Egidio Del Fabbro

Relationships among body mass index, longitudinal body composition alterations, and survival in patients with locally advanced pancreatic cancer receiving chemoradiation: a pilot study.

CONTEXT In pancreatic cancer, the presence of obesity or weight loss is associated with higher mortality. OBJECTIVES To explore the relationships among body mass index, longitudinal body composition alterations, and clinical outcomes in pancreatic cancer patients. METHODS Records of 41 patients with inoperable locally advanced pancreatic cancer who participated in a prospective chemoradiation study were reviewed. Body composition was analyzed from two sets of computed tomography images obtained before and after radiation treatment (median interval 104 days). RESULTS Median age was 59 years and 56% of patients were female. Twenty-four (59%) patients were either overweight (22%) or obese (37%). Sarcopenia was present in 26 (63%) patients. At follow-up, weight loss was experienced by 33 (81%) patients. The median losses (%) before and after treatment were weight 5% (P<0.001), skeletal muscle (SKM) 4% (P=0.003), visceral adipose tissue (VAT) 13% (P<0.001), and subcutaneous adipose tissue 11% (P=0.002). SKM loss positively correlated with age (P=0.03), baseline body mass index (P<0.001), and VAT (P=0.04) index. Obese patients experienced higher losses in weight (P=0.009), SKM (P=0.02), and VAT (P=0.02). Median survival was 12 months. In univariate analysis, age, baseline obesity, sarcopenic obesity, and losses (%) in weight, SKM, and VAT were associated with worse survival. In multivariate analysis, only age (hazard ratio=1.033, P=0.04) and higher VAT loss (hazard ratio=2.6 and P=0.03) remained significant. CONCLUSION Our preliminary findings suggest that obese patients experience higher losses in weight, SKM, and VAT, which may contribute to poorer survival in these patients.

Undocumented alcoholism and its correlation with tobacco and illegal drug use in advanced cancer patients.

The objectives of this retrospective study were to determine the frequency of undiagnosed alcoholism among patients with advanced cancer who were referred to palliative care and to explore its correlation with alcoholism, tobacco abuse, and use of illegal drugs.

The relationship between body composition and response to neoadjuvant chemotherapy in women with operable breast cancer

INTRODUCTION Overweight women diagnosed with breast cancer have greater recurrence and mortality risks. Recent studies in advanced cancer showed that the combination of sarcopenia and an overweight or obese body mass index (BMI) is associated with poor clinical outcomes. OBJECTIVES To compare pathological complete response (pCR) cases with controls and evaluate associations among a pCR, survival outcome, and sarcopenia as well as the combination of both sarcopenia and a BMI ≥25 kg/m(2). METHODS Sixty-seven breast cancer patients with a pCR to neoadjuvant chemotherapy (NC) were matched with controls who did not have a pCR to NC. Patients were matched by age, Blacks nuclear grading system, clinical cancer stage, and estrogen receptor and progesterone receptor status. Body composition was analyzed using computed tomography images taken prior to NC. RESULTS BMI was associated with pCR. Among normal weight patients, the pCR rate was higher in sarcopenic patients and the progression-free survival (PFS) interval was significantly longer than in overweight or obese BMI patients. The death hazard was 2% higher for each unit higher skeletal muscle index and 0.6% higher for each unit higher visceral adipose tissue. CONCLUSIONS Overweight patients treated with NC had a lower pCR rate and shorter PFS time. Among patients with a normal BMI, the pCR rate was better in sarcopenic patients. More research is required to evaluate the negative impact of sarcopenic obesity on prognosis and the contributors to better response rates in operable, normal weight breast cancer patients with sarcopenia.

Clinical Outcomes and Contributors to Weight Loss in a Cancer Cachexia Clinic

BACKGROUND Cancer cachexia is considered intractable, with few therapeutic options. Secondary nutrition impact symptoms (S-NIS) such as nausea may further contribute to weight loss by decreasing nutrient intake. In addition, treatable metabolic abnormalities such as hypogonadism, vitamin B12 deficiency, hypothyroidism, and hypoadrenalism could exacerbate anorexia and muscle wasting in patients with cancer cachexia. We determined the frequency and type of contributors to appetite and weight loss, and the effect of the cachexia clinic on clinical outcomes. METHODS Review of 151 consecutive patients referred to a cachexia clinic. All received dietary counseling and exercise recommendations. Assessments included weight, body mass index (BMI), S-NIS, resting energy expenditure by indirect calorimetry, serum thyroid stimulating hormone (TSH), cortisol, total testosterone, and vitamin B12. RESULTS Median weight loss in the 100 days before referral was 9% (4%-13%); median BMI at presentation was 20.8. Median number of S-NIS was 3 (2-4), most commonly treated by metoclopramide, laxatives, and antidepressants. Forty-one percent (24/59) of patients were hypermetabolic and 73% (52/71) of males hypogonadic, whereas hypoadrenalism (0/101, 0%), hypothyroidism (4/113, 4%), and low vitamin B12 (3/107, 3%) were uncommon. Poor appetite and weight loss before referral (r = 0.18, p = 0.036) were associated with increased S-NIS (r = 0.22, p = 0.008). Appetite improved (p < 0.001) and 31/92 (34%) of patients returning for a second visit gained weight. CONCLUSIONS Patients had a high frequency of multiple S-NIS, hypogonadism, and hypermetabolism. A combination of simple pharmacological and nonpharmacological interventions improved appetite significantly, and increased weight in one third of patients who were able to return for follow-up. Cachexia clinics are feasible and effective for many patients with advanced cancer.

Associations among hypogonadism, C-reactive protein, symptom burden, and survival in male cancer patients with cachexia: a preliminary report.

CONTEXT Cachexia is characterized by muscle wasting, anorexia, and elevated inflammatory markers. In patients without cancer, hypogonadism is associated with lower lean body mass, increased symptom burden, and decreased survival. Hypogonadism in cancer cachexia could exacerbate symptoms, facilitate a proinflammatory state, and decrease survival. OBJECTIVES To explore the relationships among these factors, a retrospective study of male cancer patients was conducted. METHODS The charts of 98 consecutive male patients referred to a cachexia clinic at a comprehensive cancer center were reviewed. All patients reported weight loss of >5% within the preceding six months; the median age was 60 years. Fifty-seven (58%) had serum C-reactive protein (CRP), and 68 (69%) had total testosterone evaluated. Symptoms were evaluated by the Edmonton Symptom Assessment Scale. RESULTS Median CRP was 20mg/L, and median testosterone level was 185 ng/dL (6.42 nmol/L) (normal > or = 240 ng/dL or 8.36 nmol/L). There was an inverse correlation between testosterone and CRP levels (P<0.01). Lower testosterone was associated with increased dyspnea and insomnia (P<0.05). Poor appetite and insomnia (P<0.05) correlated with elevated CRP. Survival of patients with testosterone levels < or = 185 ng/dL (6.42 nmol/L) was decreased compared with that of those with levels >185 ng/dL (13 vs. 62 weeks, P=0.004). Patients with CRP levels >10mg/L had decreased survival compared with those with levels < or = 10mg/L (15 vs. 46 weeks, P=0.01). The combination of hypogonadism and elevated CRP was associated with poorer prognosis. Elevated CRP levels were associated with increased symptom burden and decreased survival. Low testosterone was associated with decreased survival and correlated inversely with CRP levels, dyspnea, and insomnia. CONCLUSION Our preliminary results suggest that testosterone and CRP may be additive or synergistic as markers for survival in male patients and could be useful in future prognostic models.

Association between megestrol acetate treatment and symptomatic adrenal insufficiency with hypogonadism in male patients with cancer

Patients with advanced cancer may develop cachexia, which is often treated with megestrol acetate (MA). In addition to thromboembolic disease, MA may cause symptomatic suppression of the hypothalamic pituitary adrenal axis. In male patients with cancer, treatment with MA may also suppress the gonadal axis, resulting in symptomatic androgen deficiency. Three cases are presented to highlight the symptomatic burden of adrenal insufficiency and hypogonadism. Clinicians need an increased awareness of the complication of adrenal insufficiency secondary to MA treatment and a low threshold to test for adrenal and gonadal dysfunction in symptomatic male patients with advanced cancer. Cancer 2007.

Preliminary Report: Vitamin D Deficiency in Advanced Cancer Patients with Symptoms of Fatigue or Anorexia

BACKGROUND Vitamin D deficiency in noncancer patients is associated with symptoms of fatigue, muscle weakness, and depression. These symptoms are common among advanced cancer patients. We investigated the prevalence of low serum vitamin D levels in cancer patients with fatigue or poor appetite and their association with symptom burden and other correctable endocrine abnormalities. METHODS This was a retrospective review of 100 consecutive cancer patients with appetite or fatigue scores of ≥4 of 10 referred to a supportive care clinic. We investigated serum levels of 25(OH) vitamin D, cortisol, thyroid-stimulating hormone, and bioavailable testosterone. Symptoms were measured by the Edmonton Symptom Assessment Scale. Serum 25(OH) vitamin D <20 ng/mL was considered deficient; ≥20 ng/mL and <30 ng/mL were considered insufficient. RESULTS Patients were predominantly male (68%) and white (66%), with a median age of 60 years (range, 27-91 years). Gastrointestinal (30%) and lung (22%) cancers were predominant. Forty-seven patients (47%) were vitamin D deficient and 70 (70%) were insufficient. Thirteen of 70 patients (19%) with vitamin D insufficiency were on supplementation. Vitamin D deficiency was more common among nonwhites (82% versus 36%) and females. No significant association was found between vitamin D and symptoms. Hypogonadic males had a significantly lower mean 25(OH) vitamin D level than eugonadic males. CONCLUSIONS Low vitamin D levels were highly prevalent among advanced cancer patients with cachexia or fatigue. Vitamin D deficiency was more frequent among nonwhite and female patients. Vitamin D levels were also significantly lower in male patients with hypogonadism.

Is there a role for hydration at the end of life

Purpose of reviewTo review current evidence on issues central to the hydration debate. Recent findingsWorldwide, there are wide variations in hydration practice in terminally ill patients, reflecting divergent beliefs of medical providers, and the paucity in scientific evidence. This issue is particularly distressful to patients/families and nurses, yet their involvement in clinical decision-making remains insufficient. A short preliminary randomized controlled intervention trial (in advanced cancer patients) adds to the mounting evidence in support of hydration in improving neuro-cognitive symptoms associated with fluid deficits. On the other hand, majority of trials conducted in patients at the very end of life (survival days or weeks), while confirming high symptom burden, suggest no relationship to fluid status, or no significant benefit with hydration intervention. In Japan, the development of national clinical guidelines for hydration therapy in terminally ill cancer patients is a significant step forward, and brings attention to this important issue. SummaryAreas of future research should include patients at various stages of the illness trajectory and involve noncancer illnesses. Appropriately powered, randomized, double-blind studies of hydration are awaited. Till then, the recommendation is to individualize hydration decisions and include participation of patient/families and other disciplines.

Association Between Serum Cortisol and Testosterone Levels, Opioid Therapy, and Symptom Distress in Patients with Advanced Cancer

CONTEXT Patients with advanced cancer often experience symptoms such as pain, anorexia, and fatigue. Opioid therapy for the management of cancer pain may result in neurohormonal dysfunction that may contribute to a patients symptom burden. OBJECTIVES To examine the association between serum cortisol and testosterone levels, opioid therapy, and symptom distress in patients with cancer. METHODS A retrospective chart review was performed on 77 consecutive patients with advanced cancer referred for symptoms of fatigue or cachexia. We collected information regarding cortisol levels (am or random), testosterone levels (men only), morphine equivalent daily dose (MEDD), and symptom severity measured by the Edmonton Symptom Assessment Scale. Nonparametric correlation analysis was performed. RESULTS The median age was 63 years (range 24-79), and 62% were men (n=48). Most patients had gastrointestinal (n=33, 43%) or thoracic (n=21, 27%) malignancies and were Caucasian (n=46, 60%). The median random cortisol level was 19.1 μg/dL (Q1-Q3, 13.4-23.8 [normal, 4.3-22.4]), which correlated with MEDD (Spearman coefficient, 0.25, P=0.032) and symptoms including pain (0.50, P<0.001), fatigue (0.29, P=0.012), nausea (0.34, P=0.003), depression (0.24, P=0.032), and anxiety (0.25, P=0.031). Pain and nausea remained significant after Bonferroni correction. Median morning cortisol level (n=28) was 20.6 μg/dL (Q1-Q3, 16.6-25.4) and significantly correlated with pain (0.55, P=0.003) after Bonferroni correction. Patients with a MEDD <30 mg/day had a mean random cortisol level of 16.6 μg/dL, whereas patients with a MEDD ≥ 30 mg/day had a mean random cortisol level of 20.6 μg/dL (P=0.01). In 44 male patients with cancer, MEDD was inversely correlated with the total testosterone level (-0.52, P=0.001). CONCLUSION In patients with advanced cancer, elevated random cortisol levels were associated with pain and opioid use, although abnormally low levels of cortisol were found to be infrequent. Patients on higher opioid therapy (MEDD >30) had increased cortisol levels, and male patients had lower testosterone levels. Our study suggests that opioid therapy in patients with advanced cancer may inhibit gonadal function while sparing the adrenal axis. Future studies are needed.

Hypermetabolism and symptom burden in advanced cancer patients evaluated in a cachexia clinic.

Elevated resting energy expenditure (REE) may contribute to weight loss and symptom burden in cancer patients.