Publications by authors named "Canhua Xiao"

27 Publications

  • Page 1 of 1

Association of epigenetic age acceleration with risk factors, survival, and quality of life in patients with head and neck cancer.

Int J Radiat Oncol Biol Phys 2021 Apr 18. Epub 2021 Apr 18.

Emory University School of Nursing.

Purpose: Epigenetic age acceleration (EAA) is robustly linked with mortality and morbidity. This study examined risk factors of EAA and its association with overall survival (OS), progression-free survival (PFS), and quality of life (QOL) in patients with head and neck cancer (HNC) receiving radiotherapy.

Methods And Materials: Patients without distant metastasis were enrolled and followed before and end of radiotherapy, and 6-months and 12-months post-radiotherapy. EAA was calculated with DNAmPhenoAge at all four times. Risk factors included demographics, lifestyle, clinical characteristics, treatment-related symptoms, and blood biomarkers. Survival data were collected until August 2020; QOL was measured using Functional Assessment of Cancer Therapy-HNC.

Results: Increased comorbidity, HPV-unrelated, and severer treatment-related symptoms were associated with higher EAA (p=0.03 to <0.001). A non-linear association (quadratic) between body mass index (BMI) and EAA was observed: decreased BMI (when BMI<35,p=0.04) or increased BMI (when BMI≥35,p=0.01), was linked to higher EAA. Increased EAA (per year) was associated with worse OS (hazard ratio (HR)=1.11,95% CI=[1.03,1.18],p=0.004; HR=1.10,95% CI=[1.01,1.19], p=0.02, for EAA at 6-months and 12-months post-treatment, respectively), PFS (HR=1.10, 95% CI=[1.02,1.19], p=0.02; HR=1.14, 95% CI=[1.06,1.23], p<0.001; HR=1.08,95% CI=[1.02,1.14], p=0.01, for EAA before, end, and 6-months post-radiotherapy, respectively), and QOL over time (β=-0.61,p=0.001). An average of 3.25-3.33 years of age acceleration across time, which was responsible for 33% to 44% higher HRs of OS and PFS, was observed in those who died or developed recurrences compared to those who did not (all p<0.001).

Conclusion: Compared to demographic and lifestyle factors, clinical characteristics were more likely to contribute to faster biological aging in patients with HNC. Acceleration in epigenetic age resulted in more aggressive adverse events including OS and PFS. EAA could be considered as a marker for cancer outcomes, and decelerating aging could improve survival and QOL.
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http://dx.doi.org/10.1016/j.ijrobp.2021.04.002DOI Listing
April 2021

Cultural adaptation and psychometric evaluation of the Chinese version of the nurse-specific end-of-life professional caregiver survey: a cross-sectional study.

BMC Palliat Care 2021 Feb 16;20(1):32. Epub 2021 Feb 16.

Yale University School of Nursing, 400 west Campus Drive, Orange, CT, USA.

Background: Nurses' palliative and hospice care-specific education is associated with the quality of palliative and hospice care that influences health outcomes of patients with life-limiting illnesses and their caregivers. However, China lacks measures available to assess nurses' educational needs in palliative and hospice care. The End-of-Life Professional Caregiver Survey (EPCS) is a psychometrically reliable self-reporting scale to measure multidisciplinary professionals' palliative and hospice care educational needs. This study was performed to explore the psychometric properties of the Chinese version of the EPCS (EPCS-C) among Chinese nurses.

Methods: We translated and culturally adapted the EPCS into Chinese based on Beaton and colleagues' instrument adaptation process. A cross-sectional study design was used. We recruited 312 nurses from 1482 nurses in a tertiary hospital in central China using convenience sampling to complete the study. Participants completed the EPCS-C and a demographic questionnaire. Exploratory and confirmatory factor analysis was carried out to test and verify the construct validity of the nurse-specific EPCS-C. Cronbach's alpha coefficient was used to appraise the reliability of the nurse-specific EPCS-C.

Results: A three-factor structure of EPCS-C was determined, including cultural, ethical, and national values; patient- and family-centered communication; and effective care delivery. The exploratory factor analysis explained 70.82% of the total variances. The 3-factor solution of the nurse-specific EPCS-C had a satisfactory model fit: χ2 = 537.96, χ2/df = 2.96, CFI = 0.94, RMSEA = 0.079, IFI = 0.94, and GFI = 0.86. Cronbach's alpha coefficient of the overall questionnaire was 0.96.

Conclusions: The nurse-specific EPCS-C showed satisfactory reliability and validity to assess nurses' palliative and hospice care educational need. Further research is required to verify the reliability and validity of the EPCS-C in a larger sample, especially the criterion-related validity.
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http://dx.doi.org/10.1186/s12904-021-00725-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885229PMC
February 2021

The role of the gut microbiome in cancer-related fatigue: pilot study on epigenetic mechanisms.

Support Care Cancer 2021 Jun 20;29(6):3173-3182. Epub 2020 Oct 20.

School of Nursing, Emory University, 1520 Clifton Road NE, Atlanta, 30322, USA.

Purpose: Recent evidence supports a key role of gut microbiome in brain health. We conducted a pilot study to assess associations of gut microbiome with cancer-related fatigue and explore the associations with DNA methylation changes.

Methods: Self-reported Multidimensional Fatigue Inventory and stool samples were collected at pre-radiotherapy and one-month post-radiotherapy in patients with head and neck cancer. Gut microbiome data were obtained by sequencing the 16S ribosomal ribonucleic acid gene. DNA methylation changes in the blood were assessed using Illumina Methylation EPIC BeadChip.

Results: We observed significantly different gut microbiota patterns among patients with high vs. low fatigue across time. This pattern was characterized by low relative abundance in short-chain fatty acid-producing taxa (family Ruminococcaceae, genera Subdoligranulum and Faecalibacterium; all p < 0.05), with high abundance in taxa associated with inflammation (genera Family XIII AD3011 and Erysipelatoclostridium; all p < 0.05) for high-fatigue group. We identified nine KEGG Orthology pathways significantly different between high- vs. low-fatigue groups over time (all p < 0.001), including pathways related to fatty acid synthesis and oxidation, inflammation, and brain function. Gene set enrichment analysis (GSEA) was performed on the top differentially methylated CpG sites that were associated with the taxa and fatigue. All biological processes from the GSEA were related to immune responses and inflammation (FDR < 0.05).

Conclusions: Our results suggest different patterns of the gut microbiota in cancer patients with high vs. low fatigue. Results from functional pathways and DNA methylation analyses indicate that inflammation is likely to be the major driver in the gut-brain axis for cancer-related fatigue.
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http://dx.doi.org/10.1007/s00520-020-05820-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055716PMC
June 2021

Gut Microbiome Associated with the Psychoneurological Symptom Cluster in Patients with Head and Neck Cancers.

Cancers (Basel) 2020 Sep 6;12(9). Epub 2020 Sep 6.

School of Nursing, Yale University, New Haven, CT 06477, USA.

Cancer patients experience a cluster of co-occurring psychoneurological symptoms (PNS) related to cancer treatments. The gut microbiome may affect severity of the PNS via neural, immune, and endocrine signaling pathways. However, the link between the gut microbiome and PNS has not been well investigated in cancer patients, including those with head and neck cancers (HNCs). This pilot study enrolled 13 patients with HNCs, who reported PNS using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (CTCAEs). Stool specimens were collected to analyze patients' gut microbiome. All data were collected pre- and post-radiation therapy (RT). Associations between the bacterial abundances and the PNS clusters were analyzed using the linear discriminant analysis effect size; functional pathway analyses of 16S rRNA V3-V4 bacterial communities were conducted using Tax4fun. The high PNS cluster had a greater decrease in microbial evenness than the low PNS cluster from pre- to post-RT. The high and low PNS clusters showed significant differences using weighted UniFrac distance. Those individuals with the high PNS cluster were more likely to have higher abundances in phylum , order , class , and four genera (, and ), while the low PNS cluster had higher abundances in family and three genera (, and ). Both glycan metabolism (Lipopolysaccharide biosynthesis) and vitamin metabolism (folate biosynthesis and lipoic acid metabolism) were significantly different between the high and low PNS clusters pre- and post-RT. Our preliminary data suggest that the diversity and abundance of the gut microbiome play a potential role in developing PNS among cancer patients.
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http://dx.doi.org/10.3390/cancers12092531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563252PMC
September 2020

Association Among Glucocorticoid Receptor Sensitivity, Fatigue, and Inflammation in Patients With Head and Neck Cancer.

Psychosom Med 2020 06;82(5):508-516

From the School of Nursing (Xiao, Knobf), Yale University, Orange, Connecticut; and School of Nursing (Eldridge, Chico, Bruner), School of Medicine (Beitler, Higgins, Saba, Shin), and Department of Psychiatry and Behavioral Sciences, School of Medicine (Felger, Wommack, Miller), Emory University, Atlanta, Gerogia.

Objective: Fatigued cancer patients often have high peripheral inflammation; however, the biological mechanisms of this association remain unclear. We examined whether decreased sensitivity of immune cells to the anti-inflammatory effects of glucocorticoids may contribute to inflammation and fatigue in head and neck cancer (HNC) patients during treatment.

Methods: HNC patients without distant metastasis and with curative intent (n = 77) were studied 1 week before intensity-modulated radiotherapy (IMRT) and 1 month after IMRT. At each time point, fatigue was measured by the Multidimensional Fatigue Inventory-20 along with plasma inflammation markers and glucocorticoid receptor (GR) sensitivity as determined by in vitro dexamethasone suppression of lipopolysaccharide-induced interleukin 6. Linear regression models were used.

Results: In contrast to our hypothesis, GR sensitivity increased during treatment; however, increased fatigue was associated with a lesser increase in GR sensitivity from baseline to 1 month after IMRT (unstandardized estimate = 4.07, p = .02). This effect was more prominent in human papillomavirus-unrelated HNCs (unstandardized estimate = 8.22, p = .002). Lower increases in GR sensitivity were also associated with increased inflammation at 1 month after IMRT as represented by C-reactive protein, interleukin 6, and tumor necrosis factor α. Addition of inflammation markers to models of GR sensitivity predicting fatigue indicated that these inflammation markers were stronger predictors of fatigue than GR sensitivity.

Conclusions: Lower increases in GR sensitivity during HNC treatment were significantly predictive of increased fatigue and inflammation markers. Inflammation markers in turn predicted fatigue above and beyond levels of GR sensitivity. Our findings indicate that HNC patients with cancer-related fatigue may exhibit a decreased capacity for glucocorticoids to regulate inflammatory processes, as evidenced by a lower increase in GR sensitivity. Larger studies are necessary to verify the findings.
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http://dx.doi.org/10.1097/PSY.0000000000000816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905992PMC
June 2020

The State of the Science in Patient-Reported Outcomes for Patients with Lung Cancer.

Semin Respir Crit Care Med 2020 Jun 25;41(3):377-385. Epub 2020 May 25.

Henry Ford Cancer Institute, Henry Ford Health System, Detroit, Michigan.

Traditionally, clinicians have assumed the primary responsibility for evaluating disease- and treatment-related outcomes. In the past few decades, however, a series of recommendations and standards promulgated by professional societies and regulatory agencies have resulted in increased use of patient-reported outcome (PRO) measures in cancer clinical trials. PROs, such as quality of life (QOL) measures, are important in establishing overall treatment effectiveness in cancer clinical trials, and they can inform clinical decision making. This article discusses the current state of the science in PRO research for patients with lung cancer, the cancer type with the highest incidence rate and the lowest survival rate worldwide. The discussion focuses on (1) PRO and survival; (2) electronic PRO reporting and interventions; (3) PROs and immunotherapy; (4) PRO, biomarkers, and precision health; (5) key issues in applying PROs in clinical trials; and (6) future directions for research.
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http://dx.doi.org/10.1055/s-0040-1712099DOI Listing
June 2020

Pilot study of combined aerobic and resistance exercise on fatigue for patients with head and neck cancer: Inflammatory and epigenetic changes.

Brain Behav Immun 2020 08 21;88:184-192. Epub 2020 Apr 21.

School of Nursing, Emory University, 1520 Clifton Road NE, Atlanta 30322, United States.

This pilot study examined whether a combined aerobic resistance exercise program reduced fatigue and the potential inflammatory and epigenetic mechanisms in patients with head and neck cancer (HNC) receiving intensity-modulated radiotherapy. The exercise group (N = 12) received a 3-month supervised aerobic resistance exercise intervention that was initiated before a 6-week radiotherapy regimen; the control group (N = 14) received standard care. Fatigue was measured using Multidimensional Fatigue Inventory-20; physical function measures included a 6-minute walk distance (6MWD), chair stands, bicep curls, and hand grip strength. Inflammatory markers and DNA methylation data were acquired using standardized protocol. Patients were mostly white (93%) and male (81%) with a mean age of 57 years. At the end of the intervention, the exercise group had a marginal decrease in fatigue compared with the control (-5.0 vs. 4.9; P = 0.10). The exercise group had a significantly greater improvement in 6MWD (29.8 vs. -55.5 m; P = 0.04), and a marginally smaller decline in hand grip (-0.3 vs. -5.8 lbs; P = 0.05) at the end of the intervention than the control. No significant difference in inflammatory markers was observed between groups. Lower plasma interleukin (IL) 6, IL1 receptor antagonist, tumor necrosis factor α (TNFα), soluble TNF receptor II and C-reactive protein were significantly associated with increased 6MWD, chair stand, and bicep curl at the end of the intervention (p < 0.05). Among the 1152 differentially methylated sites (DMS) after intervention (p < 0.001), 163 DMS were located in gene promoter regions. Enrichment analysis suggested that the top 10 upstream regulators were associated with tumor (HNF4A, RPP38, HOXA9, SAHM1, CDK7, NDN, RPS15) and inflammation (IRF7, CRKL, ONECUT1). The top 5 diseases or functions annotations of the 62 hypermethylated DMS indicated anti-tumor and anti-inflammatory effects that might be linked to exercise. These findings suggest that exercise may improve physical performance and reduce fatigue, which could be further linked to decreased inflammation, during active radiotherapy for HNC patients. Larger studies are warranted.
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http://dx.doi.org/10.1016/j.bbi.2020.04.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415514PMC
August 2020

A Comparison of Missing-Data Imputation Techniques in Exploratory Factor Analysis.

J Nurs Meas 2019 08;27(2):313-334

University of Pennsylvania, Philadelphia, Pennsylvania.

Background And Purpose: To compare the effects of missing-data imputation techniques, mean imputation, group mean imputation, regression imputation, and multiple imputation (MI), on the results of exploratory factor analysis under different missing assumptions.

Methods: Missing data with different missing assumptions were generated from true data. The quality of imputed data was examined by correlation coefficients. Factor structures were compared indirectly by coefficients of congruence and directly by factor structures.

Results: MI had the best quality and matching factor structure to the true data for all missing assumptions with different missing rates. Mean imputation had the least favorable results in factor analysis. The imputation techniques revealed no important differences with 10% of data missing.

Conclusion: MI showed the best results, especially with larger proportions of missing data.
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http://dx.doi.org/10.1891/1061-3749.27.2.313DOI Listing
August 2019

Changing functional status within 6 months posttreatment is prognostic of overall survival in patients with head and neck cancer: NRG Oncology Study.

Head Neck 2019 11 22;41(11):3924-3932. Epub 2019 Aug 22.

Emory University/Winship Cancer Center, Atlanta, Georgia.

Background: Is posttreatment functional status prognostic of overall survival in patients with head and neck cancer (HNC).

Methods: In an HNC clinical trial, 495 patients had two posttreatment functional assessments measuring diet, public eating, and speech within 6 months. Patients were grouped by impairment (highly, moderately, modestly, or not impaired) and determined if they improved, declined, or did not change from the first assessment to the second. Multivariable Cox models estimated overall mortality.

Results: Across all three scales, the change in posttreatment patient function strongly predicted overall survival. In diet, patients who declined to highly impaired had three times the mortality of patients who were not impaired at both assessments (hazard ratio [HR] = 3.60; 95% confidence interval, 2.02-6.42). For patients improving from highly impaired, mortality was statistically similar to patients with no impairment (HR = 1.38; 95% CI, 0.82-2.31).

Conclusions: Posttreatment functional status is a strong prognostic marker of survival in patients with HNC.
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http://dx.doi.org/10.1002/hed.25922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865821PMC
November 2019

Smoking, age, nodal disease, T stage, p16 status, and risk of distant metastases in patients with squamous cell cancer of the oropharynx.

Cancer 2019 03 11;125(5):704-711. Epub 2018 Dec 11.

NRG Oncology.

Background: With an expectation of excellent locoregional control, ongoing efforts to de-intensify therapy for patients with human papillomavirus-associated squamous cell oropharyngeal cancer necessitate a better understanding of the metastatic risk for patients with this disease. The objective of this study was to determine what factors affect the risk of metastases in patients with squamous cell cancers of the oropharynx.

Methods: Under a shared use agreement, 547 patients from Radiation Therapy Oncology Group 0129 and 0522 with nonmetastatic oropharyngeal squamous cell cancers who had a known p16 status and smoking status were analyzed to assess the association of clinical features with the development of distant metastases. The analyzed factors included the p16 status, sex, T stage, N stage, age, and smoking history.

Results: A multivariate analysis of 547 patients with a median follow-up of 4.8 years revealed that an age ≥ 50 years (hazard ratio [HR], 3.28; P = .003), smoking for more than 0 pack-years (HR, 3.09; P < .001), N3 disease (HR, 2.64; P < .001), T4 disease (HR, 1.63; P = .030), and a negative p16 status (HR, 1.60; P = .044) were all factors associated with an increased risk of distant disease.

Conclusions: Age, smoking, N3 disease, T4 disease, and a negative p16 status were associated with the development of distant metastases in patients with squamous cell cancers of the oropharynx treated definitively with concurrent chemoradiation.
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http://dx.doi.org/10.1002/cncr.31820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463275PMC
March 2019

CD8+ tumor-infiltrating lymphocytes as a novel prognostic biomarker in lung sarcomatoid carcinoma, a rare subtype of lung cancer.

Cancer Manag Res 2018 13;10:3505-3511. Epub 2018 Sep 13.

Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China,

Purpose: The aim of this study was to investigate the degree of infiltration of CD8+ tumor-infiltrating lymphocytes (TILs) including high and low density in lung sarcomatoid carcinoma (LSC) and their clinicopathological significance.

Patients And Methods: The density of CD8+ TILs in paraffin-embedded tissue sections from 100 LSC patients was detected by immunohistochemical staining, and the relationship of CD8+ TILs with clinicopathological features and prognosis was analyzed.

Results: The chi-squared test showed that the degree of infiltration of CD8+ TILs was significantly correlated with the clinicopathological stage and T stage of LSC (<0.05). The univariate analysis demonstrated that tumor size, clinicopathological stage, T stage, N stage, M stage, and CD8+ TILs are risk factors that affect prognosis of the patients (<0.05). The mean overall survival (OS) of LSC patients with a high density of CD8+ TILs was 92.3 months, which was significantly higher than 31.2 months in patients with a low density of CD8+ TILs (<0.05). Cox regression multivariate analysis confirmed that the density of CD8+ TILs was an independent prognostic factor for OS time of LSC patients (hazard ratio=0.455, <0.05).

Conclusion: CD8+ TILs could be used as an effective prognostic index for LSC patients, and a high density of CD8+ TILs in tumor tissue may predict a better outcome.
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http://dx.doi.org/10.2147/CMAR.S169074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145683PMC
September 2018

Differential regulation of NF-kB and IRF target genes as they relate to fatigue in patients with head and neck cancer.

Brain Behav Immun 2018 11 11;74:291-295. Epub 2018 Sep 11.

Division of Hematology-Oncology, UCLA AIDS Institute, Molecular Biology Institute, Jonsson Comprehensive Cancer Center, and Norman Cousins Center, UCLA School of Medicine, Los Angeles, CA 90095, United States.

Previous studies have linked plasma inflammatory markers to elevated fatigue in patients with head and neck cancer (HNC). To identify the molecular mechanisms underlying this association, we conducted promoter-based bioinformatics analyses to determine the relationship between fatigue and specific gene expression profiles associated with inflammation in human papillomavirus (HPV)-related and -unrelated HNC patients undergoing treatment. Patients with newly diagnosed HNC without distant metastasis were assessed at baseline (pre-radiotherapy) and one-month post-radiotherapy. Fatigue was measured by the Multidimensional Fatigue Inventory. Genome-wide gene expression profiles were collected from peripheral blood mononuclear cells (PBMC). Promoter-based bioinformatics analyses were employed to identify transcription control pathways underlying transcriptomic correlates of fatigue in the sample as a whole and in HPV-related and HPV-unrelated HNC patients separately. In transcriptome profiling analyses of PBMC from 44 patients, TELiS bioinformatics analyses linked fatigue to increased nuclear factor-kappa B (NF-kB) transcriptional activity and decreased interferon regulatory factor family (IRF) transcription factor activity. Patients with HPV-related HNC showed lower levels of fatigue-related gene expression profile compared to HPV-unrelated HNC. Fatigue in HNC patients undergoing treatment is associated with gene expression profiles consistent with the conserved transcriptional response to adversity (CTRA) characterized by increased proinflammatory and decreased anti-antiviral transcriptional activity. Interestingly, this CTRA response was mitigated in patients with HPV-related HNC and may explain the lower level of fatigue they experience relative to HPV-unrelated HNC.
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http://dx.doi.org/10.1016/j.bbi.2018.09.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289813PMC
November 2018

Risk factors for late bowel and bladder toxicities in NRG Oncology prostate cancer trials of high-risk patients: A meta-analysis of physician-rated toxicities.

Adv Radiat Oncol 2018 Jul-Sep;3(3):405-411. Epub 2018 Jun 7.

Emory University, Atlanta, Georgia.

Purpose: A meta-analysis of sociodemographic variables and their association with late (>180 days from start of radiation therapy[RT]) bowel, bladder, and clustered bowel and bladder toxicities was conducted in patients with high-risk (clinical stages T2c-T4b or Gleason score 8-10 or prostate-specific antigen level >20) prostate cancer.

Methods And Materials: Three NRG trials (RTOG 9202, RTOG 9413, and RTOG 9406) that accrued from 1992 to 2000 were used. Late toxicities were measured with the Radiation Therapy Oncology Group Late Radiation Morbidity Scale. After controlling for study, age, Karnofsky Performance Status, and year of accrual, sociodemographic variables were added to the model for each outcome variable of interest in a stepwise fashion using the Fine-Gray regression models with an entry criterion of 0.05.

Results: A total of 2432 patients were analyzed of whom most were Caucasian (76%), had a KPS score of 90 to 100 (92%), and received whole-pelvic RT+HT (67%). Of these patients, 13 % and 16% experienced late grade ≥2 bowel and bladder toxicities, respectively, and 2% and 3% experienced late grade ≥3 bowel and bladder toxicities, respectively. Late grade ≥2 clustered bowel and bladder toxicities were seen in approximately 1% of patients and late grade ≥3 clustered toxicities were seen in 2 patients (<1%). The multivariate analysis showed that patients who received prostate-only RT+HT had a lower risk of experiencing grade ≥2 bowel toxicities than those who received whole-pelvic RT+long-term (LT) HT (hazard ratio: 0.36; 95% confidence interval, 0.18-0.73;  = .0046 and hazard ratio: 0.43; 95% confidence interval, 0.23-0.80;  = .008, respectively). Patients who received whole-pelvic RT had similar chances of having grade ≥2 bowel or bladder toxicities no matter whether they received LT or short-term HT.

Conclusions: Patients with high-risk prostate cancer who receive whole-pelvic RT+LT HT are more likely to have a grade ≥2 bowel toxicity than those who receive prostate-only RT. LT bowel and bladder toxicities were infrequent. Future studies will need to confirm these findings utilizing current radiation technology and patient-reported outcomes.
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http://dx.doi.org/10.1016/j.adro.2018.04.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128023PMC
June 2018

Associations among human papillomavirus, inflammation, and fatigue in patients with head and neck cancer.

Cancer 2018 08 9;124(15):3163-3170. Epub 2018 May 9.

Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, Atlanta, Georgia.

Background: Human papillomavirus (HPV) infection has contributed to an increased incidence of squamous cell carcinoma of the head and neck (SCCHN). Fatigue is a major side effect of SCCHN and its treatment. However, to the authors' knowledge, the association between HPV and fatigue has not been examined to date, nor is it known whether HPV influences biological mechanisms of fatigue, including inflammation.

Methods: Patients with SCCHN who were without distant metastasis were assessed at baseline (pre-radiotherapy) and 1 month and 3 months postradiotherapy. Fatigue was measured using the Multidimensional Fatigue Inventory. Peripheral inflammation was assessed by plasma C-reactive protein (CRP), interleukin 1 receptor antagonist (IL-1ra), soluble tumor necrosis factor receptor 2 (sTNFR2), and IL-6. Mixed effect models were used to examine associations.

Results: A total of 94 patients who were newly diagnosed were enrolled; 53% had HPV-related tumors. Patients with HPV-unrelated tumors had higher fatigue and higher plasma CRP, sTNFR2, and IL-6 over time, especially at baseline and 3 months after intensity-modulated radiotherapy compared with those with HPV-related tumors (all P < .05). However, fatigue and plasma sTNFR2 increased more significantly from baseline to 1 month after radiotherapy in the HPV-related group compared with the HPV-unrelated group (both P < .01). Controlling for significant covariates, HPV status and inflammation were found to be independent predictors of fatigue over time.

Conclusions: HPV status is an important marker of vulnerability to the behavioral and immune consequences of SCCHN and its treatment, providing support for different symptom management strategies. Special emphasis should be placed on addressing marked persistent fatigue in patients with HPV-unrelated tumors, whereas attention should be paid to the large increases in fatigue during treatment among patients with HPV-related tumors. Cancer 2018. © 2018 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.31537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097898PMC
August 2018

Brainstem dose is associated with patient-reported acute fatigue in head and neck cancer radiation therapy.

Radiother Oncol 2018 01 18;126(1):100-106. Epub 2017 Aug 18.

Department of Radiation Oncology, Emory University, Atlanta, USA; Winship Cancer Institute of Emory University, Atlanta, USA.

Background And Purpose: Radiation (RT) dose to the central nervous system (CNS) has been implicated as a contributor to treatment-related fatigue in head and neck cancer (HNC) patients undergoing radiation therapy (RT). This study evaluates the association of RT dose to CNS structures with patient-reported (PRO) fatigue scores in a population of HNC patients.

Materials And Methods: At pre-RT (baseline), 6th week of RT, and 1-month post-RT time points, Multidimensional Fatigue Inventory (MFI-20) scores were prospectively obtained from 124 patients undergoing definitive treatment for HNC. Medulla, pons, midbrain, total brainstem, cerebellum, posterior fossa, and pituitary dosimetry were evaluated using summary statistics and dose-volume histograms, and associations with MFI-20 scores were analyzed.

Results: Maximum dose (Dmax) to the brainstem and medulla was significantly associated with MFI-20 scores at 6th week of RT and 1-month post-RT time points, after controlling for baseline scores (p<0.05). Each 1Gy increase in medulla Dmax resulted in an increase in total MFI-20 score over baseline of 0.30 (p=0.026), and 0.25 (p=0.037), at the 6th week of RT and 1-month post-RT, respectively. Each 1Gy increase in brainstem Dmax resulted in an increase in total MFI-20 score over baseline of 0.30 (p=0.027), and 0.25 (p=0.037) at the 6th week of RT, 1-month post-RT, respectively. Statistically significant associations were not found between dosimetry for the other CNS structures and MFI-20 scores.

Conclusions: In this analysis of PRO fatigue scores from a population of patients undergoing definitive RT for HNC, maximum dose to the brainstem and medulla was associated with a significantly increased risk of acute patient fatigue.
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http://dx.doi.org/10.1016/j.radonc.2017.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841457PMC
January 2018

Advancing Symptom Science Through Symptom Cluster Research: Expert Panel Proceedings and Recommendations.

J Natl Cancer Inst 2017 04 24;109(4). Epub 2017 Jan 24.

Affiliations of authors: School of Nursing, University of California, San Francisco, San Francisco, CA (CM); College of Medicine, Thomas Jefferson University, Philadelphia, PA (ABa); University of Nebraska Medical Center, Center for Nursing Science-Omaha Division, Omaha, NE (ABe); Gryphon Scientific, Takoma Park, MD (RC); National Institute of Nursing Research, Bethesda, MD (PAG, MM, SM); Moffitt Cancer Center and Research Institute, Tampa, FL (PJ); School of Medicine, University of Colorado, Aurora, CO (JK); School of Public Health and Community Medicine, University of Washington, Seattle, WA (DP); University of Nebraska Medical Center, College of Nursing-Lincoln Division, Lincoln, NE (LZ); School of Nursing, Emory University, Atlanta, GA (CX).

An overview of proceedings, findings, and recommendations from the workshop on "Advancing Symptom Science Through Symptom Cluster Research" sponsored by the National Institute of Nursing Research (NINR) and the Office of Rare Diseases Research, National Center for Advancing Translational Sciences, is presented. This workshop engaged an expert panel in an evidenced-based discussion regarding the state of the science of symptom clusters in chronic conditions including cancer and other rare diseases. An interdisciplinary working group from the extramural research community representing nursing, medicine, oncology, psychology, and bioinformatics was convened at the National Institutes of Health. Based on expertise, members were divided into teams to address key areas: defining characteristics of symptom clusters, priority symptom clusters and underlying mechanisms, measurement issues, targeted interventions, and new analytic strategies. For each area, the evidence was synthesized, limitations and gaps identified, and recommendations for future research delineated. The majority of findings in each area were from studies of oncology patients. However, increasing evidence suggests that symptom clusters occur in patients with other chronic conditions (eg, pulmonary, cardiac, and end-stage renal disease). Nonetheless, symptom cluster research is extremely limited and scientists are just beginning to understand how to investigate symptom clusters by developing frameworks and new methods and approaches. With a focus on personalized care, an understanding of individual susceptibility to symptoms and whether a "driving" symptom exists that triggers other symptoms in the cluster is needed. Also, research aimed at identifying the mechanisms that underlie symptom clusters is essential to developing targeted interventions.
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http://dx.doi.org/10.1093/jnci/djw253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5939621PMC
April 2017

A systematic review of the association between fatigue and genetic polymorphisms.

Brain Behav Immun 2017 May 12;62:230-244. Epub 2017 Jan 12.

School of Nursing, Emory University, Atlanta, GA, United States. Electronic address:

Fatigue is one of the most common and distressing symptoms, leading to markedly decreased quality of life among a large subset of patients with a variety of disorders. Susceptibility to fatigue may be influenced by genetic factors including single nucleotide polymorphisms (SNPs), especially in the regulatory regions, of relevant genes. To further investigate the association of SNPs with fatigue in various patient populations, a systematic search was conducted on Pubmed, CINAHL, PsycINFO, and Sociological Abstracts Database for fatigue related-terms in combination with polymorphisms or genetic variation-related terms. Fifty papers in total met the inclusion and exclusion criteria for this analysis. These 50 papers were further classified into three subgroups for evaluation: chronic fatigue syndrome (CFS), cancer-related fatigue (CRF) and other disease-related fatigue. SNPs in regulatory pathways of immune and neurotransmitter systems were found to play important roles in the etiologies of CFS, CRF and other disease-related fatigue. Evidence for associations between elevated fatigue and specific polymorphisms in TNFα, IL1b, IL4 and IL6 genes was revealed for all three subgroups of fatigue. We also found CFS shared a series of polymorphisms in HLA, IFN-γ, 5-HT and NR3C1 genes with other disease-related fatigue, however these SNPs (excluding IFN-γ) were not found to be adequately investigated in CRF. Gaps in knowledge related to fatigue etiology and recommendations for future research are further discussed.
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http://dx.doi.org/10.1016/j.bbi.2017.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5947855PMC
May 2017

Quality of Life and Performance Status From a Substudy Conducted Within a Prospective Phase 3 Randomized Trial of Concurrent Standard Radiation Versus Accelerated Radiation Plus Cisplatin for Locally Advanced Head and Neck Carcinoma: NRG Oncology RTOG 0129.

Int J Radiat Oncol Biol Phys 2017 03 25;97(4):667-677. Epub 2016 Jul 25.

Emory University, Atlanta, Georgia.

Purpose/objective(s): To analyze quality of life (QOL) and performance status (PS) for head and neck cancer (HNC) patients treated on NRG Oncology RTOG 0129 by treatment (secondary outcome) and p16 status, and to examine the association between QOL/PS and survival.

Methods And Materials: Eligible patients were randomized into either an accelerated-fractionation arm or a standard-fractionation arm, and completed the Performance Status Scale for the Head and Neck (PSS-HN), the Head and Neck Radiotherapy Questionnaire (HNRQ), and the Spitzer Quality of Life Index (SQLI) at 8 time points from before treatment to 5 years after treatment.

Results: The results from the analysis of area under the curve showed that QOL/PS was not significantly different between the 2 arms from baseline to year after treatment (P ranged from .39 to .98). The results from general linear mixed models further supported the nonsignificant treatment effects until 5 years after treatment (P=.95, .90, and .84 for PSS-HN Diet, Eating, and Speech, respectively). Before treatment and after 1 year after treatment, p16-positive oropharyngeal cancer (OPC) patients had better QOL than did p16-negative patients (P ranged from .0283 to <.0001 for all questionnaires). However, QOL/PS decreased more significantly from pretreatment to the last 2 weeks of treatment in the p16-positive group than in the p16-negative group (P ranged from .0002 to <.0001). Pretreatment QOL/PS was a significant independent predictor of overall survival, progression-free survival, and local-regional failure but not of distant metastasis (P ranged from .0063 to <.0001).

Conclusions: The results indicated that patients in both arms may have experienced similar QOL/PS. p16-positive patients had better QOL/PS at baseline and after 1 year of follow-up. Patients presenting with better baseline QOL/PS scores had better survival.
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http://dx.doi.org/10.1016/j.ijrobp.2016.07.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266672PMC
March 2017

A prospective study of quality of life in breast cancer patients undergoing radiation therapy.

Adv Radiat Oncol 2016 Jan-Mar;1(1):10-16

Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.

Purpose/objective: The purpose of this study was to examine the impact of radiotherapy on quality of life (QOL) of breast cancer patients during and until 1 year post radiotherapy treatment.

Methods And Materials: Thirty-nine breast cancer patients treated with breast conserving surgery were enrolled in a prospective study prior to whole breast radiotherapy (50 Gy plus a 10 Gy boost). No patient received chemotherapy. Data were collected before, at week 6 of radiotherapy, 6 weeks, and 1 year post-radiotherapy. The primary outcome variable was quality of life (QOL), measured by Medical Outcomes Study 36-Item Short Form Version 2 (SF-36) (SF-36). Risk factors potentially associated with total SF-36 scores and its physical and mental health component summary scores were also examined including age, race, marital status, smoking history, menopausal status, endocrine treatment, cancer stage, sleep abnormalities (assessed by the Pittsburgh Sleep Quality Index) and perceived stress levels (assessed by Perceived Stress Scale). Mixed effect modeling was utilized to observe QOL changes during and after radiotherapy.

Results: Total SF-36 scores did not change significantly during and up to 1 year after radiotherapy compared to baseline measures. Nevertheless, increased BMI and increased perceived stress were predictive of reduced total SF-36 scores over time (p=0.0064, and p<0.0001, respectively). In addition, increased BMI was predictive of reduced physical component summary scores of the SF-36 (p=0.0011), while increased perceived stress was predictive of worse mental component summary scores (p<0.0001). Other proposed potential risk factors including skin toxicity from radiotherapy were not significant.

Conclusions: Radiotherapy did not worsen QOL in breast cancer patients. However, pre-radiotherapy patient characteristics including BMI and perceived stress may be used to identify women who may experience decreased physical and mental function during and up to 1 year post-radiotherapy.
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http://dx.doi.org/10.1016/j.adro.2016.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950982PMC
July 2016

Fatigue is associated with inflammation in patients with head and neck cancer before and after intensity-modulated radiation therapy.

Brain Behav Immun 2016 Feb 30;52:145-152. Epub 2015 Oct 30.

Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, 1365-B Clifton Road, Atlanta, GA 30322, United States.

Patients with head and neck cancer (HNC) receiving intensity-modulated radiation therapy (IMRT) have particularly high rates of fatigue, and pre- and post-radiotherapy fatigue are prognostic factors for pathologic tumor responses and poor survival. Although inflammation has been proposed as one of the potential mechanisms of fatigue in cancer patients, findings have not been consistent, and there is a dearth of longitudinal studies. Accordingly, we conducted a prospective study in 46 HNC patients pre- and one-month post-IMRT. Fatigue was measured by the Multidimensional Fatigue Inventory (MFI)-20 at both time points along with the assessment of peripheral blood inflammatory markers including interleukin (IL)-6, soluble tumor necrosis factor receptor 2, and C-reactive protein (CRP) and gene expression. Generalized estimating equations were used to examine the association between inflammatory markers and fatigue. Gene enrichment analysis using MetaCore software was performed using up-regulated genes that were significantly associated with IMRT and fatigue. Significant associations between fatigue and IL-6 as well as CRP, which were independent of time, were observed. In addition the change in fatigue from pre- to post-IMRT was positively associated with the change in IL-6 and CRP. Analysis of up-regulated gene transcripts as a function of IMRT and fatigue revealed overrepresentation of transcripts related to the defense response and nuclear factor kappa B. In conclusion, our findings support the hypotheses that inflammation is associated with fatigue over time in HNC patients. Future studies on how inflammation contributes to fatigue as well as strategies targeting inflammation to reduce fatigue are warranted.
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http://dx.doi.org/10.1016/j.bbi.2015.10.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867228PMC
February 2016

Preliminary patient-reported outcomes analysis of 3-dimensional radiation therapy versus intensity-modulated radiation therapy on the high-dose arm of the Radiation Therapy Oncology Group (RTOG) 0126 prostate cancer trial.

Cancer 2015 Jul 2;121(14):2422-30. Epub 2015 Apr 2.

Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California.

Background: The authors analyzed a preliminary report of patient-reported outcomes (PROs) among men who received high-dose radiation therapy (RT) on Radiation Therapy Oncology Group study 0126 (a phase 3 dose-escalation trial) with either 3-dimensional conformal RT (3D-CRT) or intensity-modulated RT (IMRT).

Methods: Patients in the 3D-CRT group received 55.8 gray (Gy) to the prostate and proximal seminal vesicles and were allowed an optional field reduction; then, they received 23.4 Gy to the prostate only. Patients in the IMRT group received 79.2 Gy to the prostate and proximal seminal vesicles. PROs were assessed at 0 months (baseline), 3 months, 6 months, 12 months, and 24 months and included bladder and bowel function assessed with the Functional Alterations due to Changes in Elimination (FACE) instrument and erectile function assessed with the International Index of Erectile Function (IIEF). Analyses included the patients who completed all data at baseline and for at least 1 follow-up assessment, and the results were compared with an imputed data set.

Results: Of 763 patients who were randomized to the 79.2-Gy arm, 551 patients and 595 patients who responded to the FACE instrument and 505 patients and 577 patients who responded to the IIEF were included in the completed and imputed analyses, respectively. There were no significant differences between modalities for any of the FACE or IIEF subscale scores or total scores at any time point for either the completed data set or the imputed data set.

Conclusions: Despite significant reductions in dose and volume to normal structures using IMRT, this robust analysis of 3D-CRT and IMRT demonstrated no difference in patient-reported bowel, bladder, or sexual functions for similar doses delivered to the prostate and proximal seminal vesicles with IMRT compared with 3D-CRT delivered either to the prostate and proximal seminal vesicles or to the prostate alone.
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http://dx.doi.org/10.1002/cncr.29362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490066PMC
July 2015

Methods for examining cancer symptom clusters over time.

Res Nurs Health 2014 Feb;37(1):65-74

Nell Hodgson Woodruff School of Nursing, Emory University, 1520 Clifton Road NE, Room 225, Atlanta, GA, 30322-4207.

In this article, we address statistical techniques appropriate for examining longitudinal changes in cancer symptom clusters. When the cluster structure is not pre-determined, researchers may examine symptom clusters either at each time point or use composite scores to examine the symptom clusters across time points. When the cluster structures are pre-determined, the statistical techniques depend on the research assumptions or purposes. Multilevel modeling, generalized estimating equations, latent growth curve modeling, and multivariate repeated-measure analysis of variance are good choices for exploring whole cluster changes over time. Alternately, confirmatory factor analysis and path analysis are appropriate techniques for examining changes in symptom relationships within clusters over time. Each technique is described, with examples and strengths and weaknesses.
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http://dx.doi.org/10.1002/nur.21572DOI Listing
February 2014

Risk factors for clinician-reported symptom clusters in patients with advanced head and neck cancer in a phase 3 randomized clinical trial: RTOG 0129.

Cancer 2014 Mar 11;120(6):848-54. Epub 2013 Dec 11.

School of Nursing, Emory University, Atlanta, Georgia.

Background: Chemoradiotherapy has become the standard of care for head and neck squamous cell carcinoma; however, those patients often experience multiple treatment-related symptoms or symptom clusters. Two symptom clusters have been identified for this population. Little is known about the risk factors of these symptom clusters.

Methods: Subjects comprised 684 patients who were treated with concurrent chemoradiotherapy in a phase 3 randomized clinical trial. This trial compared standard fractionation radiotherapy to accelerated fractionation radiotherapy. Symptom clusters were evaluated at the end of the first and the second cycle of chemotherapy, and 3 months after the start of radiotherapy. Mixed-effect modeling was used to observe risk factors for symptom clusters.

Results: Race and education were independent predictors for the head and neck cluster, whereas sex and history of tobacco use were independent predictors for the gastrointestinal cluster. Primary cancer site was only significant for the head and neck cluster when other factors were not controlled: patients with oropharyngeal cancer had more severe symptoms in the head and neck clusters than did patients with laryngeal cancer. In addition, patients receiving accelerated fractionation radiotherapy experienced more symptoms of radiomucositis, pain, and nausea at 3 months after the start of radiotherapy than those receiving standard fractionation radiotherapy.

Conclusions: Demographic characteristics were more predictive to symptom clusters, whereas clinical characteristics, such as cancer site and treatment arms, were more significant for individual symptoms. Knowing the risk factors will enhance the capability of clinicians to evaluate patients' risk of severe symptom clusters and to personalize management strategies.
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http://dx.doi.org/10.1002/cncr.28500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3947661PMC
March 2014

Symptom clusters in patients with head and neck cancer receiving concurrent chemoradiotherapy.

Oral Oncol 2013 Apr 17;49(4):360-6. Epub 2012 Nov 17.

Emory University School of Nursing, 1520 Clifton Road NE, Atlanta, GA 30322, USA.

Objectives: This study is to identify symptom clusters for head and neck (HNC) patients treated with concurrent chemoradiotherapy.

Patients And Methods: A secondary data analysis of 684 HNC patients treated on the Radiation Therapy Oncology Group (RTOG) 0129 trial comparing different RT fractionation schedules with concurrent chemotherapy was used to examine clusters. Treatment-related symptoms were measured by clinicians at three time-points during and after chemoradiotherapy using the National Cancer Institute Common Toxicity Criteria v2.0. Exploratory factor analysis was applied to identify symptom clusters, which was further verified by confirmatory factor analysis. Coefficients of congruence and alpha coefficients were employed to examine generalizability of cluster structures over different time-points and in different subgroups.

Results: Two clusters were identified. The HNC specific cluster is composed of radiodermatitis, dysphagia, radiomucositis, dry mouth, pain, taste disturbance, and fatigue. The gastrointestinal (GI) cluster involves nausea, vomiting, and dehydration. With the exception of patients 65years old or older, diagnosed with larynx cancer, or with stage III cancer, the two clusters were generalizable to different subgroups defined by age, gender, race, education, marital status, history of tobacco use, treatments, primary sites, disease stages, and tube feedings, as well as to the three symptom assessment time-points.

Conclusions: The data provides preliminary support for two stable clusters in patients with HNC. These findings may serve to inform the symptom management in clinical practice. Moreover, the findings necessitate future research to examine the generalizability of identified clusters in the late symptom phase or other treatment modalities, and to understand the underlying biological mechanism.
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http://dx.doi.org/10.1016/j.oraloncology.2012.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924732PMC
April 2013

Comparison between patient-reported and clinician-observed symptoms in oncology.

Cancer Nurs 2013 Nov-Dec;36(6):E1-E16

Author Affiliations: School of Nursing, Emory University, Atlanta, Georgia (Drs Xiao and Bruner); and School of Nursing, University of Pennsylvania, Philadelphia (Dr Polomano).

Background: Symptom assessment is critical to understand the effectiveness of cancer treatment. Traditionally, clinicians have provided the information about cancer patients' symptoms. However, current research has shown that there are discrepancies on symptom assessment results reported by patients themselves and clinicians.

Objective: The objective of this study was to present an integrative review on studies comparing patient-reported symptoms and clinician-observed symptoms in patients with a diagnosis of cancer.

Methods: This was a review of published articles from PubMed, CINAHL, and the Cochrane Database, using the key words symptom or toxicity, and patient-reported, patient-rated, patient-assessed or patient-evaluated, which were combined with cancer, oncology, neoplasm, or tumor.

Results: Clinicians have the propensity to underestimate the incidence, severity, or distress of symptoms experienced by cancer patients. These discrepancies appear to be consistently demonstrated over time and become even more apparent when symptoms are more severe and distressing to patients. In addition, patients report both symptom frequency and severity earlier than clinicians do; patients' symptom assessments are more predictable for daily health status, whereas clinicians' symptom measurements are more related to clinical outcomes.

Conclusions: Healthcare professionals must appreciate that there can be discordance between what they perceive and what patients experience and report. Further research needs to address methodological limitations and weaknesses of existing literature.

Implications For Practice: Symptoms reported by patients themselves provide the necessary and different insight into cancer and its treatment, compared with those observed by clinicians. The use of patient-reported symptoms should be incorporated into routine clinical practice and not just research studies.
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http://dx.doi.org/10.1097/NCC.0b013e318269040fDOI Listing
August 2014

Exercise training improves systolic function in hypertensive myocardium.

J Appl Physiol (1985) 2011 Dec 15;111(6):1637-43. Epub 2011 Sep 15.

Univ. of Pennsylvania School of Nursing, Biobehavioral and Health Sciences, Philadelphia, PA, USA.

The general purpose of this study was to test the effect of exercise training on the left ventricular (LV) pressure-volume relationship (LV/PV) and apoptotic signaling markers in normotensive and hypertensive hearts. Four-month-old female normotensive Wistar-Kyoto rats (WKY; n = 37) and spontaneously hypertensive rats (SHR; n = 38) were assigned to a sedentary (WKY-SED, n = 21; SHR-SED, n = 19) or treadmill-trained (WKY-TRD, n = 16; SHR-TRD, n = 19) group (∼60% Vo(2 peak), 60 min/day, 5 days/wk, 12 wk). Ex vivo LV/PV were established in isovolumic Langendorff-perfused hearts, and LV levels of Akt, phosphorylated Akt (Akt(Pi)), Bad, phosphorylated Bad (Bad(Pi)) c-IAP, x-IAP, calcineurin, and caspases 3, 8, and 9 were measured. Heart-to-body weight ratio was increased in SHR vs. WKY (P < 0.05), concomitant with increased calcineurin mRNA (P < 0.05). There was a rightward shift in the LV/PV (P < 0.05) and a reduction in systolic elastance (E(s)) in SHR vs. WKY. Exercise training corrected E(s) in SHR (P < 0.05) but had no effect on the LV/PV in WKY. Caspase 3 was increased in SHR-SED relative to WKY-SED, while Bad(Pi,) c-IAP, and x-IAP were significantly lower in SHR relative to WKY (P < 0.05). Exercise training increased Bad(Pi) in both WKY and SHR but did not alter caspase 9 activity in either group. While caspase 3 activity was increased with training in WKY (P < 0.05), it was unchanged with training in SHR. We conclude that moderate levels of regular aerobic exercise attenuate systolic dysfunction early in the compensatory phase of hypertrophy, and that a differential phenotypical response to moderate-intensity exercise exists between WKY and SHR.
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http://dx.doi.org/10.1152/japplphysiol.00292.2011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3233879PMC
December 2011

The state of science in the study of cancer symptom clusters.

Authors:
Canhua Xiao

Eur J Oncol Nurs 2010 Dec 4;14(5):417-34. Epub 2010 Jul 4.

School of Nursing, University of Pennsylvania, Claire M. Fagin Hall, 418 Curie Boulevard, Philadelphia, PA 19104-4217, USA.

Purpose: To provide an integrative review of the literature on the science of symptom clusters in patients with cancer and establish implications for future studies.

Methods: Sixty-one articles about cancer symptom clusters were selected for review from results of a search in MEDLINE, CINAHL, PsycINFO, Sociological Abstracts and Cochrane databases from 1950 to 2010.

Results: This review discusses the current research on the definitions, theoretical frameworks, measurements, outcomes, and interventions of symptom clusters in oncology. Although symptom clusters were identified as groups of several related and coexisted symptoms, researchers had different opinion on the least number of and relationships among symptoms in a cluster. Four theoretical frameworks were used, but none of them were specific to guide research in symptom clusters for general cancer population. Most-common symptom approach and all-possible symptom approach had their own characteristics and methods for cluster identification. Functional status and quality of life were major outcomes that were negatively associated with the number or severity of symptom clusters. Interventions with multiple or central symptoms in clusters were two potential ways to improve patients' symptom experience.

Conclusions: Despite advances in understanding of symptom clusters, further research is needed to define clusters operationally, and to develop appropriate theoretical frameworks. Methods of cluster identification need further comparison to see which offers the best understanding of symptom clusters. More studies with cross-sectional or longitudinal designs are necessary to explore influences of symptom clusters on patient outcomes, and interventions on symptom clusters.
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http://dx.doi.org/10.1016/j.ejon.2010.05.011DOI Listing
December 2010