Racial/ethnic disparities in inflammatory gene single-nucleotide polymorphisms as predictors of a high risk for symptom burden in patients with multiple myeloma 1 year after diagnosis.
ABSTRACT: This study was conducted to determine whether any regulatory single-nucleotide polymorphism (SNP) in an inflammatory gene was associated with a high symptom burden in patients 1 year after the diagnosis of multiple myeloma (MM).MM patients rated symptoms with the MD Anderson Symptom Inventory multiple myeloma module (MDASI-MM) and provided buccal-swab DNA samples. SNPs for 4 cytokine genes (interleukin 6 [IL6] -174G>C, IL1? -511C>T, tumor necrosis factor ? [TNF?] -308G>A, and IL10 -1082G>A) were tested. Logistic regression models were used to identify SNPs that might predict moderate/severe symptoms (rated ? 4 on the MDASI-MM 0-10 scale). For the evaluation of the relationship between SNPs and overall symptom burden, a 2-step cluster analysis was used to divide patients into subgroups with high or low symptom levels.Forty-one percent of the 344 patients enrolled had a high overall symptom burden. The most prevalent moderate/severe symptoms were fatigue (47%), pain (42%), numbness (38%), and bone aches (32%). For non-Hispanic whites, the IL1? -511 CC genotype was associated with a high overall symptom burden (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.25-4.72; P =?.004), whereas the IL6 -174 GG genotype predicted less moderate/severe fatigue (OR, 0.53; 95% CI, 0.29-0.88; P =?.013). For other patients, the IL6 -174 GG genotype predicted moderate/severe pain (OR, 3.36; 95% CI, 1.23-13.64; P =?.010).These results support growing evidence showing that inflammation is associated with cancer-related symptoms, and they suggest that racial/ethnic factors contribute to this association.
Project description:The symptom burden associated with multiple myeloma (MM) is often severe. Presently, no instrument comprehensively assesses disease-related and treatment-related symptoms in patients with MM. We sought to validate a module of the M. D. Anderson Symptom Inventory (MDASI) developed specifically for patients with MM (MDASI-MM).The MDASI-MM was developed with clinician input, cognitive debriefing, and literature review, and administered to 132 patients undergoing induction chemotherapy or stem cell transplantation. We demonstrated the MDASI-MM's reliability (Cronbach ? values); criterion validity (item and subscale correlations between the MDASI-MM and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EORTC MM module (QLQ-MY20)), and construct validity (differences between groups by performance status). Ratings from transplant patients were examined to demonstrate the MDASI-MM's sensitivity in detecting the acute worsening of symptoms post-transplantation.The MDASI-MM demonstrated excellent correlations with subscales of the 2 EORTC instruments, strong ability to distinguish clinically different patient groups, high sensitivity in detecting change in patients' performance status, and high reliability. Cognitive debriefing confirmed that the MDASI-MM encompasses the breadth of symptoms relevant to patients with MM.The MDASI-MM is a valid, reliable, comprehensive-yet-concise tool that is recommended as a uniform symptom assessment instrument for patients with MM.
Project description:Given the potential for older patients to experience exaggerated toxicity and symptoms, this study was performed to characterize patient reported outcomes in older patients following definitive radiation therapy (RT) for oropharyngeal cancer (OPC).Cancer-free head and neck cancer survivors (>6 months since treatment completion) were eligible for participation in a questionnaire-based study. Participants completed the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN). Those patients ?65 years old at treatment for OPC with definitive RT were included. Individual and overall symptom severity and clinical variables were analyzed.Of the 79 participants analyzed, 82% were male, 95% white, 41% T3/4 disease, 39% RT alone, 27% induction chemotherapy, 52% concurrent, and 18% both, and 96% IMRT. Median age at RT was 71 yrs. (range: 65-85); median time from RT to MDASI-HN was 46 mos. (2/3 > 24 mos.). The top 5 MDASI-HN items rated most severe in terms of mean (±SD) ratings (0-10 scale) were dry mouth (3.48 ± 2.95), taste (2.81 ± 3.29), swallowing (2.59 ± 2.96), mucus in mouth/throat (2.04 ± 2.68), and choking (1.30 ± 2.38) reported at moderate-severe levels (?5) by 35, 29, 29, 18, and 13%, respectively. Thirty-nine % reported none (0) or no more than mild (1-4) symptoms across all 22 MDASI-HN symptoms items, and 38% had at least one item rated as severe (?7). Hierarchical cluster analysis resulted in 3 patient groups: 1) ~65% with ranging from none to moderate symptom burden, 2) ~35% with moderate-severe ratings for a subset of classically RT-related symptoms (e.g. dry mouth, mucus, swallowing) and 3) 2 pts. with severe ratings of most items.The overall long-term symptom burden seen in this older OPC cohort treated with modern standard therapy was largely favorable, yet a higher symptom group (~35%) with a distinct pattern of mostly local and classically RT-related symptoms was identified.
Project description: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 CML-specific 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.
Project description: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 hematopoietic stem cell transplant (AuSCT) for multiple myeloma.Patients (n = 63) repeatedly reported symptom severity on the MD Anderson Symptom Inventory multiple myeloma module (MDASI-MM) and contributed blood samples periodically for up to 100 days after AuSCT for inflammatory marker assays. The temporal associations between serum inflammatory marker concentrations and symptom severity outcomes were examined by nonlinear mixed-effect modeling.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 after AuSCT, during white blood cell count nadir. Patterns of serum interleukin (IL)-6 (peak on day 9) and soluble IL-6 receptor (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, C-reactive protein, macrophage inflammatory protein (MIP)-1?, sIL-1R2, sIL-1RA, and soluble tumor necrosis factor receptor 1 were significantly related to the most severe symptoms during the first 30 days after AuSCT (all P < 0.05). By multivariate analysis, IL-6 (estimate = 0.170; P = 0.004) and MIP-1? (estimate = -0.172; P = 0.006) were temporally associated with the severity of the component symptom score.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.
Project description:PURPOSE:We hypothesized that patients with oropharyngeal cancer treated with intensity modulated proton therapy (IMPT) would have lower symptom burdens, as measured by patient-reported outcome (PRO) surveys, than patients treated with intensity modulated photon therapy (IMRT). METHODS AND MATERIALS:Patients were treated for oropharyngeal cancer from 2006 to 2015 through prospective registries with concurrent chemotherapy and IMPT or chemotherapy and IMRT and completed the MD Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN) module at various times before treatment (baseline), during treatment (acute phase), within the first 3 months after treatment (subacute phase), and afterward (chronic phase). Individual symptoms and the top 5 and top 11 most severe symptoms were summarized and compared between the radiation therapy modalities. RESULTS:PRO data were collected and analyzed from 35 patients treated with chemotherapy and IMPT and from 46 treated with chemotherapy and IMRT. The baseline symptom burdens were similar between both groups. The overall top 5 symptoms were food taste problems (mean score 4.91 on a 0-10 scale), dry mouth (4.49), swallowing/chewing difficulties (4.26), lack of appetite (4.08), and fatigue (4.00). Among the top 11 symptoms, changes in taste and appetite during the subacute and chronic phases favored IMPT (all P<.048). No differences in symptom burden were detected between modalities during the acute and chronic phases by top-11 symptom scoring. During the subacute phase, the mean (±standard deviation) top 5 MDASI scores were 5.15 ± 2.66 for IMPT versus 6.58 ± 1.98 for IMRT (P=.013). CONCLUSIONS:According to the MDASI-HN, symptom burden was lower among the IMPT patients than among the IMRT patients during the subacute recovery phase after treatment. A prospective randomized clinical trial is underway to define the value of IMPT for the management of head and neck tumors.
Project description:BACKGROUND:Identifying symptoms experienced throughout the disease trajectory is pivotal to understanding management of patient symptoms. Patient interviews to solicit input from those who have experienced these symptoms is one method to capture this perspective to validate symptoms included in patient reported outcomes (PRO) measures. METHODS:A thematic approach was used to identify themes within qualitative interviews. The MD Anderson Symptom Inventory- Brain Tumor (MDASI-BT) was completed by glioma patients. Descriptive statistics was used for analysis of the MDASI-BT. RESULTS:Thematic saturation was reached with 23 participants, with a median age of 53 (23-62), on treatment (57%) and diagnosed with a glioblastoma (48%). Patients endorsed 20 out of the 22 MDASI-BT symptoms (symptoms not reported: dry mouth, shortness of breath) during the interviews and with completion of the instrument (seizures and vomiting were not endorsed). Fatigue (55%), seizures (50%), and pain (50%) were common symptoms described by the sample. During treatment, more symptoms were identified with fatigue, hair loss, and nausea more problematic. Aside from itching and swelling (endorsed by 2 patients each), all other symptoms not included in the MDASI-BT instrument were endorsed by only one patient. CONCLUSIONS:Completion of the MDASI-BT, found patients reported on average 6.8 symptoms with 14% of reported symptoms (mean = 3) rated as moderate to severe. The findings demonstrate how applicable the MDASI-BT is in capturing significant symptoms experienced and how important it is to utilize throughout ones' care to manage symptoms effectively.
Project description:A questionnaire-based study was conducted to assess long-term patient reported outcomes (PROs) following definitive IMRT-based treatment for early stage carcinomas of the tonsillar fossa.Participants had received IMRT with or without systemic therapy for squamous carcinoma of the tonsillar fossa (T1-2 and N0-2b) with a minimum follow-up of 2years. Patients completed a validated head and neck cancer-specific PRO instrument, the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN). Symptoms were compared between treatment groups of interest and overall symptom burden was evaluated.Of 139 participants analyzed, 51% had received ipsilateral neck IMRT, and 62% single modality IMRT alone (no systemic therapy). There were no differences in mean severity ratings for the top-ranked individual symptoms or symptom interference for those treated with bilateral versus ipsilateral neck IMRT alone. However, 40% of those treated with bilateral versus 25% of those treated with ipsilateral neck RT alone reported moderate-to-severe levels of dry mouth (p=0.03). Fatigue, numbness/tingling, and constipation were rated more severe for those who had received systemic therapy (p<0.05 for each), but absolute differences were small. Overall, 51% had no more than mild symptom ratings across all 22 symptoms assessed.The long-term patient reported symptom profile in this cohort of tonsil cancer survivors treated with definitive IMRT-based treatment showed a majority of patients with no more than mild symptoms, low symptom interference, and provides an opportunity for future comparison studies with other treatment approaches.
Project description:Importance:Postoperative morbidity associated with pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PA) remains as high as 70%. However, to our knowledge, few studies have examined quality of life in this patient population. Objective:To identify symptom burden and trajectories and factors associated with high symptom burden following PD for PA. Design, Setting, and Participants:This population-based cohort study of patients undergoing PD for PA diagnosed between 2009 and 2015 linked population-level administrative health care data to routinely prospectively collected Edmonton Symptom Assessment System (ESAS) scores from 2009 to 2015, with a data analysis undertaken in 2018. Exposures:Baseline characteristics, including age, sex, income quintile, rurality, immigration status, and comorbidity burden, as well as treatment characteristics, including year of surgery and receipt of chemotherapy. Main Outcome and Measures:The outcome of interest was moderate to severe symptoms (defined as ESAS ?4) for anxiety, depression, drowsiness, lack of appetite, nausea, pain, shortness of breath, tiredness, and impaired well-being. The monthly prevalence of moderate to severe symptoms was presented graphically for each symptom. Multivariable regression models identified factors associated with the reporting of moderate to severe symptoms. Results:We analyzed 6058 individual symptom assessments among 615 patients with PA who underwent resection (285 women [46.3%]) with ESAS data. Tiredness (443 [72%]), impaired well-being (418 [68%]), and lack of appetite (400 [65%]) were most commonly reported as moderate to severe. The proportion of patients with moderate to severe symptoms was highest immediately after surgery (range, 14%-66% per symptom) and decreased over time, stabilizing around 3 months (range, 8%-42% per symptom). Female sex, higher comorbidity, and lower income were associated with a higher risk of reporting moderate to severe symptoms. Receipt of adjuvant chemotherapy was not associated with the risk of moderate to severe symptoms. Conclusions and Relevance:There is a high prevalence of symptoms following PD for PA, with improvement over the first 3 months following surgery. In what to our knowledge is the largest cohort reporting on symptom burden for this population, we have identified factors associated with symptom severity. These findings will aid in managing patients' perioperative expectations and designing strategies to improve targeted symptom management.
Project description:<h4>Importance</h4>Lower cranial neuropathy (LCNP) is a rare but potentially disabling result of radiotherapy and other head and neck cancer therapies. Survivors who develop late LCNP may experience profound functional impairment, with deficits in swallowing, speech, and voice.<h4>Objective</h4>To investigate the association of late LCNP with severity of cancer treatment-related symptoms and subsequent general functional impairment among oropharyngeal cancer (OPC) survivors.<h4>Design, setting, and participants</h4>This cross-sectional survey study analyzed 889 OPC survivors nested within a retrospective cohort of OPC survivors treated at MD Anderson Cancer Center from January 1, 2000, to December 31, 2013. Eligible survey participants were disease free and completed OPC treatment 1 year or more before the survey. Data analysis was performed from October 10, 2017, to March 15, 2018.<h4>Exposures</h4>Late LCNP defined by onset 3 months or more after cancer therapy.<h4>Main outcomes and measures</h4>The primary outcome variable was the mean of the top 5 most severely scored symptoms of all 22 core and head and neck cancer-specific symptoms from the MD Anderson Symptom Inventory Head and Neck Cancer Module (MDASI-HN). Secondary outcomes included mean MDASI-HN interference scores and single-item scores of the most severe symptoms. Multivariate models regressed MDASI-HN scores on late LCNP status, adjusting for clinical covariates.<h4>Results</h4>Overall, 36 of 889 OPC survivors (4.0%) (753 [84.7%] male; 821 [92.4%] white; median [range] age, 56 [32-84] years; median [range] survival time, 7 [1-16] years) developed late LCNP. Late LCNP was significantly associated with worse mean top 5 MDASI-HN symptom scores (coefficient, 1.54; 95% CI, 0.82-2.26), adjusting for age, survival time, sex, therapeutic modality, T stage, subsite, type of radiotherapy, smoking, and normal diet before treatment. Late LCNP was also significantly associated with single-item scores for difficulty swallowing or chewing (coefficient, 2.25; 95% CI, 1.33-3.18), mucus (coefficient, 1.97; 95% CI, 1.03-2.91), fatigue (coefficient, 1.35; 95% CI, 0.40-2.21), choking (coefficient, 1.53; 95% CI, 0.65-2.41), and voice or speech symptoms (coefficient, 2.30; 95% CI, 1.60-3.03) in multivariable models. Late LCNP was not significantly associated with mean interference scores after correction for multiple comparisons (mean interference coefficient, 0.72; 95% CI, 0.09-1.35).<h4>Conclusions and relevance</h4>In this large survey study, OPC survivors with late LCNP reported worse cancer treatment-related symptoms, a finding suggesting an association between late LCNP and symptom burden. This research may inform the development and implementation of strategies for LCNP surveillance and management.
Project description:Close to one third of patients with major depression show increases in pro-inflammatory cytokines, which are in turn associated with risk for inflammatory disease. Genetic variants that enhance immune reactivity may thus enhance inflammatory and depressive reactions to stress. The aim of the present study was to investigate a trio of functional SNPs in the promoter regions of IL6 (-174G>C, rs1800795), IL1? (-511C>T, rs16944), and TNF (-308G>A, rs1800629) as moderators of the relationship between chronic stress exposure and elevations in depressive symptoms.Participants were 444 Australian youth (mean age=20.12) whose exposure to chronic stress in the past 6months was assessed using the semi-structured UCLA Life Stress Interview, and who completed the Beck Depression Inventory II at ages 15 and 20. Between ages 22 and 25, all participants in the selected sample provided blood samples for genotyping.In line with a hypothesized moderation effect, -174G allele carriers at IL6 had fewer depressive symptoms following interpersonal stress, relative to C/C homozygotes with equal interpersonal stress exposure. However, IL6 genotype did not moderate the effects of non-interpersonal stress exposure (i.e., financial, work and health-related difficulties) on depression. Also in line with hypotheses, the -511C allele in IL1?, previously associated with higher IL-1? expression, was associated with more severe depression following chronic interpersonal stress exposure, relative to T/T homozygotes. Again, the moderating effect was specific to interpersonal stressors and did not generalize to non-interpersonal stress. TNF was not a moderator of the effects of either interpersonal or non-interpersonal stress on later depression outcomes.Findings were consistent with the hypothesis that pro-inflammatory genetic variation increases the risk of stress-induced depression. The present results provide evidence of a genetic mechanism contributing to individual differences in depressive symptomatology following interpersonal stress exposure.