Publications by authors named "Deborah W Bruner"

47 Publications

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

Mapping expanded prostate cancer index composite to EQ5D utilities to inform economic evaluations in prostate cancer: Secondary analysis of NRG/RTOG 0415.

PLoS One 2021 14;16(4):e0249123. Epub 2021 Apr 14.

Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, United States of America.

Purpose: The Expanded Prostate Cancer Index Composite (EPIC) is the most commonly used patient reported outcome (PRO) tool in prostate cancer (PC) clinical trials, but health utilities associated with the different health states assessed with this tool are unknown, limiting our ability to perform cost-utility analyses. This study aimed to map EPIC tool to EuroQoL-5D-3L (EQ5D) to generate EQ5D health utilities.

Methods And Materials: This is a secondary analysis of a prospective, randomized non-inferiority clinical trial, conducted between 04/2006 and 12/2009 at cancer centers across the United States, Canada, and Switzerland. Eligible patients included men >18 years with a known diagnosis of low-risk PC. Patient HRQoL data were collected using EPIC and health utilities were obtained using EQ5D. Data were divided into an estimation sample (n = 765, 70%) and a validation sample (n = 327, 30%). The mapping algorithms that capture the relationship between the instruments were estimated using ordinary least squares (OLS), Tobit, and two-part models. Five-fold cross-validation (in-sample) was used to compare the predictive performance of the estimated models. Final models were selected based on root mean square error (RMSE).

Results: A total of 565 patients in the estimation sample had complete information on both EPIC and EQ5D questionnaires at baseline. Mean observed EQ5D utility was 0.90±0.13 (range: 0.28-1) with 55% of patients in full health. OLS models outperformed their counterpart Tobit and two-part models for all pre-determined model specifications. The best model fit was: "EQ5D utility = 0.248541 + 0.000748*(Urinary Function) + 0.001134*(Urinary Bother) + 0.000968*(Hormonal Function) + 0.004404*(Hormonal Bother)- 0.376487*(Zubrod) + 0.003562*(Urinary Function*Zubrod)"; RMSE was 0.10462.

Conclusions: This is the first study to identify a comprehensive set of mapping algorithms to generate EQ5D utilities from EPIC domain/ sub-domain scores. The study results will help estimate quality-adjusted life-years in PC economic evaluations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249123PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046237PMC
April 2021

Do reminder emails and past due notifications improve patient completion and institutional data submission for patient-reported outcome measures?

Qual Life Res 2021 Jan 7;30(1):81-89. Epub 2020 Sep 7.

Emory University Hospital/Winship Cancer Institute, Atlanta, GA, USA.

Purpose: NRG Oncology, part of the National Cancer Institute's National Clinical Trials Network, took efforts to increase patient-reported outcome measures (PROMs) completion and institutional data submission rates within clinical trials. Lack of completion diminishes power to draw conclusions and can be a waste of resources. It is hypothesized that trials with automatic email reminders and past due notifications will have PROM forms submitted more timely with higher patient completion.

Methods: Automatic emails sent to the research associate were added to selected NRG Oncology trials. Comparisons between trials with and without automatic emails were analyzed using Chi-square tests with respect to patient completion and timeliness of form submission rates. Multivariable analyses were conducted using repeated measures generalized estimating equations. If PROMs were not completed, a form providing the reason why was submitted and counted towards form submission.

Results: For both disease sites, form submission was significantly higher within 1 month of the form's due date for the studies with automatic emails vs. those without (prostate: 79.7% vs. 75.7%, p < 0.001; breast: 59.2% vs. 31.3%, p < 0.001). No significant differences in patient completion were observed between the breast trials. The prostate trial with automatic emails had significantly higher patient completion but this result was not confirmed in the multivariable analysis.

Conclusions: Although patient completion rates were higher on trials with automatic emails, there may be confounding factors requiring future study. The automatic emails appeared to have increased the timeliness of form submission, thus supporting their continued use on NRG Oncology trials.
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http://dx.doi.org/10.1007/s11136-020-02613-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855823PMC
January 2021

Pilot Feasibility Study of a Video Intervention to Educate Patients with Breast Cancer About Clinical Trials.

J Cancer Educ 2020 Jul 11. Epub 2020 Jul 11.

Nell Hodgson Woodruff School of Nursing, Emory University, 1520 Clifton Road, Atlanta, GA, 30322, USA.

The purpose of this project was to develop and test the feasibility and preliminary efficacy of a video about cancer clinical trials (CCTs) developed for breast cancer patients. We developed 2 brief 7-min videos that focused on breast cancer patients describing their experiences participating in CCTs, supplemented with doctors and research staff explaining key research concepts. One video was culturally tailored to Black patients and the other to White patients. To assess feasibility study, participants and their care providers completed a survey to evaluate their satisfaction with the video. Eligibility criteria for the study included ≥ 21 years of age, English-speaking, no prior experience participating in a CCT, and being potentially eligible for breast CCT enrollment. Preliminary efficacy was evaluated with a pretest-posttest design using a single item asking about intent to enroll in a clinical trial. The mean age of the patient sample (n = 50) was 53.0 years, and 50.0% were Black. Participants reported that the video was in the right length, useful, and easy to understand. Providers' evaluation (n = 5) revealed that viewing the video helped prepare patients for further CCT discussion. Preliminary efficacy showed no statistically significant difference in participant interest in CCT enrollment pre- and post-video. Changes in patients' intent in enrollment were associated with age and education. Culturally adapted video interventions can be helpful in supporting both patients and providers throughout the CCT education process but additional work is needed to improve enrollment into clinical trials.
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http://dx.doi.org/10.1007/s13187-020-01826-xDOI Listing
July 2020

Characteristics of Participation in Patient-Reported Outcomes and Electronic Data Capture Components of NRG Oncology Clinical Trials.

Int J Radiat Oncol Biol Phys 2020 11 24;108(4):950-959. Epub 2020 Jun 24.

Emory University Hospital, Winship Cancer Institute, Atlanta, Georgia.

Purpose: To assess the reasons why patients do not consent to patient-reported outcome (PRO) and electronic PRO data capture components of clinical trials and potential selection bias by having a separate consent.

Methods And Materials: Selected NRG Oncology trials were included based on disease site and inclusion of PROs and electronic PRO data capture via VisionTree Optimal Care as separate consent questions. Reasons for not participating were assessed. Pretreatment characteristics between patients who did and did not consent were tested using χ and t tests for univariate comparisons and logistic regression for multivariable analyses.

Results: Ten trials were selected in head and neck, prostate, gynecologic, breast, lung, and gastrointestinal cancers, with 4 of these trials having electronic PRO data capture. Most patients consented to the PRO component (75.3%) but not electronic PRO data capture (37.8%). More white patients consented to PROs than nonwhite patients across all trials (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.45-0.63; P < .001), and more patients with education after high school consented compared with those with less education (OR, 1.71; 95% CI, 1.46-2.02; P < .001). Patients who are younger (OR, 0.63; 95% CI, 0.47-0.85; P = .002), white (OR, 0.60; 95% CI, 0.44-0.82; P = .001), and a never or former smoker (OR, 0.57; 95% CI, 0.41-0.78; P = .001) are more likely to participate in electronic PRO data capture.

Conclusions: These results suggest that a patient's race, age, and education can affect whether a patient chooses to consent or is offered to participate in PRO or electronic PRO data capture components. More investigation is needed, but this analysis provides support for making PROs integrated in the trial.
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http://dx.doi.org/10.1016/j.ijrobp.2020.06.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572717PMC
November 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

Factors Associated with Depression in African American Patients Being Treated for Cancer Pain.

Pain Manag Nurs 2020 10 5;21(5):410-415. Epub 2020 Jun 5.

Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia.

Background: Among cancer patients in the United States, African American cancer patients have the highest mortality rate and shortest survival rate. Although depression is known as a predictor of mortality in cancer and a potential barrier to health care utilization, research on depression in African American patients is limited. Cancer pain can interfere with an individual's ability to cope with depression.

Aims: To identify factors that are associated with a positive screening of depressive symptoms assessed by the PHQ-8 in African American patients treated for cancer pain.

Design: Secondary data analysis of a cross-sectional study of opioid adherence.

Setting: Medical oncology, palliative care, and radiation oncology clinics in Atlanta, Georgia.

Participants/subjects: African American patients with cancer pain in the parent study.

Methods: Independent samples t-test was used to assess variable correlations with and without depressive symptoms. Adjusted logistic regression was conducted to identify factors that were associated with presence of depressive symptoms.

Results: Mean patient age was 55.6 years, and nearly 38% had a PHQ-8 score of >10 indicating presence of moderate to severe depressive symptoms. Participants with depressive symptoms had significantly higher means for anxiety and pain interference with mood than those without depressive symptoms. Factors that were significantly associated with depressive symptoms were anxiety, pain interfering with mood, and lack of involvement with a religious congregation.

Conclusions: The findings of this study help to identify African American cancer patients at risk for depression and demonstrates the need for increased screening for depression in this underserved population.
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http://dx.doi.org/10.1016/j.pmn.2020.03.006DOI Listing
October 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

How Nurse Scientists Can Stay Productive and on Track During the Pandemic.

Authors:
Deborah W Bruner

Nurs Res 2020 Jul/Aug;69(4):252-253

Deborah W. Bruner, PhD, RN, FAAN, is Senior Vice President of Research, Emory University; Robert W. Woodruff Professor of Nursing, Nell Hodgson Woodruff School of Nursing; and Professor, Department of Radiation Oncology, Emory University School of Medicine, Atlanta, Georgia.

On March 11, 2020, with the declaration of a global pandemic by the World Health Organization, an unplanned slowdown of academic research activities has taken place. Although this is not an ideal situation for nurse scientists, it presents a number of unique opportunities for researchers to shift their focus in the short term, which may actually lead to more productivity in the long term. This commentary explores ways nurse scientists can stay on track without derailing their plans for career advancement under unprecedented circumstances.
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http://dx.doi.org/10.1097/NNR.0000000000000437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273860PMC
November 2020

Comparison of vaginal microbiota in gynecologic cancer patients pre- and post-radiation therapy and healthy women.

Cancer Med 2020 06 1;9(11):3714-3724. Epub 2020 Apr 1.

Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, USA.

Background: While the importance of commensal microbes in vaginal health is well appreciated, little is known about the effects of gynecological cancer (GynCa) and radiation therapy (RT) on the vaginal microbiome (VM) of postmenopausal women.

Methods: We studied women with GynCa, pre- (N = 65) and post-RT (N = 25) and a group of healthy controls (N = 67) by sequencing the V4 region of the 16S rRNA gene from vaginal swabs and compared the diversity and composition of VMs between the three groups accounting for potential confounding factors in multivariate analysis of variance.

Results: Comparisons of cancer vs healthy groups revealed that Lactobacillus and Bifidobacterium have significantly higher relative abundance in the healthy group, while the cancer group was enriched in 16 phylogroups associated with bacterial vaginosis (BV) and inflammation, including Sneathia, Prevotella, Peptoniphilus, Fusobacterium, Anaerococcus, Dialister, Moryella, and Peptostreptococcus. In our sample, RT affected the α-diversity and correlated with higher abundance of typically rare VM species, including several members of the Lacnospiraceae family, a taxon previously linked to vaginal dysbiosis. In addition to cancer and treatment modalities, age and vaginal pH were identified as significant parameters that structure the VM.

Conclusions: This is among the first reports identifying VM changes among postmenopausal women with cancer. RT alone seems to affect several phylogroups (12 bacterial genera), while gynecological cancer and its treatment modalities are associated with even greater significant shifts in the vaginal microbiota including the enrichment of opportunistic bacterial pathogens, which warrants further attention.
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http://dx.doi.org/10.1002/cam4.3027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286461PMC
June 2020

Improvement in Patient-Reported Outcomes With Intensity-Modulated Radiotherapy (RT) Compared With Standard RT: A Report From the NRG Oncology RTOG 1203 Study.

J Clin Oncol 2020 05 19;38(15):1685-1692. Epub 2020 Feb 19.

Vanderbilt University School of Medicine, Nashville, TN.

Purpose: In oncology trials, the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) is the standard tool for reporting adverse events (AEs), but it may underreport symptoms experienced by patients. This analysis of the NRG Oncology RTOG 1203 compared symptom reporting by patients and clinicians during radiotherapy (RT).

Patients And Methods: Patients with cervical or endometrial cancer requiring postoperative RT were randomly assigned to standard 4-field RT or intensity-modulated RT (IMRT). Patients completed the 6-item patient-reported outcomes version of the CTCAE (PRO-CTCAE) for GI toxicity assessing abdominal pain, diarrhea, and fecal incontinence at various time points. Patients reported symptoms on a 5-point scale. Clinicians recorded these AEs as CTCAE grades 1 to 5. Clinician- and patient-reported AEs were compared using McNemar's test for rates > 0%.

Results: Of 278 eligible patients, 234 consented and completed the PRO-CTCAE. Patients reported high-grade abdominal pain 19.1% ( < .0001), high-grade diarrhea 38.5% ( < .0001), and fecal incontinence 6.8% more frequently than clinicians. Similar effects were seen between grade ≥ 1 CTCAE toxicity and any-grade patient-reported toxicity. Between-arm comparison of patient-reported high-grade AEs revealed that at 5 weeks of RT, patients who received IMRT experienced fewer GI AEs than patients who received 4-field pelvic RT with regard to frequency of diarrhea (18.2% difference; = .01), frequency of fecal incontinence (8.2% difference; = .01), and interference of fecal incontinence (8.5% difference; = .04).

Conclusion: Patient-reported AEs showed a reduction in symptoms with IMRT compared with standard RT, whereas clinician-reported AEs revealed no difference. Clinicians also underreported symptomatic GI AEs compared with patients. This suggests that patient-reported symptomatic AEs are important to assess in this disease setting.
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http://dx.doi.org/10.1200/JCO.19.02381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238486PMC
May 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

Expanded validation of the EPIC bowel and urinary domains for use in women with gynecologic cancer undergoing postoperative radiotherapy.

Gynecol Oncol 2019 07 16;154(1):183-188. Epub 2019 May 16.

Emory University, 1520 Clifton Road Northeast, Room 232, Atlanta, GA 30322, USA.

Objective: Women with endometrial or cervical cancer at risk for recurrence receive postoperative radiation therapy (RT). A patient reported outcomes (PRO) instrument to assess bowel and urinary toxicities is the Expanded Prostate Cancer Index Composite (EPIC), which has been validated in men with prostate cancer. As this instrument specifically measures bowel toxicity and the degree to which this is a problem, it was used in NRG Oncology/RTOG 1203 to compare intensity modulated RT (IMRT) to standard RT. This paper reports on the expanded validation of EPIC for use in women receiving pelvic RT.

Methods: In addition to the EPIC bowel domain, urinary toxicity (EPIC urinary domain), patient reported bowel toxicities (PRO-CTCAE) and quality of life (Functional Assessment of Cancer Therapy (FACT)) were completed before, during and after treatment. Sensitivity, reliability and concurrent validity were assessed.

Results: Mean bowel and urinary scores among 278 women enrolled were significantly worse during treatment and differed between groups. Acceptable to good reliability for bowel and urinary domain scores were obtained at all time points with the exception of one at baseline. Correlations between function and bother scores within the bowel and urinary domains were consistently stronger than those across domains. Correlations between bowel domain scores and PRO-CTCAE during treatment were stronger than those with the FACT.

Conclusion: Correlations within and among the instruments indicate EPIC bowel and urinary domains are measuring conceptually discrete components of health. These EPIC domains are valid, reliable and sensitive instruments to measure PRO among women undergoing pelvic radiation.
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http://dx.doi.org/10.1016/j.ygyno.2019.04.682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918674PMC
July 2019

Tolerance doses for late adverse events after hypofractionated radiotherapy for prostate cancer on trial NRG Oncology/RTOG 0415.

Radiother Oncol 2019 06 5;135:19-24. Epub 2019 Mar 5.

Cedars-Sinai Medical Center, United States.

Purpose/objective: Hypofractionated radiotherapy (HRT) regimens for prostate cancer are emerging, but tolerance doses for late adverse events are scarce. The purpose of this study is to define dose-volume predictors for late gastrointestinal and genitourinary (GI and GU) toxicities after HRT in the multi-center NRG Oncology/RTOG 0415 low-risk prostate cancer trial (N = 521).

Material/methods: Treatment in the studied HRT arm was delivered as 70 Gy at 2.5 Gy/fraction with 3D-CRT/IMRT (N = 108/413). At a median follow-up of 5.9 years, the crude late ≥Grade 2 GI and GU toxicities were 19% and 29%, respectively. For modeling, the complete HRT cohort was randomly split into training and validation (70% and 30%; preserved toxicity rates). Within training, dose-response modeling was based on dose-volume cut-points (EQD2Gy; bladder/rectum: α/β = 6 Gy/3Gy), age, acute ≥Grade 2 toxicity, and treatment technique using univariate and multivariate logistic regression on bootstrapping (UVA and MVA). Candidate predictors were determined at p ≤ 0.05, and the selected MVA models were explored on validation where model generalizability was judged if the area under the receiver-operating curve in validation (AUC) was within AUC ± SD with p ≤ 0.05, and with an Hosmer-Lemeshow p-value (p) > 0.05.

Results: Three candidate predictors were suggested for late GI toxicity: the minimum dose to the hottest 5% rectal volume (D5%[Gy]), the absolute rectal volume <35 Gy, and acute GI toxicity (AUC = 0.59-0.63; p = 0.02-0.04). The two generalizable MVA models, i.e., D5%[Gy] with or without acute GI toxicity (AUC = 0.64, 0.65; p = 0.01, 0.03; p = 0.45-0.56), suggest that reducing late GI toxicity from 20% to 10% would require reducing D5%[Gy] from ≤65 Gy to ≤62 Gy (logistic function argument: 17+(0.24D5%[Gy])). Acute GU toxicity showed only a trend to predict late GU toxicity (AUC = 0.57; p = 0.07).

Conclusion: Late GI toxicity, following moderate HRT for low-risk prostate cancer, increases with higher doses to small rectal volumes. This work provides quantitative evidence that limiting small rectal dose 'hotspots' in clinical practice of such HRT regimens is likely to further reduce the associated rates of GI toxicity.
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http://dx.doi.org/10.1016/j.radonc.2019.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582638PMC
June 2019

Patient free text reporting of symptomatic adverse events in cancer clinical research using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

J Am Med Inform Assoc 2019 04;26(4):276-285

Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.

Objective: The study sought to describe patient-entered supplemental information on symptomatic adverse events (AEs) in cancer clinical research reported via a National Cancer Institute software system and examine the feasibility of mapping these entries to established terminologies.

Materials And Methods: Patients in 3 multicenter trials electronically completed surveys during cancer treatment. Each survey included a prespecified subset of items from the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Upon completion of the survey items, patients could add supplemental symptomatic AE information in a free text box. As patients typed into the box, structured dropdown terms could be selected from the PRO-CTCAE item library or Medical Dictionary for Regulatory Activities (MedDRA), or patients could type unstructured free text for submission.

Results: Data were pooled from 1760 participants (48% women; 78% White) who completed 8892 surveys, of which 2387 (26.8%) included supplemental symptomatic AE information. Overall, 1024 (58%) patients entered supplemental information at least once, with an average of 2.3 per patient per study. This encompassed 1474 of 8892 (16.6%) dropdowns and 913 of 8892 (10.3%) unstructured free text entries. One-third of the unstructured free text entries (32%) could be mapped post hoc to a PRO-CTCAE term and 68% to a MedDRA term.

Discussion: Participants frequently added supplemental information beyond study-specific survey items. Almost half selected a structured dropdown term, although many opted to submit unstructured free text entries. Most free text entries could be mapped post hoc to PRO-CTCAE or MedDRA terms, suggesting opportunities to enhance the system to perform real-time mapping for AE reporting.

Conclusions: Patient reporting of symptomatic AEs using a text box functionality with mapping to existing terminologies is both feasible and informative.
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http://dx.doi.org/10.1093/jamia/ocy169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402312PMC
April 2019

Quality of Life in Patients With Low-Risk Prostate Cancer Treated With Hypofractionated vs Conventional Radiotherapy: A Phase 3 Randomized Clinical Trial.

JAMA Oncol 2019 May;5(5):664-670

Henry Ford Hospital, Detroit, Michigan.

Importance: Hypofractionated radiotherapy (HRT) would be more convenient for men with low-risk prostate cancer and cost less than conventional radiotherapy (CRT) as long as HRT is noninferior to CRT in terms of survival and quality of life (QOL) is not found to be worse.

Objective: To assess differences in QOL between men with low-risk prostate cancer who are treated with HRT vs CRT.

Design, Setting, And Participants: In this phase 3 randomized clinical trial, men with low-risk prostate cancer were enrolled from sites within the National Cancer Institute's National Clinical Trials Network in the United States, Canada, and Switzerland.

Interventions: Random assignment to CRT (73.8 Gy in 41 fractions over 8.2 weeks) or to HRT (70 Gy in 28 fractions over 5.6 weeks).

Main Outcomes And Measures: Quality of life was assessed using the Expanded Prostate Index Composite questionnaire measuring bowel, urinary, sexual, and hormonal domains; the 25-item Hopkins Symptom Checklist measuring anxiety and depression; and the EuroQol-5 Dimension questionnaire measuring global QOL. All data were collected at baseline and 6, 12, 24, and 60 months. Change scores were compared between treatment arms using the Wilcoxon signed rank test. A significance level of .0125 to adjust for multiple comparisons was used for an overall 2-sided type 1 error of .05. Clinical significance was determined for the Expanded Prostate Index Composite change scores by an effect size of 0.5.

Results: Of 1092 patients analyzable for the primary end point, 962 (mean [SD] age, 66.6 [7.4] years) consented to the QOL component. No statistically significant differences with regard to baseline characteristics nor any of the QOL baseline domains were measured between arms. There were no differences in change score between arms with respect to any of the Expanded Prostate Index Composite questionnaire domain scores except at 12 months when the HRT arm had a larger decline than the CRT arm in the bowel domain (mean score, -7.5 vs -3.7, respectively; P<.001), but it did not reach clinical significance (effect size = 0.29). There were no differences between arms at any time point for the Hopkins Symptom Checklist nor EuroQol-5 Dimension questionnaire.

Conclusions And Relevance: Treatment with HRT is noninferior to CRT in men with low-risk prostate cancer in terms of disease-free survival and, as shown in the present study, in prostate cancer-specific (eg, bowel, bladder, sexual) and general QOL, as well as in anxiety and depression. This study provides evidence to affirm that HRT is a practice standard for men with low-risk prostate cancer.

Trial Registration: ClinicalTrials.gov identifier: NCT00331773.
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http://dx.doi.org/10.1001/jamaoncol.2018.6752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459051PMC
May 2019

Factors Related to Adherence to Opioids in Black Patients With Cancer Pain.

J Pain Symptom Manage 2019 01 12;57(1):28-36. Epub 2018 Oct 12.

Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia, USA; Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.

Context: Cancer pain relief is often inadequate because of poor adherence to pain medication, especially for black patients.

Objectives: The purpose of this study is to describe factors related to adherence to around-the-clock opioids among 110 black patients being treated for cancer pain.

Methods: Sociodemographic, clinical, symptoms, and social support data were collected at baseline; pain and adherence data were collected at 30 days. Associations between these variables and opioid adherence measured by Medication Event Monitoring System were estimated using multiple regression.

Results: Mean age was 56 (±10.1), the majority were women (63%) and college educated (56%). Mean pain severity at baseline equaled 4.6 (±2.3). Mean dose adherence was 60% (±28.5), while mean schedule adherence was 33.0% (±31.0). In adjusted analysis, 26% of the variance in dose adherence was explained by recent chemotherapy, changes in pain, concerns about nausea, and doctors' focus on cure versus pain control (P<0.001); 27% of the variance in schedule adherence was explained by recent chemotherapy, changes in pain, symptom burden, and concerns about doctors focus on cure versus pain control (P<0.001).

Conclusion: Findings confirm pain medication adherence is poor and pain was not well relieved. Multiple factors influence adherence to around-the-clock opioids. Clinicians need to partner with patients by providing a personalized pain treatment plan including an in-depth assessment of treatment choices and adherence.
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http://dx.doi.org/10.1016/j.jpainsymman.2018.10.491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310640PMC
January 2019

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

Patient-Reported Toxicity During Pelvic Intensity-Modulated Radiation Therapy: NRG Oncology-RTOG 1203.

J Clin Oncol 2018 08 10;36(24):2538-2544. Epub 2018 Jul 10.

Ann H. Klopp, Shannon N. Westin, and Kent Gifford, MD Anderson Cancer Center, Houston, TX; Anamaria R. Yeung, University of Florida, Gainsville, FL; Snehal Deshmukh and Stephanie L. Pugh, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; Karen M. Gil, Summa Health System; Desiree E. Doncals, Summa Akron City Hospital, Akron, OH; Lari Wenzel, University of California Medical Center at Irvine, Irvine, CA; David K. Gaffney, University of Utah, Salt Lake City, UT; William Small Jr, Loyola University Medical Center, Maywood, IL; Spencer Thompson, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Guilherme H.C. Cantuaria, Northside Hospital, Atlanta, GA; Brian P. Yaremko, London Regional Cancer Program, London, Ontario; Vijayananda Kundapur, Saskatoon Cancer Centre, Saskatoon, Saskatchewan, Canada; Amy Chang, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong; Dasarahally S. Mohan, Kaiser Permanente Cancer Treatment Center, South San Francisco, CA; Michael L. Haas, Reading Hospital, West Reading, PA; Yong Bae Kim, Yonsei University Health System-Severance Hospital, Seoul, South Korea; Catherine L. Ferguson, Georgia Regents University, Augusta; Deborah W. Bruner, Emory University, Atlanta, GA; and Lisa A. Kachnic, Vanderbilt University, Nashville, TN.

Purpose NRG Oncology/RTOG 1203 was designed to compare patient-reported acute toxicity and health-related quality of life during treatment with standard pelvic radiation or intensity-modulated radiation therapy (IMRT) in women with cervical and endometrial cancer. Methods Patients were randomly assigned to standard four-field radiation therapy (RT) or IMRT radiation treatment. The primary end point was change in patient-reported acute GI toxicity from baseline to the end of RT, measured with the bowel domain of the Expanded Prostate Cancer Index Composite (EPIC). Secondary end points included change in patient-reported urinary toxicity, change in GI toxicity measured with the Patient-Reported Outcome Common Terminology Criteria for Adverse Events, and quality of life measured with the Trial Outcome Index. Results From 2012 to 2015, 289 patients were enrolled, of whom 278 were eligible. Between baseline and end of RT, the mean EPIC bowel score declined 23.6 points in the standard RT group and 18.6 points in the IMRT group ( P = .048), the mean EPIC urinary score declined 10.4 points in the standard RT group and 5.6 points in the IMRT group ( P = .03), and the mean Trial Outcome Index score declined 12.8 points in the standard RT group and 8.8 points in the IMRT group ( P = .06). At the end of RT, 51.9% of women who received standard RT and 33.7% who received IMRT reported frequent or almost constant diarrhea ( P = .01), and more patients who received standard RT were taking antidiarrheal medications four or more times daily (20.4% v 7.8%; P = .04). Conclusion Pelvic IMRT was associated with significantly less GI and urinary toxicity than standard RT from the patient's perspective.
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http://dx.doi.org/10.1200/JCO.2017.77.4273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097832PMC
August 2018

Patient Reported Outcomes in NRG Oncology RTOG 0938, Evaluating Two Ultrahypofractionated Regimens for Prostate Cancer.

Int J Radiat Oncol Biol Phys 2018 10 18;102(2):287-295. Epub 2018 Jun 18.

Vanderbilt University Medical Center, Nashville, Tennessee.

Purpose: There is considerable interest in very short (ultrahypofractionated) radiation therapy regimens to treat prostate cancer based on potential radiobiological advantages, patient convenience, and resource allocation benefits. Our objective is to demonstrate that detectable changes in health-related quality of life measured by the bowel and urinary domains of the Expanded Prostate Cancer Index Composite (EPIC-50) were not substantially worse than baseline scores.

Methods And Materials: NRG Oncology's RTOG 0938 is a nonblinded randomized phase 2 study of National Comprehensive Cancer Network low-risk prostate cancer in which each arm is compared with a historical control. Patients were randomized to 5 fractions (7.25 Gy in 2 weeks) or 12 fractions (4.3 Gy in 2.5 weeks). The co-primary endpoints were the proportion of patients with a change in EPIC-50 bowel score at 1 year (baseline to 1 year) >5 points and in EPIC-50 urinary score >2 points tested with a 1-sample binomial test.

Results: The study enrolled 127 patients to 5 fractions (121 analyzed) and 128 patients to 12 fractions (125 analyzed). Median follow-up for all patients at the time of analysis was 3.8 years. The 1-year frequency for >5 point change in bowel score were 29.8% (P < .001) and 28.4% (P < .001) for 5 and 12 fractions, respectively. The 1-year frequencies for >2 point change in urinary score were 45.7% (P < .001) and 42.2% (P < .001) for 5 and 12 fractions, respectively. For 5 fractions, 32.9% of patients had a drop in 1-year EPIC-50 sexual score of ≥11 points (P = .34); for 12 fractions, 30.9% of patients had a drop in 1-year EPIC-50 sexual score of ≥ 11 points (P = .20). Disease-free survival at 2 years is 99.2% (95% confidence interval: 97.5-100) in the 5-fraction arm and 97.5% (95% confidence interval: 94.6-100) in the 12-fraction arm. There was no late grade 4 or 5 treatment-related urinary or bowel toxicity.

Conclusions: This study confirms that, based on changes in bowel and urinary domains and toxicity (acute and late), the 5- and 12-fraction regimens are well tolerated. These ultrahypofractionated approaches need to be compared with current standard radiation therapy regimens.
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http://dx.doi.org/10.1016/j.ijrobp.2018.06.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248906PMC
October 2018

Spirituality and Quality of Life in Black Patients With Cancer Pain.

J Pain Symptom Manage 2018 09 30;56(3):390-398. Epub 2018 May 30.

Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia, USA; Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.

Purpose: The objective of this study was to examine the associations between spirituality and overall quality of life (QOL) and individual QOL domains in black patients with cancer pain.

Methods: A secondary data analysis of a parent study exploring pain medication adherence in black patients receiving around-the-clock opioids with cancer pain was performed. All the participating patients completed Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (spirituality), Brief Pain Inventory (pain severity and interference), Edmonton Symptom Assessment Scale (symptoms), and Functional Assessment of Cancer Therapy-General (QOL). Pearson correlation and multiple linear regression analyses were conducted to examine the associations between spirituality and overall QOL and QOL domains and to identify the predictors of overall QOL and QOL domains.

Results: Black patients treated for cancer pain (n = 102) completed the study. Pearson correlation showed significant positive associations between spirituality and overall QOL (P < 0.001) and individual QOL domains (physical, social, emotional, and functional). Higher spirituality was associated with lower pain severity (P = 0.01), pain interference (P = 0.001), and total symptoms score (P < 0.001). In multiple regression analysis, the best model for the overall QOL explained 67% of the variance (P < 0.001) and included total symptoms score, pain interference, spirituality, and age. Spirituality significantly predicted QOL domains of social (P < 0.0001), emotional (P = 0.002), and functional well-being (P = 0.001) rather than physical well-being.

Conclusions: Spirituality is associated with decreased pain and lower symptom burden and may serve as a protective factor against diminished overall QOL, specifically social, emotional, and functional domains in black patients with cancer pain. There is a need to develop spirituality-based interventions along with symptom management interventions to improve QOL for this population.
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http://dx.doi.org/10.1016/j.jpainsymman.2018.05.020DOI Listing
September 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

Effect of Standard vs Dose-Escalated Radiation Therapy for Patients With Intermediate-Risk Prostate Cancer: The NRG Oncology RTOG 0126 Randomized Clinical Trial.

JAMA Oncol 2018 06 14;4(6):e180039. Epub 2018 Jun 14.

Cedars-Sinai Medical Center, Los Angeles, California.

Importance: Optimizing radiation therapy techniques for localized prostate cancer can affect patient outcomes. Dose escalation improves biochemical control, but no prior trials were powered to detect overall survival (OS) differences.

Objective: To determine whether radiation dose escalation to 79.2 Gy compared with 70.2 Gy would improve OS and other outcomes in prostate cancer.

Design, Setting, And Participants: The NRG Oncology/RTOG 0126 randomized clinical trial randomized 1532 patients from 104 North American Radiation Therapy Oncology Group institutions March 2002 through August 2008. Men with stage cT1b to T2b, Gleason score 2 to 6, and prostate-specific antigen (PSA) level of 10 or greater and less than 20 or Gleason score of 7 and PSA less than 15 received 3-dimensional conformal radiation therapy or intensity-modulated radiation therapy to 79.2 Gy in 44 fractions or 70.2 Gy in 39 fractions.

Main Outcomes And Measures: Time to OS measured from randomization to death due to any cause. American Society for Therapeutic Radiology and Oncology (ASTRO)/Phoenix definitions were used for biochemical failure. Acute (≤90 days of treatment start) and late radiation therapy toxic effects (>90 days) were graded using the National Cancer Institute Common Toxicity Criteria, version 2.0, and the RTOG/European Organisation for the Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme, respectively.

Results: With a median follow-up of 8.4 (range, 0.02-13.0) years in 1499 patients (median [range] age, 71 [33-87] years; 70% had PSA <10 ng/mL, 84% Gleason score of 7, 57% T1 disease), there was no difference in OS between the 751 men in the 79.2-Gy arm and the 748 men in the 70.2-Gy arm. The 8-year rates of OS were 76% with 79.2 Gy and 75% with 70.2 Gy (hazard ratio [HR], 1.00; 95% CI, 0.83-1.20; P = .98). The 8-year cumulative rates of distant metastases were 4% for the 79.2-Gy arm and 6% for the 70.2-Gy arm (HR, 0.65; 95% CI, 0.42-1.01; P = .05). The ASTRO and Phoenix biochemical failure rates at 5 and 8 years were 31% and 20% with 79.2 Gy and 47% and 35% with 70.2 Gy, respectively (both P < .001; ASTRO: HR, 0.59; 95% CI, 0.50-0.70; Phoenix: HR, 0.54; 95% CI, 0.44-0.65). The high-dose arm had a lower rate of salvage therapy use. The 5-year rates of late grade 2 or greater gastrointestinal and/or genitourinary toxic effects were 21% and 12% with 79.2 Gy and 15% and 7% with 70.2 Gy (P = .006 [HR, 1.39; 95% CI, 1.10-1.77] and P = .003 [HR, 1.59; 95% CI, 1.17-2.16], respectively).

Conclusions And Relevance: Despite improvements in biochemical failure and distant metastases, dose escalation did not improve OS. High doses caused more late toxic effects but lower rates of salvage therapy.

Trial Registration: clinicaltrials.gov Identifier: NCT00033631.
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http://dx.doi.org/10.1001/jamaoncol.2018.0039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885160PMC
June 2018

The Relationship Between 
Body Mass Index and Sexual Function in Endometrial Cancer
.

Oncol Nurs Forum 2018 01;45(1):25-32

Emory University.

Objectives: To explore the association between pretreatment body mass index (BMI) and post-treatment sexual function in women treated for endometrial cancer. 
.

Sample & Setting: 28 postmenopausal women treated with vaginal brachytherapy (VBT) took part in this multisite exploratory secondary analysis at the University of Pennsylvania and Northwestern University. 
.

Methods & Variables: Secondary data analysis was used to determine if pretreatment BMI is associated with post-VBT sexual function in postmenopausal women treated for endometrial cancer at baseline and at six months post-treatment. Because of small sample size, participants were dichotomized according to enrollment BMI.

Results: Both groups had poor sexual function at baseline. Although improved function was observed with time, neither group reached a score indicating healthy sexual function.
.

Implications For Nursing: Understanding factors that influence sexual health in patients with gynecologic cancer can improve post-treatment quality of life. 
.
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http://dx.doi.org/10.1188/18.ONF.25-32DOI Listing
January 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

Perceptions and practices regarding women's vaginal health following radiation therapy: A survey of radiation oncologists practicing in the United States.

Pract Radiat Oncol 2017 Sep - Oct;7(5):356-363. Epub 2017 Feb 14.

Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. Electronic address:

Purpose: Vaginal stenosis (VS) is a recognized complication of pelvic and vaginal radiation therapy (RT).

Methods And Materials: A 26-item survey assessing the signs/symptoms, risk factors, diagnosis, prevention, treatment, and impact of VS on women's sexual health was distributed to radiation oncologists. Descriptive statistics were calculated. Chi-square tests examined differences in categorical responses.

Results: A total of 233 (10.5%) participants completed the entire survey. Twelve percent, 21%, and 68% report treating gynecologic (GYN) tumors only, non-GYN pelvic tumors only, or both, respectively. Regarding risk factors, 78% believed that VS can be caused by pelvic RT alone, 91% by vaginal brachytherapy alone, and 98% by combined pelvic RT and vaginal brachytherapy. Approximately one-half of respondents felt that being postmenopausal and having a hysterectomy before radiation therapy were risk factors for VS, whereas the other half felt that these were not risk factors. All respondents agreed that VS is a clinical diagnosis. Respondents indicated that VS symptoms include dyspareunia, vaginal pain, dryness, and/or bleeding (100%, 90%, 85%, and 72%, respectively); 65% indicated all 4. The most commonly recommended treatment for VS is vaginal dilator use. Radiation oncologists who treat GYN-only versus non-GYN cancers were more likely to perform a vaginal examination, to distribute written instructions regarding vaginal dilator use (P = .002), to have vaginal bleeding reported after RT (P = .001), and to refer patients to a sexual counselor (P = .007). Most providers (73%) expressed willingness to participate in prospective research on the diagnosis and treatment of VS.

Conclusions: This is the first large-scale survey of radiation oncologists' perceptions and practices regarding VS. There is agreement among providers regarding the signs/symptoms of VS and strategies for its prevention/treatment using vaginal dilators. Further prospective and observational research is needed. This survey shows a willingness on the part of providers to take part in prospective research regarding the diagnosis, impact, and treatment of VS on women's sexual health.
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http://dx.doi.org/10.1016/j.prro.2017.02.003DOI Listing
May 2018

Exploratory Factor Analysis of NRG Oncology's University of Washington Quality of Life Questionnaire-RTOG Modification.

J Pain Symptom Manage 2017 01 27;53(1):139-145.e2. Epub 2016 Nov 27.

Emory University/Winship Cancer Institute, Atlanta, Georgia, USA.

Context: The 15-item University of Washington Quality of Life questionnaire-Radiation Therapy Oncology Group (RTOG) modification (UW-QOL-RTOG modification) has been used in several trials of head and neck cancer conducted by NRG Oncology such as RTOG 9709, RTOG 9901, RTOG 0244, and RTOG 0537.

Objectives: This study is an exploratory factor analysis (EFA) to establish validity and reliability of the instrument subscales.

Methods: EFA on the UW-QOL-RTOG modification was conducted using baseline data from NRG Oncology's RTOG 0537, a trial of acupuncture-like transcutaneous electrical nerve stimulation in treating radiation-induced xerostomia. Cronbach α coefficient was calculated to measure reliability; correlation with the University of Michigan Xerostomia Related Quality of Life Scale was used to evaluate concurrent validity; and correlations between consecutive time points were used to assess test-retest reliability.

Results: The 15-item EFA of the modified tool resulted in 11 items split into four factors: mucus, eating, pain, and activities. Cronbach α ranged from 0.71 to 0.93 for the factors and total score, consisting of all 11 items. There were strong correlations (ρ ≥ 0.60) between consecutive time points and between total score and the Xerostomia Related Quality of Life Scale total score (ρ > 0.65).

Conclusion: The UW-QOL-RTOG modification is a valid tool that can be used to assess symptom burden of head and neck cancer patients receiving radiation therapy or those who have recently completed radiation. The modified tool has acceptable reliability, concurrent validity, and test-retest reliability in this patient population, as well as the advantage of having being shortened from 15 to 11 items.
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http://dx.doi.org/10.1016/j.jpainsymman.2016.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5191964PMC
January 2017

Cultural Competency Training to Increase Minority Enrollment into Radiation Therapy Clinical Trials-an NRG Oncology RTOG Study.

J Cancer Educ 2017 Dec;32(4):721-727

Nell Hodgson Woodruff School of Nursing, Emory University, 1520 Clifton Road, Room 230, Atlanta, GA, 30322-4201, USA.

Despite initiatives to increase the enrollment of racial and ethnic minorities into cancer clinical trials in the National Cancer Institute National Cancer Clinical Trials Network (NCCTN), participation by Latino and African American populations remain low. The primary aims of this pilot study are (1) to develop a Cultural Competency and Recruitment Training Program (CCRTP) for physician investigators and clinical research associates (CRAs), (2) to determine if the CCRTP increases cultural competency scores among physician investigators and CRAs, and (3) to determine the impact of the CCRTP on minority patient recruitment into NRG Oncology Radiation Therapy Oncology Group (RTOG) clinical trials. Sixty-seven CRAs and physicians participated in an in-person or online 4-h CRRTP training. Five knowledge and attitude items showed significant improvements from pre- to post-training. A comparison between enrolling sites that did and did not participate in the CCRTP demonstrated a pre to 1-year post-incremental increase in minority accrual to clinical trials of 1.2 % among participating sites. While not statistically significant, this increase translated into an additional 300 minority patients accrued to NCCTN clinical trials in the year following the training from those sites who participated in the training.
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http://dx.doi.org/10.1007/s13187-016-1051-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118189PMC
December 2017

Randomized Phase III Noninferiority Study Comparing Two Radiotherapy Fractionation Schedules in Patients With Low-Risk Prostate Cancer.

J Clin Oncol 2016 07 4;34(20):2325-32. Epub 2016 Apr 4.

W. Robert Lee and Bridget F. Koontz, Duke University Medical Center, Durham, NC; James J. Dignam, University of Chicago, Chicago, IL; Mahul B. Amin and Howard M. Sandler, Cedars-Sinai Medical Center; Daniel Low, University of California, Los Angeles, Los Angeles; Samantha A. Seaward, Kaiser Permanente Northern California, Santa Clara, CA; Deborah W. Bruner, Emory University, Atlanta, GA; Gregory P. Swanson, Baylor Scott & White Healthcare Temple Clinic, Temple, TX; Amit B. Shah, York Cancer Center, York; James J. Dignam and Rebecca Paulus, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; David P. D'Souza, London Regional Cancer Program, London, Ontario; Ian S. Dayes, McMaster University, Hamilton, Ontario; Sergio L. Faria, McGill University Health Center, Montreal, Quebec, Canada; Jeff M. Michalski, Washington University School of Medicine, St Louis, MO; William A. Hall, Medical College of Wisconsin, Milwaukee, WI; Paul L. Nguyen, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA; Thomas M. Pisansky, Mayo Clinic, Rochester, MN; and Yuhchyau Chen, University of Rochester, Rochester, NY.

Purpose: Conventional radiotherapy (C-RT) treatment schedules for patients with prostate cancer typically require 40 to 45 treatments that take place from > 8 to 9 weeks. Preclinical and clinical research suggest that hypofractionation-fewer treatments but at a higher dose per treatment-may produce similar outcomes. This trial was designed to assess whether the efficacy of a hypofractionated radiotherapy (H-RT) treatment schedule is no worse than a C-RT schedule in men with low-risk prostate cancer.

Patients And Methods: A total of 1,115 men with low-risk prostate cancer were randomly assigned 1:1 to C-RT (73.8 Gy in 41 fractions over 8.2 weeks) or to H-RT (70 Gy in 28 fractions over 5.6 weeks). This trial was designed to establish (with 90% power and an α of .05) that treatment with H-RT results in 5-year disease-free survival (DFS) that is not worse than C-RT by more than 7.65% (H-RT/C-RT hazard ratio [HR] < 1.52).

Results: A total of 1,092 men were protocol eligible and had follow-up information; 542 patients were assigned to C-RT and 550 to H-RT. Median follow-up was 5.8 years. Baseline characteristics were not different according to treatment assignment. The estimated 5-year DFS was 85.3% (95% CI, 81.9 to 88.1) in the C-RT arm and 86.3% (95% CI, 83.1 to 89.0) in the H-RT arm. The DFS HR was 0.85 (95% CI, 0.64 to 1.14), and the predefined noninferiority criterion that required that DFS outcomes be consistent with HR < 1.52 was met (P < .001). Late grade 2 and 3 GI and genitourinary adverse events were increased (HR, 1.31 to 1.59) in patients who were treated with H-RT.

Conclusion: In men with low-risk prostate cancer, the efficacy of 70 Gy in 28 fractions over 5.6 weeks is not inferior to 73.8 Gy in 41 fractions over 8.2 weeks, although an increase in late GI/genitourinary adverse events was observed in patients treated with H-RT.
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http://dx.doi.org/10.1200/JCO.2016.67.0448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981980PMC
July 2016