Background Use of adjuvant chemotherapy in patients with early-stage lung cancer is controversial because no definite biomarker exists to identify patients who would receive added benefit from it. We aimed to develop and validate a quantitative radiomic risk score (QuRiS) and associated nomogram (QuRNom) for early-stage non-small cell lung cancer (NSCLC) that is prognostic of disease-free survival and predictive of the added benefit of adjuvant chemotherapy following surgery. MethodsWe did a retrospective multicohort study of individuals with early-stage NSCLC (stage I and II) who either received surgery alone or surgery plus adjuvant chemotherapy. We selected patients for whom we had available pretreatment diagnostic CT scans and corresponding survival information. We used radiomic texture features derived from within and outside the primary lung nodule on chest CT scans of patients from the Cleveland Clinic Foundation (Cleveland, OH, USA; cohort D 1 ) to develop QuRiS. A least absolute shrinkage and selection operator-Cox regularisation model was used for data dimension reduction, feature selection, and QuRiS construction. QuRiS was independently validated on a cohort of patients from the University of Pennsylvania (Philadephia, PA, USA; cohort D 2 ) and a cohort of patients whose CT scans were derived from The Cancer Imaging Archive (cohort D 3 ). QuRNom was constructed by integrating QuRiS with tumour and node descriptors (according to the tumour, node, metastasis staging system) and lymphovascular invasion. The primary endpoint of the study was the assessment of the performance of QuRiS and QuRNom in predicting disease-free survival. The added benefit of adjuvant chemotherapy estimated using QuRiS and QuRNom was validated by comparing patients who received adjuvant chemotherapy versus patients who underwent surgery alone in cohorts D 1 -D 3 . Findings We included: 329 patients in cohort D 1 (73 [22%] had surgery plus adjuvant chemotherapy and 256 (78%) had surgery alone); 114 patients in cohort D 2 (33 [29%] had surgery plus adjuvant chemotherapy and 81 (71%) had surgery alone); and 82 patients in cohort D 3 (24 [29%] had surgery plus adjuvant chemotherapy and 58 (71%) had surgery alone). QuRiS comprised three intratumoral and 10 peritumoral CT-radiomic features and was found to be significantly associated with disease-free survival (ie, prognostic validation of QuRiS; hazard ratio for predicted high-risk vs predicted low-risk groups 1•56, 95% CI 1•08-2•23, p=0•016 for cohort D 1 ; 2•66, 1•24-5•68, p=0•011 for cohort D 2 ; and 2•67, 1•39-5•11, p=0•0029 for cohort D 3 ). To validate the predictive performance of QuRiS, patients were partitioned into three risk groups (high, intermediate, and low risk) on the basis of their corresponding QuRiS. Patients in the high-risk group were observed to have significantly longer survival with adjuvant chemotherapy than patients who underwent surgery alone (0•27, 0•08-0•95, p=0•042, for cohort D 1 ; 0•08, 0•01-0•42, p=0•0029, for cohorts D 2 and D 3 combined). As concerns...
Background Biparametric MRI (comprising T2-weighted MRI and apparent diffusion coefficient maps) is increasingly being used to characterise prostate cancer. Although previous studies have combined Prostate Imaging-Reporting & Data System (PI-RADS)-based MRI findings with routinely available clinical variables and with deep learning-based imaging predictors, respectively, for prostate cancer risk stratification, none have combined all three. We aimed to construct an integrated nomogram (referred to as ClaD) combining deep learning-based imaging predictions, PI-RADS scoring, and clinical variables to identify clinically significant prostate cancer on biparametric MRI.Methods In this retrospective multicentre study, we included patients with prostate cancer, with histopathology or biopsy reports and a screening or diagnostic MRI scan in the axial view, from four cohorts in the USA (from University Hospitals Cleveland Medical Center, Icahn School of Medicine at Mount Sinai, Cleveland Clinic, and Long Island Jewish Medical Center) and from the PROSTATEx Challenge dataset in the Netherlands. We constructed an integrated nomogram combining deep learning, PI-RADS score, and clinical variables (prostate-specific antigen, prostate volume, and lesion volume) using multivariable logistic regression to identify clinically significant prostate cancer on biparametric MRI. We used data from the first three cohorts to train the nomogram and data from the remaining two cohorts for independent validation. We compared the performance of our ClaD integrated nomogram with that of integrated nomograms combining clinical variables with either the deep learning-based imaging predictor (referred to as DIN) or PI-RADS score (referred to as PIN) using area under the receiver operating characteristic curves (AUCs). We also compared the ability of the nomograms to predict biochemical recurrence on a subset of patients who had undergone radical prostatectomy. We report cross-validation AUCs as means for the training set and used AUCs with 95% CIs to assess the performance on the test set. The difference in AUCs between the models were tested for statistical significance using DeLong's test. We used log-rank tests and Kaplan-Meier curves to analyse survival. FindingsWe investigated 592 patients (823 lesions) with prostate cancer who underwent 3T multiparametric MRI at five hospitals in the USA between Jan 8, 2009, and June 3, 2017. The training data set consisted of 368 patients from three sites (the PROSTATEx Challenge cohort [n=204], University Hospitals Cleveland Medical Center [n=126], and Icahn School of Medicine at Mount Sinai [n=38]), and the independent validation data set consisted of 224 patients from two sites (Cleveland Clinic [n=151] and Long Island Jewish Medical Center [n=73]). The ClaD clinical nomogram yielded an AUC of 0•81 (95% CI 0•76−0•85) for identification of clinically significant prostate cancer in the validation data set, significantly improving performance over the DIN (0•74 [95% CI 0•69−0•80], p=0•0005) and PIN (0•76...
are co-founders and shareholders of Lightspeed Microscopy Inc. A. Madabhushi is an equity holder in Elucid Bioimaging and in Inspirata Inc. In addition, he has served as a scientific advisory board member for Inspirata Inc, Astrazeneca, Bristol Meyers-Squibb and Merck. Currently, A. Madabhushi serves on the advisory board of Aiforia Inc. He also has sponsored research agreements with Philips, AstraZeneca, Boehringer-Ingelheim and Bristol Meyers-Squibb. A. Madabhushi's technology has been licensed to Elucid Bioimaging. He is also involved in a NIH U24 grant with PathCore Inc, and 3 different R01 grants with Inspirata Inc.Research.
We examined pre-mobilization blood CD34þ cell count to predict ability to mobilize adequate peripheral blood progenitor cells (PBPC) /l (r ¼ 0.37, P-valueo0.0001); correlation was stronger in allogeneic donors (r ¼ 0.56, Pvalue ¼ 0.0004) and males (r ¼ 0.46, P-valueo0.0001). Based on classification and regression tree multivariate analysis, the predictive value of pre-mobilization blood CD34 þ cell count was confounded by other variables, including age, gender, mobilization regimen and malignancy type. We generated an algorithm to predict a minimum PBPC yield of 1  10 6 CD34 þ cells/kg/ leukapheresis procedure after mobilization. A threshold pre-mobilization blood CD34 þ cell count of 2.65 cells  10 6 /l was the most important decision point in predicting successful mobilization. Only 2% of subjects with pre-mobilization blood CD34 þ cell counts 42.65 cells  10 6 /l did not achieve the minimum per apheresis, whereas 24% with pre-mobilization values below threshold had inadequate mobilization. Prospectively identifying individuals at risk for mobilization failure would allow for improved treatment planning, resource utilization and time saving.
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