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.

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.

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-Hodgkin's 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 posttransplantation. 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 nonHodgkin's lymphoma.

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 = .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 < .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.

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. Cancer 2008. © American Cancer Society.