Introduction
The aim of this study was to explore the associations among physical activity (PA), inflammatory markers, and quality of life (QoL) from preradiotherapy to 1‐year postradiotherapy for ...patients with head and neck cancer (HNC).
Methods
This was an observational longitudinal study. Mixed‐effect models incorporating within‐subject correlation were used to examine the relationship among the three key variables.
Results
Aerobically active patients had significantly lower levels of sTNFR2 (but not other inflammatory markers) than aerobically inactive patients. Being aerobically active and lower inflammation were independently associated with better total QoL scores after adjusting covariates. The trend was similar for patients engaged in strength exercises.
Conclusions
Being aerobically active was associated with lower inflammation as represented by sTNFR2 but not with other inflammatory markers. Higher PA (aerobic and strength) and lower inflammation were linked to better QoL. More research is warranted to validate the association among PA, inflammation, and QoL.
Despite well-documented disparities in cancer pain outcomes among African Americans, surprisingly little research exists on adherence to analgesia for cancer pain in this group. We compared analgesic ...adherence for cancer-related pain over a 3-month period between African Americans and whites using the Medication Event Monitoring System (MEMS). Patients (N = 207) were recruited from outpatient medical oncology clinics of an academic medical center in Philadelphia (≥18 years of age, diagnosed with solid tumors or multiple myeloma, with cancer-related pain, and at least 1 prescription of oral around-the-clock analgesic). African Americans reported significantly greater cancer pain (P < .001), were less likely than whites to have a prescription of long-acting opioids (P < .001), and were more likely to have a negative Pain Management Index (P < .001). There were considerable differences between African Americans and whites in the overall MEMS dose adherence, ie, percentage of the total number of prescribed doses that were taken (53% vs 74%, P < .001). On subanalysis, analgesic adherence rates for African Americans ranged from 34% (for weak opioids) to 63% (for long-acting opioids). Unique predictors of analgesic adherence varied by race; income levels, analgesic side effects, and fear of distracting providers predicted analgesic adherence for African Americans but not for whites. Perspective: Despite evidence of disparities in cancer pain outcomes among African Americans, surprisingly little research exists on African Americans' adherence to analgesia for cancer pain. This prospective study uses objective measures to compare adherence to prescribed pain medications between African American and white patients with cancer pain.
The objective of this study was to determine the patient- and treatment-related prognostic factors associated with vaginal toxicity in patients who received intravaginal high dose rate (HDR) ...brachytherapy alone as adjuvant treatment for endometrial cancer. Secondary goals of this study included a quantitative assessment of optimal dilator use frequency and a crude assessment of clinical predictors for compliant dilator use.
We retrospectively reviewed the charts of 100 patients with histologically confirmed endometrial cancer who underwent total hysterectomy and bilateral salpingo-oophorectomy with or without lymph node dissection and adjuvant intravaginal brachytherapy between 1995 and 2009 at the Hospital of the University of Pennsylvania. The most common treatment regimen used was 21 Gy in three fractions (71 patients). Symptoms of vaginal mucosal toxicity were taken from the history and physical exams noted in the patients' charts and were graded according to the Common Toxicity Criteria for Adverse Events v. 4.02.
The incidence of Grade 1 or asymptomatic vaginal toxicity was 33% and Grade 2-3 or symptomatic vaginal toxicity was 14%. Multivariate analysis of age, active length, and dilator use two to three times a week revealed odds ratios of 0.93 (p = 0.013), 3.96 (p = 0.008), and 0.17 (p = 0.032) respectively.
Increasing age, vaginal dilator use of at least two to three times a week, and shorter active length were found to be significantly associated with a decreased risk of vaginal stenosis. Future prospective studies are necessary to validate our findings.
Background
The authors measured epigenetic age acceleration (EAA) during and after cancer treatment and its association with inflammation and fatigue, which is a debilitating symptom in patients with ...cancer.
Methods
Patients who had head and neck cancer without distant metastases were assessed before, immediately after, and at 6 months and 12 months postradiotherapy. Blood DNA methylation was assessed using a proprietary bead chip (the Illumina MethylationEPIC BeadChip). EAA was calculated using the Levine epigenetic clock (DNAmPhenoAge), adjusted for chronological age. Fatigue was assessed using the Multidimensional Fatigue Inventory‐20. Inflammatory markers were measured using standard techniques.
Results
Most patients (N = 133) were men, White, had advanced disease, and received concurrent chemoradiation. EAA changes over time were significant, with the largest increase (4.9 years) observed immediately after radiotherapy (P < .001). Increased EAA was associated with elevated fatigue (P = .003) over time, and patients who had severe fatigue experienced 3.1 years higher EAA than those who had low fatigue (P < .001), which was more prominent (5.6 years; P = .018) for patients who had human papillomavirus‐unrelated disease at 12 months posttreatment. EAA was also positively associated with inflammatory markers, including C‐reactive protein (CRP) and interleukin‐6 (IL‐6), over time (P < .001), and patients who had high CRP and IL‐6 levels exhibited increases of 4.6 and 5.9 years, respectively, in EAA compared with those who had low CRP and IL‐6 levels (P < .001). CRP and IL‐6 mediated the association between EAA and fatigue (CRP: 95% CI, 0.060‐0.279; IL‐6: 95% CI, 0.024‐0.220).
Conclusions
Patients with head and neck cancer experienced increased EAA, especially immediately after treatment completion. EAA was associated with greater fatigue and inflammation, including 1 year after treatment. Inflammation may be a target to reduce the impact of age acceleration on poor functional outcomes.
Patients with head and neck cancer experience increased epigenetic age acceleration, especially immediately after treatment completion. Epigenetic age acceleration is associated with greater fatigue and inflammation, including 1 year posttreatment.
•Fatigue was linked to increased NF-kB and decreased IRF transcriptional activities.•This link was consistent with conserved transcriptional response to adversity (CRTA).•This fatigue-related CRTA ...response was mitigated in patients with HPV-related HNCs.
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.
Abstract
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.
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.
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.
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.
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.
There is growing evidence that the metabolism is deeply intertwined with head and neck squamous cell carcinoma (HNSCC) progression and survival but little is known about circulating metabolite ...patterns and their clinical potential. We performed unsupervised hierarchical clustering of 209 HNSCC patients via pre-treatment plasma metabolomics to identify metabolic subtypes. We annotated the subtypes via pathway enrichment analysis and investigated their association with overall and progression-free survival. We stratified the survival analyses by smoking history. High-resolution metabolomics extracted 186 laboratory-confirmed metabolites. The optimal model created two patient clusters, of subtypes A and B, corresponding to 41% and 59% of the study population, respectively. Fatty acid biosynthesis, acetyl-CoA transport, arginine and proline, as well as the galactose metabolism pathways differentiated the subtypes. Relative to subtype B, subtype A patients experienced significantly worse overall and progression-free survival but only among ever-smokers. The estimated three-year overall survival was 61% for subtype A and 86% for subtype B; log-rank
= 0.001. The association with survival was independent of HPV status and other HNSCC risk factors (adjusted hazard ratio = 3.58, 95% CI: 1.46, 8.78). Our findings suggest that a non-invasive metabolomic biomarker would add crucial information to clinical risk stratification and raise translational research questions about testing such a biomarker in clinical trials.
Cancer pain relief is often inadequate because of poor adherence to pain medication, especially for black patients.
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.
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.
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).
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.
To report patient-reported outcomes (PROs) of a phase III trial evaluating total androgen suppression (TAS) combined with dose-escalated radiation therapy (RT) for patients with intermediate-risk ...prostate cancer.
Patients with intermediate-risk prostate cancer were randomly assigned to dose-escalated RT alone (arm 1) or RT plus TAS (arm 2) consisting of luteinizing hormone-releasing hormone agonist/antagonist with oral antiandrogen for 6 months. The primary PRO was the validated Expanded Prostate Cancer Index Composite (EPIC-50). Secondary PROs included Patient-Reported Outcome Measurement Information System (PROMIS)-fatigue and EuroQOL five-dimensions scale questionnaire (EQ-5D). PRO change scores, calculated for each patient as the follow-up score minus baseline score (at the end of RT and at 6, 12, and 60 months), were compared between treatment arms using a two-sample
test. An effect size of 0.50 standard deviation was considered clinically meaningful.
For the primary PRO instrument (EPIC), the completion rates were ≥86% through the first year of follow-up and 70%-75% at 5 years. For the EPIC hormonal and sexual domains, there were clinically meaningful (
< .0001) deficits in the RT + TAS arm. However, there were no clinically meaningful differences by 1 year between arms. There were also no clinically meaningful differences at any time points between arms for PROMIS-fatigue, EQ-5D, and EPIC bowel/urinary scores.
Compared with dose-escalated RT alone, adding TAS demonstrated clinically meaningful declines only in EPIC hormonal and sexual domains. However, even these PRO differences were transient, and there were no clinically meaningful differences between arms by 1 year.
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