Concurrent Chemoradiotherapy Induces Body Composition Changes in Locally Advanced Head and Neck Squamous Cell Carcinoma: Comparison between Oral Cavity and Non-Oral Cavity Cancer.

Few prospective cohort trials have evaluated the difference in treatment-interval total body composition (TBC) changes assessed by dual-energy X-ray absorptiometry (DXA) between two patient subgroups with locally advanced head and neck squamous cell carcinoma (LAHNSCC) receiving concurrent chemoradiotherapy (CCRT): oral cavity cancer with adjuvant CCRT (OCC) and non-oral cavity with primary CCRT (NOCC). This study prospectively recruited patients with LAHNSCC. Clinicopathological variables, blood nutritional/inflammatory markers, CCRT-related factors, and TBC data assessed by DXA before and after treatment were collected. Multivariate linear regression analysis identified the factors associated with treatment-interval changes in body composition parameters, including lean body mass (LBM), total fat mass (TFM), and bone mineral content (BMC). A total of 127 patients (OCC (n = 69) and NOCC (n = 58)) were eligible. Body composition parameters were progressively lost during CCRT in both subgroups. Extremities lost more muscle mass than the trunk for LBM, whereas the trunk lost more fat mass than the extremities for TFM. BMC loss preferentially occurred in the trunk region. Different factors were independently correlated with the interval changes of each body composition parameter for both OCC and NOCC subgroups, particularly mean daily calorie intake for LBM and TFM loss, and total lymphocyte count for BMC loss. In conclusion, treatment-interval TBC changes and related contributing factors differ between the OCC and NOCC subgroups.

A comparison of the MNA-SF, MUST, and NRS-2002 nutritional tools in predicting treatment incompletion of concurrent chemoradiotherapy in patients with head and neck cancer.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) treatment incompletion is a known negative prognosticator for patients with head and neck cancer (HNC). Malnutrition is a common phenomenon which leads to treatment interruption in patients with HNC. We aimed to compare the performance of three nutritional tools in predicting treatment incompletion in patients with HNC undergoing definitive CCRT. MATERIAL AND METHODS: Three nutritional assessment tools, Mini Nutritional Assessment-Short Form (MNA-SF), Malnutritional Universal Screening Tool (MUST), and Nutritional Risk Screening 2002 (NRS-2002), were prospectively assessed prior to CCRT for HNC patients. Patients were stratified into either normal nutrition or malnourished groups using different nutrition tools. Treatment incompletion and treatment-related toxicities associated with CCRT were recorded. RESULTS: A total of 461 patients were included in the study; malnourished rates ranged from 31.0 to 51.0%. The CCRT incompletion rates were 4.9-6.3% and 14.5-18.2% for normal nutrition patients and malnourished patients, respectively. The tools had significant correlations with each other (Pearson correlation 0.801-0.837, p<0.001 for all) and accurately predicted the incompletion of CCRT. MNA-SF had the highest performance in predicting treatment-related toxicity, including emergency room visits, need for hospitalization, any grade III or higher hematological adverse events, and critical body weight loss, compared to the other tools. CONCLUSIONS: MNA-SF, MUST, and NRS2002 were all shown to be competent tools for prediction of treatment incompletion and treatment-related toxicity in HNC patients undergoing CCRT. We suggest implementing nutritional assessment prior to treatment to improve the rate of treatment completion and to reduce treatment-related toxicity in HNC patients.

Limited effects of long-term daily cranberry consumption on the gut microbiome in a placebo-controlled study of women with recurrent urinary tract infections.

BACKGROUND: Urinary tract infections (UTIs) affect 15 million women each year in the United States, with > 20% experiencing frequent recurrent UTIs. A recent placebo-controlled clinical trial found a 39% reduction in UTI symptoms among recurrent UTI sufferers who consumed a daily cranberry beverage for 24 weeks. Using metagenomic sequencing of stool from a subset of these trial participants, we assessed the impact of cranberry consumption on the gut microbiota, a reservoir for UTI-causing pathogens such as Escherichia coli, which causes > 80% of UTIs. RESULTS: The overall taxonomic composition, community diversity, carriage of functional pathways and gene families, and relative abundances of the vast majority of observed bacterial taxa, including E. coli, were not changed significantly by cranberry consumption. However, one unnamed Flavonifractor species (OTU41), which represented ≤1% of the overall metagenome, was significantly less abundant in cranberry consumers compared to placebo at trial completion. Given Flavonifractor's association with negative human health effects, we sought to determine OTU41 characteristic genes that may explain its differential abundance and/or relationship to key host functions. Using comparative genomic and metagenomic techniques, we identified genes in OTU41 related to transport and metabolism of various compounds, including tryptophan and cobalamin, which have been shown to play roles in host-microbe interactions. CONCLUSION: While our results indicated that cranberry juice consumption had little impact on global measures of the microbiome, we found one unnamed Flavonifractor species differed significantly between study arms. This suggests further studies are needed to assess the role of cranberry consumption and Flavonifractor in health and wellbeing in the context of recurrent UTI. TRIAL REGISTRATION: Clinical trial registration number: ClinicalTrials.gov NCT01776021 .

Factors Predisposing Terminally Ill Cancer Patients' Preferences for Distinct Patterns/States of Life-Sustaining Treatments Over Their Last Six Months.

CONTEXT: High-quality end-of-life (EOL) care depends on thoroughly assessing terminally ill patients' preferences for EOL care and tailoring care to individual needs. Studies on predictors of EOL-care preferences were primarily cross-sectional and assessed preferences for multiple life-sustaining treatments (LSTs), making clinical applications difficult. OBJECTIVE/METHODS: We examined factors predisposing cancer patients (N = 303) to specific LST-preference states (life-sustaining preferring, comfort preferring, uncertain, and nutrition preferring) derived from six LSTs (cardiopulmonary resuscitation, intensive care unit care, chest compression, intubation with mechanical ventilation, intravenous nutrition, and tube feeding) in patients' last six months by multilevel multinomial logistic regression. RESULTS: Participants with accurate prognostic awareness and physician-patient EOL-care discussions were less likely to be in life-sustaining-preferring, uncertain, and nutrition-preferring states than in the comfort-preferring state. Better quality of life (QOL) and more depressive symptoms predisposed participants to be less likely to be in the uncertain than in the comfort-preferring state. Membership in the nutrition-preferring rather than the comfort-preferring state was significantly higher for participants in the state of moderate symptom distress with severe functional impairment than in the state of mild symptom distress with high functioning. CONCLUSION: Accurate prognostic awareness, physician-patient EOL-care discussions, QOL, depressive symptoms, and symptom-functional states predisposed terminally ill cancer patients to distinct LST-preference states. Clinicians should cultivate patients' accurate prognostic awareness and facilitate EOL-care discussions to foster realistic expectations of LST efficacy at EOL. Clinicians should enhance patients' QOL to reduce uncertainty in EOL-care decision making and provide adequate psychological support to those with more depressive symptoms who prefer comfort care only.

Quality of life and psychological distress are differentially associated with distinct symptom-functional states in terminally ill cancer patients' last year of life.

OBJECTIVE: Quality of life (QOL) and psychological distress at end of life (EOL) heavily depend on symptom distress and functional impairment, which may not deteriorate synchronously at EOL. METHODS: Using multivariate hierarchical linear modeling, we simultaneously evaluated the differential association of 5 previously identified, worsening conjoint symptom-functional states with QOL, anxiety symptoms, and depressive symptoms over 317 terminally ill cancer patients' last year of life. Quality of life, anxiety symptoms, and depressive symptoms were measured by the McGill Quality of Life Questionnaire and the Hospital Anxiety and Depression Scale, respectively. RESULTS: Quality of life, anxiety symptoms, and depressive symptoms deteriorated significantly more for patients in the 4 worst symptom-functional states (states 2-5) than in the best state (state 1). Quality of life did not differ significantly among patients in states 2 to 5. However, patients in state 4 had significantly lower anxiety-symptom levels than patients in states 2, 3, and 5, whose anxiety-symptom levels did not differ significantly. In contrast, depressive-symptom levels differed significantly between participants in any 2 of the worst symptom-functional states, except between participants in states 3 and 5 as well as between those in states 2 and 4. CONCLUSION: The 5 distinct symptom-functional states contributed to worsening QOL, anxiety symptoms, and depressive symptoms, but each was negatively and uniquely associated with psychological well-being in terminally ill cancer patients' last year of life. CLINICAL IMPLICATIONS: The psychological well-being and QOL of high-risk patients in states 3 and 5 may be improved at EOL by targeting them with appropriate symptom management interventions and facilitating their functioning.

Changes in serum α-fetoprotein level predicts treatment response and survival in hepatocellular carcinoma patients and literature review.

BACKGROUND: Oxaliplatin-based chemotherapy is an alternative systemic treatment for patients with metastatic hepatocellular carcinoma (HCC) who were refractory or intolerant to sorafenib. To date, there have been no biomarkers reported to monitor the therapeutic efficacy and to predict the outcomes of HCC patients receiving oxaliplatin-based chemotherapy. METHODS: Eighty-one HCC patients with elevated baseline α-fetoprotein (AFP) levels and extrahepatic spreading who received oxaliplatin-based chemotherapy between 2012 and 2014 were retrospectively enrolled in this study. Two AFP tests were performed, at baseline and 2-4 weeks after the initiation of chemotherapy. The change in AFP levels was calculated for survival analysis. RESULTS: In the AFP decline group (decreased compared to baseline), the median progression-free survival (PFS) and overall survival (OS) were 7.0 months and 12.3 months, respectively. In the AFP nondecline group, the median PFS and OS were 2.3 months and 3.0 months, respectively. The difference in OS between the two groups was significant (p < 0.005). In the multivariate analysis for disease progression, the best response to chemotherapy and AFP decline were independent factors, with p values of 0.004 and 0.009, respectively. In the multivariate analysis for OS, the baseline Child-Pugh score, best response to chemotherapy, and AFP decline were independent prognostic factors, with p values of 0.01, 0.001, and 0.008, respectively. Additionally, the unit change in AFP level was predictive of PFS and OS with p values of 0.007 and 0.001, respectively. CONCLUSION: The change in AFP levels 2-4 weeks after initiating oxaliplatin-based chemotherapy is useful to predict treatment response and survival.

Immunochemotherapy benefits in gastric cancer patients stratified by programmed death-1 ligand-1.

BACKGROUND: Effectiveness of protein-bound polysaccharide K (PSK) during adjuvant chemotherapy in gastric cancer patients expressing programmed death-1 ligand 1 (PD-L1) has not been investigated. Investigating this might help in triaging candidates eligible to immunochemotherapy. MATERIALS AND METHODS: In total, 918 patients with stages II and III gastric cancer, undergoing curative gastrectomy, and receiving adjuvant chemotherapy were enrolled in a prospective database, and the patients were retrospectively reviewed. We classified those patients into four cohorts stratified by PD-L1 expression and PSK administration, namely PD-L1, PSK (-,+); PD-L1, PSK (-,-); PD-L1, PSK (+,+); and PD-L1, PSK (+,-). In addition, another independent cohort of 20 patients undergoing radical gastrectomy was prospectively recruited to check their immunological cells of sera before and 2 mo after PSK administration. RESULTS: PSK treatment was an independent prognostic factor for patient's overall survival (P = 0.020), whereas PD-L1 expression per se was not. Administration of PSK prolonged patient survival in stages IIIA and IIIB (P = 0.031) but not in stage II or stage IIIC. Patients with negative expression of PD-L1, treated with PSK had longer survival than those not treated with PSK (P = 0.033). PSK did not affect the survival of patients with positive expression of PD-L1, (P = 0.421). The percentages of natural killer and natural killer T (NKT) cells, but not Th1, Th17, Treg, or IFN-γ+/CD8+ T cells, were significantly increased in PD-L1 (-) patients treated with PSK. However, these findings were not evident in PD-L1 (+) patients. CONCLUSIONS: PSK treatment preferentially confers a survival gain for patients with stage IIIA/IIIB gastric cancer, especially in the PD-L1 (-) subpopulation.

Associations of prognostic awareness/acceptance with psychological distress, existential suffering, and quality of life in terminally ill cancer patients' last year of life.

PURPOSE: Whether prognostic awareness benefits terminally ill cancer patients' psychological-existential well-being and quality of life (QOL) is unclear because of lack of well-controlled longitudinal studies. This study longitudinally evaluated the associations of accurate prognostic awareness and prognostic acceptance with psychological distress, existential suffering, and QOL while comprehensively controlling for confounders in Taiwanese terminally ill cancer patients' last year of life. PATIENTS AND METHODS: A convenience sample of 325 cancer patients was followed until death. Psychological distress and existential suffering were assessed by severe anxiety and depressive symptoms and high self-perceived sense of burden to others, respectively. Dichotomized and continuous (QOL) outcome variables were evaluated by multivariate logistic and linear regression modeling with the generalized estimating equation, respectively. RESULTS: Accurate prognostic awareness was not associated with the likelihood of severe anxiety or depressive symptoms but significantly increased the likelihood of high self-perceived sense of burden to others and was associated with poorer QOL in participants' last year of life. Participants who knew and highly accepted their prognosis were significantly less likely to experience severe anxiety symptoms than those who were unaware of or knew their prognosis but had difficulty accepting it. CONCLUSION: Knowing one's poor prognosis and confronting one's impending death without full acceptance and adequate professional psycho-spiritual support may harm more than benefit terminally ill cancer patients' psychological state, existential well-being, and QOL. These findings highlight the importance of tailoring psycho-spiritual support to cancer patients' psychological and existential needs when prognostic information is disclosed.

Relationship between pre-treatment nutritional status, serum glutamine, arginine levels and clinicopathological features in Taiwan colorectal cancer patients.

BACKGROUND AND OBJECTIVES: To examine the relationship between malnutrition criteria, serum glutamine and arginine concentrations, and clinicopathological features in Taiwan colorectal cancer patients. METHODS AND STUDY DESIGN: Three malnutrition criteria (body weight loss>5% over past 6 months, body mass index (BMI)<18.5 kg/m2, and hypoalbuminemia) and serum levels of glutamine and arginine were measured in 164 colorectal patients. Malnutrition status and serum glutamine and arginine concentrations were tested for their association with each other, as well as with the clinicopathological variables. RESULTS: Of the 164 patients, 38 (23.5%) had body weight loss, 19 (11.9%) had low BMI, and 57 (35.8%) had hypoalbuminemia. The univariate analysis showed hypoalbuminemia was correlated with advanced tumour stage, lower concentrations of glutamine, higher C-reactive protein level, and progression-free survival rate. Univariate analysis also showed glutamine levels were lower in advanced tumour stage, but arginine levels were not associated with any clinicopathologic variables. Neither the nutrition criteria used in this study nor glutamine and arginine levels were correlated with hospital stay or progression-free survival rate in multivariate analysis. CONCLUSIONS: Different nutrition assessment criteria produced different malnutrition rates in colorectal cancer patients; however, pre-treatment malnourished status and low serum glutamine and arginine concentrations were not correlated with hospital stay and progressionfree survival rate.

Trajectories of the multidimensional dying experience for terminally ill cancer patients.

CONTEXT: Studies exploring the trajectories of physical-psychological-social-spiritual dying experiences frequently treat changes in these experiences as consistent across different domains and over time. OBJECTIVE: This prospective, longitudinal investigation was designed to characterize trajectories of the multidimensional dying experience for cancer patients in their last year of life. METHODS: Trajectories of physical-psychological-social-spiritual/existential dimensions and overall quality of life (QOL) were identified among 313 cancer patients using mixed-effects models to test for linear, quadratic, or cubic changes. Changes in each variable were evaluated for clinical significance using minimal important difference. RESULTS: When patients transitioned to their end of life, symptom distress, functional dependence, anxiety, and depressive symptoms slightly increased, followed by a stable status for approximately four to six months, and accelerated dramatically to the first clinically significant changes at three to four months before death. Perceived social support and post-traumatic growth declined gradually to clinically significant changes at one and four months before death, respectively. Perceived sense of burden to others increased steadily in the last year of life, with no clinically significant changes identified. Overall QOL deteriorated gradually in the last year but did not reach a clinically significant change until 2.5 months before death. CONCLUSION: All dimensions deteriorated in the last year of life but with distinctive physical-psychological-social-spiritual/existential and overall QOL trajectories. Recognizing trajectory patterns and tipping points of accelerating deterioration in each dimension can help clinicians anticipate times of increased distress, initiate timely, effective interventions to relieve patient suffering, and facilitate high-quality end-of-life care tailored to patients' needs and preferences.

A phase II trial of biweekly oxaliplatin with simplified schedule of 48-h infusion of high-dose 5-fluorouracil and leucorvin for advanced biliary tract carcinoma.

PURPOSE: Advanced biliary tract carcinoma (BTC) is a dismal disease with no standard chemotherapy. We investigated efficacy and toxicity of biweekly oxaliplatin with 48-h infusion of 5-FU/LV in advanced BTC. METHODS: All patients had histologic confirmation of BTC, at least one measurable site of disease, and had received no prior chemotherapy. Patients were older than 20 years with ECOG performance scores (PS) of 0-2. Treatment involved 2-h infusion of oxaliplatin (85 mg/m(2)) diluted in D5W 500 ml followed by 48-h infusion of 5-FU (3,000 mg/m(2)) and LV (100 mg/m(2)) biweekly. Response evaluation was based on RECIST criteria and was carried out every two courses of treatment; toxicity evaluation was based on NCI common toxicity criteria version 3.0. RESULTS: From August 2005 to December 2006, 34 chemotherapy-naive patients with advanced BTC were enrolled and 32 intention-to-treat patients were evaluated. Partial response was 18.8%, stable disease was 31.3%, resulting in a disease control rate of 50.0%. Median time to progression and survival was 3.7 and 7 months, respectively. The most common grade 3/4 toxicities were neutropenia 15.6% (5/32), stomatitis 9.4% (3/32), thrombocytopenia 6.3% (2/32), diarrhea 6.3% (2/32) and neuropathy 3.1% (1/32). No treatment-related deaths occurred. CONCLUSIONS: The biweekly OXA and 48-h infusion of 5-FU/LV in patients with advanced BTC showed tolerable and efficacy equivalent to other combination regimens treatment.