Twenty percent of patients with follicular lymphoma (FL) experience progression of disease (POD) within 2 years of initial chemoimmunotherapy. We analyzed data from the National LymphoCare Study to ...identify whether prognostic FL factors are associated with early POD and whether patients with early POD are at high risk for death.
In total, 588 patients with stage 2 to 4 FL received first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Two groups were defined: patients with early POD 2 years or less after diagnosis and those without POD within 2 years, the reference group. An independent validation set, 147 patients with FL who received first-line R-CHOP, was analyzed for reproducibility.
Of 588 patients, 19% (n = 110) had early POD, 71% (n = 420) were in the reference group, 8% (n = 46) were lost to follow-up, and 2% (n = 12) died without POD less than 2 years after diagnosis. Five-year overall survival was lower in the early-POD group than in the reference group (50% v 90%). This trend was maintained after we adjusted for FL International Prognostic Index (hazard ratio, 6.44; 95% CI, 4.33 to 9.58). Results were similar for the validation set (FL International Prognostic Index-adjusted hazard ratio, 19.8).
In patients with FL who received first-line R-CHOP, POD within 2 years after diagnosis was associated with poor outcomes and should be further validated as a standard end point of chemoimmunotherapy trials of untreated FL. This high-risk FL population warrants further study in directed prospective clinical trials.
We assessed the incidence, prognostic features, and outcomes associated with transformation of follicular lymphoma (FL) among 2652 evaluable patients prospectively enrolled in the National LymphoCare ...Study. At a median follow-up of 6.8 years, 379/2652 (14.3%) patients transformed following the initial FL diagnosis, including 147 pathologically confirmed and 232 clinically suspected cases. Eastern Cancer Oncology Group performance status >1, extranodal sites >1, elevated lactate dehydrogenase, and B symptoms at diagnosis were associated with transformation risk. Relative to observation, patients initiating treatment at diagnosis had a reduced risk of transformation (hazard ratio HR, 0.58; 95% confidence interval CI, 0.46-0.75). The risk of transformation was similar in patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone compared with rituximab, cyclophosphamide, vincristine, and prednisone (adjusted HR, 0.94; 95% CI, 0.62-1.42). Maintenance rituximab was associated with reduced transformation risk (HR, 0.67; 95% CI, 0.46-0.97). Five-year survival from diagnosis was significantly worse for patients with vs without transformation (75%, 95% CI, 70-79 vs 85%, 95% CI, 83-86). The median overall survival posttransformation was 5 years. Forty-seven patients with evidence of transformation at the time of diagnosis shared similar prognostic factors and survival rates to those without transformation. Improved outcomes for transformation in the modern era are suggested by this observational study. This trial is registered at www.clinicaltrials.gov as #NCT00097565.
•The median posttransformation survival of 5 years suggests improved outcomes for transformed FL in the modern era.•Five-year progression-free and overall survival (66% and 88%) are favorable for patients with evidence of transformation at diagnosis.
Gastric adenocarcinoma is the fifth most common malignancy in the world and the third leading cause of cancer death in both women and men. In 2012, its estimated global incidence was 952,000 new ...cases with an estimated 723,000 deaths worldwide. It is projected to rise from 14th to eighth in all-cause mortality in the near term, primarily due to the growing and aging populations in high-incidence areas, such as Latin America and eastern Asia. Unlike any other major cancer, gastric cancer demonstrates marked geographic variability in regions and within countries, with more than 70% of incident cases concentrated in lowand middle-income countries (LMICs).
AbstractMass mortality events provide valuable insight into biological extremes and also ecological interactions more generally. The sea star wasting epidemic that began in 2013 catalyzed study of ...the microbiome, genetics, population dynamics, and community ecology of several high-profile species inhabiting the northeastern Pacific but exposed a dearth of information on the diversity, distributions, and impacts of sea star wasting for many lesser-known sea stars and a need for integration across scales. Here, we combine datasets from single-site to coast-wide studies, across time lines from weeks to decades, for 65 species. We evaluated the impacts of abiotic characteristics hypothetically associated with sea star wasting (sea surface temperature, pelagic primary productivity, upwelling wind forcing, wave exposure, freshwater runoff) and species characteristics (depth distribution, developmental mode, diet, habitat, reproductive period). We find that the 2010s sea star wasting outbreak clearly affected a little over a dozen species, primarily intertidal and shallow subtidal taxa, causing instantaneous wasting prevalence rates of 5%-80%. Despite the collapse of some populations within weeks, environmental and species variation protracted the outbreak, which lasted 2-3 years from onset until declining to chronic background rates of ∼2% sea star wasting prevalence. Recruitment began immediately in many species, and in general, sea star assemblages trended toward recovery; however, recovery was heterogeneous, and a marine heatwave in 2019 raised concerns of a second decline. The abiotic stressors most associated with the 2010s sea star wasting outbreak were elevated sea surface temperature and low wave exposure, as well as freshwater discharge in the north. However, detailed data speaking directly to the biological, ecological, and environmental cause(s) and consequences of the sea star wasting outbreak remain limited in scope, unavoidably retrospective, and perhaps always indeterminate. Redressing this shortfall for the future will require a broad spectrum of monitoring studies not less than the taxonomically broad cross-scale framework we have modeled in this synthesis.
Positron emission tomography (PET) after induction therapy in follicular lymphoma (FL) is predictive of survival in clinical trials. We describe use of PET and computed tomography (CT) after ...rituximab-based induction therapy in FL patients followed by the National LymphoCare Study and explore the association between imaging response assessment and survival. Among 1289 patients, imaging consisted of: PET ± CT (35%), CT alone (42%), other/no imaging (24%). Median follow-up was 7.6 years. In unadjusted analyses, positive PET ± CT and CT were prognostic of inferior OS (HR 1.78; 95% CI: 1.16-2.72 and HR 1.61, 95% CI: 1.13-2.29, respectively) and PFS (HR 1.63, 95% CI: 1.21-2.20 and HR 1.45, 95% CI: 1.12-1.89, respectively). Adjusting for FL International Prognostic Index, PET remained predictive of OS (HR 1.54, 95% CI: 1.01-2.36) and PFS (HR 1.54, 95% CI: 1.14-2.07). Residual disease via PET in FL is prognostic of survival in clinical practice.
Abstract
To compare the effectiveness of frontline rituximab-chemotherapy regimens in clinical practice, we examined outcomes for patients with low-grade, stage III/IV follicular lymphoma receiving ...rituximab (R) with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), R with cyclophosphamide, vincristine and prednisone (R-CVP) or R with a fludarabine-based regimen (R-Flu) as frontline therapy. In total, 611 patients meeting these criteria were identified in the National LymphoCare Study: 47% receiving R-CHOP (n = 287), 31% receiving R-CVP (n = 187) and 22% receiving R-Flu (n = 137). Overall response rates were high (R-CVP 87%, R-CHOP 93%, R-Flu 94%; p = 0.017). Median follow-up was 7.4 years. R-CVP was associated with lower 5-year overall survival (R-CVP 76%, R-CHOP 86%, R-Flu 86%; p = 0.021) and progression-free survival (R-CVP 49%, R-CHOP 58%, R-Flu 64%; p = 0.029). There were no significant differences in survival in Cox models adjusted for baseline clinical factors, practice region/setting and post-treatment R maintenance/observation.
Abstract
As part of the U.S. National Seismic Hazard Model (NSHM) update planned for 2023, two databases were prepared to more completely represent Quaternary-active faulting across the western ...United States: the NSHM23 fault sections database (FSD) and earthquake geology database (EQGeoDB). In prior iterations of NSHM, fault sections were included only if a field-measurement-derived slip rate was estimated along a given fault. By expanding this inclusion criteria, we were able to assess a larger set of faults for use in NSHM23. The USGS Quaternary Fault and Fold Database served as a guide for assessing possible additions to the NSHM23 FSD. Reevaluating available data from published sources yielded an increase of fault sections from ~650 faults in NSHM18 to ~1,000 faults proposed for use in NSHM23. EQGeoDB, a companion dataset linked to NSHM23 FSD, contains geologic slip rate estimates for fault sections included in FSD. Together, these databases serve as common input data used in deformation modeling, earthquake rupture forecasting, and additional downstream uses in NSHM development.
Na+- and Cl−-dependent uptake of neurotransmitters via transporters of the SLC6 family, including the human serotonin transporter (SLC6A4), is critical for efficient synaptic transmission. Although ...residues in the human serotonin transporter involved in direct Cl− coordination of human serotonin transport have been identified, the role of Cl− in the transport mechanism remains unclear. Through a combination of mutagenesis, chemical modification, substrate and charge flux measurements, and molecular modeling studies, we reveal an unexpected role for the highly conserved transmembrane segment 1 residue Asn-101 in coupling Cl− binding to concentrative neurotransmitter uptake.
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