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Background: The PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) trial was amended to prospectively evaluate the safety and efficacy of an individualized starting dose (ISD) regimen of niraparib for first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer. Methods: In the phase 3 PRIMA trial, patients with newly diagnosed advanced ovarian cancer with a complete/partial response to first-line platinum-based chemotherapy (N = 733) were initially treated with a fixed starting dose (FSD) regimen of 300 mg every day. Subsequently, the protocol was amended so newly enrolled patients received an ISD: 200 mg every day in patients with baseline body weight < 77 kg or baseline platelet count < 150,000/mu L, and 300 mg every day in all other patients. Efficacy and safety outcomes were assessed by starting dose. Results: Overall, 475 (64.8%) patients were assigned to an FSD (niraparib, n = 317; placebo, n = 158) and 258 (35.2%) were assigned to an ISD (niraparib, n = 170; placebo, n = 88). Efficacy in patients who received FSD or ISD was similar for the overall (FSD hazard ratio [HR], 0.59 [95% CI, 0.46-0.76] vs. ISD HR, 0.69 [95% CI, 0.48-0.98]) and the homologous recombination-deficient (FSD HR, 0.44 [95% CI, 0.30-0.64] vs. ISD HR, 0.39 [95% CI, 0.22-0.72]) populations. In patients with low body weight/platelet count, rates of grades =3 and 4 hematologic treatment-emergent adverse events, dose interruptions, and dose reductions were lower for those who received ISD than for those who received FSD. Conclusions: In PRIMA, similar dose intensity, similar efficacy, and improved safety were observed with the ISD compared with the FSD regimen.

Satellite observations from Clouds and the Earth’s Radiant Energy System (CERES) radiometers have produced over two decades of world-class data documenting time–space variations in Earth’s top-of-atmosphere (TOA) radiation budget. In addition to energy exchanges among Earth and space, climate studies require accurate information on radiant energy exchanges at the surface and within the atmosphere. The CERES Cloud Radiative Swath (CRS) data product extends the standard Single Scanner Footprint (SSF) data product by calculating a suite of radiative fluxes from the surface to TOA at the instantaneous CERES footprint scale using the NASA Langley Fu–Liou radiative transfer model. Here, we describe the CRS flux algorithm and evaluate its performance against a network of ground-based measurements and CERES TOA observations. CRS all-sky downwelling broadband fluxes show significant improvements in surface validation statistics relative to the parameterized fluxes on the SSF product, including a ∼30%–40% (∼20%) reduction in SW↓ (LW↓) root-mean-square error (RMSΔ), improved correlation coefficients, and the lowest SW↓ bias over most surface types. RMSΔ and correlation statistics improve over five different surface types under both overcast and clear-sky conditions. The global mean computed TOA outgoing LW radiation (OLR) remains within −2) of CERES observations, while the global mean reflected SW radiation (RSW) is excessive by ∼3.5% (∼9 W m−2) owing to cloudy-sky computation errors. As we highlight using data from two remote field campaigns, the CRS data product provides many benefits for studies requiring advanced surface radiative fluxes.

Cloud vertical profile measurements from the CALIPSO and CloudSat active sensors are used to improve top-of-atmosphere (TOA) shortwave (SW) broadband (BB) irradiance computations. The active sensor measurements, which occasionally miss parts of the cloud columns because of the full attenuation of sensor signals, surface clutter, or insensitivity to a certain range of cloud particle sizes, are adjusted using column-integrated cloud optical depth derived from the passive MODIS sensor. Specifically, we consider two steps in generating cloud profiles from multiple sensors for irradiance computations. First, cloud extinction coefficient and cloud effective radius (CER) profiles are merged using available active and passive measurements. Second, the merged cloud extinction profiles are constrained by the MODIS visible scaled cloud optical depth, defined as a visible cloud optical depth multiplied by (1 − asymmetry parameter), to compensate for missing cloud parts by active sensors. It is shown that the multisensor-combined cloud profiles significantly reduce positive TOA SW BB biases, relative to those with MODIS-derived cloud properties only. The improvement is more pronounced for optically thick clouds, where MODIS ice CER is largely underestimated. Within the SW BB (0.18–4 μm), the 1.04–1.90-μm spectral region is mainly affected by the CER, where both the cloud absorption and solar incoming irradiance are considerable. Significance Statement The purpose of this study is to improve shortwave irradiance computations at the top of the atmosphere by using combined cloud properties from active and passive sensor measurements. Relative to the simulation results with passive sensor cloud measurements only, the combined cloud profiles provide more accurate shortwave simulation results. This is achieved by more realistic profiles of cloud extinction coefficient and cloud particle effective radius. The benefit is pronounced for optically thick clouds composed of large ice particles.

Patients with advanced epithelial ovarian cancer (EOC) alive without progression at a landmark time-point of 10 years from diagnosis are likely cured. We report the proportion of patients with Stage III EOC who were long-term disease-free survivors (LTDFS≥10 years) following either intraperitoneal (IP) or intravenous (IV) chemotherapy as well as the predictors of LTDFS.Data from 3 mature NRG/GOG trials (104, 114, 172) were analyzed and included demographics, clinicopathologic details, route of administration, and survival outcomes of patients living ≥10 years assessed according to the Kaplan-Meier method. Cox regression survival analysis was performed to evaluate independent prognostic predictors of LTDFS.Of 1174 patients randomized, 10-year overall survival (OS) was 26% (95% CI, 23-28%) and LTDFS ≥10 years was 18% (95% CI, 16-20%). Patients with LTDFS ≥10 years had a median age of 54.6 years (p0.001). Younger age (p0.001) was the only independent prognostic factor for LTDFS≥10 years on multivariate Cox analysis.Approximately 18% of patients were LTDFS ≥10 years. They form the tail end of the survival curve and are likely cured. Our results provide a comparative benchmark to evaluate the impact of PARP inhibitors in 1st line maintenance trials on survival outcomes.

Aerosol optical depths (AODs) used for the Edition 4.1 Clouds and the Earth's Radiant Energy System (CERES) Synoptic 1∘ (SYN1deg) product are evaluated. AODs are derived from Moderate Resolution Imaging Spectroradiometer (MODIS) observations and assimilated by an aerosol transport model (the Model for Atmospheric Transport and Chemistry – MATCH). As a consequence, clear-sky AODs closely match with those derived from MODIS instruments. AODs under all-sky conditions are larger than AODs under clear-sky conditions, which is supported by ground-based AErosol RObotic NETwork (AERONET) observations. When all-sky MATCH AODs are compared with Modern-Era Retrospective analysis for Research and Applications (Version 2; MERRA-2) AODs, MATCH AODs are generally larger than MERRA-2 AODs, especially over convective regions (e.g., the Amazon, central Africa, and eastern Asia). This variation is largely due to the differing methods of assimilating the MODIS AOD data product and the use of quality flags in our assimilation. Including AODs with larger retrieval uncertainty makes AODs over the convective regions larger. When AODs are used for clear-sky irradiance computations and computed downward shortwave irradiances are compared with ground-based observations, the computed instantaneous irradiances are 1 %–2 % larger than observed irradiances. The comparison of top-of-atmosphere clear-sky irradiances with those derived from CERES observations suggests that AODs used for surface radiation observation sites are 0.01–0.03 larger, which is within the uncertainty of instantaneous MODIS AODs. However, the comparison with AERONET AODs suggests that AODs used for computations over desert sites are 0.08 larger. The cause of positive biases in downward shortwave irradiance and in AOD for the desert sites is possibly due to the dust particle size and distribution, as defined by the MATCH transport model, and the transfer of that information into the radiative transfer model.

INTRODUCTION: Electronic consultations (e-consults) may be a valuable tool in the current era of increased demand for hematologists. Despite the increasing use of e-consults in hematology, their optimal utilization and impact on patient outcomes and workload are largely unknown. METHODS: In this retrospective cohort study, we studied the hematology consult experience at Veterans Affairs Connecticut from 2006 to 2018. We included 7,664 hematology consults (3,240 e-consults and 4,424 face-to-face [FTF] consults) requested by 1,089 unique clinicians. RESULTS: We found that e-consults were rapidly adopted and used equally among physicians of different degrees of experience. The number of FTF consults did not decrease after the introduction of e-consult services. E-consults were preferentially used for milder laboratory abnormalities that had been less likely to result in a consult before their availability. Referring clinicians used e-consults preferentially for periprocedural management, anemia, leukopenia, and anticoagulation questions. Eighty-three percent of e-consults were resolved without needing an FTF visit in the year after the consult. Consults for pancytopenia, gammopathy, leukocytosis, and for patients with known malignancy were less likely to be resolved by e-consult. Among patients who were diagnosed with a new hematologic malignancy after their consult, having an e-consult before an FTF visit did not adversely affect survival. CONCLUSION: In summary, e-consults safely expanded delivery of hematology services in our health care system but increased total consult volume. We report novel data on what types of consults may be best suited to the electronic modality, the impact of e-consults on workload, and their optimal use and implementation.

BACKGROUND: Unlike fee-for-service Medicare, the Veterans Health Administration (VHA) allows for the provision of concurrent care, incorporating cancer treatment while in hospice. METHODS: We compared trends of aggressive care at end of life between Medicare and VHA decedents with advanced nonsmall cell lung cancer from 2006 to 2012, and the relation between regional level end-of-life care between Medicare and VHA beneficiaries. RESULTS: Among 18,371 Veterans and 25,283 Medicare beneficiaries, aggressive care at end of life decreased 15% in VHA and 4% in SEER (Surveillance, Epidemiology, and End Results)-Medicare (p