Benedikt Engels

Prospective, Risk-Adapted Strategy of Stereotactic Body Radiotherapy for Early-Stage Non–Small-Cell Lung Cancer: Results of a Phase II Trial

PURPOSE Validation of a prospective, risk-adapted strategy for early-stage non-small-cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS Patients with a T1-3N0M0 (American Joint Committee on Cancer 6th edition) NSCLC were accrued. Using the Radiation Therapy Oncology Group definition, patients were treated to a total dose of 60,Gy in three fractions for peripherally located lesions and four fractions for centrally located lesions. The primary endpoint was toxicity, graded according to the Radiation Therapy Oncology Group acute and late morbidity scoring system, and the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0. Secondary endpoints were local control and survival. RESULTS A total of 40 patients were included, 17 with a centrally located lesion. The lung toxicity-free survival estimate at 2 years was 74% and was related to the location (central vs. peripheral) and the size of the target volume. No dose volumetric parameters could predict the occurrence of lung toxicity. One patient died because of treatment-related toxicity. The 1-year and 2-year local progression-free survival estimates were 97% and 84%, respectively, and were related to stage (T1 vs. T2) related (p = 0.006). Local failure was not more frequent for patients treated in four fractions. The 1-year local progression-free survival estimate dropped below 80% for lesions with a diameter of more than 4 cm. CONCLUSION The proposed risk-adapted strategy for both centrally and peripherally located lesions showed an acceptable toxicity profile while maintaining excellent local control rates. The correlation between local control and tumor diameter calls for the inclusion of tumor stage as a variable in future study design.

Conformal Arc Radiotherapy for Prostate Cancer: Increased Biochemical Failure in Patients With Distended Rectum on the Planning Computed Tomogram Despite Image Guidance by Implanted Markers

PURPOSE To evaluate the effect of rectal distention on the planning computed tomogram on freedom from biochemical failure (FFBF) of prostate cancer patients treated with image-guided conformal arc radiotherapy. METHODS AND MATERIALS The outcomes of 238 patients with T1-T3N0M0 tumors were analyzed, with a median follow-up of 53 months (range, 24-93 months). In 213 patients, daily co-registration of X-rays and digitally reconstructed radiographs was used for positioning, whereas in 25 patients positioning was done using direct prostate visualization with implanted markers. The rectal average cross-sectional area was determined on the planning computed tomogram. RESULTS The 5-year freedom from Grade 3 to 4 late gastrointestinal and urinary side effect, according to the Radiation Therapy Oncology Group criteria, was 100% and 99.4% respectively. The 5-year FFBF was 88.4%. On multivariate analysis the following variables were significantly related to worse FFBF: risk group according to the National Comprehensive Cancer Network (high- to very high risk vs. intermediate- to low-risk), dose (70 vs. 78 Gy), average cross-sectional area (> or =16 vs. <16 cm(2)) and, unexpectedly, the use of implanted markers as opposed to bony structures for patient positioning. In retrospect, the margins around the clinical target volume appeared to be inadequate in the cases in which markers were used. CONCLUSION Overall, the outcome of patients treated with image-guided conformal arc radiotherapy is excellent. We were able to confirm the negative prognostic impact of a distended rectum on the planning computed tomogram described by others. The study illustrates the potential danger of image guidance techniques as to margin reduction around the clinical target volume.

Initial assessment of tumor tracking with a gimbaled linac system in clinical circumstances: A patient simulation study

PURPOSE To have an initial assessment of the Vero Dynamic Tracking workflow in clinical circumstances and quantify the performance of the tracking system, a simulation study was set up on 5 lung and liver patients. METHODS AND MATERIALS The preparatory steps of a tumor tracking treatment, based on fiducial markers implanted in the tumor, were executed allowing pursuit of the tumor with the gimbaled linac and monitoring X-rays acquisition, however, without activating the 6 MV beam. Data were acquired on workflow time-efficiency, tracking accuracy and imaging exposure. RESULTS The average time between the patient entering the treatment room and the first treatment field was about 9 min. The time for building the correlation model was 3.2 min. Tracking errors of 0.55 and 0.95 mm (1σ) were observed in PAN/TILT direction and a 2D range of 3.08 mm. A skin dose was determined of 0.08 mGy/image, with a source-to-skin distance of 900 mm and kV exposure of 1 mAs. On average 1.8 mGy/min kV skin dose was observed for 1 Hz monitoring. CONCLUSION The Vero tracking solution proved to be fully functional and showed performance comparable with other real-time tracking systems.

Treating patients with real-time tumor tracking using the Vero gimbaled linac system: Implementation and first review

PURPOSE To report on the first clinical application of a real-time tumor tracking (RTTT) solution based on the Vero SBRT gimbaled linac system for treatment of moving tumors. METHODS AND MATERIALS A first group of 10 SBRT patients diagnosed with NSCLC or oligometastatic disease in lung or liver was treated with the RTTT technique. The PTV volumes and OAR exposure were benchmarked against the widely used ITV approach. Based on data acquired during execution of RTTT treatments, a first review was performed of the process. RESULTS The 35% PTV volume reduction with RTTT of the studied single lesions SBRT irradiations of small target volumes is expected to result in a small (<1%) reduction of lung or liver NTCP. A GTV-PTV margin of 5.0mm was applied for treatment planning of RTTT. From patient data on residual geometric uncertainties, a CTV-PTV margin of 3.2mm was calculated. Reduction of the GTV-PTV margin below 5.0mm without better understanding of biological definition of tumor boundaries was discouraged. Total treatment times were reduced to 34.4 min on average. CONCLUSION A considerable PTV volume reduction was achieved applying RTTT and time efficiency for respiratory correlated SBRT was reestablished with Vero RTTT.

Clinical evaluation of a robotic 6-degree of freedom treatment couch for frameless radiosurgery.

PURPOSE To evaluate the added value of 6-degree of freedom (DOF) patient positioning with a robotic couch compared with 4DOF positioning for intracranial lesions and to estimate the immobilization characteristics of the BrainLAB frameless mask (BrainLAB AG, Feldkirchen, Germany), more specifically, the setup errors and intrafraction motion. METHODS AND MATERIALS We enrolled 40 patients with 66 brain metastases treated with frameless stereotactic radiosurgery and a 6DOF robotic couch. Patient positioning was performed with the BrainLAB ExacTrac stereoscopic X-ray system. Positioning results were collected before and after treatment to assess patient setup error and intrafraction motion. Existing treatment planning data were loaded and simulated for 4DOF positioning and compared with the 6DOF positioning. The clinical relevance was analyzed by means of the Paddick conformity index and the ratio of prescribed isodose volume covered with 4DOF to that obtained with the 6DOF positioning. RESULTS The mean three-dimensional setup error before 6DOF correction was 1.91 mm (SD, 1.25 mm). The rotational errors were larger in the longitudinal (mean, 0.23°; SD, 0.82°) direction compared with the lateral (mean, -0.09°; SD, 0.72°) and vertical (mean, -0.10°; SD, 1.03°) directions (p < 0.05). The mean three-dimensional intrafraction shift was 0.58 mm (SD, 0.42 mm). The mean intrafractional rotational errors were comparable for the vertical, longitudinal, and lateral directions: 0.01° (SD, 0.35°), 0.03° (SD, 0.31°), and -0.03° (SD, 0.33°), respectively. The mean conformity index decreased from 0.68 (SD, 0.08) (6DOF) to 0.59 (SD, 0.12) (4DOF) (p < 0.05). A loss of prescribed isodose coverage of 5% (SD, 0.08) was found with the 4DOF positioning (p < 0.05). Half a degree for longitudinal and lateral rotations can be identified as a threshold for coverage loss. CONCLUSIONS With a mask immobilization, patient setup error and intrafraction motions need to be evaluated and corrected for. The 6DOF patient positioning with a 6DOF robotic couch to correct translational and rotational setup errors improves target positioning with respect to treatment isocenter, which is in direct relation with the clinical outcome, compared with the 4DOF positioning.

Preoperative Helical Tomotherapy and Megavoltage Computed Tomography for Rectal Cancer: Impact on the Irradiated Volume of Small Bowel

PURPOSE Preoperative (chemo)radiotherapy is considered to be standard of care in locally advanced rectal cancer, but is associated with significant small-bowel toxicity. The aim of this study was to explore to what extent helical tomotherapy and daily megavolt (MV) CT imaging may reduce the irradiated volume of small bowel. METHODS AND MATERIALS A 3D-conformal radiotherapy (3D-CRT) plan with CTV-PTV margins adjusted for laser-skin marks (15, 15, and 10 mm for X, Y, and Z directions, respectively) was compared with helical tomotherapy (IMRT) using the same CTV-PTV margins, and to helical tomotherapy with margins adapted to daily MV-CT imaging (IMRT/IGRT; 8, 11, 7, and 10 mm for X, Y(ant), Y(post) and Z resp.) for 11 consecutive patients. The planning goals were to prescribe 43.7 Gy to 95% of the PTV, while minimizing the volume of small bowel receiving more than 15 Gy (V(15 SB)). RESULTS The mean PTV was reduced from 1857.4 +/- 256.6 cc to 1462.0 +/- 222.3 cc, when the CTV-PTV margins were adapted from laser-skin marks to daily MV-CT imaging (p < 0.01). The V(15 SB) decreased from 160.7 +/- 102.9 cc to 110.9 +/- 74.0 cc with IMRT and to 81.4 +/- 53.9 cc with IMRT/IGRT (p < 0.01). The normal tissue complication probability (NTCP) for developing Grade 2+ diarrhea was reduced from 39.5% to 26.5% with IMRT and to 18.0% with IMRT/IGRT (p < 0.01). CONCLUSION The combination of helical tomotherapy and daily MV-CT imaging significantly decreases the irradiated volume of small bowel and its NTCP.

Stereotactic radiotherapy for oligometastatic cancer: a prognostic model for survival

BACKGROUND Stereotactic radiotherapy (SRT) is a safe and locally effective treatment for patients with inoperable oligometastases. The challenge remains identifying subsets of patients that benefit in terms of overall survival (OS). PATIENTS AND METHODS Between 2005 and 2011, 309 patients with ≤5 metastases were treated by stereotactic body radiotherapy (n=209) and/or by intracranial single or fractionated stereotactic radiotherapy (n=107). We analyzed OS and carried out a risk factor analysis. RESULTS The median survival of all patients was 24 months. The 3-, 4- and 5-year OS rates were 32%, 25% and 19%, respectively. The following four risk factors were independently associated with impaired OS: nonadenocarcinoma histology (P<0.01), intracranial metastases (P<0.01), synchronous oligometastatic disease (P<0.01) and male gender (P=0.02). Patients with 0, 1 and 2 risk factors displayed a median survival (95% CI) of 40 (24-63), 29 (23-35) and 23 (16-29) months, respectively, and are defined as patients with good prognosis. Patients with 3 and 4 risk factors had a median survival of 9 (6-11) and 4 (1-7) months only and are defined as bad prognostic patients. CONCLUSIONS We identified subsets of oligometastatic cancer patients with good prognosis after SRT. These patients are candidates for inclusion in prospective randomized trials for defining the role of SRT in the management of oligometastases.

Assessment of Intrafractional Movement and Internal Motion in Radiotherapy of Rectal Cancer Using Megavoltage Computed Tomography

PURPOSE The aim of this study was to provide estimates of setup and internal margins of patients treated for rectal carcinoma using helical tomotherapy and to assess possible margin adaptations. Using helical tomotherapy, highly conformal dose distributions can be created, and the integrated megavoltage computed tomography (MVCT) modality allows very precise daily patient positioning. In clinical protocols, however, margins originating from traditional setup procedures are still being applied. This work investigates whether this modality can aid in redefining treatment margins. METHODS AND MATERIALS Ten patients who were treated with tomotherapy underwent MVCT scanning before and after 10 treatments. Using automatic registration the necessary setup margin was investigated by means of bony landmarks. Internal margins were assessed by delineating and describing the mesorectal movement. RESULTS Based on bony landmarks, movement of patients during treatments was limited to 2.45 mm, 1.99 mm, and 1.09 mm in the lateral, longitudinal, and vertical direction, respectively. Systematic errors were limited to <1 mm. Measured movement of the mesorectal space was -1.6 mm (+/- 4.2 mm) and 0.1 mm (+/- 4.0 mm) for left and right lateral direction. In the antero-posterior direction, mean shifts were -2 mm (+/- 6.8 mm) and -0.4 mm (+/- 3.8 mm). Mean shifts in the cranio-caudal direction were respectively -3.2 mm (+/- 5.6 mm) and -3.2 mm (+/- 6.8 mm). CONCLUSIONS The use of the integrated MVCT on the tomotherapy system can minimize the setup margin for rectal cancer, and can also be used to adequately describe the internal margin allowing for direct treatment margin adaptation.

Dosimetric comparison of different treatment modalities for stereotactic radiosurgery of arteriovenous malformations and acoustic neuromas

PURPOSE We investigated the influence of beam modulation on treatment planning by comparing four available stereotactic radiosurgery (SRS) modalities: Gamma-Knife-Perfexion, Novalis-Tx Dynamic-Conformal-Arc (DCA) and Dynamic-Multileaf-Collimation-Intensity-Modulated-radiotherapy (DMLC-IMRT), and Cyberknife. MATERIAL AND METHODS Patients with arteriovenous malformation (n = 10) or acoustic neuromas (n = 5) were planned with different treatment modalities. Paddick conformity index (CI), dose heterogeneity (DH), gradient index (GI) and beam-on time were used as dosimetric indices. RESULTS Gamma-Knife-Perfexion can achieve high degree of conformity (CI = 0.77 ± 0.04) with limited low-doses (GI = 2.59 ± 0.10) surrounding the inhomogeneous dose distribution (D(H) = 0.84 ± 0.05) at the cost of treatment time (68.1 min ± 27.5). Novalis-Tx-DCA improved this inhomogeneity (D(H) = 0.30 ± 0.03) and treatment time (16.8 min ± 2.2) at the cost of conformity (CI = 0.66 ± 0.04) and Novalis-TX-DMLC-IMRT improved the DCA CI (CI = 0.68 ± 0.04) and inhomogeneity (D(H) = 0.18 ± 0.05) at the cost of low-doses (GI = 3.94 ± 0.92) and treatment time (21.7 min ± 3.4) (p<0.01). Cyberknife achieved comparable conformity (CI = 0.77 ± 0.06) at the cost of low-doses (GI = 3.48 ± 0.47) surrounding the homogeneous (D(H) = 0.22 ± 0.02) dose distribution and treatment time (28.4min±8.1) (p<0.01). CONCLUSIONS Gamma-Knife-Perfexion will comply with all SRS constraints (high conformity while minimizing low-dose spread). Multiple focal entries (Gamma-Knife-Perfexion and Cyberknife) will achieve better conformity than High-Definition-MLC of Novalis-Tx at the cost of treatment time. Non-isocentric beams (Cyberknife) or IMRT-beams (Novalis-Tx-DMLC-IMRT) will spread more low-dose than multiple isocenters (Gamma-Knife-Perfexion) or dynamic arcs (Novalis-Tx-DCA). Inverse planning and modulated fluences (Novalis-Tx-DMLC-IMRT and CyberKnife) will deliver the most homogeneous treatment. Furthermore, Linac-based systems (Novalis and Cyberknife) can perform image verification at the time of treatment delivery.

Preoperative intensity-modulated and image-guided radiotherapy with a simultaneous integrated boost in locally advanced rectal cancer: Report on late toxicity and outcome

BACKGROUND AND PURPOSE The addition of chemotherapy to preoperative radiotherapy has been established as the standard of care for patients with cT3-4 rectal cancer. As an alternative strategy, we explored intensity-modulated and image-guided radiotherapy (IMRT-IGRT) with a simultaneous integrated boost (SIB) in a prospective phase II study. Here, we report outcome and late toxicity after a median follow-up of 54 months. METHODS AND MATERIALS A total of 108 patients were treated preoperatively with IMRT-IGRT, delivering a dose of 46 Gy in fractions of 2 Gy. Patients (n=57) displaying an anticipated circumferential resection margin (CRM) of less than 2mm based on magnetic resonance imaging received a SIB to the tumor up to a total dose of 55.2 Gy. RESULTS The absolute incidence of grade ≥3 late gastrointestinal and urinary toxicity was 9% and 4%, respectively, with a 13% rate of any grade ≥3 late toxicity. The actuarial 5-year local control (LC), progression-free survival (PFS) and overall survival (OS) were 97%, 57%, and 68%. On multivariate analysis, R1 resection and pN2 disease were associated with significantly impaired OS. CONCLUSIONS The use of preoperative IMRT-IGRT with a SIB resulted in a high 5-year LC rate and non-negligible late toxicity.