Association of Radiotherapy-Related Intestinal Injury and Cancer-related Fatigue: A Brief Review and Commentary.

Radiotherapy treatment-induced intestinal injury and gut microbial perturbation/dysbiosis have been implicated in the pathobiology of cancer-related fatigue. The objective of this brief review was to explore the available evidence of the relationship between intestinal injury and self-reported fatigue, especially among cancer patients. The scientific evidence-including our own-linking gut mucosal barrier dysfunction and gut microbial perturbation/dysbiosis induced by cancer treatment with worsening of cancer related fatigue (perhaps through the gut-brain axis) is limited but promising. Emerging data suggest that lifestyle interventions and the administration of specific probiotics may favorably modulate the gut microbiota and potentially mediate beneficial effects leading to improvements in fatigue.

Co-Occurrence of Symptoms and Gut Microbiota Composition Before Neoadjuvant Chemotherapy and Radiation Therapy for Rectal Cancer: A Proof of Concept.

PURPOSE: To examine a) whether there are significant differences in gut microbial diversity and in the abundance of gut microbial taxa; and b) differences in predicted functional pathways of the gut microbiome between those participants with high co-occurring symptoms and those with low co-occurring symptoms, prior to neoadjuvant chemotherapy and radiation therapy (CRT) for rectal cancer. METHODS: Rectal cancer patients (n = 41) provided stool samples for 16 S rRNA gene sequencing and symptom ratings for fatigue, sleep disturbance, and depressive symptoms prior to CRT. Descriptive statistics were computed for symptoms. Gut microbiome data were analyzed using QIIME2, LEfSe, and the R statistical package. RESULTS: Participants with high co-occurring symptoms (n = 19) had significantly higher bacterial abundances of Ezakiella, Clostridium sensu stricto, Porphyromonas, Barnesiella, Coriobacteriales Incertae Sedis, Synergistiaceae, Echerichia-Shigella, and Turicibacter compared to those with low co-occurring symptoms before CRT (n = 22). Biosynthesis pathways for lipopolysaccharide, L-tryptophan, and colanic acid building blocks were enriched in participants with high co-occurring symptoms. Participants with low co-occurring symptoms showed enriched abundances of Enterococcus and Lachnospiraceae, as well as pathways for ß-D-glucoronosides, hexuronide/hexuronate, and nicotinate degradation, methanogenesis, and L-lysine biosynthesis. CONCLUSION: A number of bacterial taxa and predicted functional pathways were differentially abundant in patients with high co-occurring symptoms compared to those with low co-occurring symptoms before CRT for rectal cancer. Detailed examination of bacterial taxa and pathways mediating co-occurring symptoms is warranted.

Gut microbiota and fatigue in rectal cancer patients: a cross-sectional pilot study.

CONTEXT: Although microbial-mediated disturbance of intestinal mucosal homeostasis (dysbiosis) is believed to contribute to the pathogenesis of chemotherapy and radiotherapy (CRT)-related fatigue, potential differences in the gut microbial diversity and in the abundance of gut microbial taxa between fatigued and non-fatigued patients have not been adequately examined, particularly in the rectal cancer population. PURPOSE: In this cross-sectional study, we aim to examine the differences in (a) gut microbial diversity and gut microbial abundances and (b) predicted functional pathways of the gut microbiome between rectal cancer participants with and without fatigue at the end of CRT. METHODS: Rectal cancer patients (n = 50) provided stool samples for 16S rRNA gene sequencing and symptom ratings for fatigue at the end of CRT. Gut microbiome data were analyzed using QIIME2, LEfSe, and the R statistical package. RESULTS: Fatigued (n = 35) participants showed enriched bacterial abundances of Eubacterium, Streptococcus, Adlercreutzia, and Actinomyces, as well as enriched abundances of the microbial sucrose degradation pathway, compared to non-fatigued patients at the end of CRT (n = 15). CONCLUSIONS: Differentially abundant microbial taxa were identified in fatigued and non-fatigued rectal cancer participants at the end of CRT. However, the exact role of these taxa (and identification of species) in the biology of CRT-related fatigue remains to be examined.

Gut Microbiota and Depressive Symptoms at the End of CRT for Rectal Cancer: A Cross-Sectional Pilot Study.

BACKGROUND: The role of alterations in gut microbiota composition (termed dysbiosis) has been implicated in the pathobiology of depressive symptoms; however, evidence remains limited. This cross-sectional pilot study is aimed at exploring whether depressive symptom scores changed during neoadjuvant chemotherapy and radiation therapy to treat rectal cancer, and if gut microbial taxa abundances and predicted functional pathways correlate with depressive symptoms at the end of chemotherapy and radiation therapy. METHODS: 40 newly diagnosed rectal cancer patients (ages 28-81; 23 males) were assessed for depressive symptoms using the Hamilton Rating Scale for Depression (HAM-D) and provided stool samples for 16S rRNA sequencing. Gut microbiome data were analyzed using QIIME2, and correlations and regression analyses were performed in R. RESULTS: Participants had significantly higher depressive symptoms at the end as compared to before CRT. The relative abundances of Gemella, Bacillales Family XI, Actinomyces, Streptococcus, Lactococcus, Weissella, and Leuconostocaceae were positively correlated (Spearman's rho = 0.42 to 0.32), while Coprobacter, Intestinibacter, Intestimonas, Lachnospiraceae, Phascolarctobacterium, Ruminiclostridium, Ruminococcaceae (UCG-005 and uncultured), Tyzzerella, and Parasutterella (Spearman's rho = -0.43 to - 0.31) were negatively correlated with HAM-D scores. Of the 14 predicted MetaCyc pathways that correlated with depressive symptom scores at the end of CRT, 11 (79%) were associated with biosynthetic pathways. CONCLUSIONS: Significant bacterial taxa and predicted functional pathways correlated with depressive symptoms at the end of chemotherapy and radiation therapy for rectal cancer which warrants further examination and replication of our findings.

Changes in Gut Microbiome Associated With Co-Occurring Symptoms Development During Chemo-Radiation for Rectal Cancer: A Proof of Concept Study.

PURPOSE: To examine a) whether there are significant differences in the severity of symptoms of fatigue, sleep disturbance, or depression between patients with rectal cancer who develop co-occurring symptoms and those with no symptoms before and at the end of chemotherapy and radiation therapy (CRT); b) differences in gut microbial diversity between those with co-occurring symptoms and those with no symptoms; and c) whether before-treatment diversity measurements and taxa abundances can predict co-occurrence of symptoms. METHODS: Stool samples and symptom ratings were collected from 31 patients with rectal cancer prior to and at the end of (24-28 treatments) CRT. Descriptive statistics were computed and the Mann-Whitney U test was performed for symptoms. Gut microbiome data were analyzed using R's vegan package software. RESULTS: Participants with co-occurring symptoms reported greater severity of fatigue at the end of CRT than those with no symptoms. Bacteroides and Blautia2 abundances differed between participants with co-occurring symptoms and those with no symptoms. Our random forest classification (unsupervised learning algorithm) predicted participants who developed co-occurring symptoms with 74% accuracy, using specific phylum, family, and genera abundances as predictors. CONCLUSION: Our preliminary results point to an association between the gut microbiota and co-occurring symptoms in rectal cancer patients and serves as a first step in potential identification of a microbiota-based classifier.

The Role of Gut Microbiome Perturbation in Fatigue Induced by Repeated Stress from Chemoradiotherapy: A Proof of Concept Study.

OBJECTIVES: The objectives of this proof of concept study were to (a) examine the temporal changes in fatigue and diversity of the gut microbiome over the course of chemoradiotherapy (CRT) in adults with rectal cancers; (b) investigate whether there are differences in diversity of the gut microbiome between fatigued and nonfatigued participants at the middle and at the end of CRT; and (c) investigate whether there are differences in the relative abundance of fecal microbiota at the phylum and genus levels between fatigued and nonfatigued participants at the middle and at the end of CRT. METHODS: Stool samples and symptom ratings were collected prior to the inception of CRT, at the middle (after 12-16 treatments) and at the end (after 24-28 treatments) of the CRT. Descriptive statistics and Mann-Whitney U test were computed for fatigue. Gut microbiome data were analyzed using the QIIME2 software. RESULTS: Participants (N = 29) ranged in age from 37 to 80 years. The median fatigue score significantly changed at the end of CRT (median = 23.0) compared with the median score before the initiation of CRT for the total sample (median = 17.0; p ≤ 0.05). At the middle of CRT, the alpha diversity (abundance of Operational Taxonomic Units) was lower for fatigued participants (149.30 ± 53.1) than for nonfatigued participants (189.15 ± 44.18, t(23) = 2.08, p ≤ 0.05). At the middle of CRT, the alpha diversity (abundance of Operational Taxonomic Units) was lower for fatigued participants (149.30 ± 53.1) than for nonfatigued participants (189.15 ± 44.18, Proteobacteria, Firmicutes, and Bacteroidetes were the dominant phyla for fatigued participants, and Escherichia, Bacteroides, Faecalibacterium, and Oscillospira were the most abundant genera for fatigued participants. CONCLUSION: CRT-associated perturbation of the gut microbiome composition may contribute to fatigue.

Gut microbiota differences in Island Hispanic Puerto Ricans and mainland non-Hispanic whites during chemoradiation for rectal cancer: A pilot study.

PURPOSE: To investigate whether there are differences in diversity, taxonomic composition, and predicted functional pathways of the gut microbiome between Island Hispanic Puerto Ricans (HPR) and mainland non-Hispanic whites (NHW) measured before and at the end of chemo-radiation (CRT) for Rectal Cancer. METHODS: Fifty-six stool samples of newly diagnosed rectal cancer patients (25 HPR and 31 NHW) were amplicon-sequenced during chemo-radiotherapy. 16S rRNA gene data was analyzed using QIIME2, phyloseq, and LEfSe. RESULTS: We observed similar within-sample alpha diversity for HPR and NHW participants during CRT. However, at the end of CRT, several taxa were present at significantly different abundances across both groups. Taxa enriched in the gut of HPR compared to NHW included Muribaculaceae, Prevotella 2 and 7, Gemella, Bacillales Family XI, Catenibacterium, Sutterella, Pasteurellales, and Pasteurellaceae genera, whereas over-represented taxa in NHW participants were Turicibacter and Eubacteriaceae. Significant differences in predicted HPR microbiota functions included pathways for synthesis of L-methionine and degradation of phenylethylamine and phenylacetate. CONCLUSION: In this pilot study, taxonomic analyses and functional predictions of the gut microbiomes suggest greater inflammatory potential in gut microbial functions among HPR rectal cancer patients undergoing CRT compared to that of NHW participants.

Factors Affecting the Severity of Fatigue during Radiotherapy for Prostate Cancer; an Exploratory Study.

INTRODUCTION: Limited studies have examined potential risk factors associated with the fatigue experience of a sample of Puerto Rican men treated with radiotherapy for non-metastatic prostate cancer. Identifying these factors may provide initial information about targets for individualized interventions, leading to more effective management of fatigue in this population. PURPOSE: To examine the relationship of age, body max index, depressive symptoms, physical activity, and sleep disturbance with fatigue during radiotherapy for prostate cancer. METHODS: Twenty six participants completed five inventories: demographic intake, health form, the Functional Assessment of Cancer-Therapy-fatigue, Patient-Reported Outcome Measures Information System-Sleep disturbance, and the International Physical Activity Questionnaire-Short Form before, middle/days 19-21 and completion/days 38-42 of radiotherapy. The principal investigator rated the Hamilton depression scale. Descriptive statistics were performed. Interactions and influence of variables on fatigue were assessed using bivariate correlation and multiple linear regression, respectively. RESULTS: At each study time point, sleep disturbance and depressive symptoms were strongly correlated with each other and fatigue. The linear combination of sleep disturbance and depressive symptoms was significantly related to fatigue. CONCLUSION: Given the high association of sleep disturbance and depressive symptoms with fatigue, clinicians should assess and develop interventions to manage these symptoms altogether.

Gut microbiota perturbation is associated with acute sleep disturbance among rectal cancer patients.

Cancer treatment-associated gut microbial perturbation/dysbiosis has been implicated in the pathobiology of sleep disturbance; however, evidence is scarce. Eighteen newly diagnosed rectal cancer patients (ages 52-81 years; 10 males) completed a sleep disturbance questionnaire and provided stool samples for 16s RNA gene sequencing during chemo-radiotherapy. Descriptive statistics, Wilcoxon test and regression analyses were computed. Regression analyses showed the Shannon's diversity index to be a significant factor associated with sleep disturbance. This preliminary work suggests that the biological "gut-brain axis" mechanism may be associated with symptoms of sleep disturbance.

Differences in the Severity, Distress, Interference, and Frequency on Cancer-Related Symptoms Between Island Hispanic Puerto Ricans and Mainland Non-Hispanic Whites.

The knowledge base of cancer-related symptoms is increasing; yet, limited attention has been given to provide evidence on differences in the perception of cancer symptoms between ethnic groups, especially in the Hispanic Puerto Rican (PR) population. To examine whether there are significant differences in the severity, distress, interference, and frequency of cancer symptoms between island Hispanic PR and mainland non-Hispanic whites. In this secondary data analysis, data from 109 Hispanic PR was matched by age, gender and cancer diagnosis with data from non-Hispanic whites. Cancer symptoms were assessed using the Cancer Symptom Scale (CSS). Mann-Whitney statistical test was used to evaluate pairwise differences between Hispanic PR and non-Hispanic whites on symptoms from the CSS. There were significant differences on some symptoms including PR reporting: (a) more intense itching, swelling, taste change, difficulty sleeping, bloating, depression, sadness, worry, and nervousness; (b) significantly greater distress about taste change, appetite, anxiety, depression, worry, and feeling nervous; (c) rash, anxiety, depression, sadness, and nervousness interfered the most with their daily lives; and, (d) that the frequency of occurrence of the symptoms of pain, itching, dizziness, taste change, anxiety, sadness, and nervousness was higher compared to non-Hispanic whites. PR cancer patients are at increased risk for experiencing greater severity of cancer symptoms compared to non-Hispanic whites. But because the Hispanic oncology population does not always report symptoms, risking under-assessment and under-management, this suggests there may be a greater need for symptoms surveillance for this population.

The symptom experiences of Puerto Rican children undergoing cancer treatments and alleviation practices as reported by their mothers.

Although symptoms during cancer treatments are prevalent and are important clinical outcomes of childhood cancer, the symptom experiences of Puerto Rican children along with the symptom alleviation/care practices that parents provide during cancer treatments have received limited attention. To examine the occurrence/severity of symptoms on the Therapy-Related Symptom Checklist-Children (TRSC-C), reported by mothers of Puerto Rican children undergoing cancer treatments and identifying mothers' symptom alleviation/management strategies. Descriptive study conducted between January and May 2012. Mothers of 65 Puerto Rican children/adolescents undergoing cancer treatments responded to the Spanish versions of the TRSC-C, Symptom Alleviation: Self-Care Methods, and a Demographic and Health form. The children/adolescents' mean age was 9.2 (1-17) years; 62% were boys; 56 had chemotherapy; 9 had chemoradiotherapy. Children diagnoses were 35.4% leukemia, 24.6% solid tumors, 24.6% nervous system tumors, and 15.4% other. On the TRSC-C, the symptoms experienced by 70% or more of the children were: irritability (77%), nausea (75%), and hair loss (72%). On the Symptom Alleviation: Self-Care Methods, the most commonly reported symptom alleviation category was "taking prescribed medicines." Puerto Rican mothers reported the use of alleviation practices to treat their children experiencing symptoms during pediatric cancer treatments. Patients and caregivers need to be educated about treatment-induced side effects, and the life-threatening consequences of underreporting and undermanagement. Symptoms should always be addressed at the time of initiation of primary or adjuvant cancer therapy because pretreatment symptoms may persist or get worse across the trajectory of treatment. A continuous assessment and management of symptoms during the childhood cancer trajectory can optimize clinical care and improve quality of life of patients and families.

Analysis of heart failure management at the Heart Failure and Transplantation Clinics of the Cardiovascular Center of Puerto Rico and the Caribbean.

BACKGROUND: Disease management programs (DMP) have been shown to be effective in management of patients with heart failure (HF). OBJECTIVE: To describe the experience at the Heart Failure and Transplantation Clinic of the Cardiovascular Center of Puerto Rico and the Caribbean (HFTC-CCPRC) implementing a model of DMP to a Hispanic population afflicted by HF. METHODS: A retrospective study was performed. Medical records from patients referred to the HFTC-CCPRC from 1999 to 2005 were selected for review. Information regarding drug regimen, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF) determinations by echocardiography or scintigraphic ventriculography, left ventricular dimensions measurements, maximal oxygen consumption (MVO2 max) determination, hospitalizations, and death cases were obtained from the initial evaluation and at 3, 6, and 12 months post-intervention at the HFTC-CCPRC. RESULTS: A total of 633 records were screened, from which 244 had complete information for analysis. After 12 months of treatment at the HFTC-CCPRC, NYHA functional class had decreased from 2.70 + 0.59 to 2.13 +/- 0.53 (p < 0.01). LVEF had also increased from 21.0 +/- 8.2% to 39.9 +/- 14.6% (p < 0.01). Hospitalization rate was reduced from 62.7% within the year prior to initial evaluation to 7.2% at the end of the 12-month period (p < 0.01). CONCLUSIONS: In our patient population, we found significant improvement in several parameters, including NYHA functional class, LVEF, and hospitalization rate after intervention at the HFTC-CCPRC. These findings are most likely related to improved guideline adherence, and are consistent with published data regarding the value of DMP's.