Standardized Classification of Lung Adenocarcinoma Subtypes and Improvement of Grading Assessment Through Deep Learning.

The histopathologic distinction of lung adenocarcinoma (LADC) subtypes is subject to high interobserver variability, which can compromise the optimal assessment of patient prognosis. Therefore, this study developed convolutional neural networks capable of distinguishing LADC subtypes and predicting disease-specific survival, according to the recently established LADC tumor grades. Consensus LADC histopathologic images were obtained from 17 expert pulmonary pathologists and one pathologist in training. Two deep learning models (AI-1 and AI-2) were trained to predict eight different LADC classes. Furthermore, the trained models were tested on an independent cohort of 133 patients. The models achieved high precision, recall, and F1 scores exceeding 0.90 for most of the LADC classes. Clear stratification of the three LADC grades was reached in predicting the disease-specific survival by the two models, with both Kaplan-Meier curves showing significance (P = 0.0017 and 0.0003). Moreover, both trained models showed high stability in the segmentation of each pair of predicted grades with low variation in the hazard ratio across 200 bootstrapped samples. These findings indicate that the trained convolutional neural networks improve the diagnostic accuracy of the pathologist and refine LADC grade assessment. Thus, the trained models are promising tools that may assist in the routine evaluation of LADC subtypes and grades in clinical practice.

Radiomic analysis of lung cancer for the assessment of patient prognosis and intratumor heterogeneity.

OBJECTIVE: To determine whether the radiomic features of lung lesions on computed tomography correlate with overall survival in lung cancer patients. MATERIALS AND METHODS: This was a retrospective study involving 101 consecutive patients with malignant neoplasms confirmed by biopsy or surgery. On computed tomography images, the lesions were submitted to semi-automated segmentation and were characterized on the basis of 2,465 radiomic variables. The prognostic assessment was based on Kaplan-Meier analysis and log-rank tests, according to the median value of the radiomic variables. RESULTS: Of the 101 patients evaluated, 28 died (16 dying from lung cancer), and 73 were censored, with a mean overall survival time of 1,819.4 days (95% confidence interval [95% CI]: 1,481.2-2,157.5). One radiomic feature (the mean of the Fourier transform) presented a difference on Kaplan-Meier curves (p < 0.05). A high-risk group of patients was identified on the basis of high values for the mean of the Fourier transform. In that group, the mean survival time was 1,465.4 days (95% CI: 985.2-1,945.6), with a hazard ratio of 2.12 (95% CI: 1.01-4.48). We also identified a low-risk group, in which the mean of the Fourier transform was low (mean survival time of 2,164.8 days; 95% CI: 1,745.4-2,584.1). CONCLUSION: A radiomic signature based on the Fourier transform correlates with overall survival, representing a prognostic biomarker for risk stratification in patients with lung cancer.

OBJETIVO: Associar características radiômicas de lesões pulmonares em imagens de tomografia computadorizada com a sobrevida global de pacientes com câncer de pulmão. MATERIAIS E MÉTODOS: Estudo retrospectivo composto por 101 pacientes consecutivos com neoplasia maligna confirmada por biópsia/cirurgia. As lesões foram semiautomaticamente segmentadas e caracterizadas por 2.465 variáveis radiômicas. A avaliação prognóstica foi baseada na análise de Kaplan-Meier e no teste log-rank, de acordo com a mediana dos valores das variáveis. RESULTADOS: Vinte e oito pacientes faleceram (16 por câncer de pulmão) e 73 foram censurados, com tempo médio de sobrevida de 1.819,4 dias (intervalo de confiança 95% [IC 95%]: 1.481,2-2.157,5). Uma característica radiômica (média de Fourier) apresentou diferença nas curvas de Kaplan-Meier (p < 0,05). Um grupo de pacientes de maior risco foi identificado a partir de valores altos da variável: sobrevida de 1.465,4 dias (IC 95%: 985,2-1.945,6) e razão de risco de 2,12 (IC 95%: 1,01-4,48). Um grupo de menor risco foi identificado a partir de valores baixos da variável (sobrevida de 2.164,8 dias; IC 95%: 1.745,4-2.584,1). CONCLUSÃO: Este estudo apresentou uma assinatura radiômica em imagens de tomografia computadorizada, baseada na transformada de Fourier, correlacionada com a sobrevida global de pacientes com câncer de pulmão, representando assim um biomarcador prognóstico.

Radiomic analysis of lung cancer for the assessment of patient prognosis and intratumor heterogeneity / Análise radiômica do câncer de pulmão para avaliação prognóstica do paciente e da heterogeneidade intratumoral

Abstract Objective: To determine whether the radiomic features of lung lesions on computed tomography correlate with overall survival in lung cancer patients. Materials and Methods: This was a retrospective study involving 101 consecutive patients with malignant neoplasms confirmed by biopsy or surgery. On computed tomography images, the lesions were submitted to semi-automated segmentation and were characterized on the basis of 2,465 radiomic variables. The prognostic assessment was based on Kaplan-Meier analysis and log-rank tests, according to the median value of the radiomic variables. Results: Of the 101 patients evaluated, 28 died (16 dying from lung cancer), and 73 were censored, with a mean overall survival time of 1,819.4 days (95% confidence interval [95% CI]: 1,481.2-2,157.5). One radiomic feature (the mean of the Fourier transform) presented a difference on Kaplan-Meier curves (p < 0.05). A high-risk group of patients was identified on the basis of high values for the mean of the Fourier transform. In that group, the mean survival time was 1,465.4 days (95% CI: 985.2-1,945.6), with a hazard ratio of 2.12 (95% CI: 1.01-4.48). We also identified a low-risk group, in which the mean of the Fourier transform was low (mean survival time of 2,164.8 days; 95% CI: 1,745.4-2,584.1). Conclusion: A radiomic signature based on the Fourier transform correlates with overall survival, representing a prognostic biomarker for risk stratification in patients with lung cancer.

Resumo Objetivo: Associar características radiômicas de lesões pulmonares em imagens de tomografia computadorizada com a sobrevida global de pacientes com câncer de pulmão. Materiais e Métodos: Estudo retrospectivo composto por 101 pacientes consecutivos com neoplasia maligna confirmada por biópsia/cirurgia. As lesões foram semiautomaticamente segmentadas e caracterizadas por 2.465 variáveis radiômicas. A avaliação prognóstica foi baseada na análise de Kaplan-Meier e no teste log-rank, de acordo com a mediana dos valores das variáveis. Resultados: Vinte e oito pacientes faleceram (16 por câncer de pulmão) e 73 foram censurados, com tempo médio de sobrevida de 1.819,4 dias (intervalo de confiança 95% [IC 95%]: 1.481,2-2.157,5). Uma característica radiômica (média de Fourier) apresentou diferença nas curvas de Kaplan-Meier (p < 0,05). Um grupo de pacientes de maior risco foi identificado a partir de valores altos da variável: sobrevida de 1.465,4 dias (IC 95%: 985,2-1.945,6) e razão de risco de 2,12 (IC 95%: 1,01-4,48). Um grupo de menor risco foi identificado a partir de valores baixos da variável (sobrevida de 2.164,8 dias; IC 95%: 1.745,4-2.584,1). Conclusão: Este estudo apresentou uma assinatura radiômica em imagens de tomografia computadorizada, baseada na transformada de Fourier, correlacionada com a sobrevida global de pacientes com câncer de pulmão, representando assim um biomarcador prognóstico.