Qiuling Shi

Automated Symptom Alerts Reduce Postoperative Symptom Severity After Cancer Surgery: A Randomized Controlled Clinical Trial

PURPOSE Patients receiving cancer-related thoracotomy are highly symptomatic in the first weeks after surgery. This study examined whether at-home symptom monitoring plus feedback to clinicians about severe symptoms contributes to more effective postoperative symptom control. PATIENTS AND METHODS We enrolled 100 patients receiving thoracotomy for lung cancer or lung metastasis in a two-arm randomized controlled trial; 79 patients completed the study. After hospital discharge, patients rated symptoms twice weekly for 4 weeks via automated telephone calls. For intervention group patients, an e-mail alert was forwarded to the patients clinical team for response if any of a subset of symptoms (pain, disturbed sleep, distress, shortness of breath, or constipation) reached a predetermined severity threshold. No alerts were generated for controls. Group differences in symptom threshold events were examined by generalized estimating equation modeling. RESULTS The intervention group experienced greater reduction in symptom threshold events than did controls (19% v 8%, respectively) and a more rapid decline in symptom threshold events. The difference in average reduction in symptom interference between groups was -0.36 (SE, 0.078; P = .02). Clinicians responded to 84% of e-mail alerts. Both groups reported equally high satisfaction with the automated system and with postoperative symptom control. CONCLUSION Frequent symptom monitoring with alerts to clinicians when symptoms became moderate or severe reduced symptom severity during the 4 weeks after thoracic surgery. Methods of automated symptom monitoring and triage may improve symptom control after major cancer surgery. These results should be confirmed in a larger study.

Symptom burden in cancer survivors 1 year after diagnosis

Few studies have examined risk for severe symptoms during early cancer survivorship. By using baseline data from the American Cancer Societys Study of Cancer Survivors‐I, the authors examined cancer survivors with high symptom burden, identified risk factors associated with high symptom burden, and evaluated the impact of high symptom burden on health‐related quality of life (HRQoL) 1 year postdiagnosis.

Inflammatory Cytokines are Associated with the Development of Symptom Burden in Patients with NSCLC Undergoing Concurrent Chemoradiation Therapy

Elevations in cancer treatment-induced circulating inflammatory cytokines may be partially responsible for the development of significant symptom burden (e.g., pain, fatigue, distress, disturbed sleep) during concurrent chemoradiation therapy (CXRT). Sixty-two patients undergoing CXRT for locally advanced non-small cell lung cancer (NSCLC) reported symptoms weekly for 15 weeks via the M. D. Anderson Symptom Inventory (MDASI). Serum inflammatory cytokines were assessed weekly during therapy via enzyme-linked immunosorbent assay. Dynamic changes in cytokines and associated symptom profiles were estimated using mixed-effect models. MDASI symptom severity increased gradually as CXRT dose accumulated and peaked at week 8. Serum concentrations of interleukin (IL)-6, IL-10, and serum soluble receptor 1 for tumor necrosis factor (sTNF-R1) increased significantly by week 8 (all p<.05). During CXRT, controlled for age, sex, race, body mass index, cancer recurrence, previous treatment status, total radiotherapy dose, and CXRT delivery technique, an increase in sTNF-R1 was significantly related to an increase in the mean score for all 15 MDASI symptoms (estimate, 1.74; SE, 0.69; p<.05) and to a larger radiation dose to normal lung volume (estimate, 1.77; SE, 0.71; p<.01); an increase in serum IL-6 was significantly related to increased mean severity for the five most severe symptoms (pain, fatigue, disturbed sleep, lack of appetite, sore throat) (estimate, 0.32; SE, 0.16; p<.05). These results suggest a role for over-expressed pro-inflammatory cytokines in significant worsening of symptoms in NSCLC patients undergoing CXRT, and warrant further study to identify biological targets for ameliorating treatment-related symptom burden.

Reply to symptom burden in cancer survivors 1 year after diagnosis: A report from the american cancer society's studies of cancer survivors

Background Few studies have examined risk for severe symptoms during early cancer survivorship. Using baseline data from the American Cancer Society’s Study of Cancer Survivors-I, we examined cancer survivors with high symptom burden, identified risk factors associated with high symptom burden, and evaluated the impact of high symptom burden on health-related quality of life (HRQoL) 1 year post-diagnosis.

Serum sTNF-R1, IL-6, and the development of fatigue in patients with gastrointestinal cancer undergoing chemoradiation therapy

Although evidence of inflammation and fatigue has been noted in cancer survivors, whether inflammation is linked to the expression of fatigue and other symptoms arising from concurrent chemoradiation therapy (CXRT) has not been well studied. Patients undergoing CXRT for locally advanced colorectal or esophageal cancer (n=103) reported multiple symptoms weekly via the M. D. Anderson Symptom Inventory (MDASI) from start of therapy. Serum samples were collected weekly to examine changes in inflammatory markers (interleukin (IL)-6, IL-8, IL-10, IL-1 receptor antagonist (IL-1RA), vascular endothelial growth factor (VEGF), and soluble receptor 1 for tumor necrosis factor (sTNF-R1)) via enzyme-linked immunosorbent assay. Relationships between symptom severity and inflammatory-marker concentration levels were estimated using mixed-effect regression analysis, controlled for week of therapy, age, sex, body mass index, pre-CXRT tumor stage, pre-CXRT chemotherapy, pre-CXRT statin use, and type of cancer. Fatigue was the most severe symptom over time, its development profile shared with pain, distress, drowsiness, poor appetite, and disturbed sleep. sTNF-R1 and IL-6 shared a similar pattern of symptom development, with significant increase during CXRT and decrease after completion of CXRT. Serum concentrations of sTNF-R1 were positively associated over time with the severity of fatigue (p=0.00097), while sTNF-R1 and IL-6 were positively related to the severity of a component score of the six most severe symptoms (both p<0.0001). This longitudinal study suggests a role for over-expressed sTNF-R1 and IL-6 in the development of fatigue and other severe sickness symptoms during CXRT in patients with colorectal or esophageal cancer.

Serum interleukin-6 predicts the development of multiple symptoms at nadir of allogeneic hematopoietic stem cell transplantation.

During the time of lowest white blood cell count (nadir) of allogeneic hematopoietic stem cell transplantation (allo‐HSCT), cancer patients suffer from tremendous symptom burden related to therapy that requires intensive patient care. However, the mechanism underlying the development of multiple symptoms has not been established.

Prognostic Value of Symptom Burden for Overall Survival in Patients Receiving Chemotherapy for Advanced Nonsmall Cell Lung Cancer

Patient–reported outcomes have shown independent prognostic value for patients with nonsmall cell lung cancer (NSCLC). However, translating patient‐reported outcomes into useful prognostic information for individual patients has been problematic.

Assessing Persistent Cancer Pain: A Comparison of Current Pain Ratings and Pain Recalled from the Past Week

Recent guidelines developed by the U.S. Food and Drug Administration for the use of patient-reported outcomes discuss the rating of pain and other symptoms at their current level of severity versus rating these symptoms using a recall period, such as the past 24 hours or past week. To explore whether the overall experience of cancer patients is better represented by ratings of current pain or pain recalled from the past week, we conducted a secondary analysis of Eastern Cooperative Oncology Group data from 1147 patients with cancer who had reported having persistent pain during the past week. Patients used the Brief Pain Inventory (BPI) to rate their current pain along with their pain at its worst, least, and average during the past week. T-tests were used to compare ratings of current pain and pain recalled from the past week. Linear regressions described the extent to which the various pain ratings contributed to overall pain interference, also derived from the BPI. Overall, patients rated their current pain as less severe than their worst or average pain recalled from the past week. Worst pain recalled from the past week contributed most to ratings of pain interference. These findings indicate that ratings of recalled worst pain, rather than ratings of current pain, might better reflect the overall experience of pain and its impact on function in cancer patients with persistent pain. Our results provide information that might guide the choice of recall period for cancer clinical trials with pain as a self-reported outcome.

Biological pathways and genetic variables involved in pain.

This paper summarizes current knowledge of pain-related and analgesic-related pathways as well as genetic variations involved in pain perception and management. The pain group of the GENEQOL Consortium was given the task of summarizing the current status of research on genetic variations in pain and analgesic efficacy. This review is neither exhaustive nor comprehensive; we focus primarily on single-nucleotide polymorphisms. Two categories of potential genetic pain-perception pathways were identified: neurotransmission modulators and mechanisms that affect inflammation. Four categories were identified for analgesic efficacy: genes related to receptor interaction, modulation of opioid effects, metabolism, and transport. Various genetic variations involved in these pathways are proposed as candidate genetic markers for pain perception and for individual sensitivity to analgesics. Candidate gene association studies have been used to provide evidence for the genetic modulation of pain perception and response to analgesics. However, the nature and range of genetic modulation of pain is not well addressed due to the limited number of patients and the limited number of genes and genetic variants investigated in studies to date. Moreover, personalized analgesic treatments will require a more complete understanding of the effects of genetic variants and gene–gene interactions in response to analgesics.PurposeThis paper summarizes current knowledge of pain-related and analgesic-related pathways as well as genetic variations involved in pain perception and management.MethodsThe pain group of the GENEQOL Consortium was given the task of summarizing the current status of research on genetic variations in pain and analgesic efficacy. This review is neither exhaustive nor comprehensive; we focus primarily on single-nucleotide polymorphisms.ResultsTwo categories of potential genetic pain-perception pathways were identified: neurotransmission modulators and mechanisms that affect inflammation. Four categories were identified for analgesic efficacy: genes related to receptor interaction, modulation of opioid effects, metabolism, and transport. Various genetic variations involved in these pathways are proposed as candidate genetic markers for pain perception and for individual sensitivity to analgesics.ConclusionsCandidate gene association studies have been used to provide evidence for the genetic modulation of pain perception and response to analgesics. However, the nature and range of genetic modulation of pain is not well addressed due to the limited number of patients and the limited number of genes and genetic variants investigated in studies to date. Moreover, personalized analgesic treatments will require a more complete understanding of the effects of genetic variants and gene–gene interactions in response to analgesics.

Biological pathways, candidate genes, and molecular markers associated with quality-of-life domains: an update

Background There is compelling evidence of a genetic foundation of patient-reported quality of life (QOL). Given the rapid development of substantial scientific advances in this area of research, the current paper updates and extends reviews published in 2010.ObjectivesThe objective was to provide an updated overview of the biological pathways, candidate genes, and molecular markers involved in fatigue, pain, negative (depressed mood) and positive (well-being/happiness) emotional functioning, social functioning, and overall QOL.MethodsWe followed a purposeful search algorithm of existing literature to capture empirical papers investigating the relationship between biological pathways and molecular markers and the identified QOL domains.ResultsMultiple major pathways are involved in each QOL domain. The inflammatory pathway has the strongest evidence as a controlling mechanism underlying fatigue. Inflammation and neurotransmission are key processes involved in pain perception, and the catechol-O-methyltransferase (COMT) gene is associated with multiple sorts of pain. The neurotransmitter and neuroplasticity theories have the strongest evidence for their relationship with depression. Oxytocin-related genes and genes involved in the serotonergic and dopaminergic pathways play a role in social functioning. Inflammatory pathways, via cytokines, also play an important role in overall QOL.ConclusionsWhereas the current findings need future experiments and replication efforts, they will provide researchers supportive background information when embarking on studies relating candidate genes and/or molecular markers to QOL domains. The ultimate goal of this area of research is to enhance patients’ QOL.