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Toward personalized dose-prescription in locally advanced non-small cell lung cancer: Validation of published normal tissue complication probability models.

ABSTRACT: PURPOSE:To identify published normal tissue complication probability (NTCP) models suitable for patient-specific dose-prescription in locally advanced non-small cell lung cancer (LA-NSCLC) through in-house validation. MATERIAL AND METHODS:From eight previously published candidate NTCP models (?grade 2 acute esophagitis and radiation pneumonitis; AE2, RP2), patient-specific dose-responses were calculated using model variables and fractionation-corrected doses for 241 LA-NSCLC patients treated with chemo-IMRT to 50-80?Gy@1.8-2.0?Gy between 2004 and 2014 (AE2/RP2 rate: 50%/12%). A model was judged final if it significantly predicted AE2 or RP2 (p???0.05), was discriminative and well calibrated (AUC?>?0.60; Hosmer-Lemeshow test pHL?>?0.05), which were assessed as the median over 1000 bootstrap samples. RESULTS:Models for AE2 had superior discrimination to RP2 models (AUC?=?0.63-0.65 vs. 0.51-0.65). The final AE2 model included mean esophageal dose and concurrent chemotherapy (AUC?=?0.65; p?

SUBMITTER: Thor M

PROVIDER: S-EPMC6710111 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Toward personalized dose-prescription in locally advanced non-small cell lung cancer: Validation of published normal tissue complication probability models.

Thor M M Deasy Jo J Iyer A A Bendau E E Fontanella A A Apte A A Yorke E E Rimner A A Jackson A A

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 20190527

<h4>Purpose</h4>To identify published normal tissue complication probability (NTCP) models suitable for patient-specific dose-prescription in locally advanced non-small cell lung cancer (LA-NSCLC) through in-house validation.<h4>Material and methods</h4>From eight previously published candidate NTCP models (≥grade 2 acute esophagitis and radiation pneumonitis; AE2, RP2), patient-specific dose-responses were calculated using model variables and fractionation-corrected doses for 241 LA-NSCLC patie ...[more]

PMID: 31146070

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Project description:PurposeMultiparametric magnetic resonance tomography (mpMRI) and prostate specific membrane antigen positron emission tomography (PSMA-PET/CT) are used to guide focal radiotherapy (RT) dose escalation concepts. Besides improvements of treatment effectiveness, maintenance of a good quality of life is essential. Therefore, this planning study investigates whether urethral sparing in moderately hypofractionated RT with focal RT dose escalation influences tumour control probability (TCP) and normal tissue complication probability (NTCP).Patients and methods10 patients with primary prostate cancer (PCa), who underwent 68Ga PSMA-PET/CT and mpMRI followed by radical prostatectomy were enrolled. Intraprostatic tumour volumes (gross tumor volume, GTV) based on both imaging techniques (GTV-MRI and -PET) were contoured manually using validated contouring techniques and GTV-Union was created by summing both. For each patient three IMRT plans were generated with 60 Gy to the whole prostate and a simultaneous integrated boost up to 70 Gy to GTV-Union in 20 fractions by (Plan 1) not respecting and (Plan 2) respecting dose constraints for urethra as well as (Plan 3) respecting dose constraints for planning organ at risk volume for urethra (PRV = urethra + 2mm expansion). NTCP for urethra was calculated applying a Lyman-Kutcher-Burman model. TCP-Histo was calculated based on PCa distribution in co-registered histology (GTV-Histo). Complication free tumour control probability (P+) was calculated. Furthermore, the intrafractional movement was considered.ResultsMedian overlap of GTV-Union and PRV-Urethra was 1.6% (IQR 0-7%). Median minimum distance of GTV-Histo to urethra was 3.6 mm (IQR 2 - 7 mm) and of GTV-Union to urethra was 1.8 mm (IQR 0.0 - 5.0 mm). The respective prescription doses and dose constraints were reached in all plans. Urethra-sparing in Plans 2 and 3 reached significantly lower NTCP-Urethra (p = 0.002) without significantly affecting TCP-GTV-Histo (p = p > 0.28), NTCP-Bladder (p > 0.85) or NTCP-Rectum (p = 0.85), resulting in better P+ (p = 0.006). Simulation of intrafractional movement yielded even higher P+ values for Plans 2 and 3 compared to Plan 1.ConclusionUrethral sparing may increase the therapeutic ratio and should be implemented in focal RT dose escalation concepts.

Project description:Purpose:This study aimed to analyze the potential clinical impact of the differences between planned and accumulated doses on the development and use of normal tissue complication probability (NTCP) models. Methods and Materials:Thirty patients who were previously treated with stereotactic body radiation therapy for liver cancer and for whom the accumulated dose was computed were assessed retrospectively. The linear quadratic equivalent dose at 2?Gy per fraction and generalized equivalent uniform dose were calculated for planned and accumulated doses. Stomach and duodenal Lyman-Kutcher-Burman NTCP models (?/??=?2.5; n?=?.09) were developed on the basis of planned and accumulated generalized equivalent uniform doses and the differences between the models assessed. In addition, the error in determining the probability of toxicity on the basis of the planned dose was evaluated by comparing planned doses in the NTCP model that were created from accumulated doses. Results:The standard, planned-dose NTCP model overestimates toxicity risk for both the duodenal and stomach models at doses that are below approximately 20?Gy (6 fractions) and underestimates toxicity risk for doses above approximately 20?Gy (6 fractions). Building NTCP models with accumulated rather than planned doses changes the predicted risk by up to 16% (mean: 6%; standard deviation: 7%) for duodenal toxicity and 6% (mean: 2%; standard deviation: 2%) for stomach toxicity. For a protocol that plans a 10% iso-toxicity risk to the duodenum, a 15.7?Gy (6 fractions) maximum dose constraint would be necessary when using standard NTCP models on the basis of a planned dose and a 17.6?Gy (6 fractions) maximum dose would be allowed when using NTCP models on the basis of accumulated doses. Conclusions:Assuming that accumulated dose is a more accurate representation of the true delivered dose than the planned dose, this simulation study indicates the need for prospective clinical trials to evaluate the impact of building NTCP models on the basis of accumulated doses.

Project description:Radiomics analyses commonly apply imaging features of different complexity for the prediction of the endpoint of interest. However, the prognostic value of each feature class is generally unclear. Furthermore, many radiomics models lack independent external validation that is decisive for their clinical application. Therefore, in this manuscript we present two complementary studies. In our modelling study, we developed and validated different radiomics signatures for outcome prediction after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) based on computed tomography (CT) and T2-weighted (T2w) magnetic resonance (MR) imaging datasets of 4 independent institutions (training: 122, validation 68 patients). We compared different feature classes extracted from the gross tumour volume for the prognosis of tumour response and freedom from distant metastases (FFDM): morphological and first order (MFO) features, second order texture (SOT) features, and Laplacian of Gaussian (LoG) transformed intensity features. Analyses were performed for CT and MRI separately and combined. Model performance was assessed by the area under the curve (AUC) and the concordance index (CI) for tumour response and FFDM, respectively. Overall, intensity features of LoG transformed CT and MR imaging combined with clinical T stage (cT) showed the best performance for tumour response prediction, while SOT features showed good performance for FFDM in independent validation (AUC = 0.70, CI = 0.69). In our external validation study, we aimed to validate previously published radiomics signatures on our multicentre cohort. We identified relevant publications on comparable patient datasets through a literature search and applied the reported radiomics models to our dataset. Only one of the identified studies could be validated, indicating an overall lack of reproducibility and the need of further standardization of radiomics before clinical application.

Dataset Information

Toward personalized dose-prescription in locally advanced non-small cell lung cancer: Validation of published normal tissue complication probability models.

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Toward personalized dose-prescription in locally advanced non-small cell lung cancer: Validation of published normal tissue complication probability models.

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