Gary M. Mobley

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.

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.

Symptom burden in patients undergoing autologous stem-cell transplantation

Patients who undergo autologous peripheral blood stem cell (PBSC) transplantation experience multiple symptoms that adversely affect quality of life. We assessed symptoms during the acute phase of autologous PBSC transplantation to determine the severity of individual symptoms and to determine overall symptom profiles in 100 patients with multiple myeloma or non-Hodgkins lymphoma. Study subjects completed the blood and marrow transplantation module of the M. D. Anderson Symptom Inventory before hospitalization, during conditioning, on day of transplantation, at nadir (the time of lowest white blood cell count) and on day 30 post-transplantation. Additional symptom, quality-of-life and medical status measures were collected. Symptom means were mild at baseline, intensified during conditioning, peaked at nadir and decreased by day 30. At nadir, the most severe symptoms for the entire patient sample were lack of appetite, fatigue, weakness, feeling sick, disturbed sleep, nausea and diarrhea. Cancer diagnosis was a significant predictor of changes in symptoms over time. The patterns of fatigue, pain, sleep disturbance and lack of appetite were significantly different for patients with multiple myeloma as compared with patients with non-Hodgkins lymphoma.

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.

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.

Prevalence and trajectory of disease- and treatment-related symptom burden in patients with multiple myeloma undergoing induction therapy.

e19627 Background: Patients with multiple myeloma (MM) undergoing induction therapy experience both disease- and therapy-related symptoms. This study selectively focused on the trajectory of pain, fatigue, numbness and bone aches from patient-reported outcome. METHODS MM patients (N=62) repeatedly rated symptoms via the M. D. Anderson Symptom Inventory (MDASI) (twice a week for 12 weeks, then weekly for 6 weeks). Ordinal regression analysis was used to describe symptom trajectories across time. Group-based trajectory modeling was used 1) to estimate the proportion of MM patients belonging to high, medium or low group by symptom severity; and 2) to examine the patterns of each group derived for each symptom. RESULTS During induction period, fatigue was persistently the most severe symptom, while therapy-induced neuropathy (MDASI numbness item) increased significantly from baseline (P=.0008). Group-based trajectory modeling resulted in 3 groups as the best model fit for 4 symptoms. The proportions of patients categorized as having high, medium or low symptom severity, respectively, were: for pain, 27%, 41% and 32%; for bone ache, 22%, 43% and 35%; for numbness, 22%, 48% and 30%; for fatigue, 28%, 58% and 14%. For pain, we observed a significant linear increased trend in the medium group (P<.001). For fatigue, bone ache and numbness, the medium and low groups exhibited only a slight change in slope, while the high symptom group showed a significant initial increase followed by a decrease trend (all quadratic trends, P<.001). Other than baseline performance status (P<.01), no clinical or patient factor was related to group membership. CONCLUSIONS The majority of patients reported moderate or greater fatigue, pain and bone aches throughout the induction treatment, with little evidence of reduction, while numbness/tingling dramatically increased over time. We also observed that some MM patients persistently reported low symptom burden compared to others, despite similar disease burden and therapy. These results warrant further translational studies to identify biomarker(s) related to high symptom burden, so as to guide personalized patient care during standard induction therapy.

A new symptom measure in chronic myeloid leukemia.

e19545 Background: A major barrier to effective symptom management in chronic myeloid leukemia (CML) is inadequate assessment. We aimed to develop a short, easily-understood, valid, and reliable patient-reported outcome measure of CML symptoms for research and practice. METHODS 127 patients with CML completed the 13 symptom severity and 6 interference items of the core M. D. Anderson Symptom Inventory (MDASI) plus 7 CML-specific symptom items (Table), generated from patient and expert input, measured on a 0-10 scale (0 = none, 10 = worst imaginable). 85 patients completed the same items 2 weeks later. Patients also answered a single quality-of-life (QOL) question. Demographic and disease information was collected on all patients. Multivariate analysis examined relationships among items. Psychometric procedures determined reliability and validity of the MDASI-CML. RESULTS Sample characteristics and symptom severity and interference are in the table. All items were retained as clinically significant and nonredundant. The reliability index (Cronbach α) and test-retest reliability of the 20 symptom items were 0.94 and 0.93 respectively and of the 6 interference items were 0.94 and 0.91 respectively. The MDASI-CML discriminated between patients who were employed versus those medically disabled and with good versus poor QOL. Symptom severity explained 87% of the variance in interference, with the core symptoms explaining 83% and the CML-specific symptoms explaining 76%. CONCLUSIONS We have validated an analytic tool, the MDASI-CML, for quantifying CML symptoms. The MDASI-CML is being used to assess side effects in treatment trials and to monitor symptoms in clinical care. [Table: see text] [Table: see text].

Factors contributing to high symptom burden during chemotherapy for advanced lung cancer: The risk of being underserved.

9003 Background: Patients undergoing chemotherapy for late-stage non-small cell lung cancer (NSCLC) have multiplesymptoms related to disease and therapy. We determined factors associated longitudin...