HDR brachytherapy boost using MR-only workflow for intermediate- and high-risk prostate cancer: 8-year results of a pilot study.

PURPOSE: To report 8-year clinical outcome with high-dose-rate brachytherapy (HDRBT) boost using MRI-only workflow for intermediate (IR) and high-risk (HR) prostate cancer (PC) patients. METHODS AND MATERIALS: Fifty-two patients were treated with 46-60 Gy of 3D conformal radiotherapy preceded and/or followed by a single dose of 8-10 Gy MRI-guided HDRBT. Interventions were performed in a 0.35 T MRI scanner. Trajectory planning, navigation, contouring, catheter reconstruction, and dose calculation were exclusively based on MRI images. Biochemical relapse-free- (BRFS), local relapse-free- (LRFS), distant metastasis-free- (DMFS), cancer-specific-(CCS) and overall survival (OS) were analyzed. Late morbidity was scored using the Common Terminology Criteria for Adverse Events (CTCAE 4.0) combined with RTOG (Radiation Therapy Oncology Group) scale for urinary toxicity and rectal urgency (RU) determined by Yeoh. RESULTS: Median follow-up time was 107 (range: 19-143) months. The 8-year actuarial rates of BRFS, LRFS, DMFS, CSS and OS were 85.7%, 97%, 97.6%, and 77.6%, respectively. There were no Gr.3 GI side effects. The 8-year actuarial rate of Gr.2 proctitis was 4%. The 8-year cumulative incidence of Gr.3 GU side effects was 8%, including two urinary stenoses (5%) and one cystitis (3%). EPIC urinary and bowel scores did not change significantly over time. CONCLUSIONS: MRI-only HDR-BT boost with moderate dose escalation provides excellent 8-year disease control with a favorable toxicity profile for IRPC and HRPC patients. Our results support the clinical importance of MRI across the BT workflow.

Triggered Imaging With Auto Beam Hold and Pre-/Posttreatment CBCT During Prostate SABR: Analysis of Time Efficiency, Target Coverage, and Normal Volume Changes.

PURPOSE: Our purpose was to investigate time efficiency and target coverage for prostate stereotactic ablative radiation therapy (SABR) using triggered imaging (TI) and auto beam hold. METHODS AND MATERIALS: A total of 20 patients were treated with volumetric modulated arc-based SABR. Treatment verification consisted of pre- and post-radiation therapy cone beam computed tomography (CBCT) with gold marker-based TI every 3 seconds. In case of ≥3 mm (deviation limit) displacement, the treatment was interrupted and imaging-based correction was performed. Beam interruptions, intrafractional shifts, and treatment times were recorded. Prostate, rectum, and bladder were delineated on each CBCT. Target coverage was evaluated by comparing the individual prostate delineations with 98% isodose contour volumes (% of the evaluated volumes exceeding the reference). Both inter- and intrafractional changes of bladder and rectal volumes were assessed. RESULTS: The average overall treatment time (±standard deviation) was 18 ± 11 min, with a radiation delivery time of 6 ± 3 min if no intrafractional CBCT acquisitions were necessary (91% of fractions). On average, 1.2 beam interruptions per fraction were required with 0/1 correction in 71% of the fractions. The mean residual 3-dimensional shift was 1.6 mm, exceeding the deviation limit in 8%. In the case of intrafractional CBCT and/or ≥2 corrections the treatment time dramatically increased. The 98% isodose lines did not encompass the prostate in only 8/180 (4%) evaluations in 6 different patients, leading to a loss of D98 between 0.1%-6% as a worst case scenario. The bladder volumes showed significant increases during treatment (P < .01) while rectal volumes were stable. CONCLUSIONS: Time efficiency of TI + auto beam hold with 3 mm/3 sec threshold during prostate SABR is comparable with competitive techniques, resulting in minimal 3-dimensional residual errors with maintained target coverage. Technical developments are necessary to further reduce radiation delivery time. Use of CBCT allowed full control of rectal volumes, while bladder volumes showed significant increases over time.

[Multimodal imaging during lung and abdominal stereotactic ablative radiotherapy: from cine MRI through 3D/4D CBCT to intrafractional kV verification]. / Multimodális képalkotás tüdõ- és hasi sztereotaxiás ablatív radioterápia során: a cine MRI-mérésektõl a 3D/4D CBCT-n át a kezelés alatti kV-os képi verifikációig.

Our aim was to present our treatment and verification protocols of linear accelerator-based lung and abdominal stereotactic ablative radiotherapy (SABR). During our treatments both the volumetric imaging (3D/4D CBCT/CT) and triggered kV intrafractional tumor motion control could be combined allowing a full control on the whole workflow. The most optimal kV directions from which the tumor is well detectable were defined. Tumor movements measured on cine MRI in treatment position correlated well with the ones on 4D CBCT, thus cine MRI is considered an excellent device to pre-select the appropriate image/treatment verification SABR protocol. In abdominal targets implanted markers and cine MRI are preferred due to limited image quality of CBCT with the current version. In selected lung SABR cases (≥8mm motion) the dose delivery of organs at risk (lungs - GTV, chest wall) could be reduced compared to free breathing conditions, however, the treatment time is at least two-folds higher.

Integrating functional MRI information into conventional 3D radiotherapy planning of CNS tumors. Is it worth it?

The purpose of our study was to examine the potential benefits of integrating functional MRI (fMRI) information into the 3D-based planning process for central nervous system (CNS) malignancies. Between 01.01.2008 and 01.12.2009, ten patients with astrocytoma (both low and high-grade histological type) were enrolled in this study. Before the planning process, conventional CT planning, postoperative MR, and individual functional MRI examinations were conducted. For the functional MRI examination four types of conventional stimuli were applied: acoustic, visual, somatosensory, and numeric. To examine the potential benefits of using fMRI-based information, three different types of theoretical planning were applied and compared: 3D conformal plan without fMRI information, 3D conformal plan with fMRI information, and IMRT plan with fMRI information. DVH analysis and the NTCP model were used for plan comparison. When comparing planning methods, distance-related subgroups were generated and studied. By using the additional fMRI information, a significantly higher sparing effect can be achieved on these ORs (both with conventional 3D-based planning and IMRT). In cases when the OR-PTV distance is less than 1 cm, IMRT seems to be a significantly better choice than conventional 3D-based techniques. IMRT also has an additional sparing effect on the optic tract and brainstem, especially for locations close to the midline. Our results demonstrated that using fMRI information in conventional 3D-based treatment planning has the potential benefit of significant dose reduction for the critical organs, with no compromise in PTV coverage even when using conventional 3D planning. fMRI can be widely used in low-grade cases (long life expectancy, lower acute and late toxicity) and also in cases with high-grade astrocytomas or distant metastases (higher dose to PTV with better sparing of risk organs). In cases when the OR-PTV distance is less than 1 cm, IMRT should be the choice of treatment for a higher sparing effect on functional active areas. Longer imaging and clinical follow up are needed to confirm the real sparing effect on these functional areas.

Open MR-guided high-dose-rate (HDR) prostate brachytherapy: feasibility and initial experiences open MR-guided high-dose-rate (HDR) prostate brachytherapy.

The aim of our pilot study was to demonstrate the feasibility and dosimetric quality of MR-guided HDR prostate brachytherapy in a low-field 0.35T open MRI scanner and to present our initial clinical experiences. 16 patients with intermediate- to high-risk localized prostate cancer were treated with 46-60 Gy of external beam radiotherapy preceded and/or followed by an 8 Gy MR-guided HDR boost. For interventions an MR compatible custom-made system, coaxial needles and plastic catheters were used. Template reconstruction, trajectory planning, image guidance, contouring and treatment planning were exclusively based on MR images. For treatment planning, dose-point- and anatomy-based inverse planning optimization was used. Image quality was found to be good to excellent in almost all cases. The mean catheter placement accuracy modeled by Rayleigh distribution was 2.9 mm with a sigma value of 2.3 mm. The mean and standard deviation (SD) of the dosimetric results for the target volume were the following: V100: 94.2 ± 4.3%, V150: 43.9 ± 6.8%, V200: 18.5 ± 5.9%. The mean D(0.1), D(1) and D1 values for the intraprostatic urethra were 117.6 ± 12.5%, 98.5 ± 19.9% and 122.3 ± 16.4%, respectively. Regarding the rectal wall the mean D(0.1), D(1) and D(2) values were 77.3 ± 7.2%, 64.8 ± 7.5%, and 53.2 ± 9.1%, respectively. The mean maximum dose for the inner rectal surface was 53.5 ± 9.2%. No RTOG Grade 3 or worse acute toxicities were observed. Our method seems to be a promising approach for performing feasible, accurate and high-quality MR-guided HDR prostate brachytherapy. To determine the long term side effects and outcome higher number of patients, additional follow-up is needed.

3-D conformal photon boost in the treatment of early stage breast cancer: four year follow up results.

In the treatment of early stage breast cancer, breast conserving surgery (BCS) followed by whole breast irradiation (WBI) is the standard treatment. The impact of the tumor bed boost following WBI is well-defined, but there are various delivery methods. In this study we demonstrate our 4 year experience with the 3-D conformal boost technique. Between January 2004 and June 2005, 77 early stage (Stage I-II) breast cancer patients were treated in our institute with whole breast irradiation (WBI, 50.4 Gy in 28 fractions) after breast conserving surgery. Following WBI, 3-D conformal photon boost was delivered (10-16 Gy in five to eight fractions) for all patients. The clinical outcome was retrospectively recorded in terms of survival and local control. The side effect profile (fibrosis, fat necrosis and cosmetic outcome) was also recorded and studied. In our patient group the mean follow up time was 46.8 months (median: 52, range: 17-71, SD: 14.4) The 4-year probability of local tumor control was 96% (crude rate: 74/77-96.1%), the 4-year probability of overall survival was 96% (crude rate: 74/77-96.1%) in this patient group. In case of the distant metastasis free survival the probability was 89, 5% (crude rate: 70/77-90, 1%). Probability of disease specific survival was 98% (crude rate: 76/77-98. 7%). Local relapse occurred in three cases (3.9%). In ten cases (12.9%) asymptomatic grade I-II breast fibrosis, in eight cases (10.4%) asymptomatic breast fat necrosis were registered. For 14 patients (18.2%) asymptomatic lung fibrosis was recorded on the control CT scans. In term of the relapse free survival, the close resection margin and the nodal positivity resulted in significant difference in favor of the clear resection margin group and the node negative group. In this study the 3-D conformal photon boost resulted in good local control and side effect profile. The presence of tumor bed clips resulted in significantly lower boost PTV volumes, but no correlation was found between the irradiated boost volume and the breast fibrosis. In the relapse free survival analysis, nodal negativity and clear margin status resulted in significantly better RFS.

Technical feasibility of transperineal MR-guided prostate interventions in a low-field open MRI unit: canine study.

Magnetic resonance imaging (MRI) provides superior visualization of the prostate, its substructure, surrounding tissues, and, most important, focal lesions or cancer. The purpose of our canine study was to demonstrate the feasibility of a low-field (0.35 T) transperineal system that enables precise MR image guidance of prostate interventions. The canines were placed in the right lateral decubitus position. Template reconstruction, trajectory planning, contouring were based on T2-weighted FSE images. For image guidance and target confirmation, fast gradient spoiled-echo (FSPGR) sequence was used. MR compatible coaxial needles were manually inserted through the perineum to the base of the prostate. After satisfactory position was confirmed, brachytherapy catheters were placed through the coaxial needles. The mean deviation of the needle displacements was 2.9 mm with a median value of 2.7 mm. 97% of the errors were less than 4.0 mm. The needle placement accuracy was modelled by the Rayleigh distribution with a sigma value of 2.3 mm. Visual confirmation of needle placements was demonstrated on pathology tissue slices. The time needed for each step was: anaesthesia - 15 min, setup and positioning - 15 min, initial imaging - 15 min, template registration, projection - 15 min, contouring, trajectory planning, insertion of 12 needles - 60 min Based on our canine experiences our method seems to be a promising approach for performing feasible, accurate, reliable and high-quality prostate MR guidance within a reasonable time span.

Comparison of photon with electron boost in treatment of early stage breast cancer.

In the treatment of early stage breast cancer breast conserving surgery (BCS) followed by whole breast irradiation (WBI) is a standard method. The impact of the tumor bed boost following WBI is well-defined, but there are various delivery methods. In this study the electron and the photon boost techniques were compared. For 78 early stage breast cancer patients both CT based 3D conformal photon boost and electron boost plans were created. For dosimetric comparison coverage index (CI), external volume index (EI) and conformality index (COIN) were studied. Lung volume receiving a dose of 2 Gy was also reviewed. Seventy-eight patients with 156 plans were compared. The mean tumor bed volume was measured as 61.39 cm3 the mean tumor bed-skin distance was 3.13 cm. In the case of CI and COIN significant differences were found in favor of the photon boost. In the comparison of EI no significant difference was detected between the two techniques. The mean lung volume receiving 2 Gy were 42.3 and 168.35 cm3, for photons and electrons respectively. In the adjuvant treatment of early stage breast cancer WBI followed by conformal photon boost showed to be superior to electron boost in focus of the COIN and CI.

[Tumor movements detected by multi-slice CT-based image fusion in the radiotherapy of lung cancer patients]. / A tumormozgások jelentôségének sokszeletes-CT-alapú képfúziós vizsgálata tüdôdaganatos betegek sugárkezelésénél.

The aim of our study was to detect the possible uncertainties arising from tumor movements in the daily routine treatment planning, in extreme breathing conditions. Ten patients with lung cancer were enrolled into the study. According to tumor location, five patients had peripheral and five had central tumor. After the normal planning CT scan, two more scans were made with the same CT parameters in maximal exhalation and in maximal inhalation. For planning, the normal breathing scans were used with the fusion of the maximal inhalation and maximal exhalation scans. After the fusion in all breathing phases the gross tumor volumes were contoured (GTV1, GTV2, GTV3). Around the GTV1 (normal breathing phase GTV) 3 planning target volumes (PTV) were generated with the margin of 0.5 cm, 1.5 cm and 2.5 cm (PTV1, PTV2, PTV3). Individual plans were generated to all PTVs. All GTV volumes were registered. In all cases volume deviations were registered in different breathing phases (min: 1.5%, max: 35.6%). For GTV coverage comparison the coverage index (CI) was used. In case of extreme breathing conditions, using 0.5 cm margin was sufficient to reach good coverage for central tumors. For peripheral tumors 1.5 cm margin had to be used for the acceptable coverage (CI: 0.85-1.00). In our study, extreme breathing conditions were analyzed. According to our results, CT scans used in the daily routine do not exactly represent the tumor midposition and the true tumor volume. Due to breathing synchronous tumor movements, 0.5 cm margin must be used for planning in central location. In peripheral tumors wider margin should be used.