Volker Steil

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.

Potential Effect of Robust and Simple IMRT Approach for Left-Sided Breast Cancer on Cardiac Mortality

PURPOSE Three-dimensional (3D) treatment planning has reduced the cardiac dose in postoperative radiotherapy for breast cancer; however, the overall cardiac toxicity is still an issue because of more aggressive adjuvant treatment. Toxicity models have suggested that a reduction of the heart volume treated to high doses might be particularly advantageous. We compared aperture-based multifield intensity-modulated radiotherapy (IMRT) plans to 3D-planned tangent fields using dose-volume histograms, cardiac toxicity risk, and the robustness to positioning errors. METHODS AND MATERIALS For 14 computed tomography data sets of patients with left-sided breast cancer (unfavorable thoracic geometry), a 3D treatment plan and an IMRT plan were created. The dose-volume histograms were evaluated for the target and risk organs. Excess risk of cardiac mortality was calculated for both approaches using a relative seriality model. Positioning errors were simulated by moving the isocenter. RESULTS IMRT reduced the maximal dose to the left ventricle by a mean of 30.9% (49.14 vs. 33.97 Gy). The average heart volume exposed to >30 Gy was reduced from 45 cm(3) to 5.84 cm(3). The mean dose to the left ventricle was reduced by an average of 10.7% (10.86 vs. 9.7 Gy), and the mean heart dose increased by an average of 24% (from 6.85 to 8.52 Gy). The model-based reduction of the probability for excess therapy-associated cardiac death risk was from 6.03% for the 3D plans to 0.25% for the IMRT plans. CONCLUSION Aperture-based IMRT for left-sided breast cancer significantly reduces the maximal dose to the left ventricle, which might translate into reduced cardiac mortality. Biological modeling might aid in deciding to treat with IMRT but has to be validated prospectively.

Radiobiological Aspects of Intraoperative Radiotherapy (IORT) with Isotropic Low-Energy X Rays for Early-Stage Breast Cancer

Abstract Herskind, C., Steil, V., Kraus-Tiefenbacher, U. and Wenz, F. Radiobiological Aspects of Intraoperative Radiotherapy (IORT) with Isotropic Low-Energy X Rays for Early-Stage Breast Cancer. Radiat. Res. 163, 208–215 (2005). The purpose of this study was to model the distribution of biological effect around a miniature isotropic X-ray source incorporating spherical applicators for single-dose or hypofractionated partial-breast intraoperative radiotherapy. A modification of the linear-quadratic formalism was used to calculate the relative biological effectiveness (RBE) of 50 kV X rays as a function of dose and irradiation time for late-reacting normal tissue and tumor cells. The response was modeled as a function of distance in the tissue based on the distribution of equivalent dose and published dose–response data for pneumonitis and subcutaneous fibrosis after single-dose conventional irradiation. Furthermore, the spatial distribution of tumor cell inactivation was assessed. The RBE for late reactions approached unity at the applicator surface but increased as the absorbed dose decreased with increasing distance from the applicator surface. The ED50 for pneumonitis was estimated to be reached at a depth of 6–11 mm in the tissue and that for subcutaneous fibrosis at 3–6 mm, depending on the applicator diameter and whether the effect of recovery was included. Thus lung tissue would be spared because of the thickness of the thorax wall. The RBE for tumor cells was higher than for late-reacting tissue. The applicator diameter is an important parameter in determining the range of tumor cell control in the irradiated tumor bed.

Intraoperative radiotherapy (IORT) is an option for patients with localized breast recurrences after previous external-beam radiotherapy

BackgroundFor patients suffering of recurrent breast cancer within the irradiated breast, generally mastectomy is recommended. The normal tissue tolerance does not permit a second full-dose course of radiotherapy to the entire breast after a second breast-conserving surgery (BCS). A novel option is to treat these patients with partial breast irradiation (PBI). This approach is based on the hypothesis that re-irradiation of a limited volume will be effective and result in an acceptable frequency of side effects. The following report presents a single center experience with intraoperative radiotherapy (IORT) during excision of recurrent breast cancer in the previously irradiated breast.MethodsBetween 4/02 and 11/06, 15 patients were treated for in-breast recurrences at a median of 10 years (3–25) after previous EBRT (10 recurrences in the initial tumor bed, 3 elsewhere in-breast failures, 2 invasive recurrences after previous DCIS). Additional 2 patients were selected for IORT with new primary breast cancer after previous partial breast EBRT for treatment of Hodgkins disease. IORT with a single dose of 14.7 – 20 Gy 50 kV X-rays at the applicator surface was delivered with the Intrabeam™-device (Carl Zeiss, Oberkochen, Germany).ResultsAfter a median follow-up of 26 months (1–60), no local recurrence occurred. 14 out of 17 patients are alive and free of disease progression. Two patients are alive with distant metastases. One patient died 26 months after BCS/IORT due to pulmonary metastases diagnosed 19 months after BCS/IORT. Acute toxicity after IORT was mild with no Grade 3/4 toxicities and cosmetic outcome showed excellent/good/fair results in 7/7/3 cases.ConclusionIORT for recurrent breast cancer using low energy X-rays is a valuable option for patients with recurrent breast cancer after previous radiotherapy.

Second cancer risk after 3D-CRT, IMRT and VMAT for breast cancer

PURPOSE Second cancer risk after breast conserving therapy is becoming more important due to improved long term survival rates. In this study, we estimate the risks for developing a solid second cancer after radiotherapy of breast cancer using the concept of organ equivalent dose (OED). MATERIALS AND METHODS Computer-tomography scans of 10 representative breast cancer patients were selected for this study. Three-dimensional conformal radiotherapy (3D-CRT), tangential intensity modulated radiotherapy (t-IMRT), multibeam intensity modulated radiotherapy (m-IMRT), and volumetric modulated arc therapy (VMAT) were planned to deliver a total dose of 50 Gy in 2 Gy fractions. Differential dose volume histograms (dDVHs) were created and the OEDs calculated. Second cancer risks of ipsilateral, contralateral lung and contralateral breast cancer were estimated using linear, linear-exponential and plateau models for second cancer risk. RESULTS Compared to 3D-CRT, cumulative excess absolute risks (EAR) for t-IMRT, m-IMRT and VMAT were increased by 2 ± 15%, 131 ± 85%, 123 ± 66% for the linear-exponential risk model, 9 ± 22%, 82 ± 96%, 71 ± 82% for the linear and 3 ± 14%, 123 ± 78%, 113 ± 61% for the plateau model, respectively. CONCLUSION Second cancer risk after 3D-CRT or t-IMRT is lower than for m-IMRT or VMAT by about 34% for the linear model and 50% for the linear-exponential and plateau models, respectively.

Intraoperative radiotherapy as a boost during breast-conserving surgery using low-kilovoltage X-rays: the first 5 years of experience with a novel approach.

PURPOSE Intraoperative radiotherapy (IORT) during breast-conserving surgery (BCS) has been recently introduced using different devices. We report the first 5 years of a single-center experience after introduction of a novel approach to deliver IORT as a tumor bed boost during BCS for breast cancer. METHODS AND MATERIALS A total of 155 breast cancers in 154 women (median age, 63 years; range, 30-83 years; T1/T2 = 100/55; N0/N+ = 108/47) were treated between February 2002 and December 2007 at the University Medical Center Mannheim, in whom IORT as tumor bed boost was applied using 50-kV X-rays (20 Gy) followed by 46-50 Gy whole-breast external-beam radiotherapy (EBRT). Chemotherapy, if indicated, was given before EBRT. The median interval between BCS plus IORT and EBRT was 40 days. Median follow-up was 34 months (maximum 80 months, 1 patient lost to follow-up). Overall survival and local relapse-free survival were calculated at 5 years using the Kaplan-Meier method. Seventy-nine patients were evaluated at 3-year follow-up for late toxicity according to the Late Effects in Normal Tissues-Subjective, Objective, Management, and Analytic system. RESULTS Ten patients died, 2 had in-breast relapse, and 8 developed distant metastases (5-year overall survival = 87.0%; 5-year local relapse-free survival = 98.5%). Grade 3 fibroses of the tumor bed were detected in 5% of the patients after 3 years. Skin toxicity was mild (telangiectases and hyperpigmentations in approximately 6% each). CONCLUSIONS Intraoperative radiotherapy as a tumor bed boost during BCS for breast cancer using low-kilovoltage X-rays followed by EBRT yields low recurrence and toxicity rates.

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.

Experimental validation of a commercial 3D dose verification system for intensity-modulated arc therapies

We validate the dosimetric performance of COMPASS®, a novel 3D quality assurance system for verification of volumetric-modulated arc therapy (VMAT) treatment plans that can correlate the delivered dose to the patients anatomy, taking into account the tissue inhomogeneity. The accuracy of treatment delivery was assessed by the COMPASS® for 12 VMAT plans, and the resulting assessments were evaluated using an ionization chamber and film measurements. Dose-volume relationships were evaluated by the COMPASS® for three additional treatment plans and these were used to verify the accuracy of treatment planning dose calculations. The results matched well between COMPASS® and measurements for the ionization chamber (≤3%) and film (73-99% for gamma((3%/3 mm)) < 1 and 98-100% for gamma((5%/5 mm)) < 1) for the phantom plans. Differences in dose-volume statistics for the average dose to the PTV were within 2.5% for three treatment plans. For the structures located in the low-dose region, a maximum difference of <9% was observed. In its current implementation, the system could measure the delivered dose with sufficient accuracy and could project the 3D dose distribution directly on the patients anatomy. Slight deviations were found for large open fields. These could be minimized by improving the COMPASS® in-built beam model.

Clinical Implementation of Volumetric Intensity-Modulated Arc Therapy (VMAT) with ERGO++

Background and Purpose:Volumetric modulated arc therapy (VMAT) has the potential to deliver dose distributions comparable to the established intensity-modulated radiotherapy techniques for a multitude of target paradigms. Prior to implementing VMAT into their clinical routine in December 2008, the authors evaluated the dose calculation/delivery accuracy of 24 sample VMAT plans (prostate and anal cancer target paradigms) with film and ionization dosimetry. After the start of the clinical program, in vivo measurements with a rectal probe were performed.Material and Methods:The VMAT plans were generated by the treatment-planning system (TPS) ERGO++ (Elekta, Crawley, UK) and transferred to a phantom. Film dosimetry was performed with Kodak EDR2 films, and evaluated with dose profiles and γ-index analysis. Appropriate ionization chambers were used for absolute dose measurements in the phantom and for in vivo measurements. The ionization chamber was used with localization of the measurement volume based on positioning cone-beam computed tomography.Results:Plans were transferred from ERGO++ to the record and verify (R&V) system/linear accelerator (linac). The absolute dose deviations recorded with the ionization chamber were 1.74% ± 1.62% across both indications. The γ-index analysis of the film dosimetry showed no deviation > 3%/3 mm in the high-dose region. On in vivo measurements, a deviation between calculation and measurement of 2.09% ± 2.4% was recorded, when the chamber was successfully positioned in the high-dose region.Conclusion:VMAT plans can be planned and treated reproducibly in high quality after the commissioning of the complete delivery chain consisting of TPS, R&V system and linac. The results of the individual plan verification meet the commonly accepted requirements. The first in vivo measurements confirm the reproducible precision of the delivered dose during clinical treatments.ZusammenfassungHintergrund und Ziel:Die volumetrisch modulierte Arc-Therapie (VMAT) bietet die Möglichkeit, für einige Planparadigmata zur bisher etablierten intensitätsmodulierten Strahlentherapie vergleichbare Dosisverteilungen zu generieren. Vor der im Dezember 2008 erfolgten Einführung von VMAT in die eigene klinische Routine überprüften die Autoren Dosisberechnung und Bestrahlungsgenauigkeit anhand von 24 VMAT-Plänen (Anal- und Prostatakarzinomplanungsparadigmata) mittels Film- und Ionisationsdosimetrie. Erste Patientenbestrahlungen wurden mittels rektaler In-vivo-Dosimetrie verifiziert.Material und Methodik:Die VMAT-Pläne wurden mit dem Planungssystem ERGO++ (Elekta, Crawley, UK) generiert und in einem Phantom verifiziert. Filmdosimetrie wurde mittels Kodak-EDR2-Film, Dosisprofilen und der γ-Analyse realisiert. Geeignete Ionisationskammern wurden für absolute Dosismessungen im Phantom und für die In-vivo-Dosimetrie verwendet. Ein Cone-Beam-Computertomogramm wurde für die Lokalisation des Messvolumens der Ionisationskammer im Rektum verwendet.Ergebnisse:Die Pläne wurden durchgängig fehlerfrei von ERGO++ an das „record and verify“-(R&V-)System und an den Beschleuniger übertragen. Die mittlere Abweichung der Absolutdosimetrie betrug 1,74% ± 1,62%. Die γ-Index-Analyse der Filmdosimetrie zeigte keine Abweichung > 3%/3 mm im Hochdosisbereich. Die In-vivo-Messungen ergaben nach erfolgreicher Positionierung im Hochdosisbereich eine mittlere Abweichung zwischen berechneter und applizierter Dosis von 2,09% ± 2,4%.Schlussfolgerung:VMAT-Pläne können auf Basis der klinisch zugelassenen Kette aus Planungs-, R&V- und Bestrahlungssystem nach adäquater Kommissionierung reproduzierbar erzeugt und zuverlässig bestrahlt werden. Die Ergebnisse der Individualplanverifikation erfüllen die allgemein akzeptierten Bedingungen. Erste in vivo ermittelte Dosen bestätigen die Präzision der Dosisapplikation im klinischen Einsatz.

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.