Dirk Boehmer

Potentials of on-line repositioning based on implanted fiducial markers and electronic portal imaging in prostate cancer radiotherapy

BackgroundTo evaluate the benefit of an on-line correction protocol based on implanted markers and weekly portal imaging in external beam radiotherapy of prostate cancer. To compare the use of bony anatomy versus implanted markers for calculation of setup-error plus/minus prostate movement. To estimate the error reduction (and the corresponding margin reduction) by reducing the total error to 3 mm once a week, three times per week or every treatment day.Methods23 patients had three to five, 2.5 mm Ø spherical gold markers transrectally inserted into the prostate before radiotherapy. Verification and correction of treatment position by analysis of orthogonal portal images was performed on a weekly basis. We registered with respect to the bony contours (setup error) and to the marker position (prostate motion) and determined the total error. The systematic and random errors are specified. Positioning correction was applied with a threshold of 5 mm displacement.ResultsThe systematic error (1 standard deviation [SD]) in left-right (LR), superior-inferior (SI) and anterior-posterior (AP) direction contributes for the setup 1.6 mm, 2.1 mm and 2.4 mm and for prostate motion 1.1 mm, 1.9 mm and 2.3 mm. The random error (1 SD) in LR, SI and AP direction amounts for the setup 2.3 mm, 2.7 mm and 2.7 mm and for motion 1.4 mm, 2.3 mm and 2.7 mm. The resulting total error suggests margins of 7.0 mm (LR), 9.5 mm (SI) and 9.5 mm (AP) between clinical target volume (CTV) and planning target volume (PTV). After correction once a week the margins were lowered to 6.7, 8.2 and 8.7 mm and furthermore down to 4.9, 5.1 and 4.8 mm after correcting every treatment day.ConclusionProstate movement relative to adjacent bony anatomy is significant and contributes substantially to the target position variability. Performing on-line setup correction using implanted radioopaque markers and megavoltage radiography results in reduced treatment margins depending on the online imaging protocol (once a week or more frequently).

Residual Translational and Rotational Errors after kV X-Ray Image-Guided Correction of Prostate Location Using Implanted Fiducials

Purpose:To evaluate the residual errors and required safety margins after stereoscopic kilovoltage (kV) X-ray target localization of the prostate in image-guided radiotherapy (IGRT) using internal fiducials.Patients and Methods:Radiopaque fiducial markers (FMs) have been inserted into the prostate in a cohort of 33 patients. The ExacTrac/Novalis Body™ X-ray 6d image acquisition system (BrainLAB AG, Feldkirchen, Germany) was used. Corrections were performed in left-right (LR), anterior-posterior (AP), and superior-inferior (SI) direction. Rotational errors around LR (x-axis), AP (y) and SI (z) have been recorded for the first series of nine patients, and since 2007 for the subsequent 24 patients in addition corrected in each fraction by using the Robotic Tilt Module™ and Varian Exact Couch™. After positioning, a second set of X-ray images was acquired for verification purposes. Residual errors were registered and again corrected.Results:Standard deviations (SD) of residual translational random errors in LR, AP, and SI coordinates were 1.3, 1.7, and 2.2 mm. Residual random rotation errors were found for lateral (around x, tilt), vertical (around y, table), and longitudinal (around z, roll) and of 3.2°, 1.8°, and 1.5°. Planning target volume (PTV)-clinical target volume (CTV) margins were calculated in LR, AP, and SI direction to 2.3, 3.0, and 3.7 mm. After a second repositioning, the margins could be reduced to 1.8, 2.1, and 1.8 mm.Conclusion:On the basis of the residual setup error measurements, the margin required after one to two online X-ray corrections for the patients enrolled in this study would be at minimum 2 mm. The contribution of intrafractional motion to residual random errors has to be evaluated.ZusammenfassungZiel:Der residuale Lagerungsfehler und die erforderlichen Sicherheitsabstande in der bildgestutzten Lokalisation und Positionskorrektur der Prostata sollten ermittelt werden.Patienten und Methodik:In einer Gruppe von 33 Patienten wurden rontgendichte Marker in die Prostata implantiert. Die Autoren setzten das rontgenbasierte und automatisierte Positionierungs- und Verifikationssystem ExacTrac/Novalis Body™ (BrainLAB AG, Feldkirchen) ein. Fur die erste Serie von neun Patienten erfolgten tagliche Korrekturen des initalen Translationsfehlers in mediolateraler (ML), anteroposteriorer (AP) und superoinferiorer (SI) Richtung. Rotationsfehler um die seitliche (x), vertikale (y) und longitudinale Achse (z) wurden aufgezeichnet und seit 2007 fur die ubrigen 24 Patienten unter Verwendung des Robotic Tilt Module™ und der Varian Exact Couch™ vor jeder Fraktion ausgeglichen. Nach der Positionierung erfolgte eine Verifikation der Patientenposition mittels stereoskopischer Rontgenkontrollaufnahmen. Noch bestehende residuale Fehler wurden aufgezeichnet und erneut winkelgetreu korrigiert.Ergebnisse:Der residuale translationale Fehler betrug in LR, AP und SI (1 Standardabweichung [SD]) 1,3, 1,7 und 2,2 mm. Ermittelt wurden residuale Rotationsfehler (1 SD) um x, y und z von 3,2°, 1,8° und 1,5°. Die erforderlichen Sicherheitsabstande zwischen klinischem Zielvolumen (CTV) und Planungszielvolumen (PTV) wurden in ML, AP und SI mit 2,3, 3,0 und 3,7 mm berechnet. Nach einem zweiten Korrekturschritt konnten diese Sicherheitsabstande auf 1,8, 2,1 und 1,8 mm verringert werden.Schlussfolgerung:Auf der Grundlage der nach ein (oder zwei) Lagerungskorrekturen verbleibenden Restfehler der Patienten dieser Studie ist fur das PTV ein Sicherheitsabstand von mindestens 2 mm zum CTV erforderlich. Der Beitrag der intrafraktionellen Bewegung der Prostata fur den Lokalisationsfehler verbleibt das Thema weiterer Untersuchungen.

Prognostic role of platinum sensitivity in patients with brain metastases from ovarian cancer: results of a German multicenter study

BACKGROUND Ovarian cancer is the leading cause of death in women with gynecological malignancies. Brain metastases are considered an uncommon metastatic site. Only few data exist on prognostic factors for this patient collective. PATIENTS AND METHODS A multicenter retrospective chart review was carried out including all patients with histologically confirmed ovarian cancer from six different German hospitals from 1981 to 2008. Overall, 4277 cases of patients with ovarian cancer were screened and patients with brain metastasis were identified and analyzed regarding various clinical variables and survival. RESULTS A total of 74 women with brain metastases were identified, resulting in an incidence of 1.73%. In multivariate analysis, the following clinical parameters had a significant impact on overall survival: multiple lesions [hazard ratio (HR) 4.4, 95% confidence interval (CI) 2.0-9.7] and low grading (HR 3.1, 95% CI 1.7-5.8) were associated with a negative impact. Platinum sensitivity (HR 0.23, 95% CI 0.12-0.48) was significantly associated with a favorable outcome. Good performance status (60%-80% HR 0.48, 95% CI 0.23-0.99 and 90%-100% HR 0.21, 95% CI 0.08-0.53) also had a positive impact on overall survival. CONCLUSIONS Platinum sensitivity is the most important prognostic factor in patients with ovarian cancer metastatic to the brain. This novel finding should be considered in the strategy of multimodal therapy for brain metastases in ovarian cancer.

Testicular Dose in Prostate Cancer Radiotherapy

Purpose:To determine the dose received by the unshielded testicles during a course of 20-MV conventional external-beam radiotherapy for patients with localized prostate cancer. Critical evaluation of the potential impact on fertility and hormonal impairment in these patients according to the literature.Patients and Methods:The absolute dose received by the testicles of 20 randomly selected patients undergoing radiotherapy of prostate cancer was measured by on-line thermoluminescence dosimetry. Patients were treated in supine position with an immobilization cushion under their knees. A flexible tube, containing three calibrated thermoluminescence dosimeters (TLDs) was placed on top or underneath the testicle closest to the perineal region with a day-to-day alternation. The single dose to the planning target volume was 1.8 Gy. Ten subsequent testicle measurements were performed on each patient. The individual TLDs were then read out and the total absorbed dose was calculated.Results:The mean total dose (± standard deviation) measured in a series of 10 subsequent treatment days in all patients was 49 cGy (± 36 cGy). The calculated projected doses made on a standard series of 40 fractions of external-beam radiotherapy were 196 cGy (± 145 cGy). The results of this study are appraised with the available data in the literature.Conclusion:The dose received by the unshielded testes can be assessed as a risk for permanent infertility and impairment of hormonal function in prostate cancer patients treated with external-beam radiotherapy.Ziel:Bestimmung der Strahlendosis an ungeschützten Hoden während einer Serie mit 20-MV-Photonen und konventioneller externer Strahlentherapie bei Patienten mit lokalisiertem Prostatakarzinom. Kritische Evaluation des potentiellen Einflusses auf Fertilität und hormonale Störungen dieser Patienten anhand der Literatur.Patienten und Methodik:Die absolute Hodendosis von 20 zufällig ausgewählten Patienten, die sich einer Strahlentherapie bei Prostatakarzinom unterzogen, wurde mittels Thermolumineszenzdosimetrie gemessen. Alle Patienten wurden in Rückenlage, mit einem Immobilisationskissen unter den Knien stabilisiert, behandelt. Flexible Katheter, die jeweils drei kalibrierte Thermolumineszenzdosimeter (TLD) enthielten, wurden täglich abwechselnd auf oder unter dem Hoden fixiert, der dem Perineum am nächsten lag. Die tägliche Einzeldosis für das Planungszielvolumen betrug 1,8 Gy. Zehn aufeinander folgende Hodenmessungen wurden für jeden Patienten durchgeführt. Die individuellen TLD wurden ausgewertet und die absorbierte Gesamtdosis berechnet.Ergebnisse:Die mittlere Gesamtdosis (± Standardabweichung), welche während der Serie von 10 aufeinander folgenden Behandlungstagen gemessen wurde, betrug 49 cGy (± 36 cGy). Die Hochrechnung auf eine Serie von 40 Fraktionen externer Radiatio betrug 196 cGy (± 145 cGy). Die Ergebnisse werden unter Einschluss der verfügbaren Literatur bewertet.Schlussfolgerung:Die während einer Bestrahlungsserie bei Prostatakarzinompatienten von den Hoden absorbierte Strahlendosis kann als Ursache eines erhöhten Risikos für eine bleibende Infertilität und hormonale Störung angesehen werden.

Influence of Organ at Risk Definition on Rectal Dose-Volume Histograms in Patients with Prostate Cancer Undergoing External-Beam Radiotherapy

Purpose:To evaluate rectal dose-volume relations during three-dimensional conformal radiotherapy of patients with prostate cancer by means of different rectal volume contours.Patients and Methods:55 patients with prostate cancer underwent three-dimensional conformal external-beam radiotherapy. Rectal dose-volume histograms were calculated for four separately contoured rectal volumes in all patients resulting in four groups. In group 1 the outer rectal wall was contoured two CT slices above and below the planning target volume. The rectal contour of group 2 was drawn from the anal verge up to the sigmoid. Furthermore, the posterior half of the rectum was contoured for both volumes mentioned above (groups 1a and 2a). Statistical analysis was then performed using nonparametric Wilcoxon tests.Results:The mean target dose was 72.9 Gy (standard deviation [SD] ± 2.1 Gy). The minimum target dose was 70.2 Gy. Mean rectum dose (± SD) over all patients was 50.7 Gy (± 4.6 Gy), 45.2 Gy (± 5.4 Gy), 43.2 Gy (± 4.2 Gy), and 38.7 Gy (± 5.5 Gy) for group 1, 2, 1a, and 2a, respectively. The corresponding volumes receiving ≥ 70 Gy for groups 1 and 2 were 14.0% (± 5.3%) and 11.9% (± 4.5%). These differences were statistically significant. Comparison of minimum and mean rectal dose also revealed a statistically significant difference toward higher doses in groups 1 and 1a (p < 0.001). Maximum rectal doses for groups 1 and 2 as well as for groups 1a and 2a revealed no statistically significant difference (p = 1.0).Conclusion:Data from the literature on normal-tissue complication probability (rectal bleeding) refer to different rectal contours. When applying dose restrictions to the rectum, contouring becomes a significant factor that determines the risk of rectal toxicity. The results of this study show that different ways of rectal contouring significantly influence doses to the rectum. The influence of organ at risk contouring should be considered thoroughly in conformal radiotherapy of prostate cancer patients, especially in dose escalation studies. It is recommended to calculate the doses for absolute rectal volumes and correlate these data with toxicity in order to be able to achieve comparable results among different institutions.Ziel:Aufzeigen unterschiedlicher rektaler Dosis-Volumen-Verhältnisse in der dreidimensionalen konformalen Strahlentherapie von Patienten mit Prostatakarzinom mittels verschiedener Konturierungen des rektalen Volumens.Patienten und Methodik:55 Patienten mit Prostatakarzinom erhielten eine dreidimensionale konformale Strahlentherapie. Für alle Patienten wurden rektale Dosis-Volumen-Histogramme für unterschiedliche Rektumkonturierungen angefertigt. Die unterschiedlichen Konturierungen dieser vier Gruppen waren wie folgt: In Gruppe 1 wurde die Rektumaußenkontur für den Bereich des Planungszielvolumens (PTV) plus zwei CT-Schichten ober- und unterhalb des PTV festgelegt. Die Rektumkontur der Gruppe 2 wurde vom Analring bis zum rektosigmoidalen Übergang markiert. Als weitere Risikoorgankontur wurde die dorsale Hälfte des Rektums für beide o.g. Volumina definiert, so dass sich daraus die Gruppen 1a und 2a ergaben. Die Ergebnisse der Dosis-Volumen- Berechnungen wurden mittels Wilcoxon-Tests für nichtparametrische Stichproben analysiert.Ergebnisse:Die mittlere Zielvolumendosis betrug 72,9 Gy (Standardabweichung [SD] ± 2,1 Gy). Die minimale Zielvolumendosis lag bei 70,2 Gy. Die mittlere Rektumdosis (± SD) über alle Patienten betrug 50,7 Gy (± 4,6 Gy), 45,2 Gy (± 5,4 Gy), 43,2 Gy (± 4,2 Gy) und 38,7 Gy (± 5,5 Gy) für die Gruppen 1, 2, 1a und 2a. Die berechneten Risikoorganvolumina, welche eine Dosis von ≥ 70 Gy erhielten, betrugen für die Gruppen 1 und 2 14,0% (± 5,3%) und 11,9% (± 4,5%). Diese Unterschiede waren statistisch signifikant. Auch der Vergleich der minimalen und mittleren Zielvolumendosis ergab einen statistisch signifikanten Unterschied zu höheren Dosen für die Gruppen 1 and 1a (p < 0,001). Die maximalen Rektumdosen im Vergleich der Gruppen 1 und 2 sowie der Gruppen 1a und 2a ergaben keinen signifikanten Unterschied (p = 1,0).Schlussfolgerung:Daten der Literatur bezüglich der Komplikationswahrscheinlichkeit für rektale Blutungen beziehen sich auf unterschiedliche Rektumvolumina. Bei der Festlegung von Dosisrestriktionen für das Risikoorgan Rektum kommt der Art der Rektumvolumendefinition für das Risiko rektaler Toxizität eine entscheidende Bedeutung zu. Die Ergebnisse dieser Studie zeigen, dass die Unterschiede der Rektumvolumendefinition einen signifikanten Einfluss auf die Dosisbelastung des Rektums haben. Der Einfluss der Risikoorgankonturierung muss bei der konformalen Strahlentherapie des Prostatakarzinoms sorgfältig berücksichtigt werden, insbesondere bei der Dosiseskalation. Es wird empfohlen, die Dosisbelastung für absolute Rektumvolumina zu berechnen und diese mit der Toxizität zu korrelieren, um die Ergebnisse verschiedener Institutionen vergleichbar zu machen.

Interfraction rotation of the prostate as evaluated by kilovoltage X-ray fiducial marker imaging in intensity-modulated radiotherapy of localized prostate cancer

To quantify the daily rotation of the prostate during a radiotherapy course using stereoscopic kilovoltage (kV) x-ray imaging and intraprostatic fiducials for localization and positioning correction. From 2005 to 2009, radio-opaque fiducial markers were inserted into 38 patients via perineum into the prostate. The ExacTrac/Novalis Body X-ray 6-day image acquisition system (ET/NB; BrainLab AG, Feldkirchen, Germany) was used to determine and correct the target position. During the first period in 10 patients we recorded all rotation errors but used only Y (table) for correction. For the next 28 patients we used for correction all rotational coordinates, i.e., in addition Z (superior-inferior [SI] or roll) and X (left-right [LR] or tilt/pitch) according to the fiducial marker position by use of the Robotic Tilt Module and Varian Exact Couch. Rotation correction was applied above a threshold of 1° displacement. The systematic and random errors were specified. Overall, 993 software-assisted rotational corrections were performed. The interfraction rotation errors of the prostate as assessed from the radiodense surrogate markers around the three axes Y, Z, and X were on average 0.09, -0.52, and -0.01° with standard deviations of 2.01, 2.30, and 3.95°, respectively. The systematic uncertainty per patient for prostate rotation was estimated with 2.30, 1.56, and 4.13° and the mean random components with 1.81, 2.02, and 3.09°. The largest rotational errors occurred around the X-axis (pitch), but without preferring a certain orientation. Although the error around Z (roll) can be compensated on average by a transformation with 4 coordinates, a significant error around X remains and advocates the full correction with 6 coordinates. Rotational errors as assessed via daily stereoscopic online imaging are significant and dominate around X. Rotation possibly degrades the dosimetric coverage of the target volume and may require suitable strategies for correction.

A randomized phase III adjuvant study in high-risk cervical cancer: simultaneous radiochemotherapy with cisplatin (S-RC) versus systemic paclitaxel and carboplatin followed by percutaneous radiation (PC-R): a NOGGO-AGO Intergroup Study

BACKGROUND Simultaneous adjuvant platinum-based radiochemotherapy in high-risk cervical cancer (CC) is an established treatment strategy. Sequential paclitaxel (Taxol) and platinum followed by radiotherapy may offer further advantages regarding toxicity. PATIENTS AND METHODS An open-labeled randomized phase III trial was conducted to compare paclitaxel (175 mg/m(2)) plus carboplatin (AUC5) followed by radiation (50.4 Gy) (experimental arm-A) versus simultaneous radiochemotherapy with cisplatin (40 mg/m(2)/week) (arm-B) in patients with stage IB-IIB CC after surgery. Primary objective was progression-free survival (PFS). RESULTS Overall, 271 patients were randomized and 263 were eligible for evaluation; 132 in arm-A and 131 in arm-B appropriately balanced. The estimated 2-year PFS was 81.8% [95% confidence interval (CI) 74.4-89.1] in arm-B versus 87.2% (95% CI 81.2-93.3) in arm-A (P = 0.235) and the corresponding 5-year survival rates were 85.8% in arm-A and 78.9% in arm-B (P = 0.25). Hematological grade 3/4 toxicity was higher in arm-B. Alopecia (87.9% versus 4.1%; P < 0.001) and neurotoxicity (65.9% versus 15.6%; P < 0.001) were significantly higher in arm-A. Early treatment termination was significantly more frequent in arm-B than in arm-A (32.1% versus 12.9%; P = 0.001). CONCLUSIONS Sequential chemotherapy and radiation in high-risk CC could not show any significant survival benefit; however, a different toxicity profile appeared. This sequential regime may constitute an alternative option when contraindications for immediate postoperative radiation are present.BACKGROUND Simultaneous adjuvant platinum-based radiochemotherapy in high-risk cervical cancer (CC) is an established treatment strategy. Sequential paclitaxel (Taxol) and platinum followed by radiotherapy may offer further advantages regarding toxicity. PATIENTS AND METHODS An open-labeled randomized phase III trial was conducted to compare paclitaxel (175 mg/m2) plus carboplatin (AUC5) followed by radiation (50.4 Gy) (experimental arm-A) versus simultaneous radiochemotherapy with cisplatin (40 mg/m2/week) (arm-B) in patients with stage IB-IIB CC after surgery. Primary objective was progression-free survival (PFS). RESULTS Overall, 271 patients were randomized and 263 were eligible for evaluation; 132 in arm-A and 131 in arm-B appropriately balanced. The estimated 2-year PFS was 81.8% [95% confidence interval (CI) 74.4-89.1] in arm-B versus 87.2% (95% CI 81.2-93.3) in arm-A (P=0.235) and the corresponding 5-year survival rates were 85.8% in arm-A and 78.9% in arm-B (P=0.25). Hematological grade 3/4 toxicity was higher in arm-B. Alopecia (87.9% versus 4.1%; P<0.001) and neurotoxicity (65.9% versus 15.6%; P<0.001) were significantly higher in arm-A. Early treatment termination was significantly more frequent in arm-B than in arm-A (32.1% versus 12.9%; P=0.001). CONCLUSIONS Sequential chemotherapy and radiation in high-risk CC could not show any significant survival benefit; however, a different toxicity profile appeared. This sequential regime may constitute an alternative option when contraindications for immediate postoperative radiation are present.

Oligometastases: the new paradigm and options for radiotherapy. A critical review

Traditional oncology distinguishes between two separate and incommensurable states in the evolution of solid malignancies: the localized disease, which is curable; and the disseminated status, which is per se palliative. Recently, a huge body of evidence suggests a fundamental change in the understanding of cancer, indicating an intermediate state in the trajectory of solid malignancies: the oligometastatic state. The following review will critically analyse existing hypotheses and facts from the basic sciences and try to contextualize it in regard to the clinical evidence available to date. Consecutively, it will try to draw possible clinical consequences for application of radiotherapy in this specific clinical scenario.ZusammenfassungDie traditionelle Onkologie trennt hinsichtlich therapeutischer Optionen zwei grundlegend unterschiedliche klinische Situationen: die lokalisierte Erkrankung mit kurativen Therapiechancen und die disseminierte Situation mit nur noch palliativen Lösungen. Die aktuelle Datenlage suggeriert die Notwendigkeit der Adaptation unseres klinischen Verständnisses onkologischer Erkrankungen im Sinne des Vorliegens einer intermediären, nämlich oligometastasierten Situation. Diese Arbeit setzt sich kritisch mit den Hypothesen und dem Wissen der Grundlagenforschung auseinander und kontextualisiert die vorliegende klinische Evidenz. Ziel ist die Auslotung der Radiotherapieoptionen für oligometastasierte Patienten.

Oligometastases: the new paradigm and options for radiotherapy

Traditional oncology distinguishes between two separate and incommensurable states in the evolution of solid malignancies: the localized disease, which is curable; and the disseminated status, which is per se palliative. Recently, a huge body of evidence suggests a fundamental change in the understanding of cancer, indicating an intermediate state in the trajectory of solid malignancies: the oligometastatic state. The following review will critically analyse existing hypotheses and facts from the basic sciences and try to contextualize it in regard to the clinical evidence available to date. Consecutively, it will try to draw possible clinical consequences for application of radiotherapy in this specific clinical scenario.ZusammenfassungDie traditionelle Onkologie trennt hinsichtlich therapeutischer Optionen zwei grundlegend unterschiedliche klinische Situationen: die lokalisierte Erkrankung mit kurativen Therapiechancen und die disseminierte Situation mit nur noch palliativen Lösungen. Die aktuelle Datenlage suggeriert die Notwendigkeit der Adaptation unseres klinischen Verständnisses onkologischer Erkrankungen im Sinne des Vorliegens einer intermediären, nämlich oligometastasierten Situation. Diese Arbeit setzt sich kritisch mit den Hypothesen und dem Wissen der Grundlagenforschung auseinander und kontextualisiert die vorliegende klinische Evidenz. Ziel ist die Auslotung der Radiotherapieoptionen für oligometastasierte Patienten.

Appropriate patient instructions can reduce prostate motion

BackgroundInterfraction prostate motion must be compensated by increased safety margins. If filling status of rectum and bladder is constant, motion should be reduced. We attempted to reduce interfraction motion errors by proper patient instruction.MethodIn 38 patients pairs of radio-opaque fiducial markers were implanted prior to definitive radiotherapy. Patients were positioned either according to skin marks or infrared body marker. We measured prostate displacement, i.e. pelvic bones versus intraprostatic marker position, via ExacTrac (two orthogonal radiographies) in 1252 fractions. Systematic and random setup and displacement errors were determined and safety margins estimated.ResultsIn our study interfraction prostate displacement is < 1 mm in RL direction, and < 2 mm in AP and SI direction. Systematic errors are slightly below random errors (< 1.5 mm). Positioning according skin marks results in higher inaccuracies of ±1.5 – 2 mm in RL and ±2 – 2.5 mm in AP/SI direction.ConclusionsIn case of appropriate patient instructions (constant organ filling) the positioning via bone fusion requires CTV-PTV margins of 2 mm in RL, 4 mm in AP, and 5 mm in SI direction. Studies without any description of patient instruction found much higher margins of > 1 cm in AP and SI direction.