S. Quint

In vivo dosimetry for prostate cancer patients using an electronic portal imaging device (EPID); demonstration of internal organ motion

PURPOSE To investigate the use of a commercially available video-based EPID for in vivo dosimetry during treatment of prostate cancer patients. METHODS For 10 prostate cancer patients, the inter-fraction variation within measured portal dose images (PDIs) was assessed and measured PDIs were compared with corresponding predicted PDIs based on the planning CT scan of the patient. RESULTS For the lateral fields, the average standard deviation in the measured on-axis portal doses during the course of a treatment was 0.9%; for the anterior fields this standard deviation was 2.2%. The difference between the average on-axis measured portal dose and the predicted portal dose was 0.3+/-2.1% (1 SD) for the lateral fields and 0.7+/-3.4% (1 SD) for the anterior fields. Off-axis differences between measured and predicted portal doses were regularly much larger (up to 15%) and were caused by frequently occurring gas pockets inside the rectum of the patients during treatment or during acquisition of the planning CT scan. The detected gas pockets did sometimes extend into the gross tumour volume (GTV) area as outlined in the planning CT scans, implying a shift of the anterior rectum wall and prostate in the anterior direction (internal organ motion). CONCLUSIONS The developed procedures for measurement and prediction of PDIs allow accurate dosimetric quality control of the treatment of prostate cancer patients. Comparing measured PDIs with predicted PDIs can reveal internal organ motion.

On-line set-up corrections during radiotherapy of patients with gynecologic tumors

PURPOSE Positioning of patients with gynecologic tumors for radiotherapy has proven to be relatively inaccurate. To improve the accuracy and reduce the margins from clinical target volume (CTV) to planning target volume (PTV), on-line set-up corrections were investigated. METHODS AND MATERIALS Anterior-posterior portal images of 14 patients were acquired using the first six monitor units (MU) of each irradiation fraction. The set-up deviation was established by matching three user-defined landmarks in portal and simulator image. If the two-dimensional deviation exceeded 4 mm, the table position was corrected. A second portal image was acquired using 30 MU of the remaining dose. This image was analyzed off-line using a semiautomatic contour match to obtain the final set-up accuracy. To verify the landmark match accuracy, the contour match was retrospectively performed on the six MU images as well. RESULTS The standard deviation (SD) of the distribution of systematic set-up deviations after correction was < 1 mm in left-right and cranio-caudal directions. The average random deviation was < 2 mm in these directions (1 SD). Before correction, all standard deviations were 2 to 3 mm. The landmark match procedure was sufficiently accurate and added on average 3 min to the treatment time. The application of on-line corrections justifies a CTV-to-PTV margin reduction to about 5 mm. CONCLUSIONS On-line set-up corrections significantly improve the positioning accuracy. The procedure increases treatment time but might be used effectively in combination with off-line corrections.

Individualized nonadaptive and online-adaptive intensity-modulated radiotherapy treatment strategies for cervical cancer patients based on pretreatment acquired variable bladder filling computed tomography scans

PURPOSE To design and evaluate individualized nonadaptive and online-adaptive strategies based on a pretreatment established motion model for the highly deformable target volume in cervical cancer patients. METHODS AND MATERIALS For 14 patients, nine to ten variable bladder filling computed tomography (CT) scans were acquired at pretreatment and after 40 Gy. Individualized model-based internal target volumes (mbITVs) accounting for the cervix and uterus motion due to bladder volume changes were generated by using a motion-model constructed from two pretreatment CT scans (full and empty bladder). Two individualized strategies were designed: a nonadaptive strategy, using an mbITV accounting for the full-range of bladder volume changes throughout the treatment; and an online-adaptive strategy, using mbITVs of bladder volume subranges to construct a library of plans. The latter adapts the treatment online by selecting the plan-of-the-day from the library based on the measured bladder volume. The individualized strategies were evaluated by the seven to eight CT scans not used for mbITVs construction, and compared with a population-based approach. Geometric uniform margins around planning cervix-uterus and mbITVs were determined to ensure adequate coverage. For each strategy, the percentage of the cervix-uterus, bladder, and rectum volumes inside the planning target volume (PTV), and the clinical target volume (CTV)-to-PTV volume (volume difference between PTV and CTV) were calculated. RESULTS The margin for the population-based approach was 38 mm and for the individualized strategies was 7 to 10 mm. Compared with the population-based approach, the individualized nonadaptive strategy decreased the CTV-to-PTV volume by 48% ± 6% and the percentage of bladder and rectum inside the PTV by 5% to 45% and 26% to 74% (p < 0.001), respectively. Replacing the individualized nonadaptive strategy by an online-adaptive, two-plan library further decreased the percentage of bladder and rectum inside the PTV (0% to 10% and -1% to 9%; p < 0.004) and the CTV-to-PTV volume (4-96 ml). CONCLUSIONS Compared with population-based margins, an individualized PTV results in better organ-at-risk sparing. Online-adaptive radiotherapy further improves organ-at-risk sparing.

Reduction of irradiated small bowel volume and accurate patient positioning by use of a bellyboard device in pelvic radiotherapy of gynecological cancer patients

PURPOSE To reduce the volume of small bowel within pelvic treatment fields for gynecological cancer using a bellyboard device and to determine the accuracy of the prone treatment position. MATERIALS AND METHODS Fifteen consecutive patients with a gynecologic malignancy who were treated with postoperative pelvic radiotherapy were selected for this study. The volume of small bowel within the treatment fields was calculated for both the supine and prone treatment positions. The patients were treated in the prone position in a so-called bellyboard device. During treatment sessions electronic portal images were obtained. An off-line setup verification and correction protocol was used and the setup accuracy of the positioning in the bellyboard was determined. RESULTS The average volume of small bowel within the treatment fields was 229 cm(3) and 66 cm(3) in the supine and prone treatment, respectively, which means an average volume reduction in the prone position of 64% (95% CI 56-72%), as compared with the supine position. For the position of the patient in the field, the systematic error defined by the standard deviation (SD) of the mean difference per patient between simulation and treatment images was 1.7 mm in the lateral direction, 2.1 mm in the craniocaudal direction and 1.7 mm in the ventrodorsal direction. On average, only 0.4 setup correction per patient was required to achieve this accuracy. The random day-to-day variations were 1.9 (1SD), 2.6 and 2.3 mm, respectively. Standard deviations of the systematic differences between patient positioning relative to the bellyboard were 6.2 mm in lateral direction and 9.1 mm in craniocaudal direction. CONCLUSIONS Treatment of gynecological cancer patients in the prone position using a bellyboard reduces the volume of irradiated small bowel. An off-line verification and correction protocol ensures accurate patient positioning. Daily setup variations using the bellyboard were small (1 SD<3 mm). Therefore for pelvic radiotherapy in patients with a gynecological malignancy, the use of a bellyboard is recommended.

Detection of organ movement in cervix cancer patients using a fluoroscopic electronic portal imaging device and radiopaque markers

PURPOSE To investigate the use of a fluoroscopic electronic portal imaging device (EPID) and radiopaque markers to detect internal cervix movement. METHODS AND MATERIALS For 10 patients with radiopaque markers clamped to the cervix, electronic portal images were made during external beam irradiation. Bony structures and markers in the portal images were registered with the same structures in the corresponding digitally reconstructed radiographs of the planning computed tomogram. RESULTS The visibility of the markers in the portal images was good, but their fixation should be improved. Generally, the correlation between bony structure displacements and marker movement was poor, the latter being substantially larger. The standard deviations describing the systematic and random bony anatomy displacements were 1.2 and 2.6 mm, 1.7 and 2.9 mm, and 1.6 and 2.7 mm in the lateral, cranial-caudal, and dorsal-ventral directions, respectively. For the marker movement those values were 3.4 and 3.4 mm, 4.3 and 5.2 mm, 3.2 and 5.2 mm, respectively. Estimated clinical target volume to planning target volume (CTV-PTV) planning margins (approximately 11 mm) based on the observed overall marker displacements (bony anatomy + internal cervix movement) are only marginally larger than the margins required to account for internal marker movement alone. CONCLUSIONS With our current patient setup techniques and methods of setup verification and correction, the required CTV-PTV margins are almost fully determined by internal organ motion. Setup verification and correction using radiopaque markers might allow decreasing those margins, but technical improvements are needed.

Clinical Implementation of an Online Adaptive Plan-of-the-Day Protocol for Nonrigid Motion Management in Locally Advanced Cervical Cancer IMRT

PURPOSE To evaluate the clinical implementation of an online adaptive plan-of-the-day protocol for nonrigid target motion management in locally advanced cervical cancer intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS Each of the 64 patients had four markers implanted in the vaginal fornix to verify the position of the cervix during treatment. Full and empty bladder computed tomography (CT) scans were acquired prior to treatment to build a bladder volume-dependent cervix-uterus motion model for establishment of the plan library. In the first phase of clinical implementation, the library consisted of one IMRT plan based on a single model-predicted internal target volume (mpITV), covering the target for the whole pretreatment observed bladder volume range, and a 3D conformal radiation therapy (3DCRT) motion-robust backup plan based on the same mpITV. The planning target volume (PTV) combined the ITV and nodal clinical target volume (CTV), expanded with a 1-cm margin. In the second phase, for patients showing >2.5-cm bladder-induced cervix-uterus motion during planning, two IMRT plans were constructed, based on mpITVs for empty-to-half-full and half-full-to-full bladder. In both phases, a daily cone beam CT (CBCT) scan was acquired to first position the patient based on bony anatomy and nodal targets and then select the appropriate plan. Daily post-treatment CBCT was used to verify plan selection. RESULTS Twenty-four and 40 patients were included in the first and second phase, respectively. In the second phase, 11 patients had two IMRT plans. Overall, an IMRT plan was used in 82.4% of fractions. The main reasons for selecting the motion-robust backup plan were uterus outside the PTV (27.5%) and markers outside their margin (21.3%). In patients with two IMRT plans, the half-full-to-full bladder plan was selected on average in 45% of the first 12 fractions, which was reduced to 35% in the last treatment fractions. CONCLUSIONS The implemented online adaptive plan-of-the-day protocol for locally advanced cervical cancer enables (almost) daily tissue-sparing IMRT.

Inter-fraction bladder filling variations and time trends for cervical cancer patients assessed with a portable 3-dimensional ultrasound bladder scanner

BACKGROUND AND PURPOSE For cervical cancer patients, bladder filling variations may result in inadequate EBRT target coverage, unless large safety margins are used. For a group of patients who received full bladder instructions, inter-fraction variations and time trends in bladder volume were quantified, and a 3D ultrasound (US) scanner was tested for on-line bladder volume measurements. METHODS AND MATERIALS For 24 patients, the bladder volume was measured with US at the time of the planning CT scan, and twice weekly during the course of RT. Comparisons of US with planning CT were used to assess the bladder scanner accuracy. Patients were treated in prone on a belly board, EPID images were acquired to correlate set-up errors with bladder filling variations. RESULTS Measured US and CT bladder volumes were strongly correlated (R = 0.97, slope 1.1 +/- 0.1). The population mean bladder volume at planning of 378 +/- 209 ml (1 SD) reduced to 109 +/- 88 ml (1 SD) in week 6, a reduction by 71% (average reduction 46 ml/week), revealing a large inter-fraction time trend. Intra-patient variation in bladder volume during RT was 168 ml (1 SD) (range 70-266 ml). Rotation around the LR axis was significantly correlated with bladder volume changes. CONCLUSIONS Despite a full bladder instruction, bladder volumes reduced dramatically during treatment, implying large time trends in target position of these patients. The portable US scanner provides a quick and reliable measurement of the bladder volume, which might assist future online treatment adaptation.

Toward an individualized target motion management for IMRT of cervical cancer based on model-predicted cervix–uterus shape and position

BACKGROUND AND PURPOSE To design and evaluate a 3D patient-specific model to predict the cervix-uterus shape and position. METHODS AND MATERIALS For 13 patients lying in prone position, 10 variable bladder filling CT-scans were acquired, 5 at planning and 5 after 40Gy. The delineated cervix-uterus volumes in 2-5 pre-treatment CT-scans were used to generate patient-specific models that predict the cervix-uterus geometry by bladder volume. Model predictions were compared to delineations, excluding those used for model construction. The prediction error was quantified by the margin required around the predicted volumes to accommodate 95% of the delineated volume and by the predicted-to-delineated surface distance. RESULTS The prediction margin was significantly smaller (average 50%) than the margin encompassing the cervix-uterus motion. The prediction margin could be decreased (from 7 to 5mm at planning and from 10 to 8mm after 40Gy) by increasing (from 2 to 5) the number of CT-scans used for the model construction. CONCLUSION For most patients, even with a model based on only two CT-scans, the prediction error was well below the margin encompassing the cervix-uterus motion. The described approach could be used to create prior to treatment, an individualized treatment strategy.

Increasing treatment accuracy for cervical cancer patients using correlations between bladder-filling change and cervix–uterus displacements: Proof of principle

PURPOSE To investigate application of pre-treatment established correlations between bladder-filling changes and cervix-uterus displacements in adaptive therapy. MATERIALS AND METHODS Thirteen cervical cancer patients participated in this prospective study. Pre-treatment, and after delivery of 40 Gy, a full bladder CT-scan was acquired, followed by voiding the bladder and acquisition of 4 other 3D scans in a 1h period with a naturally filling bladder (variable bladder filling CT-scans, VBF-scans). For the pre-treatment VBF-scans, linear correlations between bladder volume change and displacements of the tip of the uterus (ToU) and the center of mass (CoM) of markers implanted in the fornices of the vagina relative to the full bladder planning scan were established. Prediction accuracy of these correlation models was assessed by comparison with actual displacements in CT-scans, both pre-treatment and after 40 Gy. Inter-fraction ToU and marker-CoM displacements were derived from the established correlations and twice-weekly performed in-room bladder volume measurements, using a 3D ultrasound scanner. RESULTS Target displacement in VBF-scans ranged from up to 65 mm in a single direction to almost 0mm, depending on the patient. For pre-treatment VBF-scans, the linear correlation models predicted the mean 3D position change for the ToU of 26.1 mm±10.8 with a residual of only 2.2 mm±1.7. For the marker-CoM, the 8.4 mm±5.3 mean positioning error was predicted with a residual of 0.9 mm±0.7. After 40Gy, the mean ToU displacement was 26.8 mm±15.8, while prediction based on the pre-treatment correlation models yielded a mean residual error of 9.0 mm±3.7. Target positioning errors in the fractioned treatments were very large, especially for the ToU (-18.5mm±11.2 for systematic errors in SI-direction). CONCLUSIONS Pre-treatment acquired VBF-scans may be used to substantially enhance treatment precision of cervical cancer patients. Application in adaptive therapy is promising and warrants further investigation. For highly conformal (IMRT) treatments, the use of a full bladder drinking protocol results in unacceptably large systematic set-up errors.

Surgical clips for position verification and correction of non-rigid breast tissue in simultaneously integrated boost (SIB) treatments

BACKGROUND AND PURPOSE The aim of this study is to investigate whether surgical clips in the lumpectomy cavity are representative for position verification of both the tumour bed and the whole breast in simultaneously integrated boost (SIB) treatments. MATERIALS AND METHODS For a group of 30 patients treated with a SIB technique, kV and MV planar images were acquired throughout the course of the fractionated treatment. The 3D set-up error for the tumour bed was derived by matching the surgical clips (3-8 per patient) in two almost orthogonal planar kV images. By projecting the 3D set-up error derived from the planar kV images to the (u, v)-plane of the tangential beams, the correlation with the 2D set-up error for the whole breast, derived from the MV EPID images, was determined. The stability of relative clip positions during the fractionated treatment was investigated. In addition, for a subgroup of 15 patients, the impact of breathing was determined from fluoroscopic movies acquired at the linac. RESULTS The clip configurations were stable over the course of radiotherapy, showing an inter-fraction variation (1 SD) of 0.5mm on average. Between the start and the end of the treatment, the mean distance between the clips and their center of mass was reduced by 0.9 mm. A decrease larger than 2mm was observed in eight patients (17 clips). The top-top excursion of the clips due to breathing was generally less than 2.5mm in all directions. The population averages of the difference (+/-1 SD) between kV and MV matches in the (u, v)-plane were 0.2+/-1.8mm and 0.9+/-1.5mm, respectively. In 30% of the patients, time trends larger than 3mm were present over the course of the treatment in either or in both kV and MV match results. Application of the NAL protocol based on the clips reduced the population mean systematic error to less than 2mm in all directions, both for the tumour bed and the whole breast. Due to the observed time trends, these systematic errors can be further reduced to about 1mm by using an eNAL protocol instead. CONCLUSIONS The relative positions of implanted surgical clips in the lumpectomy cavity after breast-conserving surgery remain stable during the course of radiotherapy treatment. Application of a NAL or eNAL set-up correction protocol based on surgical clips allows for adequate treatment of both the tumour bed and the whole breast with tight CTV-PTV margins.