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.

Karnofsky Performance Status as A Predictive Factor for Cancer-Related Fatigue Treatment with Astragalus Polysaccharides (PG2) Injection-A Double Blind, Multi-Center, Randomized Phase IV Study.

Fatigue is a common and debilitating symptom in patients with advanced cancer, resulting in poor quality of life and reduced treatment efficacy. Phytotherapeutic agents have shown potential effects to relieve cancer-related fatigue in these patients. The aim of this study was to evaluate the efficacy and safety of Astragalus Polysaccharides injection and identify predictive factors associated with this treatment. Patients with advanced cancer receiving palliative care with moderate to severe cancer-related fatigue were enrolled in this study for two treatment cycles. Fatigue improvement response rates were analyzed as the primary endpoint at the end of the first cycle to determine treatment efficacy. The drug safety profile was evaluated by the reporting of adverse events. Three hundred and ten patients were enrolled in this study and 214 patients were included ITT population. Improvement in fatigue scores by at least 10% was observed in greater than 65% of subjects after one treatment cycle compared to scores at baseline. Patients with higher Karnofsky Performance Status (KPS) responded better to the Astragalus Polysaccharides injection. Drug-related adverse event rates were less than 9%. This study identified KPS as a promising predictive factor for the therapeutic efficacy of Astragalus Polysaccharides injection.

Terminally Ill Taiwanese Cancer Patients' and Family Caregivers' Agreement on Patterns of Life-Sustaining Treatment Preferences Is Poor to Fair and Declines Over a Decade: Results From Two Independent Cross-Sectional Studies.

CONTEXT/OBJECTIVE: Temporal changes have not been examined in patient-caregiver agreement on life-sustaining treatment (LST) preferences at end of life (EOL). We explored the extent of and changes in patient-caregiver agreement on LST-preference patterns for two independent cohorts of Taiwanese cancer patient-family caregiver dyads recruited a decade apart. METHODS: We surveyed preferences for cardiopulmonary resuscitation, intensive care unit care, cardiac massage, intubation with mechanical ventilation, intravenous nutritional support, tube feeding, and dialysis among 1049 and 1901 dyads in 2003-2004 and 2011-2012, respectively. LST-preference patterns were examined by multi-group latent class analysis. Extent of patient-caregiver agreement on LST-preference patterns was determined by percentage agreement and kappa coefficients. RESULTS: For both patients and family caregivers, we identified seven distinct LST-preference classes. Patient-caregiver agreement on LST-preference patterns was poor to fair across both study cohorts, indicated by 24.4%-43.5% agreement and kappa values of 0.06 (95% CI: 0.04, 0.09) to 0.27 (0.23, 0.30), and declined significantly over time. Agreement on LST-preference patterns was most likely when both patients and caregivers uniformly rejected LSTs. When patients disagreed with caregivers on LST-preference patterns, discrepancies were most likely when patients totally rejected LSTs but caregivers uniformly preferred LSTs or preferred nutritional support but rejected other treatments. CONCLUSION: Patients and family caregivers had poor-to-fair agreement on LST-preference patterns, and agreement declined significantly over a decade. Encouraging an open dialogue between patients and their family caregivers about desired EOL care would facilitate patient-caregiver agreement on LST-preference patterns, thus honoring terminally ill cancer patients' wishes when they cannot make EOL-care decisions.

Short- and long-term use of medication for psychological distress after the diagnosis of cancer.

PURPOSE: This study investigated the short- and long-term use of medication for psychological distress after the diagnosis of cancer. METHODS: Longitudinal data from the Taiwan National Health Insurance database were used to follow 35,137 cancer patients for 2.5 years after being diagnosed in 2006 and 2007. RESULTS: Among those patients who survived for at least 180 days, 20.9 % had used psychotropic medications; sedatives were the most frequently prescribed (14.3 %), followed by antidepressants (5.5 %), anxiolytics (3.6 %), and antipsychotics (2.7 %). Lung cancer, prostate cancer, and oral cancer showed a significant association with the regular use of medication in the first 180 days. Among patients who survived for at least 2.5 years, 4.8 % still used psychotropic medication on a regular basis. Lung cancer and prostate cancer were associated with such prolonged use. CONCLUSIONS: This longitudinal study found that the type of cancer was significantly associated with the use of psychotropic drugs after the diagnosis was made. It provided information about the trajectory of that use and found that a small number of patients were still using those medications after 2.5 years.

Clinical Outcomes of Taiwanese Patients with cT4 Oral Cavity Squamous Cell Carcinoma: Toward the Identification of the Optimal Initial Treatment Approach for cT4b Patients.

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend that patients with oral cavity squamous cell carcinoma (OSCC) and cT4b disease should be either included in clinical trials or treated with a nonsurgical approach. However, surgery may be feasible in selected patients with adequate safety margins. Using the nationwide Taiwanese Cancer Registry Database, we examined the prognosis of cT4b OSCC patients in relation to their treatment approach. METHODS: Of the 18,910 patients with previously untreated first primary OSCC identified between 2004 and 2010, 492 (2.6 %) had cT4b tumors. Of them, 327 (66 %) received initial treatment with surgery, whereas 165 (34 %) were initially treated with a nonsurgical approach. Of the latter group, 78 patients subsequently underwent surgery. A 5-year disease-specific survival (DSS) ≥45 % was considered as a favorable outcome. RESULTS: Better 5-year DSS and overall survival (OS) rates were observed in cT4b patients initially treated with surgery (vs. nonsurgery; DSS, 51 vs. 38 %; OS, 43 vs. 27 %, respectively, p < 0.001). Of the participants initially treated with surgery, patients with cN0-2 disease had better 5-year survival rates (DSS: cN0, 59 %; cN1, 53 %; cN2, 46 %; OS: cN0, 49 %; cN1, 50 %; cN2, 37 %) than those with cN3 disease (DSS: 0 %; OS: 0 %). Among cT4b patients who initially received a nonsurgical treatment, subjects who subsequently underwent surgery showed better outcomes. CONCLUSIONS: Primary surgery is performed in approximately two-thirds of cT4b OSCC patients, with cN0-2 cases showing a good prognosis. Patients who initially received a nonsurgical approach can subsequently be treated with surgery and achieve favorable outcomes.

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.

Pegylated liposomal doxorubicin (Lipo-Dox®) combined with cyclophosphamide and 5-fluorouracil is effective and safe as salvage chemotherapy in taxane-treated metastatic breast cancer: an open-label, multi-center, non-comparative phase II study.

BACKGROUND: Anthracycline and taxane are classes of drugs that are frequently used in the adjuvant and palliative settings of metastatic breast cancer (MBC); however, treatment failure occurs in most cases. Limited data demonstrated favorable response in MBC after previous taxane-based treatment. The aim of this study was to evaluate the efficacy and safety of pegylated liposomal doxorubicin (Lipo-Dox®) used as part of a combination salvage therapy for patients with MBC whose tumors progressed during or after taxane-based treatment. METHODS: Patients with MBC who failed to respond to previous taxane-based treatments were recruited. Treatment with pegylated liposomal doxorubicin (40 mg/m(2)), cyclophosphamide (500 mg/m(2)), and 5-fluorouracil (500 mg/m(2)) was administered every 3 weeks. Tumor response to treatment was determined by using the Response Evaluation Criteria in Solid Tumor criteria version 1.0, and left ventricular ejection fraction was measured before and after treatment using echocardiography. Each patient was followed for 30 days after the last dose of study medication or until resolution/stabilization of any drug-related adverse event. RESULTS: Forty-five patients were recruited. As of December 2012, the median follow-up duration was 29.8 months, the overall response rate was 41.9 %, the median progression-free survival was 8.2 months, and the median overall survival was 36.6 months for all treated patients. Grade 3/4 neutropenia, leucopenia, and neutropenic fever were observed in 14 %, 9 %, and 1 % of the cycles, respectively. Other non-hematologic adverse effects were mild to moderate and were manageable. No decrease in left ventricular ejection function was noted. CONCLUSION: This regimen of combined of pegylated liposomal doxorubicin, cyclophosphamide, and 5-fluorouracil exhibited a promising overall response rate, progression-free survival rate, and overall survival rate, with a safe cardiac toxicity profile and manageable adverse effects. This regimen could be considered as a treatment option for patients with MBC whose tumors progressed during or after taxane-based treatment.

Omega-3 fatty acid-, micronutrient-, and probiotic-enriched nutrition helps body weight stabilization in head and neck cancer cachexia.

OBJECTIVE: To evaluate whether an oral nutritional supplement enriched with omega-3 fatty acids, micronutrients, and probiotics affected body weight (BW) changes, serum albumin and prealbumin levels in patients with head and neck cancer (HNC) cachexia. STUDY DESIGN: Sixty-eight HNC patients were randomly assigned to receive either an Ethanwell/Ethanzyme (EE) regimen enriched with omega-3 fatty acids, micronutrients, and probiotics, or control (Isocal) for a 3-month period. Analysis of covariance was used to examine the association between BW change and variables. RESULTS: Patients with body mass index (BMI) <19 and those receiving the EE regimen consumed fewer daily calories but showed significantly increased BW and maintained higher serum albumin and prealbumin levels than other patients (P<.05). Their BW changes were significantly associated with changes in serum albumin and prealbumin levels. CONCLUSIONS: EE regimen improved BW as well as serum albumin and prealbumin levels in HNC patients with BMI <19.

Reduction of splenic immunosuppressive cells and enhancement of anti-tumor immunity by synergy of fish oil and selenium yeast.

Growing evidence has shown that regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) abnormally increase in cancer cachectic patients. Suppressions of Tregs and MDSCs may enhance anti-tumor immunity for cancer patients. Fish oil and selenium have been known to have many biological activities such as anti-inflammation and anti-oxidation. Whether fish oil and/or selenium have an additional effect on population of immunosuppressive cells in tumor-bearing hosts remained elusive and controversial. To gain insights into their roles on anti-tumor immunity, we studied the fish oil- and/or selenium-mediated tumor suppression and immunity on lung carcinoma, whereof cachexia develops. Advancement of cachexia in a murine lung cancer model manifested with such indicative symptoms as weight loss, chronic inflammation and disturbed immune functionality. The elevation of Tregs and MDSCs in spleens of tumor-bearing mice was positively correlated with tumor burdens. Consumption of either fish oil or selenium had little or no effect on the levels of Tregs and MDSCs. However, consumption of both fish oil and selenium together presented a synergistic effect--the population of Tregs and MDSCs decreased as opposed to increase of anti-tumor immunity when both fish oil and selenium were supplemented simultaneously, whereby losses of body weight and muscle/fat mass were alleviated significantly.

Early nutritional support in non-metastatic stage IV oral cavity cancer patients undergoing adjuvant concurrent chemoradiotherapy: analysis of treatment tolerance and outcome in an area endemic for betel quid chewing.

PURPOSE: Non-metastatic stage IV oral cavity cancer patients undergoing concurrent chemoradiotherapy (CCRT) are at risk of malnutrition because of postoperative eating problems and CCRT-related complications. A high percentage of betel quid use, which is associated with metabolic disorders, is found in oral cavity cancer patients in Taiwan. The aim of this study is to evaluate the effect of an early and intensive nutritional support program, comprising individualized counseling, nasogastric tube feeding, and mandatory hospitalization, throughout the CCRT period for such cases in an area where betel quid use is prevalent. METHODS: We retrospectively analyzed 35 patients with nutritional support (NI) and 23 patients with no specifically designed nutrition program (NC). RESULTS: The NI group had better maintenance of body weight (p < 0.001) and higher serum albumin levels (p < 0.002) than the NC group. There was no difference in the total dose of radiation completed in the two groups; in contrast, the percentage of NI group patients who had radiation therapy (RT) breaks was lower and who completed planned chemotherapy was higher than in the NC group. Furthermore, more NC group patients suffered from sepsis during the treatment period, and fewer were alive 2 years after treatment. CONCLUSIONS: An early and intensive nutrition support may be beneficial to minimizing body weight loss, offering better treatment tolerance and probable survival benefits for patients with non-metastatic stage IV oral cavity cancers undergoing CCRT in endemic betel quid chewing areas.

Mitomycin C (MMC) with weekly 24-hour infusions of high-dose 5-fluorouracil and leucovorin in patients with advanced gastric cancer.

BACKGROUND: We have reported a 33% response rate with 5-fluorouracil/leucovorin (5-FU/LV) treatment along with a median survival of 7 months in patients with advanced gastric cancer. Subsequently, mitomycin C (MMC) became our target agent for the combination because of its activity towards gastric cancer. METHODS: From May 1998 to December 2000, a total of 37 chemo-naive patients with advanced gastric cancer were included. There were 20 men and 17 women with a median age of 58 (range, 21-73) years. The regimen consisted of 2600 mg/m2 5-FU and 100 mg/m2 LV admixed in an outpatient infusion pump administered for 24 hours every week for 6 weeks, followed by a 2-week break; then 10 mg/m2 MMC was given once every 8 weeks. The treatment continued until disease progression or unacceptable toxicity was noted, or the patient refused. RESULTS: In total, 404 treatments of 5-FU/LV were given. The mean number of treatments was 10 (range, 1 to 24). The intent to treat response rate was 40.5% (15/37) with 5.4% (2/37) showing a complete response. The median time to disease progression was 4.5 months. The median survival time was 8.0 months. All of the patients were evaluated for toxicity. Less than 10% of the patients developed grade III/IV toxicity. CONCLUSION: MMC with weekly 24-hour infusions of high-dose 5-FU and LV produced moderate activity in patients with advanced gastric cancer, and patients showed acceptable toxicity.