Defining the role of dietary intake in determining weight change in patients with cancer cachexia.

BACKGROUND & AIMS: Weight loss is a cardinal feature of cachexia and is frequently associated with reduced food intake and anorexia. It is still unclear how much reduced food intake contributes to cancer-related weight loss and how effective increasing dietary energy and protein is in combating this weight loss. The relationship between weight change and both diet and change in dietary intake, was examined in patients with advanced stage cancer referred to a multidisciplinary clinic for management of cancer cachexia. METHODS: A retrospective study of data for each of the first three clinic visits for patients seen between 2009 and 2015. Data on weight change, dietary intake and change in dietary intake were compared. Regression analysis was used to determine independent explanatory factors for weight change, including the impact of appetite level and a marker of systemic inflammation. RESULTS: Of 405 eligible patients, 320 had data on dietary intake available. Dietary intake varied widely at baseline: 26.9% reported very poor diet and only 17% were consuming recommended levels of energy and protein. A highly significant positive correlation was found between dietary energy or protein intake and weight change, both before and after being seen in the clinic. Anorexia was also significantly correlated with weight loss at each clinic visit. However, there was no similar overall correlation between change in dietary intake and change in weight. CONCLUSIONS: Many patients with advanced cancer and weight loss are consuming diets that would likely be insufficient to maintain weight even in healthy individuals. Higher consumption of protein and energy correlates with greater weight gain, but it is impossible to predict the response to increased nutritional intake when patients are first assessed. There is a pressing need to improve understanding of factors that modulate metabolic responses to dietary intake in patients with cancer cachexia.

Does the presence of emphysema increase the risk of radiation pneumonitis in lung cancer patients?

Introduction: Radiotherapy (rt) plays an important role in the treatment of lung cancer. One of the most common comorbidities in patients with lung cancer is pulmonary emphysema. The literature offers conflicting data about whether emphysema increases the occurrence and severity of radiation pneumonitis (rp). As a result, whether high doses of rt (with curative intent) should be avoided in patients with emphysema is still unclear. Objective: We measured the documented incidence of rp in patients with and without emphysema who received curative radiation treatment. Methods: This retrospective cohort study considered patients in the lung cancer clinical database of the Peter Brojde Lung Cancer Centre. Data from the database has been used previously for research studies, including a recent publication about emphysema grading, based on the percentage of lung occupied by emphysema on computed tomography (ct) imaging. Results: Using previously published methods, chest ct imaging for 498 patients with lung cancer was scored for the presence of emphysema. The analysis considered 114 patients who received at least 30 Gy radiation. Of those 114 patients, 64 (56%) had emphysema, with approximately 23% having severe or very severe disease. The incidence of rp was 34.4% in patients with emphysema (n = 22) and 32.0% in patients with no emphysema (n = 16, p = 0.48). No difference in the incidence of rp was evident between patients with various grades of emphysema (p = 0.96). Similarly, no difference in the incidence of rp was evident between the two treatment protocols-that is, definitive rt 17 (37%) and combined chemotherapy-rt 21 (31%, p = 0.5). Conclusions: In our cohort, the presence of emphysema on chest ct imaging was not associated with an increased risk of rp. That finding suggests that patients with lung cancer and emphysema should be offered rt when clinically indicated. However, further prospective studies will be needed for confirmation.

Lung cancer care trajectory at a Canadian centre: an evaluation of how wait times affect clinical outcomes.

BACKGROUND: Lung cancer continues to be one of the most common cancers in Canada, with approximately 28,400 new cases diagnosed each year. Although timely care can contribute substantially to quality of life for patients, it remains unclear whether it also improves patient outcomes. In this work, we used a set of quality indicators that aim to describe the quality of care in lung cancer patients. We assessed adherence with existing guidelines for timeliness of lung cancer care and concordance with existing standards of treatment, and we examined the association between timeliness of care and lung cancer survival. METHODS: Patients with lung cancer diagnosed between 2010 and 2015 were identified from the Pulmonary Division Lung Cancer Registry at our centre. RESULTS: We demonstrated that the interdisciplinary pulmonary oncology service successfully treated most of its patients within the recommended wait times. However, there is still work to be done to decrease variation in wait time. Our results demonstrate a significant association between wait time and survival, supporting the need for clinicians to optimize the patient care trajectory. INTERPRETATION: It would be helpful for Canadian clinicians treating patients with lung cancer to have wait time guidelines for all treatment modalities, together with standard definitions for all time intervals. Any reductions in wait times should be balanced against the need for thorough investigation before initiating treatment. We believe that our unique model of care leads to an acceleration of diagnostic steps. Avoiding any delay associated with referral to a medical oncologist for treatment could be an acceptable strategy with respect to reducing wait time.

A comparison of the effects of medical Qigong and standard exercise therapy on symptoms and quality of life in patients with advanced cancer.

PURPOSE: Patients with advanced cancer frequently experience anxiety, depression and poor quality of life (QOL), as well as physical symptoms such as fatigue and weakness. Physical exercise has potential to help control these symptoms but the optimal training prescription is still not clear. We performed a study comparing medical Qigong (QG) and standard endurance and strength training (SET) in patients with advanced stage non-small cell lung (NSCLC) and gastrointestinal (GI) cancers. METHODS: A randomized, cross-over study was performed in patients with advanced NSCLC and GI cancers receiving or eligible for chemotherapy. Patients received supervised QG or SET twice-weekly for 6 weeks. Psychological functioning, QOL, symptoms and physical functioning were assessed before and after each intervention period. RESULTS: Nineteen patients completed both interventions. Comparing interventions revealed no difference between QG and SET on change in anxiety or depression scores or QOL. However, SET treatment was better at improving perceived strength (P = 0.05) and walking distance (P = 0.02). The order in which interventions were performed had a significant impact on the improvement in certain symptoms (sleep quality, breathlessness, P < 0.05), QOL (P = 0.01) and walking distance (P = 0.008). In all cases, the beneficial effects of the exercise interventions were markedly reduced during the second interval. CONCLUSIONS: QG and SET are equivalent in their impact on many aspects of psychological function in cancer patients. However, SET leads to greater improvements in exercise capacity and helps reduce some symptoms. The reduction in beneficial effect of SET on exercise function when offered as the second intervention is a new finding that warrants further study.

The potential role for acupuncture in treating symptoms in patients with lung cancer: an observational longitudinal study.

BACKGROUND: Most lung cancer patients experience multiple symptoms related either to the disease or its treatment. The commonly reported symptoms are pain, depression, anxiety, nausea, and poor well-being. The aim of the present study was to evaluate the effect of acupuncture as a potential treatment modality in symptomatic lung cancer patients. METHODS: This prospective observational study enrolled 33 lung cancer patients from the Peter Brojde Lung Cancer Centre between August 2010 and May 2012. All patients received 45-minute sessions of acupuncture, 1-2 times weekly for a minimum of 4 sessions. Symptom severity was assessed using the Edmonton Symptom Assessment System (esas) before and after completion of acupuncture. RESULTS: The study cohort included 30 patients with non-small- cell lung cancer and 3 with small-cell lung cancer. Mean age was 62 years (range: 36-88 years); 17 of the patients were women. Most of the patients had advanced-stage cancer (73%) and good performance status (Eastern Cooperative Oncology Group 0-1: 88%). Of these patients, 67% received anticancer treatment (chemotherapy or radiotherapy, or both) with acupuncture. Of the remaining 10 patients, 8 received acupuncture after a complete surgical resection of their tumour, and because of their advanced age, 2 received acupuncture and best supportive care. The median number of acupuncture sessions was 7 (interquartile range: 4-13 sessions). Statistically significant improvements in pain, appetite, nausea, nervousness, and well-being were observed. A clinically important improvement (2 points on the esas) was reported by 61% of patients for pain and by 33% for well-being. A significant positive correlation between improved well-being and the number of acupuncture sessions was observed. This correlation remained significant even after controlling for treatment and narcotic use. Receiver operating characteristic analysis demonstrated that a minimum of 6 acupuncture sessions are required for a 70% chance of a clinically important improvement in well-being. CONCLUSIONS: The present study is the first to demonstrate that acupuncture may be an effective approach for improving symptoms-in particular, pain and well-being-in lung cancer patients. Acupuncture is a safe and minimally invasive procedure, and it is potentially useful even in patients undergoing anticancer treatment.

Muscle wasting and changes in muscle protein metabolism in chronic obstructive pulmonary disease.

Loss of skeletal muscle mass is now recognised as an important feature of chronic obstructive pulmonary disease (COPD) which contributes to symptoms and influences prognosis. The changes in skeletal muscle remain poorly understood, largely because only a few studies have been performed to define the adaptations in whole body and muscle protein metabolism in COPD. The first sections of this review summarise background information about skeletal muscle wasting in COPD, and focuses on the studies concerned with amino acid profiles and protein synthesis and degradation rates. To aid interpretation some discussion of the techniques commonly used is included. A variety of different catabolic factors may determine whether chronic obstructive pulmonary disease patients become cachectic. The precise role for each one of these factors as well as the intracellular pathways activated in muscle as a result of chronic obstructive pulmonary disease are unknown and remain to be defined. Details of the actions of a range of different catabolic factors and potential mechanisms will be discussed.

Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy.

Muscle wasting is a debilitating consequence of fasting, inactivity, cancer, and other systemic diseases that results primarily from accelerated protein degradation by the ubiquitin-proteasome pathway. To identify key factors in this process, we have used cDNA microarrays to compare normal and atrophying muscles and found a unique gene fragment that is induced more than ninefold in muscles of fasted mice. We cloned this gene, which is expressed specifically in striated muscles. Because this mRNA also markedly increases in muscles atrophying because of diabetes, cancer, and renal failure, we named it atrogin-1. It contains a functional F-box domain that binds to Skp1 and thereby to Roc1 and Cul1, the other components of SCF-type Ub-protein ligases (E3s), as well as a nuclear localization sequence and PDZ-binding domain. On fasting, atrogin-1 mRNA levels increase specifically in skeletal muscle and before atrophy occurs. Atrogin-1 is one of the few examples of an F-box protein or Ub-protein ligase (E3) expressed in a tissue-specific manner and appears to be a critical component in the enhanced proteolysis leading to muscle atrophy in diverse diseases.

What do we really know about the ubiquitin-proteasome pathway in muscle atrophy?

Studies of many different rodent models of muscle wasting have indicated that accelerated proteolysis via the ubiquitin-proteasome pathway is the principal cause of muscle atrophy induced by fasting, cancer cachexia, metabolic acidosis, denervation, disuse, diabetes, sepsis, burns, hyperthyroidism and excess glucocorticoids. However, our understanding about how muscle proteins are degraded, and how the ubiquitin-proteasome pathway is activated in muscle under these conditions, is still very limited. The identities of the important ubiquitin-protein ligases in skeletal muscle, and the ways in which they recognize substrates are still largely unknown. Recent in-vitro studies have suggested that one set of ubquitination enzymes, E2(14K) and E3(alpha), which are responsible for the 'N-end rule' system of ubiquitination, plays an important role in muscle, especially in catabolic states. However, their functional significance in degrading different muscle proteins is still unclear. This review focuses on the many gaps in our understanding of the functioning of the ubiquitin-proteasome pathway in muscle atrophy, and highlights the strengths and limitations of the different experimental approaches used in such studies.

Nutritional status of patients undergoing lung cancer operations.

BACKGROUND: Patients referred for lung cancer operations were reported to be nutritionally depleted. This may be relevant in determining patient outcome after surgical procedures. A study was undertaken to measure a range of nutritional variables including dietary intake of patients referred to a regional cardiothoracic center for curative lung cancer operations. METHODS: Anthropometric measurements, grip strength, fat-free mass (FFM), serum protein concentrations, lymphocyte count, creatinine-height index, subjective global assessment, and data on daily intakes of energy, protein, and vitamin C were collected prospectively. Anthropometric indices were also measured in a group of control patients with mild chronic obstructive pulmonary disease. RESULTS: Sixty patients and 22 control patients were recruited. Weight, skin-fold thickness, and grip strength were not significantly different between patients and control patients, and both groups were similar to the general population. However, 8 patients (13.3%) had a body mass index (BMI) less than 20, and 14 patients (24.1%) had a fat-free mass index less than 15. Serum albumin and transferrin concentrations and lymphocyte count were very rarely depressed but prealbumin and retinol-binding protein levels were below normal in 11.9% and 8.3% of patients, respectively. Thirty percent of patients reported low energy intake, 13% reported a low protein intake, and 61.7% had reduced vitamin C intake. CONCLUSIONS: Severe nutritional depletion was uncommon in patients referred for operations for lung cancer and its frequency may have been overestimated in some previous reports. A low intake of vitamin C was common in our patients but its clinical significance is unclear.

The influence of nutritional status on complications after operations for lung cancer.

BACKGROUND: Nutritional status is known to play an important role in determining outcome after many types of operations but its importance relative to nonnutritional indices in patients undergoing an operation for lung cancer is unclear. METHODS: Detailed nutritional and nonnutritional assessment of 52 patients undergoing surgical resection of lung cancer was performed. The frequency of postoperative complications and length of intercostal drainage time were recorded, and the relation between preoperative indices and postoperative outcome was assessed. RESULTS: Patients who died or needed reventilation had poorer nutritional status, worse lung function, and lower maximum expiratory pressures than those who did not. Using multiple logistic regression, the best model (R2 = 0.39) to predict death combined operation type, preoperative carbon monoxide transfer factor (% predicted), and maximum expiratory pressure (% predicted). Operation type and the fat-free mass index (FFMI) alone were only slightly less informative (R2 = 0.35). For reventilation the best model (R2 = 0.80) combined operation type, body mass index (BMI), and maximum expiratory pressure (% predicted). Intercostal drainage time after lobectomy was significantly related only to preoperative lymphocyte count (p = 0.004) and subjective global assessment score (p = 0.02). CONCLUSIONS: Impaired nutrition is an important predictor of death and the need for reventilation after an operation for lung cancer, and the selection of patients for lung resection might be improved by measuring simple nutritional indices such as BMI and the FFMI.