Sabine Mai

Volumetric modulated arc therapy (VMAT) vs. serial tomotherapy, step-and-shoot IMRT and 3D-conformal RT for treatment of prostate cancer

INTRODUCTION Volumetric modulated arc therapy (VMAT), a complex treatment strategy for intensity-modulated radiation therapy, may increase treatment efficiency and has recently been established clinically. This analysis compares VMAT against established IMRT and 3D-conformal radiation therapy (3D-CRT) delivery techniques. METHODS Based on CT datasets of 9 patients treated for prostate cancer step-and-shoot IMRT, serial tomotherapy (MIMiC), 3D-CRT and VMAT were compared with regard to plan quality and treatment efficiency. Two VMAT approaches (one rotation (VMAT1x) and one rotation plus a second 200 degrees rotation (VMAT2x)) were calculated for the plan comparison. Plan quality was assessed by calculating homogeneity and conformity index (HI and CI), dose to normal tissue (non-target) and D(95%) (dose encompassing 95% of the target volume). For plan efficiency evaluation, treatment time and number of monitor units (MU) were considered. RESULTS For MIMiC/IMRT(MLC)/VMAT2x/VMAT1x/3D-CRT, mean CI was 1.5/1.23/1.45/1.51/1.46 and HI was 1.19/1.1/1.09/1.11/1.04. For a prescribed dose of 76 Gy, mean doses to organs-at-risk (OAR) were 50.69 Gy/53.99 Gy/60.29 Gy/61.59 Gy/66.33 Gy for the anterior half of the rectum and 31.85 Gy/34.89 Gy/38.75 Gy/38.57 Gy/55.43 Gy for the posterior rectum. Volumes of non-target normal tissue receiving > or =70% of prescribed dose (53 Gy) were 337 ml/284 ml/482 ml/505 ml/414 ml, for > or =50% (38 Gy) 869 ml/933 ml/1155 ml/1231 ml/1993 ml and for > or =30% (23 Gy) 2819 ml/3414 ml/3340 ml/3438 ml /3061 ml. D(95%) was 69.79 Gy/70.51 Gy/71,7 Gy/71.59 Gy/73.42 Gy. Mean treatment time was 12 min/6 min/3.7 min/1.8 min/2.5 min. CONCLUSION All approaches yield treatment plans of improved quality when compared to 3D-conformal treatments, with serial tomotherapy providing best OAR sparing and VMAT being the most efficient treatment option in our comparison. Plans which were calculated with 3D-CRT provided good target coverage but resulted in higher dose to the rectum.

Cetuximab-Based Treatment of Metastatic Anal Cancer: Correlation of Response with KRAS Mutational Status

Background: No standard chemotherapy regimen can be defined for patients with metastatic squamous cell carcinoma of the anus due to the low incidence of this disease and the high cure rate of localized tumors. Anal cancers universally express the epidermal growth factor receptor (EGFR) and KRAS mutations have not been reported in anal cancer thus far. Methods: We report on 7 patients with metastatic anal cancer treated with cetuximab – a chimeric antibody against EGFR – on a compassionate use basis along with the results of KRAS mutational analysis. Results: Marked tumor shrinkage was noted in several patients using cetuximab monotherapy or cetuximab/irinotecan combination as first or subsequent treatment line (usually after failure of cisplatin-based regimens). Two out of seven patients harbored KRAS mutations. Both patients had progressive disease receiving cetuximab, while the remaining 5 patients had either a partial remission (n = 3), a minor remission (n = 1) or no change lasting ≥6 months after previous rapid tumor progression. Conclusion: Cetuximab-based treatment appears to be a valuable treatment option for patients with metastatic KRAS wild-type anal cancer after failure of or as an alternative to cisplatin/5-fluorouracil-based therapy.

Evaluation of Possible Prostate Displacement Induced by Pressure Applied during Transabdominal Ultrasound Image Acquisition

Background and Purpose:For accurate positioning of the prostate in external radiotherapy, transabdominal ultrasound localization and positioning systems are available. Reports have stated that probe pressure applied during image acquisition causes clinically relevant prostate displacement. The aim of this study was to investigate the prostate displacement due to the pressure applied during transabdominal ultrasound image acquisition with the BAT® ultrasound system.Material and Methods:For ten patients who had undergone iodine-125 seed implantation for brachytherapy of prostate cancer, X-ray simulations were performed before and during ultrasound image acquisition. The iodine seeds are visible on the X-ray images, representing the position of the prostate. The simulator’s crosshair, indicating the isocenter, was used as reference coordinate system. For each patient the change in prostate position was calculated based on the seed positions during and after ultrasound examination.Results:A maximum displacement of the prostate of 2.3 mm in anteroposterior and 1.9 mm in craniocaudal direction and a rotational change of up to 2.5° were observed. If the system was not handled correctly and too much pressure was applied, a shift of the prostate of up to 10 mm could be induced.Conclusion:Compared to the prostate displacement due to changes in rectal filling, which according to Crook et al. can be as much as 1.7 cm, the maximum displacement of less than 0.3 cm caused by the probe pressure is negligible. However, proper education of the staff and preparation of the patient are essential for the safe use of the system.Hintergrund und Ziel:Zur genauen Positionierung der Prostata in der Teletherapie stehen Ultraschall-Lokalisationssysteme zur Verfügung. Ziel der Studie war zu untersuchen, ob der Druck, der während der BAT®-Ultraschallaufnahme ausgeübt wird, eine klinisch relevante Verschiebung der Prostata bewirkt, die den Nutzen eines solchen Systems für die Patientenpositionierung in Frage stellt.Material und Methodik:Von zehn Patienten mit Iod-125-Seed-Implantaten wurden während und nach der Ultraschallaufnahme Röntgensimulationsaufnahmen angefertigt. Die in den Röntgenaufnahmen sichtbaren Seeds repräsentieren die Lage der Prostata. Das Fadenkreuz des Simulators wurde als Referenzkoordinatensystem verwendet. Für jeden Patienten wurde die Lageänderung der Prostata aus der Änderung der Seedpositionen bestimmt.Ergebnisse:Bei korrekter Anwendung des Ultraschallsystems wurde die Prostata maximal bis zu 2,3 mm in anteroposteriorer und 1,9 mm in kraniokaudaler Richtung verschoben und um maximal 2.5° rotiert. Durch falsche Handhabung des Systems mit zu hohem Druck konnte eine Verschiebung der Prostata um bis zu 10 mm bewirkt werden.Schlussfolgerung:Im Vergleich zu der natürlichen Lagevariation der Prostata durch unterschiedlich starke Rektumfüllung, die nach Crook et al. bis zu 1,7 cm betragen kann, ist eine maximale Verschiebung von weniger als 0,3 cm durch den Schallkopfdruck vernachlässigbar. Um das Potential des Systems voll zu nutzen, müssen eine korrekte Handhabung und Patientenvorbereitung gewährleistet sein.

Optimization of dose distributions for adjuvant Locoregional radiotherapy of gastric cancer by IMRT

Background and Purpose: Locoregional relapse is a problem frequently encountered with advanced gastric cancer. Data from the randomized Intergroup trial 116 suggest effectiveness of adjuvant radiochemotherapy, albeit with significant toxicity. The potential of intensity-modulated radiotherapy (IMRT) to reduce toxicity by significantly reducing maximum and median doses to organs at risk while still applying sufficient dose to the target volume in the upper abdomen was studied. Patient and Methods: For a typical configuration of target volumes and organs, a step-and-shoot IMRT plan (eight beam orientations), developed as a class solution for treatment of tumors in the upper abdomen (Figures 1 to 3), a conventional plan, a combination of the conventional plan with a kidney-sparing boost plan, and a conventional plan with noncoplanar ap and pa fields for improved kidney sparing were compared with respect to coverage of target volume and dose to organs at risk with a dose of 45 Gy delivered as the median dose to the target volume. Results: When using the conventional three-dimensionally planned box techniques, the right kidney could be kept below tolerance, but median dose to the left kidney amounted to between 14.8 and 26.9 Gy, depending on the plan. IMRT reduced the median dose to the left kidney to 10.5 Gy, while still keeping the dose to the right kidney < 8 Gy. Liver was spared better with IMRT. Dose to the lungs was not significantly different, and dose to the spinal cord was higher (but well below tolerance) with IMRT. The dose distribution within the target volume was less homogeneous than for the conventional plans. With regard to target coverage, > 90% of prescription dose were delivered to > 90% of target volume with IMRT (Table 1). Conclusion: IMRT has the potential to deliver efficient doses to target volumes in the upper abdomen, while delivering dose to organs at risk in a more advantageous fashion than a conventional technique. For clinical implementation, the possibility of extensive organ motion in the upper abdomen has to be taken into account for treatment planning and patient positioning. The multitude of potential risks related to its application has to be the subject of thorough follow-up and further studies.Hintergrund und Ziel: Die adjuvante Therapie des fortgeschrittenen Magenkarzinoms wird kontrovers diskutiert. Der Intergroup- Trial 116 wies jedoch erstmals die prinzipielle Effizienz einer adjuvanten Radiochemotherapie nach. Des Weiteren stellt bei suffizienter strahlentherapeutischer Einfassung der Zielregion jedoch die Toxizität dieser Behandlungsstrategie ein Problem dar. Es wurde daher versucht, durch Einsatz der intensitätsmodulierten Strahlentherapie (IMRT) bei einem typischen Zielvolumen im Oberbauch die mediane und maximale Risikoorganbelastung bei vergleichbarer Zielvolumenabdeckung zu reduzieren. Patient und Methodik: Für eine typische Konfiguration von Zielvolumen und Risikoorganen wurden eine als „class solution“ entwickelte Acht-Felder-IMRT-Technik (Abbildungen 1 bis 3), ein konventioneller Plan, eine Kombination dieses konventionellen Plans mit einem nierenschonenden Boostplan und ein konventioneller Plan mit nonkoplanarer Ausrichtung von a.p. und p.a. Feld zur besseren Nierenschonung hinsichtlich Zielvolumeneinfassung und Belastung der Risikoorgane verglichen. Ergebnisse: Mit konventionellen Techniken konnte zwar die rechte Niere ausreichend geschont werden, die linke Niere wurde jedoch je nach Plan mit einer medianen Dosis zwischen 14,8 und 26,9 Gy belastet. IMRT reduzierte die mediane linksseitige Nierendosis auf 10,5 Gy, während die mediane rechtsseitige Nierendosis immer noch < 8 Gy gehalten werden konnte. Die Leberbelastung war bei IMRT ebenfalls reduziert. Die Lungendosen unterschieden sich nicht wesentlich. Die Rückenmarkdosis war bei IMRT höher als bei konventioneller Bestrahlung, jedoch deutlich unter der Toleranz. Die Dosisverteilung im Zielvolumen war bei IMRT inhomogener, auch mittels IMRT konnten zuverlässig > 90% der Verschreibungsdosis auf > 90% des Zielvolumens appliziert werden (Tabelle 1). Schlussfolgerung: IMRT moduliert die Belastung der Risikoorgane im Oberbauch gegenüber einer konventionell 3-D-geplanten Technik günstiger, sodass Ausschöpfung und Einhaltung der Organtoleranzen erleichtert werden. Bei der klinischen Implementierung muss die besondere Mobilität der Oberbauchorgane bei der Planung und der Patientenpositionierung berücksichtigt werden. Die zahlreichen technischen und biologischen Unwägbarkeiten der Anwendung der IMRT insbesondere in dieser Region erfordern die vorsichtige Implementierung, langfristige Nachbeobachtung und weitere Untersuchungen.

Accuracy of Ultrasound-Based (BAT) Prostate-Repositioning: A Three-Dimensional On-Line Fiducial-Based Assessment With Cone-Beam Computed Tomography

PURPOSE To assess the accuracy of ultrasound-based repositioning (BAT) before prostate radiation with fiducial-based three-dimensional matching with cone-beam computed tomography (CBCT). PATIENTS AND METHODS Fifty-four positionings in 8 patients with 125I seeds/intraprostatic calcifications as fiducials were evaluated. Patients were initially positioned according to skin marks and after this according to bony structures based on CBCT. Prostate position correction was then performed with BAT. Residual error after repositioning based on skin marks, bony anatomy, and BAT was estimated by a second CBCT based on user-independent automatic fiducial registration. RESULTS Overall mean value (MV+/-SD) residual error after BAT based on fiducial registration by CBCT was 0.7+/-1.7 mm in x (group systematic error [M]=0.5 mm; SD of systematic error [Sigma]=0.8 mm; SD of random error [sigma]=1.4 mm), 0.9+/-3.3 mm in y (M=0.5 mm, Sigma=2.2 mm, sigma=2.8 mm), and -1.7+/-3.4 mm in z (M=-1.7 mm, Sigma=2.3 mm, sigma=3.0 mm) directions, whereas residual error relative to positioning based on skin marks was 2.1+/-4.6 mm in x (M=2.6 mm, Sigma=3.3 mm, sigma=3.9 mm), -4.8+/-8.5 mm in y (M=-4.4 mm, Sigma=3.7 mm, sigma=6.7 mm), and -5.2+/-3.6 mm in z (M=-4.8 mm, Sigma=1.7 mm, sigma=3.5 mm) directions and relative to positioning based on bony anatomy was 0+/-1.8 mm in x (M=0.2 mm, Sigma=0.9 mm, sigma=1.1 mm), -3.5+/-6.8 mm in y (M=-3.0 mm, Sigma=1.8 mm, sigma=3.7 mm), and -1.9+/-5.2 mm in z (M=-2.0 mm, Sigma=1.3 mm, sigma=4.0 mm) directions. CONCLUSIONS BAT improved the daily repositioning accuracy over skin marks or even bony anatomy. The results obtained with BAT are within the precision of extracranial stereotactic procedures and represent values that can be achieved with several users with different education levels. If sonographic visibility is insufficient, CBCT or kV/MV portal imaging with implanted fiducials are recommended.

Frameless stereotactic radiosurgery of a solitary liver metastasis using active breathing control and stereotactic ultrasound.

Background and Purpose:Radiosurgery of liver metastases is effective but a technical challenge due to respiration-induced movement. The authors report on the initial experience of the combination of active breathing control (ABC®) with stereotactic ultrasound (B-mode acquisition and targeting [BAT®]) for frameless radiosurgery.Patients and Methods:A patient with a solitary, inoperable liver metastasis from cholangiocellular carcinoma is presented (Figure 4). ABC® (Figure 3) was used for tumor/liver immobilization. Tumor/liver position was controlled and corrected using ultrasound (BAT®; Figure 1). The tumor was irradiated with a single dose of 24 Gy.Results:Using ABC®, the motion of the tumor was significantly reduced and the overall positioning error was < 5 mm (Figure 2). BAT® allowed a rapid localization of the lesion during breath hold which could be performed without difficulties for 20 s. Overall treatment time was acceptable (30 min).Conclusion:Frameless stereotactic radiotherapy with the combination of ABC® and BAT® allows the delivery of high single doses to targets accessible to ultrasound with high precision comparable to a frame-based approach.Hintergrund und Ziel:Die Radiochirurgie solitärer Lebermetastasen ist effektiv, stellt jedoch aufgrund der Atembewegung des Targets eine technische Herausforderung dar. Die Autoren berichten über die initiale Erfahrung mit der rahmenlosen Radiochirurgie durch die Kombination einer aktiven Atmungskontrolle („active breathing control“ [ABC®]) mit dem stereotaktischen Ultraschall („B-mode acquisition and targeting“ [BAT®]).Patient und Methodik:Präsentiert wird ein Patient mit einer solitären Lebermetastase bei cholangiozellulärem Karzinom (Abbildung 4). ABC® (Abbildung 3) wurde zur Immobilisation des Tumors bzw. der Leber verwendet. Die Position des Tumors bzw. der Leber wurde mit Ultraschall (BAT®) kontrolliert und ggf. korrigiert (Abbildung 1). Der Tumor wurde mit einer Einzeldosis von 24 Gy konformal bestrahlt.Ergebnisse:Durch ABC® konnte die Leber-/Tumorbewegung minimiert werden, die gesamte Positionierungsunsicherheit betrug < 5 mm (Abbildung 2). BAT® erlaubte eine schnelle Lokalisierung des Zielvolumens unter Atemanhalt, was wiederholt über 20 s vom Patienten problemlos ausgeführt wurde. Die Gesamtbehandlungszeit war gegenüber einer ungetriggerten Behandlung kaum verlängert (30 min).Schlussfolgerung:Die rahmenlose Stereotaxie durch Kombination von ABC® und BAT® erlaubt, bei sonographisch zugänglichen Zielvolumina hohe Dosen zu applizieren. Die erreichte Präzision liegt im Bereich jener von rahmenbasierten Verfahren.

Development of a Novel Method for Intraoperative Radiotherapy During Kyphoplasty for Spinal Metastases (Kypho-IORT)

PURPOSE Approximately 30% of patients with cancer receive bone metastases, of which 50% are in the spine. Approximately 20% present with unstable lesions requiring surgical intervention, followed by fractionated radiotherapy over 2-4 weeks to prevent early regrowth. Because of the limited survival time of patients with metastatic cancer, novel treatment concepts shortening the overall treatment time or hospitalization are desirable. In this study, we established a novel approach for intraoperative radiotherapy during kyphoplasty (Kypho-IORT), a method that combines stabilizing surgery and radiotherapy within one visit, after estimating the percentage of eligible patients for this treatment. METHODS AND MATERIALS To estimate the percentage of eligible patients, 53 planning CTs (897 vertebrae) of patients with spinal metastases were evaluated. The number of infiltrated vertebrae were counted and classified in groups eligible or not eligible for Kypho-IORT. The Kypho-IORT was performed in a donated body during a standard balloon kyphoplasty using the INTRABEAM system and specially designed applicators. A single dose of 10 Gy (in 10 mm) was delivered over 4 min to the vertebra. This was verified using two ionization chambers and a Monte Carlo simulation. RESULTS The estimation of eligible patients resulted in 34% of the evaluated patients, and thus 34% of patients with instable spinal metastases are suitable for Kypho-IORT. This study shows also that, using the approach presented here, it is possible to perform an IORT during kyphoplasty with an additional 15 min operation time. The measurement in the donated body resulted in a maximum dose of 3.8 Gy in the spinal cord. However, the Monte Carlo depth dose simulation in bone tissue showed 68% less dose to the prescription depth. CONCLUSION We present for the first time a system using an x-ray source that can be used for single-dose IORT during kyphoplasty. The described Kypho-IORT can decrease the overall treatment time for up to 34% of patients who usually receive radiotherapy for spinal metastases.

A fast radiotherapy paradigm for anal cancer with volumetric modulated arc therapy (VMAT)

Background/PurposeRadiotherapy (RT) volumes for anal cancer are large and of moderate complexity when organs at risk (OAR) such as testis, small bowel and bladder are at least partially to be shielded. Volumetric intensity modulated arc therapy (VMAT) might provide OAR-shielding comparable to step-and-shoot intensity modulated radiotherapy (IMRT) for this tumor entity with better treatment efficiency.Materials and methodsBased on treatment planning CTs of 8 patients, we compared dose distributions, comformality index (CI), homogeneity index (HI), number of monitor units (MU) and treatment time (TTT) for plans generated for VMAT, 3D-CRT and step-and-shoot-IMRT (optimized based on Pencil Beam (PB) or Monte Carlo (MC) dose calculation) for typical anal cancer planning target volumes (PTV) including inguinal lymph nodes as usually treated during the first phase (0-36 Gy) of a shrinking field regimen.ResultsWith values of 1.33 ± 0.21/1.26 ± 0.05/1.3 ± 0.02 and 1.39 ± 0.09, the CIs for IMRT (PB-Corvus/PB-Hyperion/MC-Hyperion) and VMAT are better than for 3D-CRT with 2.00 ± 0.16. The HIs for the prescribed dose (HI36) for 3D-CRT were 1.06 ± 0.01 and 1.11 ± 0.02 for VMAT, respectively and 1.15 ± 0.02/1.10 ± 0.02/1.11 ± 0.08 for IMRT (PB-Corvus/PB-Hyperion/MC-Hyperion). Mean TTT and MUs for 3D-CRT is 220s/225 ± 11MU and for IMRT (PB-Corvus/PB-Hyperion/MC-Hyperion) is 575s/1260 ± 172MU, 570s/477 ± 84MU and 610s748 ± 193MU while TTT and MU for two-arc-VMAT is 290s/268 ± 19MU.ConclusionVMAT provides treatment plans with high conformity and homogeneity equivalent to step-and-shoot-IMRT for this mono-concave treatment volume. Short treatment delivery time and low primary MU are the most important advantages.

Einfluss von bildgestützter translatorischer Isozentrumskorrektur auf die Dosisverteilung bei 3-D-Konformationsbestrahlung der Prostata

Hintergrund und Ziel:Interfraktionäre Prostatabewegungen während der Strahlentherapie durch unterschiedliche Ausdehnungen des Rektums können sich negativ auf die Behandlungsqualität auswirken. Die Autoren untersuchten den Einfluss einer bildgestützten linearen Translationskorrektur des Isozentrums auf die Dosisverteilung bei einer dreidimensionalen konformen Bestrahlungstechnik.Material und Methodik:Die Planungs-CTs von sieben Patienten mit leerem und erweitertem Rektum wurden analysiert. Es wurde je ein Referenzplan für Planungszielvolumen (PTV) und Boost (Prostata) auf dem CT-Datensatz mit leerem Rektum mit einer Vier-Felder-Technik berechnet. Der Bestrahlungsplan wurde auf das CT mit erweitertem Rektum übertragen. Dabei wurde zunächst keine Lagekorrektur des Isozentrums durchgeführt, und der Patient wurde relativ zu knöchernen Strukturen ausgerichtet. Danach wurde die Lage des Isozentrums durch eine lineare Translation korrigiert. Die dosimetrischen Konsequenzen und klinischen Auswirkungen wurden analysiert bzw. abgeschätzt.Ergebnisse:Organbewegungen verminderten die Dosisabdeckung der Prostata (95%-Isodose) während einzelner simulierter Behandlungsfraktionen um bis zu –21,0 Prozentpunkte (%-P; Boostplan) und bis zu –14,9%-P in den Samenblasen (PTV-Plan). Die mittlere Dosis im Rektum stieg um bis zu 18,3%-P (PTV-Plan) an. Eine bildgestützte lineare Translationskorrektur (Mittel 6,4 ± 3,4 mm; Maximum 10,8 mm) verbesserte die Dosisabdeckung der Prostata (95%-Isodose) um bis zu 12,7%-P (Boostplan), während die mittlere Dosis im Rektum um bis zu –8,9%-P (PTV-Plan) im Vergleich zum unkorrigierten Plan reduziert werden konnte. Für die Gesamtbehandlung wurde näherungsweise eine Reduktion der Nebenwirkungswahrscheinlichkeit beim Rektum durch die Lagekorrektur um ca. 5%-P errechnet.Schlussfolgerung:Bildgestützte Isozentrumskorrektur durch lineare Translation kann die Behandlungsqualität beim Prostatakarzinom verbessern, wenn geometrische Diskrepanzen innerhalb gewisser Grenzen bleiben.Background and Purpose:Interfractional prostate motion during radiotherapy due to variation in rectal distension can have negative consequences. The authors investigated the dosimetric consequences of a linear translational position correction based on image guidance when a three-dimensional conformal treatment technique was used.Material and Methods:Planning CTs of seven patients with empty and distended rectum were analyzed. A reference plan for the planning target volume (PTV) and the boost were calculated on the CT dataset with the empty rectum with a standard four-field technique. The treatment plan was transferred to the CT with the distended rectum for an uncorrected setup (referenced to bony anatomy) and a corrected setup after position correction of the isocenter. The dosimetric consequences were analyzed.Results:Organ motion decreased the coverage of the prostate by the 95% isodose during simulated single treatment fractions by up to –21.0 percentage points (%-p; boost plan) and by up to –14.9%-p for the seminal vesicles (PTV plan). The mean rectum dose increased by up to 18.3%-p (PTV plan). Linear translational correction (mean 6.4 ± 3.4 mm, maximum 10.8 mm) increased the coverage of the prostate by the 95% isodose by up to 12.7%-p (boost plan), while the mean rectum dose was reduced by up to –8.9%-p (PTV plan). For the complete treatment a reduction of complication probability of the rectum of approximately 5%-p was calculated.Conclusion:The use of an image guidance system with linear translational correction can improve radiation treatment accuracy for prostate cancer, if geometric changes are within certain limits.

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.