Publications by authors named "Cielito Reyes-Gibby"

63 Publications

Genetic Factors associated with Pain Severity, Daily Opioid Dose Requirement, and Pain Response among Advanced Cancer Patients receiving Supportive Care.

J Pain Symptom Manage 2021 Apr 10. Epub 2021 Apr 10.

Department of Palliative care, Rehabilitation Medicine, and Integrative Medicine UT MD Anderson Cancer Center, Houston, United States.

Background: Current understanding of genetic factors associated with pain severity, and improvement of pain with opioids in advanced cancer patients (AC) is inadequate for delivery of personalized pain therapy(PPT). Therefore, the aim of this study was to determine the genetic factors associated with pain severity, daily opioid dose, and pain response in AC patients receiving supportive care.

Methods: In this prospective study, AC patients were eligible if they had cancer pain ≥4/10 on Edmonton Symptom Assessment Scale (ESAS) - Pain Item and needed opioid rotation for pain control by specialist at the outpatient supportive care center. Pain phenotype was assessed using logistic regression models and SKATO (Gene-block) analysis.

Results: 174/178 (98%) patient samples were analyzed. After adjustment for demographic and clinical variables, pain severity was negatively associated with intron variant alleles in OPRM1 rs9322446, P = 0.02; rs2270459, P=0.038; rs62052210, P= 0.038. Opioid daily dose was positively associated NFKBIA rs2233419 P=0.008, rs2233417 P=0.007, rs3138054 P=0.008, rs1050851, P= 0.015;ORPM1 rs9479759, P= 0.046, rs2003185, P= 0.047, rs636433, P= 0.044; COMT (rs9306234, P= 0.014, rs165728, P= 0.014, rs2020917, P= 0.036, rs165728, P= 0.034); ARRB2 (rs1045280, P= 0.045); and pain response to opioids was negatively associated OPRM1 rs1319339 p=0.024, rs34427887 P=0.048, and COMT rs4646316 P=0.03, rs35478083 P=0.028 respectively. SKATO analysis showed association between pain severity and CXCL8 (P=0.0056), and STAT6 (P=0.0297) genes respectively, and pain response with IL-6 (P=0.00499).

Conclusions: This study identified that SNPs of OPRM1, COMT, NFKBIA, CXCL8, IL-6, STAT6,and ARRB2 genes were associated with pain severity, opioid daily dose, and pain response in AC receiving supportive care. Additional studies are needed to validate our findings for PPT.

Key Message: This study shows unique SNPs of OPRM1, COMT, NFKBIA, CXCL8, IL-6, STAT6, and ARRB2 genes were associated with cancer pain severity, and pain response after supportive care consultation in advanced cancer patients. Additional studies are needed to validate our findings for personalized pain therapy.
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http://dx.doi.org/10.1016/j.jpainsymman.2021.03.024DOI Listing
April 2021

Cancer pain management in the emergency department: a multicenter prospective observational trial of the Comprehensive Oncologic Emergencies Research Network (CONCERN).

Support Care Cancer 2021 Jan 22. Epub 2021 Jan 22.

Departments of Emergency Medicine and Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Purpose: Many patients with cancer seek care for pain in the emergency department (ED). Prospective research on cancer pain in this setting has historically been insufficient. We conducted this study to describe the reported pain among cancer patients presenting to the ED, how pain is managed, and how pain may be associated with clinical outcomes.

Methods: We conducted a multicenter cohort study on adult patients with active cancer presenting to 18 EDs in the USA. We reported pain scores, response to medication, and analgesic utilization. We estimated the associations between pain severity, medication utilization, and the following outcomes: 30-day mortality, 30-day hospital readmission, and ED disposition.

Results: The study population included 1075 participants. Those who received an opioid in the ED were more likely to be admitted to the hospital and were more likely to be readmitted within 30 days (OR 1.4 (95% CI: 1.11, 1.88) and OR 1.56 (95% CI: 1.17, 2.07)), respectively. Severe pain at ED presentation was associated with increased 30-day mortality (OR 2.30, 95% CI: 1.05, 5.02), though this risk was attenuated when adjusting for clinical factors (most notably functional status).

Conclusions: Patients with severe pain had a higher risk of mortality, which was attenuated when correcting for clinical characteristics. Those patients who required opioid analgesics in the ED were more likely to require admission and were more at risk of 30-day hospital readmission. Future efforts should focus on these at-risk groups, who may benefit from additional services including palliative care, hospice, or home-health services.
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http://dx.doi.org/10.1007/s00520-021-05987-3DOI Listing
January 2021

Diagnosis and management of immune-related adverse effects of immune checkpoint therapy in the emergency department.

J Am Coll Emerg Physicians Open 2020 Dec 30;1(6):1637-1659. Epub 2020 Aug 30.

Department of Emergency Medicine The University of Texas MD Anderson Cancer Center Houston Texas USA.

Rapid advances in cancer immunotherapy using immune checkpoint inhibitors have led to significantly improved survival. Rapid identification of the toxicity syndromes associated with these therapeutic agents is very important for emergency physicians because the population of patients diagnosed with cancer is increasing and cancer therapies including immune checkpoint inhibitors have become the first-line treatment for more and more types of cancer. The emergency medicine literature lags behind rapid advances in oncology, and oncology guidelines for rapid recognition and management of these emerging toxicity syndromes are not familiar to emergency physicians. In this review article, we discuss the clinical presentation and management of immune-related adverse effects during the critical first hours of emergency care. We also suggest a workflow for the recognition and treatment of emergencies arising from serious immune-related adverse effects, including but not limited to colitis, adrenal crisis, myocarditis, pneumonitis, myasthenic crisis, diabetic ketoacidosis, bullous pemphigus, and hemophagocytic lymphohistiocytosis. Rapid advances in cancer therapy are bringing new diagnostic and therapeutic challenges to emergency providers, and therefore it is crucial to raise awareness and provide guidelines for the management of new treatment-related toxicities.
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http://dx.doi.org/10.1002/emp2.12209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771833PMC
December 2020

Characteristics of cancer patients with COVID-19 in a cancer hospital.

Ann Palliat Med 2021 Feb 18;10(2):1763-1771. Epub 2020 Nov 18.

Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: Cancer patients are vulnerable to the coronavirus disease (COVID-19) given their compromised immune system. The purpose of this study was to describe the presenting symptoms, inpatient stay trajectory, and survival outcomes, for cancer patients infected with COVID-19; who presented to the emergency department (ED) of a single center during the early months of the pandemic.

Methods: We reviewed the electronic medical records of all cancer patients diagnosed with COVID-19 at our institution for demographic information, clinical presentation, laboratory findings, treatment intervention and outcomes. All patients had at least 14 days of follow-up. We determined their survival outcomes as of August 5, 2020.

Results: Twenty-eight cancer patients were diagnosed with COVID-19, and 16 (57%) presented to the ED during the study period. The median age of patients who presented to the ED was 61 years, 69% were women, and the median length of hospitalization was 11 days. There was no difference between the groups (ED vs. no ED visit) for demographics, treatment status or solid tumor versus hematologic malignancies or treatments. Dyspnea was a significant symptom with 67% of ED patients experiencing it versus only 17% of those that did not come to the ED (P=0.009). Do not resuscitate orders were initiated in eight patients, as early as two days from ED presentation and two of these patients died, while 88% of patients were discharged alive.

Conclusions: Most cancer patients with COVID-19 infection admitted though the ED experienced dyspnea and were discharged from the hospital. We did not notice a statistically significant difference between cancer types or type of therapy. A broad differential is of utmost importance when caring for cancer patients with COVID-19 due to the complexity of this population. Early goals of care discussion should be initiated in the ED.
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http://dx.doi.org/10.21037/apm-20-1447DOI Listing
February 2021

Oral microbiome and onset of oral mucositis in patients with squamous cell carcinoma of the head and neck.

Cancer 2020 Dec 5;126(23):5124-5136. Epub 2020 Sep 5.

Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Oral mucositis (OM) is a debilitating sequela for patients treated for squamous cell carcinoma of the head and neck (HNSCC). This study investigated whether oral microbial features before treatment or during treatment are associated with the time to onset of severe OM in patients with HNSCC.

Methods: This was a cohort study of newly diagnosed patients with locoregional HNSCC who received chemotherapy with or without radiotherapy from April 2016 to September 2017. OM was based on the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0. The oral microbiome was characterized on the basis of the 16S ribosomal RNA V4 region with the Illumina platform. A mixture cure model was used to generate hazard ratios for the onset of severe OM.

Results: Eighty-six percent of the patients developed OM (n = 57 [33 nonsevere cases and 24 severe cases]) with a median time to onset of OM of 21 days. With adjustments for age, sex, and smoking status, genera abundance was associated with the hazard for the onset of severe OM as follows: 1) at the baseline (n = 66), Cardiobacterium (P = .03) and Granulicatella (P = .04); 2) immediately before the development of OM (n = 57), Prevotella (P = .03), Fusobacterium (P = .03), and Streptococcus (P = .01); and 3) immediately before the development of severe OM (n = 24), Megasphaera (P = .0001) and Cardiobacterium (P = .03). There were no differences in α-diversity between the baseline samples and Human Microbiome Project data.

Conclusions: Changes in the abundance of genera over the course of treatment were associated with the onset of severe OM. The mechanism and therapeutic implications of these findings need to be investigated in future studies.
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http://dx.doi.org/10.1002/cncr.33161DOI Listing
December 2020

Clinical and Cancer-Related Predictors for Venous Thromboembolism in Cancer Patients Presenting to the Emergency Department.

J Emerg Med 2020 Jun 4;58(6):932-941. Epub 2020 May 4.

Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: The accurate detection of cancer-associated venous thromboembolism (VTE) can avoid unnecessary diagnostic imaging or laboratory tests.

Objective: We sought to determine clinical and cancer-related risk factors of VTE that can be used as predictors for oncology patients presenting to the emergency department (ED) with suspected VTE.

Methods: We retrospectively analyzed all consecutive patients who presented with suspicion of VTE to The University of Texas MD Anderson Cancer Center ED between January 1, 2009, and January 1, 2013. Logistic regression models were used to identify risk factors that were associated with VTE. The ability of these factors to predict VTE was externally validated using a second cohort of patients who presented to King Hussein Cancer Center ED between January 1, 2009, and January 1, 2016.

Results: Cancer-related covariates associated with the occurrence of VTE were high-risk cancer type (odds ratio [OR] 3.64 [95% confidence interval {CI} 2.37-5.60], p < 0.001), presentation within 6 months of the cancer diagnosis (OR 1.92 [95% CI 1.62-2.28], p < 0.001), active cancer (OR 1.35 [95% CI 1.10-1.65], p = 0.003), advanced stage (OR 1.40 [95% CI 1.01-1.94], p = 0.044), and the presence of brain metastasis (OR 1.73 [95% CI 1.32-2.27], p < 0.001). When combined, these factors along with other clinical factors showed high prediction performance for VTE in the external validation cohort.

Conclusions: Cancer risk group, presentation within 6 months of cancer diagnosis, active and advanced cancer, and the presence of brain metastases along with other related clinical factors can be used to predict VTE in patients with cancer presenting to the ED.
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http://dx.doi.org/10.1016/j.jemermed.2020.03.039DOI Listing
June 2020

Serious immune-related adverse events in patients with head and neck cancer after checkpoint blockade: Systematic review.

Head Neck 2019 11 15;41(11):4036-4050. Epub 2019 Aug 15.

Department of Emergency Medicine, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Immune checkpoint inhibitors confer significant clinical benefit by bolstering immune-system activity, however, they also produce a spectrum of immune-related adverse events (irAEs). Rapid recognition and timely treatment of these patients is essential for improved outcomes.

Methods: We conducted a systematic review of English-language articles in MEDLINE, EMBASE, Web of Science, PubMed, and Cochrane CENTRAL databases on patients with head and neck cancer treated with immune checkpoint inhibitors who developed treatment-related adverse events.

Results: Of 1715 unique citations, 11 studies met inclusion criteria. Eight patients with serious irAEs were reported from case reports and case series. Overall, 46 treatment-related AEs were identified from the pooled 791 patients with at least 12 having potential relevance to irAEs. The most frequent AEs observed in patients receiving PD-1 inhibitors involved the endocrine, cutaneous, and gastrointestinal systems.

Conclusions: Characterizing irAEs in longitudinal studies is needed for developing strategies for their prompt recognition and management.
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http://dx.doi.org/10.1002/hed.25911DOI Listing
November 2019

Validation of the Emergency Severity Index (Version 4) for the Triage of Adult Emergency Department Patients With Active Cancer.

J Emerg Med 2019 Sep 26;57(3):354-361. Epub 2019 Jul 26.

Department of Emergency Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio.

Background: Patients with active cancer account for a growing percentage of all emergency department (ED) visits and have a unique set of risks related to their disease and its treatments. Effective triage for this population is fundamental to facilitating their emergency care.

Objectives: We evaluated the validity of the Emergency Severity Index (ESI; version 4) triage tool to predict ED-relevant outcomes among adult patients with active cancer.

Methods: We conducted a prespecified analysis of the observational cohort established by the National Cancer Institute-supported Comprehensive Oncologic Emergencies Research Network's multicenter (18 sites) study of ED visits by patients with active cancer (N = 1075). We used a series of χ tests for independence to relate ESI scores with 1) disposition, 2) ED resource use, 3) hospital length of stay, and 4) 30-day mortality.

Results: Among the 1008 subjects included in this analysis, the ESI distribution skewed heavily toward high acuity (>95% of subjects had an ESI level of 1, 2, or 3). ESI was significantly associated with patient disposition and ED resource use (p values < 0.05). No significant associations were observed between ESI and the non-ED based outcomes of hospital length of stay or 30-day mortality.

Conclusion: ESI scores among ED patients with active cancer indicate higher acuity than the general ED population and are predictive of disposition and ED resource use. These findings show that the ESI is a valid triage tool for use in this population for outcomes directly relevant to ED care.
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http://dx.doi.org/10.1016/j.jemermed.2019.05.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478143PMC
September 2019

Analysis of Diagnoses, Symptoms, Medications, and Admissions Among Patients With Cancer Presenting to Emergency Departments.

JAMA Netw Open 2019 03 1;2(3):e190979. Epub 2019 Mar 1.

Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, Department of Medicine, University of Washington School of Medicine, Seattle.

Importance: Better understanding of the emergency care needs of patients with cancer will inform outpatient and emergency department (ED) management.

Objective: To provide a benchmark description of patients who present to the ED with active cancer.

Design, Setting, And Participants: This multicenter prospective cohort study included 18 EDs affiliated with the Comprehensive Oncologic Emergencies Research Network (CONCERN). Of 1564 eligible patients, 1075 adults with active cancer were included from February 1, 2016, through January 30, 2017. Data were analyzed from February 1 through August 1, 2018.

Main Outcomes And Measures: The proportion of patients reporting symptoms (eg, pain, nausea) before and during the ED visit, ED and outpatient medications, most common diagnoses, and suspected infection as indicated by ED antibiotic administration. The proportions observed, admitted, and with a hospital length of stay (LOS) of no more than 2 days were identified.

Results: Of 1075 participants, mean (SD) age was 62 (14) years, and 51.8% were female. Seven hundred ninety-four participants (73.9%; 95% CI, 71.1%-76.5%) had undergone cancer treatment in the preceding 30 days; 674 (62.7%; 95% CI, 59.7%-65.6%) had advanced or metastatic cancer; and 505 (47.0%; 95% CI, 43.9%-50.0%) were 65 years or older. The 5 most common ED diagnoses were symptom related. Of all participants, 82 (7.6%; 95% CI, 6.1%-9.4%) were placed in observation and 615 (57.2%; 95% CI, 54.2%-60.2%) were admitted; 154 of 615 admissions (25.0%; 95% CI, 21.7%-28.7%) had an LOS of 2 days or less (median, 3 days; interquartile range, 2-6 days). Pain during the ED visit was present in 668 patients (62.1%; 95% CI, 59.2%-65.0%; mean [SD] pain score, 6.4 [2.6] of 10.0) and in 776 (72.2%) during the prior week. Opioids were administered in the ED to 228 of 386 patients (59.1%; 95% CI, 18.8%-23.8%) with moderate to severe ED pain. Outpatient opioids were prescribed to 368 patients (47.4%; 95% CI, 3.14%-37.2%) of those with pre-ED pain, including 244 of 428 (57.0%; 95% CI, 52.2%-61.8%) who reported quite a bit or very much pain. Nausea in the ED was present in 336 (31.3%; 95% CI, 28.5%-34.1%); of these, 160 (47.6%; 95% CI, 12.8%-17.1%) received antiemetics in the ED. Antibiotics were administered in the ED to 285 patients (26.5%; 95% CI, 23.9%-29.2%). Of these, 209 patients (73.3%; 95% CI, 17.1%-21.9%) were admitted compared with 427 of 790 (54.1%; 95% CI, 50.5%-57.6%) not receiving antibiotics.

Conclusions And Relevance: This initial prospective, multicenter study profiling patients with cancer who were treated in the ED identifies common characteristics in this patient population and suggests opportunities to optimize care before, during, and after the ED visit. Improvement requires collaboration between specialists and emergency physicians optimizing ED use, improving symptom control, avoiding unnecessary hospitalizations, and appropriately stratifying risk to ensure safe ED treatment and disposition of patients with cancer.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.0979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583275PMC
March 2019

Genome-wide association study identifies genes associated with neuropathy in patients with head and neck cancer.

Sci Rep 2018 06 8;8(1):8789. Epub 2018 Jun 8.

Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.

Neuropathic pain (NP), defined as pain initiated or caused by a primary lesion or dysfunction in the nervous system, is a debilitating chronic pain condition often resulting from cancer treatment. Among cancer patients, neuropathy during cancer treatment is a predisposing event for NP. To identify genetic variants influencing the development of NP, we conducted a genome-wide association study in 1,043 patients with squamous cell carcinoma of the head and neck, based on 714,494 tagging single-nucleotide polymorphisms (SNPs) (130 cases, 913 controls). About 12.5% of the patients, who previously had cancer treatment, had neuropathy-associated diagnoses, as defined using the ICD-9/ICD-10 codes. We identified four common SNPs representing four genomic regions: 7q22.3 (rs10950641; SNX8; P = 3.39 × 10), 19p13.2 (rs4804217; PCP2; P = 2.95 × 10), 3q27.3 (rs6796803; KNG1; P = 6.42 × 10) and 15q22.2 (rs4775319; RORA; P = 1.02 × 10), suggesting SNX8, PCP2, KNG1 and RORA might be novel target genes for NP in patients with head and neck cancer. Future experimental validation to explore physiological effects of the identified SNPs will provide a better understanding of the biological mechanisms underlying NP and may provide insights into novel therapeutic targets for treatment and management of NP.
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http://dx.doi.org/10.1038/s41598-018-27070-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993794PMC
June 2018

Adverse Effects of Immune Checkpoint Therapy in Cancer Patients Visiting the Emergency Department of a Comprehensive Cancer Center.

Ann Emerg Med 2019 01 5;73(1):79-87. Epub 2018 Jun 5.

Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address:

Study Objective: Cancer immunotherapy is evolving rapidly and is transforming cancer care. During the last decade, immune checkpoint therapies have been developed to enhance the immune response; however, specific adverse effects related to autoimmunity are increasingly apparent. This study aims to fill the knowledge gap related to the spectrum of immune-related adverse effects among cancer patients visiting emergency departments (EDs).

Methods: We performed a retrospective review of patients treated with immune checkpoint therapy who visited the ED of a comprehensive cancer center between March 1, 2011, and February 29, 2016. Immune-related adverse effects from the ED visits were identified and profiled. We analyzed the association of each immune-related adverse effect with overall survival from the ED visit to death.

Results: We identified 1,026 visits for 628 unique patients; of these, 257 visits (25.0%) were related to one or more immune-related adverse effects. Diarrhea was the most common one leading to an ED visit. The proportions of ED visits associated with diarrhea, hypophysitis, thyroiditis, pancreatitis, or hepatitis varied significantly by immune checkpoint therapy agent. Colitis was significantly associated with better prognosis, whereas pneumonitis was significantly associated with worse survival.

Conclusion: Cancer patients treated with ipilimumab, nivolumab, or pembrolizumab may have a spectrum of immune-related adverse effects that require emergency care. Future studies will need to update this profile as further novel immunotherapeutic agents are added.
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http://dx.doi.org/10.1016/j.annemergmed.2018.04.019DOI Listing
January 2019

Oncologic emergencies in a cancer center emergency department and in general emergency departments countywide and nationwide.

PLoS One 2018 20;13(2):e0191658. Epub 2018 Feb 20.

Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.

Background: Although cancer patients (CPs) are increasingly likely to visit emergency department (ED), no population-based study has compared the characteristics of CPs and non-cancer patients (NCPs) who visit the ED and examined factors associated with hospitalization via the ED. In this study, we (1) compared characteristics and diagnoses between CPs and NCPs who visited the ED in a cancer center or general hospital; (2) compared characteristics and diagnoses between CPs and NCPs who were hospitalized via the ED in a cancer center or general hospital; and (3) investigated important factors associated with such hospitalization.

Methods And Findings: We analyzed patient characteristic and diagnosis [based on International Classification of Diseases-9 (ICD-9) codes] data from the ED of a comprehensive cancer center (MDACC), 24 general EDs in Harris County, Texas (HCED), and the National Hospital Ambulatory Medical Care Survey (NHAMCS) from 1/1/2007-12/31/2009. Approximately 3.4 million ED visits were analyzed: 47,245, 3,248,973, and 104,566 visits for MDACC, HCED, and NHAMCS, respectively, of which 44,143 (93.4%), 44,583 (1.4%), and 632 (0.6%) were CP visits. CPs were older than NCPs and stayed longer in EDs. Lung, gastrointestinal (excluding colorectal), and genitourinary (excluding prostate) cancers were the three most common diagnoses related to ED visits at general EDs. CPs visiting MDACC were more likely than CPs visiting HCED to be privately insured. CPs were more likely than NCPs to be hospitalized. Pneumonia and influenza, fluid and electrolyte disorders, and fever were important predictive factors for CP hospitalization; coronary artery disease, cerebrovascular disease, and heart failure were important factors for NCP hospitalization.

Conclusions: CPs consumed more ED resources than NCPs and had a higher hospitalization rate. Given the differences in characteristics and diagnoses between CPs and NCPs, ED physicians must pay special attention to CPs and be familiar with their unique set of oncologic emergencies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191658PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819770PMC
March 2018

Processing and Analyzing Human Microbiome Data.

Methods Mol Biol 2017 ;1666:649-677

Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

The human microbiome is associated with complex disorders such as diabetes, cancer, obesity and cardiovascular disorders. Recent technological developments have allowed researchers to fully quantify the composition of the microbiome using culture-independent approaches, resulting in a large amount of microbiome data, which provide invaluable opportunities to assess the important contributions of the microbiome to human health and disease. In this chapter, we discuss and evaluate multiple statistical approaches for processing, summarizing, and analyzing microbiome data. Specifically, we provide programming scripts for processing microbiome data using QIIME and calculating alpha and beta diversities, assessing the association between diversities and outcomes of interest using R programs, as well as interpretation of results. We illustrate the methods in the context of analyzing the foregut microbiome in esophageal adenocarcinoma.
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http://dx.doi.org/10.1007/978-1-4939-7274-6_31DOI Listing
May 2018

Identifying novel genes and biological processes relevant to the development of cancer therapy-induced mucositis: An informative gene network analysis.

PLoS One 2017 5;12(7):e0180396. Epub 2017 Jul 5.

Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.

Mucositis is a complex, dose-limiting toxicity of chemotherapy or radiotherapy that leads to painful mouth ulcers, difficulty eating or swallowing, gastrointestinal distress, and reduced quality of life for patients with cancer. Mucositis is most common for those undergoing high-dose chemotherapy and hematopoietic stem cell transplantation and for those being treated for malignancies of the head and neck. Treatment and management of mucositis remain challenging. It is expected that multiple genes are involved in the formation, severity, and persistence of mucositis. We used Ingenuity Pathway Analysis (IPA), a novel network-based approach that integrates complex intracellular and intercellular interactions involved in diseases, to systematically explore the molecular complexity of mucositis. As a first step, we searched the literature to identify genes that harbor or are close to the genetic variants significantly associated with mucositis. Our literature review identified 27 candidate genes, of which ERCC1, XRCC1, and MTHFR were the most frequently studied for mucositis. On the basis of this 27-gene list, we used IPA to generate gene networks for mucositis. The most biologically significant novel molecules identified through IPA analyses included TP53, CTNNB1, MYC, RB1, P38 MAPK, and EP300. Additionally, uracil degradation II (reductive) and thymine degradation pathways (p = 1.06-08) were most significant. Finally, utilizing 66 SNPs within the 8 most connected IPA-derived candidate molecules, we conducted a genetic association study for oral mucositis in the head and neck cancer patients who were treated using chemotherapy and/or radiation therapy (186 head and neck cancer patients with oral mucositis vs. 699 head and neck cancer patients without oral mucositis). The top ranked gene identified through this association analysis was RB1 (rs2227311, p-value = 0.034, odds ratio = 0.67). In conclusion, gene network analysis identified novel molecules and biological processes, including pathways related to inflammation and oxidative stress, that are relevant to mucositis development, thus providing the basis for future studies to improve the management and treatment of mucositis in patients with cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0180396PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498049PMC
October 2017

Discharge or admit? Emergency department management of incidental pulmonary embolism in patients with cancer: a retrospective study.

Int J Emerg Med 2017 Dec 6;10(1):19. Epub 2017 Jun 6.

Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1468, Houston, TX, 77030, USA.

Background: Hospitalization and early anticoagulation therapy remain standard care for patients who present to the emergency department (ED) with pulmonary embolism (PE). For PEs discovered incidentally, however, optimal therapeutic strategies are less clear-and all the more so when the patient has cancer, which is associated with a hypercoagulable state that exacerbates the threat of PE.

Methods: We conducted a retrospective review of a historical cohort of patients with cancer and incidental PE who were referred for assessment to the ED in an institution whose standard of care is outpatient treatment of selected patients and use of low-molecular-weight heparin for anticoagulation. Eligible patients had received a diagnosis of incidental PE upon routine contrast enhanced chest CT for cancer staging. Survival data was collected at 30 days and 90 days from the date of ED presentation and at the end of the study.

Results: We identified 193 patients, 135 (70%) of whom were discharged and 58 (30%) of whom were admitted to the hospital. The 30-day survival rate was 92% overall, 99% for the discharged patients and 76% for admitted patients. Almost all (189 patients, 98%) commenced anticoagulation therapy in the ED; 170 (90%) of these received low-molecular-weight heparin. Patients with saddle pulmonary artery incidental PEs were more likely to die within 30 days (43%) than were those with main or lobar (11%), segmental (6%), or subsegmental (5%) incidental PEs. In multivariate analysis, Charlson comorbidity index (age unadjusted), hypoxemia, and incidental PE location (P = 0.004, relative risk 33.5 (95% CI 3.1-357.4, comparing saddle versus subsegmental PE) were significantly associated with 30-day survival. Age, comorbidity, race, cancer stage, tachycardia, hypoxemia, and incidental PE location were significantly associated with hospital admission.

Conclusions: Selected cancer patients presenting to the ED with incidental PE can be treated with low-molecular-weight heparin anticoagulation and safely discharged. Avoidance of unnecessary hospitalization may decrease in-hospital infections and death, reduce healthcare costs, and improve patient quality of life. Because the natural history and optimal management of this condition is not well described, information supporting the creation of straightforward evidence-based practice guidelines for ED teams treating this specialized patient population is needed.
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http://dx.doi.org/10.1186/s12245-017-0144-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461224PMC
December 2017

The Use of Cardiac Resynchronization Therapy in Cancer Patients with Heart Failure.

J Clin Exp Res Cardiol 2017 Apr 27;3(1). Epub 2017 Apr 27.

Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1468, Houston, TX 77030-4009,

Objectives: Investigate the use of cardiac resynchronization therapy (CRT) in cancer patients with heart failure (HF); assess factors associated with ischemic and non-ischemic HF.

Background: Many newer cancer therapies are cardiotoxic; thus, the incidence of HF has been increasing in this high-risk patient population. CRT has beneficial effects on morbidity, mortality, and left ventricular function in patients with non-ischemic cardiomyopathy, yet cancer patients and survivors who develop severe HF and are eligible for CRT often do not receive it.

Methods: Review of 2 years of echocardiography and electrocardiography data from cancer patients.

Results: Of 272 patients meeting inclusion criteria for CRT placement (LVEF ≤35%, QRS duration ≥120 ms), 131 (48.2%) had HF with ischemic etiology and 141 (51.8%) had HF with non-ischemic etiology. Most patients had solid tumors, including breast, lung, sarcoma, and lymphoma (73.2%, n=199). Only 21.3% (58/272; 27 ischemic; 31 non-ischemic) underwent CRT placement, who were mostly women and those with solid tumors. Non-ischemic HF was significantly associated with younger age (<65 years) (OR=0.91; 95% CI=0.87-0.95) and female sex (OR=2.5; 95% CI=1.1-6.0). As expected, ischemic HF was significantly associated with history of myocardial infarction, diabetes, and cardiovascular disease.

Conclusions: CRT is underutilized in cancer patients with HF. Most of the cancer patients who did not receive CRT had non-ischemic HF secondary to chemotherapy. CRT may be less utilized in those patients due to shortened life expectancy, yet evidence suggests that CRT has beneficial effects on morbidity, mortality, and left ventricular function. Its use may improve patient quality of life and allow oncologists to continue cancer treatments that could prolong survival.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6022845PMC
http://dx.doi.org/10.15744/2394-6504.3.105DOI Listing
April 2017

Cohort study of oncologic emergencies in patients with head and neck cancer.

Head Neck 2017 06 27;39(6):1195-1204. Epub 2017 Mar 27.

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Treatments for head and neck squamous cell carcinoma (HNSCC) are associated with toxicities that lead to emergency department presentation.

Methods: We utilized data from an ongoing prospective cohort of newly diagnosed, previously untreated patients (N = 298) with HNSCC to evaluate the association between clinical and epidemiologic factors and risk for and frequency of emergency department presentation. Time to event was calculated from the date of treatment initiation to emergency department presentation, date of death, or current date. Frequency of emergency department presentation was the sum of emergency department visits during the follow-up time.

Results: History of hypertension, normal/underweight body mass index (BMI), and probable depression predicted increased risk for emergency department presentation. BMI and severe pain were associated with higher frequency of emergency department presentations.

Conclusion: Clinical and epidemiologic factors can help predict patients with HNSCC who will present to the emergency department. Such knowledge may improve treatment-related patient outcomes and quality of life. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1195-1204, 2017.
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http://dx.doi.org/10.1002/hed.24748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429871PMC
June 2017

Correction to: Processing and Analyzing Human Microbiome Data.

Methods Mol Biol 2017 ;1666:E1

Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

The original version of this chapter was inadvertently published without including the dbGaP acknowledgment. The updated chapter now contains that information.
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http://dx.doi.org/10.1007/978-1-4939-7274-6_32DOI Listing
January 2017

Genome-wide association study suggests common variants within RP11-634B7.4 gene influencing severe pre-treatment pain in head and neck cancer patients.

Sci Rep 2016 Sep 27;6:34206. Epub 2016 Sep 27.

Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.

Pain is often one of the first signs of squamous cell carcinoma of the head and neck (HNSCC). Pain at diagnosis is an important prognostic marker for the development of chronic pain, and importantly, for the overall survival time. To identify variants influencing severe pre-treatment pain in 1,368 patients newly diagnosed with HNSCC, we conducted a genome-wide association study based on 730,525 tagging SNPs. The patients were all previously untreated for cancer. About 15% of the patients had severe pre-treatment pain, defined as pain score ≥7 (0 = "no pain" and 10 = "worst pain"). We identified 3 common genetic variants in high linkage disequilibrium for severe pre-treatment pain, representing one genomic region at 1q44 (rs3862188, P = 3.45 × 10; rs880143, P = 3.45 × 10; and rs7526880, P = 4.92 × 10), which maps to the RP11-634B7.4 gene, a novel antisense gene to three olfactory receptor genes. Olfactory receptor genes, upstream effectors of the MAPK signaling cascade, might be novel target genes for pain in HNSCC patients. Future experimental validation to explore biological mechanisms will be key to defining the role of the intronic variants and non-coding RNA for pain in patients with HNSCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037456PMC
http://dx.doi.org/10.1038/srep34206DOI Listing
September 2016

Cardiac Troponin Is a Predictor of Septic Shock Mortality in Cancer Patients in an Emergency Department: A Retrospective Cohort Study.

PLoS One 2016 14;11(4):e0153492. Epub 2016 Apr 14.

Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, Texas 77030, United States of America.

Background: Septic shock may be associated with myocardial damage; however, the prognostic value of cardiac enzymes in cancer patients with septic shock is unknown. In this study, we evaluated the prognostic significance of cardiac enzymes in combination with established prognostic factors in predicting the 7-day mortality rate of patients with septic shock, and we constructed a new scoring system, Septic Oncologic Patients in Emergency Department (SOPED), which includes cardiac enzymes, to predict 7-day mortality rates.

Methods And Findings: We performed a retrospective cohort study of 375 adult cancer patients with septic shock who visited the emergency department of a comprehensive cancer center between 01/01/2004 and 12/31/2013. The 7-day and 28-day mortality rates were 19.7% and 37.6%, respectively. The creatine kinase myocardial band fraction and troponin-I were significantly higher in patients who died in ≤7 days and ≤28 days than in those who did not. In Cox regression models, troponin-I >0.05 ng/mL plus Predisposition, Infection, Response, and Organ Failure (PIRO2011) or Mortality in Emergency Department Sepsis (MEDS) score was a significant predictor of survival for ≤7 days. With our new SOPED scoring system, the receiver operating characteristic area under the curve was 0.836, higher than those for PIRO2011 and MEDS.

Conclusions: Troponin-I >0.05 ng/mL was an important predictor of short-term mortality (≤7 days). The SOPED scoring system, which incorporated troponin-I, was more prognostically accurate than were other scores for 7-day mortality. Large multicenter studies are needed to verify our results and prospectively validate the prognostic performance of the SOPED score.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0153492PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831781PMC
September 2016

Presenting Symptoms in the Emergency Department as Predictors of Intensive Care Unit Admissions and Hospital Mortality in a Comprehensive Cancer Center.

J Oncol Pract 2016 05 12;12(5):e554-63. Epub 2016 Apr 12.

Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.

Purpose: The identification of patients at high risk for poor outcomes may allow for earlier palliative care and prevent futile interventions. We examined the association of presenting symptoms on risk of intensive care unit (ICU) admission and hospital death among patients with cancer admitted through an emergency department (ED).

Methods: We queried MD Anderson Cancer Center databases for all patients who visited the ED in 2010. Presenting symptoms, ICU admissions, and hospital deaths were reviewed; patient data analyzed; and risk factors for ICU admission and hospital mortality identified.

Results: The main presenting symptoms were pain, fever, and respiratory distress. Of the patients with cancer who visited the ED, 5,362 (58%) were admitted to the hospital at least once (range, 1 to 13 admissions), 697 (13%) were admitted to the ICU at least once, and 587 (11%) died during hospitalization (31% of 233 patients with hematologic malignancies and 27% of 354 patients with solid tumors died in the ICU; P < .001). In multivariable logistic regression, presenting symptoms of respiratory distress or altered mental status; lung cancer, leukemia, or lymphoma; and nonwhite race were independent predictors of hospital death. Patients who died had a longer median length of hospital stay than patients discharged alive (14 v 6 days for hematologic malignancies and 7 v 5 days for solid tumors; P < .001).

Conclusion: Patients with cancer admitted through an ED experience high ICU admission and hospital mortality rates. Patients with advanced cancer and respiratory distress or altered mental status may benefit from palliative care that avoids unnecessary interventions.
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http://dx.doi.org/10.1200/JOP.2015.009019DOI Listing
May 2016

MAPK1/ERK2 as novel target genes for pain in head and neck cancer patients.

BMC Genet 2016 Feb 13;17:40. Epub 2016 Feb 13.

Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, U.S.A..

Background: Genetic susceptibility plays an important role in the risk of developing pain in individuals with cancer. As a complex trait, multiple genes underlie this susceptibility. We used gene network analyses to identify novel target genes associated with pain in patients newly diagnosed with squamous cell carcinoma of the head and neck (HNSCC).

Results: We first identified 36 cancer pain-related genes (i.e., focus genes) from 36 publications based on a literature search. The Ingenuity Pathway Analysis (IPA) analysis identified additional genes that are functionally related to the 36 focus genes through pathway relationships yielding a total of 82 genes. Subsequently, 800 SNPs within the 82 IPA-selected genes on the Illumina HumanOmniExpress-12v1 platform were selected from a large-scale genotyping effort. Association analyses between the 800 candidate SNPs (covering 82 genes) and pain in a patient cohort of 1368 patients with HNSCC (206 patients with severe pain vs. 1162 with non-severe pain) showed the highest significance for MAPK1/ERK2, a gene belonging to the MAP kinase family (rs8136867, p value = 8.92 × 10(-4); odds ratio [OR] = 1.33, 95 % confidence interval [CI]: 1.13-1.58). Other top genes were PIK3C2G (a member of PI3K [complex], rs10770367, p value = 1.10 × 10(-3); OR = 1.46, 95 % CI: 1.16-1.82), TCRA (the alpha chain of T-cell receptor, rs6572493, p value = 2.84 × 10(-3); OR = 0.70, 95 % CI: 0.55-0.88), PDGFC (platelet-derived growth factor C, rs6845322, p value = 4.88 × 10(-3); OR = 1.32, 95 % CI: 1.09-1.60), and CD247 (a member of CD3, rs2995082, p value = 7.79 × 10(-3); OR = 0.76, 95 % CI: 0.62-0.93).

Conclusions: Our findings provide novel candidate genes and biological pathways underlying pain in cancer patients. Further study of the variations of these candidate genes could inform clinical decision making when treating cancer pain.
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http://dx.doi.org/10.1186/s12863-016-0348-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752805PMC
February 2016

Risk for Opioid Misuse Among Emergency Department Cancer Patients.

Acad Emerg Med 2016 Feb 29;23(2):151-8. Epub 2016 Jan 29.

Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.

Objectives: One of the most challenging areas of emergency medicine practice is the management and treatment of severe and persistent pain, including cancer-related pain. Emergency departments (EDs) in the United States frequently provide care for patients with cancer and an increasing concern is the potential for opioid misuse in this patient group. The authors determined the risk for opioid misuse among ED cancer patients with pain and assessed demographic and clinical factors associated with increased misuse risk. The Texas state prescription monitoring program was also queried for evidence of multiple opioid prescriptions for comparing low- and high-risk groups.

Methods: The Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R) was administered to assess risk for opioid misuse among cancer patients presenting to the ED of a comprehensive cancer center in the United States. Eligibility criteria included: 1) presentation for treatment of chronic cancer-related pain while taking a prescribed schedule II opioid for analgesia, 2) age of 18 years or older, 3) ability to speak English, and 4) ability to understand the study and give written informed consent.

Results: Of 934 ED patients screened for the study, 290 were eligible and 209 participated (72% response rate). On the basis of the recommended SOAPP-R cutoff score of 18, a total of 71 of the 209 patients (34%) were categorized as having a high risk of misuse. Of note, 15% and 4% of all patients reported past or current use of illicit substances, respectively. The total number of annual opioid prescriptions (17.8 vs. 12.6; p = 0.023) differed between the high- versus low-risk groups. Multivariable analyses showed that depression (odds ratio [OR] = 3.06, 95% confidence interval [CI] = 1.45 to 6.48; p = 0.003), poor coping (OR = 1.08, 95% CI = 1.03 to 1.13; p = 0.001), and illicit substance use (OR = 28.30, 95% CI = 2.97 to 269.24; p = 0.029) were significantly associated with high risk of opioid misuse.

Conclusions: The risk of opioid misuse among cancer patients is substantial. Screening for opioid misuse in the ED is feasible.
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http://dx.doi.org/10.1111/acem.12861DOI Listing
February 2016

Informative gene network for chemotherapy-induced peripheral neuropathy.

BioData Min 2015 12;8:24. Epub 2015 Aug 12.

Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 USA.

Background: Host genetic variability has been implicated in chemotherapy-induced peripheral neuropathy (CIPN). A dose-limiting toxicity for chemotherapy agents, CIPN is also a debilitating condition that may progress to chronic neuropathic pain. We utilized a bioinformatics approach, which captures the complexity of intracellular and intercellular interactions, to identify genes for CIPN.

Methods: Using genes pooled from the literature as a starting point, we used Ingenuity Pathway Analysis (IPA) to generate gene networks for CIPN.

Results: We performed IPA core analysis for genes associated with platinum-, taxane- and platinum-taxane-induced neuropathy. We found that IL6, TNF, CXCL8, IL1B and ERK1/2 were the top genes in terms of the number of connections in platinum-induced neuropathy and TP53, MYC, PARP1, P38 MAPK and TNF for combined taxane-platinum-induced neuropathy.

Conclusion: Neurotoxicity is common in cancer patients treated with platinum compounds and anti-microtubule agents and CIPN is one of the debilitating sequela. The bioinformatic approach helped identify genes associated with CIPN in cancer patients.
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http://dx.doi.org/10.1186/s13040-015-0058-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534051PMC
August 2015

Gene network analysis shows immune-signaling and ERK1/2 as novel genetic markers for multiple addiction phenotypes: alcohol, smoking and opioid addiction.

BMC Syst Biol 2015 Jun 5;9:25. Epub 2015 Jun 5.

Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

Background: Addictions to alcohol and tobacco, known risk factors for cancer, are complex heritable disorders. Addictive behaviors have a bidirectional relationship with pain. We hypothesize that the associations between alcohol, smoking, and opioid addiction observed in cancer patients have a genetic basis. Therefore, using bioinformatics tools, we explored the underlying genetic basis and identified new candidate genes and common biological pathways for smoking, alcohol, and opioid addiction.

Results: Literature search showed 56 genes associated with alcohol, smoking and opioid addiction. Using Core Analysis function in Ingenuity Pathway Analysis software, we found that ERK1/2 was strongly interconnected across all three addiction networks. Genes involved in immune signaling pathways were shown across all three networks. Connect function from IPA My Pathway toolbox showed that DRD2 is the gene common to both the list of genetic variations associated with all three addiction phenotypes and the components of the brain neuronal signaling network involved in substance addiction. The top canonical pathways associated with the 56 genes were: 1) calcium signaling, 2) GPCR signaling, 3) cAMP-mediated signaling, 4) GABA receptor signaling, and 5) G-alpha i signaling.

Conlusions: Cancer patients are often prescribed opioids for cancer pain thus increasing their risk for opioid abuse and addiction. Our findings provide candidate genes and biological pathways underlying addiction phenotypes, which may be future targets for treatment of addiction. Further study of the variations of the candidate genes could allow physicians to make more informed decisions when treating cancer pain with opioid analgesics.
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http://dx.doi.org/10.1186/s12918-015-0167-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456775PMC
June 2015

Survival patterns in squamous cell carcinoma of the head and neck: pain as an independent prognostic factor for survival.

J Pain 2014 Oct 17;15(10):1015-22. Epub 2014 Jul 17.

Department of Head and Neck, University of Texas M.D. Anderson Cancer Center, Houston, Texas.

Unlabelled: Survival outcomes in patients with squamous cell carcinoma of the head and neck (HNSCC) vary by extent of disease, behavioral factors, and socioeconomic factors. We assessed the extent to which pretreatment pain influences survival in 2,340 newly diagnosed patients with HNSCC, adjusting for disease stage, symptoms, pain medications, comorbidities, smoking, alcohol consumption, age, sex, and race/ethnicity. Patients rated their pain at presentation to the cancer center (0 = "no pain" and 10 = "pain as bad as you can imagine"). Survival time was calculated from the date of diagnosis to the date of death of any cause or last follow-up. Five-year overall survival was calculated for all the variables assessed in the study. Severe pain (≥7) was most prevalent among those with oral cancer (20.4%; pharynx = 18.8%; larynx = 16.1%) and significantly varied by tumor stage, fatigue severity, smoking status, comorbid lung disease, and race (all P < .05) across cancer diagnoses. Overall 5-year survival varied by pain for oral (severe pain = 31% vs nonsevere pain = 52%; P < .001) and pharyngeal cancer (severe pain = 33% vs nonsevere pain = 53%; P < .001). Multivariable analyses showed that pain persisted as an independent prognostic factor for survival. Pain reported prior to treatment should be considered in understanding survival outcomes in HNSCC patients.

Perspective: Pretreatment pain was an independent predictor of survival in a large sample of HNSCC patients even after accounting for tumor node metastasis stage, fatigue, age, race/ethnicity, smoking, and alcohol intake. Therefore, symptoms at presentation and before cancer treatment are important factors to be considered in understanding survival outcomes in HNSCC patients.
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http://dx.doi.org/10.1016/j.jpain.2014.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418559PMC
October 2014

Depressive symptoms among cancer patients in a Philippine tertiary hospital: prevalence, factors, and influence on health-related quality of life.

J Palliat Med 2013 Oct 18;16(10):1280-4. Epub 2013 Sep 18.

1 Palliative Care, Benavides Cancer Institute, University of Santo Tomas Hospital , Manila, Philippines .

Background: The World Health Organization recognizes depression as one of the most burdensome diseases in the world. Among cancer patients, depression is significantly associated with shorter survival, independent of the influence of biomedical prognostic factors. Although cancer is the third leading cause of morbidity and mortality among Filipinos, little is known about depressive symptoms and their influence on health-related quality of life in this population. We assessed the prevalence of, and factors associated with, depressive symptoms and their influence on health-related quality of life in Filipino patients with cancer.

Methods: The Patient Health Questionnaire (PHQ)-8 and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 were administered to all inpatients and outpatients, age >=18 years presenting for cancer treatment.

Results: Twenty-two percent (n=53/247) were categorized as depressed, using a PHQ-8 cutoff of ≥10. Depressed patients scored lower on cognitive, emotional, role, physical, and social functioning than those who scored PHQ<10 (all P<0.001). Depression varied by disease status, performance status and marital status (all P<0.001). However, only performance status (OR [odds ratio]=2.20; 95% CI=1.60, 3.00) and disease status (OR=2.4; 95% CI=1.13, 5.22) were significantly associated with depression in the multivariable model.

Conclusions: Depression is prevalent in Filipino cancer patients. The findings provide empirical support for the development of mental health services in this understudied population. This study, the first to assess the prevalence of and factors associated with depression in Filipino cancer patients, needs further validation.
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http://dx.doi.org/10.1089/jpm.2013.0022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3791049PMC
October 2013

Symptom clusters of pain, depressed mood, and fatigue in lung cancer: assessing the role of cytokine genes.

Support Care Cancer 2013 Nov 13;21(11):3117-25. Epub 2013 Jul 13.

Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Unit 1468, 1155 Pressler Street, Houston, TX, 77030-4009, USA,

Purpose: Symptom clusters, the multiple, co-occurring symptoms experienced by cancer patients, are debilitating and affects quality of life. We assessed if a panel of immune-response genes may underlie the co-occurrence of severe pain, depressed mood, and fatigue and help identify patients with severe versus non-severe symptom clusters.

Methods: Symptoms were assessed at presentation, prior to cancer treatment in 599 newly diagnosed lung cancer patients. We applied cluster analyses to determine the patients with severe versus non-severe symptom clusters of pain, depressed mood, and fatigue.

Results: Two homogenous clusters were identified. One hundred sixteen patients (19 %) comprised the severe symptom cluster, reporting high intensity of pain, depressed mood, and fatigue and 183 (30 %) patients reported low intensity of these symptoms. Using Bayesian model averaging methodology, we found that of the 55 single nucleotide polymorphisms assessed, an additive effect of mutant alleles in endothelial nitric oxide synthase (-1474 T/A) (posterior probability of inclusion (PPI) = 0.78, odds ratio (OR) = 0.54, 95 % credible interval (CI) = (0.31, 0.93)); IL1B T-31C (PPI = 0.72, OR = 0.55, 95 % CI = (0.31, 0.97)); TNFR2 Met(196)Arg (PPI = 0.70, OR = 1.85, 95 % CI = (1.03, 3.36)); PTGS2 exon 10+837T > C (PPI = 0.69, OR = 0.54, 95 % CI = (0.28, 0.99)); and IL10RB Lys(47)Glu (PPI = 0.68; OR = 1.74; 95 % CI = (1.04, 2.92)) were predictive for symptom clusters.

Conclusions: Genetic polymorphisms may facilitate identification of high-risk patients and development of individualized symptom therapies.
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http://dx.doi.org/10.1007/s00520-013-1885-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923575PMC
November 2013

English proficiency, knowledge, and receipt of HPV vaccine in Vietnamese-American women.

J Community Health 2013 Oct;38(5):805-11

Department of Health Sciences, College of Health and Human Development, California State University Northridge, Northridge, CA 91330, USA.

Cervical cancer is one of the most important disease burdens experienced by Vietnamese-American women. Human papillomavirus (HPV) is the etiological agent in almost all cases of cervical cancer. We surveyed Vietnamese-American women to determine receipt of HPV vaccine and assessed if limited English proficiency and knowledge related to HPV vaccine were associated with HPV vaccine uptake. Of the 113 Vietnamese-American women who participated in the study, 58 % (n = 68) was born in Vietnam. The mean years of residency in the United States was 12.75 years. Only 16 (14 %) reported receiving HPV vaccine and 11 (9 %) reported receiving all three shots. Thirteen women responded that they are not at all likely to receive HPV vaccine. Of the whole sample, 47 % (n = 53) reported proficiency in spoken and written English. English proficiency was significantly associated with receipt of HPV vaccine (OR = 4.4; confidence interval (95 % CI) = 1.2; 16.50; p = 0.03). Of the knowledge items, 70 % (n = 79) responded correctly that HPV increases the risk for cervical cancer. However, as many as 60 % responded incorrectly, that HPV infection can be cured with medication. The item, "People infected with HPV can be cured with medication," was the most important variable associated with receipt of HPV vaccine. Specifically, those with correct response were 3.8 times more likely to report receiving the HPV vaccine (OR = 3.8; 95 % CI = 1.1; 13.5; p = 0.04). Important public health needs are the development and evaluation of educational programs on HPV and cervical cancer that are designed for Vietnamese-American women.
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http://dx.doi.org/10.1007/s10900-013-9680-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5204260PMC
October 2013

Biopsychosocial approach to persistent post-mastectomy pain: What can we conclude?

Pain 2013 May 1;154(5):623-624. Epub 2013 Mar 1.

Department of Symptom Research, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Unit 1450, Houston, TX 77030, USA Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Unit 1468, Houston, TX 77030, USA.

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http://dx.doi.org/10.1016/j.pain.2013.02.020DOI Listing
May 2013