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Modelling duodenum radiotherapy toxicity using cohort dose-volume-histogram data.

ABSTRACT: Gastro-intestinal toxicity is dose-limiting in abdominal radiotherapy and correlated with duodenum dose-volume parameters. We aimed to derive updated NTCP model parameters using published data and prospective radiotherapy quality-assured cohort data.A systematic search identified publications providing duodenum dose-volume histogram (DVH) statistics for clinical studies of conventionally-fractionated radiotherapy. Values for the Lyman-Kutcher-Burman (LKB) NTCP model were derived through sum-squared-error minimisation and using leave-one-out cross-validation. Data were corrected for fraction size and weighted according to patient numbers, and the model refined using individual patient DVH data for two further cohorts from prospective clinical trials.Six studies with published DVH data were utilised, and with individual patient data included outcomes for 531 patients in total (median follow-up 16months). Observed gastro-intestinal toxicity rates ranged from 0% to 14% (median 8%). LKB parameter values for unconstrained fit to published data were: n=0.070, m=0.46, TD50(1) [Gy]=183.8, while the values for the model incorporating the individual patient data were n=0.193, m=0.51, TD50(1) [Gy]=299.1.LKB parameters derived using published data are shown to be consistent to those previously obtained using individual patient data, supporting a small volume-effect and dependence on exposure to high threshold dose.

SUBMITTER: Holyoake DLP

PROVIDER: S-EPMC5486774 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Modelling duodenum radiotherapy toxicity using cohort dose-volume-histogram data.

Holyoake Daniel L P DLP Aznar Marianne M Mukherjee Somnath S Partridge Mike M Hawkins Maria A MA

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 20170606 3

<h4>Background and purpose</h4>Gastro-intestinal toxicity is dose-limiting in abdominal radiotherapy and correlated with duodenum dose-volume parameters. We aimed to derive updated NTCP model parameters using published data and prospective radiotherapy quality-assured cohort data.<h4>Material and methods</h4>A systematic search identified publications providing duodenum dose-volume histogram (DVH) statistics for clinical studies of conventionally-fractionated radiotherapy. Values for the Lyman-K ...[more]

PMID: 28600084

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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 purpose of this work is to evaluate the performance of applying patient dosimetric information induced by individual uniform-intensity radiation fields in organ-at risk (OAR) dose-volume histogram (DVH) prediction, and extend to DVH prediction of planning target volume (PTV). Ninety nasopharyngeal cancer intensity-modulated radiation therapy (IMRT) plans and 60 rectal cancer volumetric modulated arc therapy (VMAT) plans were employed in this study. Of these, 20 nasopharyngeal cancer cases and 15 rectal cancer cases were randomly selected as the testing data. The DVH prediction was performed using two methods. One method applied the individual dose-volume histograms (IDVHs) induced by a series of fields with uniform-intensity irradiation and the other method applied the distance-to-target histogram and the conformal-plan-dose-volume histogram (DTH + CPDVH). The determination coefficient R2 and mean absolute error (MAE) were used to evaluate DVH prediction accuracy. The PTV DVH prediction was performed using the IDVHs. The PTV dose coverage was evaluated using D98, D95, D1 and uniformity index (UI). The OAR dose was compared using the maximum dose, V30 and V40. The significance of the results was examined with the Wilcoxon signed rank test. For PTV DVH prediction using IDVHs, the clinical plan and IDVHs prediction method achieved mean UI values of 1.07 and 1.06 for nasopharyngeal cancer, and 1.04 and 1.05 for rectal cancer, respectively. No significant difference was found between the clinical plan results and predicted results using the IDVHs method in achieving PTV dose coverage (D98, D95, D1 and UI) for both nasopharyngeal cancer and rectal cancer (p-values ≥ 0.052). For OAR DVH prediction, no significant difference was found between the IDVHs and DTH + CPDVH methods for the R2, MAE, the maximum dose, V30 and V40 (p-values ≥ 0.087 for all OARs). This work evaluates the performance of dosimetric information of several individual fields with uniform-intensity radiation for DVH prediction, and extends its application to PTV DVH prediction. The results indicated that the IDVHs method is comparable to the DTH + CPDVH method in accurately predicting the OAR DVH. The IDVHs method quantified the input features of the PTV and showed reliable PTV DVH prediction, which is helpful for plan quality evaluation and plan generation.

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Modelling duodenum radiotherapy toxicity using cohort dose-volume-histogram data.

Publications

Modelling duodenum radiotherapy toxicity using cohort dose-volume-histogram data.

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