An assessment of interfractional uterine and cervical motion: Implications for radiotherapy target volume definition in gynaecological cancer

PURPOSE: To assess interfractional movement of the uterus and cervix in patients with gynaecological cancer to aid selection of the internal margin for radiotherapy target volumes. METHODS AND MATERIALS: Thirty-three patients with gynaecological cancer had an MRI scan performed on two consecutive days. The two sets of T2-weighted axial images were co-registered, and the uterus and cervix outlined on each scan. Points were identified on the anterior uterine body (Point U), posterior cervix (Point C) and upper vagina (Point V). The displacement of each point in the antero-posterior (AP), supero-inferior (SI) and lateral directions between the two scans was measured. The changes in point position and uterine body angle were correlated with bladder volume and rectal diameter. RESULTS: The mean difference (+/-1SD) in Point U position was 7mm (+/-9.0) in the AP direction, 7.1mm (+/-6.8) SI and 0.8mm (+/-1.3) laterally. Mean Point C displacement was 4.1mm (+/-4.4) SI, 2.7mm (+/-2.8) AP, 0.3 (+/-0.8) laterally, and Point V was 2.6mm (+/-3.0) AP and 0.3mm (+/-1.0) laterally. There was correlation for uterine SI movement in relation to bladder filling, and for cervical and vaginal AP movement in relation to rectal filling. CONCLUSION: Large movements of the uterus can occur, particularly in the superior-inferior and anterior-posterior directions, but cervical displacement is less marked. Rectal filling may affect cervical position, while bladder filling has more impact on uterine body position, highlighting the need for specific instructions on bladder and rectal filling for treatment. We propose an asymmetrical margin with CTV-PTV expansion of the uterus, cervix and upper vagina of 15mm AP, 15mm SI and 7mm laterally and expansion of the nodal regions and parametria by 7mm in all directions.     

Motion and deformation of the target volumes during IMRT for cervical cancer: What margins do we need?

BACKGROUND AND PURPOSE: For cervical cancer patients the CTV consists of multiple structures, exhibiting complex inter-fraction changes. The purpose of this study is to use weekly MR imaging to derive PTV margins that accommodate these changes. MATERIALS AND METHODS: Twenty patients with cervical cancer underwent a T2-weighted MRI exam before and weekly during IMRT. The CTV, GTV and surrounding organs were delineated. PTV margins were derived from the boundaries of the GTV and CTV in the six main directions and correlated with changes in the volumes of organs at risk. RESULTS: Around the GTV a margin of 12, 14, 12, 11, 4 and 8mm to the anterior, posterior, right lateral, left lateral, superior and inferior directions was needed. The CTV required margins of 24, 17, 12, 16, 11 and 8mm. The shift of the GTV and CTV in the AP directions correlated weakly with the change in rectal volume. For the bladder the correlations were even weaker. CONCLUSIONS: We used weekly MRI scans to derive inhomogeneous PTV margins that accommodate changes in GTV and CTV. The weak correlations with rectum and bladder volume suggest that measures to control filling status of these organs may not be very effective.     

Influence of organ motion on conformal vs. intensity-modulated pelvic radiotherapy for prostate cancer

PURPOSE: To compare an intensity-modulated radiotherapy (IMRT) planning approach for prostate pelvic RT with a conformal RT (CRT) approach taking into account the influence of organ-at-risk (OAR) motion. METHODS AND MATERIALS: A total of 20 male patients, each with one planning computed tomography scan and five to eight treatment computed tomography scans, were used for simulation of IMRT and CRT for delivery of a prescribed dose of 50 Gy to the prostate, seminal vesicles, and pelvic lymph nodes. Planning was done in Eclipse without correcting for OAR motion. Evaluation was performed using the CRT and IMRT dose matrices and the planning and treatment OAR outlines. The generalized equivalent uniform dose (gEUD) was calculated for 894 OAR volumes using a volume-effect parameter of 4, 12, and 8 for bowel, rectum and bladder, respectively. For the bowel, the gEUD was normalized to a reference volume of 200 cm(3). For each patient and each OAR, an average of the treatment gEUDs (gEUD(treat)) was calculated for CRT and IMRT. The paired t test was used to compare IMRT with CRT and gEUD(treat) with gEUD(plan). RESULTS: The mean gEUD(treat) was reduced from 43 to 40 Gy, 47 to 46 Gy, and 48 to 45 Gy with IMRT for the bowel, rectum, and bladder, respectively (p < 0.001). Differences between the gEUD(plan) and gEUD(treat) were not significant (p > 0.05) for any OAR but was >6% for the bowel in 6 of 20 patients. CONCLUSION: Intensity-modulated RT reduced the bowel, rectum, and bladder gEUDs also under influence of OAR motion. Neither CRT nor IMRT was robust against bowel motion, but IMRT was not less robust than CRT.     

Influence of intrafraction motion on margins for prostate radiotherapy

PURPOSE: To assess the impact of intrafraction intervention on margins for prostate radiotherapy. METHODS AND MATERIALS: Eleven supine prostate patients with three implanted transponders were studied. The relative transponder positions were monitored for 8 min and combined with previously measured data on prostate position relative to skin marks. Margins were determined for situations of (1) skin-based positioning, and (2) pretreatment transponder positioning. Intratreatment intervention was simulated assuming conditions of (1) continuous tracking, and (2) a 3-mm threshold for position correction. RESULTS: For skin-based setup without and with inclusion of intrafraction motion, prostate treatments would have required average margins of 8.0, 7.3, and 10.0 mm and 8.2, 10.2, and 12.5 mm, about the left-right, anterior-posterior, and cranial-caudal directions, respectively. Positioning by prostate markers at the start of the treatment fraction reduced these values to 1.8, 5.8, and 7.1 mm, respectively. Interbeam adjustment further reduced margins to an average of 1.4, 2.3, and 1.8 mm. Intrabeam adjustment yielded margins of 1.3, 1.5, and 1.5 mm, respectively. CONCLUSION: Significant reductions in margins might be achieved by repositioning the patient before each beam, either radiographically or electromagnetically. However, 2 of the 11 patients would have benefited from continuous target tracking and threshold-based intervention.     

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 40 Gy. 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 5 mm at planning and from 10 to 8 mm after 40 Gy) 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.     

4D-MRI analysis of lung tumor motion in patients with hemidiaphragmatic paralysis

Purpose

To investigate the complex breathing patterns in patients with hemidiaphragmatic paralysis due to malignant infiltration using four-dimensional magnetic resonance imaging (4D-MRI).

Patients and methods

Seven patients with bronchial carcinoma infiltrating the phrenic nerve were examined using 1.5 T MRI. The motion of the tumor and of both hemi-diaphragms were measured on dynamic 2D TrueFISP and 4D FLASH MRI sequences.

Results

For each patient, 3-6 breathing cycles were recorded. The respiratory-induced mean cranio-caudal displacement of the tumor was 6.6 mm (±2.8 SD). The mean displacement anterior-posterior was 7.4 mm (±2.6), while right-left movement was about 7.4 mm (±4.5). The mediastinum moved sidewards during inspiration, realizing a “mediastinal shift”. The paralyzed hemidiaphragm and the tumor showed a paradox motion during respiration in five patients. In two patients, the affected hemidiaphragm had a regular, however minimal and asynchronous motion during respiration. Respiratory variability of both tumor and diaphragm motions was about 20% although patients were instructed to breath normally. The findings showed significant differences compared to breathing patterns of patients without diaphragm dysfunction.

Conclusion

4D-MRI is a promising tool to analyze complex breathing patterns in patients with lung tumors. It should be considered for use in planning of radiotherapy to account for individual tumor motion.     

Daily CT localization for correcting portal errors in the treatment of prostate cancer

Introduction: Improved prostate localization techniques should allow the reduction of margins around the target to facilitate dose escalation in high-risk patients while minimizing the risk of normal tissue morbidity. A daily CT simulation technique is presented to assess setup variations in portal placement and organ motion for the treatment of localized prostate cancer.

Methods and Materials: Six patients who consented to this study underwent supine position CT simulation with an alpha cradle cast, intravenous contrast, and urethrogram. Patients received 46 Gy to the initial Planning Treatment Volume (PTV₁) in a four-field conformal technique that included the prostate, seminal vesicles, and lymph nodes as the Gross Tumor Volume (GTV₁). The prostate or prostate and seminal vesicles (GTV₂) then received 56 Gy to PTV₂. All doses were delivered in 2-Gy fractions.

After 5 weeks of treatment (50 Gy), a second CT simulation was performed. The alpha cradle was secured to a specially designed rigid sliding board. The prostate was contoured and a new isocenter was generated with appropriate surface markers. Prostate-only treatment portals for the final conedown (GTV₃) were created with a 0.25-cm margin from the GTV to PTV. On each subsequent treatment day, the patient was placed in his cast on the sliding board for a repeat CT simulation. The daily isocenter was recalculated in the anterior/posterior (A/P) and lateral dimension and compared to the 50-Gy CT simulation isocenter. Couch and surface marker shifts were calculated to produce portal alignment. To maintain proper positioning, the patients were transferred to a stretcher while on the sliding board in the cast and transported to the treatment room where they were then transferred to the treatment couch. The patients were then treated to the corrected isocenter. Portal films and electronic portal images were obtained for each field.

Results: Utilizing CT–CT image registration (fusion) of the daily and 50-Gy baseline CT scans, the isocenter changes were quantified to reflect the contribution of positional (surface marker shifts) error and absolute prostate motion relative to the bony pelvis. The maximum daily A/P shift was 7.3 mm. Motion was less than 5 mm in the remaining patients and the overall mean magnitude change was 2.9 mm. The overall variability was quantified by a pooled standard deviation of 1.7 mm. The maximum lateral shifts were less than 3 mm for all patients. With careful attention to patient positioning, maximal portal placement error was reduced to 3 mm.

Conclusion: In our experience, prostate motion after 50 Gy was significantly less than previously reported. This may reflect early physiologic changes due to radiation, which restrict prostate motion. This observation is being tested in a separate study. Intrapatient and overall population variance was minimal. With daily isocenter correction of setup and organ motion errors by CT imaging, PTV margins can be significantly reduced or eliminated. We believe this will facilitate further dose escalation in high-risk patients with minimal risk of increased morbidity. This technique may also be beneficial in low-risk patients by sparing more normal surrounding tissue.     

Planning target margin calculations for prostate radiotherapy based on intrafraction and interfraction motion using four localization methods

PURPOSE: To determine planning target volume (PTV) margins for prostate radiotherapy based on the internal margin (IM) (intrafractional motion) and the setup margin (SM) (interfractional motion) for four daily localization methods: skin marks (tattoo), pelvic bony anatomy (bone), intraprostatic gold seeds using a 5-mm action threshold, and using no threshold. METHODS AND MATERIALS: Forty prostate cancer patients were treated with external radiotherapy according to an online localization protocol using four intraprostatic gold seeds and electronic portal images (EPIs). Daily localization and treatment EPIs were obtained. These data allowed inter- and intrafractional analysis of prostate motion. The SM for the four daily localization methods and the IM were determined. RESULTS: A total of 1532 fractions were analyzed. Tattoo localization requires a SM of 6.8 mm left-right (LR), 7.2 mm inferior-superior (IS), and 9.8 mm anterior-posterior (AP). Bone localization requires 3.1, 8.9, and 10.7 mm, respectively. The 5-mm threshold localization requires 4.0, 3.9, and 3.7 mm. No threshold localization requires 3.4, 3.2, and 3.2 mm. The intrafractional prostate motion requires an IM of 2.4 mm LR, 3.4 mm IS and AP. The PTV margin using the 5-mm threshold, including interobserver uncertainty, IM, and SM, is 4.8 mm LR, 5.4 mm IS, and 5.2 mm AP. CONCLUSIONS: Localization based on EPI with implanted gold seeds allows a large PTV margin reduction when compared with tattoo localization. Except for the LR direction, bony anatomy localization does not decrease the margins compared with tattoo localization. Intrafractional prostate motion is a limiting factor on margin reduction.     

Adaptive radiotherapy for invasive bladder cancer: a feasibility study

PURPOSE: To evaluate the feasibility of adaptive radiotherapy (ART) in combination with a partial bladder irradiation. METHODS AND MATERIALS: Twenty-one patients with solitary T1-T4 N0M0 bladder cancer were treated to the bladder tumor + 2 cm margin planning target volume (PTV(CONV)). During the first treatment week, five daily computed tomography (CT) scans were made immediately before or after treatment. In the second week, a volume was constructed encompassing the gross tumor volumes (GTVs) on the planning scan and the five CT scans (GTV(ART)). The GTV(ART) was expanded with a 1 cm margin for the construction of a PTV(ART). Starting in the third week, patients were treated to PTV(ART). Repeat CT scans were used to evaluate treatment accuracy. RESULTS: On 5 of 91 repeat CT scans (5%), the GTV was not adequately covered by the PTV(ART). On treatment planning, there was only one scan in which the GTV was not adequately covered by the 95% isodose. On average, the treatment volumes were reduced by 40% when comparing PTV(ART) with PTV(CONV) (p < 0.0001). CONCLUSION: The adaptive strategy for bladder cancer is an effective way to deal with treatment errors caused by variations in bladder tumor position and leads to a substantial reduction in treatment volumes.     

Changes in the pelvic anatomy after an IMRT treatment fraction of prostate cancer

PURPOSE: To quantify the three-dimensional variations of pelvic anatomy after a single treatment fraction. METHODS AND MATERIALS: Forty-six prostate cancer patients underwent computed tomography (CT) scanning with an in-room CT-on-rail system, before and immediately after one intensity-modulated radiotherapy (IMRT) session. To study the soft-tissue anatomy changes, the pre- and post-treatment CT images were registered using the bony structure with an in-house image registration software system. The center of volume for both the prostate and seminal vesicles was used to assess the relative displacement of the same structure after the treatment fraction. RESULTS: During one treatment fraction (21 +/- 4 min), both the prostate and seminal vesicles showed statistically significant systematic trends in the superior and anterior directions of the patient's anatomy. The net increase in bladder volume was huge (127 +/- 79 cm(3)), yet this change did not translate into large target displacements. Although the population mean displacements in either direction were 1.3 +/- 2.9 mm for the prostate and 1.2 +/- 4.1 mm for the seminal vesicles in the anterior direction, a few patients had displacements as large as 8.4 mm and 15.6 mm, respectively. These large displacements correlated strongly (p < 0.001) with large rectal volume increases caused by gaseous build-up in the rectum. CONCLUSION: The observed intrafraction variations in anatomy during prostate IMRT sessions suggest that, for any given fraction, the organ motion and volume changes can potentially lead to compromised target coverage in about 15% of patients in whom the prostate position shifted >4 mm.     

Evaluation of inter-fraction prostate motion using kilovoltage cone beam computed tomography during radiotherapy

Aims

The success of delivering the prescribed radiation dose to the prostate while sparing adjacent sensitive tissues is largely dependent on the ability to accurately target the prostate during treatment. Kilovoltage cone beam computed tomography (CBCT) imaging can be used to monitor and compensate for inter-fraction prostate motion, but this procedure increases treatment session time and adds incidental radiation dose to the patient. We carried out a retrospective study of CBCT data to evaluate the systematic and random correction shifts of the prostate with respect to bones and external marks.

Materials and methods

A total of 449 daily CBCT studies from 17 patients undergoing intensity-modulated radiotherapy (IMRT) for localised prostate cancer were analysed. The difference between patient set-up correction shifts applied by radiation therapists (via matching prostate position in CBCT and planning computed tomography) and shifts obtained by matching bony anatomy in the same studies was used as a measure of the daily inter-fraction internal prostate motion.

Results

The average systematic and random shifts in prostate positions, calculated over all fractions versus only 10 fractions, were not found to be significantly different.

Discussion

The measured prostate shifts with respect to bony anatomy and external marks after the first 10 imaging sessions were shown to provide adequate predictive power for defining patient-specific margins in future fractions without a need for ongoing computed tomography imaging. Different options for CBCT imaging schedule are proposed that will reduce the treatment session time and imaging dose to radiotherapy patients while ensuring appropriate prostate cover and normal tissue sparing.     

Reduction of dose delivered to the rectum and bulb of the penis using MRI delineation for radiotherapy of the prostate

PURPOSE: The prostate volume delineated on MRI is smaller than on CT. The purpose of this study was to determine the influence of MRI- vs. CT-based prostate delineation using multiple observers on the dose to the target and organs at risk during external beam radiotherapy. MATERIALS AND METHODS: CT and MRI scans of the pelvic region were made of 18 patients and matched three-dimensionally on the bony anatomy. Three observers delineated the prostate using both modalities. A fourth observer delineated the rectal wall and the bulb of the penis. The planning treatment volume (PTV) was generated from the delineated prostates with a margin of 10 mm in three-dimensions. A three-field treatment plan with a prescribed dose of 78 Gy to the International Commission on Radiation Units and Measurements point was automatically generated from each PTV. Dose-volume histograms were calculated of all PTVs, rectal walls, and penile bulbs. The equivalent uniform dose was calculated for the rectal wall using a volume exponent (n = 0.12). RESULTS: The equivalent uniform dose of the CT rectal wall in plans based on the CT-delineated prostate was, on average, 5.1 Gy (SEM 0.5) greater than in the plans based on the MRI-delineated prostate. For the MRI rectal wall, this difference was 3.6 Gy (SEM 0.4). Allowing for the same equivalent uniform dose to the CT rectal wall, the prescribed dose to the PTV could be raised from 78 to 85 Gy when using the MRI-delineated prostate for treatment planning. The mean dose to the bulb of the penis was 11.6 Gy (SEM 1.8) lower for plans based on the MRI-delineated prostate. The mean coverage (volume of the PTV receiving > or =95% of the prescribed dose) was 99.9% for both modalities. The interobserver coverage (coverage of the PTV by a treatment plan designed for the PTV delineated by another observer in the same modality) was 97% for both modalities. The MRI rectum was significantly more ventrally localized than the CT rectum, probably because of the rounded tabletop and no knee support on the MRI scanner. CONCLUSIONS: The dose delivered to the rectal wall and bulb of the penis is significantly reduced with treatment plans based on the MRI-delineated prostate compared with the CT-delineated prostate, allowing a dose escalation of 2.0-7.0 Gy for the same rectal wall dose. The interobserver coverage was the same for CT and MRI delineation of the prostate. A statistically significant difference in position between the CT- and MRI-delineated rectum was observed, probably owing to a different tabletop and use of knee support.     

Evaluation of intrafraction prostate motion tracking using the Clarity Autoscan system for safety margin validation

BackgroundThe purpose of the study was to monitor intrafraction prostate motion in real-time using transperineal 4D ultrasound (TPUS) and analyze trajectories to validate clinical safety margins.Methods401 trajectories of US monitoring sessions were retrospectively evaluated for 14 patients treated for prostate cancer. The Elekta Clarity Autoscan system was used for intrafraction monitoring along the 3 directions: superior-inferior (SI), left-right (LR) and anterior-posterior (AP).ResultsThe intrafraction monitoring resulted in a mean prostate displacement of (-0.06 ± 0.49) mm, (-0.09 ± 0.61) mm and (-0.01 ± 0.78) mm in the SI, LR and AP directions, respectively. Even though large deviations up to 8 mm were detected, the frequency of occurrence was less than 0.1%. The prostate moved within ±2 mm in 99%, 98.1%, and 96.6% of the treatment time in the SI, LR and AP directions, respectively. During 100 s of monitoring, the median displacement increased from 0.2 mm to 0.8 mm and the maximum displacements increased from 5.2 mm to 7.8 mm. The majority of displacement values (99%) were within the clinical safety margins which ensures a good target coverage.ConclusionsThe largest variation of intrafraction prostate displacement was observed along the AP direction. Throughout most of the treatment time, the prostate moved within a few millimeters. The extent of prostate displacement increased for longer monitoring times. During most of the tracking time, the prostate position was within the clinically safety margins.     

Intrafraction motion in patients with cervical cancer: The benefit of soft tissue registration using MRI

Background and purpose

During radiation delivery, target volumes change their position and shape due to intrafraction motion. The extent of these changes and the capability to correct for them will contribute to the benefit of an MRI-accelerator in terms of PTV margin reduction. Therefore, we investigated the primary CTV motion within a typical IMRT delivery time for cervical cancer patients for various correction techniques: no registration, rigid bony anatomy registration, and rigid soft tissue registration.

Materials and methods

Twenty-two patients underwent 2-3 offline MRI exams before and during their radiation treatment. Each MRI exam included four sagittal and four axial MRI scans alternately within 16 min. We addressed the CTV motion by comparing subsequent midsagittal CTV delineations and investigated the correlation with intrafraction bladder filling.

Results

The maximum (residual) motions within 16 min for all points on the CTV contour for 90% of the MRI exams without registration, with rigid bony anatomy registration, and with rigid soft tissue registration were 10.6, 9.9, and 4.0 mm. A significant but weak correlation was found between intrafraction bladder filling and CTV motion.

Conclusions

Considerable intrafraction CTV motion is observed in cervical cancer patients. Intrafraction MRI-guided soft tissue registration using an MRI-accelerator will correct for this motion.