Wonders & Worries: evaluation of a child centered psychosocial intervention for families who have a parent/primary caregiver with cancer

Abstract

Objective

Scant evidence exists to guide interventions for children who have a parent with cancer. This study evaluated the outcomes of a community based psychosocial intervention targeted to children dealing with parental or primary caregiver cancer. This curriculum provided an age-appropriate understanding of the illness, facilitated the expression of feelings, identified individual coping skills to help ease feelings related to parent's cancer, and enhanced the family's ability to communicate about the disease.

Methods

Families whose children participated in the six-week curriculum-based intervention completed a questionnaire that included demographic information, a five-item assessment of changes in parenting abilities, and a nine-item assessment of changes in children's behavioral issues. The prevalence of each reported item was determined through a secondary analyses of cross-sectional data derived from a multi-year sample of these survey results.

Results

A sample of 156 families responded to the survey between 2009 and 2014. A majority of families described improvement in all five areas of parenting abilities assessed including communication skills and confidence in parenting. Amelioration of multiple children's issues was reported including improved communication skills (87%), reduced anxiety (84%), increased feeling of security at home (90%), and improved school performance (73%).

Conclusions

The results reported here suggest that this child centered psychosocial intervention promoted positive adaptation by actively supporting families and children while a parent/primary caregiver coped with a cancer diagnosis. Future research is planned utilizing a randomized controlled study design to formally evaluate the effectiveness and preventative impact of this manualized six-week curriculum. Copyright © 2016 John Wiley & Sons, Ltd.

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Multimodal cancer care in poor prognosis cancers: Resection drives long-term outcomes

Background and Objectives

Hospitals with high complex oncologic surgical volume have improved short-term outcomes. However, for long-term outcomes, the influence of other therapies must be considered. We compared effects of resection with other therapies on long-term outcomes across U.S. hospitals.

Methods

We examined claims in the Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset for patients with esophageal (EC) and pancreatic (PC) cancers between 2005–2009, with follow-up through 2011, performing multivariable Cox proportional hazards analyses. We stratified hospitals by volume and compared rates of treatments in the context of survival.

Results

We studied 905 EC and 3,293 PC patients at 138 and 375 hospitals, respectively. For EC, resection rates were significantly higher (32.9% vs. 9.5%, P < 0.001) in the highest versus lowest volume hospitals. Adjusted survival was also statistically significantly better (48.5% vs. 43.1%, P < 0.001). For PC, resection rates were also statistically significantly higher (30.1% vs. 12.0%, P < 0.001) with higher adjusted survival (21.5% vs. 19.9%, P = 0.01). We did not find variation in rates of other cancer treatments across hospitals.

Conclusions

A significant association exists between long-term survival and rates of cancer-directed surgery across hospitals, without variation in rates of other therapies. Access to resection appears to be key to reducing variation in long-term survival. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

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Issue Information – Information for Authors

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Issue Information – Table of Contents

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Issue Information – UICC

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Quality of life in patients with metastatic breast cancer treated with metronomic chemotherapy

Future Oncology Ahead of Print.


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Nodal metastases in thyroid cancer: prognostic implications and management

Future Oncology Ahead of Print.


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A PDGF-E2F-USP1-ID2 axis is required for proneural glioma

Glioblastoma (GBM) is the most aggressive primary brain tumor and responds poorly to currently available therapies. Transcriptomic characterization of GBM has identified distinct molecular subtypes of GBM. Gain-of-function alterations leading to enhanced platelet-derived growth factor (PDGF) signaling are commonly observed in the proneural subtype of GBM and can drive gliomagenesis. However, little is known about the downstream effectors of PDGF signaling in GBM. Using a mouse model of proneural glioma and comparative transcriptomics, we determined that PDGF signaling upregulated ubiquitin specific peptidase 1 (Usp1) to promote the survival of murine proneural glioma cells. Mechanistically, we found that PDGF signaling regulated the expression of the E2F transcription factors, which directly bound to and activated Usp1. Furthermore, PDGF-mediated expression of USP1 led to the stabilization of Inhibitor of DNA-binding 2 (ID2), which we found to be required for glioma cell survival. Genetic ablation of Id2 delayed tumor-induced mortality, and pharmacological inhibition of USP1, resulting in decreased ID2 levels, also delayed tumorigenesis in mice. Notably, decreased USP1 expression was associated with prolonged survival in patients with proneural GBM, but not with other subtypes of GBM. Collectively, our findings describe a signaling cascade downstream of PDGF that sustains proneural GBM cells, and suggest that inhibition of the PDGF-E2F-USP1-ID2 axis could serve as a therapeutic strategy for proneural GBM featuring increased PDGF signaling.

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C GAMP, Where Is Thy STING?

Endoplasmic reticulum (ER) stress responses through the IRE-1/XBP-1 pathway are required for the function of STING (TMEM173), an ER-resident transmembrane protein critical for cytoplasmic DNA sensing, IFN production, and cancer control. Here we show that the IRE-1/XBP-1 pathway functions downstream of STING and that STING agonists selectively trigger mitochondria-mediated apoptosis in normal and malignant B cells. Upon stimulation, STING was degraded less efficiently in B cells, implying that prolonged activation of STING can lead to apoptosis. Transient activation of the IRE-1/XBP-1 pathway partially protected agonist-stimulated malignant B cells from undergoing apoptosis. In Eμ-TCL1 mice with chronic lymphocytic leukemia, injection of the STING agonist 3′3′-cGAMP induced apoptosis and tumor regression. Similarly efficacious effects were elicited by 3′3′-cGAMP injection in syngeneic or immunodeficient mice grafted with multiple myeloma. Thus, in addition to their established ability to boost antitumoral immune responses, STING agonists can also directly eradicate malignant B cells. Cancer Res; 1–16. ©2016 AACR.

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Quality of life in patients with metastatic breast cancer treated with metronomic chemotherapy

Future Oncology Ahead of Print.


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Nodal metastases in thyroid cancer: prognostic implications and management

Future Oncology Ahead of Print.


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Acute renal allograft rejection after immune checkpoint inhibitor therapy for metastatic melanoma

This case of acute renal allograft rejection following treatment with immune checkpoint inhibitor therapy for metastatic melanoma highlights specific concerns regarding use of anti-PD-1 agents such as nivolumab. Given rates of adverse events are generally much lower with anti-PD-1 antibodies compared with anti-CTLA-4 antibodies, there is potential for error in the generalisation of perceived safety.

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Safety of the PD-1 antibody Pembrolizumab in Patients with High Grade Adverse Events under Ipilimumab Treatment

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Insertion of central venous catheters (CVCs): any changes in the past ten years?

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Minimal residual disease-based effect and long-term outcome of first-line dasatinib combined with chemotherapy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia

First-line incorporation of dasatinib into chemotherapy is effective for achieving a good quality molecular response and durable disease-free survival in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia. Quantitatively monitoring minimal residual disease kinetics is important to identify a subgroup of patients at high risk of treatment failure.

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Ocular Toxicities of MEK inhibitors and other targeted therapies

Novel agents that target different cellular pathways have been related to a wide spectrum of ophthalmologic adverse events. We discuss ophthalmologic toxicities associated with molecular targeted therapies, with particular focus on MEK retinopathy, including its nomenclature, incidence, symptoms and management.

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Fueling Basic Discovery: NCI’s Cooperative Human Tissue Network

Human biospecimens, as any cancer researcher will tell you, are a foundational resource in basic and clinical cancer research. And with the launch last year of President Obama's Precision Medicine Initiative and his announcement in January about the launch of the National Cancer Moonshot Initiative, NCI-supported biospecimen programs have taken on renewed importance.

Quality biospecimens are critical to achieving the type of progress envisioned by both of these initiatives, whether it's for conducting genomic analyses that will allow us to better understand cancer progression, discovering and validating biomarkers that can predict prognosis or response to therapy, or identifying new targets for therapy.

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A Conversation with Elizabeth Jaffee

Editor's Note: Dr. Elizabeth Jaffee is Deputy Director of the Sidney Kimmel Comprehensive Cancer Center, Co-Director of the Cancer Immunology Program, and Professor of Oncology at John Hopkins Medicine. Recently RAS Central editors spoke with Dr. Jaffee about her career developing immunotherapies for cancer.

How did you first get interested in immunotherapy? When I was in college in 1977 to 1981, Milstein and Kohler's hybridoma technology had just come out, I think it was in 1976, and I was really taken aback by it. I was a biochem major but I was very interested in virology and the immune system. Then I heard a lecture by David Baltimore and I really got excited and I did research using hybridoma technology as an undergrad to try to understand, believe it or not, heavy chain switching, which of course didn't really get understood until molecular technologies were improved. But it was a good project in the context of the time, and I kept thinking and I read some of the history of cancer. I had read about patients with infections developing immune response to cancer, the whole Coley story. Then I took a year after completing my internal medicine residency to do a year of NIH funded research, basically a year in which you do a small research project and you take some didactic classes. I worked with a cancer immunologist at the University of Pittsburgh, John Kirkwood, and that's when T cells were becoming understood better, because IL2 had been cloned and you could now isolate and grow T cells. The field was starting to boom, and then I came to Hopkins with the concept that that's what I was going to do. I got involved in these genetically modified vaccines which basically looked at all different cytokines to see what would cause the cascade of events that could induce an antitumor response.

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Impact of high self-perceived burden to others with preferences for end-of-life care and its determinants for terminally ill cancer patients: a prospective cohort study

Abstract

Background/Objective

Self-perceived burden to others (SPB) is a major concern of terminally ill cancer patients and is frequently factored into end-of-life (EOL) care decision-making. However, changes in and determinants of SPB and its longitudinal impact on preferences for EOL care over the dying process have not been investigated. Our study was aimed at filling this gap in knowledge.

Methods

A convenience sample of 325 cancer patients was followed until death. High SPB was identified as scoring >20 on the Self-perceived Burden Scale. Preferences for EOL care included EOL-care goals, life-sustaining treatments, and hospice care. Factors potentially precipitating/minimizing patients' high SPB included demographics, disease characteristics and burden, and social support and were examined by multivariate logistic regression modeling with the generalized estimating equation.

Results

Prevalence of high SPB increased as death approached (51.78%, 58.26%, 62.66%, and 65.38% for 181–365, 91–180, 31–90, and 1–30 days before death, respectively). High SPB was precipitated by women, younger age, having inadequate financial resources, without religious affiliation, and suffering from severe symptom distress and heavy functional dependence but was independent of time proximity to patient death, disease characteristics, and social support. Furthermore, high SPB was not associated with EOL-care preferences, whether aggressive life-sustaining treatments or hospice care.

Conclusions

High SPB was prevalent among terminally ill cancer patients but independent of preferences for EOL care. Cancer patients' SPB may be lessened by adequate symptom relief to facilitate functional independence. These strategies to ease SPB may improve the quality of death and dying. Copyright © 2016 John Wiley & Sons, Ltd.

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Characterization of functionally active gene fusions in human papillomavirus related oropharyngeal squamous cell carcinoma

ABSTRACT

The Cancer Genome Atlas (TCGA) sequencing analysis of head and neck squamous cell carcinoma (HNSCC) recently reported on gene fusions, however few human papillomavirus (HPV) positive samples were included, and the functional relevance of identified fusions was not explored. We therefore performed an independent analysis of gene fusions in HPV-positive oropharyngeal SCC (OPSCC). RNA sequencing was performed on 47 HPV-positive OPSCC primary tumors and 25 normal mucosal samples from cancer unaffected controls on an Illumina TruSeq platform. MapSplice2 was used for alignment and identification of fusion candidates. Putative fusions with less than five spanning reads, detected in normal tissues, or that mapped to the same gene were filtered out. Selected fusions were validated by RT-PCR and Sanger sequencing. Within 47 HPV-positive OPSCC tumors, 282 gene fusions were identified. Most fusions (85.1%) occurred in a single tumor, and the remaining fusions recurred in 2-16 tumors. Gene fusions were associated with significant up regulation of 16 genes (including EGFR and ERBB4) and down regulation of four genes (PTPRT, ZNF750, DLG2, SLCO5A1). Expression of these genes followed similar patterns of up regulation and down regulation in tumors without these fusions compared to normal tissue. Five of six gene fusions selected for validation were confirmed through RT-PCR and sequencing. This integrative analysis provides a method of prioritizing functionally relevant gene fusions that may be expanded to other tumor types. These results demonstrate that gene fusions may be one mechanism by which functionally relevant genes are altered in HPV-positive OPSCC. This article is protected by copyright. All rights reserved.

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XPG Promotes Homologous Recombination Repair and Genomic Stability [DNA Repair]

The nucleotide excision repair enzyme XPG has a noncatalytic role in HRR and genomic stability.

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FDA Approves Eribulin for Advanced Liposarcoma [News in Brief]

The FDA approved eribulin for treatment of advanced liposarcoma based on data from a phase III study showing that it increased overall survival by about 7 months compared with a commonly used chemotherapy, dacarbazine.

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AML Fusions Require Epigenetic Modifiers to Transform Cells [Epigenetics]

PRMT1 and KDM4C are essential for transformation of AML cells harboring MLL or MOZ–TIF2 fusions.

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PI3K Promotes Glycolysis through Release of Cytoskeletal Aldolase [Metabolism]

PI3K induces cytoskeletal reorganization, leading to release and activation of actin-bound aldolase.

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Atezolizumab Shows Antitumor Activity in Renal Cell Carcinoma [Immunotherapy]

The anti–PD-L1 antibody atezolizumab is safe and active in patients with metastatic RCC.

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Personalized Medicine in Melanoma [Research Articles]

Targeted therapies and immunotherapies have transformed melanoma care, extending median survival from ~9 to over 25 months, but nevertheless most patients still die of their disease. The aim of precision medicine is to tailor care for individual patients and improve outcomes. To this end, we developed protocols to facilitate individualized treatment decisions for patients with advanced melanoma, analyzing 364 samples from 214 patients. Whole exome sequencing (WES) and targeted sequencing of circulating tumor DNA (ctDNA) allowed us to monitor responses to therapy and to identify and then follow mechanisms of resistance. WES of tumors revealed potential hypothesis-driven therapeutic strategies for BRAF wild-type and inhibitor-resistant BRAF-mutant tumors, which were then validated in patient-derived xenografts (PDX). We also developed circulating tumor cell–derived xenografts (CDX) as an alternative to PDXs when tumors were inaccessible or difficult to biopsy. Thus, we describe a powerful technology platform for precision medicine in patients with melanoma.

Significance: Although recent developments have revolutionized melanoma care, most patients still die of their disease. To improve melanoma outcomes further, we developed a powerful precision medicine platform to monitor patient responses and to identify and validate hypothesis-driven therapies for patients who do not respond, or who develop resistance to current treatments. Cancer Discov; 6(3); 286–99. ©2015 AACR.

This article is highlighted in the In This Issue feature, p. 217

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Epigenetic Changes in B-Cell Maturation Underlie Diverse CLL Phenotypes [Leukemia]

DNA methylation analysis indicates that CLL arises from a continuum of B-cell development states.

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FAN1 Acts as a Tumor Suppressor Preventing Genomic Instability [Genomic Instability]

The FAN1–FANCD2 complex prevents chromosomal instability and tumorigenesis independent of ICL repair.

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Super-Enhancers Distinguish Medulloblastoma Subtypes [Medulloblastoma]

Super-enhancer–regulated transcription factors give insight into cell of origin of medulloblastoma subtypes.

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Tumors Resistant to EGFR Inhibitors Can Arise via Different Mechanisms [Drug Resistance]

Drug-resistant EGFR^T790M mutations can preexist or be acquired de novo during drug treatment.

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Medulloblastoma Subtypes Are Distinguished by MYC-MIZ1 Interaction [Medulloblastoma]

MYC–MIZ1-mediated repression of target genes is essential in group 3 (G3) medulloblastoma.

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B Cells Promote Pancreatic Tumorigenesis [In the Spotlight]

Summary: Three recent studies, approaching the question from different angles and using different and/or overlapping models, provide compelling evidence for the involvement of tumor-infiltrating B cells in the initiation and progression of pancreatic ductal adenocarcinoma. These studies highlight the need for a better understanding of pancreatic tumor–immune system interactions and the immunologic mechanisms that promote or inhibit tumorigenesis, paving the way for better treatment strategies. Cancer Discov; 6(3); 230–2. ©2016 AACR.

See related article by Pylayeva-Gupta et al., p. 247.

See related article by Lee et al., p. 256.

See related article by Gunderson et al., p. 270.

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Phosphorylated ABRAXAS Promotes BRCA1 Accumulation at DNA Damage Sites [Structural Biology]

IR-induced phosphorylation of ABRAXAS promotes BRCA1 dimerization and accumulation at DSBs.

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HIF1{alpha} and B Cells in Pancreatic Neoplasia [Research Articles]

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths worldwide, with an exceedingly low 5-year survival rate. PDAC tumors are characterized by an extensive desmoplastic stromal response and hypovascularity, suggesting that tumor hypoxia could regulate PDAC initiation and/or progression. Using a well-defined, autochthonous Kras^G12D-driven murine model, as well as human tumors, we demonstrate that hypoxia and stabilization of hypoxia-inducible factor 1α (HIF1α), a principal mediator of hypoxic adaptation, emerge early during preinvasive stages of PDAC. Surprisingly, pancreas-specific Hif1a deletion drastically accelerated Kras^G12D-driven pancreatic neoplasia and was accompanied by significant increases in intrapancreatic B lymphocytes, featuring prominent influx of a rare "B1b" B-cell subtype. Finally, treatment of HIF1α-deficient mice with B cell–depleting αCD20 monoclonal antibodies inhibited progression of pancreatic intraepithelial neoplasia (PanIN). Our data reveal a previously unrecognized role for B cells in promoting pancreatic tumorigenesis and implicate HIF1α as a critical regulator of PDAC development.

Significance: We show here that pancreas-specific Hif1a deletion promotes PDAC initiation, coincident with increased intrapancreatic accumulation of B cells, and that B-cell depletion suppresses pancreatic tumorigenesis. We therefore demonstrate a protective role for HIF1α in pancreatic cancer initiation and uncover a previously unrecognized function of B cells. Cancer Discov; 6(3); 256–69. ©2015 AACR.

See related commentary by Roghanian et al., p. 230.

See related article by Pylayeva-Gupta et al., p. 247.

See related article by Gunderson et al., p. 270.

This article is highlighted in the In This Issue feature, p. 217

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A phase 1/2a study to test the safety and immunogenicity of a p16INK4a peptide vaccine in patients with advanced human papillomavirus-associated cancers

BACKGROUND

The cyclin-dependent kinase inhibitor p16^INK4a is strongly and consistently overexpressed in all human papillomavirus (HPV)-associated cancers. Therefore, the authors hypothesized that p16^INK4a may be a vaccine target antigen for HPV-associated cancers. To test this hypothesis, the authors performed a phase 1/2a first-in-human trial to evaluate the safety and immunogenicity of a p16^INK4a-based peptide vaccine.

METHODS

A total of 26 patients with different, advanced, p16^INK4a-overexpressing, HPV DNA-positive cancers were included after the completion of standard treatment. According to protocol, 12 subcutaneous injections of a p16^INK4 peptide (P16_37-63) mixed in a water-in-oil emulsion with immunoadjuvant activity (Montanide ISA-51 VG) were administered over a 6-month period.

RESULTS

A total of 20 patients received at least 4 injections and were evaluable for immune responses against P16_37-63. Clusters of differentiation (CD) 4 T cells were detected in 14 of 20 patients (3 of whom had preexisting CD4 T cells before vaccination), CD8 T cells were detected in 5 of 20 patients, and antibodies were detected in 14 of 20 patients (1 of whom had preexisting antibodies). No suspected unexpected serious adverse reaction or serious adverse drug reaction was documented. All reported serious adverse events were expected and not considered to be related to study therapy. None of the patients discontinued trial participation due to unacceptable toxicities and no dose-limiting toxicities occurred. Tumor response could be assessed in 14 patients. Of these, 9 patients (64%) had stable disease as their best overall response and 5 patients (36%) developed progressive disease.

CONCLUSIONS

Vaccination with the p16^INK4a-derived peptide P16_37-63 appears to induce cellular and humoral immune responses and does not cause severe toxicities. The results of the current study pave the way for the further clinical development of p16^INK4a-based cancer immunotherapeutics. Cancer 2016. © 2016 American Cancer Society.

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Solutions that enable ablative radiotherapy for large liver tumors: Fractionated dose painting, simultaneous integrated protection, motion management, and computed tomography image guidance

The emergence and success of stereotactic body radiation therapy (SBRT) for the treatment of lung cancer have led to its rapid adoption for liver cancers. SBRT can achieve excellent results for small liver tumors. However, the vast majority of physicians interpret SBRT as meaning doses of radiation (range, 4-20 Gray [Gy]) that may not be ablative but are delivered within about 1 week (ie, in 3-6 fractions). Adherence to this approach has limited the effectiveness of SBRT for large liver tumors (>7 cm) because of the need to reduce doses to meet organ constraints. The prognosis for patients who present with large liver tumors is poor, with a median survival ≤12 months, and most of these patients die from tumor-related liver failure. Herein, the authors present a comprehensive solution to achieve ablative SBRT doses for patients with large liver tumors by using a combination of classic, modern, and novel concepts of radiotherapy: fractionation, dose painting, motion management, image guidance, and simultaneous integrated protection. The authors discuss these concepts in the context of large, inoperable liver tumors and review how this approach can substantially prolong survival for patients, most of whom otherwise have a very poor prognosis and few effective treatment options. Cancer 2016. © 2016 American Cancer Society.

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Therapeutic radiation and the potential risk of second malignancies

Radiation has long been associated with carcinogenesis. Nevertheless, it is an important part of multimodality therapy for many malignancies. It is critical to assess the risk of secondary malignant neoplasms (SMNs) after radiation treatment. The authors reviewed the literature with a focus on radiation and associated SMNs for primary hematologic, breast, gynecologic, and pediatric tumors. Radiation appeared to increase the risk of SMN in all of these; however, this risk was found to be associated with age, hormonal influences, chemotherapy use, environmental influences, genetic predisposition, infection, and immunosuppression. The risk also appears to be altered with modern radiotherapy techniques. Practitioners of all specialties who treat cancer survivors in follow-up should be aware of this potential risk. Cancer 2016. © 2016 American Cancer Society.

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Rising population of survivors of oral squamous cell cancer in the United States

BACKGROUND

The incidence of oropharyngeal cancer (OPC) and a subset of oral cavity cancer (OCC) is increasing in the United States. To the authors' knowledge, the presumed growing prevalence of survivors of OPC and OCC has not been investigated to date.

METHODS

Retrospective analysis of Surveillance, Epidemiology, and End Results data (1975-2012) estimated changes in incidence, 5-year cause-specific survival, and prevalence for OPC and OCC. Changes in incidence, cause-specific survival and prevalence were estimated by linear regression and expressed as the percentage change (B). Differences in incidence trends over time were determined by joinpoint analysis.

RESULTS

The incidence of OPC increased by 62.6% from 1975 through 2012. Notable increases in OPC incidence were observed among men, white individuals, and those of younger ages. The 5-year survival for OPC increased significantly for all sexes, races, and individuals aged >30 years, with white individuals and males experiencing the largest increase in survival. By contrast, the incidence of OCC declined by 22.3% during the same time period. OCC incidence decreased across all groups but increased among individuals aged 30 to 39 years. Significant increases in survival were observed for OCC, except for those who were female, black, and aged <40 years. The prevalence of survivors of OPC increased from 2000 to 2012 (B, 115.1 per 100,000 individuals per year; P<.0001), whereas the prevalence of survivors of OCC significantly decreased (B, −15.8 per 100,000 individuals per year; P<.0001).

CONCLUSIONS

The prevalence of survivors of OPC is increasing, whereas the prevalence of survivors of OCC is declining. These data portend significant implications for long-term care planning for survivors of OPC and OCC. Cancer 2016. © 2016 American Cancer Society.

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Cervical Osteoradionecrosis following Accelerated Fractionation Radiotherapy for Laryngeal Cancer

Publication date: Available online 7 March 2016
Source:Practical Radiation Oncology
Author(s): Mark Zaki, Yiqing Xu, Michael Joiner, Harold Kim, Michael Dominello




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Genetic variants involved in oxidative stress, base excision repair, DNA methylation, and folate metabolism pathways influence myeloid neoplasias susceptibility and prognosis

Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) share common features: elevated oxidative stress, DNA repair deficiency, and aberrant DNA methylation. We performed a hospital-based case-control study to evaluate the association in variants of genes involved in oxidative stress, folate metabolism, DNA repair, and DNA methylation with susceptibility and prognosis of these malignancies. To that end, 16 SNPs (one per gene: CAT, CYBA, DNMT1, DNMT3A, DNMT3B, GPX1, KEAP1, MPO, MTRR, NEIL1, NFE2F2, OGG1, SLC19A1, SOD1, SOD2, and XRCC1) were genotyped in 191 patients (101 MDS and 90 AML) and 261 controls. We also measured oxidative stress (reactive oxygen species/total antioxidant status ratio), DNA damage (8-hydroxy-2′-deoxyguanosine), and DNA methylation (5-methylcytosine) in 50 subjects (40 MDS and 10 controls). Results showed that five genes (GPX1, NEIL1, NFE2L2, OGG1, and SOD2) were associated with MDS, two (DNMT3B and SLC19A1) with AML, and two (CYBA and DNMT1) with both diseases. We observed a correlation of CYBA TT, GPX1 TT, and SOD2 CC genotypes with increased oxidative stress levels, as well as NEIL1 TT and OGG1 GG genotypes with higher DNA damage. The 5-methylcytosine levels were negatively associated with DNMT1 CC, DNMT3A CC, and MTRR AA genotypes, and positively with DNMT3B CC genotype. Furthermore, DNMT3A, MTRR, NEIL1, and OGG1 variants modulated AML transformation in MDS patients. Additionally, DNMT3A, OGG1, GPX1, and KEAP1 variants influenced survival of MDS and AML patients. Altogether, data suggest that genetic variability influence predisposition and prognosis of MDS and AML patients, as well AML transformation rate in MDS patients. © 2016 Wiley Periodicals, Inc.

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Molecular evolution of colorectal cancer: from multistep carcinogenesis to the big bang

Abstract

Colorectal cancer is characterized by exquisite genomic instability either in the form of microsatellite instability or chromosomal instability. Microsatellite instability is the result of mutation of mismatch repair genes or their silencing through promoter methylation as a consequence of the CpG island methylator phenotype. The molecular causes of chromosomal instability are less well characterized. Genomic instability and field cancerization lead to a high degree of intratumoral heterogeneity and determine the formation of cancer stem cells and epithelial–mesenchymal transition mediated by the TGF-β and APC pathways. Recent analyses using integrated genomics reveal different phases of colorectal cancer evolution. An initial phase of genomic instability that yields many clones with different mutations (big bang) is followed by an important, previously not detected phase of cancer evolution that consists in the stabilization of several clones and a relatively flat outgrowth. The big bang model can best explain the coexistence of several stable clones and is compatible with the fact that the analysis of the bulk of the primary tumor yields prognostic information.

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Epigenetic suppression of neprilysin regulates breast cancer invasion

Epigenetic suppression of neprilysin regulates breast cancer invasion

Oncogenesis 5, e207 (March 2016). doi:10.1038/oncsis.2016.16

Authors: H M Stephen, R J Khoury, P R Majmudar, T Blaylock, K Hawkins, M S Salama, M D Scott, B Cosminsky, N K Utreja, J Britt & R E Conway

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Death receptor 6 (DR6) is required for mouse B16 tumor angiogenesis via the NF-κB, P38 MAPK and STAT3 pathways

Death receptor 6 (DR6) is required for mouse B16 tumor angiogenesis via the NF-κB, P38 MAPK and STAT3 pathways

Oncogenesis 5, e206 (March 2016). doi:10.1038/oncsis.2016.9

Authors: X Yang, B Shi, L Li, Z Xu, Y Ge, J Shi, Y Liu & D Zheng

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For avid glucose tumors, the SUV peak is the most reliable parameter for [ 18 F]FDG-PET/CT quantification, regardless of acquisition time

Abstract

Background

This study is an assessment of the impact of acquisition times on SUV with [¹⁸F]FDG-PET/CT on healthy livers (reference organ with stable uptake over time) and on tumors.

Methods

One hundred six [¹⁸F]FDG-PET/CT were acquired in list mode over a single-bed position (livers (n = 48) or on tumors (n = 58)). Six independent datasets of different durations were reconstructed (from 1.5 to 10 min). SUV_max (hottest voxel), SUV_peak (maximum average SUV within a 1-cm³ spherical volume), and SUV_average were measured within a 3-cm-diameter volume of interest (VOI) in the right lobe of the liver. For [¹⁸F]FDG avid tumors (SUV_max ≥ 5), the SUV_max, SUV_peak, and SUV_41% (isocontour threshold method) were computed.

Results

For tumors, SUV_peak values did not vary with acquisition time. SUV_max displayed significant differences between 1.5- and 5–10-min reconstruction times. SUV_41% was the most time-dependent parameter. For the liver, the SUV_average was the sole parameter that did not vary over time.

Conclusions

For [¹⁸F]FDG avid tumors, with short acquisition times, i.e., with new generations of PET systems, the SUV_peak may be more robust than the SUV_max. The SUV_average over a 3-cm-diameter VOI in the right lobe of the liver appears to be a good method for a robust and reproducible assessment of the hepatic metabolism.

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The conglomeration of diagnostic, prognostic and therapeutic potential of serum miR-199a and its association with clinicopathological features in epithelial ovarian cancer

Abstract

Epithelial ovarian cancer (EOC) is the most lethal cause of morbidity and mortality worldwide. miRNA deregulation evinces a remarkable role in ovarian cancer tumorigenesis. miRNA-199a (miR-199a) is known to be involved in cancer development and progression. Although miR-199a has been studied in various cell types, its correlation with clinicopathological features in EOC has not been documented. In this study, we identified the clinicopathological hallmarks which might be perturbed due to the downregulation of serum miR-199a in EOC. Seventy serum samples from histopathologically confirmed EOC patients and 70 controls were collected. Total RNA from serum was isolated by Trizol method, polyadenylated and reverse transcribed into cDNA. Expression level of miR-199a was detected by using miRNA qRT-PCR. Relative expression was determined with matched controls using U6 snRNA as reference. Level of miR-199a expression was compared with distinct clinicopathological features. Expression of miR-199a was found to be significantly downregulated in comparison with matched normal controls. The expression level of miR-199a was found to be significantly associated with tumor stage, lymph node metastasis, and distal metastasis. Receiver operating characteristic (ROC) curve for diagnostic potential yielded significant area under the curve (AUC) with a considerable sensitivity and specificity. ROC curves for prognosis yielded significant AUCs for histological grade, distal metastasis, lymph node status, and survival. Our findings suggest that miR-199a downregulation might be a potential indicator for disease progression promoting the aggressive tumor progression and be identified as a diagnostic marker to predict the prognosis and survival in EOC patients.

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Antigen-specific T cell response from dendritic cell vaccination using side population cell-associated antigens targets hepatocellular carcinoma

Abstract

Dendritic cell (DC) vaccination targeting cancer stem cells is an effective way to suppress tumor progression and reduce the metastasis and recurrence. In the present study, we explored the suitability of side population (SP) cells as source of antigens for DC vaccination against hepatocellular carcinoma (HCC) in a mouse model. In this study, we identified the "stem-like" characteristics of SP cells in the MHCC97 and Hepa 1-6 HCC cell lines. We found that SP cells express high levels of tumor-associated antigens and MHC class I molecules. Although loading with cell lysates did not change the characteristics of DCs, SP cell lysate-pulsed DCs induced antigen-specific T cell responses, including T cell proliferation and increased IFN-γ production by stimulated CD8⁺ T cells. We investigated the cytotoxicity of T cells stimulated by SP cell lysate-pulsed DCs in nude mice co-injected with MHCC97 cells. To mimic the in vivo environment, we also confirmed the result in mouse HCC cell line Hepa 1-6 induced tumor-bearing C57/BL6 immune competent mice, and we demonstrated that vaccination with DCs loaded with Hepa 1-6 SP cell lysates could induce a T cell response in vivo and suppress the tumor growth. Our results may have applications for anti-HCC immunotherapy by targeting the cancer stem cells and may provide new insight for cancer vaccines.

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The value of serum RASSF10 hypermethylation as a diagnostic and prognostic tool for gastric cancer

Abstract

The tumor-suppressing role of Ras-association domain family 10 (RASSF10) has been described in several types of cancers. Here, we evaluated the potential use of the hypermethylation status of the RASSF10 promoter in serum as a new diagnostic and prognostic tool in gastric cancer (GC). We used bisulfite sequencing polymerase chain reaction to examine RASSF10 methylation levels in serum and/or tumor samples from 82 GC, 45 chronic atrophic gastritis (CAG), and 50 healthy control patients. In the serum of GC patients, the median level of RASSF10 methylation was higher at 47.84 % than those in the serum of CAG and healthy control patients at 11.89 and 11.35 %, respectively. The median level of RASSF10 methylation in GC tumor tissue was similarly high at 62.70 %. Furthermore, RASSF10 methylation levels were highly correlated between paired serum and tumor samples from GC patients. We performed receiver-operating characteristic curve analyses to verify that serum RASSF10 methylation levels could effectively distinguish GC from control patients. Moreover, multivariate analyses showed that high serum RASSF10 methylation levels in GC patients were associated with large tumors, lymph node metastasis, and high carcinoembryonic antigen (CEA) levels. Survival analyses showed that GC patients with high serum RASSF10 methylation levels had shorter overall and disease-free survival after D2 lymphadenectomy than those with low levels. High serum RASSF10 methylation levels were also an independent predictor of tumor recurrence and GC patient survival. In conclusion, serum RASSF10 promoter methylation levels can serve as a valuable indicator for the diagnosis and prognosis of GC in the clinic.

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Perioperative circulating tumor cells in surgical patients with non-small cell lung cancer: does surgical manipulation dislodge cancer cells thus allowing them to pass into the peripheral blood?

Abstract

Purpose

We herein evaluated the status of circulating tumor cells (CTC) dislodged from the tumor during surgery in patients who underwent pulmonary resection for non-small cell lung cancer (NSCLC) to assess the clinical implications.

Methods

Tumor cells in the peripheral arterial blood before surgery (Before) and immediately after lung resection (After) and in the blood from the pulmonary vein of the resected lung were detected using a size selective method. The clinicopathological characteristics and the prognosis were then analyzed according to the CTC status: no tumor cells detected (N), single tumor cell or total number less than 4 cells (S), and existence of clustered cells (C).

Results

According to the CTC status, the patients were classified into the following three groups: Before-C and After-C, Group I (n = 6); Before-S or N and After-C, Group II (n = 9); and Before-S or N and After-S or N, Group III (n = 8). Group III showed a high rate of p-stage IA, smaller tumor size, lower CEA level, lower SUVmax level, and a higher relapse-free survival rate than the other groups.

Conclusions

CTCs were detected in patients after undergoing lung resection, some of which may have been dislodged by the surgical procedure. The presence of clustered CTCs after the operation indicated an unfavorable outcome.

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Human Papillomavirus (HPV) Vaccination Motivators, Barriers, and Brochure Preferences Among Parents in Multicultural Hawai‘i: a Qualitative Study

Abstract

The human papillomavirus (HPV) vaccine can prevent cervical and other cancers. Unfortunately, according to the National Immunization Survey—Teen 2014 data, completion of the HPV vaccine was only 38 % for 13- to 17-year-old girls and 31 % for 13- to17-year-old boys in the USA, and prevalence was similar in Hawai'i. Parents' acceptability of the HPV vaccine is critical for the vaccine uptake, and this can be increased by educational materials and interventions. However, HPV materials are not widely distributed in Hawai'i. The purpose of this qualitative study was to identify HPV vaccination barriers, motivators, and brochure preferences among parents of teens in multicultural Hawai'i. Twenty parents were interviewed in person or by telephone. Four major themes emerged: (1) the physician is critical in the decision to vaccinate, (2) parental perception of the child's sexual activity guides the timing of their willingness to vaccinate, (3) HPV health education materials should be provided and discussed by the physician, and (4) parents would prefer an educational brochure that features local faces and testimonials, includes an immunization chart, and addresses barriers to vaccination. These findings informed the development of HPV health education materials tailored to Asian Americans and Pacific Islanders in Hawai'i.

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Evolving Strategies for the Treatment of Chronic Lymphocytic Leukemia in the Upfront Setting

Abstract

Chronic lymphocytic leukemia (CLL) is a disease of marked clinical heterogeneity, and while some patients have a normal life expectancy, others develop rapidly progressive disease shortly after diagnosis. The current standard for upfront treatment of CLL is chemoimmunotherapy for younger fit patients, FCR (fludarabine, cyclophosphamide, and rituximab) being the prototype. For older patients, BR (bendamustine and rituximab) exhibits excellent activity with decreased toxicity. For the frailest patients, CD20 monoclonal antibodies with or without chlorambucil have proven to be efficacious. The novel oral kinase inhibitors ibrutinib and idelalisib are FDA-approved in the relapsed/refractory setting, and ibrutinib is approved upfront for those with del(17p). These drugs have produced long-term durable responses in the relapsed/refractory setting, and studies are underway using these as single agent upfront or in combination with both chemotherapy and monoclonal antibodies. Here, we review standard upfront therapies and new agents and combinations that are on the horizon for CLL.

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Management patterns of patients with cerebral metastases who underwent multiple stereotactic radiosurgeries

Abstract

With escalating focus on cost containment, there is increasing scrutiny on the practice of multiple stereotactic radiosurgeries (SRSs) for patients with cerebral metastases distant to the initial tumor site. Our goal was to determine the survival patterns of patients with cerebral metastasis who underwent multiple SRSs. We retrospectively analyzed survival outcomes of 801 patients with 3683 cerebral metastases from primary breast, colorectal, lung, melanoma and renal histologies consecutively treated at the University of California, San Diego/San Diego Gamma Knife Center (UCSD/SDGKC), comparing the survival pattern of patients who underwent a single (n = 643) versus multiple SRS(s) (n = 158) for subsequent cerebral metastases. Findings were recapitulated in an independent cohort of 2472 patients, with 26,629 brain metastases treated with SRS at the Katsuta Hospital Mito GammaHouse (KHMGH). For the UCSD/SDGKC cohort, no significant difference in median survival was found for patients undergoing 1, 2, 3, or ≥4 SRS(s) (median survival of 167, 202, 129, and 127 days, respectively). Median intervals between treatments consistently ranged 140–178 days irrespective of the number of SRS(s) (interquartile range 60–300; p = 0.25). Patients who underwent >1 SRSs tend to be younger, with systemic disease control, harbor lower cumulative tumor volume but increased number of metastases, and have primary melanoma (p < 0.001, <0.001, <0.001, 0.02, and 0.009, respectively). Comparable results were found in the KHMGH cohort. Using an independent validation study design, we demonstrated comparable overall survival between judiciously selected patients who underwent a single or multiple SRS(s).

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Combined inhibition of vascular endothelial growth factor receptor signaling with temozolomide enhances cytotoxicity against human glioblastoma cells via downregulation of Neuropilin-1

Abstract

Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor with grave prognosis. Despite the growing understanding of the complex signaling networks responsible for the initiation and progression of GBM, many experimental therapies have fallen short of their treatment goals. In the present study, we investigated the novel molecular mechanisms responsible for synergistic action of temozolomide (TMZ) and anti-VEGF therapy in GBM cells. We tested the combined effects of TMZ and VEGF blockade in four human GBM cell lines: TMZ-sensitive U251-MG and U373-MG cells, and TMZ-resistant CRT-MG and LN215-MG cells, which correlated with MGMT promoter methylation status. Treatment of TMZ along with a sublethal dosage range of SU1498, a chemical inhibitor of the VEGF receptor signaling, induced significant cell death in both TMZ-sensitive and TMZ-resistant GBM cells without changing the status of the MGMT promoter methylation. Treatment with TMZ specifically reduced the expression of NRP-1, a coreceptor of VEGF but not those of VEGF-R1 and VEGF-R2. We further confirmed the key role of NRP-1 by showing that the reduction of NRP-1 by siRNA also increased the SU1498-induced cytotoxicity of LN215-MG. These results collectively indicate that combined treatment of TMZ can sensitize GBM cells to blockade of autocrine VEGF signaling through specific down-regulation of NRP-1, which provide a rationale for further evaluation and a potential clinical trial of combinatorial therapy of TMZ and SU1498 or other VEGF inhibitors for intractable brain tumors.

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Management patterns of patients with cerebral metastases who underwent multiple stereotactic radiosurgeries

Abstract

With escalating focus on cost containment, there is increasing scrutiny on the practice of multiple stereotactic radiosurgeries (SRSs) for patients with cerebral metastases distant to the initial tumor site. Our goal was to determine the survival patterns of patients with cerebral metastasis who underwent multiple SRSs. We retrospectively analyzed survival outcomes of 801 patients with 3683 cerebral metastases from primary breast, colorectal, lung, melanoma and renal histologies consecutively treated at the University of California, San Diego/San Diego Gamma Knife Center (UCSD/SDGKC), comparing the survival pattern of patients who underwent a single (n = 643) versus multiple SRS(s) (n = 158) for subsequent cerebral metastases. Findings were recapitulated in an independent cohort of 2472 patients, with 26,629 brain metastases treated with SRS at the Katsuta Hospital Mito GammaHouse (KHMGH). For the UCSD/SDGKC cohort, no significant difference in median survival was found for patients undergoing 1, 2, 3, or ≥4 SRS(s) (median survival of 167, 202, 129, and 127 days, respectively). Median intervals between treatments consistently ranged 140–178 days irrespective of the number of SRS(s) (interquartile range 60–300; p = 0.25). Patients who underwent >1 SRSs tend to be younger, with systemic disease control, harbor lower cumulative tumor volume but increased number of metastases, and have primary melanoma (p < 0.001, <0.001, <0.001, 0.02, and 0.009, respectively). Comparable results were found in the KHMGH cohort. Using an independent validation study design, we demonstrated comparable overall survival between judiciously selected patients who underwent a single or multiple SRS(s).

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Combined inhibition of vascular endothelial growth factor receptor signaling with temozolomide enhances cytotoxicity against human glioblastoma cells via downregulation of Neuropilin-1

Abstract

Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor with grave prognosis. Despite the growing understanding of the complex signaling networks responsible for the initiation and progression of GBM, many experimental therapies have fallen short of their treatment goals. In the present study, we investigated the novel molecular mechanisms responsible for synergistic action of temozolomide (TMZ) and anti-VEGF therapy in GBM cells. We tested the combined effects of TMZ and VEGF blockade in four human GBM cell lines: TMZ-sensitive U251-MG and U373-MG cells, and TMZ-resistant CRT-MG and LN215-MG cells, which correlated with MGMT promoter methylation status. Treatment of TMZ along with a sublethal dosage range of SU1498, a chemical inhibitor of the VEGF receptor signaling, induced significant cell death in both TMZ-sensitive and TMZ-resistant GBM cells without changing the status of the MGMT promoter methylation. Treatment with TMZ specifically reduced the expression of NRP-1, a coreceptor of VEGF but not those of VEGF-R1 and VEGF-R2. We further confirmed the key role of NRP-1 by showing that the reduction of NRP-1 by siRNA also increased the SU1498-induced cytotoxicity of LN215-MG. These results collectively indicate that combined treatment of TMZ can sensitize GBM cells to blockade of autocrine VEGF signaling through specific down-regulation of NRP-1, which provide a rationale for further evaluation and a potential clinical trial of combinatorial therapy of TMZ and SU1498 or other VEGF inhibitors for intractable brain tumors.

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The conglomeration of diagnostic, prognostic and therapeutic potential of serum miR-199a and its association with clinicopathological features in epithelial ovarian cancer

Abstract

Epithelial ovarian cancer (EOC) is the most lethal cause of morbidity and mortality worldwide. miRNA deregulation evinces a remarkable role in ovarian cancer tumorigenesis. miRNA-199a (miR-199a) is known to be involved in cancer development and progression. Although miR-199a has been studied in various cell types, its correlation with clinicopathological features in EOC has not been documented. In this study, we identified the clinicopathological hallmarks which might be perturbed due to the downregulation of serum miR-199a in EOC. Seventy serum samples from histopathologically confirmed EOC patients and 70 controls were collected. Total RNA from serum was isolated by Trizol method, polyadenylated and reverse transcribed into cDNA. Expression level of miR-199a was detected by using miRNA qRT-PCR. Relative expression was determined with matched controls using U6 snRNA as reference. Level of miR-199a expression was compared with distinct clinicopathological features. Expression of miR-199a was found to be significantly downregulated in comparison with matched normal controls. The expression level of miR-199a was found to be significantly associated with tumor stage, lymph node metastasis, and distal metastasis. Receiver operating characteristic (ROC) curve for diagnostic potential yielded significant area under the curve (AUC) with a considerable sensitivity and specificity. ROC curves for prognosis yielded significant AUCs for histological grade, distal metastasis, lymph node status, and survival. Our findings suggest that miR-199a downregulation might be a potential indicator for disease progression promoting the aggressive tumor progression and be identified as a diagnostic marker to predict the prognosis and survival in EOC patients.

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Antigen-specific T cell response from dendritic cell vaccination using side population cell-associated antigens targets hepatocellular carcinoma

Abstract

Dendritic cell (DC) vaccination targeting cancer stem cells is an effective way to suppress tumor progression and reduce the metastasis and recurrence. In the present study, we explored the suitability of side population (SP) cells as source of antigens for DC vaccination against hepatocellular carcinoma (HCC) in a mouse model. In this study, we identified the "stem-like" characteristics of SP cells in the MHCC97 and Hepa 1-6 HCC cell lines. We found that SP cells express high levels of tumor-associated antigens and MHC class I molecules. Although loading with cell lysates did not change the characteristics of DCs, SP cell lysate-pulsed DCs induced antigen-specific T cell responses, including T cell proliferation and increased IFN-γ production by stimulated CD8⁺ T cells. We investigated the cytotoxicity of T cells stimulated by SP cell lysate-pulsed DCs in nude mice co-injected with MHCC97 cells. To mimic the in vivo environment, we also confirmed the result in mouse HCC cell line Hepa 1-6 induced tumor-bearing C57/BL6 immune competent mice, and we demonstrated that vaccination with DCs loaded with Hepa 1-6 SP cell lysates could induce a T cell response in vivo and suppress the tumor growth. Our results may have applications for anti-HCC immunotherapy by targeting the cancer stem cells and may provide new insight for cancer vaccines.

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Classic Architecture with Multicentricity and Local Recurrence, and Absence of TERT Promoter Mutations are Correlates of BRAF V600E Harboring Pediatric Papillary Thyroid Carcinomas

Abstract

This study is aimed to investigate the BRAF ^V600E and TERT promoter mutation profile of 50 pediatric papillary thyroid carcinomas (PTCs) to refine their clinicopathological correlates. The median age at the time of surgery was 16 years (range, 6–18). No TERT promoter mutations were identified in this series. The BRAF ^V600E mutation was present in 15 (30 %) tumors. From genotype-histologic variant correlation perspective, 13 of 24 classic variant PTCs and 2 of 7 diffuse sclerosing variant PTCs were found to harbor BRAF ^V600E mutation. One cribriform-morular variant, 3 solid variant, and 15 follicular variant PTCs were BRAF wild type. While tumors with distant metastasis were BRAF wild type, two of five tumors with extrathyroidal extension (ETE) harbored BRAF ^V600E mutation. Nine of 15 BRAF ^V600E harboring tumors had central lymph node metastases. There was no significant correlation with BRAF ^V600E mutation and age, gender, tumor size, ETE, central lymph node metastasis, the status of pT, pN1a-b, and distant metastasis. An adverse correlation between BRAF ^V600E mutation and disease-free survival (DFS) was noted in the entire cohort; however, the predictive value of BRAF ^V600E mutation disappeared within the group of tumors displaying classic architecture as well as classic variant PTCs. The present cohort identifies that the classic architecture with multicentricity and local recurrence are correlates of BRAF ^V600E harboring pediatric PTCs. While the small size of this cohort is one of the limitations, neither the BRAF mutation status nor the classic tumor architecture does seem to be an independent prognosticator of DFS in this series. Evidence also suggests that TERT promoter mutations do not seem to play a major role in the pathogenesis of pediatric PTCs.

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An Unusual Solitary Thyroid Nodule with Bloody Follicles: Metastatic Renal Cell Carcinoma Within an Infiltrative Follicular Variant Papillary Carcinoma

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Obesity and Metabolic Syndrome Among Adult Survivors of Childhood Leukemia

Opinion statement

Treatment-related obesity and the metabolic syndrome in adult survivors of childhood acute lymphoblastic leukemia (ALL) are risk factors for cardiovascular disease. Both conditions often begin during therapy. Preventive measures, including dietary counseling and tailored exercise, should be initiated early in the course of survivorship, with referral to specialists to optimize success. However, among adults who develop obesity or the metabolic syndrome and who do not respond to lifestyle therapy, medical intervention may be indicated to manage underlying pathology, such as growth hormone deficiency, or to mitigate risk factors of cardiovascular disease. Because no specific clinical trials have been done in this population to treat metabolic syndrome or its components, clinicians who follow adult survivors of childhood ALL should use the existing American Heart Association/National Heart Lung and Blood Institute Scientific Statement to guide their approach.

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Obesity and Metabolic Syndrome Among Adult Survivors of Childhood Leukemia

Opinion statement

Treatment-related obesity and the metabolic syndrome in adult survivors of childhood acute lymphoblastic leukemia (ALL) are risk factors for cardiovascular disease. Both conditions often begin during therapy. Preventive measures, including dietary counseling and tailored exercise, should be initiated early in the course of survivorship, with referral to specialists to optimize success. However, among adults who develop obesity or the metabolic syndrome and who do not respond to lifestyle therapy, medical intervention may be indicated to manage underlying pathology, such as growth hormone deficiency, or to mitigate risk factors of cardiovascular disease. Because no specific clinical trials have been done in this population to treat metabolic syndrome or its components, clinicians who follow adult survivors of childhood ALL should use the existing American Heart Association/National Heart Lung and Blood Institute Scientific Statement to guide their approach.

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Human Papillomavirus (HPV) Vaccination Motivators, Barriers, and Brochure Preferences Among Parents in Multicultural Hawai‘i: a Qualitative Study

Abstract

The human papillomavirus (HPV) vaccine can prevent cervical and other cancers. Unfortunately, according to the National Immunization Survey—Teen 2014 data, completion of the HPV vaccine was only 38 % for 13- to 17-year-old girls and 31 % for 13- to17-year-old boys in the USA, and prevalence was similar in Hawai'i. Parents' acceptability of the HPV vaccine is critical for the vaccine uptake, and this can be increased by educational materials and interventions. However, HPV materials are not widely distributed in Hawai'i. The purpose of this qualitative study was to identify HPV vaccination barriers, motivators, and brochure preferences among parents of teens in multicultural Hawai'i. Twenty parents were interviewed in person or by telephone. Four major themes emerged: (1) the physician is critical in the decision to vaccinate, (2) parental perception of the child's sexual activity guides the timing of their willingness to vaccinate, (3) HPV health education materials should be provided and discussed by the physician, and (4) parents would prefer an educational brochure that features local faces and testimonials, includes an immunization chart, and addresses barriers to vaccination. These findings informed the development of HPV health education materials tailored to Asian Americans and Pacific Islanders in Hawai'i.

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Erratum to: IκBα mediates prostate cancer cell death induced by combinatorial targeting of the androgen receptor

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