Daily Image-guided Radiation Therapy Research Articles

Impact of Stomach Deformability on PTV Coverage in Patients with Gastric MALTs Treated with Deep Inspiration Breath Hold (DIBH) and Daily CT-based Image-guided Radiation Therapy (IGRT)

Patients with extranodal marginal zone lymphomas of the stomach (gastric MALTs) have excellent prognoses. DIBH with CT-based IGRT is used to minimize unwanted dose to heart and lungs. However, the stomach presents unique challenges for RT given its deformability, which may not be adequately compensated by standard 6-dimensional shifts. We conducted a dosimetry study to evaluate our hypothesis that DIBH, CT-based IGRT, and fasting after midnight may not be sufficient to compensate for stomach deformability. Patients included were treated with DIBH and had daily IGRT with cone-beam CTs (CBCTs). All patients were simulated in alpha cradles with arms up. The CTV consisted of stomach with a 1.0 to 1.5cm CTV to PTV margin. Patients were instructed to fast after midnight. CBCTs used for daily image guidance prior to RT were collected. The stomach was contoured on each CBCT and then overlayed on the simulation scan. The stomach volume outside the PTV was calculated both in absolute volume and as a percentage of daily stomach volume. The relative location of the volume of stomach outside the PTV was also recorded. Five patients with biopsy-proven gastric MALTs who received definitive dose RT were included. Patients were followed for at least 11 months (range: 11 - 20 mo.), and all achieved a complete pathological response. Seventy daily CBCTs were used in the analysis. Across all images, the daily stomach volume was smaller than the CTV by a mean 99.3cc (range: <305.3cc - >108.9cc). The mean volume of stomach outside the PTV was 7.8cc (range: 0 - 75.5cc). This represented 3.1% of the daily stomach volume (range: 0 - 18.7%). Per patient, the mean percent volume outside the PTV ranged from 0.4% to 6.9%. In 3 of the 5 patients, the percent volume outside the PTV was <2.5%. The stomach was most often anterior to the PTV (31.4% of images). Medial and posterior extensions were the next most frequent, representing 21.4% and 14.3% of images, respectively. Of all the daily stomach contours, 15.7% remained wholly within the PTV. DIBH with daily IGRT in patients with gastric MALTs may result in moderate underdosing of the stomach due to its deformability. Daily stomach volumes were different in size from the CTV, and patients had an average of 0.4% to 6.9% of stomach volume outside the PTV. Regions of decreased coverage were most frequently seen anteriorly. Future dosimetry studies may suggest non-isometric PTV expansions to better cover these areas.

AlignRT®, Catalyst™ and RPM™ in locoregional radiotherapy of breast cancer with DIBH. Is IGRT still needed?

In locoregional radiotherapy of breast cancer with deep inspiration breath hold (DIBH), setup accuracy may depend on hospital protocol. At present, comparison between different positioning devices is challenging due to differing hospital protocols. The aim of this study was to evaluate the setup accuracy obtained with surface-guided radiation therapy (SGRT; AlignRT®, Catalyst™) or with lasers and real-time position management (RPM™) in DIBH. A total of 1692 image pairs were analyzed in three groups: positioning using AlignRT® surface guidance system (Group A, n = 45), Catalyst™ (Group C, n = 50) and conventional lasers and tattoos (Group L, n = 46). We evaluated residual errors for the bony chest wall, th1 and humeral head in kV images with laser- or SGRT-based setup with and without daily image-guided radiation therapy (IGRT). Less isocenter variance was found in Group A than in Group L or C (p ≤ 0.05) and in Group C than in L (p = 0.02-0.6). With SGRT only, the smallest random rotation error was found in Group A (p = 0.01). With daily IGRT, only a small difference was found for residual errors between the groups. Setup with SGRT improves the isocenter reproducibility compared to lasers and RPM™. Only small differences were found in setup accuracy between the SGRT devices. Due to improved isocenter accuracy, daily orthogonal IGRT is suggested in all the groups.

Dosimetric Impact of Simulated Daily Adaptive Radiotherapy with Significantly Reduced Setup Margins in the Definitive Treatment of Head and Neck Cancer

<h3>Purpose/Objective(s)</h3> Even when treating head and neck cancer (HNC) with daily image-guided radiation therapy, setup margins of 3-5 mm are required to ensure adequate coverage of disease due to setup error. These margins lead to additional normal tissue dose that may compromise acute and long-term quality-of-life. The use of daily adaptive radiotherapy (ART) using an online adaptive system significantly reduces the need for a PTV margin, since the targets and organs-at-risk (OAR) are recontoured each fraction. In this study, we hypothesized using daily ART (simulated) with 1 mm margins based on our involved nodal radiotherapy (INRT) paradigm would improve coverage and reduce OAR dose. <h3>Materials/Methods</h3> Ten patients with HNC treated on our institutional phase II INRT trial were selected for this study. Cone-beam CT scans were uploaded to the ETHOS emulator for daily adaptive replanning which was simulated using fractions 5, 10, 15, 20, 25, 30, and 35. Two plans were generated with a 1 mm (reduced) and a 5 mm (conventional) PTV expansion. The dose grid from the delivered, conventional margin plan was transposed onto the CBCT and adapted contours. Separately, a reduced target margin plan optimized on the online adaptive system was created. PTV coverage (70 Gy-gross/primary disease, 66.5 Gy-suspicious nodes, 63 Gy-extended volume surrounding the primary disease) and D1 were calculated for target structures along with the dose to OARs. Comparisons performed via paired two tailed t-test. <h3>Results</h3> Six patients with oropharynx cancer and four patients with larynx cancer were included. Median V100% coverage for 70 Gy (96% vs 95.6%), 66.5 Gy (98.5% vs 76.5%), and 63 Gy (98.9% vs 74.9%) were improved with the adaptive planning (all p-values<0.03). Plan homogeneity was improved in the ART plan (e.g., PTV70 median D1% 72.8 Gy vs 74.8 Gy, all p-values<0.02). The total median dose reduction was 10.8 Gy (interquartile range, IQR 8.0-12.6 Gy) for the ipsilateral submandibular gland (SMG), 12.2 Gy (IQR 7.3-23.5 Gy) for the contralateral SMG, 8.3 Gy (IQR 3.8-12.6 Gy) for the ipsilateral parotid, 8.1 Gy (IQR 4.4-11.0 Gy) for the contralateral parotid, 7.0 Gy (IQR 4.5-9.1 Gy) for larynx, 6.6 Gy (IQR 2.7-8.4 Gy) for oral cavity, and 8.6 Gy (IQR 5.9-12.1 Gy) for constrictors. <h3>Conclusion</h3> Simulated daily ART using a 1 mm PTV margin provided significant improvement over conventional PTV margins in coverage and critical OAR dosimetry. This small proof-of-concept study suggests this approach may lead to improved quality-of-life while preserving or improving tumor coverage. Further evaluation is needed to assess the resources needed to implement daily adaptations. A phase II randomized trial of daily ART is underway to determine if dosimetric improvements lead to similar gains in patient-reported outcomes.

Online Adaptive Radiotherapy and Opportunity Cost

<h3>Purpose/Objective(s)</h3> Changes in patient anatomy and tumor geometry pose a challenge to ensuring consistent target coverage and organs-at-risk (OAR) sparing; online adaptive radiotherapy (ART) has been used to account for these inter-fractional changes by facilitating replanning prior to each treatment. This project explores the opportunity cost of CT-based online ART by evaluating the time and human resource requirements for adaptive versus conventional image-guided radiation therapy (IGRT). This study seeks to quantify time requirements for ART and, using time driven activity-based costing (TDABC), determine the cost of this time to determine if the dosimetric benefit is worthwhile. <h3>Materials/Methods</h3> Online ART for pelvic disease sites was evaluated using Ethos based planning technology. Time, which at our facility is best represented by the duration between two cone beam CT (CBCT) scans taken for each adaptive fraction, was used as a broadly applicable and transferable metric, representing the additional time required for adaptive treatment on top of standard IGRT. Dosimetric impact was also considered. All parties (dosimetrist, therapists, physicist, physician) need to be present for the duration of treatment planning given the rapid response time required. Using recently validated TDABC at this facility, the per fraction cost of ART was determined, reflecting the added cost of ART on top of IGRT. <h3>Results</h3> Preliminary data suggests a time difference of approximately 7 versus 24 minutes for daily IGRT and ART, respectively. Each adaptive fraction requires more staffing for the duration of this time delaying completion of other tasks and functionally increasing resource utilization. <h3>Conclusion</h3> While online ART decreases the uncertainty of anatomical shifts, the added human resources required per fraction complicate the workflow of daily treatment and increase expense. This has an even greater impact on the implementation of ART in the context of the alternative payment model. Moreover, online ART removes physicians from clinical time. This opportunity cost is likely to be similar across different disease sites, unlike toxicity benefits which may vary more depending on anatomic location and require further longitudinal studies. Regardless, the implementation of progressively complex radiotherapy technologies, like ART, requires consideration of the time and human resource requirements and subsequent opportunity cost.

Comparing treatment uncertainty for ultra- vs. standard-hypofractionated breast radiation therapy based on in-vivo dosimetry

Background and purposePostoperative ultrahypofractionated radiation therapy (UHFRT) in 5 fractions (fx) for breast cancer patients is as effective and safe as conventionally hypofractionated RT (HFRT) in 15 fx, liberating time for higher-level daily online Image-Guided Radiation Therapy (IGRT) corrections. In this retrospective study, treatment uncertainties occurring in patients treated with 5fx (5fx-group) were evaluated using electronic portal imaging device (EPID)-based in-vivo dosimetry (EIVD) and compared with the results from patients treated with conventionally HFRT (15fx-group) to validate the new technique and to evaluate if the shorter treatment schedule could have a positive effect on the treatment uncertainties.Materials and methodsEPID-based integrated transit dose images were acquired for each treatment fraction in the 5fx-group (203 patients) and on the first 3 days of treatment and weekly thereafter in the 15fx-group (203 patients). A total of 1015 EIVD measurements in the 5fx-group and 1144 in the 15fx-group were acquired. Of the latter group, 755 had been treated with online IGRT correction (i.e., Online-IGRT 15fx-group).ResultsIn the 15fx-group 12.0% of fractions failed (FFs) compared to 3.8% in the 5fx-group and 6.9% in the online-IGRT 15fx-group. Causes for FFs in the 15fx-group compared with the 5fx-group were patient positioning (7.4% vs. 2.2%), technical issues (3.1% vs. 1.2%) and breast swelling (1.4% vs. 0.5%). In the online-IGRT 15fx-group, 2.5% were attributed to patient positioning, 3.8% to technical issues and 0.5% to breast swelling.ConclusionsEIVD demonstrated that UHFRT for breast cancer results in less FFs compared to standard HFRT. A large proportion of this decrease could be explained by using daily online IGRT.

Impact of Body Mass Index and Abdominal Subcutaneous Fat Thickness of Setup Errors in Postoperative Cervical Cancer Patients Underwent Daily Image-Guided Radiation Therapy

The purpose of this study was to investigate the relationship between body mass index (BMI) and abdominal subcutaneous fat thickness (SFT) and setup errors for postoperative cervical cancer patients treated with adjuvant radiotherapy, aiming to provide reference for precise individual radiotherapy.Ninety-two postoperative cervical cancer patients underwent volumetric-modulated arc therapy (VMAT) in Peking Union Medical College Hospital between August 2019 and August 2020 were enrolled. The BMI and SFT were measured before treatment. The daily shifts, systematic errors, and random errors in the anterior-posterior (AP), superior-inferior (SI), and left-right (LR) directions were recorded. Planning target volume (PTV) margins were calculated based on the equation of MPTV = 2.5Σ + 0.7δ among each BMI and SFT categories. Receiver operating characteristics (ROC) curve, linear regression, spearman rank correlation coefficient, and Kolmogorov-Smirnov test were employed.The median BMI for all patients was 22.1 kg/m2 (range, 15.2-29.7 kg/m2). Of the 92 patients, 9.8% (n = 9) were underweight; 67.4% (n = 62) were normal weight; 22.8% (n = 21) were excess weight. There was a strong correlation between BMI and SFT (P < 0.001). SFT level of underweight < 21.3 mm and SFT level of excess weight ≥ 26.3 mm were observed in 31 and 37 patients, respectively. On linear regression, mean absolute SI shifts were moderately correlated with BMI (P = 0.044) and SFT (P = 0.046). Mean absolute AP and LR shifts did not significantly correlate with BMI and SFT. The margin of AP direction was reduced to 4 mm to significantly diminish the inclusion of rectum in the PTV.For postoperative cervical cancer patients with excess weight or heavy abdominal SFT, a PTV margin of 10 mm in SI direction may be insufficient in the absence of image-guided radiation therapy (IGRT). A PTV margin of AP direction should be moderately reduced while internal target volume (ITV) is considered.D. Wang: None. K. Hu: None. F. Zhang: None.

Impact of IGRT Frequency Upon Errors in Head and Neck Radiation: A Retrospective Analysis of Different Schedules.

The relationship between image guided radiation therapy (IGRT) frequency and errors remains unclear. We present this data obtained from various IGRT frequencies in head and neck cancer patients. All consecutive head and neck cancer patients receiving radiation with curative intent and daily IGRT using kV cone beam CT (CBCT) scans, between June and December 2018, were included in the study. Translational displacements in medial-lateral (ML), superior-inferior (SI) and anterior-posterior (AP) direction were documented daily. Four IGRT scenarios were simulated retrospectively with reducing frequency, namely, 50% (Displacement data of every alternate fraction), 30% (Displacement data of 1st 3 fractions followed by once weekly), 20% (Displacement data of once weekly fraction) and 10% (Displacement data of 1st 3 fractions). Displacement data for once weekly was documented from shifts acquired on treatment day 1, 6,11, 16 and so on. Mean Displacements (MD), Systematic Errors (Σ), Random Errors (σ) and Planning Target Volume (PTV) margins were calculated for daily and simulated scenarios (Table 1). Thirty-one patients were analyzed with a median age of 54.5 years (Inter-Quartile Range - 42.75 - 67), predominantly males (77.4%), commonly involving oral cavity (54.8%) and oropharynx (25.8%) and treated post-operatively (64.5%). A total of 831 CBCT scans were analyzed, demonstrating MD in ML, SI and AP were normally distributed across all the image guidance scenarios, except in SI direction for daily format (Kolmogorov-Smirnov test of normality; Skewness - 3.32, p = .05). MD in the three directions were <0.1cm, reflected in Σ (< 0.2cm) for daily and simulated IGRT scenarios; σ for different formats revealed that in SI direction, for daily format was 0.7cm, whereas it was around 0.2cm for simulated scenarios and these differences were demonstrated in PTV margin calculation, 1cm in SI direction based upon daily IGRT data and around 0.5cm based upon simulated IGRT scenarios; margin estimation was similar in ML and AP direction for daily and simulated IGRT scenarios (Table 1). MD >0.5cm were around 2-3% in ML and SI direction, and 5% in AP direction; whereas MD >0.3cm were ranging between 10-20%. Systematic and random errors were similar across all simulated IGRT scenarios, inconclusive for superiority of one schedule over another, however higher random errors were observed with daily format in SI direction. This further validates the need for more data in determining the optimum IGRT frequency.Tabled 1Abstract 2565; TableIGRT FrequencyMLSIAPErrors (Σ = standard deviation (SD) from values of mean displacement for all patients; σ = root mean square of SD of all patients)ΣσΣσΣσDaily0.110.200.210.700.120.2250%0.110.210.120.210.140.2230%0.130.220.140.200.120.2520%0.150.240.150.200.130.2710%0.150.250.140.200.140.28PTV Margin (Van Herk’s Formula) (2.5Σ + 0.7σ) (cm)MLSIAPDaily0.421.000.4650%0.430.440.5030%0.490.480.4820%0.540.510.5010%0.560.490.56 Open table in a new tab

Dosimetric Analysis of Multiple Breath-Hold Segmented Volumetric Modulated Arc Radiation Therapy Plans with and without Fiducial Markers for Pancreatic Cancer

Given the proximity of the target volume to critical structures, radiation therapy for pancreatic cancer is challenging. The present study aimed to estimate planning target volume (PTV) margins of pancreatic tumors using daily image guided radiation therapy (IGRT) and to compare the dosimetric outcomes with and without fiducial markers (with-FM and without-FM) during multiple breath-hold segmented volumetric modulated arc therapy (MBHS-VMAT). Based on re-planned VMAT technique, two types of PTV margins, with-FM or without-FM, were retrospectively estimated in 10 patients with unresected pancreatic cancer. Daily IGRT shifts based on MBHS-cone-beam volume CT obtained prior to daily fractionated MBHS-VMAT and cone-beam motion CT under fractionated MBHS-VMAT were recorded and evaluated to estimate the two PTV margin types. Accordingly, 10 patients, 270 3D images, and 1080 2D images were considered. Appropriate margins were estimated using the equation M = 2.5Σ + 0.7σ. Regarding the treatment plans, the organs at risk (OAR) included the kidneys, liver, stomach, duodenum, jejunum, and spinal cord. The prescribed dose was 55 Gy in 25 fractions and was set to encompass 95% of the PTV. For both the plans, the planning objectives used in the optimizer were constant and were based on NCCN guidelines. Homogeneity and conformity indices, doses to OARs with attention to the digestive tract (stomach, duodenum, and jejunum), and PTV doses were evaluated between the two margin types. The respective PTV margins in the lateral, vertical, and longitudinal directions were 4, 4, and 5 mm with-FM and 7, 6, and 10 mm without-FM. For each patient, treatment planning implied two PTV margin types. For the digestive tract, a consistent trend indicated a significantly (p <0.05) lower V45, V50, and V55 using the with-FM MBHS-VMAT technique; these respective values decreased by 4.9%, 3.8% and 2.0% using with-FM MBHS-VMAT plans. There were no differences (p >0.05) in digestive tract (mean), PTV, liver dose (mean), and total kidney (V18) between the two margin types. Conformity and homogeneity indexes were also similar. The pancreas carries the potential for significant motion. In the absence of fiducial markers, our data suggest that the PTV margin will increase from 5 to 10 mm. These margins would surely overlap the surrounding bowel, duodenum, and/or stomach, suggesting that the dose coverage of margin-based PTVs is not be feasible. Our comparison shows that with-FM plans provide superior OAR-sparing abilities (particularly for the digestive tract) without decreasing target coverage.Abstract TU_41_3298; Table 1Comparison of various parameters for the two margin typesWith-FMWithout-FMp-valueDigestive tractV458.4 %13.3 %< 0.05V504.2 %8.0 %< 0.05V551.1 %3.1 %< 0.05Dmean, digestive tract (Gy)22.125.60.118PTVD2 (Gy)59.959.80.543D98 (Gy)53.853.40.342D50 (Gy)58.558.30.384LiverDmean, liver (Gy)8.410.30.190KidneysV1814.6 %16.6 %0.668 Open table in a new tab

Anisotropic Bladder Planning Target Volume in Bladder Radiation Therapy

PurposeThis study aimed to investigate 3 planning target volume (PTV) margin expansions and determine the most appropriate volume to be used in bladder preservation therapy when using daily cone beam computed tomography (CBCT). We aimed to establish whether a smaller PTV expansion is feasible without risking geographical miss. Methods and materialsThe study included patients with bladder cancer who were treated with a hypofractionated course of radiation therapy delivered with intensity modulated radiation therapy. The clinical target volume (CTV) was the whole empty bladder, and the PTV consisted of a 1.5-cm margin around the bladder (PTV1.5 cm). Patients underwent daily CBCT imaging before treatment to assess the bladder volume and ensure accurate positioning. We investigated 2 additional smaller PTV margin expansions to determine the most appropriate volume to be used with CBCT as a daily image guided radiation therapy modality. These margins were created retrospectively on every CBCT. The first additional volume was a uniform PTV margin of the surrounding 1 cm (PTV1 cm). When considering that the majority of the internal bladder movement was due to the variation in filling that occurs in the superior and anterior directions, a second volume of an anisotropic PTV margin with a 1.5-cm superior/anterior and 1 cm in other directions (PTV1/1.5 cm) was created. We recorded the frequency and measured the volume of bladder falling out of each PTV based on the daily CBCT. ResultsFor the purpose of this study, we considered an arbitrary 5 cm3 of CTV falling out of the designated PTV as a clinically significant volumetric miss. The frequency of such a miss when applying the uniform PTV1 cm was 1%. However, when applying the uniform PTV1.5 cm and anisotropic PTV1/1.5 cm margins, the frequency was 0.5% and 0.5%, respectively. ConclusionsThe anisotropic PTV expansion of 1.5 cm superiorly and anteriorly and 1 cm in all other directions around the bladder (CTV) provides a safe PTV approach when daily CBCT imaging is used to localize an empty bladder.

Daily Image Guidance With Cone Beam Computed Tomography May Reduce Radiation Pneumonitis in Unresectable Non-Small Cell Lung Cancer

To investigate the impact of daily image-guided radiation therapy technique on clinical outcomes in patients with inoperable non-small cell lung cancer treated with definitive chemoradiation therapy. We compared patients with inoperable non-small cell lung cancer receiving daily cone beam computed tomography (CBCT) after an initial 4-dimensional computed tomography (4DCT) simulation (n=76) with those receiving daily 2-dimensional orthogonal kilovoltage (kV) imaging (n=48). The primary endpoint was time to grade ≥2 radiation pneumonitis (RP2), estimated with the cumulative incidence method, compared with Gray's test, and modeled with the Fine-Gray method. Median follow-up was 40.6months (range, 5.9-58.1months) for the CBCT group and 75.8months (range, 9.9-107.8months) for the orthogonal kV group. Four-dimensional computed tomography simulation was used in 100% (n=76) of the CBCT group and 56% (n=27) of the orthogonal kV group (P< .0001). The 1-year cumulative incidence of RP2 was lower in the CBCT group than in the orthogonal kV group (24% vs 44%, P=.020). On multivariate analysis, daily imaging with CBCT after an initial 4DCT simulation was associated with a decreased risk of RP2 (adjusted hazard ratio 0.43, 95% confidence interval 0.22-0.82, P=.011), a finding that persisted among only patients who received 4DCT simulation (adjusted hazard ratio 0.48, 95% confidence interval 0.23-0.98, P=.045). There was no difference in locoregional progression, distant metastasis, any progression, or overall survival between groups. Daily image guided radiation therapy with CBCT compared with 2-dimensional orthogonal kV imaging was associated with a decreased risk of RP2. Clinicians could consider the implications of localization methods during curative intent radiation therapy.

Effect of imaging frequency on PTV margins and geographical miss during image guided radiation therapy for prostate cancer

BackgroundThe relationship between frequency of imaging during image guided radiation therapy (IGRT) and planning target volume (PTV) margin remains unclear. This issue is of practical significance given resource and time intensive nature of IGRT. The purpose of this study was to evaluate PTV margins with predefined and commonly used less-than-daily IGRT schedules using data obtained from patients treated with daily IGRT for prostate cancer. Methods and materialsDaily setup error and 3-dimensional daily alignment data for a total of 108 consecutive patients with prostate cancer treated with 2700 fractions of daily image guidance on tomotherapy were retrospectively analyzed. Five IGRT scenarios were simulated: alternate day, twice weekly, once weekly, first 3 days only, and no image guidance. The daily alignment data were modeled to simulate the 5 predefined scenarios by applying appropriate corrections to determine the PTV margin for each image guidance scenario. The data were also analyzed to predict possible geographical miss in any direction using 2 frequently used PTV margins of 7 and 5 mm for all the scenarios. ResultsDecreasing the frequency of image guidance increased the mean systematic error and the standard deviation of the systematic error. With decreased image guidance frequency, an increase in PTV margins was required to achieve adequate coverage of the clinical target volume. With reduction in image guidance from 50% to 12%, a gradual increase in percentage of fractions with predicted geographical miss using an isotropic PTV margin of 7 or 5 mm was seen. With every 15% decrease in imaging, a 5% increased risk of geographical miss was estimated. ConclusionsThe use of less-than-daily IGRT requires larger PTV margins for patients treated with intensity modulated radiation therapy for prostate cancer. With every 15% reduction, a 5% increased risk of geographical miss was estimated.

Daily Positioning Variations in Image Guided Radiation Therapy of Pancreatic Cancer

Margin reduction and hypo-fractionated treatment of pancreatic cancer is increasing in interest and practice in radiation oncology, but pancreatic motion has the potential to limit clinical efficacy. This study details the magnitude of observed positional variations of pancreatic tumors treated with radiation therapy utilizing the results of daily image guided radiation therapy (IGRT). Daily IGRT shifts based on cone-beam CT (CBCT) and mega-voltage CT (MVCT) were recorded and evaluated in order to estimate positioning variations of pancreatic target volumes. A total of 72 patients and 1159 3D-images captured immediately prior to daily conventionally fractionated RT were considered. Overall positioning variations, inter-patient variations, and correlations between position variations and patient-specific factors including PTV volume, tumor location (head/body/tail of pancreas), and central or lateral positioning of the PTV were estimated. Statistical analysis of the positioning variations included Kolmogorov-Smirnov (KS) testing for normality of distributions. Estimation of appropriate margins was carried out based on M=2.5Σ+0.7σ assuming the measured inter-fraction shifts are representative of intra-fraction motion, and present a conservative estimate of spatial expansions to ensure coverage of the CTV. Mean and standard deviation of IGRT shifts for all patients was 0.2±5.2 mm in lateral directions, -0.3±4.3 mm in vertical directions, and -0.7±5.5 mm in longitudinal directions. The systematic variation (the standard deviation of inter-patient average shifts) was 2.6 mm, 2.6 mm, and 3.0 mm in lateral, vertical, and longitudinal directions. The random variation (the average of inter-patient standard deviations) was 3.9 mm, 3.0 mm, and 4.1 mm lateral, vertical, and longitudinal directions. Combined, these results suggest uniform margins about the CTV up to 10.4 mm are sufficient to account for observed positioning variations during IGRT. For each patient, KS testing implies the patient-specific shifts were representative of Gaussian distributions for 70/72 patients and 2/216 patient-specific directional distributions. The patient-specific distributions were not correlated with PTV volume, central or lateral location of the PTV, or whether the tumor was in the pancreatic head, tail, or body. Pancreas is a mobile organ with potential for large motion; our results suggest this motion is normally distributed and well-represented by Gaussian distributions. If intra- and inter- fraction motion are similar, which is plausible if pancreas motion is due to breathing and gastrointestinal motion, our data suggest margins of 10.4 mm will account for these spatial variations. These margins will surely overlap with surrounding bowel, duodenum, and/or stomach and imply dose escalation of margin-based PTVs may not be feasible.

Impact of prone versus supine positioning on small bowel dose with pelvic intensity modulated radiation therapy

PurposeTo report the results of a prospective study that compares small bowel doses during prone and supine pelvic intensity modulated radiation therapy. Methods and materialsTen patients receiving pelvic radiation therapy each had 2 intensity modulated radiation therapy plans generated: supine and prone on a belly board (PBB). Computed tomography on rails was performed weekly throughout treatment in both positions (10 scans per patient). After image fusion, doses to small bowel (SB) loops and clinical target volume were calculated for each scan. Changes between the planned and received doses were analyzed and compared between positions. The impact of bladder filling on SB dose was also assessed. ResultsProne treatment was associated with significantly lower volumes of SB receiving ≥20 Gy. On average, prone on a belly board positioning reduced the volume of SB receiving a given dose of radiation by 28% compared with supine positioning. Target coverage throughout the treatment course was similar in both positions with an average minimum clinical target volume dose of 88% of the prescribed prone dose and 89% of the supine (P = .54). For supine treatment, SB dose was inversely correlated with bladder filling (P = .001-.013; P > .15 for prone). For 96% of treatments, the volume of SB that received a given dose deviated >10% from the plan. The deviation between the planned and delivered doses to SB did not differ significantly between the positions. ConclusionsProne positioning on a belly board during pelvic IMRT consistently reduces the volume of SB that receives a broad range of radiation doses. Prone IMRT is associated with interfraction dose variation to SB that is similar to that of supine positioning. These findings suggest that prone positioning with daily image guided radiation therapy is an effective method for maximizing SB sparing during pelvic IMRT.

Margin reduction from image guided radiation therapy for soft tissue sarcoma: Secondary analysis of Radiation Therapy Oncology Group 0630 results

PurposeSix imaging modalities were used in Radiation Therapy Oncology Group (RTOG) 0630, a study of image guided radiation therapy (IGRT) for primary soft tissue sarcomas of the extremity. We analyzed all daily patient-repositioning data collected in this trial to determine the impact of daily IGRT on clinical target volume–to–planning target volume (CTV-to-PTV) margin. Methods and materialsDaily repositioning data, including shifts in right-left (RL), superior-inferior (SI), and anterior-posterior (AP) directions and rotations for 98 patients enrolled in RTOG 0630 from 18 institutions were analyzed. Patients were repositioned daily on the basis of bone anatomy by using pretreatment images, including kilovoltage orthogonal images (KVorth), megavoltage orthogonal images (MVorth), KV fan-beam computed tomography (KVCT), KV cone beam CT (KVCB), MV fan-beam CT (MVCT), and MV cone beam CT (MVCB). Means and standard deviations (SDs) for each shift and rotation were calculated for each patient and for each IGRT modality. The Student’s t tests and F-tests were performed to analyze the differences in the means and SDs. Necessary CTV-to-PTV margins were estimated. ResultsThe repositioning shifts and day-to-day variations were large and generally similar for the 6 imaging modalities. Of the 2 most commonly used modalities, MVCT and KVorth, there were no statistically significant differences in the shifts and rotations (P = .15 and .59 for the RL and SI shifts, respectively; and P = .22 for rotation), except for shifts in AP direction (P = .002). The estimated CTV-to-PTV margins in the RL, SI, and AP directions would be 13.0, 10.4, and 11.7 mm from MVCT data, respectively, and 13.1, 8.6, and 10.8 mm from KVorth data, respectively, indicating that margins substantially larger than 5 mm used with daily IGRT would be required in the absence of IGRT. ConclusionsThe observed large daily repositioning errors and the large variations among institutions imply that daily IGRT is necessary for this tumor site, particularly in multi-institutional trials. Otherwise, a CTV-to-PTV margin of 1.5 cm is required to account for daily setup variations.

Impact of intrafractional respiratory-induced prostate mobility on PTV size.

Daily image-guided radiation therapy significantly reduces setup errors, but it does not minimize intrafractional target mobility; respiratory-induced target motion is one of the reasons for this. Therefore, the main aim of this study was to evaluate the impact of respiratory-induced prostate motion on the clinical target volume (CTV) margins. The analysis comprised 50 videos stored in digital format and recorded in a group of 50 patients during image-guided radiation therapy for prostate cancer. Fluoroscopy time was 10 seconds. Respiratory motion of the prostate in the anterior-posterior and lateral direction was assessed on the basis of a fiducial marker (GoldAnchor) implanted into the prostate before the treatment planning procedure. The average values and standard deviations of respiratory-induced prostate motion in the superior-inferior and left-right (lateral) directions were 2.6 ± 2.1 mm and 0.7 ± 0.7 mm, respectively. The CTV margins calculated according to the van Herk formula based on respiratory prostate motion were 8 mm in the superior-inferior direction and 2 mm in the lateral direction. Respiratory-induced prostate mobility during radiotherapy is significant especially in the superior-inferior direction, and can thus induce a geographical error. This confirms the need for determining CTV margins for this type of respiratory-induced mobility.

Intrathoracic Anatomical Changes During Stereotactic Lung Radiation Therapy: Implications for Daily IGRT

Purpose/Objective(s)To determine the intra-thoracic anatomical changes (ITACs) during stereotactic lung radiation therapy (SBRT) and evaluated their implications of this changes on the daily image guided radiation therapy (IGRT).Materials/Methods23 patients with primary lung carcinomas or lung metastasis treated between 2012 and 2015 in our center with SBRT from 3 to 8 fractions (50-60 Gy) were retrospective analyzed. 138 CBCT were examined to define the ITACs during the course of the treatment. The patients were initially positioned in customized immobilization cradles and then aligned with stereotactic X ray and CBCT. On a second step, image guided radiation therapy (IGRT) was evaluated in order to compare the differences between soft tissue target registration and bony anatomy matching for each translational dimension in 83 daily cone beam CT (CBCT).ResultsIn 10 patients (43%) 13 ITAC’S were identified. Types of observed ITACs were tumor regression (23%), changes in atelectasis (38%), tumor progression (30%), and infiltrative changes (0.1%). Pleural effusion was not found. The difference in the couch shift obtained from the bone (stereotactic X ray) and soft tissue registration (CBCT) of 83 images was 0.03 mm for vertical, 0.03 mm for longitudinal, 0 mm for lateral axis.ConclusionITACs during SBRT are less frequent than those reported during conventionally fractionated radiation therapy. The impact of these changes perhaps is clinically irrelevant for the positioning with soft tissue registration. A larger sample is needed to validate these data. Purpose/Objective(s)To determine the intra-thoracic anatomical changes (ITACs) during stereotactic lung radiation therapy (SBRT) and evaluated their implications of this changes on the daily image guided radiation therapy (IGRT). To determine the intra-thoracic anatomical changes (ITACs) during stereotactic lung radiation therapy (SBRT) and evaluated their implications of this changes on the daily image guided radiation therapy (IGRT). Materials/Methods23 patients with primary lung carcinomas or lung metastasis treated between 2012 and 2015 in our center with SBRT from 3 to 8 fractions (50-60 Gy) were retrospective analyzed. 138 CBCT were examined to define the ITACs during the course of the treatment. The patients were initially positioned in customized immobilization cradles and then aligned with stereotactic X ray and CBCT. On a second step, image guided radiation therapy (IGRT) was evaluated in order to compare the differences between soft tissue target registration and bony anatomy matching for each translational dimension in 83 daily cone beam CT (CBCT). 23 patients with primary lung carcinomas or lung metastasis treated between 2012 and 2015 in our center with SBRT from 3 to 8 fractions (50-60 Gy) were retrospective analyzed. 138 CBCT were examined to define the ITACs during the course of the treatment. The patients were initially positioned in customized immobilization cradles and then aligned with stereotactic X ray and CBCT. On a second step, image guided radiation therapy (IGRT) was evaluated in order to compare the differences between soft tissue target registration and bony anatomy matching for each translational dimension in 83 daily cone beam CT (CBCT). ResultsIn 10 patients (43%) 13 ITAC’S were identified. Types of observed ITACs were tumor regression (23%), changes in atelectasis (38%), tumor progression (30%), and infiltrative changes (0.1%). Pleural effusion was not found. The difference in the couch shift obtained from the bone (stereotactic X ray) and soft tissue registration (CBCT) of 83 images was 0.03 mm for vertical, 0.03 mm for longitudinal, 0 mm for lateral axis. In 10 patients (43%) 13 ITAC’S were identified. Types of observed ITACs were tumor regression (23%), changes in atelectasis (38%), tumor progression (30%), and infiltrative changes (0.1%). Pleural effusion was not found. The difference in the couch shift obtained from the bone (stereotactic X ray) and soft tissue registration (CBCT) of 83 images was 0.03 mm for vertical, 0.03 mm for longitudinal, 0 mm for lateral axis. ConclusionITACs during SBRT are less frequent than those reported during conventionally fractionated radiation therapy. The impact of these changes perhaps is clinically irrelevant for the positioning with soft tissue registration. A larger sample is needed to validate these data. ITACs during SBRT are less frequent than those reported during conventionally fractionated radiation therapy. The impact of these changes perhaps is clinically irrelevant for the positioning with soft tissue registration. A larger sample is needed to validate these data.

Image Guidance-Based Target Volume Margin Expansion in IMRT of Head and Neck Cancer.

This study quantifies the setup uncertainties to optimize the planning target volume (PTV) margin based on daily image guidance, its dosimetric impact, and radiobiological implication for intensity-modulated radiation therapy (IMRT) in head and neck cancer. Ten patients were retrospectively chosen who had been treated with IMRT and with daily image-guided radiation therapy (IGRT). The daily setup errors of the 10 patients from on-board imaging for the entire treatment were analyzed. Planning target volumes were generated by expanding the clinical target volumes (CTVs) with 0 to 10 mm margins. The IMRT plans with the same dose-volume constraints were created in an Eclipse treatment planning system. The effect of volume expansion was analyzed with biological indices such as tumor control probability, normal tissue complication probability (NTCP), and equivalent uniform dose. Analysis of 906 daily setup corrections using daily IGRT showed that 98% of the daily setups are within ± 5 mm. The relative increase in PTV-CTV volume from 0 to 10 mm margins provides nearly 4-fold volume increase and is linearly related to monitor unit (MU). The increase in MU is about 5%/mm margin increase. The relative increase in NTCP of parotids from 5 to 10 mm margins is 3.2 ± 1.15. Increase in PTV margin increases extra tissue volume with a corresponding increase in MU for treatment and NTCP values. Even a small margin increase (eg, 1 mm) may result in increase of more than 20% in relative extra volume and 15% in NTCP value of organs at risk (OARs). With image guidance, the setup uncertainty could be achieved within ± 5 mm for 98% of the treatments, and a margin <5 mm for PTV may seem desirable to reduce the extra tissue irradiated, but at the expense of a more demanding setup accuracy.

Stereotactic ultrasound for target volume definition in a patient with prostate cancer and bilateral total hip replacement

PurposeTarget-volume definition for prostate cancer in patients with bilateral metal total hip replacements (THRs) is a challenge because of metal artifacts in the planning computed tomography (CT) scans. Magnetic resonance imaging (MRI) can be used for matching and prostate delineation; however, at a spatial and temporal distance from the planning CT, identical rectal and vesical filling is difficult to achieve. In addition, MRI may also be impaired by metal artifacts, even resulting in spatial image distortion. Here, we present a method to define prostate target volumes based on ultrasound images acquired during CT simulation and online-matched to the CT data set directly at the planning CT. Methods and materialsA 78-year-old patient with cT2cNxM0 prostate cancer with bilateral metal THRs was referred to external beam radiation therapy. T2-weighted MRI was performed on the day of the planning CT with preparation according to a protocol for reproducible bladder and rectal filling. The planning CT was obtained with the immediate acquisition of a 3-dimensional ultrasound data set with a dedicated stereotactic ultrasound system for online intermodality image matching referenced to the isocenter by ceiling-mounted infrared cameras. MRI (offline) and ultrasound images (online) were thus both matched to the CT images for planning. Daily image guided radiation therapy (IGRT) was performed with transabdominal ultrasound and compared with cone beam CT. ResultsBecause of variations in bladder and rectal filling and metal-induced image distortion in MRI, soft-tissue–based matching of the MRI to CT was not sufficient for unequivocal prostate target definition. Ultrasound-based images could be matched, and prostate, seminal vesicles, and target volumes were reliably defined. Daily IGRT could be successfully completed with transabdominal ultrasound with good accordance between cone beam CT and ultrasound. ConclusionsFor prostate cancer patients with bilateral THRs causing artifacts in planning CTs, ultrasound referenced to the isocenter of the CT simulator and acquired with intermodal online coregistration directly at the planning CT is a fast and easy method to reliably delineate the prostate and target volumes and for daily IGRT.

Creation of a More Comprehensive Target Volume for Esophageal Cancers by Combining Respiratory Gated Simulation and Daily Image Guided Radiation Therapy (IGRT)

Creation of a More Comprehensive Target Volume for Esophageal Cancers by Combining Respiratory Gated Simulation and Daily Image Guided Radiation Therapy (IGRT)

Target point correction optimized based on the dose distribution of each fraction in daily IGRT

Purpose: To use daily re-calculated dose distributions for optimization of target point corrections (TPCs) in image guided radiation therapy (IGRT). This aims to adapt fractioned intensity modulated radiation therapy (IMRT) to changes in the dose distribution induced by anatomical changes. Methods: Daily control images from an in-room on-rail spiral CT-Scanner of three head-and-neck cancer patients were analyzed. The dose distribution was re-calculated on each control CT after an initial TPC, found by a rigid image registration method. The clinical target volumes (CTVs) were transformed from the planning CT to the rigidly aligned control CTs using a deformable image registration method. If at least 95% of each transformed CTV was covered by the initially planned D95 value, the TPC was considered acceptable. Otherwise the TPC was iteratively altered to maximize the dose coverage of the CTVs. Results: In 14 (out of 59) fractions the criterion was already fulfilled after the initial TPC. In 10 fractions the TPC can be optimized to fulfill the coverage criterion. In 31 fractions the coverage can be increased but the criterion is not fulfilled. In another 4 fractions the coverage cannot be increased by the TPC optimization. Conclusions: The dose coverage criterion allows selection of patients who would benefit from replanning. Using the criterion to include daily re-calculated dose distributions in the TPC reduces the replanning rate in the analysed three patients from 76% to 59% compared to the rigid image registration TPC.