Toxicity In Prostate Cancer Radiotherapy Research Articles

PO-1529 Association between age-related parameters and acute toxicity in prostate cancer radiotherapy

PO-1529 Association between age-related parameters and acute toxicity in prostate cancer radiotherapy

Planning With Patient-Specific Rectal Sub-Region Constraints Decreases Probability of Toxicity in Prostate Cancer Radiotherapy

Background: A rectal sub-region (SRR) has been previously identified by voxel-wise analysis in the inferior-anterior part of the rectum as highly predictive of rectal bleeding (RB) in prostate cancer radiotherapy. Translating the SRR to patient-specific radiotherapy planning is challenging as new constraints have to be defined. A recent geometry-based model proposed to optimize the planning by determining the achievable mean doses (AMDs) to the organs at risk (OARs), taking into account the overlap between the planning target volume (PTV) and OAR. The aim of this study was to quantify the SRR dose sparing by using the AMD model in the planning, while preserving the dose to the prostate.Material and Methods: Three-dimensional volumetric modulated arc therapy (VMAT) planning dose distributions for 60 patients were computed following four different strategies, delivering 78 Gy to the prostate, while meeting the genitourinary group dose constraints to the OAR: (i) a standard plan corresponding to the standard practice for rectum sparing (STDpl), (ii) a plan adding constraints to SRR (SRRpl), (iii) a plan using the AMD model applied to the rectum only (AMD_RECTpl), and (iv) a final plan using the AMD model applied to both the rectum and the SRR (AMD_RECT_SRRpl). After PTV dose normalization, plans were compared with regard to dose distributions, quality, and estimated risk of RB using a normal tissue complication probability model.Results: AMD_RECT_SRRpl showed the largest SRR dose sparing, with significant mean dose reductions of 7.7, 3, and 2.3 Gy, with respect to the STDpl, SRRpl, and AMD_RECTpl, respectively. AMD_RECT_SRRpl also decreased the mean rectal dose by 3.6 Gy relative to STDpl and by 3.3 Gy relative to SRRpl. The absolute risk of grade ≥1 RB decreased from 22.8% using STDpl planning to 17.6% using AMD_RECT_SRRpl considering SRR volume. AMD_RECT_SRRpl plans, however, showed slightly less dose homogeneity and significant increase of the number of monitor units, compared to the three other strategies.Conclusion: Compared to a standard prostate planning, applying dose constraints to a patient-specific SRR by using the achievable mean dose model decreased the mean dose by 7.7 Gy to the SRR and may decrease the relative risk of RB by 22%.

Multi-atlas-based segmentation of prostatic urethra from planning CT imaging to quantify dose distribution in prostate cancer radiotherapy

Background and purposeSegmentation of intra-prostatic urethra for dose assessment from planning CT may help explaining urinary toxicity in prostate cancer radiotherapy. This work sought to: i) propose an automatic method for urethra segmentation in CT, ii) compare it with previously proposed surrogate models and iii) quantify the dose received by the urethra in patients treated with IMRT. Materials and methodsA weighted multi-atlas-based urethra segmentation method was devised from a training data set of 55 CT scans of patients receiving brachytherapy with visible urinary catheters. Leave-one-out cross validation was performed to quantify the error between the urethra segmentation and the catheter ground truth with two scores: the centerlines distance (CLD) and the percentage of centerline within a certain distance from the catheter (PWR). The segmentation method was then applied to a second test data set of 95 prostate cancer patients having received 78Gy IMRT to quantify dose to the urethra. ResultsMean CLD was 3.25±1.2mm for the whole urethra and 3.7±1.7mm, 2.52±1.5mm, and 3.01±1.7mm for the top, middle, and bottom thirds, respectively. In average, 53% of the segmented centerlines were within a radius<3.5mm from the centerline ground truth and 83% in a radius<5mm. The proposed method outperformed existing surrogate models. In IMRT, urethra DVH was significantly higher than prostate DVH from V74Gy to V79Gy. ConclusionA multi-atlas-based segmentation method was proposed enabling assessment of the dose within the prostatic urethra.

Interindividual registration and dose mapping for voxelwise population analysis of rectal toxicity in prostate cancer radiotherapy

Recent studies revealed a trend toward voxelwise population analysis in order to understand the local dose/toxicity relationships in prostate cancer radiotherapy. Such approaches require, however, an accurate interindividual mapping of the anatomies and 3D dose distributions toward a common coordinate system. This step is challenging due to the high interindividual variability. In this paper, the authors propose a method designed for interindividual nonrigid registration of the rectum and dose mapping for population analysis. The method is based on the computation of a normalized structural description of the rectum using a Laplacian-based model. This description takes advantage of the tubular structure of the rectum and its centerline to be embedded in a nonrigid registration-based scheme. The performances of the method were evaluated on 30 individuals treated for prostate cancer in a leave-one-out cross validation. Performance was measured using classical metrics (Dice score and Hausdorff distance), along with new metrics devised to better assess dose mapping in relation with structural deformation (dose-organ overlap). Considering these scores, the proposed method outperforms intensity-based and distance maps-based registration methods. The proposed method allows for accurately mapping interindividual 3D dose distributions toward a single anatomical template, opening the way for further voxelwise statistical analysis.

Dose–volume effects for pelvic bone marrow in predicting hematological toxicity in prostate cancer radiotherapy with pelvic node irradiation

PurposeTo prospectively identify clinical/dosimetric predictors of acute/late hematologic toxicity (HT) in chemo-naÏve patients treated with whole-pelvis radiotherapy (WPRT) for prostate cancer. Material and methodsData of 121 patients treated with adjuvant/salvage WPRT were analyzed (static-field IMRT n=19; VMAT/Rapidarc n=57; Tomotherapy n=45). Pelvic bone marrow (BM) was delineated as ilium (IL), lumbosacral, lower and whole pelvis (WP), and the relative DVHs were calculated. HT was graded both according to CTCAE v4.03 and as variation in percentage relative to baseline. Logistic regression was used to analyze association between HT and clinical/DVHs factors. ResultsSignificant differences (p<0.005) in the DVH of BM volumes between different techniques were found: Tomotherapy was associated with larger volumes receiving low doses (3–20Gy) and smaller receiving 40–50Gy. Lower baseline absolute values of WBC, neutrophils and lymphocytes (ALC) predicted acute/late HT (p⩽0.001). Higher BM V40 was associated with higher risk of acute Grade3 (OR=1.018) or late Grade2 lymphopenia (OR=1.005). Two models predicting lymphopenia were developed, both including baseline ALC, and BM WP-V40 (AUC=0.73) and IL-V40+smoking (AUC=0.904) for acute/late respectively. ConclusionsSpecific regions of pelvic BM predicting acute/late lymphopenia, a risk factor for viral infections, were identified. The 2-variable models including specific constraints to BM may help reduce HT.

Parametrized rectal dose and associations with late toxicity in prostate cancer radiotherapy.

We investigated possible associations between planned dose-volume parameters and rectal late toxicity in 170 patients having radical prostate cancer radiotherapy. For each patient, the rectum was outlined from anorectal junction to sigmoid colon, and rectal dose was parametrized using dose-volume (DVH), dose-surface (DSH) and dose-line (DLH) histograms. Generation of DLHs differed from previous studies in that the rectal dose was parametrized without first unwrapping onto 2-dimensional dose-surface maps. Patient-reported outcomes were collected using a validated Later Effects in Normal Tissues Subjective, Objective, Management and Analytic questionnaire. Associations between dose and toxicity were assessed using a one-sided Mann-Whitney U test. Associations (p < 0.05) were found between equieffective dose (EQD23) and late toxicity as follows: overall toxicity with DVH and DSH at 13-24 Gy; proctitis with DVH and DSH at 25-36 Gy and with DVH, DSH and DLH at 61-67 Gy; bowel urgency with DVH and DSH at 10-20 Gy. None of these associations met statistical significance following the application of a Bonferroni correction. Independently confirmed associations between rectal dose and late toxicity remain elusive. Future work to increase the accuracy of the knowledge of the rectal dose, either by accounting for interfraction and intrafraction rectal motion or via stabilization of the rectum during treatment, may be necessary to allow for improved dose-toxicity comparisons. This study is the first to use parametrized DLHs to study associations with patient-reported toxicity for prostate radiotherapy showing that it is feasible to model rectal dose mapping in three dimensions.

PO-0906: Is the anal sphincter a key structure for gastrointestinal toxicity in prostate cancer radiotherapy?

PO-0906: Is the anal sphincter a key structure for gastrointestinal toxicity in prostate cancer radiotherapy?

OC-0565: Identification of a rectal sub-region at risks of toxicity in prostate cancer radiotherapy

OC-0565: Identification of a rectal sub-region at risks of toxicity in prostate cancer radiotherapy

Reducing rectal injury during external beam radiotherapy for prostate cancer

Rectal bleeding and faecal incontinence are serious injuries that men with prostate cancer who receive radiotherapy can experience. Although technical advances--including the use of intensity-modulated radiotherapy coupled with image-guided radiotherapy--have enabled the delivery of dose distributions that conform to the shape of the tumour target with steep dose gradients that reduce the dose given to surrounding tissues, radiotherapy-associated toxicity can not be avoided completely. Many large-scale prospective studies have analysed the correlations of patient-related and treatment-related parameters with acute and late toxicity to optimize patient selection and treatment planning. The careful application of dose-volume constraints and the tuning of these constraints to the individual patient's characteristics are now considered the most effective ways of reducing rectal morbidity. Additionally, the use of endorectal balloons (to reduce the margins between the clinical target volume and planning target volume) and the insertion of tissue spacers into the region between the prostate and anterior rectal wall have been investigated as means to further reduce late rectal injury. Finally, some drugs and other compounds are also being considered to help protect healthy tissue. Overall, a number of approaches exist that must be fully explored in large prospective trials to address the important issue of rectal toxicity in prostate cancer radiotherapy.

Voxel-based population analysis for correlating local dose and rectal toxicity in prostate cancer radiotherapy

The majority of current models utilized for predicting toxicity in prostate cancer radiotherapy are based on dose–volume histograms. One of their main drawbacks is the lack of spatial accuracy, since they consider the organs as a whole volume and thus ignore the heterogeneous intra-organ radio-sensitivity. In this paper, we propose a dose-image-based framework to reveal the relationships between local dose and toxicity. In this approach, the three-dimensional (3D) planned dose distributions across a population are non-rigidly registered into a common coordinate system and compared at a voxel level, therefore enabling the identification of 3D anatomical patterns, which may be responsible for toxicity, at least to some extent. Additionally, different metrics were employed in order to assess the quality of the dose mapping. The value of this approach was demonstrated by prospectively analyzing rectal bleeding (⩾Grade 1 at 2 years) according to the CTCAE v3.0 classification in a series of 105 patients receiving 80 Gy to the prostate by intensity modulated radiation therapy (IMRT). Within the patients presenting bleeding, a significant dose excess (6 Gy on average, p < 0.01) was found in a region of the anterior rectal wall. This region, close to the prostate (1 cm), represented less than 10% of the rectum. This promising voxel-wise approach allowed subregions to be defined within the organ that may be involved in toxicity and, as such, must be considered during the inverse IMRT planning step.

2037 POSTER Principal Components Analysis of Dose Distribution for Characterizing Toxicity in Prostate Cancer Radiotherapy

2037 POSTER Principal Components Analysis of Dose Distribution for Characterizing Toxicity in Prostate Cancer Radiotherapy

2036 POSTER Voxel Based Analysis of Dose for Prediction of Urinary and Rectal Toxicity in Prostate Cancer Radiotherapy

2036 POSTER Voxel Based Analysis of Dose for Prediction of Urinary and Rectal Toxicity in Prostate Cancer Radiotherapy

Rectal Dose Constraints for Intensity Modulated Radiation Therapy of the Prostate

Prostate dose escalation appears to have resulted in increased cancer control. Such escalation has been made possible by the ability to deliver more conformal treatment that spares normal tissue from the higher radiation doses. The supposition is that this has enabled higher doses, but without an increase in toxicity. The most disabling toxicity in prostate cancer radiotherapy is rectal. We evaluated the current status of conformal radiation and late rectal toxicity with the goal of determining whether reasonable rectal dose and volume constraints can be determined. Although the literature is inexact, we believe that some generalized constraints can be recommended and show that those recommendations are consistent with what is being used at experienced centers.

Ultrasonic Multifeature Tissue Analysis for the Prostate: Implications for Monitoring Outcome in Prostate Cancer Radiotherapy

Ultrasonic multifeature analysis has been investigated in prostate cancer detection because of its ability to measure physical properties of biological tissue. We conducted a feasibility study to determine if this ultrasound technique can also quantitatively assess radiation-induced changes inside the prostate gland. This study was undertaken with the ultimate goal of developing a noninvasive imaging technique to evaluate tumor control as well as radiation toxicity in prostate cancer radiotherapy.