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Graphs in 54-year-old man with squamous cell carcinoma lung cancer belong to partial response group. (a, c) T2-weighted with fat suppression images and apparent diffusion coefficient (ADC) maps (b, d) obtained before (a, b) and after the first cycle (c, d) of chemotherapy. From the T2-weighted with fat suppression images, no significant decrease in tumor size was detected (a, c) after the first cycle of chemotherapy, while the ADC value increased from 1 . 36 × 10 - 3 mm²/s to 2 . 16 × 10 - 3 mm²/s (b, d).
Source publication
Purpose:
To determine whether change of apparent diffusion coefficient (ADC) value could predict early response to chemotherapy in lung cancer.
Materials and methods:
Twenty-five patients with advanced non-small cell lung cancer underwent chest MR imaging including DWI before and at the end of the first cycle of chemotherapy. The tumor's mean AD...
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Citations
... Chemotherapy breaks down cell membranes and reduces cell size and density, which makes it easier for molecules to diffuse after treatment starts [20]. Since ADC readings may increase before tumor size decreases, DW-MRI may assess therapy response earlier in advanced NSCLC [21]. ...
Background
PET/CT is currently the gold standard for lung cancer staging, and it is also used to identify distant and nodal metastases. High-resolution MRI can also be used to diagnose and provide morphological details about lung cancer. Standardized uptake value ‘SUV’ calculated from PET/CT gives information about tumor behavior where the SUV reflects metabolic tumor activity. Apparent diffusion coefficient ‘ADC’ calculated from DW-MRI is a quantitative imaging marker aiming to assess tumor cellularity which reflects tumor behavior. The study aimed to correlate ADC assessed by DW-MRI and metabolic activity determined by SUV max in PET/CT in local and nodal staging of newly diagnosed NSCLC.
Results
Our study involved twenty-one patients who were pathologically proven to be NSCLC, 19 males (90.5%) and 2 females (9.5%), with a median age of 61 years (ranging from 37 to 84 years). Among all NSCLC primary mass lesions, we observed a statistically significant inverse correlation between SUV max achieved from PET/CT and ADC max, ADC mean, and ADC min calculated from DW-MR ( r = − 0.509 and p = 0.019, r = − 0.472 and p = 0.031 and r = − 0.434 and p = 0.049 for correlation between SUV max of PET/CT and ADC max, ADC mean and ADC min of DW-MR, respectively). Additionally, we observed another statistically significant inverse correlation between SUV max achieved from PET/CT and ADC max, ADC mean, and ADC min calculated from DW-MR in NSCLC mediastinal lymph nodes ( r = − 0.699 and p = 0.011, r = − 0.58 and p = 0.048 and r = − 0.629 and p = 0.028 for correlation between SUV max of PET/CT and ADC max, ADC mean and ADC min of DW-MR, respectively).
Conclusions
ADC values calculated from DW-MRI might act as a new prognostic tool owing to its significant inverse correlation with SUV max achieved from PET/CT in NSCLC primary mass lesions as well as mediastinal lymph nodes.
... Meanwhile, studies are trying to conclude that DW-MRI may have a better potential for early prediction of early tumor response to therapy and prognosis in advanced lung cancer, and ADC may represent a new prognostic biomarker. 13,[19][20][21] Tsuchida et al 22 evaluated 28 patients of advanced lung cancer for response assessment and concluded that DW-MRI could help in prognosis in advanced lung cancer patients. Ohno et al 19 concluded that DWI may have a better potential than 18-FDG PET-CT for prediction of tumor response to therapy in NSCLC patients before chemo-radiotherapy. ...
Background Diffusion-weighted magnetic resonance imaging (DW-MRI) sequences report the cellularity in tissues and 18-fluorodeoxyglucose (18-FDG) positron emission tomography–computed tomography (PET-CT) provides information on glucose metabolism in cells, associated to tumor aggressiveness. The aim of this study was to assess the correlation between quantitative diffusion-weighted magnetic resonance parameters and maximum standardized uptake value (SUVmax) using 18-FDG PET-CT in lung cancer and metastatic lymph nodes.
Methods Histologically proven 29 patients of lung cancers were subjected to 18-FDG PET-CT and DW-MRI (parameters: repetition time/time to echo [TR/TE] = 4,000/76 ms; b -values = 0, 400, and 800 s/mm ² ) between June 2018 and June 2019. SUVmax was calculated on the PET-CT images representing region of interest (ROI) in the tumor. The apparent diffusion coefficient (ADC) values were quantified by placing an ROI over the tumor at a high b -value of 800 mm ² /s. Statistical analyses for correlation between SUVmax and ADC were done using Pearson's correlation coefficient ( r ).
Results Significant negative correlation was observed between analyses of ADC and SUVmax for primary lesions of all nonsmall-cell lung cancers (NSCLCs; p < 0.05) and its histological subtype adenocarcinoma ( p < 0.05) but not squamous cell carcinomas ( p = 0.35). Significant negative correlation was also observed for metastatic lymph nodes of adenocarcinoma ( p < 0.05) but not for metastatic lymph nodes of all NSCLCs ( p = 0.05) or squamous cell carcinomas ( p = 0.55).
Conclusions Diffusion-weighted imaging (DWI) with ADC may represent a new prognostic marker due to a significant negative correlation between ADC determined by DWI and SUVmax by PET-CT in NSCLCs. Furthermore, DWI-MRI of the thorax can be added to routine 18-FDG PET-CT for staging and response assessment in lung cancer in prospects.
... In previous studies, the best-validated predictive biomarkers for chemotherapy response were a high expression of ERCC1 (platinum resistance) [19,20] and high expression of RRM1 (gemcitabine resistance) [21], but neither are currently used in clinical implementation [22]. Recently published studies focused on imaging biomarkers, such as contrastenhanced computerized tomography (CECT) [23], magnetic resonance diffusion-weighted imaging (DWI) [24], and dual-input perfusion CT analysis [25] after two cycles of treatment, are difficult to apply in resource-limited settings. ...
The outcomes of advanced non-small cell lung cancer (NSCLC) patients have been significantly improved with novel therapies, such as tyrosine kinase inhibitors and immune checkpoint inhibitors. However, in resource-limited countries, platinum-doublet chemotherapy is mainly used as a first-line treatment. We investigate clinical parameters to predict the response after chemotherapy, which may be useful for patient selection. A clinical prediction score (CPS) was developed, based on data from a retrospective cohort study of unresectable stage IIIB or IV NSCLC patients who were treated with platinum-doublet chemotherapy in the first-line setting with at least two cycles and an evaluated response by RECIST 1.1 at Surin Hospital Cancer Center, Thailand, between July 2014 and December 2018. The clinical parameters in the prediction model were derived by risk regression analysis. There were 117 responders (CR or PR) and 90 non-responders (SD or PD). The clinical prediction score was developed by six clinical parameters including gender, age, smoking status, ECOG, pre-treatment albumin, and histologic subtype. The AuROC of the model was 0.71 (95% CI 0.63–0.78). The internal validation was performed using a bootstrap technique and showed a consistent AuROC of 0.66 (95% CI 0.59–0.72). The prediction score ranged from 0–13, with a score of 0–8 meaning a low probability (PPV = 50%) and a score of 8.5–13 meaning a high probability (PPV = 83.7%) for chemotherapy response. Advanced NSCLC patients who cannot access novel therapies and have a CPS of 8.5–13 have a high probability for chemotherapy response in the first-line setting. This CPS could be used for risk communication and making decisions with patients, especially in regard to chemotherapy.
... However, heterogeneity of tumor biology, small study cohorts and lack of standardization hampers validation of these criteria. Alongside PET/CT and perfusion CT, multiparametric MRI has shown promising initial results in characterization of pulmonary tumors [17] and assessment of treatment response [8,[18][19][20][21]. ...
Background
To explore the prognostic value of serial dynamic contrast-enhanced (DCE) MRI in patients with advanced pulmonary adenocarcinoma undergoing first-line therapy with either tyrosine-kinase inhibitors (TKI) or platinum-based chemotherapy (PBC).
Methods
Patients underwent baseline (day 0, n = 98), and post-therapeutic DCE MRI (PBC: day + 1, n = 52); TKI: day + 7, n = 46) at 1.5T. Perfusion curves were acquired at 10, 40, and 70 s after contrast application and analysed semiquantitatively. Treatment response was evaluated at 6 weeks by CT (RECIST 1.1); progression-free survival (PFS) and overall survival were analysed with respect to clinical and perfusion parameters. Relative uptake was defined as signal difference between contrast and non-contrast images, divided by the non-contrast signal. Predictors of survival were selected using Cox regression analysis. Median follow-up was 825 days.
Results
In pre-therapeutic and early post-therapeutic MRI, treatment responders (n = 27) showed significantly higher relative contrast uptake within the tumor at 70 s after application as compared to non-responders (n = 71, p ≤ 0.02), response defined as PR by RECIST 1.1 at 6 weeks. There was no significant change of perfusion at early MRI after treatment. In multivariate regression analysis of selected parameters, the strongest association with PFS were relative uptake at 40 s in the early post-treatment MRI and pre-treatment clinical data (presence of liver metastases, ECOG performance status).
Conclusion
Higher contrast uptake within the tumor at pre-treatment and early post-treatment MRI was associated with treatment response and better prognosis. DCE MRI of pulmonary adenocarcinoma may provide important prognostic information.
... ADC change after therapy has proven prognostic of overall survival (OS) in a study mixed of patients with SCLC and NSCLC (Tsuchida et al. 2013). Other studies of patients with NSCLC have confirmed predictive and prognostic value of ADC change during therapy (Weiss et al. 2016;Yabuuchi et al. 2011;Yu et al. 2014), though baseline ADC did not show prognostic value (Usuda et al. 2018;Yu et al. 2014). The objectives of this study were to pilot the potential of FLT-PET and DWI-MRI early after treatment start in patients with SCLC; for early evaluation of tumor biology during treatment and for early response evaluation. ...
... ADC change after therapy has proven prognostic of overall survival (OS) in a study mixed of patients with SCLC and NSCLC (Tsuchida et al. 2013). Other studies of patients with NSCLC have confirmed predictive and prognostic value of ADC change during therapy (Weiss et al. 2016;Yabuuchi et al. 2011;Yu et al. 2014), though baseline ADC did not show prognostic value (Usuda et al. 2018;Yu et al. 2014). The objectives of this study were to pilot the potential of FLT-PET and DWI-MRI early after treatment start in patients with SCLC; for early evaluation of tumor biology during treatment and for early response evaluation. ...
... × 10 − 3 mm 2 /s, and absolute ADC after treatment was not associated with final response or OS. The change of ADC from baseline to early after treatment has shown predictive and prognostic value in patients with NSCLC (Weiss et al. 2016;Tsuchida et al. 2013;Yabuuchi et al. 2011;Yu et al. 2014). It seems ADC early after treatment start is less valuable than an ADC-change from baseline. ...
Background
Small cell lung cancer (SCLC) is an aggressive cancer often presenting in an advanced stage and prognosis is poor. Early response evaluation may have impact on the treatment strategy.
Aim
We evaluated ¹⁸F-fluorothymidine-(FLT)-PET/diffusion-weighted-(DW)-MRI early after treatment start to describe biological changes during therapy, the potential of early response evaluation, and the added value of FLT-PET/DW-MRI.
Methods
Patients with SCLC referred for standard chemotherapy were eligible. FLT-PET/DW-MRI of the chest and brain was acquired within 14 days after treatment start. FLT-PET/DW-MRI was compared with pretreatment FDG-PET/CT. Standardized uptake value (SUV), apparent diffusion coefficient (ADC), and functional tumor volumes were measured. FDG-SUVpeak, FLT-SUVpeak, and ADCmedian; spatial distribution of aggressive areas; and voxel-by-voxel analyses were evaluated to compare the biological information derived from the three functional imaging modalities. FDG-SUVpeak, FLT-SUVpeak, and ADCmedian were also analyzed for ability to predict final treatment response.
Results
Twelve patients with SCLC completed FLT-PET/MRI 1–9 days after treatment start. In nine patients, pretreatment FDG-PET/CT was available for comparison. A total of 16 T-sites and 12 N-sites were identified. No brain metastases were detected. FDG-SUVpeak was 2.0–22.7 in T-sites and 5.5–17.3 in N-sites. FLT-SUVpeak was 0.6–11.5 in T-sites and 1.2–2.4 in N-sites. ADCmedian was 0.76–1.74 × 10− 3 mm²/s in T-sites and 0.88–2.09 × 10⁻³ mm²/s in N-sites. FLT-SUVpeak correlated with FDG-SUVpeak, and voxel-by-voxel correlation was positive, though the hottest regions were dissimilarly distributed in FLT-PET compared to FDG-PET. FLT-SUVpeak was not correlated with ADCmedian, and voxel-by-voxel analyses and spatial distribution of aggressive areas varied with no systematic relation. LT-SUVpeak was significantly lower in responding lesions than non-responding lesions (mean FLT-SUVpeak in T-sites: 1.5 vs. 5.7; p = 0.007, mean FLT-SUVpeak in N-sites: 1.6 vs. 2.2; p = 0.013).
Conclusions
FLT-PET and DW-MRI performed early after treatment start may add biological information in patients with SCLC. Proliferation early after treatment start measured by FLT-PET is a promising predictor for final treatment response that warrants further investigation.
Trial registration
Clinicaltrials.gov, NCT02995902. Registered 11 December 2014 - Retrospectively registered.
... The increase in ADC value was significant from 2 weeks after chemotherapy, which was similar to the results of previous studies of other cancers. [8][9][10][11] The increase in ADC value was related to necrosis and reduced cell density. Chemotherapy leads to cell death which causes a decrease in cell density and consequentially higher ADC values. ...
... Previously published studies suggested that the changes in ADC values could predict the early efficacy of treatment in the tumor. 8,10,11,14,15 In this study, statistically significant differences in the changes of tumor size can be found at 4 weeks after chemotherapy, while significant differences in the changes of ADC values can be detected at 2 weeks after chemotherapy (Tables 2-4). This result demonstrates that ADC changes may precede dimensional ones in accordance with the previous published studies. ...
Objective:
To determine whether change in apparent diffusion coefficient value could predict early response to chemotherapy in breast cancer liver metastases.
Materials and methods:
We retrospectively studied 42 patients (86 lesions) with breast cancer liver metastases who had undergone conventional magnetic resonance imaging and diffusion-weighted imaging (b = 0.700 s/mm2) before and after chemotherapy. Maximum diameter and mean apparent diffusion coefficient value (×10-3 mm2/s) of liver metastases from breast cancer were evaluated. The grouping reference was based on magnetic resonance imaging according to Response Evaluation Criteria in Solid Tumors (RECIST). Analysis of variance and receiver-operating characteristic analyses were performed.
Results:
Eighty-six metastases were classified as 40 responders and 46 nonresponders. A statistically significant correlation was found between prechemotherapy and postchemotherapy apparent diffusion coefficient values in responders, which were 0.9 ± 0.16 × 10-3 mm2/s, 1.05 ± 0.12 × 10-3 mm2/s, 1.26 ± 0.12 × 10-3 mm2/s, and 1.33 ± 0.87 × 10-3 mm2/s, respectively. No statistically significant difference was found between prechemotherapy and postchemotherapy apparent diffusion coefficient values in nonresponders. Differences were statistically significant between responders and nonresponders at prechemotherapy, 2 weeks after chemotherapy, and 4 weeks after chemotherapy ( P = 0.014, P = .001, and P = .000, respectively). Receiver operating characteristic curves showed that apparent diffusion coefficient values could predict treatment response early at 2 weeks after chemotherapy with 64.5% sensitivity and 91.8% specificity.
Conclusion:
The change in apparent diffusion coefficient value may be a sensitive indicator to predict early response to chemotherapy in breast cancer liver metastases.
... In 1999 European Organization for Research and Treatment of Cancer (EORTC) published guidelines for measurement of clinical and subclinical tumor response using FDG-PET [34]. In 2009 a new set of guidelines Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) [29,35] was proposed and even though the acceptance of these criteria have been quite slow, recent publications support the use of PERCIST over the more simple EORTC criteria [36][37][38][39][40][41][42][43][44][45][46][47][48][49]. This study applied, for the first time in a PET/MR setting, PERCIST measurement. ...
... Our results together with the results of similar study done in patients with lymphoma, indicates that response is probably seen slightly later with DW-MRI as compared to FDG-PET [42]. Early response evaluation in the literature tends to be done after, rather than during the first cycle of chemotherapy [24,[47][48][49] and together with the relatively low number of observations in our study, this could be a possible explanation for this difference. ...
Purpose: With the increasing number of therapy options available for patients with lung cancer, early response evaluation is needed. We performed this pilot study to assess the feasibility of early, repeated Positron emission tomography-magnetic resonance (PET/MR), the impact of timing and the capability for response prediction in lung tumors during chemotherapy. Methods: Patients with stage IV non-small cell lung cancer referred for chemotherapy were prospectively recruited. Fluorine-18-Fluorodeoxyglucose(18F-FDG)-PET/MR scans were performed prior to, during and after the first or second cycle of chemotherapy. Primary tumors were defined on all scans and size, FDG-uptake and apparent diffusion coefficient (ADC) were measured. Early response was described over time and a Standard Linear Mixed Model was applied to analyze changes over time. Results: 45 FDG-PET/MR scans were performed in 11 patients. Whereas the overall changes measured by ADC did not change significantly, there was an overall significant decrease in FDG-uptake from pre to post treatment scans. There was no difference in the FDG-uptake measured 1 or 3 weeks after therapy, but uptake measured 2 weeks after therapy differed from measurements at week 3. Changes measured in patients scanned during the first treatment cycle appeared more pronounced than during the second cycle. Conclusions: This pilot study indicates that response evaluation shortly after initiation of chemotherapy appears concordant with later evaluation and probably more reliable than evaluation midway between cycles. Responses during or after the first cycle of chemotherapy rather than during subsequent cycles are likely to be more readily measured.
... The net displacement of these molecules diffusing across an area of tissue per second is the apparent diffusion coefficient (ADC). ADC has proven useful in detection, characterization and treatment response monitoring of malignant diseases [1][2][3][4]. In therapy response monitoring of newer targeted anti-cancer therapies, longitudinal non-invasive assessment of the entire tumor volume might be useful [5]. ...
... Furthermore, susceptibility effects of the air-filled lung parenchyma, as well as cardiac and respiratory motion, make chest DWI extra challenging. Despite these difficulties, DWI of the lungs has been explored for differentiation between central lung tumors and pulmonary atelectasis, differentiating benign from malignant lung nodules [7,8], correlation between ADC and lung cancer grade [9][10][11][12], prediction of treatment outcomes, and follow-up monitoring of tumors [2,3,[13][14][15]. ...
... However, concerns have been raised about less detailed anatomical information and less precise ADC quantification because of volume averaging using FB [16]. Several recent lung cancer DWI studies have used RT acquisition [2,3,[10][11][12], but it is still not established which acquisition method that is most robust for measuring ADC. Cui et al evaluated the inter-and intra-observer agreement of ADC measurements in FB, BH, and RT of lung cancer, and found no significant differences between the methods [17], but they focused on the agreement of ADCs on a single slice between different observers and readings at different times of the same DWI scan. ...
Purpose:
The aim of this study was to compare respiratory-triggered (RT) and free breathing (FB) diffusion weighted imaging (DWI) techniques regarding apparent diffusion coefficient (ADC) measurements and repeatability in non-squamous non-small cell lung cancer (NSCLC) measuring the total tumor volume.
Material and methods:
A total of 57 magnetic resonance imaging (MRI) examinations were analyzed. DWI was obtained by a single-shot spin-echo echo-planar imaging sequence, and for each MRI examination 2 consecutive RT and 2 consecutive FB DWI sequences were performed. Two radiologists independently read the images and made measurements. For each tumor the mean ADC value of the whole tumor volume was calculated. The difference in mean ADCs between FB and RT DWI was evaluated using the paired-sample t-test. The repeatability of ADC measurements related to imaging method was evaluated by intra class correlations (ICC) for each of the FB and RT DWI pairs.
Results:
There were no significant differences in mean ADCs between FB and RT (Reader 1 p = 0.346, Reader 2 p = 0.583). The overall repeatability of ADC measurement was good for both acquisition methods, with ICCs > 0.9. Subgroup analysis showed somewhat poorer repeatability in small tumors (50 ml or less) and tumors in the lower lung zones for the RT acquisition, with ICC as low as 0.72.
Conclusions:
No difference in ADC measurement or repeatability between FB and RT DWI in whole lesion ADC measurements of adenocarcinomas in the lung was demonstrated. The results imply that in this setting the FB acquisition method is accurate and possibly more robust than the RT acquisition technique.
... (depending on lesion size and location in the chest) [9,10]. Methods of deriving ADC suffer from inconsistent methodology across different centres, both in data acquisition and analysis; a wide variety of lesion segmentation methodologies and software packages have been presented for ADC quantitation (Table 1 [ [11][12][13][14][15][16][17][18][19][20]. However, even when acquisition and analysis methods are standardised, uncertainty resulting from different scanner platforms and different post-processing algorithms between institutions, which is inherent in multicentre trials, is unknown. ...
PurposeTo determine the test-retest repeatability of Apparent Diffusion Coefficient (ADC) measurements across institutions and MRI vendors, plus investigate the effect of post-processing methodology on measurement precision. Methods
Thirty malignant lung lesions >2 cm in size (23 patients) were scanned on two occasions, using echo-planar-Diffusion-Weighted (DW)-MRI to derive whole-tumour ADC (b = 100, 500 and 800smm-2). Scanning was performed at 4 institutions (3 MRI vendors). Whole-tumour volumes-of-interest were copied from first visit onto second visit images and from one post-processing platform to an open-source platform, to assess ADC repeatability and cross-platform reproducibility. ResultsWhole-tumour ADC values ranged from 0.66-1.94x10-3mm2s-1 (mean = 1.14). Within-patient coefficient-of-variation (wCV) was 7.1% (95% CI 5.7–9.6%), limits-of-agreement (LoA) -18.0 to 21.9%. Lesions >3 cm had improved repeatability: wCV 3.9% (95% CI 2.9–5.9%); and LoA -10.2 to 11.4%. Variability for lesions <3 cm was 2.46 times higher. ADC reproducibility across different post-processing platforms was excellent: Pearson’s R2 = 0.99; CoV 2.8% (95% CI 2.3-3.4%); and LoA -7.4 to 8.0%. ConclusionA free-breathing DW-MRI protocol for imaging malignant lung tumours achieved satisfactory within-patient repeatability and was robust to changes in post-processing software, justifying its use in multi-centre trials. For response evaluation in individual patients, a change in ADC >21.9% will reflect treatment-related change. Key Points• In lung cancer, free-breathing DWI-MRI produces acceptable images with evaluable ADC measurement.• ADC repeatability coefficient-of-variation is 7.1% for lung tumours >2 cm.• ADC repeatability coefficient-of-variation is 3.9% for lung tumours >3 cm.• ADC measurement precision is unaffected by the post-processing software used.• In multicentre trials, 22% increase in ADC indicates positive treatment response.
... DWI combined with ADC mapping has been investigated for use in lung cancer cases including mass-lesion detection, characterization, and to assess the patient's treatment response [6][7][8][9][10][11]15]. However, there are two problems to be addressed when considering DWI. ...
Purpose
Investigating the diagnostic accuracy of histogram analyses of apparent diffusion coefficient (ADC) values for determining non-small cell lung cancer (NSCLC) tumor grades, lymphovascular invasion, and pleural invasion.
Materials and methods
We studied 60 surgically diagnosed NSCLC patients. Diffusion-weighted imaging (DWI) was performed in the axial plane using a navigator-triggered single-shot, echo-planar imaging sequence with prospective acquisition correction. The ADC maps were generated, and we placed a volume-of-interest on the tumor to construct the whole-lesion histogram. Using the histogram, we calculated the mean, 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of ADC, skewness, and kurtosis. Histogram parameters were correlated with tumor grade, lymphovascular invasion, and pleural invasion. We performed a receiver operating characteristics (ROC) analysis to assess the diagnostic performance of histogram parameters for distinguishing different pathologic features.
Results
The ADC mean, 10th, 25th, 50th, 75th, 90th, and 95th percentiles showed significant differences among the tumor grades. The ADC mean, 25th, 50th, 75th, 90th, and 95th percentiles were significant histogram parameters between high- and low-grade tumors. The ROC analysis between high- and low-grade tumors showed that the 95th percentile ADC achieved the highest area under curve (AUC) at 0.74. Lymphovascular invasion was associated with the ADC mean, 50th, 75th, 90th, and 95th percentiles, skewness, and kurtosis. Kurtosis achieved the highest AUC at 0.809. Pleural invasion was only associated with skewness, with the AUC of 0.648.
Conclusions
ADC histogram analyses on the basis of the entire tumor volume are able to stratify NSCLCs' tumor grade, lymphovascular invasion and pleural invasion.
