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.

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.

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• The MD Anderson SymptomInventory for CML can be used to collect patientreported symptoms for research and clinical practice.• Thirty percent of patients in chronic-phase CML and on TKIs experience moderate symptoms that interfere with daily functioning.We developed a module of the MD Anderson Symptom Inventory (MDASI) for patients with chronic myeloid leukemia (CML). To develop the MDASI-CML, we identified CMLspecific symptoms from qualitative interviews with 35 patients. A list of candidate symptoms was reduced by a panel of patients, caregivers, and clinicians to the 13 core MDASI symptom items and 6 CML-specific items; these items were subsequently administered to 30 patients. Cognitive debriefing confirmed that the items were clear, relevant, and easy to use. One additional CML-specific symptom item was added, for a total of 7. The refined MDASI-CML was administered to 152 patients once every 2 weeks for 1 year. The content, concurrent, known-group, and construct validity of the MDASI-CML were evaluated. The internal consistency and test-retest reliabilities of the module were adequate. Longitudinal analysis showed relatively stable symptom severity scores over time. The most severe symptoms were fatigue, drowsiness, disturbed sleep, muscle soreness and cramping, and trouble remembering things. Approximately one-third of the patients who completed the MDASI-CML reported persistent moderate-to-severe symptoms. The MDASI-CML is a valid and reliable symptom assessment instrument that can be used in clinical studies of symptom status in patients with CML. This trial was registered at www.clinicaltrials.gov as #NCT01046305. (Blood. 2013;122(5):641-647)

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Acknowledging caregivers' contributions, giving focused information as needed, and providing a safe environment in which to build coherent caregiving stories can assist caregivers. Research is needed to confirm the effectiveness of interventions with caregivers and to understand patients' role in the dynamics of informal caregiving.

Purpose Increasing research suggests that inflammation mediates symptom development. In this longitudinal study, we examined inflammatory factors related to the development of high symptom burden during autologous stem cell transplant (AuSCT) for multiple myeloma. Experimental Design Patients (n = 63) repeatedly reported symptom severity on the M. D. Anderson Symptom Inventory multiple myeloma module (MDASI-MM) and contributed blood samples periodically for up to 100 days post-AuSCT for inflammatory marker assays. The temporal associations between serum inflammatory marker concentrations and symptom severity outcomes were examined by nonlinear mixed-effect modeling. Results Fatigue, pain, disturbed sleep, lack of appetite, and drowsiness were consistently the most-severe MDASI-MM symptoms during the study. Peak symptom severity occurred on day 8 post-AuSCT, during white blood cell count nadir. Patterns of serum IL-6 (peak on day 9) and sIL-6R (nadir on day 8) expression paralleled symptom development over time (both P < 0.0001). By univariate analysis, serum IL-6, sIL-6R, IL-10, CRP, MIP-1α, sIL-1R2, sIL-1RA, and sTNF-R1 were significantly related to the most-severe symptoms during the first 30 days post-AuSCT (all P < 0.05). By multivariate analysis, IL-6 (estimate = 0.170, P = 0.004) and MIP-1α (estimate = −0.172, P = 0.006) were temporally associated with the severity of the component symptom score. Conclusions Systemic inflammatory response was associated with high symptom burden during the acute phase of AuSCT. Additional research is needed to understand how the inflammatory response is mechanistically associated with symptom expression and whether suppression of this response can reduce symptoms without compromising tumor control.

The Carboniferous Bear Gulch Limestone of the central Montana Big Snowy Trough is a lithographic limestone analogous to the plattenkalk carbonates of the Mesozoic European/Middle Eastern Tethyan belt. It contains an excellently preserved chitinous and phosphatic marine fauna. Petrographic and field studies synthesized with palaeontological data provide insights into depositional history. Tectonic activity initiated development of small en echelon basins. Rims of these basins were sites of high primary productivity. Photosynthesis by subtidal cyanobacterial mats and algae caused in situ precipitation of micrite. Cyanobacteria and algae also provided a food source for benthic and nektonic organisms, which provided food for predators. Respiration in turn provided carbon dioxide for continued photosynthesis. Thus a balanced ecosystem evolved. Productivity in the water column used up available oxygen, resulting in dysaerobic to anaerobic conditions in the bottom waters and sediments. This plus high sedimentation rates of carbonate ooze transported downslope, aided in preservation of whole‐body fossils. There are no likely modern analogues known for the Bear Gulch Limestone. However, comparisons with Mesozoic plattenkalke demonstrate that it is most closely analogous to those deposited in shallow water back‐reef areas of the Tethyan carbonate platform, rather than to those deposited in the deeper water shelf‐edge environment. This is in agreement with the water depth of roughly 40 m estimated for the Bear Gulch Limestone.