Role of the vulnerable elders survey-13 screening tool in predicting treatment plan modification for older adults with cancer

Background: The Vulnerable Elders Survey (VES-13) is commonly used to identify older patients who may benefit from Comprehensive Geriatric Assessment (CGA) prior to cancer treatment. The optimal cut point of the VES-13 to identify those whose final oncologic treatment plan would change after CGA is unclear. We hypothesized that patients with high positive VES-13 scores (7–10)have a higher likelihood of a change in treatment compared to low positive scores (3–6).Methods: Retrospective review of a customized database of all patients seen for pre-treatment assessment in an academic geriatric oncology clinic from June 2015 to June 2019. Various VES-13 cut points were analyzed to identify those individuals whose treatment was modified after CGA. Area under the curve (AUC) was calculated and subgroups of patients treated locally or systemically were also examined to determine if performance varied by treatment modality.Results: We included 386 patients with mean age 81, 58% males. Gastrointestinal cancer was the most common site (31%) and 60% were planned to receive curative treatment. The final treatment plan was modified in 59% overall, with 52.7% modified with VES-13 scores 7–10, 50.8% with scores 3–6 and 28.1% with scores <3 (P = 0.002). VES-13 performance in predicting treatment modification was similar for cut points 3 (AUC 0.58), 4 (0.59), 5 (0.59), and 6 (0.59) and in those considering local treatment vs. chemotherapy.Conclusions: A positive VES-13 score was associated with final oncologic treatment plan modification. A high positive score was not superior to the conventional cut point of ≥3.     

LKB1-PTEN axis controls Th1 and Th17 cell differentiation via regulating mTORC1

Journal of Molecular Medicine - Immuno-environmental change triggers CD4+ T cell differentiation. T cell specialization activates metabolic signal pathways to meet energy requirements. Defective T...     

Changes in bone mineral density in men starting androgen deprivation therapy and the protective role of vitamin D

Summary

Androgen deprivation therapy in 80 men was associated with declines in bone mineral density (BMD), which were greatest in the first year, and in the lumbar spine compared to controls. Vitamin D use was associated with improved BMD in the lumbar spine and in the first year.

Introduction

Decreased BMD is a common side effect of androgen deprivation therapy (ADT), leading to increased risk of fractures. Although loss of BMD appears to be greatest within the first year of starting ADT, there are few long-term studies of change in BMD, and risk factors for bone loss are not well-characterized.

Methods

Men aged 50+ with nonmetastatic prostate cancer starting continuous ADT were enrolled in a prospective longitudinal study. BMD was determined by dual-energy x-ray absorptiometry at baseline and yearly for 3 years. Matched controls were men with prostate cancer not receiving ADT. Multivariable regression analysis examined predictors of BMD loss.

Results

Eighty ADT users and 80 controls were enrolled (mean age 69 years); 52.5 % had osteopenia and 8.1 % had osteoporosis at baseline. After 1 year, in adjusted models, ADT was associated with significant losses in lumbar spine BMD compared to controls (?2.57 %, p?=?0.006), with a trend towards greater declines at the total hip (p?=?0.09). BMD changes in years 2 and 3 were much smaller and not statistically different from controls. Use of vitamin D but not calcium was associated with improved BMD in the lumbar spine in year 1 (+6.19 %, p?<?0.001) with smaller nonsignificant increases at other sites (+0.86 % femoral neck, +0.86 % total hip, p?>?0.10) primarily in the first year.

Conclusions

Loss of BMD associated with ADT is greatest at the lumbar spine and in the first year. Vitamin D but not calcium may be protective particularly in the first year of ADT use.     

Analysis of active surveillance uptake for low-risk localized prostate cancer in Canada: a Canadian multi-institutional study

Purpose

Although the uptake of active surveillance (AS) appears to be increasing in published series, the uptake in most geographic regions remains largely unknown. Our aim was to examine practice patterns around the use of AS in low-risk prostate cancer in Canada. In addition, we examined regional variations in AS uptake, predictors of AS uptake, and persistent use for 12 months.

Methods

This is a retrospective multicentre review of low-risk patients who underwent a prostate biopsy in 2010 in six centres in four provinces (BC, QC, MB and ON). AS was identified based on chart review and required a minimum of 6 months of follow-up after diagnosis without any active treatment.

Results

Of 986 patients, 781 patients (mean age 64 years) were incident cases and over three-quarters (77.3 %) chose AS at diagnosis. There were significant differences in uptake of AS by centre (range 65.0–98.0 %, p ≤ 0.05). Key multivariate predictors of pursuing AS included older age (OR 1.34, p = 0.044), centre (p = 0.021), lower number of cores (OR 1.09, p = 0.025), lower number of positive biopsy cores (OR 0.52, p < 0.001), and lower percent core involvement (OR 0.84, p < 0.001). In total, 516 (85.4 %) men remained on AS over 12 months. Maintenance with AS over 12 months differed by centre, ranging from 64.1 to 93.9 % (p = 0.001). Predictors of maintenance with AS over 12 months included older age, centre, and lower number of positive cores.

Conclusions

Active surveillance is widely practiced across Canada, but important regional differences were observed. Further analyses are required to understand the root causes of differences and to determine whether AS uptake is changing over time.

     

BJ‐2266 ameliorates experimental autoimmune encephalomyelitis through down‐regulation of the JAK/STAT signaling pathway

CD4⁺ T cells differentiate into distinct effector subsets upon antigenic stimulation. Cytokines, and micro‐environmental factors present during T‐cell priming, direct differentiation of naïve CD4⁺ T cells into pro‐inflammatory Th1 and Th17 cells. From extensive screening of 2,4,5‐trimethylpyridin‐3‐ol derivatives with various functional groups at C(6)‐position, BJ‐2266, a 6‐thioureido‐derivative, showed potent inhibitory activity on in vitro T helper (Th)‐cell differentiation. This compound inhibited IFN‐γ and IL‐17 production from polyclonal CD4⁺ T cells and ovalbumin (OVA)‐specific CD4⁺ T cells that were activated by T‐cell receptor (TCR) engagement. We assessed the inhibitory effect of BJ‐2266 in experimental autoimmune encephalomyelitis (EAE). Our results suggest that BJ‐2266 treatment significantly suppresses EAE disease progression with reduced generation of Th1 and Th17 cells. Notably, Th‐cell differentiation was significantly suppressed by BJ‐2266 treatment with no effect on apoptosis, activation and proliferation of activated T cells. Furthermore, adoptive transfer of BJ‐2266 treated MOG‐reactive Th1 and Th17 cells led to a lower EAE disease score and better clinical recovery from EAE. The underlying mechanism of BJ‐2266 effect involved the inhibition of JAK/STAT phosphorylation that is critical for Th‐cell differentiation. We conclude that BJ‐2266 regulates the JAK/STAT pathway in response to cytokine signals and subsequently suppresses the differentiation of Th‐cell responses.     

Impact of androgen deprivation therapy on depressive symptoms in men with nonmetastatic prostate cancer

BACKGROUND:

Up to 50% of prostate cancer (PC) patients receive androgen deprivation therapy (ADT), often for several years. Although depression has been reported after a diagnosis of PC, whether ADT leads to or worsens depression is not clear.

METHODS:

Three groups were assembled: ADT users (men initiating continuous ADT), PC controls (PC patients who were not on ADT), and healthy controls. All 3 cohorts were matched on age, education, and physical function, and none had metastases. Depression was measured at study entry and again at 3, 6, and 12 months using the 15‐item Geriatric Depression Scale (GDS). Our primary outcomes were worsening depressive symptoms and incident depression (defined as a GDS score ≥5), analyzed using adjusted linear regression and logistic regression, respectively.

RESULTS:

Of the 257 participants (mean age, 69.1 years), baseline characteristics including GDS score and prior depression were similar across cohorts. In adjusted analyses of initially nondepressed patients, ADT use was not a significant predictor of change in GDS score at 3 months (P = .42), 6 months (P = .25), or 12 months (P = 0.19). Among ADT users, 8%‐9% of participants developed incident depression compared with 0%‐4% among PC controls and 4%‐6% among healthy controls over 3‐12 months (P>.05 at all time points). In a separate analysis of patients with depression at baseline, there was no effect of ADT on depressive symptoms at 3, 6, or 12 months (P = .11, .74, and .12, respectively).

CONCLUSION:

Twelve months of ADT use were not associated with worsening depressive symptoms among nondepressed or depressed patients with nonmetastatic PC. Cancer 2012;. © 2011 American Cancer Society.     

Predictors of early mortality after radical nephrectomy with renal vein or inferior vena cava thrombectomy – a population‐based study

Study Type – Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Surgical volume has been well established as a predictor of outcomes for several complex surgical procedures, yet few studies have evaluated this relationship with regards to radical nephrectomy with either renal vein or inferior vena cava thrombectomy. In addition, most published literature consists of single‐institution series from centres of excellence. We performed a population‐level analysis and identified surgeon volume as a significant predictor of short‐term mortality for this procedure. Such findings have potential implications regarding future policy and regionalization of care.

OBJECTIVE

• ? To study the short‐term mortality associated with radical nephrectomy with renal vein or inferior vena cava thrombectomy and the variables associated with this adverse outcome.

METHODS

• ? Using the Ontario Cancer Registry, we identified 433 patients in the province of Ontario, Canada undergoing radical nephrectomy with venous thrombectomy between 1995 and 2004.
• ? We determined mortality rates at postoperative days 30 and 90.
• ? Other variables analysed include pathological tumour characteristics, surgeon graduation year, hospital/surgeon academic status, surgery year and hospital/surgeon volume.
• ? We used multivariable logistic regression to assess outcomes.

RESULTS

• ? Overall mortality was 2.8% (30‐day) and 5.8% (90‐day).
• ? Surgeons performing a single nephrectomy with venous thrombectomy performed 14% of the cases and had the highest 30‐day (6.7%) and 90‐day (10%) mortality. The mortality rate for surgeons performing more than one surgery was 2.1% (30‐day) and 5.1% (90‐day).
• ? In recent years, this procedure was performed more commonly by the highest volume surgeons – 67% of cases in 2004 vs 40% in 1995.
• ? Significant predictors of 30‐day mortality included procedure year and low surgeon volume.
• ? Significant predictors of 90‐day mortality included procedure year, low surgeon volume, left‐sided tumour and increasing hospital volume.

CONCLUSIONS

• ? For radical nephrectomy with venous thrombectomy, surgeon volume predicts short‐term mortality, emphasizing the importance of experience in patient outcome.
• ? Despite a shift towards high‐volume surgeons, 13.8% of cases continued to be performed by low‐volume providers.
• ? If these results are confirmed in other jurisdictions, radical nephrectomy with venous thrombectomy should be regionalized and performed by surgeons who manage these cases regularly.