Salvage Reirradiation for Locally Recurrent Prostate Cancer: Results From a Prospective Study With 7.2 Years of Follow-Up.

PURPOSE: There are no well-established re-treatment options for local recurrence after primary curative radiation therapy for prostate cancer (PCa), as prospective studies with long-term follow-up are lacking. Here, we present results from a prospective study on focal salvage reirradiation with external-beam radiation therapy with a median follow-up of 7.2 years. MATERIALS AND METHODS: From 2013 to 2017, 38 patients with biopsy-proven locally recurrent PCa >2 years after previous treatment and absence of grade 2-3 toxicity from the first course of radiation were included. The treatment was 35 Gy in five fractions to the MRI-based target volume and 6 months of androgen-deprivation therapy starting 3 months before radiation. The Phoenix criteria defined biochemical recurrence-free survival (bRFS), and toxicity was scored according to Radiation Therapy Oncology Group criteria. RESULTS: Median age was 70 years, and median time from primary radiation to prostate-specific antigen (PSA) recurrence was 83 months. The actuarial 2-year and 5-year bRFS were 81% (95% CI, 69 to 94) and 58% (95% CI, 49 to 74), respectively. The actuarial 5-year local recurrence-free survival was 93% (95% CI, 82 to 100), metastasis-free survival was 82% (95% CI, 69 to 95), and overall survival was 87% (95% CI, 76 to 98). Two patients (5%) had durable grade 3 genitourinary toxicity, one combined with GI grade 3 toxicity. A PSA doubling time ≤6 months at salvage, a Gleason score >7, and a PSA nadir ≥0.1 ng/mL predicted a worse outcome. CONCLUSION: Reirradiation with EBRT for locally recurrent PCa after primary curative radiation therapy is clinically feasible and demonstrated a favorable outcome with acceptable toxicity in this prospective study with long-term follow-up.

Improving knowledge-based treatment planning for lung cancer radiotherapy with automatic multi-criteria optimized training plans.

BACKGROUND: Knowledge-based planning (KBP) is a method for automated radiotherapy treatment planning where appropriate optimization objectives for new patients are predicted based on a library of training plans. KBP can save time and improve organ at-risk sparing and inter-patient consistency compared to manual planning, but its performance depends on the quality of the training plans. We used another system for automated planning, which generates multi-criteria optimized (MCO) plans based on a wish list, to create training plans for the KBP model, to allow seamless integration of knowledge from a new system into clinical routine. Model performance was compared for KBP models trained with manually created and automatic MCO treatment plans. MATERIAL AND METHODS: Two RapidPlan models with the same 30 locally advanced non-small cell lung cancer patients included were created, one containing manually created clinical plans (RP_CLIN) and one containing fully automatic multi-criteria optimized plans (RP_MCO). For 15 validation patients, model performance was compared in terms of dose-volume parameters and normal tissue complication probabilities, and an oncologist performed a blind comparison of the clinical (CLIN), RP_CLIN, and RP_MCO plans. RESULTS: The heart and esophagus doses were lower for RP_MCO compared to RP_CLIN, resulting in an average reduction in the risk of 2-year mortality by 0.9 percentage points and the risk of acute esophageal toxicity by 1.6 percentage points with RP_MCO. The oncologist preferred the RP_MCO plan for 8 patients and the CLIN plan for 7 patients, while the RP_CLIN plan was not preferred for any patients. CONCLUSION: RP_MCO improved OAR sparing compared to RP_CLIN and was selected for implementation in the clinic. Training a KBP model with clinical plans may lead to suboptimal output plans, and making an extra effort to optimize the library plans in the KBP model creation phase can improve the plan quality for many future patients.

An organ deformation model using Bayesian inference to combine population and patient-specific data.

Objective.Organ deformation models have the potential to improve delivery and reduce toxicity of radiotherapy, but existing data-driven motion models are based on either patient-specific or population data. We propose to combine population and patient-specific data using a Bayesian framework. Our goal is to accurately predict individual motion patterns while using fewer scans than previous models.Approach.We have derived and evaluated two Bayesian deformation models. The models were applied retrospectively to the rectal wall from a cohort of prostate cancer patients. These patients had repeat CT scans evenly acquired throughout radiotherapy. Each model was used to create coverage probability matrices (CPMs). The spatial correlations between these estimated CPMs and the ground truth, derived from independent scans of the same patient, were calculated.Main results.Spatial correlation with ground truth were significantly higher for the Bayesian deformation models than both patient-specific and population-derived models with 1, 2 or 3 patient-specific scans as input. Statistical motion simulations indicate that this result will also hold for more than 3 scans.Significance.The improvement over previous models means that fewer scans per patient are needed to achieve accurate deformation predictions. The models have applications in robust radiotherapy planning and evaluation, among others.

Patient selection, inter-fraction plan robustness and reduction of toxicity risk with deep inspiration breath hold in intensity-modulated radiotherapy of locally advanced non-small cell lung cancer.

Background: State-of-the-art radiotherapy of locally advanced non-small cell lung cancer (LA-NSCLC) is performed with intensity-modulation during free breathing (FB). Previous studies have found encouraging geometric reproducibility and patient compliance of deep inspiration breath hold (DIBH) radiotherapy for LA-NSCLC patients. However, dosimetric comparisons of DIBH with FB are sparse, and DIBH is not routinely used for this patient group. The objective of this simulation study was therefore to compare DIBH and FB in a prospective cohort of LA-NSCLC patients treated with intensity-modulated radiotherapy (IMRT). Methods: For 38 LA-NSCLC patients, 4DCTs and DIBH CTs were acquired for treatment planning and during the first and third week of radiotherapy treatment. Using automated planning, one FB and one DIBH IMRT plan were generated for each patient. FB and DIBH was compared in terms of dosimetric parameters and NTCP. The treatment plans were recalculated on the repeat CTs to evaluate robustness. Correlations between ΔNTCPs and patient characteristics that could potentially predict the benefit of DIBH were explored. Results: DIBH reduced the median Dmean to the lungs and heart by 1.4 Gy and 1.1 Gy, respectively. This translated into reductions in NTCP for radiation pneumonitis grade ≥2 from 20.3% to 18.3%, and for 2-year mortality from 51.4% to 50.3%. The organ at risk sparing with DIBH remained significant in week 1 and week 3 of treatment, and the robustness of the target coverage was similar for FB and DIBH. While the risk of radiation pneumonitis was consistently reduced with DIBH regardless of patient characteristics, the ability to reduce the risk of 2-year mortality was evident among patients with upper and left lower lobe tumors but not right lower lobe tumors. Conclusion: Compared to FB, DIBH allowed for smaller target volumes and similar target coverage. DIBH reduced the lung and heart dose, as well as the risk of radiation pneumonitis and 2-year mortality, for 92% and 74% of LA-NSCLC patients, respectively. However, the advantages varied considerably between patients, and the ability to reduce the risk of 2-year mortality was dependent on tumor location. Evaluation of repeat CTs showed similar robustness of the dose distributions with each technique.

Substantial Sparing of Organs at Risk with Modern Proton Therapy in Lung Cancer, but Altered Breathing Patterns Can Jeopardize Target Coverage.

Enhancing treatment of locally advanced non-small cell lung cancer (LA-NSCLC) by using pencil beam scanning proton therapy (PBS-PT) is attractive, but little knowledge exists on the effects of uncertainties occurring between the planning (Plan) and the start of treatment (Start). In this prospective simulation study, we investigated the clinical potential for PBS-PT under the influence of such uncertainties. Imaging with 4DCT at Plan and Start was carried out for 15 patients that received state-of-the-art intensity-modulated radiotherapy (IMRT). Three PBS-PT plans were created per patient: 3D robust single-field uniform dose (SFUD), 3D robust intensity-modulated proton therapy (IMPT), and 4D robust IMPT (4DIMPT). These were exposed to setup and range uncertainties and breathing motion at Plan, and changes in breathing motion and anatomy at Start. Target coverage and dose-volume parameters relevant for toxicity were compared. The organ at risk sparing at Plan was greatest with IMPT, followed by 4DIMPT, SFUD and IMRT, and persisted at Start. All plans met the preset criteria for target robustness at Plan. At Start, three patients had a lack of CTV coverage with PBS-PT. In conclusion, the clinical potential for heart and lung toxicity reduction with PBS-PT was substantial and persistent. Altered breathing patterns between Plan and Start jeopardized target coverage for all PBS-PT techniques.

Impact of RBE variations on risk estimates of temporal lobe necrosis in patients treated with intensity-modulated proton therapy for head and neck cancer.

BACKGROUND: Temporal lobe necrosis (TLN) is a potential late effect after radiotherapy for skull base head and neck cancer (HNC). Several photon-derived dose constraints and normal tissue complication probability (NTCP) models have been proposed, however variation in relative biological effectiveness (RBE) may challenge the applicability of these dose constraints and models in proton therapy. The purpose of this study was therefore to investigate the influence of RBE variations on risk estimates of TLN after Intensity-Modulated Proton Therapy for HNC. MATERIAL AND METHODS: Seventy-five temporal lobes from 45 previously treated patients were included in the analysis. Sixteen temporal lobes had radiation associated Magnetic Resonance image changes (TLIC) suspected to be early signs of TLN. Fixed (RWDFix) and variable RBE-weighed doses (RWDVar) were calculated using RBE = 1.1 and two RBE models, respectively. RWDFix and RWDVar for temporal lobes were compared using Friedman's test. Based on RWDFix, six NTCP models were fitted and internally validated through bootstrapping. Estimated probabilities from RWDFix and RWDVar were compared using paired Wilcoxon test. Seven dose constraints were evaluated separately for RWDFix and RWDVar by calculating the observed proportion of TLIC in temporal lobes meeting the specific dose constraints. RESULTS: RWDVar were significantly higher than RWDFix (p < 0.01). NTCP model performance was good (AUC:0.79-0.84). The median difference in estimated probability between RWDFix and RWDVar ranged between 5.3% and 20.0% points (p < 0.01), with V60GyRBE and DMax at the smallest and largest differences, respectively. The proportion of TLIC was higher for RWDFix (4.0%-13.1%) versus RWDVar (1.3%-5.3%). For V65GyRBE ≤ 0.03 cc the proportion of TLIC was less than 5% for both RWDFix and RWDVar. CONCLUSION: NTCP estimates were significantly influenced by RBE variations. Dmax as model predictor resulted in the largest deviations in risk estimates between RWDFix and RWDVar. V65GyRBE ≤ 0.03 cc was the most consistent dose constraint for RWDFix and RWDVar.

Enhancing Radiotherapy for Locally Advanced Non-Small Cell Lung Cancer Patients with iCE, a Novel System for Automated Multi-Criterial Treatment Planning Including Beam Angle Optimization.

In this study, the novel iCE radiotherapy treatment planning system (TPS) for automated multi-criterial planning with integrated beam angle optimization (BAO) was developed, and applied to optimize organ at risk (OAR) sparing and systematically investigate the impact of beam angles on radiotherapy dose in locally advanced non-small cell lung cancer (LA-NSCLC). iCE consists of an in-house, sophisticated multi-criterial optimizer with integrated BAO, coupled to a broadly used commercial TPS. The in-house optimizer performs fluence map optimization to automatically generate an intensity-modulated radiotherapy (IMRT) plan with optimal beam angles for each patient. The obtained angles and dose-volume histograms are then used to automatically generate the final deliverable plan with the commercial TPS. For the majority of 26 LA-NSCLC patients, iCE achieved improved heart and esophagus sparing compared to the manually created clinical plans, with significant reductions in the median heart Dmean (8.1 vs. 9.0 Gy, p = 0.02) and esophagus Dmean (18.5 vs. 20.3 Gy, p = 0.02), and reductions of up to 6.7 Gy and 5.8 Gy for individual patients. iCE was superior to automated planning using manually selected beam angles. Differences in the OAR doses of iCE plans with 6 beams compared to 4 and 8 beams were statistically significant overall, but highly patient-specific. In conclusion, automated planning with integrated BAO can further enhance and individualize radiotherapy for LA-NSCLC.

Reducing systematic errors due to deformation of organs at risk in radiotherapy.

PURPOSE: In radiotherapy (RT), the planning CT (pCT) is commonly used to plan the full RT-course. Due to organ deformation and motion, the organ shapes seen at the pCT will not be identical to their shapes during RT. Any difference between the pCT organ shape and the organ's mean shape during RT will cause systematic errors. We propose to use statistical shrinkage estimation to reduce this error using only the pCT and the population mean shape computed from training data. METHODS: The method was evaluated for the rectum in a cohort of 37 prostate cancer patients that had a pCT and 7-10 treatment CTs with rectum delineations. Deformable registration was performed both within-patient and between patients, resulting in point-to-point correspondence between all rectum shapes, which enabled us to compute a population mean rectum. Shrinkage estimates were found by combining the pCTs linearly with the population mean. The method was trained and evaluated using leave-one-out cross validation. The shrinkage estimates and the patient mean shapes were compared geometrically using the Dice similarity index (DSI), Hausdorff distance (HD), and bidirectional local distance. Clinical dose/volume histograms, equivalent uniform dose (EUD) and minimum dose to the hottest 5% volume (D5%) were compared for the shrinkage estimate and the pCT. RESULTS: The method resulted in moderate but statistically significant increase in similarity to the patient mean shape over the pCT. On average, the HD was reduced from 15.6 to 13.4 mm, while the DSI was increased from 0.74 to 0.78. Significant reduction in the bias of volume estimates was found in the DVH-range of 52.5-65 Gy, where the bias was reduced from -1.3 to -0.2 percentage points, but no significant improvement was found in EUD or D5%, CONCLUSIONS: The results suggest that shrinkage estimation can reduce systematic errors due to organ deformations in RT. The method has potential to increase the accuracy in RT of deformable organs and can improve motion modeling.

Mixed Effect Modeling of Dose and Linear Energy Transfer Correlations With Brain Image Changes After Intensity Modulated Proton Therapy for Skull Base Head and Neck Cancer.

PURPOSE: Intensity modulated proton therapy (IMPT) could yield high linear energy transfer (LET) in critical structures and increased biological effect. For head and neck cancers at the skull base this could potentially result in radiation-associated brain image change (RAIC). The purpose of the current study was to investigate voxel-wise dose and LET correlations with RAIC after IMPT. METHODS AND MATERIALS: For 15 patients with RAIC after IMPT, contrast enhancement observed on T1-weighted magnetic resonance imaging was contoured and coregistered to the planning computed tomography. Monte Carlo calculated dose and dose-averaged LET (LETd) distributions were extracted at voxel level and associations with RAIC were modelled using uni- and multivariate mixed effect logistic regression. Model performance was evaluated using the area under the receiver operating characteristic curve and precision-recall curve. RESULTS: An overall statistically significant RAIC association with dose and LETd was found in both the uni- and multivariate analysis. Patient heterogeneity was considerable, with standard deviation of the random effects of 1.81 (1.30-2.72) for dose and 2.68 (1.93-4.93) for LETd, respectively. Area under the receiver operating characteristic curve was 0.93 and 0.95 for the univariate dose-response model and multivariate model, respectively. Analysis of the LETd effect demonstrated increased risk of RAIC with increasing LETd for the majority of patients. Estimated probability of RAIC with LETd = 1 keV/µm was 4% (95% confidence interval, 0%, 0.44%) and 29% (95% confidence interval, 0.01%, 0.92%) for 60 and 70 Gy, respectively. The TD15 were estimated to be 63.6 and 50.1 Gy with LETd equal to 2 and 5 keV/µm, respectively. CONCLUSIONS: Our results suggest that the LETd effect could be of clinical significance for some patients; LETd assessment in clinical treatment plans should therefore be taken into consideration.

Clinical iterative model development improves knowledge-based plan quality for high-risk prostate cancer with four integrated dose levels.

BACKGROUND: Manual volumetric modulated arc therapy (VMAT) treatment planning for high-risk prostate cancer receiving whole pelvic radiotherapy (WPRT) with four integrated dose levels is complex and time consuming. We have investigated if the radiotherapy planning process and plan quality can be improved using a well-tuned model developed through a commercial system for knowledge-based planning (KBP). MATERIAL AND METHODS: Treatment plans from 69 patients treated for high-risk prostate cancer with manually planned VMAT were used to develop an initial KBP model (RapidPlan, RP). Prescribed doses were 50, 60, 67.5, and 72.5 Gy in 25 fractions to the pelvic lymph nodes, prostate and seminal vesicles, prostate gland, and prostate tumour(s), respectively. This RP model was in clinical use from July 2019 to February 2020, producing another set of 69 clinically delivered treatment plans for a new patient group, which were used to develop a second RP model. Both models were validated on an independent group of 40 patients. Plan quality was compared by D 98% and the Paddick conformity index for targets, mean dose (D mean) and generalised equivalent uniform dose (gEUD) for bladder, bowel bag and rectum, and number of monitor units (MU). RESULTS: Target coverage and conformity was similar between manually created and RP treatment plans. Compared to the manually created treatment plans, the final RP model reduced average D mean and gEUD with 2.7 Gy and 1.3 Gy for bladder, 1.2 Gy and 0.9 Gy for bowel bag, and 2.7 Gy and 0.8 Gy for rectum, respectively (p < .05). For rectum, the interpatient variation (i.e., 95% confidence interval) of DVHs was reduced by 23%. CONCLUSION: KBP improved plan quality and consistency among treatment plans for high-risk prostate cancer. Model tuning using KBP-based clinical plans further improved model outcome.

Ten-Year Results From a Phase II Study on Image Guided, Intensity Modulated Radiation Therapy With Simultaneous Integrated Boost in High-Risk Prostate Cancer.

PURPOSE: There is no consensus on how to treat high-risk prostate cancer, and long-term results from hypofractionated radiation therapy are lacking. We report 10-year results after image guided, intensity modulated radiation therapy with hypofractionated simultaneous integrated boost and elective pelvic field. METHODS AND MATERIALS: Between 2007 and 2009, 97 consecutive patients with high-risk prostate cancer were included, treated with 2.7 to 2.0 Gy × 25 Gy to the prostate, seminal vesicles, and elective pelvic field. Toxicity was scored according to Radiation Therapy Oncology Group criteria and biochemical disease-free survival (BFS) defined by the Phoenix definition. Patients were subsequently divided into 3 groups: high risk (HR; n = 32), very high risk (VHR; n = 50), and N+/s-prostate-specific antigen (PSA) ≥100 (n = 15). Differences in outcomes were examined using Kaplan-Meier analyses. RESULTS: BFS in the patients at HR and VHR was 64%, metastasis-free survival 80%, prostate cancer-specific survival 90%, and overall survival (OS) 72%. VHR versus HR subgroups demonstrated significantly different BFS, 54% versus 79% (P = .01). Metastasis-free survival and prostate cancer-specific survival in the VHR group versus HR group were 76% versus 87% (P = .108) and 74% versus 100% (P = .157). Patients reaching nadir PSA <0.1 (n = 80) had significantly better outcomes than the rest (n = 17), with BFS 70% versus 7% (P < .001). Acute grade 2 gastrointestinal tract (GI) and genitourinary tract (GU) toxicity occurred in 27% and 40%, grade 3 GI and GU toxicity in 1% and 3%. Late GI and GU grade 2 toxicity occurred in 1% and 8%. CONCLUSIONS: High-risk prostate cancer patients obtained favorable 10-year outcomes with low toxicity. There were significantly better results in the HR versus the VHR group, both better than the N+/PSA ≥100 group. A nadir PSA value < 0.1 predicted good prognosis.

The influence of inter-fractional anatomy variation on secondary cancer risk estimates following radiotherapy.

PURPOSE: In silico studies comparing estimated risks of radiation-induced secondary cancer (SC) are frequently performed in assessment of radiotherapy techniques. Since inter-patient anatomy variations can result in considerable differences in estimated risk we aimed to explore the influence of inter-fractional organ motion patterns on SC risk. METHODS: Volumetric modulated arc therapy (VMAT) and intensity-modulated proton therapy (IMPT) plans were generated on the planning CT (pCT) scans of eight prostate cancer patients. In addition, the treatment plans were re-calculated on 8-9 repeat CTs (rCTs) of each patient acquired throughout the treatment course. Relative risk (RR) of SC (VMAT/IMPT) was calculated for the planned and the re-calculated dose distributions using the organ equivalent dose concept adapted to a linear and a bell-shaped competition dose-response model. RESULTS: Day-to-day variations in anatomy lead to fluctuations in SC risk estimates of the same order of magnitude as those caused by inter-patient variations. Using the competition model, the RR range for bladder cancer based on the pCTs was 0.4-3.4, while a considerably wider range was found when including all rCTs (0.2-6.7). There was nevertheless a correlation in RR based on repeat CTs for individual patients, indicating that patient-specific SC risks could be estimated. CONCLUSIONS: The estimated relative risks varied considerably across rCTs and could change the risk in favour of VMAT/IMPT depending on the anatomy of the day. The results demonstrate the importance of performing in silico studies of SC risk on a cohort of patients or multiple CTs when structures subject to organ motion are involved.

A coverage probability based method to estimate patient-specific small bowel planning volumes for use in radiotherapy.

BACKGROUND AND PURPOSE: The aim of this work was to develop a statistical method for generation of patient-specific planning organ-at-risk volumes (PRVs) for the small bowel (SB), by efficient use of a few repeat CT scans. MATERIALS AND METHODS: The PRVs are generated from a coverage probability (CP) matrix of the small bowel wall (SBW) by thresholding. To estimate the CPs, we extend a previously published 'relative frequency of coverage' approach by adding a 'soft margin' around each SBW instance. This prevents the CP matrix from containing any holes, thus making it more robust. As the number of CTs approach infinity, the 'soft margin' approaches zero and the CP matrix converges to the 'relative frequency of coverage'. The PRVs were evaluated by using the bootstrap method in three patients with different degrees of SB motion: The PRVs from randomly sampled subsets of CTs were compared to the PRVs generated from all 10-11 CT scans, by analysis of sensitivity and specificity. Furthermore, the PRVs generated for CP=0.005 (i.e. generous patient-specific PRVs) and for CP=0.03 (i.e. tight patient-specific PRVs) were compared to an intestinal cavity (IC) approach and a population based PRV approach of 10 and 30 mm isotropic planning margins around SB. RESULTS: The sensitivity and specificity of the PRVs depend on the number of CT scans and the CP threshold. With three CT scans and a threshold of 0.03, an average sensitivity of 94-96% and specificity of 86-97% was obtained. All investigated SB planning volumes had an average overlap >89% of both SB and SBW. The tight patient-specific PRVs and the 10mm margins had the lowest relative volumes, followed by the generous patient-specific PRVs, the 30 mm margins and the ICs. CONCLUSIONS: Based on a few CTs, our method generates patient-specific SB PRVs which are both sensitive and specific. Compared to conventional approaches, the patient-specific PRVs are either similar or better in predicting for SB voxels, and at the same time they occupy a smaller or similar volume in the patient.

Semi-automated segmentation of the sigmoid and descending colon for radiotherapy planning using the fast marching method.

A fast and accurate segmentation of organs at risk, such as the healthy colon, would be of benefit for planning of radiotherapy, in particular in an adaptive scenario. For the treatment of pelvic tumours, a great challenge is the segmentation of the most adjacent and sensitive parts of the gastrointestinal tract, the sigmoid and descending colon. We propose a semi-automated method to segment these bowel parts using the fast marching (FM) method. Standard 3D computed tomography (CT) image data obtained from routine radiotherapy planning were used. Our pre-processing steps distinguish the intestine, muscles and air from connective tissue. The core part of our method separates the sigmoid and descending colon from the muscles and other segments of the intestine. This is done by utilizing the ability of the FM method to compute a specified minimal energy functional integrated along a path, and thereby extracting the colon centre line between user-defined control points in the sigmoid and descending colon. Further, we reconstruct the tube-shaped geometry of the sigmoid and descending colon by fitting ellipsoids to points on the path and by adding adjacent voxels that are likely voxels belonging to these bowel parts. Our results were compared to manually outlined sigmoid and descending colon, and evaluated using the Dice coefficient (DC). Tests on 11 patients gave an average DC of 0.83 (+/-0.07) with little user interaction. We conclude that the proposed method makes it possible to fast and accurately segment the sigmoid and descending colon from routine CT image data.

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.

Intensity-modulated radiotherapy of pelvic lymph nodes in locally advanced prostate cancer: planning procedures and early experiences.

PURPOSE: We present planning and early clinical outcomes of a study of intensity-modulated radiotherapy (IMRT) for locally advanced prostate cancer. METHODS AND MATERIALS: A total of 43 patients initially treated with an IMRT plan delivering 50 Gy to the prostate, seminal vesicles, and pelvic lymph nodes, followed by a conformal radiotherapy (CRT) plan delivering 20 Gy to the prostate and seminal vesicles, were studied. Dose-volume histogram (DVH) data for the added plans were compared with dose-volume histogram data for the sum of two CRT plans for 15 cases. Gastrointestinal (GI) and genitourinary (GU) toxicity, based on the Radiation Therapy Oncology Group scoring system, was recorded weekly throughout treatment as well as 3 to 18 months after treatment and are presented. RESULTS: Treatment with IMRT both reduced normal tissue doses and increased the minimum target doses. Intestine volumes receiving more than 40 and 50 Gy were significantly reduced (e.g., at 50 Gy, from 81 to 19 cm(3); p = 0.026), as were bladder volumes above 40, 50, and 60 Gy, rectum volumes above 30, 50, and 60 Gy, and hip joint muscle volumes above 20, 30, and 40 Gy. During treatment, Grade 2 GI toxicity was reported by 12 of 43 patients (28%), and Grade 2 to 4 GU toxicity was also observed among 12 patients (28%). With 6 to 18 months of follow-up, 2 patients (5%) experienced Grade 2 GI effects and 7 patients (16%) experienced Grade 2 GU effects. CONCLUSIONS: Use of IMRT for pelvic irradiation in prostate cancer reduces normal tissue doses, improves target coverage, and has a promising toxicity profile.

Planning organ at risk volume margins for organ motion of the intestine.

BACKGROUND AND PURPOSE: To account for internal organ motion and set-up uncertainties around organs at risk (OR) in radiotherapy (RT), the ICRU report no 62 introduced the planning organ at risk volume (PRV). In the present study, we have quantified PRV margins for the intestine, which is an important OR in pelvic RT. MATERIALS AND METHODS: The present study was based on intestine contours outlined in a total of 149 CT scans of 20 male bladder cancer patients (20 planning scans, 129 during treatment). From these data, we created location probability maps of the intestine for each patient. A commercial treatment planning system was used to add 3D isotropic intestine PRV margins (from 5 to 30 mm, in intervals of 5 mm) around the intestine planning outline. We then derived the fraction of patients for which a given PRV encompassed various degrees of intestine motion (85%, 90% and 95% of volumes with different probabilities of intestinal occupancy). As a measure of the specificity of the PRV, we also derived the fraction of the PRV containing volumes with zero probability of intestinal occupancy. RESULTS: Isotropic margins of up to 30 mm are required to account for all intestine motion in 90% of the patients, while isotropic margins of 5 - 10 mm will encompass 85 - 95% of the volumes having a probability of intestinal occupancy of > or = 75% in the same fraction of patients. Intestine PRVs are not very specific and will also include volumes where the intestine will rarely or never be located. CONCLUSIONS: Large intestinal motion was found, but isotropic PRV margins of 5-10 mm will include the major part of volumes with a large probability of intestinal occupancy in most patients.