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.

Measuring the symptom burden of lung cancer: the validity and utility of the lung cancer module of the M. D. Anderson Symptom Inventory.

We conducted a study to establish the psychometric properties of a module of the M. D. Anderson Symptom Inventory (MDASI) developed specifically for patients with lung cancer (MDASI-LC). The MDASI measures 13 common "core" symptoms of cancer and its treatment. The MDASI-LC includes the 13 core MDASI symptom items and three lung cancer-specific items: coughing, constipation, and sore throat. MDASI-LC items were administered to three cohorts of patients with lung cancer undergoing either chemotherapy or chemoradiotherapy. Known-group validity and criterion (concurrent) validity of the MDASI-LC were evaluated using the Eastern Cooperative Oncology Group performance status and the 12-item Short-Form Health Survey. The internal consistency and test-retest reliability of the module were adequate, with Cronbach coefficient α-values of 0.83 or higher for all module items and subscales. The sensitivity of the MDASI-LC to changes in patient performance status (disease progression) and to continuing cancer treatment (effects of treatment) was established. Cognitive debriefing of a subset of participants provided evidence for content validity and indicated that the MDASI core items and three additional lung cancer-specific items were clear, relevant to patients, and easy to understand; only two patients suggested additional symptom items. As expected, the item "sore throat" was sensitive only for patients receiving chemoradiotherapy. The MDASI-LC is a valid, reliable, and sensitive symptom-assessment instrument whose use can enhance clinical studies of symptom status in patients with lung cancer and epidemiological and prevalence studies of symptom severity across various cancer types.

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.

Asking the community about cutpoints used to describe mild, moderate, and severe pain.

UNLABELLED: Clinical practice guidelines recommend that numeric rating scales be used to document the severity of perceived pain, yet patients and clinicians often opt to use simpler classification systems such as mild, moderate, or severe. To assess how well the numeric scales correlate with the tri-level classification system for describing pain severity, we conducted a subanalysis of a larger population-based study of pain management preferences. Our primary objective was to identify the numeric boundaries used by 287 adults to describe pain as mild, moderate, or severe. We examined differences in the means of the upper and lower limits for mild, moderate, and severe pain according to demographic characteristics and type of pain. Ranges reported for each pain level were 1.3 to 3.6 (mild), 4.3 to 6.5 (moderate), and 7.5 to 9.8 (severe). The primary finding was that "healthy" community adults rated the pain severity cutpoints much as patients with clinical pain did, 1 to 4 for mild, 5 to 6 for moderate, and 7 to 10 for severe. These results suggest that numeric rating scales can be used in clinical practice with both patients and community-dwelling adults. Our findings also support encouraging the general public to use a 0 to 10 scale to rate their pain intensity. PERSPECTIVE: Methods used to describe numeric cutpoints for mild, moderate, and severe pain were applied to community adults. Having standard categories to describe pain severity might increase clinicians' confidence in using a numeric scale to make treatment decisions. Further studies of cutpoint methodology and its clinical importance are warranted.

An urban community's preferences for hypothetical outcomes of analgesic pain treatment.

We assessed preferences of urban residents regarding hypothetical treatment outcomes related to analgesic use to determine how well subjects understood the severity of the outcomes, describe community preferences for these outcomes, and identify predictors of preferences. In a cross-sectional telephone survey, we obtained mean ratings for hypothetical outcomes that included two dimensions of clinical pain (pain severity and potential side effects): A=moderate pain, three side effects; B=mild pain, three side effects; C=moderate pain, one side effect. We focused on 111 respondents who rated Outcome A, moderate pain with three side effects, as the worst condition (the logical choice). Being Spanish speaking predicted preferences across treatment Outcomes A and B. Spanish-speaking subjects and those in fair to poor health tended to view all three outcomes more negatively than other respondents. Knowledge of public preferences can help clinicians better understand factors that influence treatment choices and may help them motivate their patients to adhere to analgesic regimens.

Levels of symptom burden during chemotherapy for advanced lung cancer: differences between public hospitals and a tertiary cancer center.

PURPOSE: We compared risk factors for high disease- and treatment-related symptom burden over 15 weeks of therapy in medically underserved patients with advanced non-small-cell lung cancer and in patients treated at a tertiary cancer center. PATIENTS AND METHODS: We monitored symptom severity weekly during chemotherapy. Patients were recruited from a tertiary cancer center (n=101) and three public hospitals treating the medically underserved (n=80). We used a composite symptom-severity score and group-based trajectory analysis to form two groups: one with consistently more severe symptoms and another with less severe symptoms. We examined predictors of group membership. RESULTS: Seventy percent of the sample (n=126) reported low symptom-severity levels that decreased during therapy; 30% (n=55) had consistently severe symptoms throughout the study. In multivariate analysis, patients with good performance status being treated in public hospitals were significantly more likely than patients treated at the tertiary cancer center to be in the high-symptom group (odds ratio, 5.6; 95% CI, 2.1 to 14.6; P = .001) and to report significantly higher symptom interference (P = .001). Other univariate predictors of high-symptom group membership included variables associated with being medically underserved (eg, having less education, being single, and being nonwhite). No group differences by ethnicity were observed in the public hospitals. Medically underserved patients were less likely to receive adequate pain management. CONCLUSION: Patients with advanced lung cancer and good performance status treated at public hospitals were more likely than those treated at a tertiary cancer center to experience substantial symptoms during chemotherapy.

Prognostic value of symptom burden for overall survival in patients receiving chemotherapy for advanced nonsmall cell lung cancer.

BACKGROUND: 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. METHODS: A total of 94 patients with advanced NSCLC and an Eastern Cooperative Oncology Group performance status (PS) of 0 to 2 who qualified for chemotherapy rated symptom severity using the M. D. Anderson Symptom Inventory before and after their first chemotherapy cycle. Prognostic values of baseline symptoms and changes in symptom severity were examined by Cox proportional hazards models. RESULTS: In multivariate analysis, controlled for demographic and other factors, baseline coughing rated > or =4 independently predicted significantly higher risk for shorter survival (hazards ratio [HR], 8.69; P < .0001). Patients with coughing > or =4 and a PS of 2 were more likely to have shorter survival (HR, 20.6; P < .0001) than patients with coughing <4 and a PS of 0 to 1. A 1-point or greater increase in severity of fatigue (P < .05), shortness of breath, or poor appetite (P < .01) from baseline to the end of the first chemotherapy cycle was also found to be independently associated with higher risk for poor survival. CONCLUSIONS: An increased risk for shorter survival was indicated by moderate to severe coughing at baseline or by increased fatigue or shortness of breath during the first chemotherapy cycle in patients with advanced NSCLC. Although cross-validation is needed, these data suggest that an individual patient's symptom severity scores, quickly obtainable in the clinic, might contribute clinically useful information for treatment planning for that patient. Society.

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

BACKGROUND: 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. METHODS: To explore the role of inflammatory cytokines in the development of treatment-related symptoms, we studied dynamic changes in symptoms and in serum concentrations of inflammatory cytokines (interleukin [IL]-6, IL-8, soluble tumor necrosis factor receptor 1 [sTNF-R1], IL-1 receptor antagonist, and IL-12p40p70) from pretherapy throughout the first 30 days of allo-HSCT in 30 patients with acute myelogenous leukemia or myelodysplastic syndrome. We measured multiple symptoms repeatedly using the M. D. Anderson Symptom Inventory. Mixed-effects modeling was used to analyze longitudinal data. RESULTS: In response to conditioning and stem-cell infusion, serum levels of IL-6 and the severity of multiple symptoms increased rapidly and peaked at nadir. From baseline to nadir (approximately Day 8 post-transplantation), increase in IL-6 was significantly associated with worsening of the most severe symptoms (fatigue, poor appetite, pain, drowsiness, dry mouth, and disturbed sleep; P< .01). During the first 30 days after transplantation, increases in IL-6 (P< .001) and sTNF-R1 (P< .05) significantly predicted the increasing severity of these symptoms. CONCLUSIONS: These results suggest that release of systemic inflammatory cytokines, mainly IL-6, corresponds to an increase in treatment-related multiple-symptom burden during the nadir period of allo-HSCT.

Longitudinal study of the relationship between chemoradiation therapy for non-small-cell lung cancer and patient symptoms.

PURPOSE: Cancer patients undergoing aggressive therapy suffer from multiple nonspecific treatment-related symptoms. The goal of this prospective study was to establish a profile of the development of different symptoms over the time of therapy and to examine symptom-related functional interference in patients with non-small-cell lung cancer (NSCLC) undergoing concurrent chemoradiation therapy (CXRT). PATIENTS AND METHODS: Patients with locally advanced unresectable (stage II-IIIB) NSCLC were recruited for the study (N = 64). The M.D. Anderson Symptom Inventory (MDASI) was used to measure multiple symptoms before and weekly for 12 weeks after the start of CXRT. Mixed-effect growth curve models were used to estimate symptom development during CXRT. RESULTS: Approximately 63% of patients suffered from moderate to severe levels of multiple symptoms by the end of CXRT. Symptom clusters with four development patterns appeared over the time of CXRT. With some variation between patients, all symptoms had a significant impact on the level of interference (all P < .001). Fatigue, distress, and sadness were the single strongest predictors of total symptom interference (each R2 > or = 0.49). Physical symptoms had greater impact on interference with function when they were moderate to severe, whereas affective symptoms had the largest effect on interference when they were mild to moderate. CONCLUSION: Longitudinal analysis identified symptom clusters that have different development patterns in NSCLC patients receiving CXRT, providing a base for more accurate symptom management and suggesting the need for further study to identify potential mechanisms that might lead to better symptom control or prevention.