Real-world predictors of survival in patients with limited-stage small-cell lung cancer in Manitoba, Canada

BackgroundAlthough therapy for limited-stage small-cell lung cancer (LS-SCLC) is administered with curative intent, most patients relapse and eventually die of recurrent disease. Chemotherapy (CT) with concurrent radiotherapy (RT) remains the standard of care for LS-SCLC; however, this could evolve in the near future. Therefore, understanding the current prognostic factors associated with survival is essential.ObjectiveThis real-world analysis examines factors associated with long-term survival in patients with LS-SCLC treated with CT in Manitoba, Canada.MethodsA retrospective cohort study was conducted using Manitoba Cancer Registry and CancerCare Manitoba records. Eligible patients were aged >18 years and had cytologically confirmed LS-SCLC diagnosed between January 1, 2004, and December 31, 2018, for which they received CT ± RT. Baseline patient, disease, and treatment characteristics and survival duration, characterized as short (<6 months), medium (6−24 months), and long term (>24 months), were extracted. Overall survival (OS) was estimated at one, two, and five years and assessed using Kaplan-Meier methods and Cox proportional hazards models.ResultsOver the 15-year study period, 304 patients met the eligibility criteria. Long-term survivors comprised 39.1% of the cohort; at diagnosis, this subgroup was younger, more likely to have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, and have normal lactate dehydrogenase, sodium, and hemoglobin levels. OS estimates for the entire cohort at one, two, and five years were 66%, 38%, and 18%, respectively. In the ECOG PS 0 subgroup, OS estimates at one, two, and five years were 85%, 52%, and 24%, respectively; OS estimates were 60%, 35%, and 17%, respectively, for ECOG PS 1−2 and were 47%, 23%, and 10%, respectively, for ECOG PS 3−4. OS was significantly higher among patients with normal serum sodium and hemoglobin levels than those with abnormal levels. Univariable hazard regression models found that ECOG PS, age at diagnosis, receipt of prophylactic cranial irradiation (PCI), and thoracic RT were associated with survival. On multivariable hazard regression, ECOG PS and receipt of PCI were associated with survival.ConclusionSurvival for greater than two years in patients with LS-SCLC treated with CT ± RT was associated with ECOG PS and receipt of PCI

Real-world predictors of survival in patients with extensive-stage small-cell lung cancer in Manitoba, Canada: a retrospective cohort study

BackgroundExtensive-stage small-cell lung cancer (ES-SCLC) is an incurable cancer with poor prognosis in which characteristics predictive of long-term survival are debated. The utility of agents such as immune checkpoint inhibitors highlights the importance of identifying key characteristics and treatment strategies that contribute to long-term survival and could help guide therapeutic decisions.ObjectiveThis real-world analysis examines the characteristics, treatment patterns, and clinical outcomes of patients receiving chemotherapy without immunotherapy for ES-SCLC in Manitoba, Canada.MethodsA retrospective cohort study assessed patient characteristics, treatment, and survival duration (short: <6 months; medium: 6–24 months; long: >24 months) using the Manitoba Cancer Registry and CancerCare Manitoba records. Eligible patients were aged >18 years with cytologically confirmed ES-SCLC diagnosed between January 1, 2004, and December 31, 2018, and received cytotoxic chemotherapy (CT). The one-, two-, and five-year probabilities of overall survival (OS) were assessed relative to patient, disease, and treatment characteristics using Kaplan-Meier methods and Cox proportional hazards models.ResultsThis analysis included 537 patients. Cisplatin was used in 56.1% of patients, 45.6% received thoracic radiotherapy (RT), and few received prophylactic cranial irradiation (PCI). In the overall cohort, one-, two- and five-year OS rates were 26%, 8%, and 3%, respectively. For patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, OS rates at one, two, and five years were 43%, 17%, and 10%, respectively, vs. 27%, 8%, and 2% for those with ECOG PS 1–2, and 16%, 3%, and 3% for those with ECOG PS 3–4. In long-term survivors, ECOG PS scores were lower and abnormal laboratory test results were less frequent. Overall, 74.4% of long-term survivors received thoracic RT and 53.5% received PCI. Known poor prognostic factors – including brain/liver metastases, high lactate dehydrogenase (LDH), abnormal sodium, and low hemoglobin levels – were less common but still seen in long-term survivors.ConclusionAlthough rare, patients with ES-SCLC may experience long-term survival with CT ± thoracic RT ± PCI. Factors predicting long-term survival include traditional prognostic factors such as ECOG PS, LDH level, and receipt of thoracic RT or PCI. These findings support current treatment algorithms for ES-SCLC and provide baseline survival estimates to assess the real-world impact of adding immune checkpoint inhibitors in the future

Estimating Disease Heritability from Electronic Healthcare Records: A Proof-of-Concept Study.

Objective A family history of a chronic disease often predicts disease risk, with predictive value determined by heritability, the proportion of variation in risk explained by inherited genetic factors. Our objective was to assess the validity of disease heritability estimates from electronic healthcare records (EHRs) that capture family relationships and disease diagnoses. Approach A population-based investigation was conducted using healthcare records from Manitoba, Canada for 1970 to 2021. We constructed family relationships for up to four generations using health insurance registration information containing unique family and individual identifiers. Health histories for family members were created using diagnosis codes in hospital and physician visit records. Linear mixed-effects models were used to estimate heritability (h) for 130 chronic health conditions using open-source Clinical Classifications Software that defines clinically-meaningful disease categories. Comparisons between EHR-derived estimates and genetically-derived estimates from published studies were used to assess validity of the methodology. Results Health insurance registration data were used to construct 10,000 families that included 116,879 individuals. Median family size was 9 (interquartile range: 8). Median observation time was 39.6 years (interquartile range: 25.7). Males comprised half (51.0%) of family members. A total of 272,114 familial relationships were identified; slightly more than half (53%) were first degree (i.e., child and parent) relationships. One-third (33.2%) of families were comprised of four generations; only 15.3% were comprised of two generations. Heritability estimates were consistent with published genetically-derived estimates for several conditions, including diabetes (EHR h = 0.29 vs. 0.22), anemia (EHR h = 0.21 vs. 0.20), and asthma (EHR h = 0.34 vs. 0.33). However, inconsistencies were identified for pancreatic disorders, gastrointestinal conditions, some mental health conditions, and heart disease. Conclusion EHRs provide a promising approach to explore heritability of selected health conditions in large, diverse populations. Inconsistencies between EHR-derived and genetically-derived estimates are indicative of the limitations of diagnoses recorded for administrative purposes. Future research will explore sex-specific heritability estimates and effects of change in disease diagnosis coding over time

Nuclear Factor I/B is an Oncogene in Small Cell Lung Cancer

Small cell lung cancer (SCLC) is an aggressive cancer often diagnosed after it has metastasized. Despite the need to better understand this disease, SCLC remains poorly characterized at the molecular and genomic levels. Using a genetically engineered mouse model of SCLC driven by conditional deletion of Trp53 and Rb1 in the lung, we identified several frequent, high-magnitude focal DNA copy number alterations in SCLC. We uncovered amplification of a novel, oncogenic transcription factor, Nuclear factor I/B (Nfib), in the mouse SCLC model and in human SCLC. Functional studies indicate that NFIB regulates cell viability and proliferation during transformation.National Cancer Institute (U.S.) (grant P30-CA14051)David H. Koch Institute for Integrative Cancer Research at MIT (Ludwig Center for Molecular Oncology)Howard Hughes Medical InstituteAlfred P. Sloan Foundation (Research Fellowship)International Association for the Study of Lung Cance

Dust Reverberation Mapping in Distant Quasars from Optical and Mid-Infrared Imaging Surveys

The size of the dust torus in Active Galactic Nuclei (AGN) and their high-luminosity counterparts, quasars, can be inferred from the time delay between UV/optical accretion disk continuum variability and the response in the mid-infrared (MIR) torus emission. This dust reverberation mapping (RM) technique has been successfully applied to $\sim 70$ $z\lesssim 0.3$ AGN and quasars. Here we present first results of our dust RM program for distant quasars covered in the SDSS Stripe 82 region combining $\sim 20$-yr ground-based optical light curves with 10-yr MIR light curves from the WISE satellite. We measure a high-fidelity lag between W1-band (3.4 $\mu$m) and $g$ band for 587 quasars over $0.3\lesssim z\lesssim 2$ (\left\sim 0.8) and two orders of magnitude in quasar luminosity. They tightly follow (intrinsic scatter $\sim 0.17$ dex in lag) the IR lag-luminosity relation observed for $z<0.3$ AGN, revealing a remarkable size-luminosity relation for the dust torus over more than four decades in AGN luminosity, with little dependence on additional quasar properties such as Eddington ratio and variability amplitude. This study motivates further investigations in the utility of dust RM for cosmology, and strongly endorses a compelling science case for the combined 10-yr Vera C. Rubin Observatory Legacy Survey of Space and Time (optical) and 5-yr Nancy Grace Roman Space Telescope 2$\mu$m light curves in a deep survey for low-redshift AGN dust RM with much lower luminosities and shorter, measurable IR lags. The compiled optical and MIR light curves for 7,384 quasars in our parent sample are made public with this work.Comment: Accepted for publication in Ap

The Role of Immunotherapy in the Treatment of Malignant Pleural Mesothelioma

Malignant pleural mesothelioma is a rare and aggressive malignancy arising from mesothelial cells that line the serous membranes of the body. Cytotoxic chemotherapy has been a mainstay of therapy, resulting in a modest improvement in overall survival, but toxicity limits the eligible patient population. Few targeted agents beyond bevacizumab have demonstrated superior efficacy compared to placebos. With an improved understanding of the relationship between the immune system and cancer progression, immunotherapies are playing a greater role in the treatment of many cancers. Several early- and late-phase trials in malignant pleural mesothelioma, including assessments of the first-line efficacy of combination ipilimumab/nivolumab treatment, have now demonstrated promising results for both immune checkpoint inhibition and cell-based therapies. These immune therapies are likely to play a central role in the treatment of this disease going forward

Economic aspects of information in environmental economics

Information may resolve uncertainty and uncertainty is pervasive. Thus, seeking, producing and trading of information are common economic activities. This is also true in the economics of the environment and for the different stakeholders therein involved. The central aim of this research is to investigate some theoretical aspects of the value and effects of information in environmental economics. Information is valuable either as a decision aid in contexts where either health and environmental characteristics of goods are uncertain or as the object of direct valuation under different provision rules. In a choice context three questions arise providing grounds for empirical investigations.EThOS - Electronic Theses Online ServiceGBUnited Kingdo