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.

Differences in fatigue severity in a sample of adult cancer patients.

AIMS AND OBJECTIVES: To describe differences in fatigue severity in a sample of adult Puerto Rican patients during and postcancer treatments. BACKGROUND: Hispanics, including Puerto Ricans, are an understudied population who are under-represented in clinical trials, especially in symptom research. Although symptom management is a clinical priority in oncology care, treatment-related differences in Puerto Rican cancer patients' report of fatigue severity have not been well described. DESIGN/METHODS: A cross-sectional survey was conducted from data of self-report of 138 Puerto Rican patients during and postcancer treatments at two ambulatory facilities located in San Juan, Puerto Rico. Fatigue severity was assessed using the Fatigue subscale from the Functional Assessment of Cancer Therapy-Fatigue quality of life questionnaire Spanish version. Differences in fatigue severity across type of treatment (radiation therapy, chemotherapy, combined radiation chemotherapy and post-treatment) were evaluated using nonparametric (Kruskal-Wallis and Mann-Whitney test) statistical tests. RESULTS: The majority of the participants had prostate (33%) and breast (32%) cancers and were receiving radiation therapy (43%) or chemotherapy (28%). The Kruskal-Wallis test showed that there was a statistically significant difference in fatigue scores between the different four treatment conditions, χ2 (3) = 39.1, p = .001 with patients on combined radiation chemotherapy or chemotherapy alone experiencing more severe fatigue. CONCLUSIONS: Findings from the current study suggest that type of treatment is a key component of the symptom burden of fatigue among the Puerto Rican oncology population. Specially, patients receiving combined therapy or chemotherapy alone were at increased risk for experiencing severe fatigue, compared to radiation therapy and post-treatment patients. RELEVANCE TO CLINICAL PRACTICE: With the worldwide increase in migration of Puerto Rican families, nurses need to recognise that type of treatment is a key component of the symptom burden of fatigue among the Puerto Rican population. The results of this study will improve understanding of treatment-related fatigue to identify therapeutic targets and improve quality of life of patients.

Validation of the Spanish version of the Cancer Symptom Scale in Hispanic cancer patients.

AIM: To assess the validity of the translated Spanish Cancer Symptom Scale. BACKGROUND: Instruments to facilitate comprehensive and objective assessments of the cancer symptom experience in underrepresented populations are essential. METHODS: The Cancer Symptom Scale was translated into Spanish, and a back translation was conducted. During June 2016, a sample of 121 Hispanic Puerto Rican patients with any cancer diagnosis, all undergoing cancer treatments, completed four paper surveys. A subgroup of 15 patients agreed to complete the Spanish Cancer Symptom Scale a second time after a short delay of 1 to 2 hours. Construct validity and reliability (internal consistency via Cronbach alpha and test-retest reliability) was evaluated. RESULTS: All the Intensity Items of the Spanish Cancer Symptom Scale correlated significantly with the matched items on the MD Anderson Symptom Inventory. In a subgroup of 77 participants, each Cancer Symptom Scale subscale total of scores correlated significantly with the total scores from the Functional Assessment of Cancer Therapy-General. Discriminant validity was demonstrated between those receiving chemotherapy and those from post treatment. The Spanish Cancer Symptom Scale internal consistency reliability was 0.98. CONCLUSION: The Spanish Cancer Symptom Scale has excellent evidence of validity and reliability for assessing cancer-therapy-related symptoms.

The Health related Quality of Life of Puerto Ricans during Cancer Treatments; A Pilot Study.

OBJECTIVE: To examine the health related quality of life (HRQOL) experienced by 79 Puerto Rican adults during cancer treatments. METHODS: This study used a descriptive, cross-sectional design. Participants completed a demographics form and the Functional Assessment of Cancer Therapy-General QOL questionnaire (FACT-G). Descriptive statistics were generated. RESULTS: Participants were ages 28-78; most of the participants had breast (38.0%), prostate (14.0%) and cervical and ovarian cancers (10.1%) treated with chemotherapy (45.6%). The participants had a mean total score on the FACT-G of 75.2 (SD = 18.9). As a group, the functional well-being was the most affected (mean 17.2, SD 6.8), and the Social/Familial was the least affected (mean 20.7, SD 6.0). CONCLUSION: Cancer is the leading cause of death in the island of Puerto Rico. Female Puerto Rican cancer patients in this study sample had increased risk for experiencing worse: overall HRQOL, physical well-being and emotional well-being compared to males. Given that the Hispanic oncology population does not always report symptoms, risking under-assessment and under management, this suggests there may be a greater need for HRQOL 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.

Use and medicalization of marihuana in cancer patients.

Anecdotal reports and some clinical studies suggest that marihuana (Cannabis sativa) is effective in treating a variety of conditions such as glaucoma, migraine, pain, spasticity of multiple sclerosis, anorexia, insomnia, depression, nausea and vomiting. One of the diseases mostly associated to a beneficial effect from marihuana is cancer. Twenty-one states of the United States including the District of Columbia have approved the use of marihuana for cancer and other medical conditions. In Puerto Rico, public debate on criminal penalty removal and medicalization of marihuana has intensified. It is considered essential for health professionals to have strong scientific evidence on the effectiveness and safety of medications or substances when recommending them for treating illness. This article discusses scientific evidence and information provided by prestigious organizations on the effectiveness and safety of marihuana and its derivatives in cancer patients.

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.

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.

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.

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.

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.

Symptom Burden: Experiences of Puerto Rican Men With Prostate Cancer Prior to External Beam Radiation Therapy.

BACKGROUND: Prostate cancer is the most frequently diagnosed cancer in men in Puerto Rico, and external beam radiation therapy (EBRT) is a popular treatment. Although symptom management is a clinical priority of comprehensive oncology care, symptom assessment at the time of primary or adjuvant EBRT has received limited attention. OBJECTIVES: This article examines the prevalence and severity of symptoms experienced by 54 Puerto Rican men prior to EBRT. METHODS: Participants completed a demographic form and the MD Anderson Symptom Inventory. Descriptive statistics were generated. FINDINGS: Most participants had received hormonal treatment, and about a third had received no treatment prior to EBRT. About a third of those who received hormonal treatment reported experiencing side effects before EBRT, and disturbed sleep, numbness and tingling, fatigue, and dry mouth were the most severe. Puerto Rican men with prostate cancer who receive hormonal treatment are at increased risk for experiencing symptom burden prior to EBRT. Greater need for symptom surveillance, treatment, and control may be needed among this population.