Longitudinal radiomics of cone-beam CT images from non-small cell lung cancer patients : evaluation of the added prognostic value for overall survival and locoregional recurrence

Background and purpose: The prognostic value of radiomics for non-small cell lung cancer (NSCLC) patients has been investigated for images acquired prior to treatment, but no prognostic model has been developed that includes the change of radiomic features during treatment. Therefore, the aim of this study was to investigate the potential added prognostic value of a longitudinal radiomics approach using cone-beam computed tomography (CBCT) for NSCLC patients. Materials and methods: This retrospective study includes a training dataset of 141 stage I-IV NSCLC patients and three external validation datasets of 94, 61 and 41 patients, all treated with curative intended (chemo) radiotherapy. The change of radiomic features extracted from CBCT images was summarized as the slope of a linear regression. The CBCT slope-features and CT-extracted features were used as input for a Cox proportional hazards model. Moreover, prognostic performance of clinical parameters was investigated for overall survival and locoregional recurrence. Model performances were assessed using the Kaplan-Meier curves and c-index. Results: The radiomics model contained only CT-derived features and reached a c-index of 0.63 for overall survival and could be validated on the first validation dataset. No model for locoregional recurrence could be developed that validated on the validation datasets. The clinical parameters model could not be validated for either overall survival or locoregional recurrence. Conclusion: In this study we could not confirm our hypothesis that longitudinal CBCT-extracted radiomic features contribute to improved prognostic information. Moreover, performance of baseline radiomic features or clinical parameters was poor, probably affected by heterogeneity within and between datasets

Analytical variables influencing the performance of a miRNA based laboratory assay for prediction of relapse in stage I non-small cell lung cancer (NSCLC)

<p>Abstract</p> <p>Background</p> <p>Laboratory assays are needed for early stage non-small lung cancer (NSCLC) that can link molecular and clinical heterogeneity to predict relapse after surgical resection. We technically validated two miRNA assays for prediction of relapse in NSCLC. Total RNA from seventy-five formalin-fixed and paraffin-embedded (FFPE) specimens was extracted, labeled and hybridized to Affymetrix miRNA arrays using different RNA input amounts, ATP-mix dilutions, array lots and RNA extraction- and labeling methods in a total of 166 hybridizations. Two combinations of RNA extraction- and labeling methods (assays I and II) were applied to a cohort of 68 early stage NSCLC patients.</p> <p>Results</p> <p>RNA input amount and RNA extraction- and labeling methods affected signal intensity and the number of detected probes and probe sets, and caused large variation, whereas different ATP-mix dilutions and array lots did not. Leave-one-out accuracies for prediction of relapse were 63% and 73% for the two assays. Prognosticator calls ("no recurrence" or "recurrence") were consistent, independent on RNA amount, ATP-mix dilution, array lots and RNA extraction method. The calls were not robust to changes in labeling method.</p> <p>Conclusions</p> <p>In this study, we demonstrate that some analytical conditions such as RNA extraction- and labeling methods are important for the variation in assay performance whereas others are not. Thus, careful optimization that address all analytical steps and variables can improve the accuracy of prediction and facilitate the introduction of microRNA arrays in the clinic for prediction of relapse in stage I non-small cell lung cancer (NSCLC).</p

Accuracy of dose calculation based on artefact corrected Cone Beam CT images of lung cancer patients

Background and purpose: Accurate Cone Beam CT (CBCT) based dose calculations are hindered by limited CBCT image quality. Using retrospective artefact corrections, this paper investigated the accuracy of dose calculations performed directly on CBCT images of lung cancer patients. Materials and methods: Dose calculations were made directly on clinical and artefact corrected CBCT images of 21 lung cancer patients with a re-simulation CT (rCT) image acquired during radiotherapy. The original treatment plan was copied to the rCT and CBCT images and dose was recalculated. Dose comparisons were made using gamma analysis and dose statistics. Gamma comparisons were made using 2%/2 mm and 1%/1 mm criteria, and pass rates of the clinical and improved CBCT images were calculated using the rCT based dose as reference. Results: Dose distributions calculated on the artefact corrected CBCT images had a median 2%/2 mm gamma pass rate of 99.4% when compared to the reference rCT. Doses calculated on the clinical CBCT images had a median 2%/2 mm gamma pass rate of 93.1%. Wilcoxon signed rank test showed the pass rates in the entire CBCT field of view different at p<0.001. Clinical CBCT image based dose calculations overestimated the dose, while the improved CBCT doses were in closer agreement with the rCT doses. Conclusions: Comprehensive artefact correction of CBCT images allowed highly accurate dose calculations to be performed directly on CBCT images of lung cancer patients, following the standard CT-based workflow in a treatment planning system. Keywords: Image guided radiotherapy, Adaptive radiotherapy, Dose of the day, Cone Beam C

Age dependent prognosis in concurrent chemo-radiation of locally advanced NSCLC

<div><p></p><p><b>Background.</b> Clinical trials indicate that the benefit of adding concurrent chemotherapy to radiotherapy of locally advanced non-small cell lung cancer (NSCLC) for fit elderly is similar to the benefit for younger patients. However, since elderly patients are under-represented in most trials, the results might be due to selection bias, thus reports from a cohort of consecutively treated patients are warranted. The current single institution study reports on the influence of age on survival of locally advanced NSCLC patients treated with radiotherapy combined with or without concurrent chemotherapy.</p><p><b>Material and methods.</b> Altogether, 478 patients completed radical radiotherapy in doses of 60–66 Gy/30–33 fractions from 1995 to June 2012; 137 of the patients had concurrent chemotherapy. The data was analyzed in age groups < 60, 60–69, and ≥ 70 years.</p><p><b>Results.</b> In the analyses of overall and lung cancer specific survival the hazard ratio was related to the use of concurrent chemotherapy was 0.49 (95% CI 0.29; 0.82), 0.68 (95% CI 0.48; 0.98) and 1.01 (95% CI 0.67; 1.51) for the age groups < 60, 60–69, and ≥ 70, respectively.</p><p><b>Conclusion.</b> Use of concurrent chemotherapy to radiotherapy of locally advanced NSCLC was associated with a survival benefit in patient younger than 70 years which was not the case for patients older than 70 years, indicating the need to be careful when selecting elderly patients for concurrent chemo-radiation.</p></div