Comparative assessment of standard and immune response criteria for evaluation of response to PD-1 monotherapy in unresectable HCC.

PURPOSE: To assess response to programmed death-1 (PD-1) monotherapy (nivolumab) in hepatocellular carcinoma (HCC) patients using RECIST1.1, modified RECIST (mRECIST), and immune RECIST (iRECIST). A secondary objective was to identify clinicolaboratory and imaging variables predictive of progressive disease (PD) and overall survival (OS). METHODS: Patients with HCC treated with nivolumab at a single institution from 5/2016 to 12/2019 with MRI or CT performed ≥ 4 weeks post treatment were retrospectively assessed. Patients who received concurrent locoregional, radiation, or other systemic therapies were excluded. Response was assessed by 2 observers in consensus using RECIST1.1, mRECIST, and iRECIST at 3/6/9/12-month time points. Time to progression (TTP) and OS were recorded. Clinicolaboratory and imaging variables were evaluated as predictors of PD and OS using uni-/multivariable and Cox regression analyses. RESULTS: Fifty-eight patients (42M/16F) were included. 118 target lesions (TL) were identified before treatment. Baseline mean TL size was 49.1 ± 43.5 mm (range 10-189 mm) for RECIST1.1/iRECIST and 46.3 ± 42.3 mm (range 10-189 mm) for mRECIST. Objective response rate (ORR) was 21% for mRECIST/iRECIST/RECIST1.1, with no cases of pseudoprogression. Median OS and median TTP were 717 days and 127 days for RECIST1.1/mRECIST/iRECIST-iUPD (unconfirmed PD). Older age, MELD/Child-Pugh scores, AFP, prior transarterial radioembolization (TARE), and larger TL size were predictive of PD and/or poor OS using mRECIST/iRECIST. The strongest predictor of PD (HR = 2.49, 95% CI 1.29-4.81, p = 0.007) was TARE. The strongest predictor of poor OS was PD by mRECIST/iRECIST at 3 months (HR = 2.26, 95% CI 1.00-5.10, p = 0.05) with borderline significance. CONCLUSION: Our results show ORR of 21%, equivalent for mRECIST, iRECIST, and RECIST1.1 in patients with advanced HCC clinically treated with nivolumab.

Community Assessment of the Predictability of Cancer Protein and Phosphoprotein Levels from Genomics and Transcriptomics.

Cancer is driven by genomic alterations, but the processes causing this disease are largely performed by proteins. However, proteins are harder and more expensive to measure than genes and transcripts. To catalyze developments of methods to infer protein levels from other omics measurements, we leveraged crowdsourcing via the NCI-CPTAC DREAM proteogenomic challenge. We asked for methods to predict protein and phosphorylation levels from genomic and transcriptomic data in cancer patients. The best performance was achieved by an ensemble of models, including as predictors transcript level of the corresponding genes, interaction between genes, conservation across tumor types, and phosphosite proximity for phosphorylation prediction. Proteins from metabolic pathways and complexes were the best and worst predicted, respectively. The performance of even the best-performing model was modest, suggesting that many proteins are strongly regulated through translational control and degradation. Our results set a reference for the limitations of computational inference in proteogenomics. A record of this paper's transparent peer review process is included in the Supplemental Information.

Do transportation subsidies and living allowances improve tuberculosis control outcomes among internal migrants in urban Shanghai, China?

INTRODUCTION: Tuberculosis (TB) in internal migrants is one of three threats for TB control in China. To address this threat, a project was launched in eight of the 19 districts of Shanghai in 2007 to provide transportation subsidies and living allowances for all migrant TB cases. This study aims to determine if this project contributed to improved TB control outcomes among migrants in urban Shanghai. METHODS: This was a community intervention study. The data were derived from the TB Management Information System in three project districts and three non-project districts in Shanghai between 2006 and 2010. The impact of the project was estimated in a difference-in-difference (DID) analysis framework, and a multivariable binary logistic regression analysis. RESULTS: A total of 1872 pulmonary TB (PTB) cases in internal migrants were included in the study. The treatment success rate (TSR) for migrant smear-positive cases in project districts increased from 59.9% in 2006 to 87.6% in 2010 (P < 0.001). The crude DID improvement of TSR was 18.9%. There was an increased probability of TSR in the project group before and after the project intervention period (coefficient = 1.156, odds ratio = 3.178, 95% confidence interval: 1.305-7.736, P = 0.011). CONCLUSION: The study showed the project could improve treatment success in migrant PTB cases. This was a short-term programme using special financial subsidies for all migrant PTB cases. It is recommended that project funds be continuously invested by governments with particular focus on the more vulnerable PTB cases among migrants.