Quantitative assessment of articular cartilage degeneration using 3D ultrashort echo time cones adiabatic T1ρ (3D UTE-Cones-AdiabT1ρ) imaging.

OBJECTIVES: To evaluate articular cartilage degeneration using quantitative three-dimensional ultrashort-echo-time cones adiabatic-T1ρ (3D UTE-Cones-AdiabT1ρ) imaging. METHODS: Sixty-six human subjects were recruited for this study. Kellgren-Lawrence (KL) grade and Whole-Organ Magnetic-Resonance-Imaging Score (WORMS) were evaluated by two musculoskeletal radiologists. The human subjects were categorized into three groups, namely normal controls (KL0), doubtful-minimal osteoarthritis (OA) (KL1-2), and moderate-severe OA (KL3-4). WORMS were regrouped to encompass the extent of lesions and the depth of lesions. The UTE-Cones-AdiabT1ρ values were obtained using 3D UTE-Cones data acquisitions preceded by seven paired adiabatic full passage pulses that corresponded to seven spin-locking times (TSLs) of 0, 12, 24, 36, 48, 72, and 96 ms. The performance of the UTE-Cones-AdiabT1ρ technique in evaluating the degeneration of knee cartilage was assessed via the ANOVA comparisons with subregional analysis and Spearman's correlation coefficient as well as the receiver-operating-characteristic (ROC) curve. RESULTS: UTE-Cones-AdiabT1ρ showed significant positive correlations with KL grade (r = 0.15, p < 0.05) and WORMS (r = 0.57, p < 0.05). Higher UTE-Cones-AdiabT1ρ values were observed in both larger and deeper lesions in the cartilage. The differences in UTE-Cones-AdiabT1ρ values among different extent and depth groups of cartilage lesions were all statistically significant (p < 0.05). Subregional analyses showed that the correlations between UTE-Cones-AdiabT1ρ and WORMS varied with the location of cartilage. The AUC value of UTE-Cones-AdiabT1ρ for mild cartilage degeneration (WORMS=1) was 0.8. The diagnostic threshold value of UTE-Cones-AdiabT1ρ for mild cartilage degeneration was 39.4 ms with 80.8% sensitivity. CONCLUSIONS: The 3D UTE-Cones-AdiabT1ρ sequence can be useful in quantitative evaluation of articular cartilage degeneration. KEY POINTS: • The 3D UTE-Cones-AdiabT1ρ sequence can distinguish mild cartilage degeneration from normal cartilage with a diagnostic threshold value of 39.4 ms for mild cartilage degeneration with 80.8% sensitivity. • Higher UTE-Cones-AdiabT1ρ values were observed in both larger and deeper lesions in the articular cartilage. • UTE-Cones-AdiabT1ρ is a promising biomarker for quantitative evaluation of early cartilage degeneration.

Modelled Economic Analysis for Dacomitinib-A Cost Effectiveness Analysis in Treating Patients With EGFR-Mutation-Positive Non-Small Cell Lung Cancer in China.

OBJECTIVES: To establish the cost-effectiveness of dacomitinib compared to gefitinib from the Chinese healthcare system perspective. PATIENTS: Advanced non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations. METHODS: Partitioned survival analysis was undertaken to examine the cost-effectiveness of dacomitinib utilising individual patient data (IPD) from the pivotal randomised controlled trial (RCT) (ARCHER 1050). The three health states modelled were progression-free, post-progression, and death. Parametric survival distributions were fitted to IPD against the Kaplan-Meier survival curves corresponding to progression-free survival (PFS) and overall survival (OS) outcomes by randomised groups. Costs included drug acquisition and administration, outpatient management (outpatient consultation and examinations), and best supportive care costs. Utility weights were sourced from the pivotal trial and other published literature. The incremental cost-effectiveness ratio (ICER) was calculated with costs and quality-adjusted life years (QALYs) discounted at an annual rate of 5%. Both deterministic and probabilistic sensitivity analyses were undertaken. RESULTS: In the base case, dacomitinib (CNY 265,512 and 1.95 QALY) was associated with higher costs and QALY gains compared to gefitinib (CNY 247,048 and 1.61 QALYs), resulting in an ICER of CNY 58,947/QALY. Using the empirical WTP/QALY threshold, dacomitinib is a cost-effective treatment strategy for patients with EGFR-mutation-positive advanced NSCLC. The probabilistic sensitivity analysis suggested that dacomitinib had a 97% probability of being cost-effective. CONCLUSIONS: Dacomitinib is a cost-effective treatment strategy in treating patients with EGFR-mutation-positive NSCLC from the Chinese healthcare system perspective. The uncertainty around the cost-effectiveness of dacomitinib could be reduced if long-term survival data become available. CLINICAL TRIAL REGISTRATION: NCT01024413.

Assessment of the expression of the immune checkpoint molecules PD-1, CTLA4, TIM-3 and LAG-3 across different cancers in relation to treatment response, tumor-infiltrating immune cells and survival.

Immune checkpoint molecules have been identified as crucial regulators of the immune response, which motivated the emergence of immune checkpoint-targeting therapeutic strategies. However, the prognostic significance of the immune checkpoint molecules PD-1, CTLA4, TIM-3 and LAG-3 remains controversial. The aim of our study was to conduct a systematic assessment of the expression of these immune checkpoint molecules across different cancers in relation to treatment response, tumor-infiltrating immune cells and survival. Oncomine and PrognoScan database analyses were used to investigate the expression levels and prognostic values of these immune checkpoint molecule genes across various cancers. Then, we used Kaplan-Meier plotter to validate the associations between the checkpoint molecules and cancer survival identified in the PrognoScan analysis. TIMER analysis was used to evaluate immune cell infiltration data from The Cancer Genome Atlas. Finally, we used Gene Expression Profiling Interactive Analysis to investigate the prognostic value of these four checkpoint molecules and assess the correlations between these four checkpoint molecules and genetic markers. These immune checkpoint molecules may potentially serve as prognostic factors and therapeutic targets in breast cancer, ovarian cancer and lung cancer. The prognostic roles of these checkpoint molecules varied greatly across cancers, which implied a noteworthy amount of heterogeneity among tumors, even within the same molecular subtype. In addition, the expression patterns of these checkpoint molecules were closely associated with treatment response and provided some useful direction when choosing chemotherapeutic drugs. These findings enhance our understanding of these checkpoints in cancer treatment and identify strategies to promote synergistic activities in the context of other immunotherapies.