Neil MacDonald

Cancer Cachexia in the Age of Obesity: Skeletal Muscle Depletion Is a Powerful Prognostic Factor, Independent of Body Mass Index

PURPOSE Emerging evidence suggests muscle depletion predicts survival of patients with cancer. PATIENTS AND METHODS At a cancer center in Alberta, Canada, consecutive patients with cancer (lung or GI; N = 1,473) were assessed at presentation for weight loss history, lumbar skeletal muscle index, and mean muscle attenuation (Hounsfield units) by computed tomography (CT). Univariate and multivariate analyses were conducted. Concordance (c) statistics were used to test predictive accuracy of survival models. RESULTS Body mass index (BMI) distribution was 17% obese, 35% overweight, 36% normal weight, and 12% underweight. Patients in all BMI categories varied widely in weight loss, muscle index, and muscle attenuation. Thresholds defining associations between these three variables and survival were determined using optimal stratification. High weight loss, low muscle index, and low muscle attenuation were independently prognostic of survival. A survival model containing conventional covariates (cancer diagnosis, stage, age, performance status) gave a c statistic of 0.73 (95% CI, 0.67 to 0.79), whereas a model ignoring conventional variables and including only BMI, weight loss, muscle index, and muscle attenuation gave a c statistic of 0.92 (95% CI, 0.88 to 0.95; P < .001). Patients who possessed all three of these poor prognostic variables survived 8.4 months (95% CI, 6.5 to 10.3), regardless of whether they presented as obese, overweight, normal weight, or underweight, in contrast to patients who had none of these features, who survived 28.4 months (95% CI, 24.2 to 32.6; P < .001). CONCLUSION CT images reveal otherwise occult muscle depletion. Patients with cancer who are cachexic by the conventional criterion (involuntary weight loss) and by two additional criteria (muscle depletion and low muscle attenuation) share a poor prognosis, regardless of overall body weight.

Nutritional recommendations for the management of sarcopenia.

The Society for Sarcopenia, Cachexia, and Wasting Disease convened an expert panel to develop nutritional recommendations for prevention and management of sarcopenia. Exercise (both resistance and aerobic) in combination with adequate protein and energy intake is the key component of the prevention and management of sarcopenia. Adequate protein supplementation alone only slows loss of muscle mass. Adequate protein intake (leucine-enriched balanced amino acids and possibly creatine) may enhance muscle strength. Low 25(OH) vitamin D levels require vitamin D replacement.

An Eicosapentaenoic Acid Supplement Versus Megestrol Acetate Versus Both for Patients With Cancer-Associated Wasting: A North Central Cancer Treatment Group and National Cancer Institute of Canada Collaborative Effort

PURPOSE Studies suggest eicosapentaenoic acid (EPA), an omega-3 fatty acid, augments weight, appetite, and survival in cancer-associated wasting. This study determined whether an EPA supplement-administered alone or with megestrol acetate (MA)-was more effective than MA. PATIENTS AND METHODS Four hundred twenty-one assessable patients with cancer-associated wasting were randomly assigned to an EPA supplement 1.09 g administered bid plus placebo; MA liquid suspension 600 mg/d plus an isocaloric, isonitrogenous supplement administered twice a day; or both. Eligible patients reported a 5-lb, 2-month weight loss and/or intake of less than 20 calories/kg/d. RESULTS A smaller percentage taking the EPA supplement gained >or= 10% of baseline weight compared with those taking MA: 6% v 18%, respectively (P =.004). Combination therapy resulted in weight gain of >or= 10% in 11% of patients (P =.17 across all arms). The percentage of patients with appetite improvement (North Central Cancer Treatment Group Questionnaire) was not statistically different: 63%, 69%, and 66%, in EPA-, MA-, and combination-treated arms, respectively (P =.69). In contrast, 4-week Functional Assessment of Anorexia/Cachexia Therapy scores suggested MA-containing arms experienced superior appetite stimulation compared with the EPA arm, with scores of 40, 55, and 55 in EPA-, MA-, and combination-treated arms, respectively (P =.004). Survival was not significantly different among arms. Global quality of life was not significantly different among groups. With the exception of increased impotence in MA-treated patients, toxicity was comparable. CONCLUSION This EPA supplement, either alone or in combination with MA, does not improve weight or appetite better than MA alone.

Understanding and managing cancer cachexia

Mrs MJ is a 56-year-old architect with a husband and two children. You performed a mastectomy and axillary dissection on her after neoadjuvant chemotherapy for locally advanced breast cancer 2 years ago. Unfortunately, she developed widespread disease with metastases to liver, lung, and bone. After several more rounds of chemotherapy, she is currently on antiestrogen therapy. Her disease appears stable. You have continued to follow her and she comes to see you for her routine visit. You notice that she is much thinner than you remember, but otherwise looks well. You ask her about her weight loss. She says: “I don’t really know what it is! I can eat, my bowels are working, but I simply don’t want to. I force myself to swallow food, but I keep losing weight anyway.” On clinical examination, you notice her muscle wasting and recognize the signs of cancer cachexia. You want to know more about how to manage this phenomenon.

Pattern of Care at the End of Life: Does Age Make a Difference in What Happens to Women With Breast Cancer?

PURPOSE In the last 40 years, palliative care has become the standard of care at the end of life. However, there are limited data about the degree of access to such care at the population level. METHODS Using administrative databases, a care-oriented profile score was created to describe the care received during the last 6 months of life for 2,291 women who were dying of breast cancer in the province of Quebec, Canada, during the years 1992 to 1998. The care received was described through indicators of care that would reflect a palliative care philosophy. An ordinal score was developed for comparisons among age groups of women using a proportional odds ordinal regression model. RESULTS We found that only 6.9% of women died at home, while 69.6% of them died in acute care beds. While most women (75%) had few indicators indicating provision of palliative care during the last 6 months of life, younger women (< 50 years) were even less likely (odds ratio, 0.70; 95% CI, 0.54 to 0.90) to receive such care compared with middle aged women (50 to 59 years; serving as the reference group), while older women (> 70 years) were more likely (odds ratio, 1.85; 95% CI, 1.49 to 2.29). CONCLUSION Our study indicates that a sizeable proportion of women terminally ill from breast cancer do not have access to palliative care-an issue that health care policy makers may wish to explore further.

Prevalence of emotional distress in newly diagnosed lung cancer patients.

Goals of workDistress is defined by the National Comprehensive Cancer Network as a multifactorial unpleasant emotional experience of a psychological, social, and/or spiritual nature that may interfere with the ability to cope effectively with cancer. We investigated the prevalence and associated symptoms of distress in newly diagnosed lung cancer patients.Patients and methodsBetween November 2005 and July 2007, 98 newly diagnosed lung cancer patients completed an assessment. The Distress Thermometer (DT) and Edmonton Symptom Assessment Scale (ESAS) were used as screening tools.Main resultsFifty (51%) patients reported clinically significant distress (≥4) on the DT. Of those, 26 (52%) patients reported high levels of depression, nervousness, or both on ESAS. The remaining 24 (48%) patients had elevated levels of distress but no significant depression or nervousness. A correlation between the DT and the total ESAS score was observed (Pearson correlation = 0.46). The ten items of the ESAS together explained 46% of the variability in DT scores. The depression and nervousness ESAS items were significant predictors of DT score (p < 0.01 for both items). However, once the two psychosocial items, depression and nervousness, were removed from the total ESAS score, leaving only physical symptoms and the sleeplessness item, the predictive power of the model decreased to R² = 0.12.ConclusionsThe prevalence of distress in lung cancer patients is high. The DT appears to discriminate between physical and emotional distress. This easily measured score may determine which patients require further intervention for emotional distress.

Ethical issues in palliative care research revisited

We wish to comment on the article by Ms Louise de Raeve, entitled ’Ethical issues in palliative care research’.1 Ms de Raeve argues from both a Kantian and a risk/benefit perspective that ’strong moral grounds exist for objecting to research in the field of palliative care’. In the closing lines of the paper, she comments that she has been ’deliberately provocative’ because her concern is that ’there is inadequate moral scrutiny of the process’ in palliative care research. A key point in Ms de Raeve’s argument is that the dying represent a special client class. She observes:

Flexible modeling improves assessment of prognostic value of C-reactive protein in advanced non-small cell lung cancer

Background:C-reactive protein (CRP) is gaining credibility as a prognostic factor in different cancers. Coxs proportional hazard (PH) model is usually used to assess prognostic factors. However, this model imposes a priori assumptions, which are rarely tested, that (1) the hazard ratio associated with each prognostic factor remains constant across the follow-up (PH assumption) and (2) the relationship between a continuous predictor and the logarithm of the mortality hazard is linear (linearity assumption).Methods:We tested these two assumptions of the Coxs PH model for CRP, using a flexible statistical model, while adjusting for other known prognostic factors, in a cohort of 269 patients newly diagnosed with non-small cell lung cancer (NSCLC).Results:In the Coxs PH model, high CRP increased the risk of death (HR=1.11 per each doubling of CRP value, 95% CI: 1.03–1.20, P=0.008). However, both the PH assumption (P=0.033) and the linearity assumption (P=0.015) were rejected for CRP, measured at the initiation of chemotherapy, which kept its prognostic value for approximately 18 months.Conclusion:Our analysis shows that flexible modeling provides new insights regarding the value of CRP as a prognostic factor in NSCLC and that Coxs PH model underestimates early risks associated with high CRP.

A prospective evaluation of an interdisciplinary nutrition-rehabilitation program for patients with advanced cancer

BACKGROUND Cancer can affect many dimensions of a patients life, and in turn, it should be targeted using a multimodal approach. We tested the extent to which an interdisciplinary nutrition-rehabilitation program can improve the well-being of patients with advanced cancer. METHODS Between January 10, 2007, and September 29, 2010, 188 patients with advanced cancer enrolled in the 10-12-week program. Body weight, physical function, symptom severity, fatigue dimensions, distress level, coping ability, and overall quality of life were assessed at the start and end of the program. RESULTS Of the enrolled patients, 70% completed the program. Patients experienced strong improvements in the physical and activity dimensions of fatigue (effect sizes: 0.8-1.1). They also experienced moderate reductions in the severity of weakness, depression, nervousness, shortness of breath, and distress (effect sizes: 0.5-0.7), and moderate improvements in Six Minute Walk Test distance, maximal gait speed, coping ability, and quality of life (effect sizes: 0.5-0.7) Furthermore, 77% of patients either maintained or increased their body weight. CONCLUSIONS Interdisciplinary nutrition-rehabilitation can be advantageous for patients with advanced cancer and should be considered an integrated part of standard palliative care.

A model for the treatment of cancer pain

Abstract Previous suggested protocols for the management of cancer pain have focused solely on the use of systemic analgesics. Studies of other modalities of pain management have reported the effectiveness of single methods of therapy (such as nerve blocks or surgical ablation). In response to the increasing recognition that cancer pain may be difficult to manage with any single-modality therapy, we used an expert (or consensual) panel method to propose how multiple therapies (analgesics, neuroablative procedures, and other non-drug therapies) might be combined in the management of patients with progressive pain. The product of this method is a decision tree suggesting the steps at which to consider various combined therapies dependent upon response to prior treatment. The decision tree is expected to have utility as an educational tool as well as a basis for generating testable hypotheses about the effectiveness of combined therapies for future clinical research.