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Radiomics Analysis of 3D Dose Distributions to Predict Toxicity of Radiotherapy for Cervical Cancer.

ABSTRACT: Standard treatment for locally advanced cervical cancer (LACC) is chemoradiotherapy followed by brachytherapy. Despite radiation therapy advances, the toxicity rate remains significant. In this study, we compared the prediction of toxicity events after radiotherapy for locally advanced cervical cancer (LACC), based on either dose-volume histogram (DVH) parameters or the use of a radiomics approach applied to dose maps at the voxel level. Toxicity scores using the Common Terminology Criteria for Adverse Events (CTCAE v4), spatial dose distributions, and usual clinical predictors for the toxicity of 102 patients treated with chemoradiotherapy followed by brachytherapy for LACC were used in this study. In addition to usual DVH parameters, 91 radiomic features were extracted from rectum, bladder and vaginal 3D dose distributions, after discretization into a fixed bin width of 1 Gy. They were evaluated for predictive modelling of rectal, genitourinary (GU) and vaginal toxicities (grade ≥ 2). Logistic Normal Tissue Complication Probability (NTCP) models were derived using clinical parameters only or combinations of clinical, DVH and radiomics. For rectal acute/late toxicities, the area under the curve (AUC) using clinical parameters was 0.53/0.65, which increased to 0.66/0.63, and 0.76/0.87, with the addition of DVH or radiomics parameters, respectively. For GU acute/late toxicities, the AUC increased from 0.55/0.56 (clinical only) to 0.84/0.90 (+DVH) and 0.83/0.96 (clinical + DVH + radiomics). For vaginal acute/late toxicities, the AUC increased from 0.51/0.57 (clinical only) to 0.58/0.72 (+DVH) and 0.82/0.89 (clinical + DVH + radiomics). The predictive performance of NTCP models based on radiomics features was higher than the commonly used clinical and DVH parameters. Dosimetric radiomics analysis is a promising tool for NTCP modelling in radiotherapy.

SUBMITTER: Lucia F

PROVIDER: S-EPMC8151048 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundBetter knowledge of the dose-toxicity relationship is essential for safe dose escalation to improve local control in cervical cancer radiotherapy. The conventional dose-toxicity model is based on the dose volume histogram, which is the parameter lacking spatial dose information. To overcome this limit, we explore a comprehensive rectal dose-toxicity model based on both dose volume histogram and dose map features for accurate radiation toxicity prediction.MethodsForty-two cervical cancer patients treated with combined external beam radiotherapy (EBRT) and brachytherapy (BT) were retrospectively studied, including 12 with Grade???2 rectum toxicity and 30 patients with Grade 0-1 toxicity (non-toxicity patients). The cumulative equivalent 2-Gy rectal surface dose was deformably summed using the deformation vector fields obtained through a recent developed local topology preserved non-rigid point matching algorithm. The cumulative three-dimensional (3D) dose was flattened and mapped to a two-dimensional (2D) plane to obtain the rectum surface dose map (RSDM). The dose volume parameters (DVPs) were calculated from the 3D rectum surface, while the texture features and the dose geometric parameters (DGPs) were extracted from the 2D RSDM. Representative features further computed from DVPs, textures and DGPs by principle component analysis (PCA) and statistical analysis were respectively fed into a support vector machine equipped with a sequential feature selection procedure. The predictive powers of the representative features were compared with the GEC-ESTRO dosimetric parameters D0.1/1/2cm3.ResultsSatisfactory predictive accuracy of sensitivity 74.75 and 84.75%, specificity 72.67 and 79.87%, and area under the receiver operating characteristic curve (AUC) 0.82 and 0.91 were respectively achieved by the PCA features and statistical significant features, which were superior to the D0.1/1/2cm3 (AUC 0.71). The relative area in dose levels of 64Gy, 67Gy, 68Gy, 87Gy, 88Gy and 89Gy, perimeters in dose levels of 89Gy, as well as two texture features were ranked as the important factors that were closely correlated with rectal toxicity.ConclusionsOur extensive experimental results have demonstrated the feasibility of the proposed scheme. A future large patient cohort study is still needed for model validation.

Project description:PurposeThe role of radiotherapy for unresectable pancreatic cancer is controversial. A benefit of additional radiotherapy is supported by some observations. A dose-effect relationship was recently found by dose escalation employing image guided and intensity modulated radiotherapy.MethodsWe retrospectively evaluated 28 consecutive patients, all with history of extensive prior therapies for unresectable locally advanced/ recurrent pancreatic cancer (LAPC/LRPC). Treatment was delivered by helical tomotherapy after daily position verification with computed tomography. Dose to the planned target volume (PTV) was 51 Gy, while the dose to the macroscopic tumor was escalated by a simultaneous integrated boost to a median cumulative dose of 66 Gy (60-66 Gy). Concomitant chemotherapy consisted mainly of capecitabine (n = 23).Results10 of 28 patients presented acute toxicities > grade 2, one patient succumbed to gastrointestinal bleeding after treatment. No correlations of toxicities and dose volume histograms (DVH) of retrospectively delineated small bowel loops were observed, although average small bowel volume receiving ? 20 Gy was 374 ml. DVH analyses revealed a correlation of splenic parameters and acute toxicity: Vomiting, anorexia, dehydration, hematologic toxicity, fatigue, combined gastro-intestinal toxicity wit R-values between 0.392 and 0.561 (all p-values > 0.05). Only one patient developed late toxicities > grade 2. With an average follow-up time in surviving patients of 14 months median overall survival time was 19 months and median time to local recurrence 13 months. In 8 patients with available imaging of local recurrence: 5 in field recurrences, 2 marginal recurrences and one lymph node recurrence outside the high dose radiation field were observed. In univariate analysis only ?CA-19-9 during radiotherapy was associated with local control (p = 0.029) and overall survival (p = 0.049).ConclusionDose escalated normo-fractionated radiotherapy for LAPC/LRPC seems feasible and suitable to prolong local control and in consequence long-term survival. However, in-field local progression is still frequently observed and possibilities to increase the local effectiveness should be evaluated. Exposure of the spleen was predictive for acute toxicity and should be further investigated.

Project description:The paper considers the fractionation problem in intensity modulated proton therapy (IMPT). Conventionally, IMPT fields are optimized independently of the fractionation scheme. In this work, we discuss the simultaneous optimization of fractionation scheme and pencil beam intensities.This is performed by allowing for distinct pencil beam intensities in each fraction, which are optimized using objective and constraint functions based on biologically equivalent dose (BED). The paper presents a model that mimics an IMPT treatment with a single incident beam direction for which the optimal fractionation scheme can be determined despite the nonconvexity of the BED-based treatment planning problem.For this model, it is shown that a small α∕β ratio in the tumor gives rise to a hypofractionated treatment, whereas a large α∕β ratio gives rise to hyperfractionation. It is further demonstrated that, for intermediate α∕β ratios in the tumor, a nonuniform fractionation scheme emerges, in which it is optimal to deliver different dose distributions in subsequent fractions. The intuitive explanation for this phenomenon is as follows: By varying the dose distribution in the tumor between fractions, the same total BED can be achieved with a lower physical dose. If it is possible to achieve this dose variation in the tumor without varying the dose in the normal tissue (which would have an adverse effect), the reduction in physical dose may lead to a net reduction of the normal tissue BED. For proton therapy, this is indeed possible to some degree because the entrance dose is mostly independent of the range of the proton pencil beam.The paper provides conceptual insight into the interdependence of optimal fractionation schemes and the spatial optimization of dose distributions. It demonstrates the emergence of nonuniform fractionation schemes that arise from the standard BED model when IMPT fields and fractionation scheme are optimized simultaneously. Although the projected benefits are likely to be small, the approach may give rise to an improved therapeutic ratio for tumors treated with stereotactic techniques to high doses per fraction.

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Radiomics Analysis of 3D Dose Distributions to Predict Toxicity of Radiotherapy for Cervical Cancer.

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