Efficacy of post-induction therapy for high-risk neuroblastoma patients with end-induction residual disease.

BACKGROUND: High-risk neuroblastoma patients with end-induction residual disease commonly receive post-induction therapy in an effort to increase survival by improving the response before autologous stem cell transplantation (ASCT). The authors conducted a multicenter, retrospective study to investigate the efficacy of this approach. METHODS: Patients diagnosed between 2008 and 2018 without progressive disease with a partial response or worse at end-induction were stratified according to the post-induction treatment: 1) no additional therapy before ASCT (cohort 1), 2) post-induction "bridge" therapy before ASCT (cohort 2), and 3) post-induction therapy without ASCT (cohort 3). χ2 tests were used to compare patient characteristics. Three-year event-free survival (EFS) and overall survival (OS) were estimated by the Kaplan-Meier method and survival curves were compared by log-rank test. RESULTS: The study cohort consisted of 201 patients: cohort 1 (n = 123), cohort 2 (n = 51), and cohort 3 (n = 27). Although the end-induction response was better for cohort 1 than cohorts 2 and 3, the outcomes for cohorts 1 and 2 were not significantly different (P = .77 for EFS and P = .85 for OS). Inferior outcomes were observed for cohort 3 (P < .001 for EFS and P = .06 for OS). Among patients with end-induction stable metastatic disease, 3-year EFS was significantly improved for cohort 2 versus cohort 1 (P = .04). Cohort 3 patients with a complete response at metastatic sites after post-induction therapy had significantly better 3-year EFS than those with residual metastatic disease (P = .01). CONCLUSIONS: Prospective studies to confirm the benefits of bridge treatment and the prognostic significance of metastatic response observed in this study are warranted.

Association of Post-discharge Service Types and Timing with 30-Day Readmissions, Length of Stay, and Costs.

BACKGROUND: Although early follow-up after discharge from an index admission (IA) has been postulated to reduce 30-day readmission, some researchers have questioned its efficacy, which may depend upon the likelihood of readmission at a given time and the health conditions contributing to readmissions. OBJECTIVE: To investigate the relationship between post-discharge services utilization of different types and at different timepoints and unplanned 30-day readmission, length of stay (LOS), and inpatient costs. DESIGN, SETTING, AND PARTICIPANTS: The study sample included 583,199 all-cause IAs among 2014 Medicare fee-for-service beneficiaries that met IA inclusion criteria. MAIN MEASURES: The outcomes were probability of 30-day readmission, average readmission LOS per IA discharge, and average readmission inpatient cost per IA discharge. The primary independent variables were 7 post-discharge health services (institutional outpatient, primary care physician, specialist, non-physician provider, emergency department (ED), home health care, skilled nursing facility) utilized within 7 days, 14 days, and 30 days of IA discharge. To examine the association with post-discharge services utilization, we employed multivariable logistic regressions for 30-day readmissions and two-part models for LOS and inpatient costs. KEY RESULTS: Among all IA discharges, the probability of unplanned 30-day readmission was 0.1176, the average readmission LOS per discharge was 0.67 days, and the average inpatient cost per discharge was $5648. Institutional outpatient, home health care, and primary care physician visits at all timepoints were associated with decreased readmission and resource utilization. Conversely, 7-day and 14-day specialist visits were positively associated with all three outcomes, while 30-day visits were negatively associated. ED visits were strongly associated with increases in all three outcomes at all timepoints. CONCLUSION: Post-discharge services of different types and at different timepoints have varying impacts on 30-day readmission, LOS, and costs. These impacts should be considered when coordinating post-discharge follow-up, and their drivers should be further explored to reduce readmission throughout the health care system.

Risk-stratifying capacity of PET/CT metabolic tumor volume in stage IIIA non-small cell lung cancer.

OBJECTIVES: Stage IIIA non-small cell lung cancer (NSCLC) is heterogeneous in tumor burden, and its treatment is variable. Whole-body metabolic tumor volume (MTVWB) has been shown to be an independent prognostic index for overall survival (OS). However, the potential of MTVWB to risk-stratify stage IIIA NSCLC has previously been unknown. If we can identify subgroups within the stage exhibiting significant OS differences using MTVWB, MTVWB may lead to adjustments in patients' risk profile evaluations and may, therefore, influence clinical decision making regarding treatment. We estimated the risk-stratifying capacity of MTVWB in stage IIIA by comparing OS of stratified stage IIIA with stage IIB and IIIB NSCLC. METHODS: We performed a retrospective review of 330 patients with clinical stage IIB, IIIA, and IIIB NSCLC diagnosed between 2004 and 2014. The patients' clinical TNM stage, initial MTVWB, and long-term survival data were collected. Patients with TNM stage IIIA disease were stratified by MTVWB. The optimal MTVWB cutoff value for stage IIIA patients was calculated using sequential log-rank tests. Univariate and multivariate cox regression analyses and Kaplan-Meier OS analysis with log-rank tests were performed. RESULTS: The optimal MTVWB cut-point was 29.2 mL for the risk-stratification of stage IIIA. We identified statistically significant differences in OS between stage IIB and IIIA patients (p < 0.01), between IIIA and IIIB patients (p < 0.01), and between the stage IIIA patients with low MTVWB (below 29.2 mL) and the stage IIIA patients with high MTVWB (above 29.2 mL) (p < 0.01). There was no OS difference between the low MTVWB stage IIIA and the cohort of stage IIB patients (p = 0.485), or between the high MTVWB stage IIIA patients and the cohort of stage IIIB patients (p = 0.459). Similar risk-stratification capacity of MTVWB was observed in a large range of cutoff values from 15 to 55 mL in stage IIIA patients. CONCLUSIONS: Using MTVWB cutoff points ranging from 15 to 55 mL with an optimal value of 29.2 mL, stage IIIA NSCLC may be effectively stratified into subgroups with no significant survival difference from stages IIB or IIIB NSCLC. This may result in more accurate survival estimation and more appropriate risk adapted treatment selection in stage IIIA NSCLC.

Preventive Care: How Mammography Utilization Changes as Women Age.

OBJECTIVE: To evaluate the impact of comorbid conditions and age on mammography use. METHODS: We used data from the 2011 to 2015 Medical Expenditure Panel Survey, which contained records for 40,752 women over the age of 40. Use was defined as a mammogram within the previous 1 or 2 years, analyzed separately. A logit model was employed to evaluate associations between use and comorbidities and age. Statistical significance was defined by a P < .05 by two-sided test. RESULTS: Of the 36,575 women in our study sample, 45.9%, 43.6%, 3.9%, and 5.7% reported a history of hypertension (HTN), hyperlipidemia (HLD), prior heart attack (MI), and prior stroke, respectively. Among women without a comorbid condition, there was 47.3% annual mammography use. HTN and HLD were associated with increased use (2.5 and 6.8 percentage points [pp], P< .01). In comparison, prior MI was associated with decreased annual use (-8.2 pp, P < .01). Prior stroke was not significantly associated with annual mammography (-1.5 pp, P = .42). Results were similar for biennial use. The age trend in use showed that the age with maximum screening use was approximately 60 years. DISCUSSION: Mammography use was higher in patients with HTN and HLD and lower in patients with prior MI and stroke, which may reflect differences in comorbidity-related general health care use. Use increased until it peaked around age 60. An understanding of how mammography use naturally evolves as people age may help better target specific populations and improve overall use of preventive care.

Whole body metabolic tumor volume is a prognostic marker in patients with newly diagnosed stage 3B non-small cell lung cancer, confirmed with external validation.

PURPOSE: TNM Stage 3B encompasses a wide range of primary tumor and nodal metastatic tumor burden. This study aimed to evaluate the prognostic value of quantitative FDG PET/CT parameters in patients with newly diagnosed Stage 3B Non-Small Cell Lung Cancer (NSCLC). MATERIALS AND METHODS: Institutional review board approved retrospective study identified patients diagnosed with Stage 3B NSCLC (8th edition TNM classification) on baseline FDG PET/CT at two medical centers (Medical centers A and B), between Feb 2004 and Dec 2014. Patients were excluded if they had prior NSCLC treatment or recent diagnosis of a second primary cancer. Quantitative FDG PET/CT parameters including whole body metabolic tumor volume (MTVwb), total lesion glycolysis (TLGwb), and maximum standardized uptake value (SUVmaxwb) were measured from baseline PET/CT using Edge method with Mimvista software. The primary endpoint was overall survival (OS). Cox proportional hazard regression and Kaplan-Meier overall survival analyses were used to test for an association between OS and quantitative FDG PET/CT parameters. The distributions of MTVwb, TLGwb, SUVmaxwb were skewed, so a natural logarithm transformation was applied and the transformed variables [(ln(MTVwb), ln(TLGwb), and ln(SUVmaxwb)] were used in the analysis. RESULTS: The training set included 110 patients from center A with Stage 3B NSCLC. 78.2% of patients expired during follow-up. Median OS was 14 months. 1-year, 2-year, and 5-year OS was 56.5%, 34.6% and 13.9%, respectively. Univariate Cox regression analysis showed no significant difference in OS on the basis of age, gender, histology, ln(TLGwb), or ln(SUVmaxwb). ln(MTVwb) was positively associated with OS [hazard ratio (HR) of 1.23, p = 0.037]. This association persisted on multivariate Cox regression analysis (HR 1.28, p = 0.043), with adjustments for age, gender, treatment and tumor histology. External validation with 44 patients from center B confirmed increasing MTVwb was associated significantly worse OS. An MTVwb cut-off point of 85.6 mL significantly stratified Stage 3B NSCLC patient prognosis. CONCLUSION: MTVwb is a prognostic marker for OS in patients with Stage 3B NSCLC, independent of age, gender, treatment, and tumor histology.

Case-control association study of WLS variants in opioid and cocaine addicted populations.

The opioid receptor family is involved in the development and maintenance of drug addiction. The mu-opioid receptor (MOR) mediates the rewarding effects of multiple drugs, including opiates and cocaine. A number of proteins interact with MOR, potentially modulating MOR function and altering the physiological consequences of drug use. These mu-opioid receptor interacting proteins (MORIPs) are potential therapeutic targets for the treatment of addiction. The Wntless (WLS) protein was recently identified as a MORIP in a yeast two-hybrid screen. In this study, we conducted a case-control association analysis of 16 WLS genetic variants in opioid and cocaine addicted individuals of both African-American (opioid n=336, cocaine n=908) and European-American (opioid n=335, cocaine n=336) ancestry. Of the analyzed SNPs, three were nominally associated with opioid addiction and four were nominally associated with cocaine addiction. None of these associations were significant following multiple testing correction. These data suggest that the common variants of WLS analyzed in this study are not associated with opioid or cocaine addiction. However, this study does not exclude the possibilities that rare variants in WLS may affect susceptibility to drug addiction, or that common variants with small effect size may fall below the detection level of our analysis.