Intrafraction motion of the prostate during an IMRT session: a fiducial-based 3D measurement with Cone-beam CT

Background: Image-guidance systems allow accurate interfractional repositioning of IMRT treatments, however, these may require up to 15 minutes. Therefore intrafraction motion might have an impact on treatment precision. 3D geometric data regarding intrafraction prostate motion are rare; we therefore assessed its magnitude with pre- and post-treatment fiducial-based imaging with cone-beam-CT (CBCT). Methods: 39 IMRT fractions in 5 prostate cancer patients after (125)I-seed implantation were evaluated. Patient position was corrected based on the (125)I-seeds after pre-treatment CBCT. Immediately after treatment delivery, a second CBCT was performed. Differences in bone- and fiducial position were measured by seed-based grey-value matching. Results: Fraction time was 13.6 +/- 1.6 minutes. Median overall displacement vector length of (125)Iseeds was 3 mm (M = 3 mm, Sigma = 0.9 mm, sigma = 1.7 mm; M: group systematic error, Sigma: SD of systematic error, sigma: SD of random error). Median displacement vector of bony structures was 1.84 mm (M = 2.9 mm, Sigma = 1 mm, sigma = 3.2 mm). Median displacement vector length of the prostate relative to bony structures was 1.9 mm (M = 3 mm, Sigma = 1.3 mm, sigma = 2.6 mm). Conclusion: a) Overall displacement vector length during an IMRT session is < 3 mm. b) Positioning devices reducing intrafraction bony displacements can further reduce overall intrafraction motion. c) Intrafraction prostate motion relative to bony structures is < 2 mm and may be further reduced by institutional protocols and reduction of IMRT duration

PATIENT-SPECIFIC 3D PRETREATMENT AND POTENTIAL 3D ONLINE DOSE VERIFICATION OF MONTE CARLO-CALCULATED IMRT PROSTATE TREATMENT PLANS

Purpose: Fast and reliable comprehensive quality assurance tools are required to validate the safety and accuracy of complex intensity-modulated radiotherapy (IMRT) plans for prostate treatment. In this study, we evaluated the performance of the COMPASS system for both off-line and potential online procedures for the verification of IMRT treatment plans. Methods and Materials: COMPASS has a dedicated beam model and dose engine, it can reconstruct three-dimensional dose distributions on the patient anatomy based on measured fluences using either the MatriXX two-dimensional (2D) array (offline) or a 2D transmission detector (T2D) (online). For benchmarking the COMPASS dose calculation, various dose-volume indices were compared against Monte Carlo-calculated dose distributions for five prostate patient treatment plans. Gamma index evaluation and absolute point dose measurements were also performed in an inhomogeneous pelvis phantom using extended dose range films and ion chamber for five additional treatment plans. Results: MatriXX-based dose reconstruction showed excellent agreement with the ion chamber (<0.5%, except for one treatment plan, which showed 1.5%), film (similar to 100% pixels passing gamma criteria 3%/3 mm) and mean dose-volume indices (<2%). The T2D based dose reconstruction showed good agreement as well with ion chamber (<2%), film (similar to 99% pixels passing gamma criteria 3%/3 mm), and mean dose-volume indices (<5.5%). Conclusion: The COMPASS system qualifies for routine prostate IMRT pretreatment verification with the MatriXX detector and has the potential for on-line verification of treatment delivery using T2D. (C) 2011 Elsevier Inc

Recurrent benign copy number variants & issues in interpretation of variants of unknown significance identified by cytogenetic microarray in Indian patients with intellectual disability

Background & objectives: Cytogenetic microarray (CMA) is now recommended as a first-tier clinical diagnostic test in cases with idiopathic intellectual disability and/or developmental delay (ID/DD). Along with clinically relevant variants, CMA platforms also identify variants of unknown significance (VUS). This study was done to look for utility and various issues in interpretation of copy number variants (CNVs) in Indian patients with ID/DD. Methods: The CMA was performed in 86 Indian patients with idiopathic ID/DD with or without dysmorphic features. CNV was reported if copy number gain was >400 kb in size and copy number loss was > 200 kb in size. Results: Pathogenic CNVs were found in 18 of 86 (20.9%) patients. One large (14 Mb size) de novo heterozygous copy number gain was found in one patient. VUS (total 31) were present in 17 of 86 (19.7%) patients. Five novel recurrent benign CNVs were also present in our patients. Interpretation & conclusions: Our findings highlight the difficulties in interpretation of CNVs identified by CMA. More Indian data on VUS and recurrent benign CNVs will be helpful in the interpretation of CMA in patients with ID/DD

Evaluation of a 2D detector array for patient-specific VMAT QA with different setups

For pre-treatment plan verification of advanced treatment techniques such as intensity-modulated arc therapy, a fast and reliable dosimetric device is required. In this study, we investigated the suitability of MatriXX in different setups for verification of volumetric modulated arc therapy (VMAT) plans. If MatriXX is used in a stationary phantom (MULTICube), the measured dose is dependent on the beam angle. For the first setup (MatriXX/MULTICube), we developed correction factors (CFs) for each detector element (1020 CFs). We investigated the accuracy of these CFs by verifying 12 VMAT plans. In the second setup, we also assessed the suitability of MatriXX in a dedicated holder. Using this setup (MatriXX/Holder), 30 additional VMAT plans were verified. Deviations of up to similar to 17% and similar to 11% were noted for one of the ion chambers at 90 degrees and 180 degrees gantry positions. The influence of the beam angle dependence (MULTICube) can explicitly be seen when a gamma criterion of 2%/2 mm was chosen. An overall improvement of 4.3% of passing pixels (pp) was noted after applying beam angular-dependent CFs. When the gamma criterion was 3%/3 mm, the %pp was >= 95% without and similar to 100% with correction. With the second setup, MatriXX/holder, we showed excellent agreement between measurements and calculations. The % pp averaged over all plans (30 VMAT treatment plans) was nearly similar to 100%. The combination of MatriXX with MULTICube or with holder proved to be a fast and reliable method for pretreatment verification of arc therapy with sufficient accuracy

SU‐E‐T‐441: Sensitivity of a 3D‐Verification System to VMAT Delivery Errors

Purpose: VMAT offers continuous dose delivery in the form of arcs while dynamically changing position of collimators and dose rate. The aim of the present study is to investigate the sensitivity of a 3D‐verification system to different VMAT delivery errors. Methods: Three VMAT plans were generated with MONACO TPS (v2.0, Elekta‐CMS, Maryland Heights, MO) for brain tumor paradigms. With in‐house software, we modified the plans introducing the following errors: (i) One set of leaf bank was opened by 1mm, 2mm and individual leaves were randomly opened (0mm–2mm). (ii) Both sets of leaf banks were shifted by +/−1mm and +/− 2mm. (iii) Gantry angle was shifted by +/−0.5°, +/−1°, +/−2° and randomly shifted (−2° to +2°). All these plans (a total of 45) were delivered to a MatriXX‐based COMPASS system (v2.0, IBA‐Dosimetry,Germany). 3D‐dose distribution was reconstructed onto the patient anatomy based on the measured fluences. Dose—volume parameters for target (D95) and critical organs (Davg) were compared and analyzed. Results: For three reference plans, the maximum dose‐difference (MDD) between MONACO and COMPASS was about 10% (Davg‐lens). However, the absolute dose‐difference (ADD) for the same was 4cGy. For plans with errors in one set of leaf bank, the MDD and ADD were 10% and 13cGy for Davg‐optic nerve, respectively. With errors in both leaf banks, the MDD and ADD were 15% and 21cGy for Davg‐optic nerve, respectively. With gantry angle errors, the MDD and ADD were 50% and 20cGy, respectively. For PTV‐D95, the MDD noticed was 6% and the ADD was 16cGy for different kind of errors. Conclusions: Any increase in aperture size (error in one leaf bank) showed systematic deviations. Shifts in both leaf banks up to 2mm and gantry angle difference (2°) showed considerable deviations. Errors greater than 2mm/2° can be detected with COMPASS system in most of the cases. © 2011, American Association of Physicists in Medicine. All rights reserved

Clinical utility of multiplex ligation-dependent probe amplification technique in identification of aetiology of unexplained mental retardation: A study in 203 Indian patients

Background & objectives: Developmental delay (DD)/mental retardation also described as intellectual disability (ID), is seen in 1-3 per cent of general population. Diagnosis continues to be a challenge at clinical level. With the advancement of new molecular cytogenetic techniques such as cytogenetic microarray (CMA), multiplex ligation-dependent probe amplification (MLPA) techniques, many microdeletion/microduplication syndromes with DD/ID are now delineated. MLPA technique can probe 40-50 genomic regions in a single reaction and is being used for evaluation of cases with DD/ID. In this study we evaluated the clinical utility of MLPA techniques with different probe sets to identify the aetiology of unexplained mental retardation in patients with ID/DD. Methods: A total of 203 randomly selected DD/ID cases with/without malformations were studied. MLPA probe sets for subtelomeric regions (P070/P036) and common microdeletions/microduplications (P245-A2) and X-chromosome (P106) were used. Positive cases with MLPA technique were confirmed using either fluorescence in situ hybridization (FISH) or follow up confirmatory MLPA probe sets. Results: The overall detection rate was found to be 9.3 per cent (19 out of 203). The detection rates were 6.9 and 7.4 per cent for common microdeletion/microduplication and subtelomeric probe sets, respectively. No abnormality was detected with probe set for X-linked ID. The subtelomeric abnormalities detected included deletions of 1p36.33, 4p, 5p, 9p, 9q, 13q telomeric regions and duplication of 9pter. The deletions/duplications detected in non telomeric regions include regions for Prader Willi/Angelman regions, Williams syndrome, Smith Magenis syndrome and Velocardiofacial syndrome. Interpretation & conclusions: Our results show that the use of P245-A2 and P070/P036-E1 probes gives good diagnostic yield. Though MLPA cannot probe the whole genome like cytogenetic microarray, due to its ease and relative low cost it is an important technique for evaluation of cases with DD/ID

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

We validate the dosimetric performance of COMPASS (R), a novel 3D quality assurance system for verification of volumetric-modulated arc therapy (VMAT) treatment plans that can correlate the delivered dose to the patient's anatomy, taking into account the tissue inhomogeneity. The accuracy of treatment delivery was assessed by the COMPASS (R) 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 (R) for three additional treatment plans and these were used to verify the accuracy of treatment planning dose calculations. The results matched well between COMPASS (R) 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 patient's anatomy. Slight deviations were found for large open fields. These could be minimized by improving the COMPASS (R) in-built beam model

Comparison of anisotropic aperture based intensity modulated radiotherapy with 3D-conformal radiotherapy for the treatment of large lung tumors

Purpose/objective(s): IMRT allows dose escalation for large lung tumors, but respiratory motion may compromise delivery. A treatment plan that modulates fluence predominantly in the transversal direction and leaves the fluence identical in the direction of the breathing motion may reduce this problem. Materials/methods: Planning-CT-datasets of 20 patients with Stage I-IV non small cell lung cancer (NSCLC) formed the basis of this study. A total of two IMRT plans and one 3D plan were created for each patient. Prescription dose was 60 Gy to the CTV and 70 Gy to the GTV. For the 3D plans an energy of 18 MV photons was used. IMRT plans were calculated for 6 MV photons with 13 coplanar and with 17 noncoplanar beams. Robustness of the used method of anisotropic modulation toward breathing motion was tested in a 13-field IMRT plan. Results: As a consequence of identical prescription doses, mean target doses were similar for 3D and IMRT. Differences between 3D and 13- and 17-field IMRT were significant for CTV Dmin (43 Gy vs. 49.1 Gy vs. 48.6 Gy: p < 0.001) and CTV D-95 (53.2 Gy vs. 55.0 Gy vs. 55.4 Gy; p = 0.001). The D-mean of the contralateral lung was significantly lower in the 17-field plans (17-field IMRT vs. 13- vs. 3D: 12.5 Gy vs. 14.8 Gy vs. 15.8 Gy: p < 0.05). The spinal cord dose limit of 50 Gy was always respected in IMRT plans and only in 17 of 20 3D-plans. Heart D-max was only marginally reduced with IMRT (3D vs. 13- vs. 17-field IMRT: 38.2 Gy vs. 36.8 Gy vs. 37.8 Gy). Simulated breathing motion caused only minor changes in the IMRT dose distribution (similar to 0.5-1 Gy). Conclusions: Anisotropic modulation of IMRT improves dose delivery over 3D-RT and renders IMRT plans robust toward breathing induced organ motion, effectively preventing interplay effects. (C) 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 102 (2012) 268-27

A new strategy for online adaptive prostate radiotherapy based on cone-beam CT

Purpose: Interfractional organ motion and patient positioning errors during prostate radiotherapy can have deleterious clinical consequences. It has become clinical practice to re-position the patient with image-guided translational position correction before each treatment to compensate for those errors. However, tilt errors can only be corrected with table corrections in six degrees of freedom or 'full" adaptive treatment planning strategies. Organ shape deformations can only be corrected by 'full" plan adaptation. This study evaluates the potential of instant treatment plan adaptation (fast isodose line adaptation with real-time close manipulating tools) based on cone-beam CT (CBCT) to further improve treatment quality. Methods and Materials: Using in-house software, CBCTs were modified to approximate a correct density calibration. To evaluate the dosimetric accuracy, dose distributions based on CBCTs were compared with dose distributions calculated on conventional planning CTs (PCT)for four datasets (one inhomogeneous phantom, three patient datasets). To determine the potential dosimetric benefit of a 'full" plan adaptation over translational position correction, dose distributions were re-optimized using graphical "online" close modification tools for three additional patients' CT-datasets with a substantially distended rectum while the original plans have been created with an empty rectum (single treatment fraction estimates). Results: Absolute close deviations of lip to 51% in comparison to the PCT were observed when uncorrected CBCTs were used for replanning. After density calibration of the CBCTs, 97% of the dose deviations were, <= 3% (gamma index: 3%/3 mm). Translational position correction restored the PTV dose (D(95)) to 73% of the corresponding dose of the reference plan. After plan adaptation, larger improvements of dose restoration to 95% were observed. Additionally, the rectal dose (D(30)) was further decreased by 42 percentage points (mean of three patient datasets). Conclusions: An accurate dose calculation based on CBCT-datasets is possible when density distributions are corrected. The presented adaptive strategy has the potential to reduce close delivery, errors due to organ deformations to a minimum