Bruno Speleers

Intensity-Modulated Radiotherapy as Primary Therapy for Prostate Cancer: Report on Acute Toxicity After Dose Escalation With Simultaneous Integrated Boost to Intraprostatic Lesion

PURPOSE To report on the acute toxicity of a third escalation level using intensity-modulated radiotherapy for prostate cancer (PCa) and the acute toxicity resulting from delivery of a simultaneous integrated boost (SIB) to an intraprostatic lesion (IPL) detected on magnetic resonance imaging (MRI), with or without spectroscopy. METHODS AND MATERIALS Between January 2002 and March 2007, we treated 230 patients with intensity-modulated radiotherapy to a third escalation level as primary therapy for prostate cancer. If an IPL (defined by MRI or MRI plus spectroscopy) was present, a SIB was delivered to the IPL. To report on acute toxicity, patients were seen weekly during treatment and 1 and 3 months after treatment. Toxicity was scored using the Radiation Therapy Oncology Group toxicity scale, supplemented by an in-house-developed scoring system. RESULTS The median dose to the planning target volume was 78 Gy. An IPL was found in 118 patients. The median dose to the MRI-detected IPL and MRI plus spectroscopy-detected IPL was 81 Gy and 82 Gy, respectively. No Grade 3 or 4 acute gastrointestinal toxicity developed. Grade 2 acute gastrointestinal toxicity was present in 26 patients (11%). Grade 3 genitourinary toxicity was present in 15 patients (7%), and 95 patients developed Grade 2 acute genitourinary toxicity (41%). No statistically significant increase was found in Grade 2-3 acute gastrointestinal or genitourinary toxicity after a SIB to an IPL. CONCLUSION The results of our study have shown that treatment-induced acute toxicity remains low when intensity-modulated radiotherapy to 80 Gy as primary therapy for prostate cancer is used. In addition, a SIB to an IPL did not increase the severity or incidence of acute toxicity.

Volumetric Arc Therapy and Intensity-Modulated Radiotherapy for Primary Prostate Radiotherapy With Simultaneous Integrated Boost to Intraprostatic Lesion With 6 and 18 MV: A Planning Comparison Study

PURPOSE The aim of the present study was to compare intensity-modulated radiotherapy (IMRT) with volumetric arc therapy (VMAT), in the treatment of prostate cancer with maximal dose escalation to the intraprostatic lesion (IPL), without violating the organ-at-risk constraints. Additionally, the use of 6-MV photons was compared with 18-MV photons for all techniques. METHODS AND MATERIALS A total of 12 consecutive prostate cancer patients with an IPL on magnetic resonance imaging were selected for the present study. Plans were made for three IMRT field setups (three, five, and seven fields) and one VMAT field setup (single arc). First, optimal plans were created for every technique using biologic and physical planning aims. Next, an additional escalation to the IPL was planned as high as possible without violating the planning aims of the first step. RESULTS No interaction between the technique and photon energy (p=.928) occurred. No differences were found between the 6- and 18-MV photon beams, except for a reduction in the number of monitor units needed for 18 MV (p<.05). All techniques, except for three-field IMRT, allowed for dose escalation to a median dose of ≥93±6 Gy (mean±standard deviation) to the IPL. VMAT was superior to IMRT for rectal volumes receiving 20-50 Gy (p<.05). CONCLUSION VMAT allowed for dose escalation to the IPL with better sparing of the rectum than static three-, five-, and seven-field IMRT setups. High-energy photons had no advantage over low-energy photons.

Hypofractionated whole breast irradiation for patients with large breasts: A randomized trial comparing prone and supine positions

BACKGROUND AND PURPOSE Comparison of acute toxicity of whole-breast irradiation (WBI) in prone and supine positions. MATERIALS AND METHODS This non-blinded, randomized, prospective, mono-centric trial was undertaken between December 29, 2010, and December 12, 2012. One hundred patients with large breasts were randomized between supine multi beam (MB) and prone tangential field (TF) intensity modulated radiotherapy (IMRT). Dose-volume parameters were assessed for the breast, heart, left anterior descending coronary artery (LAD), ipsilateral lung and contralateral breast. The primary endpoint was acute moist skin desquamation. Secondary endpoints were dermatitis, edema, pruritus and pain. RESULTS Prone treatment resulted in: improved dose coverage (p<0.001); better homogeneity (p<0.001); less volumes of over-dosage (p=0.001); reduced acute skin desquamation (p<0.001); a 3-fold decrease of moist desquamation p=0.04 (chi-square), p=0.07 (Fishers exact test)); lower incidence of dermatitis (p<0.001), edema (p=0.005), pruritus (p=0.06) and pain (p=0.06); 2- to 4-fold reduction of grades 2-3 toxicity; lower ipsilateral lung (p<0.001) and mean LAD (p=0.007) dose; lower, though statistically non-significant heart and maximum LAD. CONCLUSIONS This study provides level I evidence for replacing the supine standard treatment by prone IMRT for whole-breast irradiation in patients with large breasts. A confirmatory trial in a multi-institutional setting is warranted.

Whole breast radiotherapy in prone and supine position: is there a place for multi-beam IMRT?

BackgroundEarly stage breast cancer patients are long-term survivors and finding techniques that may lower acute and late radiotherapy-induced toxicity is crucial. We compared dosimetry of wedged tangential fields (W-TF), tangential field intensity-modulated radiotherapy (TF-IMRT) and multi-beam IMRT (MB-IMRT) in prone and supine positions for whole-breast irradiation (WBI).MethodsMB-IMRT, TF-IMRT and W-TF treatment plans in prone and supine positions were generated for 18 unselected breast cancer patients. The median prescription dose to the optimized planning target volume (PTVoptim) was 50 Gy in 25 fractions. Dose-volume parameters and indices of conformity were calculated for the PTVoptim and organs-at-risk.ResultsProne MB-IMRT achieved (p<0.01) the best dose homogeneity compared to WTF in the prone position and WTF and MB-IMRT in the supine position. Prone IMRT scored better for all dose indices. MB-IMRT lowered lung and heart dose (p<0.05) in supine position, however the lowest ipsilateral lung doses (p<0.001) were in prone position. In left-sided breast cancer patients population averages for heart sparing by radiation dose was better in prone position; though non-significant. For patients with a PTVoptim volume ≥600 cc heart dose was consistently lower in prone position; while for patients with smaller breasts heart dose metrics were comparable or worse compared to supine MB-IMRT. Doses to the contralateral breast were similar regardless of position or technique. Dosimetry of prone MB-IMRT and prone TF-IMRT differed slightly.ConclusionsMB-IMRT is the treatment of choice in supine position. Prone IMRT is superior to any supine treatment for right-sided breast cancer patients and left-sided breast cancer patients with larger breasts by obtaining better conformity indices, target dose distribution and sparing of the organs-at-risk. The influence of treatment techniques in prone position is less pronounced; moreover dosimetric differences between TF-IMRT and MB-IMRT are rather small.

Alternated prone and supine whole-breast irradiation using IMRT: setup precision, respiratory movement and treatment time.

PURPOSE The objective of this study was to compare setup precision, respiration-related breast movement and treatment time between prone and supine positions for whole-breast irradiation. METHODS AND MATERIALS Ten patients with early-stage breast carcinoma after breast-conserving surgery were treated with prone and supine whole breast-irradiation in a daily alternating schedule. Setup precision was monitored using cone-beam computed tomography (CBCT) imaging. Respiration-related breast movement in the vertical direction was assessed by magnetic sensors. The time needed for patient setup and for the CBCT procedure, the beam time, and the length of the whole treatment slot were also recorded. RESULTS Random and systematic errors were not significantly different between positions in individual patients for each of the three axes (left-right, longitudinal, and vertical). Respiration-related movement was smaller in prone position, but about 80% of observations showed amplitudes <1 mm in both positions. Treatment slots were longer in prone position (21.2 ± 2.5 min) than in supine position (19.4 ± 0.8 min; p = 0.044). CONCLUSION Comparison of setup precision between prone and supine position in the same patient showed no significant differences in random and systematic errors. Respiratory movement was smaller in prone position. The longer treatment slots in prone position can probably be attributed to the higher repositioning need.

Heart dose reduction by prone deep inspiration breath hold in left-sided breast irradiation

BACKGROUND AND PURPOSE Cardiac disease has been related to heart dose after left-sided breast radiotherapy. This trial evaluates the heart sparing ability and feasibility of deep inspiration breath hold (DIBH) in the prone position for left-sided whole breast irradiation (WBI). MATERIALS AND METHODS Twelve patients underwent CT-simulation in supine shallow breathing (SB), supine DIBH, prone SB and prone DIBH. A validation cohort of 38 patients received prone SB and prone DIBH CT-scans; the last 30 patients were accepted for prone DIBH treatment. WBI was planned with a prescription dose of 40.05 Gy. RESULTS DIBH was able to reduce (p<0.001) heart dose in both positions, with results for prone DIBH at least as favorable as for supine DIBH. Mean heart dose was lowered from 2.2 Gy for prone SB to 1.3 Gy for prone DIBH (p<0.001), while preserving the lung sparing ability of prone positioning. Moreover prone DIBH nearly consistently reduced mean heart dose to less then 2 Gy, regardless of breast volume. All patients were able to perform the simulation procedure, 28/30 patients were treated with prone DIBH. CONCLUSIONS This trial demonstrates the ability and feasibility of prone DIBH to acquire optimal heart and lung sparing for left-sided WBI.

An Anatomically Validated Brachial Plexus Contouring Method for Intensity Modulated Radiation Therapy Planning

PURPOSE To develop contouring guidelines for the brachial plexus (BP) using anatomically validated cadaver datasets. Magnetic resonance imaging (MRI) and computed tomography (CT) were used to obtain detailed visualizations of the BP region, with the goal of achieving maximal inclusion of the actual BP in a small contoured volume while also accommodating for anatomic variations. METHODS AND MATERIALS CT and MRI were obtained for 8 cadavers positioned for intensity modulated radiation therapy. 3-dimensional reconstructions of soft tissue (from MRI) and bone (from CT) were combined to create 8 separate enhanced CT project files. Dissection of the corresponding cadavers anatomically validated the reconstructions created. Seven enhanced CT project files were then automatically fitted, separately in different regions, to obtain a single dataset of superimposed BP regions that incorporated anatomic variations. From this dataset, improved BP contouring guidelines were developed. These guidelines were then applied to the 7 original CT project files and also to 1 additional file, left out from the superimposing procedure. The percentage of BP inclusion was compared with the published guidelines. RESULTS The anatomic validation procedure showed a high level of conformity for the BP regions examined between the 3-dimensional reconstructions generated and the dissected counterparts. Accurate and detailed BP contouring guidelines were developed, which provided corresponding guidance for each level in a clinical dataset. An average margin of 4.7 mm around the anatomically validated BP contour is sufficient to accommodate for anatomic variations. Using the new guidelines, 100% inclusion of the BP was achieved, compared with a mean inclusion of 37.75% when published guidelines were applied. CONCLUSION Improved guidelines for BP delineation were developed using combined MRI and CT imaging with validation by anatomic dissection.

Deformation field validation and inversion applied to adaptive radiation therapy.

Development and implementation of chronological and anti-chronological adaptive dose accumulation strategies in adaptive intensity-modulated radiation therapy (IMRT) for head-and-neck cancer. An algorithm based on Newton iterations was implemented to efficiently compute inverse deformation fields (DFs). Four verification steps were performed to ensure a valid dose propagation: intra-cell folding detection finds zero or negative Jacobian determinants in the input DF; inter-cell folding detection is implemented on the resolution of the output DF; a region growing algorithm detects undefined values in the output DF; DF domains can be composed and displayed on the CT data. In 2011, one patient with nonmetastatic head and neck cancer selected from a three phase adaptive DPBN study was used to illustrate the algorithms implemented for adaptive chronological and anti-chronological dose accumulation. The patient received three (18)F-FDG-PET/CTs prior to each treatment phase and one CT after finalizing treatment. Contour propagation and DF generation between two consecutive CTs was performed in Atlas-based autosegmentation (ABAS). Deformable image registration based dose accumulations were performed on CT1 and CT4. Dose propagation was done using combinations of DFs or their inversions. We have implemented a chronological and anti-chronological dose accumulation algorithm based on DF inversion. Algorithms were designed and implemented to detect cell folding.

Whole Abdominopelvic Radiotherapy Using Intensity-Modulated Arc Therapy in the Palliative Treatment of Chemotherapy-Resistant Ovarian Cancer With Bulky Peritoneal Disease: A Single-Institution Experience

PURPOSE To retrospectively review our experience with whole abdominopelvic radiotherapy (WAPRT) using intensity-modulated arc therapy in the palliative treatment of chemotherapy-resistant ovarian cancer with bulky peritoneal disease. METHODS AND MATERIALS Between April 2002 and April 2008, 13 patients were treated with WAPRT using intensity-modulated arc therapy. We prescribed a dose of 33 Gy to be delivered in 22 fractions of 1.5 Gy to the abdomen and pelvis. All patients had International Federation of Gynecology and Obstetrics Stage III or IV ovarian cancer at the initial diagnosis. At referral, the median age was 61 years, and the patients had been heavily pretreated with surgery and chemotherapy. All patients had symptoms from their disease, including gastrointestinal obstruction or subobstruction in 6, minor gastrointestinal symptoms in 2, pain in 4, ascites in 1, and vaginal bleeding in 2. A complete symptom or biochemical response required complete resolution of the patients symptoms or cancer antigen-125 level. A partial response required ≥50% resolution of these parameters. The actuarial survival was calculated from the start of radiotherapy. RESULTS The median overall survival was 21 weeks, with a 6-month overall survival rate of 45%. The 9 patients who completed treatment obtained a complete symptom response, except for ascites (partial response). The median and mean response duration (all symptoms grouped) was 24 and 37 weeks, respectively. Of the 6 patients presenting with obstruction or subobstruction, 4 obtained a complete symptom response (median duration, 16 weeks). CONCLUSION WAPRT delivered using intensity-modulated arc therapy offers important palliation in the case of peritoneal metastatic ovarian cancer. WAPRT resolved intestinal obstruction for a substantial period.

Prone left-sided whole-breast irradiation: Significant heart dose reduction using end-inspiratory versus end-expiratory gating

PURPOSE To quantify the influence on heart dose metrics of prone left-sided whole-breast irradiation in an end-inspiratory phase (PrIN) versus an end-expiratory phase (PrEX). PATIENTS AND METHODS Twenty patients underwent CT-simulation in PrIN and PrEX. Dynamic intensity-modulated radiotherapy was planned for whole-breast irradiation with a median prescription dose of 40.05Gy in 15 fractions and maximal sparing of the organs at risk. Dose-volume parameters were analyzed for heart, left anterior descending coronary artery, ipsilateral lung and both breasts. RESULTS PrIN consistently reduced (P<0.001) heart and left anterior descending coronary artery dose metrics compared to PrEX. Population averages for maximum and mean heart dose were 6.2Gy and 1.3Gy for PrIN versus 21.4Gy and 2.5Gy for PrEX, respectively. Moreover, a maximum heart dose less than 10Gy was achieved in 80% of patients for PrIN. Target dose distribution, ipsilateral lung and contralateral breast sparing by radiation dose were similar for both procedures. CONCLUSIONS Inspiratory gating consistently reduced heart dose metrics pointing to a possible benefit of breathing-adapted radiotherapy for prone left-sided whole-breast irradiation.