James F. Grutsch

Bioelectrical impedance phase angle as a prognostic indicator in advanced pancreatic cancer

Bioelectrical impedance analysis (BIA) is an easy-to-use, non-invasive and reproducible technique to evaluate changes in body composition and nutritional status. Phase angle, determined by BIA, has been found to be a prognostic indicator in several chronic conditions, such as HIV, liver cirrhosis, chronic obstructive pulmonary disease and lung cancer, and in patients undergoing dialysis. The present study investigated the prognostic role of phase angle in advanced pancreatic cancer. We evaluated a case series of fifty-eight stage IV pancreatic cancer patients treated at Cancer Treatment Centers of America at Midwestern Regional Medical Center (Zion, IL, USA) between January 2000 and July 2003. BIA was conducted on all patients using a bioelectrical impedance analyser that operated at 50 kHz. The phase angle was calculated as capacitance (Xc)/resistance (R) and expressed in degrees. The Kaplan-Meier method was used to calculate survival. Cox proportional hazard models were constructed to evaluate the prognostic effect of phase angle independent of other clinical and nutritional variables. The correlations between phase angle and traditional nutritional measures were evaluated using Pearson and Spearman coefficients. Patients with phase angle <5.0 degrees had a median survival time of 6.3 (95% CI 3.5, 9.2) months (n 29), while those with phase angle >5.0 degrees had a median survival time of 10.2 (95% CI 9.6, 10.8) months (n 29); this difference was statistically significant (P=0.02). The present study demonstrates that phase angle is a strong prognostic indicator in advanced pancreatic cancer. Similar studies in other cancer settings with larger sample sizes are needed to further validate the prognostic significance of the phase angle.

Bioelectrical impedance phase angle as a prognostic indicator in breast cancer

BackgroundBioelectrical impedance analysis (BIA) is an easy-to-use, non-invasive, and reproducible technique to evaluate changes in body composition and nutritional status. Phase angle, determined by bioelectrical impedance analysis (BIA), detects changes in tissue electrical properties and has been hypothesized to be a marker of malnutrition. Since malnutrition can be found in patients with breast cancer, we investigated the prognostic role of phase angle in breast cancer.MethodsWe evaluated a case series of 259 histologically confirmed breast cancer patients treated at Cancer Treatment Centers of America. Kaplan Meier method was used to calculate survival. Cox proportional hazard models were constructed to evaluate the prognostic effect of phase angle independent of stage at diagnosis and prior treatment history. Survival was calculated as the time interval between the date of first patient visit to the hospital and the date of death from any cause or date of last contact/last known to be alive.ResultsOf 259 patients, 81 were newly diagnosed at our hospital while 178 had received prior treatment elsewhere. 56 had stage I disease at diagnosis, 110 had stage II, 46 had stage III and 34 had stage IV. The median age at diagnosis was 49 years (range 25 – 74 years). The median phase angle score was 5.6 (range = 1.5 – 8.9). Patients with phase angle <= 5.6 had a median survival of 23.1 months (95% CI: 14.2 to 31.9; n = 129), while those > 5.6 had 49.9 months (95% CI: 35.6 to 77.8; n = 130); the difference being statistically significant (p = 0.031). Multivariate Cox modeling, after adjusting for stage at diagnosis and prior treatment history found that every one unit increase in phase angle score was associated with a relative risk of 0.82 (95% CI: 0.68 to 0.99, P = 0.041). Stage at diagnosis (p = 0.006) and prior treatment history (p = 0.001) were also predictive of survival independent of each other and phase angle.ConclusionThis study demonstrates that BIA-derived phase angle is an independent prognostic indicator in patients with breast cancer. Nutritional interventions targeted at improving phase angle could potentially lead to an improved survival in patients with breast cancer.

Bioelectrical impedance phase angle in clinical practice: implications for prognosis in stage IIIB and IV non-small cell lung cancer

BackgroundA frequent manifestation of advanced lung cancer is malnutrition, timely identification and treatment of which can lead to improved patient outcomes. Bioelectrical impedance analysis (BIA) is an easy-to-use and non-invasive technique to evaluate changes in body composition and nutritional status. We investigated the prognostic role of BIA-derived phase angle in advanced non-small cell lung cancer (NSCLC).MethodsA case series of 165 stages IIIB and IV NSCLC patients treated at our center. The Kaplan Meier method was used to calculate survival. Cox proportional hazard models were constructed to evaluate the prognostic effect of phase angle, independent of stage at diagnosis and prior treatment history.Results93 were males and 72 females. 61 had stage IIIB disease at diagnosis while 104 had stage IV. The median phase angle was 5.3 degrees (range = 2.9 – 8). Patients with phase angle <= 5.3 had a median survival of 7.6 months (95% CI: 4.7 to 9.5; n = 81), while those with > 5.3 had 12.4 months (95% CI: 10.5 to 18.7; n = 84); (p = 0.02). After adjusting for age, stage at diagnosis and prior treatment history we found that every one degree increase in phase angle was associated with a relative risk of 0.79 (95% CI: 0.64 to 0.97, P = 0.02).ConclusionWe found BIA-derived phase angle to be an independent prognostic indicator in patients with stage IIIB and IV NSCLC. Nutritional interventions targeted at improving phase angle could potentially lead to an improved survival in patients with advanced NSCLC.

The relationship between bioelectrical impedance phase angle and subjective global assessment in advanced colorectal cancer

BackgroundBioelectrical Impedance (BIA) derived phase angle is increasingly being used as an objective indicator of nutritional status in advanced cancer. Subjective Global Assessment (SGA) is a subjective method of nutritional status. The objective of this study was to investigate the association between BIA derived phase angle and SGA in advanced colorectal cancer.MethodsWe evaluated a case series of 73 stages III and IV colorectal cancer patients. Patients were classified as either well-nourished or malnourished using the SGA. BIA was conducted on all patients and phase angle was calculated. The correlation between phase angle and SGA was studied using Spearman correlation coefficient. Receiver Operating Characteristic curves were estimated using the non-parametric method to determine the optimal cut-off levels of phase angle.ResultsWell-nourished patients had a statistically significantly higher (p = 0.005) median phase angle score (6.12) as compared to those who were malnourished (5.18). The Spearman rank correlation coefficient between phase angle and SGA was found to be 0.33 (p = 0.004), suggesting better nutritional status with higher phase angle scores.A phase angle cut-off of 5.2 was 51.7% sensitive and 79.5% specific whereas a cut-off of 6.0 was 82.8% sensitive and 54.5% specific in detecting malnutrition. Interestingly, a phase angle cut-off of 5.9 demonstrated high diagnostic accuracy in males who had failed primary treatment for advanced colorectal cancer.ConclusionOur study suggests that bioimpedance phase angle is a potential nutritional indicator in advanced colorectal cancer. Further research is needed to elucidate the optimal cut-off levels of phase angle that can be incorporated into the oncology clinic for better nutritional evaluation and management.

Is serum albumin an independent predictor of survival in patients with breast cancer

BACKGROUND The medical literature shows several examples of an inverse relationship between serum albumin levels and survival in patients with advanced cancer. METHODS We investigated the effect of baseline serum levels on 180 consecutively treated patients who were diagnosed with breast cancer from March 1993 to December 1999 at our institution. We investigated the effect of low levels of serum albumin (<3.5 g/dL) using univariate and the multivariate Cox regression model. RESULTS Demographically, the median age of these patients was 51 years of age, with a range of 28 to 88 years. In this series, 28 patients have died and 9 have developed a recurrence of tumor. The patient distribution by tumor stage was 53, stage 1; 47, stage 2A; 29, stage 2B; 11, stage 3; 13, stage 4A; and 21, stage 4B. In this cohort, the overall 5-year survival was 69%. The Cox regression analysis found that normal levels of albumin (>3.5 g/dL) reduced the risk of death by 72% (p = .0033). Only tumor stage had a larger impact on survival (p < .0000). Other factors achieving statistical significance were overexpression of the HER2/Neu antigen (p = .0167) and breast antigen (p = .0116). CONCLUSION Univariate statistical analysis found that low levels of serum albumin adversely affected survival by a statistically significant level for all stages of breast cancer. We found that a baseline serum albumin level was a powerful prognostic variable, which accounted for 7.35% of the variation in patient survival time.

Circadian Clock Manipulation for Cancer Prevention and Control and the Relief of Cancer Symptoms

Life has evolved on this planet with regular daily spans of direct solar energy availability alternating with nocturnal spans of dark. Virtually every earth-borne life form has factored this circadian pattern into its biology to ensure the temporal coordination with its resonating environment, a task essential for its individual survival and that of its species. The first whole genome inspections of mutations in human colon and breast cancer have observed specific retained clock gene mutations. Single nucleotide polymorphisms within the genes of clock, clock-controlled, and melatonin pathways have been found to confer excess cancer risk or protection from cancer. Experimental studies have shown that specific core clock genes (Per2 and Per1) are tumor suppressors because their genetic absence doubles tumor numbers, and decreasing their expression in cancer cells doubles cancer growth rate, whereas their overexpression decreases cancer growth rate and diminishes tumor numbers. Experimental interference with circadian clock function increases cancer growth rate, and clinical circadian disruption is associated with higher cancer incidence, faster cancer progression, and shorter cancer patient survival. Patients with advanced lung cancer suffering greater circadian activity/sleep cycle disruption suffer greater interference with function, greater anxiety and depression, poorer nighttime sleep, greater daytime fatigue, and poorer quality of life than comparable patients who maintain good circadian integration. We must now determine whether strategies known to help synchronize the circadian clocks of normal individuals can do so in advanced cancer patients and whether doing so allows cancer patients to feel better and/or live longer. Several academic laboratories and at least 2 large pharmaceutical firms are screening for small molecules targeting the circadian clock to stabilize its phase and enhance its amplitude and thereby consolidate and coordinate circadian organization, which in turn is likely to help prevent and control human cancer. These drugs and strategies can, in turn, be used to make cancer patients with advanced disease feel and function more normally.

The use of dietary supplements in a community hospital comprehensive cancer center: implications for conventional cancer care

Goals of workThere is little data on the prevalence of use of dietary supplements in cancer, especially in light of the growing evidence that some dietary supplements can have adverse interactions with conventional cancer treatment. The purpose of this study was to investigate the use of dietary supplements among adult cancer patients in a community hospital comprehensive cancer center.Patients and methodsA survey of 227 new adult cancer patients presenting for treatment for the first time at Cancer Treatment Centers of America at Midwestern Regional Medical Center, between November 2001 and October 2003. Patients completed the McCune Questionnaire, a validated instrument that captures information on the use of 56 dietary supplements in cancer, at admission to the hospital.ResultsOf the 227 patients, 73% used some form of dietary supplements during the 30 day period before the survey was conducted. Dietary supplement use was significantly higher (p = 0.04) in patients with colorectal (80%) and breast (75%) cancer as compared to patients with lung cancer (53%). Patients with stage II (86%) and III (76%) disease at diagnosis were more likely (p = 0.02) to use dietary supplements as compared to those with stage I (71%) disease at diagnosis, while those with stage IV (61%) disease at diagnosis were least likely to use them. Of the 80 patients who had received chemotherapy within the last 30 days, 71% had also used dietary supplements in that timeframe and 25% had consumed one or more herbal therapies that are suspected to have adverse interactions with chemotherapy. Of the 57 patients combining chemotherapy with dietary supplements, 52.6% did not consult a healthcare professional.ConclusionsIn our study, twenty-five percent of patients receiving chemotherapy were concurrently using dietary supplements suspected to have adverse interactions with chemotherapy, usually relying on information sources other than healthcare professionals. Given the prevalence rates of these agents, healthcare providers should systematically inquire about them, and consider the potential for drug-dietary supplement interactions in treatment planning.

Circadian Timing in Cancer Treatment: The Biological Foundation for an Integrative Approach:

Despite the many innovations that have occurred in cancer treatment, the age-specific mortality for most adult tumors has remained stable during the past 30 years. There have been clinically significant improvements in the outcomes of young and middle-aged patients, yet the vast majority of cancer patients are more than 50 years of age, among whom we observe few improvements in clinical outcomes. Clearly, many of todays cytotoxic agents have been shown to be effective in-vitro and in animal model systems; however, few have proved efficacious in dramatically improving survival outcomes in adult cancer. There is now increasing evidence to suggest that the administration of cytotoxic agents, at the appropriate circadian phase, can significantly increase the therapeutic index of current cancer therapies.

Actigraphic assessment of daily sleep–activity pattern abnormalities reflects self‐assessed depression and anxiety in outpatients with advanced non‐small cell lung cancer

Objectives: We measured subjectively evaluated depression and anxiety, and objectively measured daily sleep–activity patterns in inpatients and outpatients with advanced non‐small cell lung cancer (NSCLC) and determined whether cancer‐associated depression and anxiety are accompanied by characteristic circadian rhythm abnormalities.

Can changes in health related quality of life scores predict survival in stages III and IV colorectal cancer

BackgroundSeveral studies have demonstrated the predictive significance on survival of baseline quality of life (QoL) in colorectal cancer (CRC) with little information on the impact of changes in QoL scores on prognosis in CRC. We investigated whether changes in QoL during treatment could predict survival in CRC.MethodsWe evaluated 396 stages III-IV CRC patients available for a minimum follow-up of 3 months. QoL was evaluated at baseline and after 3 months of treatment using EORTC QLQ-C30. Cox regression evaluated the prognostic significance of baseline, 3-month and changes in QoL scores after adjusting for age, gender and stage at diagnosis.ResultsAfter adjusting for covariates, every 10-point increase in both baseline appetite loss and global QoL score was associated with a 7% increased risk of death with HR = 1.07 (95% CI, 1.01-1.14; P = 0.02) and (HR = 0.93 (95% CI, 0.87-0.98; P = 0.01) respectively. A lower risk of death was associated with a 10-point improvement in physical function at 3 months (HR, 0.86; 95% CI, 0.78-0.94; P = 0.001). Surprisingly, a higher risk of death was associated with a 10-point improvement in social function at 3 months (HR, 1.08; 95% CI, 1.02-1.13; P = 0.008).ConclusionsThis study provides preliminary evidence to indicate that CRC patients whose physical function improves within 3 months of treatment have a significantly increased probability of survival. These findings should be used in clinical practice to systematically address QoL-related problems of CRC patients throughout their treatment course.