Can Pretreatment MRI and Planning CT Radiomics Improve Prediction of Complete Pathological Response in Locally Advanced Rectal Cancer Following Neoadjuvant Treatment?

OBJECTIVE(S): The treatment response to neoadjuvant chemoradiation (nCRT) differs largely in individuals treated for rectal cancer. In this study, we investigated the role of radiomics to predict the pathological response in locally advanced rectal cancers at different treatment time points: (1) before the start of any treatment using baseline T2-weighted MRI (T2W-MR) and (2) at the start of radiation treatment using planning CT. METHODS: Patients on nCRT followed by surgery between June 2017 to December 2019 were included in the study. Histopathological tumour response grading (TRG) was used for classification, and gross tumour volume was defined by the radiation oncologists. Following resampling, 100 and 103 pyradiomic features were extracted from T2W-MR and planning CT images, respectively. Synthetic minority oversampling technique (SMOTE) was used to address class imbalance. Four machine learning classifiers built clinical, radiomic, and merged models. Model performances were evaluated on a held-out test dataset following 3-fold cross-validation using area under the receiver operator characteristic curves (AUC) with bootstrap 95% confidence intervals. RESULTS: One hundred and fifty patients were included; 58/150 with TRG 1 were classified as complete responders, and rest were incomplete responders (IR). Clinical models performed better (AUC = 0.68) compared to radiomics models (AUC = 0.62). Overall, the clinical + T2W-MR model showed best performance (AUC = 0.72) in predicting the pathological response prior to therapy. Clinical + Planning CT-merged models could only achieve the highest AUC of 0.66. CONCLUSION: Merging clinical and baseline T2W-MR radiomics enhances predicting pathological response in rectal cancer. Validation in larger cohorts is warranted, especially for watch and wait strategies.

Reproducibility in Radiomics: A Comparison of Feature Extraction Methods and Two Independent Datasets.

Radiomics involves the extraction of information from medical images that are not visible to the human eye. There is evidence that these features can be used for treatment stratification and outcome prediction. However, there is much discussion about the reproducibility of results between different studies. This paper studies the reproducibility of CT texture features used in radiomics, comparing two feature extraction implementations, namely the MATLAB toolkit and Pyradiomics, when applied to independent datasets of CT scans of patients: (i) the open access RIDER dataset containing a set of repeat CT scans taken 15 min apart for 31 patients (RIDER Scan 1 and Scan 2, respectively) treated for lung cancer; and (ii) the open access HN1 dataset containing 137 patients treated for head and neck cancer. Gross tumor volume (GTV), manually outlined by an experienced observer available on both datasets, was used. The 43 common radiomics features available in MATLAB and Pyradiomics were calculated using two intensity-level quantization methods with and without an intensity threshold. Cases were ranked for each feature for all combinations of quantization parameters, and the Spearman's rank coefficient, rs, calculated. Reproducibility was defined when a highly correlated feature in the RIDER dataset also correlated highly in the HN1 dataset, and vice versa. A total of 29 out of the 43 reported stable features were found to be highly reproducible between MATLAB and Pyradiomics implementations, having a consistently high correlation in rank ordering for RIDER Scan 1 and RIDER Scan 2 (rs > 0.8). 18/43 reported features were common in the RIDER and HN1 datasets, suggesting they may be agnostic to disease site. Useful radiomics features should be selected based on reproducibility. This study identified a set of features that meet this requirement and validated the methodology for evaluating reproducibility between datasets.

Teleradiology and technology innovations in radiology: status in India and its role in increasing access to primary health care.

Background: There is an inequitable distribution of radiology facilities in India. This scoping review aimed at mapping the available technology instruments to improve access to imaging at primary health care; to identify the facilitators and barriers, and the knowledge gaps for widespread adaptation of technology solutions. Methods: A search was conducted using broad inclusive terms non-specific to subtypes of medical imaging devices or informatics. Work published in the English language between 2005 and 2022, conducted primarily in India, and with full manuscripts were included. Two authors independently screened the abstracts against the inclusion criteria for full-text review and a senior author settled discrepancies. Data were extracted using DistillerSR software. Findings: 43 original articles and 52 non-academic materials were finally reviewed. The data was from 10 Indian states with n = 9 from rural settings. The broad trends in original articles were: connectivity using teleradiology (n = 7), mobile digital imaging units (n = 9), artificial intelligence (n = 16); mobile devices and smartphone applications (n = 7); data security (n = 7) and web-based technology (n = 2); public-private partnership (n = 9); cost (n = 2); concordance (n = 19); evaluation (n = 4); implementation (n = 2). Interpretation: Available evidence suggests that teleradiology when combined with AI and mobile digital imaging units can address radiologist shortages; strengthen programs aimed at population screening and emergency care. However, there is insufficient data on the scale of teleradiology networks within India; needs assessment; cost; facilitators, and barriers for implementation of technologies solutions in primary healthcare settings. Regulations governing quality standards, data protection, and confidentiality are unclear. Funding: The authors are The Lancet Citizen's Commission fellows. The Lancet Commission has received financial support from the Lakshmi Mittal and Family South Asia Institute, Harvard University; Christian Medical College, Vellore (CMC), Vellore; Azim Premji Foundation, Infosys; Kirloskar Systems Ltd.; Mahindra & Mahindra Ltd.; Rohini Nilekani Philanthropies; and Serum Institute of India. The views expressed are those of the author(s) and not necessarily those of the Lancet Citizens' Commission or its partners.

Is radiomics a useful addition to magnetic resonance imaging in the preoperative classification of PitNETs?

BACKGROUND: The WHO 2021 introduced the term pituitary neuroendocrine tumours (PitNETs) for pituitary adenomas and incorporated transcription factors for subtyping, prompting the need for fresh diagnostic methods. Current biomarkers struggle to distinguish between high- and low-risk non-functioning PitNETs. We explored if radiomics can enhance preoperative decision-making. METHODS: Pre-treatment magnetic resonance (MR) images of patients who underwent surgery between 2015 and 2019 with available WHO 2021 classification were used. The tumours were manually segmented on the T1w, T1-contrast enhanced, and T2w images using 3D Slicer. One hundred Pyradiomic features were extracted from each MR sequence. Models were built to classify (1) somatotroph and gonadotroph PitNETs and (2) high- and low-risk subtypes of non-functioning PitNETs. Feature were selected independently from the MR sequences and multi-sequence (combining data from more than one MR sequence) using Boruta and Pearson correlation. Support vector machine (SVM), logistic regression (LR), random forest (RF), and multi-layer perceptron (MLP) were the classifiers used. Data imbalance was addressed using the Synthetic Minority Oversampling TEchnique (SMOTE). Performance of the models were evaluated using area under the receiver operating curve (AUC), accuracy, sensitivity, and specificity. RESULTS: A total of 222 PitNET patients (train, n = 149; test, n = 73) were enrolled in this retrospective study. Multi-sequence-based LR model discriminated best between somatotroph and gonadotroph PitNETs, with a test AUC of 0.84, accuracy of 0.74, specificity of 0.81, and sensitivity of 0.70. Multi-sequence-based MLP model perfomed best for the high- and low-risk non-functioning PitNETs, achieving a test AUC of 0.76, accuracy of 0.67, specificity of 0.72, and sensitivity of 0.66. CONCLUSIONS: Utilizing pre-treatment MRI and radiomics holds promise for distinguishing high-risk from low-risk non-functioning PitNETs based on the latest WHO classification. This could assist neurosurgeons in making critical decisions regarding surgery or alternative management strategies for PitNETs after further clinical validation.

Multi-centre radiomics for prediction of recurrence following radical radiotherapy for head and neck cancers: Consequences of feature selection, machine learning classifiers and batch-effect harmonization.

Background and purpose: Radiomics models trained with limited single institution data are often not reproducible and generalisable. We developed radiomics models that predict loco-regional recurrence within two years of radiotherapy with private and public datasets and their combinations, to simulate small and multi-institutional studies and study the responsiveness of the models to feature selection, machine learning algorithms, centre-effect harmonization and increased dataset sizes. Materials and methods: 562 patients histologically confirmed and treated for locally advanced head-and-neck cancer (LA-HNC) from two public and two private datasets; one private dataset exclusively reserved for validation. Clinical contours of primary tumours were not recontoured and were used for Pyradiomics based feature extraction. ComBat harmonization was applied, and LASSO-Logistic Regression (LR) and Support Vector Machine (SVM) models were built. 95% confidence interval (CI) of 1000 bootstrapped area-under-the-Receiver-operating-curves (AUC) provided predictive performance. Responsiveness of the models' performance to the choice of feature selection methods, ComBat harmonization, machine learning classifier, single and pooled data was evaluated. Results: LASSO and SelectKBest selected 14 and 16 features, respectively; three were overlapping. Without ComBat, the LR and SVM models for three institutional data showed AUCs (CI) of 0.513 (0.481-0.559) and 0.632 (0.586-0.665), respectively. Performances following ComBat revealed AUCs of 0.559 (0.536-0.590) and 0.662 (0.606-0.690), respectively. Compared to single cohort AUCs (0.562-0.629), SVM models from pooled data performed significantly better at AUC = 0.680. Conclusions: Multi-institutional retrospective data accentuates the existing variabilities that affect radiomics. Carefully designed prospective, multi-institutional studies and data sharing are necessary for clinically relevant head-and-neck cancer prognostication models.

Utility of Mid-treatment DWI in Selecting Pathological Responders to Neoadjuvant Chemoradiotherapy in Locally Advanced Esophageal Cancer.

PURPOSE: Pathological complete response correlates with better clinical outcomes in locally advanced esophageal cancer (LA-EC). However, there is lack of prognostic markers to identify patients in the current setting of neoadjuvant chemoradiotherapy (NACRT) followed by surgery. This study evaluates the utility of mid-treatment diffusion-weighted imaging (DWI) in identifying pathological responders of NACRT. METHODS: Twenty-four patients with LA-EC on NACRT were prospectively recruited and underwent three MRI (baseline, mid-treatment, end-of-RT) scans. DWI-derived apparent diffusion coefficient (ADC) mean and minimum were used as a surrogate to evaluate the treatment response, and its correlation to pathological response was assessed. RESULTS: Mid-treatment ADC mean was significantly higher among patients with pathological response compared to non-responders (p = 0.011). ADC difference (ΔADC) between baseline and mid-treatment correlated with tumor response (p = 0.007). ADC at other time points did not correlate to pathological response. CONCLUSION: In this study, mid-treatment ADC values show potential to be a surrogate for tumor response in NACRT. However, larger trials are required to establish DW-MRI as a definite biomarker for tumor response.

Framework for Machine Learning of CT and PET Radiomics to Predict Local Failure after Radiotherapy in Locally Advanced Head and Neck Cancers.

CONTEXT: Cancer Radiomics is an emerging field in medical imaging and refers to the process of converting routine radiological images that are typically qualitatively interpreted to quantifiable descriptions of the tumor phenotypes and when combined with statistical analytics can improve the accuracy of clinical outcome prediction models. However, to understand the radiomic features and their correlation to molecular changes in the tumor, first, there is a need for the development of robust image analysis methods, software tools and statistical prediction models which is often limited in low- and middle-income countries (LMIC). AIMS: The aim is to build a framework for machine learning of radiomic features of planning computed tomography (CT) and positron emission tomography (PET) using open source radiomics and data analytics platforms to make it widely accessible to clinical groups. The framework is tested in a small cohort to predict local disease failure following radiation treatment for head-and-neck cancer (HNC). The predictors were also compared with the existing Aerts HNC radiomics signature. SETTINGS AND DESIGN: Retrospective analysis of patients with locally advanced HNC between 2017 and 2018 and 31 patients with both pre- and post-radiation CT and evaluation PET were selected. SUBJECTS AND METHODS: Tumor volumes were delineated on baseline PET using the semi-automatic adaptive-threshold algorithm and propagated to CT; PyRadiomics features (total of 110 under shape/intensity/texture classes) were extracted. Two feature-selection methods were tested for model stability. Models were built based on least absolute shrinkage and selection operator-logistic and Ridge regression of the top pretreatment radiomic features and compared to Aerts' HNC-signature. Average model performance across all internal validation test folds was summarized by the area under the receiver operator curve (ROC). RESULTS: Both feature selection methods selected CT features MCC (GLCM), SumEntropy (GLCM) and Sphericity (Shape) that could predict the binary failure status in the cross-validated group and achieved an AUC >0.7. However, models using Aerts' signature features (Energy, Compactness, GLRLM-GrayLevelNonUniformity and GrayLevelNonUniformity-HLH wavelet) could not achieve a clear separation between outcomes (AUC = 0.51-0.54). CONCLUSIONS: Radiomics pipeline included open-source workflows which makes it adoptable in LMIC countries. Additional independent validation of data is crucial for the implementation of radiomic models for clinical risk stratification.

Comparison of regional lung perfusion response on longitudinal MAA SPECT/CT in lung cancer patients treated with and without functional tissue-avoidance radiation therapy.

OBJECTIVE: The effect of functional lung avoidance planning on radiation dose-dependent changes in regional lung perfusion is unknown. We characterized dose-perfusion response on longitudinal perfusion single photon emission computed tomography (SPECT)/CT in two cohorts of lung cancer patients treated with and without functional lung avoidance techniques. METHODS: The study included 28 primary lung cancer patients: 20 from interventional (NCT02773238) (FLARE-RT) and eight from observational (NCT01982123) (LUNG-RT) clinical trials. FLARE-RT treatment plans included perfused lung dose constraints while LUNG-RT plans adhered to clinical standards. Pre- and 3 month post-treatment macro-aggregated albumin (MAA) SPECT/CT scans were rigidly co-registered to planning four-dimensional CT scans. Tumour-subtracted lung dose was converted to EQD2 and sorted into 5 Gy bins. Mean dose and percent change between pre/post-RT MAA-SPECT uptake (%ΔPERF), normalized to total tumour-subtracted lung uptake, were calculated in each binned dose region. Perfusion frequency histograms of pre/post-RT MAA-SPECT were analyzed. Dose-response data were parameterized by sigmoid logistic functions to estimate maximum perfusion increase (%ΔPERFmaxincrease), maximum perfusion decrease (%ΔPERFmaxdecrease), dose midpoint (Dmid), and dose-response slope (k). RESULTS: Differences in MAA perfusion frequency distribution shape between time points were observed in 11/20 (55%) FLARE-RT and 2/8 (25%) LUNG-RT patients (p < 0.05). FLARE-RT dose response was characterized by >10% perfusion increase in the 0-5 Gy dose bin for 8/20 patients (%ΔPERFmaxincrease = 10-40%), which was not observed in any LUNG-RT patients (p = 0.03). The dose midpoint Dmid at which relative perfusion declined by 50% trended higher in FLARE-RT compared to LUNG-RT cohorts (35 GyEQD2 vs 21 GyEQD2, p = 0.09), while the dose-response slope k was similar between FLARE-RT and LUNG-RT cohorts (3.1-3.2, p = 0.86). CONCLUSION: Functional lung avoidance planning may promote increased post-treatment perfusion in low dose regions for select patients, though inter-patient variability remains high in unbalanced cohorts. These preliminary findings form testable hypotheses that warrant subsequent validation in larger cohorts within randomized or case-matched control investigations. ADVANCES IN KNOWLEDGE: This novel preliminary study reports differences in dose-response relationships between patients receiving functional lung avoidance radiation therapy (FLARE-RT) and those receiving conventionally planned radiation therapy (LUNG-RT). Following further validation and testing of these effects in larger patient populations, individualized estimation of regional lung perfusion dose-response may help refine future risk-adaptive strategies to minimize lung function deficits and toxicity incidence.

Impact of tumour motion compensation and delineation methods on FDG PET-based dose painting plan quality for NSCLC radiation therapy.

INTRODUCTION: To quantitatively estimate the impact of different methods for both boost volume delineation and respiratory motion compensation of [18F] FDG PET/CT images on the fidelity of planned non-uniform 'dose painting' plans to the prescribed boost dose distribution. METHODS: Six locally advanced non-small cell lung cancer (NSCLC) patients were retrospectively reviewed. To assess the impact of respiratory motion, time-averaged (3D AVG), respiratory phase-gated (4D GATED) and motion-encompassing (4D MIP) PET images were used. The boost volumes were defined using manual contour (MANUAL), fixed threshold (FIXED) and gradient search algorithm (GRADIENT). The dose painting prescription of 60 Gy base dose to the planning target volume and an integral dose of 14 Gy (total 74 Gy) was discretized into seven treatment planning substructures and linearly redistributed according to the relative SUV at every voxel in the boost volume. Fifty-four dose painting plan combinations were generated and conformity was evaluated using quality index VQ0.95-1.05, which represents the sum of planned dose voxels within 5% deviation from the prescribed dose. Trends in plan quality and magnitude of achievable dose escalation were recorded. RESULTS: Different segmentation techniques produced statistically significant variations in maximum planned dose (P < 0.02), as well as plan quality between segmentation methods for 4D GATED and 4D MIP PET images (P < 0.05). No statistically significant differences in plan quality and maximum dose were observed between motion-compensated PET-based plans (P > 0.75). Low variability in plan quality was observed for FIXED threshold plans, while MANUAL and GRADIENT plans achieved higher dose with lower plan quality indices. CONCLUSIONS: The dose painting plans were more sensitive to segmentation of boost volumes than PET motion compensation in this study sample. Careful consideration of boost target delineation and motion compensation strategies should guide the design of NSCLC dose painting trials.

Hybrid positron emission tomography segmentation of heterogeneous lung tumors using 3D Slicer: improved GrowCut algorithm with threshold initialization.

This paper presents an improved GrowCut (IGC), a positron emission tomography-based segmentation algorithm, and tests its clinical applicability. Contrary to the traditional method that requires the user to provide the initial seeds, the IGC algorithm starts with a threshold-based estimate of the tumor and a three-dimensional morphologically grown shell around the tumor as the foreground and background seeds, respectively. The repeatability of IGC from the same observer at multiple time points was compared with the traditional GrowCut algorithm. The algorithm was tested in 11 nonsmall cell lung cancer lesions and validated against the clinician-defined manual contour and compared against the clinically used 25% of the maximum standardized uptake value [SUV-(max)], 40% [Formula: see text], and adaptive threshold methods. The time to edit IGC-defined functional volume to arrive at the gross tumor volume (GTV) was compared with that of manual contouring. The repeatability of the IGC algorithm was very high compared with the traditional GrowCut ([Formula: see text]) and demonstrated higher agreement with the manual contour with respect to threshold-based methods. Compared with manual contouring, editing the IGC achieved the GTV in significantly less time ([Formula: see text]). The IGC algorithm offers a highly repeatable functional volume and serves as an effective initial guess that can well minimize the time spent on labor-intensive manual contouring.