a b s t r a c tBackground: Treatment decisions for multimodal therapy in soft tissue sarcoma (STS) patients greatly depend on the differentiation between low-grade and high-grade tumors. We developed MRI-based radiomics grading models for the differentiation between low-grade (G1) and high-grade (G2/G3) STS. Methods: The study was registered at ClinicalTrials.gov (number NCT03798795). Contrast-enhanced T1-weighted fat saturated (T1FSGd), fat-saturated T2-weighted (T2FS) MRI sequences, and tumor grading following the French Federation of Cancer Centers Sarcoma Group obtained from pre-therapeutic biopsies were gathered from two independent retrospective patient cohorts. Volumes of interest were manually segmented. After preprocessing, 1394 radiomics features were extracted from each sequence. Features unstable in 21 independent multiple-segmentations were excluded. Least absolute shrinkage and selection operator models were developed using nested cross-validation on a training patient cohort (122 patients). The influence of ComBatHarmonization was assessed for correction of batch effects. Findings: Three radiomic models based on T2FS, T1FSGd and a combined model achieved predictive performances with an area under the receiver operator characteristic curve (AUC) of 0.78, 0.69, and 0.76 on the independent validation set (103 patients), respectively. The T2FS-based model showed the best reproducibility. The radiomics model involving T1FSGd-based features achieved significant patient stratification. Combining the T2FS radiomic model into a nomogram with clinical staging improved prognostic performance and the clinical net benefit above clinical staging alone. Interpretation: MRI-based radiomics tumor grading models effectively classify low-grade and high-grade soft tissue sarcomas.

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Purpose: Non-small cell lung cancer (NSCLC) is a fatal disease with poor prognosis. A membrane-bound form of Hsp70 (mHsp70) which is selectively expressed on high-risk tumors serves as a target for mHsp70-targeting natural killer (NK) cells. Patients with advanced mHsp70-positive NSCLC may therefore benefit from a therapeutic intervention involving mHsp70-targeting NK cells. The randomized phase II clinical trial (EudraCT2008-002130-30) explores tolerability and efficacy of ex vivo-activated NK cells in patients with NSCLC after radiochemotherapy (RCT). Patients and Methods: Patients with unresectable, mHsp70positive NSCLC (stage IIIa/b) received 4 cycles of autologous NK cells activated ex vivo with TKD/IL2 [interventional arm (INT)] after RCT (60-70 Gy, platinum-based chemotherapy) or RCT alone [control arm (CTRL)]. The primary objective was progression-free survival (PFS), and secondary objectives were the assessment of quality of life (QoL, QLQ-LC13), toxicity, and immunobiological responses. Results: The NK-cell therapy after RCT was well tolerated, and no differences in QoL parameters between the two study arms were detected. Estimated 1-year probabilities for PFS were 67% [95% confidence interval (CI), 19%-90%] for the INT arm and 33% (95% CI, 5%-68%) for the CTRL arm (P ¼ 0.36, 1-sided logrank test). Clinical responses in the INT group were associated with an increase in the prevalence of activated NK cells in their peripheral blood. Conclusions: Ex vivo TKD/IL2-activated, autologous NK cells are well tolerated and deliver positive clinical responses in patients with advanced NSCLC after RCT.