Associations between Measured and Patient-Reported Physical Function and Survival in Advanced NSCLC.

Background: There is a lack of tools for selecting patients with advanced lung cancer who benefit the most from systemic treatment. Patient-reported physical function (PRPF) has been identified as a prognostic factor in this setting, but little is known about the prognostic value in advanced non-small-cell lung cancer (NSCLC). The aim of this study was to investigate if measured physical performance was an independent or stronger prognostic factor than PRPF in patients with advanced NSCLC receiving platinum-doublet chemotherapy. Methods: We analyzed patients from a randomized trial comparing immediate and delayed pemetrexed therapy in stage III/IV NSCLC (n = 232) who performed timed up and go (TUG) and 5 m walk test (5 mWT) and reported physical function on the EORTC QLQ-C30 before chemotherapy commenced. Results: Overall, 208 patients performed TUG and 5 mWT and were included in the present study. Poor physical function was significantly associated with poor survival (TUG: HR 1.05, p < 0.01, 5 mWT: HR 1.05, p = 0.03, PRPF: 1.01, p < 0.01), but only PRPF remained an independent prognostic factor in multivariable analyses adjusting for baseline characteristics (HR 1.01, p = 0.03). Conclusions: Patient-reported, but not measured, physical performance was an independent prognostic factor for survival in patients with advanced NSCLC receiving platinum-doublet chemotherapy.

Prognostic Value of Post First-Line Chemotherapy Glasgow Prognostic Score in Advanced Non-Small Cell Lung Cancer.

Background: The Glasgow prognostic score (GPS) is an established inflammatory prognostic index in cancer patients. Most studies have only measured GPS at baseline (B-GPS). Effective cancer therapy may reduce inflammation, and we investigated whether re-assessing GPS after first-line chemotherapy (E-GPS) provided more prognostic information than B-GPS in a phase III trial of advanced non-squamous non-small cell lung cancer (NSCLC). Methods: Glasgow prognostic score was assessed before and after carboplatin/vinorelbine chemotherapy. When assessing GPS, C-reactive protein (CRP) ⩾ 10 mg/L and albumin < 35 mg/L are defined as abnormal values. GPS 0: both values normal, GPS 1: one abnormal value, and GPS 2: both values abnormal. Results: Glasgow prognostic score at baseline and E-GPS were available in 138 patients. Median age was 67 years, 51% were women, and 94% had performance status 0-1. B-GPS was not a statistically significant prognostic factor (B-GPS 1 vs 0: hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 0.9-2.0; B-GPS 2 vs 0: HR = 1.46, 95% CI = 0.9-2.3), while E-GPS was (E-GPS 1 vs 0: HR = 1.57, 95% CI = 1.0-2.4; E-GPS 2 vs 0: HR = 2.77, 95% CI = 1.7-4.5). E-GPS was associated with treatment response (P < .01), whereas B-GPS was not. Conclusion: Glasgow prognostic score at baseline after first-line chemotherapy provided more prognostic information than baseline GPS in patients with advanced non-squamous NSCLC and was associated with treatment response. ClinicalTrialsgov Identifier: NCT02004184.

Study protocol: the Norwegian Triple-S Cohort Study - establishing a longitudinal health survey of children and adolescents with experiences of maltreatment.

BACKGROUND: Child maltreatment is prevalent and associated with both short- and long-term health problems. Previous studies have established child maltreatment as a risk factor for a wide range of problems over the life course such as mental- and somatic health problems, self-harm, alcohol- and drug abuse and decreased work-life participation. Still, there are few large and well-conducted longitudinal studies focusing on describing prevalence and identifying risk factors and long-term consequences of child maltreatment. The purpose of the current study is to recruit a large number of children and adolescents exposed to maltreatment and follow them long-term. METHODS/DESIGN: The current study is a longitudinal cohort study and will use a multi-informant design (child/adolescent, caregiver, and administrative data). Participants will be recruited from the Stine Sofie Centre (SSC), a learning and coping centre for children and adolescents (≤18 years) exposed to maltreatment, which includes physical and emotional abuse, neglect and/or sexual abuse. Questionnaire-based assessments from self-reports (as well as parent-reports) will be carried out at regular time intervals throughout their lives, on topics such as abuse, negative life events, mental and somatic health problems, resilience and coping, satisfaction with health services, social-, family-, and school function, as well as self-harm and substance abuse. Participants will be assessed upon entry to the centre and followed up annually until they reach 18 years and bi-annually after. Given written consent, participants' responses will be linked to relevant national registries in order to examine predictive factors and important outcomes in terms of subsequent health, education, criminal records and work affiliation. DISCUSSION: This study will examine short- and long-term consequences of child maltreatment across a range of health-related outcomes in a longitudinal perspective. Results from the current study might have implications for the development of preventive and intervention programs related to child maltreatment and the organization and follow-up of the services these children receive. The current study will hopefully contribute with knowledge of risk-factors, short- and long-term health-related and other issues that can contribute to practices aimed at improving the overall life-course for children and adolescents who have experienced childhood maltreatment.

Randomized phase III trial comparing switch-maintenance pemetrexed with observation followed by pemetrexed at progression in advanced NSCLC.

Objectives: Two phase III trials show that maintenance pemetrexed therapy after platinum-doublet chemotherapy prolongs overall survival (OS) and progression free survival (PFS) in advanced non-squamous non-small-cell lung cancer (NSCLC). However, few patients in the control arms received pemetrexed at progression in these trials, performance status (PS) two patients were ineligible and few of the participants were elderly. Thus, we designed this study comparing immediate switch-maintenance pemetrexed therapy with pemetrexed at progression after platinum-doublet chemotherapy.Methods: Patients with stage IIIB/IV non-squamous NSCLC, ≥18 years, PS 0-2, and non-progression after four courses of carboplatin/vinorelbine were randomized to receive immediate maintenance pemetrexed therapy or observation followed by pemetrexed at progression. The primary endpoint was OS, secondary endpoints were PFS, toxicity and health related quality of life (HRQoL).Results: 105 patients were randomized between May 2014 and September 2017. Median age was 67 years, 36% were >70 years, 9% had PS 2, 91% stage IV and 47% were women. In the observation arm, 73% received pemetrexed at progression. Patients in the maintenance arm had a numerically longer OS (median 12.0 vs. 10.0 months; p = .10) and a statistically significant longer PFS (median 3.1 vs. 1.9 months; p < .01). In multivariable analyses adjusting for baseline characteristics, there was a trend toward improved OS (HR 0.65, 95% CI 0.42-1.01); p = .05), and a significantly improved PFS (HR 0.53, 95% CI 0.35-0.80; p < .01). There were no significant differences in toxicity or HRQoL between the treatment arms.Conclusion: There was a trend toward prolonged OS and significantly longer PFS from switch- maintenance pemetrexed therapy when 73% of patients in the control arm received pemetrexed at progression. ClinicalTrials.gov Identifier: NCT02004184.

Associations between adverse childhood experiences and adversities later in life. Survey data from a high-risk Norwegian sample.

BACKGROUND: A history of childhood abuse and neglect (CAN) is associated with exposure to later negative life events. CAN at an early age, multiple cooccurring exposures (cumulative events), and a high severity and frequency of exposure have potential detrimental long-term effects. OBJECTIVE: The present study examines the relationship between the severity of CAN and the prevalence of school difficulties and hardship at school, adult adversity and mental health. PARTICIPANTS AND SETTINGS: Participants were recruited from in- and outpatient mental health or substance abuse treatment facilities, child protective services (CPS), and prisons (N = 809, age range = 13-66, mean age = 27.62, SD = 10.47). METHODS: Exposure to childhood maltreatment was assessed by the Childhood Trauma Questionnaire Short Form (CTQ-SF). After adjusting for gender and age, we conducted a risk ratio regression analysis to investigate associations between severity of child abuse and neglect and hardship at school, adult adversity and adult mental health. RESULTS: The moderate and severe level groups of CAN had statistically significant higher risk ratios for experiences of school difficulties, hardship at school, adult adversity and mental health problems. A robust dose-response was found between severity levels. CONCLUSION: At an individual level the findings highlight the association between exposure to abuse and adult adversity, underscoring the importance of targeting individuals with high risk of exposure to CAN to reduce the negative long-term risk for Polyvictimization.