Canhua Xiao

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

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.

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

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.

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.

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).

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

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.

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

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.

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

Purpose The purpose of this study was to examine the impact of radiation therapy on quality of life (QOL) of breast cancer patients during and until 1 year after radiation therapy treatment. Methods and materials Thirty-nine breast cancer patients treated with breast-conserving surgery were enrolled in a prospective study before whole breast radiation therapy (50 Gy plus a 10-Gy boost). No patient received chemotherapy. Data were collected before, at week 6 of radiation therapy, and 6 weeks and 1 year after radiation therapy. The primary outcome variable was quality of life (QOL), measured by Medical Outcomes Study 36-Item Short Form Version 2 (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 the Perceived Stress Scale). Mixed effect modeling was used to observe QOL changes during and after radiation therapy. Results Total SF-36 scores did not change significantly during and up to 1 year after radiation therapy compared with baseline measures. Nevertheless, increased body mass index (BMI) and increased perceived stress were predictive of reduced total SF-36 scores over time (P = .0064, and P < .0001, respectively). In addition, increased BMI was predictive of reduced physical component summary scores of the SF-36 (P = .0011), whereas increased perceived stress was predictive of worse mental component summary scores (P < .0001). Other proposed potential risk factors including skin toxicity from radiation therapy were not significant. Conclusions Radiation therapy did not worsen QOL in breast cancer patients. However, pre-radiation therapy 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 after radiation therapy.

Methods for examining cancer symptom clusters over time.

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.

A systematic review of the association between fatigue and genetic polymorphisms

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.

Preliminary Patient Reported Outcomes Analysis of 3DCRT versus IMRT on the High Dose Arm of the Radiation Therapy Oncology Group (RTOG) 0126 Prostate Cancer Trial

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).

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

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.