Planning CT Simulation Research Articles

GPP02 Presentation Time: 8:10 AM: Evaluating the Relationship Between Vaginal Apex ``Dog Ears'' and Patterns of Recurrence in Endometrial Cancer Following Adjuvant Image Guided Vaginal Cuff Brachytherapy

<h3>Purpose</h3> The vaginal cuff is a common site of tumor recurrence following surgery for endometrial cancer, and adjuvant vaginal cuff brachytherapy (VCB) is indicated to reduce the risk of local recurrence. Following hysterectomy, many patients have redundant tissue at the lateral apex of the vaginal cuff ("dog ears"). This extra tissue may extend irregularly beyond the typical cylindrical dose distribution of radiation delivered during single channel VCB and it is hypothesized that they are a potential site of local treatment failure even after VCB. The effects of the presence and size of vaginal cuff "dog ears" on tumor recurrence is not yet fully understood. The aim of this study is to evaluate the prevalence and size of extra tissue at the vaginal apex, and whether these factors predict disease recurrence in patients treated with adjuvant VCB for endometrial cancer. <h3>Materials and Methods</h3> We retrospectively reviewed the medical records of 219 patients with early-stage endometrial cancer treated with image-guided single channel VCB at our institution from 2012 - 2021 with available brachytherapy planning CT simulation images. "Dog ears" were defined as the presence of additional soft tissue extending at least 10 mm from the apex of the vaginal cuff perpendicular to the surface of the brachytherapy applicator as defined on a coronal or axial CT simulation. Patient characteristics and outcomes including stage, size and laterality of dog ears, presence of air gaps, and patterns of failure were collected. Vaginal cuff recurrence (VCR) failure free survival was calculated from time of first brachytherapy to VCR and was estimated by the product limit method of Kaplan and Meier. Fisher's exact test was used to compare categorical variables and a multivariate logistic regression model was developed to evaluate the association of overall treatment failure with various factors of interest. <h3>Results</h3> We found that 57.5% of patients (n = 126) met our criteria for having "dog ears," which, on average, extended 23.8 mm (SD = 6.4) from the brachytherapy applicator. In total, 13 patients (5.9%) developed a VCR, 12 (5.5%) developed a regional recurrence, and 16 (7.3%) developed distant recurrence. There was no statistically significant difference in VCRs between patients with dog ears and those without dog ears (7.1% vs 4.3%, p=0.56). The various surgical approaches (abdominal, laparoscopic, transvaginal) did not have an increased propensity to result in dog ears (p=0.74). The 3-year probability of VCR failure-free survival is 86%. On multivariate analysis (MVA), no factors predicted for overall treatment failure including the presence of dog ears, maximum dimension of dog ears, FIGO stage, presence of air gaps at the applicator surface on post insertion CT images, or brachytherapy duration. There was a trend toward increased risk of recurrence with higher grade histology on MVA (p=0.0805). <h3>Conclusions</h3> In this investigation of a single institution experience with single-channel image-guided VCB, the presence of "dog ears" at the vaginal apex is prevalent; however, VCR remains low with distant metastases being the predominant site of failure. While dog ears appear to have little impact on overall recurrence patterns, these may be a factor to consider when planning adjuvant brachytherapy including choosing alternate applicators.

Academic patterns of practice regarding CT simulation scans and radiology review

ObjectiveCurrently, there are no consensus guidelines about handling incidental radiological findings on radiotherapy planning CT simulation scans. Retrospective studies analyzing incidental findings on CT simulations show a small, but not insignificant, rate of both oncologic and non-oncologic findings. These findings may have medico-legal, financial, and clinical implications. Given a lack of guidelines, we obtained a formal survey of multiple academic institutions to evaluate how CT simulations are handled in regard to incidental findings. MethodsA formal survey was developed consisting of 12 questions related to institutional practices regarding CT simulation scans. From 7/18/21 to 8/27/21 and 5/6/22 to 5/24/22, the survey was administered electronically by REDCap to key personnel at Academic Radiation Oncology Programs identified through the American Society for Radiation Oncology (ASTRO) with inclusion criteria including an active ACGME approved Radiation Oncology residency program. ResultsIn total, 88 academic radiation oncology programs were surveyed with total of 45 responses (51%). 1 out of 45 departments who responded has formal guidelines regarding workup of incidental findings. There is variability about sending CT simulation scans for official radiology review if an incidental finding is identified. ConclusionsBased on a measurable rate of incidental findings on radiotherapy planning CT simulations and their possible implications, our survey illustrates a likely need for consensus recommendations for handling such findings to improve patient care and safety.

PO-1684 Fast delivery of IMRT to metastatic disease without planning CT simulation.

PO-1684 Fast delivery of IMRT to metastatic disease without planning CT simulation.

RADT-07. DETERMINATION OF THE OPTIMAL TIME INTERVAL BETWEEN POST-OPERATIVE MRI AND CT SIMULATION FOR STEREOTACTIC RADIOSURGERY PLANNING

Abstract BACKGROUND The incidence of brain metastasis is approximately 200,000 worldwide annually. Stereotactic radiation therapy of post-operative cavity reduces local recurrence. Surgical cavity size changes significantly with 96.5% demonstrating volumetric change during post-operative period. We sought to define the optimal time interval that preserved the volumetric dimensions between the post-surgical MRI and the CT simulation used for stereotactic radiosurgery planning. METHODS Seven patients with brain metastasis that underwent surgical resection and stereotactic radiation treatment at Albany Medical Center from February 2019 to April 2020 were included in the study. A total of 8 target lesions were included. Brain lab planning system was used for contouring the target volume. A postoperative MRI within 24-48 hours after surgery was obtained. 3 patients required an additional interim MRI 16-50 days after surgery. The planning CT simulation was performed 2 days prior and up to 15 days after the post-operative/interim MRI and target volumes were compared. RESULTS The average volume of the post-surgical cavity contoured by the neurosurgeons on the post-operative/interim MRI was 15.96 cc (± 7.79 cc, range of 6.54 -24.9 cc). The average volume of the post-surgical cavity contoured by the radiation oncologists on the planning CT was 15.71 (± 7.49 cc, range of 6.53 -24.31 cc). There was no noticeable change in volume size between post-operative/interim MRI and planning CT up to the period of 15 days. LIMITATION This was a retrospective pilot study with a small sample size and patients recruited from a single center. CONCLUSION There is no change in size of the cavity volume for up to 15 days between post-operative/interim MRI and planning CT. This knowledge will help understand the optimal time interval between post-operative MRI and CT simulation for the stereotactic radiation therapy planning.

GENE-03. CASE REPORT: CHOROID PLEXUS CARCINOMA TREATED WITH STEREOTACTIC RADIOSURGERY IN 2-YEAR-OLD WITH LI FRAUMENI SYNDROME

CASE REPORT: The child was diagnosed with choroid plexus carcinoma (CPC) at age 8 months. The tumor was positive for TP53 genomic alteration. Germline genetic test sent at age 10 months returned positive for heterozygous TP53 pathogenic mutation. She underwent surgical resection, chemotherapy, and repeat resection at 13 months. At 31 months, she had three small nodules concerning for recurrent disease surrounding the large surgical cavity. Repeat surgical resection was declined by her family. She therefore underwent stereotactic radiosurgery (SRS) to each lesion to a dose of 24 Gy in 1 fraction. Anesthesia was required at the time of planning CT simulation and at the time of treatment. At one year since the procedure, she has demonstrated no further recurrent disease and no evidence of secondary malignancy at this time. DISCUSSION: Retrospective studies approximate rates of p53 mutations in children with CPC at 40%. Radiation is avoided—unless absolutely necessary—in children less than 3 years old because of the risks of neurocognitive delay, endocrine and growth toxicities, and the risk of secondary malignancies. Patients with Li Fraumeni syndrome have further dramatic increase in rates of developing secondary malignancies after exposure to ionizing radiation. SRS provides dose escalation while minimizing ionizing radiation dose to normal surrounding tissue. CONCLUSIONS: Any child diagnosed with CPC should undergo genetic testing for p53 germline mutation because of high pre-test probability. In selected cases, SRS provides an alternative to surgery as local control for limited CPC. SRS minimizes the dose of ionizing radiation delivered to normal tissues in patients with p53 mutation, or in young patients in whom less-focused radiation techniques may cause increased negative neurocognitive effects. Because of the short treatment course, SRS also minimizes the number of days under anesthesia required for young patients, thereby minimizing risk incurred by repeated anesthetic requirements.

Prostate Cancer Upstaging by Planning MRI and its Impact on Treatment Decisions

Planning magnetic resonance imaging (MRI) has shown potential in reducing radiation related toxicities for prostate cancer (PC) via improved prostate delineation. Utilization of MRI may also permit improved tumor detection and more accurate T-stage classification. However, it is unclear how to incorporate MRI detected changes in T-stage in clinical practice. Our purpose was to characterize how planning MRI changed T-stage and subsequent treatment-related decisions. MRI planning was established at our center in January 2016. All patients undergoing MRI planning for PC until January 2018 were analyzed. All patients were evaluated in consultation with a treatment recommendation prior to planning. NCCN guidelines were used for risk stratification. T1 and T2 images were fused to the planning CT simulation. Radiation planning was according to institutional guidelines. All MRIs were radiologist interpreted prior to completion of radiation planning. Treatment modifications based on MRI results were at the discretion of the treating radiation oncologist. One hundred thirty-seven patients were included in this retrospective analysis. Seventy-nine patients (58%) had a different T-stage on planning MRI than clinical evaluation, of which 13 (10%) were downstaged and 66 (48%) were upstaged. Twenty-one patients (15%) had an increase in their risk category with 17 of these patients moving from low/intermediate to high/very high risk categories. Sixteen of these 17 patients had discussions regarding modification of treatments with 6 patients (4%) altering the initial treatment plan based on MRI findings. 6 patients had hormone therapy added or prolonged; 4 patients had pelvic node irradiation; and 2 patients had radiation dose modified. Planning MRI interpretation by qualified radiologists can potentially impact treatment decisions. The application of MRI-based staging can potentially identify patients requiring more aggressive therapy, but may potentially lead to over-treatment of others. MRI results should be discussed with patients for informed decision-making.

Temporalis Muscle Width as a Measure of Sarcopenia Independently Predicts Overall Survival in Patients with Newly Diagnosed Glioblastoma

Multiple prognostic factors, including age and performance status, are used to determine treatment recommendations in newly diagnosed glioblastoma (GBM). Sarcopenia, or clinically evident muscle wasting, has recently been shown to correlate with shorter overall survival (OS) in patients with newly diagnosed brain metastases. The prognostic value of sarcopenia and the optimal method to evaluate sarcopenia in patients with GBM are unclear. Measurements of the psoas and temporalis muscles have been used to quantify sarcopenia. We sought to develop a method to reproducibly quantify sarcopenia using the temporalis muscle, and evaluate the potential correlation between sarcopenia and outcomes for patients with GBM. We conducted a retrospective analysis of post-operative treatment planning CT simulation scans of 87 newly diagnosed GBM patients from 2012 to 2016. All patients received standard of care chemoradiation therapy including conventionally fractionated radiotherapy to a total dose of 6000 cGy in 30 fractions with concurrent temozolomide. We measured the temporalis muscle width (TMW) bilaterally on four axial CT slices to approximate muscle volume and evaluated the potential correlation between the TMW and OS. Selection of axial slices was defined by bony orbital anatomy: supraorbital, superior quartile (equidistant from supraorbital and mid-orbital), mid-orbital, and inferior quartile (equidistant from mid-orbital and infraorbital) locations. TMW measured on the inferior quartile slice correlated most strongly with OS. TMW was dichotomized at the median measurement (wide, >1.58 cm vs. narrow, ≤1.58 cm). OS for patients with wide TMW (>1.58 cm) was statistically significantly greater than that of patients with narrow TMW (<1.58 cm): 28.3 mo vs 22.2 mo, independent of age, gender, body mass index, Karnofsky Performance Status and resection type ((HR(wide/narrow)=0.42, 95% CI=(0.20, 0.90), adjusted p=0.03). This was especially pronounced in the following patient subsets: females (HR(wide/narrow)=0.26, 95% CI=(0.07, 0.92), p=0.04), and age ≤ 60 years (HR=0.32, 95% CI=(0.13, 0.81), adjusted p=0.02). The temporalis muscle width was used to quantify sarcopenia and found to be independently prognostic of OS in our GBM cohort. Prospective validation of sarcopenia is needed to evaluate its potential in determining optimal patient treatment.

Feasibility study of toxicity outcomes using GEC-ESTRO contouring guidelines on CT based instead of MRI-based planning in locally advanced cervical cancer patients

PurposeTo report late rectal and bladder toxicity outcomes of a CT-based image-guided brachytherapy (IGBT) technique for treatment of cervical cancer. Methods and MaterialsBetween 2008 and 2014, 95 women with International Federation of Gynecology and Obstetrics stage IB to IVA cervical carcinoma treated with definitive concurrent cisplatin-based chemotherapy and external beam radiation therapy 50.4 Gy in 28 fractions followed by planned prescription dose of 7 Gy × 4 fractions of high-dose-rate IGBT was retrospectively reviewed. At each implantation, all patients had a urinary catheter in situ and received bowel enema before undergoing planning CT simulation. A high-risk clinical target volume (HRCTV) as per GEC-ESTRO guidelines and the entire cervix, rectum, and bladder was contoured on the simulation CT according to Radiation Therapy Oncology Group Gynaecology Contouring Atlas. Reported doses to HRCTV and organs at risk were recorded. Toxicities were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events version 3. ResultsThe median followup time was 29 months. The mean HRCTV equivalent dose in 2 Gy fractions (EQD2) of external beam radiation therapy combined with brachytherapy was 80 Gy (standard deviation [SD], 11), and the rectal doses to 2 cm3 (D2cc) EQD2 and bladder D2cc EQD2 were 74 Gy (SD, 6) and 79 Gy (SD, 15), respectively. Twenty-two patients (23%) had grade 2 proctitis and 10 patients (11%) had grade 3 proctitis. Four patients (4%) had grade 2 cystitis and two patients (2%) had grade 3 cystitis. No patients had ≥ grade 4 toxicity. ConclusionsDespite CT-based brachytherapy planning, reported organ at risk toxicity was still significant compared with reported MRI-based planning series. Coimplementation of interstitial IGBT using the European Study on MRI-guided Brachytherapy in Locally Advanced Cervical Cancer (EMBRACE) protocol or using intensity-modulated radiation therapy during the external beam phase treatment might help to limit these late toxicities.

Internal target volume for post-hysterectomy vaginal recurrences of cervical cancers during image-guided radiotherapy.

The outcome of post-surgical recurrences of cervical cancer may be improved through radiation dose escalation, which hinges on accurate identification and treatment of the target. The present study quantifies target motion during course of image-guided radiotherapy (IGRT) for vault cancers. All patients underwent planning CT simulation after bladder-filling protocol. A daily pre-treatment megavoltage CT was performed. All translations and rotations were recorded. Post-registration displacement of gross tumour volume (GTV) and centre of mass (COM) of GTV was independently recorded by two observers for fractions one to seven. Day 1 image sets served as reference images against which the displacements of COM were measured. We calculated the displacements of common volume (CV) and encompassing volume (EV) of GTV for both the observers. A total of 90 image data sets of 15 patients were available for evaluation. Individual patient GTV and average GTV by both the observers were comparable. The average shifts for EV were 2.4 mm [standard deviation (SD) ±1.2] in the mediolateral, 4.2 mm (SD ±2.8) in the anteroposterior and 4.0 mm (SD ±2.1) in superoinferior directions. Similarly, the average shifts for CV were 1.9 mm (SD ±0.6) in the mediolateral, 3.7 mm (SD ±2.7) in the anteroposterior and 4.4 mm (SD ±2.7) in superoinferior directions. Using Stroom's/van Herk's formula, the minimum recommended margins would be 4.5/5.2, 8.2/9.4 and 7.3/8.3 mm, respectively, for lateral, anteroposterior and superoinferior directions. Differential directional internal margin is recommended in patients undergoing IGRT for post-surgical recurrence of cervical cancers. Internal organ motion of vault cancers can be accounted for by a directional margin to the gross tumour.

Multivariate analysis of factors predicting prostate dose in intensity-modulated radiotherapy

We conducted a multivariate analysis to determine relationships between prostate radiation dose and the state of surrounding organs, including organ volumes and the internal angle of the levator ani muscle (LAM), based on cone-beam computed tomography (CBCT) images after bone matching. We analyzed 270 CBCT data sets from 30 consecutive patients receiving intensity-modulated radiation therapy for prostate cancer. With patients in the supine position on a couch with the HipFix system, data for center of mass (COM) displacement of the prostate and the state of individual organs were acquired and compared between planning CT and CBCT scans. Dose distributions were then recalculated based on CBCT images. The relative effects of factors on the variance in COM, dose covering 95% of the prostate volume (D95%), and percentage of prostate volume covered by the 100% isodose line (V100%) were evaluated by a backward stepwise multiple regression analysis. COM displacement in the anterior-posterior direction (COMAP) correlated significantly with the rectum volume (δVr) and the internal LAM angle (δθ; R = 0.63). Weak correlations were seen for COM in the left-right (R = 0.18) and superior-inferior directions (R = 0.31). Strong correlations between COMAP and prostate D95% and V100% were observed (R ≥ 0.69). Additionally, the change ratios in δVr and δθ remained as predictors of prostate D95% and V100%. This study shows statistically that maintaining the same rectum volume and LAM state for both the planning CT simulation and treatment is important to ensure the correct prostate dose in the supine position with bone matching.

SU-E-J-42: Comparison between Rigid and Deformable Image Registrations for Target Volume Delineation in Radiotherapy of Head-and-Neck Cancers

Purpose: Deformable image registration promises to solve the problem of co‐registering images acquired at different patient positioning and has recently become clinically available. This study seeks to compare deformable registration with rigid body registration among FDG‐PET/CT and CTimages in the delineation of target volumes of head‐and‐neck cancers. Methods: Eight patients with head‐and‐neck cancers were retrospectively selected based on the availability of FDG‐PET/CT images acquired within one month of planning CT simulation. FDG‐PET/CT, planning CTimages, and the treated clinical target volume (CTV) were imported from ADAC Pinnacle into Velocity AI program where they were co‐registered around the regions of CTV using rigid body transformation and multi‐pass deformable registration respectively. Following rigid and deformable registrations of FDG‐PET/CT with planning CT, gross tumor volumes (GTVs) were automatically generated using an adaptive threshold technique with FDG‐PET and then the GTV‐rigid and GTV‐deformable of each patient were compared in terms of volume. The target centers of the GTV‐rigid and GTV‐deformable were calculated to measure the registration discrepancy. Results: Deformable image registration significantly reduced the registration error due to different head and neck positioning between the planning CT acquisition and the FDG‐PET/CT. We found that the volume of GTV‐deformable increased by (5.2±4.0) percent compared to those of GTV‐ rigid. We observed significant shape changes between the GTV‐rigid and GTV‐deformable. The center‐of‐mass shifts between the GTV‐rigid and GTV‐deformable are 2.8±1.7 mm in the anterior‐posterior direction, 2.8±2.7mm in the lateral direction, and 5.2±4.4mm in the superior‐inferior direction. Conclusions: Significant shape and positional changes of GTVs were observed in the comparison between rigid body registration and deformable image registration, although the volume of GTV changed very little between the two techniques. Further assessment is still needed such as volume and positional analysis of normal structures before the full implementation of the deformable image registration technique in the clinic.

SU-FF-J-101: Is Daily Image-Guided Patient Positioning Necessary for Lung Irradiation?

Purpose:Image‐guidedradiotherapy(IGRT) delivers unwanted and unnegligible dose during the imaging process and requires additional resources. In this work, we determine whether it is necessary to use IGRT daily for lung irradiation. Method and Materials:Image and couch shift data for 27 lungtumor patients treated with conventional fractionation schemes, using MV cone‐beam CT (MVCBCT) for patient positioning, were analyzed. Among these patients, 13 (group I) received MVCBCT for each fraction (326 scans). The rest (group II, 14 patients) received MVCBCT for each fraction in the first and the last week of the treatment and only one scan per week in between (158 scans). Group II was treated when IGRT first became available and the variability in setup was being assessed. All patients were immobilized with alpha cradle during planning CT simulation and treatment. MVCBCTs were registered with the planning CT based on bony anatomy alignment. The components of planning‐target‐volume (PTV) margin to account for setup errors were calculated, using a four‐parameter population margin recipe. Results: Random errors along anterior‐posterior (AP), left‐right (LR) and superior‐inferior (SI) were found to be 2.9 mm, 3.1 mm, 4.4 mm for group I and 2.5 mm, 3.1 mm, 3.9 mm for group II. Systematic errors along AP, LR and SI were 2.3 mm, 2.3 mm, 2.7 mm for group I and 1.9 mm, 1.8 mm, 3.9 mm for group II. The resulting PTV margins were 10.0 mm, 6.8 mm, 10.5 mm for group I and 6.2 mm, 6.9 mm, 10.5 mm for group II. The margin difference along AP was statistically significant (p=0.003). Conclusion: The frequency of IGRT positioning depends on the PTV margin used. For lung irradiation using alpha cradle immobilization, an additional margin of 3 mm along the AP direction may be needed if IGRT repositioning is not used daily.

Repeat Computed Tomography Simulation to Assess Lumpectomy Cavity Volume During Whole-Breast Irradiation

To determine whether the lumpectomy cavity (LPC) decreases in volume during whole-breast radiotherapy (RT) and what factors influence the decrease. Forty-three women with 44 breast lesions were prospectively enrolled. Eligible patients underwent lumpectomy followed by a CT simulation (CT1) within 60 days of surgery. Patients were treated to the entire breast to a dose of 45-50.4 Gy. After 21-23 treatments, a second planning CT simulation (CT2) was done. The LPC was contoured on CT2, and the volumes (LCV) were compared between CT1 and CT2. The median LCV on CT1 and CT2 was 38.2 cm(3) and 21.7 cm(3), respectively. The median percent change and volume decrease between CT1 and CT2 was -32.0% and 11.2 cm(3), respectively (n = 44). The LCV decreased in 38 of 44 patients (86%). There was a significant correlation between initial LCV and decrease in volume (p = 0.001) and initial LCV and percent decrease in volume (p < 0.001). There was no correlation between time from surgery to CT1, to start of RT, or to CT2 and change in volume. Patients who undergo lumpectomy almost always have a decrease in their LCV during whole-breast RT. There was a correlation between the initial LCV and decrease in volume on repeat CT simulation. Evaluating patients for this change can potentially lead to decreased doses of radiation to the remaining breast and other critical structures when delivering a small-field boost. Repeat CT simulation should be considered in patients with larger cavities or cavities near critical structures.

Repositioning accuracy of a commercially available thermoplastic mask system

Background and purposeTo evaluate the repositioning accuracy of a commercially available thermoplastic mask system for single dose radiosurgery treatments and fractionated treatment courses. Patients and methodsThe repositioning accuracy of the Raycast©-HP mask system (Orfit Industries, Wijnegem, Belgium) was analyzed. Twenty-two patients that were treated by intensity-modulated radiation therapy (IMRT) or intensity modulated radiosurgery (IMRS) for 43 intracranial lesions, underwent repeated CT imaging during their course of treatment, or as a positional control immediately before radiosurgery. We evaluated multiple anatomical landmark coordinates and their respective shifts in consecutive repeated CT-controls. An iterative optimization algorithm allowed for the calculation of the x, y and z-components of translation of the target isocenter(s) for each repeated CT, as well as rotation in the respective CT data sets. In addition to absolute target isocenter translation, the total magnitude vector (i.e. sum-vector) of isocenter motion was calculated along with patient rotations about the three principle axes. ResultsFifty-five control CT datasets were analyzed for the target isocenter's respective position relative to the original treatment planning CT simulation. Mean target isocenter translation was 0.74±0.53, 0.75±0.60 and 0.93±0.78 mm in x, y and z-directions, respectively. Mean rotation about the x, y and z-axes was 0.67±0.66, 0.61±0.63 and 0.67±0.61 degrees, respectively. The respective median and mean magnitude vectors of isocenter translation were 1.28 and 1.59±0.84 mm. Analysis of the accuracy of the first setup control, representative of setup accuracy for radiosurgery treatments, compared with setup accuracy throughout a fractionated radiation treatment course were statistically equivalent (P=0.15), thus indicating no measurable deterioration of setup accuracy throughout the treatment course. ConclusionsThe analyzed Orfit thermoplastic mask system performed favorably compared with other mask immobilization systems for which peer-reviewed repositioning data exist. While the performance of the system for fractionated treatment courses was considered to be excellent, use of this mask system for radiosurgery immobilization in our clinic is subject to additional quality assurance measures to prohibit the delivery of treatments with target dislocations larger than 2 mm. The measured data in the present study should enable the users of this system to assign appropriate margins for the generation of planning target volumes.