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We present 7 years of clinical experience with single-agent pembrolizumab immune checkpoint inhibitor immunotherapy in non-small cell lung cancers (NSCLC) from four UK cancer centres. This multi-institutional retrospective cohort study included 226 metastatic NSCLC patients. Outcomes were number and severity of immune-related adverse events (irAEs), median progression-free survival (mPFS) and median overall survival (mOS). Within our cohort, 119/226 (53%) patients developed irAEs. Of these, 54/119 (45%) experienced irAEs affecting two or more organ systems. The most common irAEs were diarrhoea and rash. The development of an irAE was associated with better mOS (20.7 versus 8.0 months; P < 0.001) and mPFS (12.0 versus 3.9 months; P < 0.001). The development of grade 3/4 toxicities was associated with worse outcomes compared with the development of grade 1/2 toxicities (mOS 6.1 months versus 25.2 months, P < 0.01; mPFS 5.6 months versus 19.3 months, P = 0.01, respectively). Females had a higher proportion of reported grade 3/4 toxicities (13/44 [29.5%] versus 10/74 [13.5%], P = 0.03). Using a multiple Cox regression model, the presence of irAEs was associated with a better overall survival (hazard ratio = 0.42, 95% confidence interval 0.29–0.61; P < 0.01) and better PFS (hazard ratio 0.38, 95% confidence interval 0.27–0.53; P < 0.001). In this multicentre retrospective cohort study, the development of at least one irAE was associated with significantly longer mPFS and mOS; however, more severe grade 3 and 4 irAEs were associated with worse outcomes. Delayed-onset irAEs, after the 3-month timepoint, were associated with better clinical outcomes. • Multi-institution experience (n = 226) of pembrolizumab monotherapy in advanced lung cancer. • Development of immune-related adverse events (irAEs) associated with improved outcomes. • Onset of irAEs at >3 months from treatment start associated with better outcomes. • Patients with CTCAE grade 1–2 toxicity did better than those with grade 3–4 toxicity. [ABSTRACT FROM AUTHOR]

Background: Radiomics is increasingly utilized to distinguish pulmonary nodules between lung adenocarcinoma (LUAD) and tuberculosis (TB). However, it remains unclear whether different segmentation criteria, such as the inclusion or exclusion of the cavity region within nodules, affect the results. Methods: A total of 525 patients from two medical centers were retrospectively enrolled. The radiomics features were extracted according to two regions of interest (ROI) segmentation criteria. Multiple logistic regression models were trained to predict the pathology: (1) The clinical model relied on clinical‐radiological semantic features; (2) The radiomics models (radiomics+ and radiomics−) utilized radiomics features from different ROIs (including or excluding cavities); (3) the composite models (composite+ and composite−) incorporated both above. Results: In the testing set, the radiomics+/− models and the composite+/− models still possessed efficient prediction performance (AUC ≥ 0.94), while the AUC of the clinical model was 0.881. In the validation set, the AUC of the clinical model was only 0.717, while that of the radiomics+/− models and the composite+/− models ranged from 0.801 to 0.825. The prediction performance of all the radiomics+/− and composite+/− models were significantly superior to that of the clinical model (p < 0.05). Whether the ROI segmentation included or excluded the cavity had no significant effect on these models (radiomics+ vs. radiomics−, composite+ model vs. composite−) (p > 0.05). Conclusions: The present study established a machine learning‐based radiomics strategy for differentiating LUAD from TB lesions. The ROI segmentation including or excluding the cavity region may exert no significant effect on the predictive ability. [ABSTRACT FROM AUTHOR]

Introduction The introduction of the two week rule (TWR) cancer referral system aimed to expedite the diagnosis and treatment of patients with lung cancer. There have been concerns that the system may even lead to delays and there remains little evidence to support its use. We therefore used prospective data to assess the effectiveness of this system. Methods We prospectively collected data on patients referred in 2010 with suspected lung cancer to a large West London lung cancer centre. We evaluated final diagnosis, performance status, lung cancer staging, time until seen in specialist clinic and time until first treatment for patients referred under the TWR compared with patients referred via our in-house abnormal radiology referral service. Results In total 249 patients were included in the study (181 from radiology reporting and 68 from GP referrals via the 2 week wait). 83 (33%) cancers were diagnosed from a total of 249 referrals. Patients referred from the radiology department were significantly more likely to have a diagnosis of lung cancer (73/181, 40%) than patients referred under the TWR (10/68, 15%; p<0.001). The mean time from date of referral to seeing a specialist was similar in both groups. All patients diagnosed with lung cancer referred through the TWR had an abnormal chest radiograph. More patients with a performance status 0-1 and earlier stage disease were referred from radiology than through the TWR. Conclusions A robust radiology referral system is an effective alternative method to diagnosing lung cancer than the TWR. Patients referred from radiology are significantly more likely to have lung cancer. We propose that out-patient clinic slots are reserved for urgent radiology referrals rather than all being allocated to TWR appointments amenable to direct GP bookings. More work is needed to develop this referral pathway further. [ABSTRACT FROM AUTHOR]

Lung cancer represents the second most common malignancy worldwide and lymph node (LN) involvement serves as a crucial prognostic factor for tailoring treatment approaches. Invasive methods, such as mediastinoscopy and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), are employed for preoperative LN staging. Among the preoperative non-invasive diagnostic methods, computed tomography (CT) and, recently, positron emission tomography (PET)/CT with fluorine-18-fludeoxyglucose ([18F]FDG) are routinely recommended by several guidelines; however, they can both miss pathologically proven LN metastases, with an incidence up to 26% for patients staged with [18F]FDG PET/CT. These undetected metastases, known as occult LN metastases (OLMs), are usually cases of micro-metastasis or small LN metastasis (shortest radius below 10 mm). Hence, it is crucial to find novel approaches to increase their discovery rate. Radiomics is an emerging field that seeks to uncover and quantify the concealed information present in biomedical images by utilising machine or deep learning approaches. The extracted features can be integrated into predictive models, as numerous reports have emphasised their usefulness in the staging of lung cancer. However, there is a paucity of studies examining the detection of OLMs using quantitative features derived from images. Hence, the objective of this review was to investigate the potential application of PET- and/or CT-derived quantitative radiomic features for the identification of OLMs. [ABSTRACT FROM AUTHOR]

Purpose: The study aimed to predict acute radiation esophagitis (ARE) with grade ≥ 2 for patients with locally advanced lung cancer (LALC) treated with intensity-modulated radiation therapy (IMRT) using multi-omics features, including radiomics and dosiomics. Methods: 161 patients with stage IIIA−IIIB LALC who received chemoradiotherapy (CRT) or radiotherapy by IMRT with a prescribed dose from 45 to 70 Gy from 2015 to 2019 were enrolled retrospectively. All the toxicity gradings were given following the Common Terminology Criteria for Adverse Events V4.0. Multi-omics features, including radiomics, dosiomics (including dose−volume histogram dosimetric parameters), were extracted based on the planning CT image and three-dimensional dose distribution. All data were randomly divided into training cohorts (N = 107) and testing cohorts (N = 54). In the training cohorts, features with reliably high outcome relevance and low redundancy were selected under random patient subsampling. Four classification models (using clinical factors (CF) only, using radiomics features (RFs) only, dosiomics features (DFs) only, and the hybrid features (HFs) containing clinical factors, radiomics and dosiomics) were constructed employing the Ridge classifier using two-thirds of randomly selected patients as the training cohort. The remaining patient was treated as the testing cohort. A series of models were built with 30 times training–testing splits. Their performances were assessed using the area under the ROC curve (AUC) and accuracy. Results: Among all patients, 51 developed ARE grade ≥ 2, with an incidence of 31.7%. Next, 8990 radiomics and 213 dosiomics features were extracted, and 3, 6, 12, and 13 features remained after feature selection in the CF, DF, RF and DF models, respectively. The RF and HF models achieved similar classification performance, with the training and testing AUCs of 0.796 ± 0.023 (95% confidence interval (CI [0.79, 0.80])/0.744 ± 0.044 (95% CI [0.73, 0.76]) and 0.801 ± 0.022 (95% CI [0.79, 0.81]) (p = 0.74), respectively. The model performances using CF and DF features were poorer, with training and testing AUCs of 0.573 ± 0.026 (95% CI [0.56, 0.58])/ 0.509 ± 0.072 (95% CI [0.48, 0.53]) and 0.679 ± 0.027 (95% CI [0.67, 0.69])/0.604 ± 0.041 (95% CI [0.53, 0.63]) compared with the above two models (p < 0.001), respectively. Conclusions: In LALC patients treated with CRT IMRT, the ARE grade ≥ 2 can be predicted using the pretreatment radiotherapy image features. To predict ARE, the multi-omics features had similar predictability with radiomics features; however, the dosiomics features and clinical factors had a limited classification performance. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer-related death in many countries, and an accurate histopathological diagnosis is of great importance in subsequent treatment. The aim of this study was to establish the random forest (RF) model based on radiomic features to automatically classify and predict lung adenocarcinoma (ADC), lung squamous cell carcinoma (SCC), and small cell lung cancer (SCLC) on unenhanced computed tomography (CT) images. Eight hundred and fifty-two patients (mean age: 61.4, range: 29–87, male/female: 536/316) with preoperative unenhanced CT and postoperative histopathologically confirmed primary lung cancers, including 525 patients with ADC, 161 patients with SCC, and 166 patients with SCLC, were included in this retrospective study. Radiomic features were extracted, selected, and then used to establish the RF classification model to analyse and classify primary lung cancers into three subtypes, including ADC, SCC, and SCLC according to histopathological results. The training (446 ADC, 137 SCC, and 141 SCLC) and testing cohorts (79 ADC, 24 SCC, and 25 SCLC) accounted for 85% and 15% of the whole datasets, respectively. The prediction performance of the RF classification model was evaluated by F1 scores and the receiver operating characteristic (ROC) curve. On the testing cohort, the areas under the ROC curve (AUC) of the RF model in classifying ADC, SCC, and SCLC were 0.74, 0.77, and 0.88, respectively. The F1 scores achieved 0.80, 0.40, and 0.73 in ADC, SCC, and SCLC, respectively, and the weighted average F1 score was 0.71. In addition, for the RF classification model, the precisions were 0.72, 0.64, and 0.70; the recalls were 0.86, 0.29, and 0.76; and the specificities were 0.55, 0.96, and 0.92 in ADC, SCC, and SCLC. The primary lung cancers were feasibly and effectively classified into ADC, SCC, and SCLC based on the combination of RF classification model and radiomic features, which has the potential for noninvasive predicting histological subtypes of primary lung cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: Acute radiation pneumonitis (ARP) is one of the common radiation toxicities in patients with non-small-cell lung cancer (NSCLC) treated by radiotherapy. The prediction for ARP can benefit clinical management and thereby improve the quality of life of patients. Markers derived from radiomics and dosiomics features can be adopted to predict ARP. Moreover, the features from lung subregions can improve the prediction for ARP compared to the whole lung region. The previous studies using lung subregion features for predicting ARP ignored the low-dose covered lung region. In this manuscript, we proposed an incremental-dose-interval-based lung subregion segmentation method by covering the low-dose lung region for ARP modeling and evaluated its effectiveness in improving ARP predictions using pre-treatment CT radiomics features and planning dose features for patients with NSCLC treated by radiotherapy. The performance among ARP models using features from our proposed lung subregion and the whole lung were compared for both multi-omics and single-omics. The results could provide insight into the subregion's ability to predict the ARP and could be useful in predicting the risk of radiation-induced toxicity. This manuscript and its results were neither published in any conferences nor journals. Purpose: To evaluate the effectiveness of features obtained from our proposed incremental-dose-interval-based lung subregion segmentation (IDLSS) for predicting grade ≥ 2 acute radiation pneumonitis (ARP) in lung cancer patients upon intensity-modulated radiotherapy (IMRT). (1) Materials and Methods: A total of 126 non-small-cell lung cancer patients treated with IMRT were retrospectively analyzed. Five lung subregions (SRs) were generated by the intersection of the whole lung (WL) and five sub-regions receiving incremental dose intervals. A total of 4610 radiomics features (RF) from pre-treatment planning computed tomographic (CT) and 213 dosiomics features (DF) were extracted. Six feature groups, including WL-RF, WL-DF, SR-RF, SR-DF, and the combined feature sets of WL-RDF and SR-RDF, were generated. Features were selected by using a variance threshold, followed by a Student t-test. Pearson's correlation test was applied to remove redundant features. Subsequently, Ridge regression was adopted to develop six models for ARP using the six feature groups. Thirty iterations of resampling were implemented to assess overall model performance by using the area under the Receiver-Operating-Characteristic curve (AUC), accuracy, precision, recall, and F1-score. (2) Results: The SR-RDF model achieved the best classification performance and provided significantly better predictability than the WL-RDF model in training cohort (Average AUC: 0.98 ± 0.01 vs. 0.90 ± 0.02, p < 0.001) and testing cohort (Average AUC: 0.88 ± 0.05 vs. 0.80 ± 0.04, p < 0.001). Similarly, predictability of the SR-DF model was significantly stronger than that of the WL-DF model in training cohort (Average AUC: 0.88 ± 0.03 vs. 0.70 ± 0.030, p < 0.001) and in testing cohort (Average AUC: 0.74 ± 0.08 vs. 0.65 ± 0.06, p < 0.001). By contrast, the SR-RF model significantly outperformed the WL-RF model only in the training set (Average AUC: 0.93 ± 0.02 vs. 0.85 ± 0.03, p < 0.001), but not in the testing set (Average AUC: 0.79 ± 0.05 vs. 0.77 ± 0.07, p = 0.13). (3) Conclusions: Our results demonstrated that the IDLSS method improved model performance for classifying ARP with grade ≥ 2 when using dosiomics or combined radiomics-dosiomics features. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer remains the leading cause of cancer-related mortality worldwide. Although early-stage non-small cell lung cancer (NSCLC) is likely to be controlled with stereotactic body radiation therapy (SBRT), approximately 18% of patients lead to recurrence. The aim of this study was to identify prognostic factors and establish a predictive model for survival outcomes of patients with non-metastatic NSCLC treated with SBRT. Several radiomic features were selected as predictive factors and two prediction models were established from the pre-treatment computed tomography images of 250 patients in the training cohort. One radiomic factor remained a significant prognostic factor of overall survival (OS) (p = 0.044), and one predicting model could estimate OS time (mean: 37.8 months) similar to the real OS time (33.7 months). In this study, we identified one radiomic factor and one prediction model that can be widely used. Stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) leads to recurrence in approximately 18% of patients. We aimed to extract the radiomic features, with which we predicted clinical outcomes and to establish predictive models. Patients with primary non-metastatic NSCLC who were treated with SBRT between 2002 and 2022 were retrospectively reviewed. The 358 primary tumors were randomly divided into a training cohort of 250 tumors and a validation cohort of 108 tumors. Clinical features and 744 radiomic features derived from primary tumor delineation on pre-treatment computed tomography were examined as prognostic factors of survival outcomes by univariate and multivariate analyses in the training cohort. Predictive models of survival outcomes were established from the results of the multivariate analysis in the training cohort. The selected radiomic features and prediction models were tested in a validation cohort. We found that one radiomic feature showed a significant difference in overall survival (OS) in the validation cohort (p = 0.044) and one predicting model could estimate OS time (mean: 37.8 months) similar to the real OS time (33.7 months). In this study, we identified one radiomic factor and one prediction model that can be widely used. [ABSTRACT FROM AUTHOR]

Purpose. 4D-CT is routine imaging for lung cancer patients treated with stereotactic body radiotherapy. No studies have investigated optimal 4D phase selection for radiomics. We aim to determine how phase data should be used to identify prognostic biomarkers for distant failure, and test whether stability assessment is required. A phase selection approach will be developed to aid studies with different 4D protocols and account for patient differences. Methods. 186 features were extracted from the tumour and peritumour on all phases for 258 patients. Feature values were selected from phase features using four methods: (A) mean across phases, (B) median across phases, (C) 50% phase, and (D) the most stable phase (closest in value to two neighbours), coined personalised selection. Four levels of stability assessment were also analysed, with inclusion of: (1) all features, (2) stable features across all phases, (3) stable features across phase and neighbour phases, and (4) features averaged over neighbour phases. Clinical-radiomics models were built for twelve combinations of feature type and assessment method. Model performance was assessed by concordance index (c-index) and fraction of new information from radiomic features. Results. The most stable phase spanned the whole range but was most often near exhale. All radiomic signatures provided new information for distant failure prediction. The personalised model had the highest c-index (0.77), and 58% of new information was provided by radiomic features when no stability assessment was performed. Conclusion. The most stable phase varies per-patient and selecting this improves model performance compared to standard methods. We advise the single most stable phase should be determined by minimising feature differences to neighbour phases. Stability assessment over all phases decreases performance by excessively removing features. Instead, averaging of neighbour phases should be used when stability is of concern. The models suggest that higher peritumoural intensity predicts distant failure. [ABSTRACT FROM AUTHOR]

Radiomics studies to predict lymph node (LN) metastasis has only focused on either primary tumor or LN alone. However, combining radiomics features from multiple sources may reflect multiple characteristic of the lesion thereby increasing the discriminative performance of the radiomic model. Therefore, the present study intends to evaluate the efficiency of integrative nomogram, created by combining clinical parameters and radiomics features extracted from gross tumor volume (GTV), peritumoral volume (PTV) and LN, for the preoperative prediction of LN metastasis in clinical cT1N0M0 adenocarcinoma. A primary cohort of 163 patients (training cohort, 113; and internal validation cohort, 50) and an external validation cohort of 53 patients with clinical stage cT1N0M0 were retrospectively included. Features were extracted from three regions of interests (ROIs): GTV; PTV (5.0 mm around the tumor) and LN on pre-operative contrast enhanced computed tomography (CT). LASSO logistic regression method was used to build radiomic signatures. Multivariable regression analysis was used to build a nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. The discriminative performance of nomogram was validated both internally and externally. The radiomic signatures using the features of GTV, PTV and LN showed a good ability in predicting LN metastasis with an area under the curve (AUC) of 0.74 (95% CI 0.60–0.88), 0.72 (95% CI 0.57–0.87) and 0.64 (95% CI 0.48–0.80) respectively in external validation cohort. The integration of different signature together further increases the discriminatory ability: GTV + PTV (GPTV): AUC 0.75 (95% CI 0.61–0.89) and GPTV + LN: AUC 0.76 (95% CI 0.61–0.91) in external validation cohort. An integrative nomogram of clinical parameters and radiomic features demonstrated further increase in discriminatory ability with AUC of 0.79 (95% CI 0.66–0.93) in external validation cohort. The nomogram showed good calibration. Decision curve analysis demonstrated that the radiomic nomogram was clinically useful. The integration of information from clinical parameters along with CT radiomics information from GTV, PTV and LN was feasible and increases the predictive performance of the nomogram in predicting LN status in cT1N0M0 adenocarcinoma patients suggesting merit of information integration from multiple sources in building prediction model. [ABSTRACT FROM AUTHOR]

We propose a multi-view data analysis approach using radiomics and dosiomics (R&D) texture features for predicting acute-phase weight loss (WL) in lung cancer radiotherapy. Baseline weight of 388 patients who underwent intensity modulated radiation therapy (IMRT) was measured between one month prior to and one week after the start of IMRT. Weight change between one week and two months after the commencement of IMRT was analyzed, and dichotomized at 5% WL. Each patient had a planning CT and contours of gross tumor volume (GTV) and esophagus (ESO). A total of 355 features including clinical parameter (CP), GTV and ESO (GTV&ESO) dose-volume histogram (DVH), GTV radiomics, and GTV&ESO dosiomics features were extracted. R&D features were categorized as first- (L1), second- (L2), higher-order (L3) statistics, and three combined groups, L1 + L2, L2 + L3 and L1 + L2 + L3. Multi-view texture analysis was performed to identify optimal R&D input features. In the training set (194 earlier patients), feature selection was performed using Boruta algorithm followed by collinearity removal based on variance inflation factor. Machine-learning models were developed using Laplacian kernel support vector machine (lpSVM), deep neural network (DNN) and their averaged ensemble classifiers. Prediction performance was tested on an independent test set (194 more recent patients), and compared among seven different input conditions: CP-only, DVH-only, R&D-only, DVH + CP, R&D + CP, R&D + DVH and R&D + DVH + CP. Combined GTV L1 + L2 + L3 radiomics and GTV&ESO L3 dosiomics were identified as optimal input features, which achieved the best performance with an ensemble classifier (AUC = 0.710), having statistically significantly higher predictability compared with DVH and/or CP features (p < 0.05). When this performance was compared to that with full R&D-only features which reflect traditional single-view data, there was a statistically significant difference (p < 0.05). Using optimized multi-view R&D input features is beneficial for predicting early WL in lung cancer radiotherapy, leading to improved performance compared to using conventional DVH and/or CP features. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the performance of radiomic-based quantitative analysis on CT images in predicting invasiveness of lung adenocarcinoma manifesting as pure ground-glass nodules (pGGNs). Methods: A total of 275 lung adenocarcinoma cases, with 322 pGGNs resected surgically and confirmed pathologically, from January 2015 to October 2017 were enrolled in this retrospective study. All nodules were split into training and test cohorts randomly with a ratio of 4:1 to establish models to predict between pGGN-like adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IVA). Radiomic feature extraction was performed using Pyradiomics with semi-automatically segmented tumor regions on CT scans that were contoured with an in-house plugin for 3D-Slicer. Random forest (RF) and support vector machine (SVM) were used for feature selection and predictive model building in the training cohort. Three different predictive models containing conventional, radiomic, and combined models were built on the basis of the selected clinical, radiological, and radiomic features. The predictive performance of each model was evaluated through the receiver operating characteristic curve (ROC) and the area under the curve (AUC). The predictive performance of two radiologists (A and B) and our radiomic predictive model were further investigated in the test cohort to see if radiomic predictive model could improve radiologists' performance in prediction between pGGN-like AIS/MIA and IVA. Results: Among 322 nodules, 48 (14.9%) were AIS and 102 (31.7%) were MIA with 172 (53.4%) for IVA. Age, diameter, density, and nine meaningful radiomic features were selected for model building in the training cohort. Three predictive models showed good performance in prediction between pGGN-like AIS/MIA and IVA (AUC > 0.8, P < 0.05) in both training and test cohorts. The AUC values in the test cohort were 0.824 (95% CI, 0.723–0.924), 0.833 (95% CI, 0.733–0.934), and 0.848 (95% CI, 0.750–0.946) for conventional, radiomic, and combined models, respectively. The predictive accuracy was 73.44 and 59.38% for radiologist A and radiologist B in the test cohort and was improved dramatically to 79.69 and 75.00% with the aid of our radiomic predictive model. Conclusion: The predictive models built in our study showed good predictive power with good accuracy and sensitivity, which provided a non-invasive, convenient, economic, and repeatable way for the prediction between IVA and AIS/MIA representing as pGGNs. The radiomic predictive model outperformed two radiologists in predicting pGGN-like AIS/MIA and IVA, and could significantly improve the predictive performance of the two radiologists, especially radiologist B with less experience in medical imaging diagnosis. The selected radiomic features in our research did not provide more useful information to improve the combined predictive model's performance. [ABSTRACT FROM AUTHOR]

Purpose: To design and validate a preprocessing procedure dedicated to T2-weighted MR images of lung cancers so as to improve the ability of radiomic features to distinguish between adenocarcinoma and other histological types. Materials and Methods: A discovery set of 52 patients with advanced lung cancer who underwent T2-weighted MR imaging at 3 Tesla in a single center study from August 2017 to May 2019 was used. Findings were then validated using a validation set of 19 additional patients included from May to October 2019. Tumor type was obtained from the pathology report after trans-thoracic needle biopsy, metastatic lymph node or metastasis samples, or surgical excisions. MR images were preprocessed using N4ITK bias field correction and by normalizing voxel intensities with fat as a reference region. Segmentation and extraction of radiomic features were performed with LIFEx software on the raw images, on the N4ITK-corrected images and on the fully preprocessed images. Two analyses were conducted where radiomic features were extracted: (1) from the whole tumor volume (3D analysis); (2) from all slices encompassing the tumor (2D analysis). Receiver operating characteristic (ROC) analysis was used to identify features that could distinguish between adenocarcinoma and other histological types. Sham experiments were also designed to control the number of false positive findings. Results: There were 31 (12) adenocarcinomas and 21 (7) other histological types in the discovery (validation) set. In 2D, preprocessing increased the number of discriminant radiomic features from 8 without preprocessing to 22 with preprocessing. 2D analysis yielded more features able to identify adenocarcinoma than 3D analysis (12 discriminant radiomic features after preprocessing in 3D). Preprocessing did not increase false positive findings as no discriminant features were identified in any of the sham experiments. The greatest sensitivity of the 2D analysis applied to preprocessed data was confirmed in the validation set. Conclusion: Correction for magnetic field inhomogeneities and normalization of voxel values are essential to reveal the full potential of radiomic features to identify the tumor histological type from MR T2-weighted images, with classification performance similar to those reported in PET/CT and in multiphase CT in lung cancers. [ABSTRACT FROM AUTHOR]

This work seeks to evaluate the combatting batch effect (ComBat) harmonization algorithm's ability to reduce the variation in radiomic features arising from different imaging protocols and independently verify published results. The Gammex computed tomography (CT) electron density phantom and Quasar body phantom were imaged using 32 different chest imaging protocols. 107 radiomic features were extracted from 15 spatially varying spherical contours between 1.5 cm and 3 cm in each of the lung300 density, lung450 density, and wood inserts. The Kolmogorov–Smirnov test was used to determine significant differences in the distribution of the features and the concordance correlation coefficient (CCC) was used to measure the repeatability of the features from each protocol variation class (kVp, pitch, etc) before and after ComBat harmonization. P-values were corrected for multiple comparisons using the Benjamini–Hochberg–Yekutieli procedure. Finally, the ComBat algorithm was applied to human subject data using six different thorax imaging protocols with 135 patients. Spherical contours of un-irradiated lung (2 cm) and vertebral bone (1 cm) were used for radiomic feature extraction. ComBat harmonization reduced the percentage of features from significantly different distributions to 0%–2% or preserved 0% across all protocol variations for the lung300, lung450 and wood inserts. For the human subject data, ComBat harmonization reduced the percentage of significantly different features from 0%–59% for bone and 0%–19% for lung to 0% for both. This work verifies previously published results and demonstrates that ComBat harmonization is an effective means to harmonize radiomic features extracted from different imaging protocols to allow comparisons in large multi-institution datasets. Biological variation can be explicitly preserved by providing the ComBat algorithm with clinical or biological variables to protect. ComBat harmonization should be tested for its effect on predictive models. [ABSTRACT FROM AUTHOR]

Radiomic analysis has recently demonstrated versatile uses in improving diagnostic and prognostic prediction accuracy for lung cancer. However, since lung tumors are subject to substantial motion due to respiration, the stability of radiomic features over the respiratory cycle of the patient needs to be investigated to better evaluate the robustness of the inter-patient feature variability for clinical applications, and its impact in such applications needs to be assessed. A full panel of 841 radiomic features, including tumor intensity, shape, texture, and wavelet features, were extracted from individual phases of a four-dimensional (4D) computed tomography on 20 early-stage non-small-cell lung cancer (NSCLC) patients. The stability of each radiomic feature was assessed across different phase images of the same patient using the coefficient of variation (COV). The relationship between individual COVs and tumor motion magnitude was inspected. Population COVs, the mean COVs of all 20 patients, were used to evaluate feature motion stability and categorize the radiomic features into 4 different groups. The two extremes, the Very Small group (COV≤5%) and the Large group (COV>20%), each accounted for about a quarter of the features. Shape features were the most stable, with COV≤10% for all features. A clinical study was subsequently conducted using 140 early-stage NSCLC patients. Radiomic features were employed to predict the overall survival with a 500-round bootstrapping. Identical multiple regression model development process was applied, and the model performance was compared between models with and without a feature pre-selection step based on 4D COV to pre-exclude unstable features. Among the systematically tested cutoff values, feature pre-selection with 4D COV≤5% achieved the optimal model performance. The resulting 3-feature radiomic model significantly outperformed its counterpart with no 4D COV pre-selection, with P = 2.16x10-27 in the one-tailed t-test comparing the prediction performances of the two models. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-small cell lung cancer (NSCLC) is the most common cause of brain metastasis (BM). Approximately 50% of patients with metastatic NSCLC harbor BMs. Within the past decade, Gamma Knife radiosurgery (GKRS) has become one of the first-line treatments for BMs. Ability to predict treatment response after GKRS can therefore guide treatment strategy. This study aimed to determine whether pre-radiosurgical neuroimaging radiomics can predict survival and local tumor control after GKRS. Based on the collected magnetic resonance images and clinical characteristics of the 237 NSCLC BM patients with BMs (for survival prediction) and 256 NSCLC patients with 976 BMs (for prediction of local tumor control), we concluded that the identified radiomic features could provide valuable additional information to enhance the prediction of BM responses after GKRS. The proposed approach provided physicians with an intuitive way to predict the patient outcome based on pre-radiosurgical magnetic resonance images. The diagnosis of brain metastasis (BM) is commonly observed in non-small cell lung cancer (NSCLC) with poor outcomes. Accordingly, developing an approach to early predict BM response to Gamma Knife radiosurgery (GKRS) may benefit the patient treatment and monitoring. A total of 237 NSCLC patients with BMs (for survival prediction) and 256 patients with 976 BMs (for prediction of local tumor control) treated with GKRS were retrospectively analyzed. All the survival data were recorded without censoring, and the status of local tumor control was determined by comparing the last MRI follow-up in patients' lives with the pre-GKRS MRI. Overall 1763 radiomic features were extracted from pre-radiosurgical magnetic resonance images. Three prediction models were constructed, using (1) clinical data, (2) radiomic features, and (3) clinical and radiomic features. Support vector machines with a 30% hold-out validation approach were constructed. For treatment outcome predictions, the models derived from both the clinical and radiomics data achieved the best results. For local tumor control, the combined model achieved an area under the curve (AUC) of 0.95, an accuracy of 90%, a sensitivity of 91%, and a specificity of 89%. For patient survival, the combined model achieved an AUC of 0.81, an accuracy of 77%, a sensitivity of 78%, and a specificity of 80%. The pre-radiosurgical radiomics data enhanced the performance of local tumor control and survival prediction models in NSCLC patients with BMs treated with GRKS. An outcome prediction model based on radiomics combined with clinical features may guide therapy in these patients. [ABSTRACT FROM AUTHOR]