impression between a noninvasive head holder (Vogele Bale Hohner [VBH]; Wellhoefer Dosimetry, Schwarzenbruck, Germany) developed at the University of Innsbruck and the thermoplastic mask fixation system for use in fractionated external radiotherapy. We present a case report of an actual patient fixated in the VBH head holder during radiation therapy. MATERIALS AND METHODS The VBH head holder consists of an individualized vacuum dental cast connected to a head plate via two hydraulic arms allowing noninvasive, reproducible head fixation of even uncooperative patients. Accuracy was tested and compared with that of the thermoplastic mask using the Phillips EasyGuide navigation system on five volunteers. Specific external registration points served as landmarks and their positions were compared after each repositioning. System and operator inaccuracy were also taken into account. The times taken for production and repositioning of the respective fixation devices were compared, and subjective impressions were noted. RESULTS Mean VBH head holder repositioning accuracy was 1.02 mm while that of the thermoplastic mask was 3.05 mm. 69% of mask repositionings showed a deviation > 2 mm and 41% > 3 mm (as opposed to 8% and 1% respectively for the VBH head holder) Those points located farthest away from the respective plane of fixation showed the largest deviations. Both production and repositioning times were similar between the systems; depending upon the patient, the VBH head holder was generally better tolerated than the mask system. CONCLUSION Due to its significantly better repositioning accuracy compared to that of the thermoplastic mask, the VBH head holder is especially suited for external radiation requiring precise repositioning due to critical tissues in immediate surrounding of the area to be irradiated.

Image-Guided Radiotherapy for Liver Cancer Using Respiratory-Correlated Computed Tomography and Cone-Beam Computed Tomography

PURPOSE To evaluate a novel four-dimensional (4D) image-guided radiotherapy (IGRT) technique in stereotactic body RT for liver tumors. METHODS AND MATERIALS For 11 patients with 13 intrahepatic tumors, a respiratory-correlated 4D computed tomography (CT) scan was acquired at treatment planning. The target was defined using CT series reconstructed at end-inhalation and end-exhalation. The liver was delineated on these two CT series and served as a reference for image guidance. A cone-beam CT scan was acquired after patient positioning; the blurred diaphragm dome was interpreted as a probability density function showing the motion range of the liver. Manual contour matching of the liver structures from the planning 4D CT scan with the cone-beam CT scan was performed. Inter- and intrafractional uncertainties of target position and motion range were evaluated, and interobserver variability of the 4D-IGRT technique was tested. RESULTS The workflow of 4D-IGRT was successfully practiced in all patients. The absolute error in the liver position and error in relation to the bony anatomy was 8 +/- 4 mm and 5 +/- 2 mm (three-dimensional vector), respectively. Margins of 4-6 mm were calculated for compensation of the intrafractional drifts of the liver. The motion range of the diaphragm dome was reproducible within 5 mm for 11 of 13 lesions, and the interobserver variability of the 4D-IGRT technique was small (standard deviation, 1.5 mm). In 4 patients, the position of the intrahepatic lesion was directly verified using a mobile in-room CT scanner after application of intravenous contrast. CONCLUSION The results of our study have shown that 4D image guidance using liver contour matching between respiratory-correlated CT and cone-beam CT scans increased the accuracy compared with stereotactic positioning and compared with IGRT without consideration of breathing motion.

Intra-fractional uncertainties in image-guided intensity-modulated radiotherapy (IMRT) of prostate cancer

PurposeTo evaluate intra-fractional uncertainties during intensity-modulated radiotherapy (IMRT) of prostate cancer.Patients and MethodsDuring IMRT of 21 consecutive patients, kilovolt (kV) cone-beam computed tomography (CBCT) images were acquired prior to and immediately after treatment: a total of 252 treatment fractions with 504 CBCT studies were basis of this analysis. The prostate position in anterior-posterior (AP) direction was determined using contour matching; patient set-up based on the pelvic bony anatomy was evaluated using automatic image registration. Internal variability of the prostate position was the difference between absolute prostate and patient position errors. Intra-fractional changes of prostate position, patient position, rectal distension in AP direction and bladder volume were analyzed.ResultsWith a median treatment time of 16 min, intra-fractional drifts of the prostate were > 5 mm in 12% of all fractions and a margin of 6 mm was calculated for compensation of this uncertainty. Mobility of the prostate was independent from the bony anatomy with poor correlation between absolute prostate motion and motion of the bony anatomy (R2 = 0.24). A systematic increase of bladder filling by 41 ccm on average was observed; however, these changes did not influence the prostate position. Small variations of the prostate position occurred independently from intra-fractional changes of the rectal distension; a weak correlation between large internal prostate motion and changes of the rectal volume was observed (R2 = 0.55).ConclusionClinically significant intra-fractional changes of the prostate position were observed and margins of 6 mm were calculated for this intra-fractional uncertainty. Repeated or continuous verification of the prostate position may allow further margin reduction.ZusammenfassungZielZiel der Arbeit war die Analyse von intrafraktionellen Fehlern in der intensitätsmodulierten Strahlentherapie (IMRT) des Prostatakarzinoms.Patienten und MethodikBei 21 Patienten wurde vor und nach der IMRT-Behandlung ein Kilovolt-Cone-Beam-CT (kV CBCT) aufgenommen. Basierend auf 252 Behandlungsfraktionen und 504 CBCT-Studien wurde die Position der Prostata in anterior-posteriorer (AP) Richtung mittels manueller Konturregistrierung und die Lagerung des Patienten durch automatische Registrierung des Beckenskeletts ermittelt. Die interne Lagevariabilität der Prostata war definiert als die Differenz der Positionsfehler bezüglich Prostata und knöcherner Anatomie. Intrafraktionelle Veränderungen wurden für die Position der Prostata und des Patienten, die Füllung der Blase und die AP-Weite des Rektums bestimmt.ErgebnisseBei einer medianen Behandlungszeit von 16 min waren intrafraktionelle Veränderungen der Prostataposition in 12% der Fraktionen > 5 mm; ein Sicherheitssaum von 6 mm wurde zur Kompensation berechnet. Die Beweglichkeit der Prostata war im Wesentlichen unabhängig von dem pelvinen Knochenskelett (R2 = 0,24). Eine systematische Zunahme des Blasenvolumens um durchschnittlich 41 ccm wurde während der Behandlung gemessen; dies hatte aber keinen Einfluss auf die AP-Position der Prostata. Während kleine Bewegungen der Prostata unabhängig von Änderungen der Rektumweite waren, wurde für interne Prostatabewegungen > 5 mm eine Korrelation (R2 = 0,55) mit intrafraktionellen Änderungen der Rektumweite beobachtet.SchlussfolgerungIntrafraktionelle Änderungen der Prostataposition waren von klinisch relevantem Ausmaß und benötigen einen Sicherheitssaum von 6 mm. Die kontinuierliche oder wiederholte Verifikation der Prostataposition könnte eine weitere Verkleinerung der Sicherheitssäume ermöglichen.

Reproducibility of Patient Positioning for Fractionated Extracranial Stereotactic Radiotherapy Using a Double-Vacuum Technique

Background and Purpose:Precise reproducible patient positioning is a prerequisite for conformal fractionated radiotherapy. A fixation system based on double-vacuum technology is presented which can be used for conventional as well as hypofractionated stereotactic extracranial radiotherapy.Material and Methods:To form the actual vacuum mattress, the patient is pressed into the mattress with a vacuum foil which can also be used for daily repositioning and fixation. A stereotactic frame can be positioned over the region of interest on an indexed base plate. Repositioning accuracy was determined by comparing daily, pretreatment, orthogonal portal images to the respective digitally reconstructed radiographs (DRRs) in ten patients with abdominal and pelvic lesions receiving extracranial fractionated (stereotactic) radiotherapy. The three-dimensional (3-D) vectors and 95% confidence intervals (CI) were calculated from the respective deviations in the three axes. Time required for initial mold production and daily repositioning was also determined.Results:The mean 3-D repositioning error (187 fractions) was 2.5 ± 1.1 mm. The largest single deviation (10 mm) was observed in a patient treated in prone position. Mold production took an average of 15 min (10–30 min). Repositioning times are not necessarily longer than using no positioning aid at all.Conclusion:The presented fixation system allows reliable, flexible and efficient patient positioning for extracranial stereotactic radiotherapy.Hintergrund und Ziel:Voraussetzung für eine konformale fraktionierte Strahlentherapie ist eine präzise reproduzierbare Positionierung des Patienten und des Zielvolumens. Vorgestellt wird ein auf dem Doppelvakuumprinzip basierendes Fixationssystem, das sowohl für konventionelle als auch extrakranielle stereotaktische Bestrahlungen eingesetzt werden kann.Material und Methodik:Mittels einer Fixationsfolie, mit der er auch zusätzlich fixiert werden kann, wird der Patient vor der Abformung in die Vakuummatratze hineingepresst. Eine exakt auf einer indexierten Bodenplatte positionierbare Plexiglashaube dient als stereotaktischer Rahmen. Bei zehn Patienten mit Zielvolumina im Abdomen und Becken wurden vor jeder Bestrahlung orthogonale digitale Verifikationsaufnahmen angefertigt. Diese wurden mit den digital rekonstruierten Röntgenbildern (DRRs) des dreidimensionalen (3-D) Planungssystems verglichen. Aus den Abweichungen der drei Raumrichtungen wurden die 3-D-Vektoren als Maß für die Repositionierungsgenauigkeit errechnet.Ergebnisse:Der Mittelwert der für alle Patienten errechneten 3-D-Vektoren (187 Fraktionen) betrug 2,5 ± 1,1 mm. Der mit 10 mm größte 3-D-Vektor wurde bei einem in Bauchlage bestrahlten Patienten beobachtet. Die initiale Abformung dauerte im Durchschnitt 15 min (10–30 min). Der tägliche zeitliche Lagerungsaufwand am Bestrahlungsgerät ist nur unwesentlich länger als ohne Fixationshilfe.Schlussfolgerung:Das vorgestellte Fixierungssystem ermöglicht eine zuverlässige, flexible und effiziente Patientenpositionierung für die stereotaktische Bestrahlung extrakranieller Tumoren.

A new pneumatic vibrator for functional magnetic resonance imaging of the human sensorimotor cortex.

The aim of the study was to implement a vibrotactile stimulator using functional magnetic resonance imaging (fMRI). A fMRI compatible vibration device consisting of a pneumatically driven dual membrane pump was developed. Brain activation during 50 Hz vibrotactile stimulation of the right hand-palm were compared to a right 2 Hz finger-to-thumb-tapping in ten healthy, right-handed male volunteers. The vibration paradigm showed a comparable activation pattern with respect to finger-to-thumb-tapping in the contralateral perirolandic region. The advantage of the new vibration device is the possibility to elicit the vibratory-tonic-reflex due to the higher amplitude in context with the high frequency than established devices. This reflex is considered to be responsible for the activation in the primary motor cortex and the current paradigm might prove useful in future neurosurgical planning in patients with perirolandic lesions.

A Simple and Non-Invasive Vacuum Mouthpiece-Based Head Fixation System for High Precision Radiotherapy

Purpose: To demonstrate why conventional non-invasive mouthpiece-based fixation has not achieved the expected accuracy and to suggest a solution of the problem. Patients and Methods: The Vogele Bale Hohner (VBH) head holder is a non-invasive vacuum mouthpiece-based head fixation system. Feasibility and repositioning accuracy were evaluated by portal image analysis in 12 patients with cranial tumors intended for stereotactic procedures, fixated with the newest version (VBH HeadFix-ARC®). Results: Portal image analysis (8 patients evaluated in 2-D, 4 patients in 3-D) showed that even in routine external beam radiation therapy, treatment can be applied to within a mean 2-D and 3-D accuracy of under 2 mm (SD 0.92 mm and 1.2 mm, respectively) with cost and repositioning time per patient and patient comfort comparable to that of common thermoplastic masks. Conclusion: These preliminary results show that high repositioning accuracy does not rule out simple and quick application and patient comfort. Paramount, however, is tensionless repositioning via the vacuum mouthpiece.Ziel: Fixationssysteme, die auf konventionellen (nicht Vakuum-)Mundstücken basieren, erreichen oftmals nicht die erwartete Genauigkeit. Die vorliegende Arbeit beschäftigt sich mit den möglichen Ursachen und bietet entsprechende Lösungen. Patienten und Methoden: Der Vogele-Bale-Hohner-(VBH-)Head-Holder ist ein nicht invasives, auf einem Vakuummundstück (Abbildung 1) basierendes Kopffixationssystem (Abbildungen 2 und 3). Bei zwölf Patienten mit kraniellen Tumoren wurde mit der neuesten Version (VBH HeadFix-ARC®) die Repositionsgenauigkeit mittels Portal Imaging untersucht. Ergebnisse: Die Portal-Imaging-Auswertung (acht Patienten in 2-D, vier Patienten in 3-D) bestätigte, dass eine Bestrahlung im Kopfbereich auch in der klinischen Routine mit einer mittleren Genauigkeit von unter 2 mm (Standardabweichung 0,92 bzw. 1,2 mm) appliziert werden kann, während Kosten, Repositionsdauer und Akzeptanz der Patienten vergleichbar sind mit denen thermoplastischer Masken. Schlussfolgerung: Diese vorläufigen Ergebnisse zeigen, dass eine hohe Repositionierungsgenauigkeit ein einfaches, schnelles und für den Patienten angenehmes System nicht ausschließt. Ausschlaggebend ist die spannungsfreie Lagerung mittels Vakuummundstück.

Clinical practice of image-guided spine radiosurgery - results from an international research consortium

BackgroundSpinal radiosurgery is a quickly evolving technique in the radiotherapy and neurosurgical communities. However, the methods of spine radiosurgery have not been standardized. This article describes the results of a survey about the methods of spine radiosurgery at five international institutions.MethodsAll institutions are members of the Elekta Spine Radiosurgery Research Consortium and have a dedicated research and clinical focus on image-guided radiosurgery. The questionnaire consisted of 75 items covering all major steps of spine radiosurgery.ResultsStrong agreement in the methods of spine radiosurgery was observed. In particular, similarities were observed with safety and quality assurance playing an important role in the methods of all institutions, cooperation between neurosurgeons and radiation oncologists in case selection, dedicated imaging for target- and organ-at-risk delineation, application of proper safety margins for the target volume and organs-at-risk, conformal planning and precise image-guided treatment delivery, and close clinical and radiological follow-up. In contrast, three major areas of uncertainty and disagreement were identified: 1) Indications and contra-indications for spine radiosurgery; 2) treatment dose and fractionation and 3) tolerance dose of the spinal cord.ConclusionsResults of this study reflect the current practice of spine radiosurgery in large academic centers. Despite close agreement was observed in many steps of spine radiosurgery, further research in form of retrospective and especially prospective studies is required to refine the details of spinal radiosurgery in terms of safety and efficacy.

Single-Institution Results of Primary External-Beam Radiation for the Treatment of T1–T3 Prostate Cancer

Purpose:To evaluate survival and toxicity rates after primary external-beam radiation for the treatment of prostate cancer.Patients and Methods:Data of 306 patients treated with conformal external beam radiation between 1996 and 2001 were collected. These were evaluated in terms of overall, cause-specific and disease-free survival as well as toxicity. Furthermore, an investigation of possible risk factors was performed.Results:Toxicity rates compared favorably with other series with 5.2% RTOG 1–2 and no RTOG > 2 long-term side effects. Actuarial 5-year overall survival rates with and without biochemical failure were 77% versus 78%, cancer-specific survival was 85.41% versus 100%, and disease-free survival was 71.54%, respectively. Potential risk factors for cancer-related death were biochemical failure, initial serum prostate-specific antigen (PSA) and Gleason score.Conclusion:Toxicity rates were found to be surprisingly low compared to other series, which is likely due to low daily dose and consistent MR-based treatment planning. In terms of survival, no significant differences to other trials could be observed. Initial PSA and Gleason score were significant predictors for treatment outcome in terms of survival.Ziel:Evaluierung von Überleben und Toxizität nach primärer perkutaner Strahlentherapie in der Behandlung des Prostatakarzinoms.Patienten und Methodik:Die Daten von 306 zwischen 1996 und 2001 mittels konformaler externer Radiatio behandelten Patienten wurden erhoben und ausgewertet. Anschließend wurden die Ergebnisse im Hinblick auf Gesamtüberleben, tumorspezifisches Überleben und rezidivfreies Überleben sowie Toxizität analysiert. Zusätzlich wurde versucht, Risikofaktoren zu finden, welche mit einem schlechteren Outcome assoziiert sind.Ergebnisse:Im Vergleich mit anderen Studien wurden deutlich niedrigere Toxizitätsraten festgestellt, mit Langzeitnebenwirkungsraten im urogenitalen Bereich von 5,2% RTOG 1–2 und keinerlei Grad-3- und Grad-4-Toxizität. Das aktuarische 5-Jahres-Gesamtüberleben betrug 77% bzw. 78% in Abhängigkeit vom Auftreten eines biochemischen Rezidivs. Das tumorspezifische Überleben betrug 85,41% bzw. 100%, das rezidivfreie Überleben 71,54%. Als potentielle Risikofaktoren für tumorspezifische Todesfälle erwiesen sich sowohl das biochemische Rezidiv als auch initiales Serum-PSA (prostataspezifisches Antigen) und Gleason-Score.Schlussfolgerung:Verglichen mit anderen Studien wurde ein überraschend günstiges Nebenwirkungsprofil festgestellt, welches mit hoher Wahrscheinlichkeit auf niedrigere Einzelfraktionsdosen sowie konsequente MR-basierte Bestrahlungsplanung zurückzuführen ist. Hingegen konnte im Hinblick auf die Überlebensraten kein wesentlicher Unterschied zu Vergleichsarbeiten beobachtet werden. Initialer PSA-Wert und Gleason-Score scheinen die signifikantesten Parameter im Hinblick auf das Überleben zu sein.