Zhongze Li

Effects of a Palliative Care Intervention on Clinical Outcomes in Patients With Advanced Cancer: The Project ENABLE II Randomized Controlled Trial

CONTEXT There are few randomized controlled trials on the effectiveness of palliative care interventions to improve the care of patients with advanced cancer. OBJECTIVE To determine the effect of a nursing-led intervention on quality of life, symptom intensity, mood, and resource use in patients with advanced cancer. DESIGN, SETTING, AND PARTICIPANTS Randomized controlled trial conducted from November 2003 through May 2008 of 322 patients with advanced cancer in a rural, National Cancer Institute-designated comprehensive cancer center in New Hampshire and affiliated outreach clinics and a VA medical center in Vermont. INTERVENTIONS A multicomponent, psychoeducational intervention (Project ENABLE [Educate, Nurture, Advise, Before Life Ends]) conducted by advanced practice nurses consisting of 4 weekly educational sessions and monthly follow-up sessions until death or study completion (n = 161) vs usual care (n = 161). MAIN OUTCOME MEASURES Quality of life was measured by the Functional Assessment of Chronic Illness Therapy for Palliative Care (score range, 0-184). Symptom intensity was measured by the Edmonton Symptom Assessment Scale (score range, 0-900). Mood was measured by the Center for Epidemiological Studies Depression Scale (range, 0-60). These measures were assessed at baseline, 1 month, and every 3 months until death or study completion. Intensity of service was measured as the number of days in the hospital and in the intensive care unit (ICU) and the number of emergency department visits recorded in the electronic medical record. RESULTS A total of 322 participants with cancer of the gastrointestinal tract (41%; 67 in the usual care group vs 66 in the intervention group), lung (36%; 58 vs 59), genitourinary tract (12%; 20 vs 19), and breast (10%; 16 vs 17) were randomized. The estimated treatment effects (intervention minus usual care) for all participants were a mean (SE) of 4.6 (2) for quality of life (P = .02), -27.8 (15) for symptom intensity (P = .06), and -1.8 (0.81) for depressed mood (P = .02). The estimated treatment effects in participants who died during the study were a mean (SE) of 8.6 (3.6) for quality of life (P = .02), -24.2 (20.5) for symptom intensity (P = .24), and -2.7 (1.2) for depressed mood (P = .03). Intensity of service did not differ between the 2 groups. CONCLUSION Compared with participants receiving usual oncology care, those receiving a nurse-led, palliative care-focused intervention addressing physical, psychosocial, and care coordination provided concurrently with oncology care had higher scores for quality of life and mood, but did not have improvements in symptom intensity scores or reduced days in the hospital or ICU or emergency department visits. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00253383.

Immune response in patients with newly diagnosed glioblastoma multiforme treated with intranodal autologous tumor lysate-dendritic cell vaccination after radiation chemotherapy.

Patients with glioblastoma multiforme (GBM) are profoundly immunosuppressed and may benefit from restoration of an antitumor immune response in combination with conventional radiation therapy and temozolomide (TMZ). The optimal strategies to evaluate clinically relevant immune responses to treatment have yet to be determined. The primary objective of our study was to determine immunologic response to cervical intranodal vaccination with autologous tumor lysate-loaded dendritic cells (DCs) in patients with GBM after radiation therapy and TMZ. We used a novel hierarchical clustering analysis of immune parameters measured before and after vaccination. Secondary objectives were to assess treatment feasibility and to correlate immune response with progression-free survival (PFS) and overall survival. Ten eligible patients received vaccination. Tumor-specific cytotoxic T-cell response measured after vaccination was enhanced for the precursor frequency of CD4+ T and CD4+ interferon &ggr;-producing cells. Hierarchical clustering analysis of multiple functional outcomes discerned 2 groups of patients according to their immune response, and additionally showed that patients in the top quintile for at least one immune function parameter had improved survival. There were no serious adverse events related to DC vaccination. All patients were alive at 6 months after diagnosis and the 6-month PFS was 90%. The median PFS was 9.5 months and overall survival was 28 months. In patients with GBM, immune therapy with DC vaccination after radiation and TMZ resulted in tumor-specific immune responses that were associated with prolonged survival. Our data suggest that DC vaccination in combination with radiation and chemotherapy in patients with GBM is feasible, safe, and may induce tumor-specific immune responses.

Genus β human papillomaviruses and incidence of basal cell and squamous cell carcinomas of skin: population based case-control study

Objective To investigate the association between genus β human papillomaviruses and the incidence of non-melanocytic skin cancer in the general population. Design Population based case-control study. Setting New Hampshire, USA. Participants 2366 skin cancer cases and controls from the general population aged 25 to 74 years (663 squamous cell carcinoma, 898 basal cell carcinoma, 805 controls), with plasma samples tested for L1 antibodies to 16 genus β human papillomaviruses by multiplex serology. Main outcome measures Odds ratios for squamous cell carcinoma and basal cell carcinoma associated with seropositivity to β human papillomaviruses. Results Squamous cell carcinoma, but not basal cell carcinoma, cases had a higher prevalence of each of the individual β human papillomaviruses assayed compared with controls. The odds ratios for squamous cell carcinoma increased with the number of β types positive (odds ratio for one type positive 0.99 (95% confidence interval 0.74 to 1.33); two to three types positive 1.44 (1.03 to 2.01); four to eight types positive 1.51 (1.03 to 2.20); more than eight types positive 1.71 (1.12 to 2.62); P for trend (categorical)<0.001; P for trend (continuous)=0.003). With limited statistical power, the association was stronger among long term users of systemic glucocorticoids (odds ratio 3.21, 1.22 to 8.44) than among non-users (1.23, 0.97 to 1.55). Conclusions These findings support a relation between genus β human papillomavirus infection and the incidence of squamous cell carcinoma of the skin in the general population, as well as potential enhancement of risk by immunosuppression.

Tumor Angiogenesis Change Estimated by Using Diffuse Optical Spectroscopic Tomography: Demonstrated Correlation in Women Undergoing Neoadjuvant Chemotherapy for Invasive Breast Cancer?

PURPOSE To investigate if changes in tumor angiogenesis associated with complete pathologic response (pCR) or partial pathologic response (pPR) to treatment can be demonstrated by using diffuse optical spectroscopic (DOS) tomography. MATERIALS AND METHODS All participants in this prospective, HIPAA-compliant, institutional review board-approved study provided written informed consent. Eleven women with invasive breast carcinoma were imaged with DOS tomography prior to, during, and at completion of neoadjuvant chemotherapeutic regimens. By using region of interest (ROI) analysis, the DOS measure of total tissue hemoglobin (Hb(T)) was temporally correlated with quantitative measures of existing (CD31-expressing) and tumor-induced (CD105-expressing) vessels, in pretreatment and posttreatment tissue specimens, to assess change. RESULTS Quantified angiogenesis alone in pretreatment core biopsy specimens did not predict treatment response, but mean vessel density (MVD) and mean vessel area (MVA) of CD105-expressing vessels were significantly decreased in women with pCR (n = 7) (P < .001 and P = .003, respectively). MVA of CD105-expressing vessels was also significantly reduced at comparison of pre- and posttreatment residual tumor for women with pPR (n = 4) (P = .033). A longitudinal analysis showed significant decreases (P = .001) in mean Hb(T) levels during neoadjuvant chemotherapy in breast abnormality ROIs for women with pCR but not women with pPR. For women with pCR, but not women with pPR, pretreatment MVD of CD105-expressing vessels correlated with pretreatment Hb(T) (P ≤ .001). CONCLUSION DOS tomographic examinations in women with breast cancer who are receiving neoadjuvant chemotherapy show a mean decrease in Hb(T) with time in patients with pCR only. Observed pretreatment and posttreatment correlates with quantified angiogenesis markers confirm the likely biologic origin for this DOS signature and support its potential to predict angiogenic tissue response early in the treatment cycle. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11100699/-/DC1.

Malignancy Is Associated with Dermatomyositis But Not Polymyositis in Northern New England, USA

Objective. To retrospectively evaluate the association of idiopathic inflammatory myopathy (IIM) and malignancy in patients seen at 1 academic center over a 23-year period. Methods. Patients were identified using the International Classification of Diseases, 9th edition (ICD-9) codes and diagnoses, then confirmed by chart review. Population cancer statistics obtained from the US Centers for Disease Control for Vermont and New Hampshire were used for comparison. Results. Chart review confirmed IIM in 198 of 483 patients initially identified by ICD-9 codes. Within 5 years of diagnosis with IIM, malignancy developed in 32 patients (16.2%), 24 of whom (75%) had dermatomyositis (DM). Malignancy and DM developed within 1 year in 75%. The cancer risk associated with DM was much greater than the risk associated with other IIM. The most frequent tumor types were breast, lung, pancreas, and colon. DM patients with cancer were more frequently male and ≥ 45 years of age than those without cancer. There were no cases of interstitial lung disease among patients with cancer and any form of IIM. The incidence of cancer was increased in patients with DM compared to age- and sex-matched population controls, both over a 5-year interval surrounding the diagnosis of DM and over the lifetime interval following diagnosis. Conclusion. The risk of cancer in IIM is concentrated among patients with DM. The association between DM and cancer was enhanced by its temporal relationship (< 1 year) in 87.5% of these cases. Patients with malignancy-associated DM were more frequently male and over age 45 and less likely to have interstitial lung disease.

A case-control study of polymorphisms in xenobiotic and arsenic metabolism genes and arsenic-related bladder cancer in New Hampshire.

Arsenic is associated with bladder cancer risk even at low exposure levels. Genetic variation in enzymes involved in xenobiotic and arsenic metabolism may modulate individual susceptibility to arsenic-related bladder cancer. Through a population-based case-control study in NH (832 cases and 1191 controls), we investigated gene-environment interactions between arsenic metabolic gene polymorphisms and arsenic exposure in relation to bladder cancer risk. Toenail arsenic concentrations were used to classify subjects into low and high exposure groups. Single nucleotide polymorphisms (SNPs) in GSTP1, GSTO2, GSTZ1, AQP3, AS3MT and the deletion status of GSTM1 and GSTT1 were determined. We found evidence of genotype-arsenic interactions in the high exposure group; GSTP1 Ile105Val homozygous individuals had an odds ratio (OR) of 5.4 [95% confidence interval (CI): 1.5-20.2; P for interaction=0.03] and AQP3 Phe130Phe carriers had an OR=2.2 (95% CI: 0.8-6.1; P for interaction=0.10). Bladder cancer risk overall was associated with GSTO2 Asn142Asp (homozygous; OR=1.4; 95% CI: 1.0-1.9; P for trend=0.06) and GSTZ1 Glu32Lys (homozygous; OR=1.3; 95% CI: 0.9-1.8; P for trend=0.06). Our findings suggest that susceptibility to bladder cancer may relate to variation in genes involved in arsenic metabolism and oxidative stress response and potential gene-environment interactions requiring confirmation in other populations.

Patient perspectives on participation in the ENABLE II randomized controlled trial of a concurrent oncology palliative care intervention: Benefits and burdens:

Background: ENABLE (Educate, Nurture, Advise Before Life Ends) II was one of the first randomized controlled trials (RCTs) examining the effects of a concurrent oncology palliative care intervention on quality of life, mood, and symptom control for advanced cancer patients and their caregivers. However, little is known about how participants experience early palliative care and the benefits and burdens of participating in a palliative care clinical trial. Aim: To gain a deeper understanding of participants’ perspectives of the intervention and palliative care trial participation. Design: A qualitative descriptive study using thematic analysis to determine benefits and burdens of a new palliative care intervention and trial participation. Setting/participants: Of the 72 participants who were alive when the study commenced, 53 agreed to complete an in-depth, semi-structured interview regarding the ENABLE II intervention and clinical trial participation. Results: Participants’ perceptions of intervention benefits were represented by four themes: enhanced problem-solving skills, better coping, feeling empowered, and feeling supported or reassured. Three themes related to trial participation: helping future patients and contributing to science, gaining insight through completion of questionnaires, and trial/intervention aspects to improve. Conclusions: The benefits of the intervention and the positive aspects of trial participation outweighed trial “burdens”. This study raises additional important questions relevant to future trial design and intervention development: when should a palliative care intervention be initiated and what aspects of self-care and healthy living should be offered in addition to palliative content for advanced cancer patients when they are feeling well?

Cutaneous alpha, beta and gamma human papillomaviruses in relation to squamous cell carcinoma of the skin: A population-based study

Human papillomavirus (HPV) infection is common worldwide and, in immunodeficient populations, may contribute to the pathogenesis of keratinocyte cancers, particularly squamous cell carcinomas (SCC). However, their role in SCC in the general population is less clear. We conducted a comprehensive analysis to investigate the independent effects of seropositivity for cutaneous alpha, beta and gamma HPV types on risk of SCC, and a meta‐analysis of the available literature. In a population‐based case‐control study from New Hampshire, USA (n = 1,408), histologically confirmed SCC cases and controls were tested for L1 antibodies to alpha, beta and gamma cutaneous HPV types 2–5, 7–10, 15, 17, 20, 23, 24, 27b, 36, 38, 48–50, 57, 65, 75–77, 88, 92, 95, 96, 101, 103 and 107 using multiplex serology. An increasing risk of SCC with number of beta HPVs to which an individual tested positive was observed even among those seronegative for gamma types (p for trend = 0.016) with an odds ratio of 1.95 (95% confidence interval (CI) = 1.07–3.56) for four or more beta types positive. In a meta‐analysis of six case‐control studies, increased SCC risks in relation to beta HPV seropositivity were found across studies (meta odds ratio = 1.45, CI = 1.27–1.66). While the prevalence of gamma HPVs assayed was somewhat higher among SCC cases than controls, the association was only weakly evident among those seronegative for beta HPVs. Overall, the association between cutaneous HPVs and skin cancers appears to be specific to SCC and to genus beta HPVs in a general US population.

Receptivity to television fast-food restaurant marketing and obesity among U.S. youth.

BACKGROUND Advertisement of fast food on TV may contribute to youth obesity. PURPOSE The goal of the study was to use cued recall to determine whether TV fast-food advertising is associated with youth obesity. METHODS A national sample of 2541 U.S. youth, aged 15-23 years, were surveyed in 2010-2011; data were analyzed in 2012. Respondents viewed a random subset of 20 advertisement frames (with brand names removed) selected from national TV fast-food restaurant advertisements (n=535) aired in the previous year. Respondents were asked if they had seen the advertisement, if they liked it, and if they could name the brand. A TV fast-food advertising receptivity score (a measure of exposure and response) was assigned; a 1-point increase was equivalent to affirmative responses to all three queries for two separate advertisements. Adjusted odds of obesity (based on self-reported height and weight), given higher TV fast-food advertising receptivity, are reported. RESULTS The prevalence of overweight and obesity, weighted to the U.S. population, was 20% and 16%, respectively. Obesity, sugar-sweetened beverage consumption, fast-food restaurant visit frequency, weekday TV time, and TV alcohol advertising receptivity were associated with higher TV fast-food advertising receptivity (median=3.3 [interquartile range: 2.2-4.2]). Only household income, TV time, and TV fast-food advertising receptivity retained multivariate associations with obesity. For every 1-point increase in TV fast-food advertising receptivity score, the odds of obesity increased by 19% (OR=1.19, 95% CI=1.01, 1.40). There was no association between receptivity to televised alcohol advertisements or fast-food restaurant visit frequency and obesity. CONCLUSIONS Using a cued-recall assessment, TV fast-food advertising receptivity was found to be associated with youth obesity.

Cued Recall of Alcohol Advertising on Television and Underage Drinking Behavior

IMPORTANCE Alcohol is the most common drug among youth and a major contributor to morbidity and mortality worldwide. Billions of dollars are spent annually marketing alcohol. OBJECTIVE To examine the reach of television alcohol advertising and its effect on drinking among underage youth. DESIGN, SETTING, AND PARTICIPANTS Longitudinal telephone- and web-based surveys conducted in 2011 and 2013 involving 2541 US adolescents 15 to 23 years of age at baseline, with 1596 of these adolescents completing the follow-up survey. Cued recall of television advertising images for top beer and distilled spirits brands that aired nationally in 2010-2011 (n = 351). Images were digitally edited to remove branding, and the respondents were queried about 20 randomly selected images. An alcohol advertising receptivity score was derived (1 point each for having seen the ad and for liking it, and 2 points for correct brand identification). Fast-food ads that aired nationally in 2010-2011 (n = 535) were similarly queried to evaluate message specificity. MAIN OUTCOMES AND MEASURES Among the underage youth at baseline, we determined (1) the onset of drinking among those who never drank, (2) the onset of binge drinking among those who were never binge drinkers, and (3) the onset of hazardous drinking among those with an Alcohol Use Disorders Identification Test consumption subscore of less than 4. Multivariate regressions were used to predict each outcome, controlling for covariates (demographics, drinking among friends and parents, and sensation seeking), weighting to the US population, and using multiple imputation to address loss to follow-up. RESULTS Underage participants were only slightly less likely than participants of legal drinking age to have seen alcohol ads (the mean percentage of ads seen were 23.4%, 22.7%, and 25.6%, respectively, for youth 15-17, 18-20, and 21-23 years of age; P < .005). The transition to binge and hazardous drinking occurred for 29% and 18% of youth 15 to 17 years of age and for 29% and 19% of youth 18 to 20 years years of age, respectively. Among underage participants, the alcohol advertising receptivity score independently predicted the onset of drinking (adjusted odds ratio [AOR], 1.69 [95% CI, 1.17-2.44]), the onset of binge drinking (AOR, 1.38 [95% CI, 1.08-1.77]), and the onset of hazardous drinking (AOR, 1.49 [95% CI, 1.19-1.86]). Fast-food advertising receptivity was not associated with any drinking outcome. CONCLUSIONS AND RELEVANCE Receptivity to television alcohol advertising predicted the transition to multiple drinking outcomes. The findings are consistent with the idea that marketing self-regulation has failed to keep television alcohol advertising from reaching large numbers of underage persons and affecting their drinking patterns.