Efficacy and correlative analyses of avelumab plus axitinib versus sunitinib in sarcomatoid renal cell carcinoma: post hoc analysis of a randomized clinical trial.

BACKGROUND: Among patients with advanced renal cell carcinoma (RCC), those with sarcomatoid histology (sRCC) have the poorest prognosis. This analysis assessed the efficacy of avelumab plus axitinib versus sunitinib in patients with treatment-naive advanced sRCC. METHODS: The randomized, open-label, multicenter, phase III JAVELIN Renal 101 trial (NCT02684006) enrolled patients with treatment-naive advanced RCC. Patients were randomized 1 : 1 to receive either avelumab plus axitinib or sunitinib following standard doses and schedules. Assessments in this post hoc analysis of patients with sRCC included efficacy (including progression-free survival) and biomarker analyses. RESULTS: A total of 108 patients had sarcomatoid histology and were included in this post hoc analysis; 47 patients in the avelumab plus axitinib arm and 61 in the sunitinib arm. Patients in the avelumab plus axitinib arm had improved progression-free survival [stratified hazard ratio, 0.57 (95% confidence interval, 0.325-1.003)] and a higher objective response rate (46.8% versus 21.3%; complete response in 4.3% versus 0%) versus those in the sunitinib arm. Correlative gene expression analyses of patients with sRCC showed enrichment of gene pathway scores for cancer-associated fibroblasts and regulatory T cells, CD274 and CD8A expression, and tumors with The Cancer Genome Atlas m3 classification. CONCLUSIONS: In this subgroup analysis of JAVELIN Renal 101, patients with sRCC in the avelumab plus axitinib arm had improved efficacy outcomes versus those in the sunitinib arm. Correlative analyses provide insight into this subtype of RCC and suggest that avelumab plus axitinib may increase the chance of overcoming the aggressive features of sRCC.

Updated efficacy results from the JAVELIN Renal 101 trial: first-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma.

BACKGROUND: The phase 3 JAVELIN Renal 101 trial (NCT02684006) demonstrated significantly improved progression-free survival (PFS) with first-line avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma (aRCC). We report updated efficacy data from the second interim analysis. PATIENTS AND METHODS: Treatment-naive patients with aRCC were randomized (1 : 1) to receive avelumab (10 mg/kg) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were PFS and overall survival (OS) among patients with programmed death ligand 1-positive (PD-L1+) tumors. Key secondary end points were OS and PFS in the overall population. RESULTS: Of 886 patients, 442 were randomized to the avelumab plus axitinib arm and 444 to the sunitinib arm; 270 and 290 had PD-L1+ tumors, respectively. After a minimum follow-up of 13 months (data cut-off 28 January 2019), PFS was significantly longer in the avelumab plus axitinib arm than in the sunitinib arm {PD-L1+ population: hazard ratio (HR) 0.62 [95% confidence interval (CI) 0.490-0.777]}; one-sided P < 0.0001; median 13.8 (95% CI 10.1-20.7) versus 7.0 months (95% CI 5.7-9.6); overall population: HR 0.69 (95% CI 0.574-0.825); one-sided P < 0.0001; median 13.3 (95% CI 11.1-15.3) versus 8.0 months (95% CI 6.7-9.8)]. OS data were immature [PD-L1+ population: HR 0.828 (95% CI 0.596-1.151); one-sided P = 0.1301; overall population: HR 0.796 (95% CI 0.616-1.027); one-sided P = 0.0392]. CONCLUSION: Among patients with previously untreated aRCC, treatment with avelumab plus axitinib continued to result in a statistically significant improvement in PFS versus sunitinib; OS data were still immature. CLINICAL TRIAL NUMBER: NCT02684006.

An example of aerosol pattern variability over bright surface using high resolution MODIS MAIAC: The eastern and western areas of the Dead Sea and environs.

The extreme rate of evaporation of the Dead Sea (DS) has serious implicatios for the surrounding area, including atmospheric conditions. This study analyzes the aerosol properties over the western and eastern parts of the DS during the year 2013, using MAIAC (Multi-Angle Implementation of Atmospheric Correction) for MODIS, which retrieves aerosol optical depth (AOD) data at a resolution of 1km. The main goal of the study is to evaluate MAIAC over the study area and determine, for the first time, the prevailing aerosol spatial patterns. First, the MAIAC-derived AOD data was compared with data from three nearby AERONET sites (Nes Ziona - an urban site, and Sede Boker and Masada - two arid sites), and with the conventional Dark Target (DT) and Deep Blue (DB) retrievals for the same days and locations, on a monthly basis throughout 2013. For the urban site, the correlation coefficient (r) for DT/DB products showed better performance than MAIAC (r=0.80, 0.75, and 0.64 respectively) year-round. However, in the arid zones, MAIAC showed better correspondence to AERONET sites than the conventional retrievals (r=0.58-0.60 and 0.48-0.50 respectively). We investigated the difference in AOD levels, and its variability, between the Dead Sea coasts on a seasonal basis and calculated monthly/seasonal AOD averages for presenting AOD patterns over arid zones. Thus, we demonstrated that aerosol concentrations show a strong preference for the western coast, particularly during the summer season. This preference, is most likely a result of local anthropogenic emissions combined with the typical seasonal synoptic conditions, the Mediterranean Sea breeze, and the region complex topography. Our results also indicate that a large industrial zone showed higher AOD levels compared to an adjacent reference-site, i.e., 13% during the winter season.

Spatial and temporal variability in desert dust and anthropogenic pollution in Iraq, 1997-2010.

Satellite imaging has emerged as a method for monitoring regional air pollution and detecting areas of high dust concentrations. Unlike ground observations, continuous data monitoring is available with global coverage of terrestrial and atmospheric components. In this study we test the utility of different sources of satellite data to assess air pollution concentrations in Iraq. SeaWiFS and MODIS Deep Blue (DB) aerosol optical depth (AOD) products were evaluated and used to characterize the spatial and temporal pollution levels from the late 1990s through 2010. The AOD and Ångström exponent (an indicator of particle size, since smaller Ångström exponent values reflect a source that includes larger particles) were correlated on 50 × 50 km spatial resolution. Generally, AOD and Ångström exponent were inversely correlated, suggesting a significant contribution of coarse particles from dust storms to AOD maxima. Although the majority of grid cells exhibited this trend, a weaker relationship in other locations suggested an additional contribution of fine particles from anthropogenic sources. Tropospheric NO2 densities from the OMI satellite were elevated over cities, also consistent with a contribution from anthropogenic sources. Our analysis demonstrates the use of satellite imaging data to estimate relative pollution levels and source contributions in areas of the world where direct measurements are not available. IMPLICATIONS: The authors demonstrated how satellite data can be used to characterize exposures to dust and to anthropogenic pollution for future health related studies. This approach is of a great potential to investigate the associations between subject-specific exposures to different pollution sources and their health effects in inaccessible regions and areas where ground monitoring is unavailable.

Spatio-temporal behavior of brightness temperature in Tel-Aviv and its application to air temperature monitoring.

This study applies remote sensing technology to assess and examine the spatial and temporal Brightness Temperature (BT) profile in the city of Tel-Aviv, Israel over the last 30 years using Landsat imagery. The location of warmest and coldest zones are constant over the studied period. Distinct diurnal and temporal BT behavior divide the city into four different segments. As an example of future application, we applied mixed regression models with daily random slopes to correlate Landsat BT data with monitored air temperature (Tair) measurements using 14 images for 1989-2014. Our preliminary results show a good model performance with R(2) = 0.81. Furthermore, based on the model's results, we analyzed the spatial profile of Tair within the study domain for representative days.

Reflectance spectroscopy is an effective tool for monitoring soot pollution in an urban suburb.

This study examines whether converting the fossil fuel of the Tel Aviv power station from oil to gas influences air pollution in the local urban environment. To this end, the spectral properties of accumulated dust on tree leaves and paper bags were assessed before (2004) and after (2006) the conversion. The sampling site was a garden in a neighborhood located 2700m downwind of the power station. In addition, air pollution concentrations and particulate matter parameters recorded by a local meteorological station were analyzed (PM(10), NO(x), NO(2), NO, and SO(2)). Although differences in the average monthly concentration of pollution parameters are mostly insignificant between the two periods, the accumulated particulate matter exhibits considerably different spectral patterns. All first period samples exhibit a distinctly concave slope in the spectral region between 400 and 1400nm, indicative of high amounts of soot, most likely due to the combustion products of fuel oil exhausted by the power plant. In contrast, the second period samples exhibit spectra that indicate reduced soot content and even appear slightly convex, evidencing the presence of dust of mineral origin, a feature likely masked by the soot in the first period. Thus, the spectral data support that the power plant conversion results in less pollution. More generally, this study corroborates that VIS-NIR-SWIR spectroscopy characterizes key properties of the particulate layer accumulating on sampled surfaces and thus, is a powerful method for monitoring the urban environment.

Application of visible, near-infrared, and short-wave infrared (400-2500 nm) reflectance spectroscopy in quantitatively assessing settled dust in the indoor environment. Case study in dwellings and office environments.

The aim of this study was to apply a novel sensitive technique, involving reflectance spectroscopy in the 400-2500-nm region, to assess dust loads. A spectral library was created to enable identification of the possible sources of settled dust in indoor samples -- mineral versus organic-anthropogenic. Two field experiments were carried out at different dates, the first in dwellings and the second in office environments. Two main spectral patterns were found. Type A spectra indicate a high proportion of minerals in the sample and are characteristic of dust samples taken from the dwelling environment during April (when there were 5 dust storm events). Type B spectra denote a high proportion of organic matter in the sample and are characteristic of the dust samples taken from the offices during March (when there were only 2 dust storm events). The spectral shape within the visible range can be used to estimate the relative amount of mineral and organic components in the sample. Multivariate data analysis, based on Partial Least Squares (PLS) regression, was utilized to predict the relationship between the reflectance of a dust sample and its mass. The relative Root Mean Square Error of Predictions (%RMSEP) generated for the dust sampled in dwellings (6.5%) and offices (7.0%) are quite impressive considering the relatively small amounts of settled dust and its precise gravimetric weight accurate to +/-0.01 mg (min and max values are 0.1-3.2 mg). In addition, PLS regression analysis was used to identify which variables influence dust load. Possible applications of the proposed method are discussed.

Scintigraphic functional hyposplenism in amyloidosis.

UNLABELLED: Functional asplenia or hyposplenism may predispose patients to spontaneous splenic rupture and potentially increase the risk of serious infection. In addition, hyposplenism may be a marker of more extensive systemic amyloidosis and has been correlated to a reduction in survival. Decreased splenic function is generally diagnosed by the presence of abnormal red blood cell morphology and decreased splenic uptake on 99mTc-sulfur colloid or microlite scans. We compared liver spleen scans with red cell morphology and anatomic imaging results in all patients with biopsy-proven amyloidosis who presented to the nuclear medicine department over a 12-yr period. Patients were referred from a center for amyloid disease for work-up of suspected hepatic involvement. METHODS: Between 1983 and 1995, 23 liver spleen scans from 21 patients (one patient had three scans) with known amyloidosis were referred for the assessment of degree of hepatic involvement with amyloid. All scans were retrospectively reviewed, and the degree of splenic uptake was graded. Medical records were reviewed for evidence of splenomegaly on physical exam. Extent of splenic involvement also was assessed by anatomical imaging (CT or MRI) in 45% of cases. Peripheral smear reports were reviewed for the presence of abnormal red cell morphology consistent with hyposplenism. RESULTS: Splenic activity was moderately or markedly reduced in 22 of 23 liver spleen scans (21 patients). Eight of these scans had correlative anatomic splenic imaging: four were abnormal and four were normal. Forty-one percent of available peripheral smears contained abnormal red cell morphology. Nine patients had palpable splenomegaly at the time of the liver spleen scan. Splenic pathologic studies were available for three patients (two autopsy, one surgical) and demonstrated diffuse splenic infiltration with amyloidosis. One patient had spontaneous splenic rupture. Fourteen patients died, four of overwhelming infection. CONCLUSION: Reduced splenic uptake on liver spleen scans for patients with suspected hepatic infiltration with amyloid is a common finding. Liver spleen scanning appears to be a more sensitive marker of splenic amyloidosis than clinical parameters or anatomical imaging.