(GLAS), FRCS (ED), FRCS (ENG)

Transcription

1 EVENT HIGHLIGHTS Professor Michael J. Tisdale discussed the biochemistry of cancer cachexia (p 2). Consensus statement on the definition and classification of cancer cachexia (p 2). Nutrition screening and assessment are important tools for identifying patients at risk for malnutrition who can then benefit from early nutrition intervention (p 4). Results from a recent study show that resting energy expenditure decreases along with weight during radiotherapy in patients with head and neck cancer (p 5). 1 The 2nd International Conference on Cancer Nutrition Therapy was held on March 29-30, 2011, at the historic 17th century Royal College of Physicians in Edinburgh, Scotland. This 2nd International Conference was held to build upon discussions from the 1st Conference convened last year in Istanbul, Turkey, where 170 attendees from 10 countries heard 12 key opinion leaders discuss cancer nutrition and how to bridge the gap between science and clinical practice in nutritional oncology. Additionally, Abbott Nutrition partnered with the Biochemical Society to support investigators and their research with an abstract submission program. This year, the conference was again chaired by Kenneth C.H. Fearon, MD, FRCS (GLAS), FRCS (ED), FRCS (ENG), Professor of Surgical Oncology, University of Edinburgh, Scotland, and included 21 speakers and moderators from 14 countries with experience in surgical, radiation, and medical oncology, pediatric oncology, gastroenterology, and nutrition. One hundred sixty-five health care professionals including oncologists, surgeons, internists, palliative care specialists, hematologists, basic scientists, and dietitians from 27 countries attended this year s conference. CONFERENCE VISION The vision for this year s conference was to bring together professionals from multi-disciplinary fields involving nutrition and cancer in order to facilitate scientific exchanges and debates on bridging the gap between science and clinical practice in nutrition in cancer. A Festschrift was held at the conference to honor Michael J. Tisdale, PhD, DSc, Aston University, Birmingham, United Kingdom, for his important contributions to the field of cancer cachexia and nutritional science.

2 BASIC SCIENCE Professor Tisdale began the conference by reviewing the biochemistry of cancer cachexia stating that it involves the loss of both muscle and fat. Patients with cachexia can lose up to 85% of body fat.1 Both tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) are elevated in the serum of patients with cancer and induce lipolysis.1 Levels of zinc-α2-glycoprotein (ZAG), secreted by adipose tissue, liver, and cachexia-inducing tumors, are increased in the serum of pancreatic cancer patients with cachexia.4 Professor Tisdale noted that muscle loss is confined to skeletal muscle while visceral protein is preserved.5 Muscle loss is a result of both decreased protein synthesis and increased protein degradation. In addition to TNFα and IL-6, another factor that may be involved in muscle atrophy in cancer cachexia is proteolyis inducing factor (PIF), a tumor produced sulphated glycoprotein. PIF induced weight loss occurs without a change in appetite and results in muscle mass loss without a loss in fat mass.6 PIF expression is positively correlated with weight loss7 and is not found in patients without weight loss. The role of ZAG and PIF in cancer cachexia was discussed further by Chen Bing, MB, PhD, University of Liverpool, United Kingdom, and Jim Ross, BSc, PhD, University of Edinburgh, Scotland. 2 Josep Argilés, PhD, Universitat de Barcelona, Spain, described how cancer is an inflammatory condition. Inflammatory status can predict survival in cancer patients and can be assessed by the Glasgow Prognostic Score which is based on CRP and albumin levels independent of tumor stage, performance status, or treatment.8 Survival was noted to be significantly prolonged in patients treated with anti-inflammatory drugs compared to those given placebo.9 Professor Argilés also discussed the role of antiinflammatory drugs and antiinflammatory nutrients, including ω-3 polyunsaturated fatty acids, amino acids such as leucine, arginine, and methionine, and other nutrients such as betahydroxy-beta-methylbutyrate (HMB), resveratrol, and oligosaccharides. TRANSLATIONAL SCIENCE Professor Kenneth Fearon discussed classification, assessment and early intervention for cancer cachexia. He was the chair of an international panel that developed a recently published consensus statement on the definition and classification of cancer cachexia.10 The definition agreed upon by the experts is listed in the box below. Cancer cachexia is a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. The pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism.

3 BASIC SCIENCE A diagnosis of cancer cachexia is made based on: involuntary weight loss of >5% over 6 months, or involuntary weight loss >2% with a BMI <20, or involuntary weight loss >2% with an appendicular skeletal muscle index consistent with sarcopenia (males <7.26 kg/m2; females <5.45 kg/m2) Cancer cachexia progresses through 3 clinically relevant stages: precachexia, cachexia, and refractory cachexia. Not all patients will progress through all 3 phases. Professor Fearon reviewed a management algorithm for cancer cachexia. Patients should first be screened for cachexia and then assessed based on stage of cachexia. Cancer cachexia should be managed using a multimodal therapeutic approach that involves early intervention, nutrition, exercise, anti-inflammatory therapy, oncological management, etc.11 If one looks at cachexia as being the result of anorexia plus metabolic change, intervention strategies should include appetite stimulants plus oral nutritional supplements to increase food intake. To modulate metabolism, an anti-inflammatory approach suggested included anti-inflammatory/ anabolic medications and eicosapentaenoic acid (EPA). In a recently published study in patients with lung cancer receiving chemotherapy, fish oil supplements were found to promote weight gain and reduce muscle loss.12 Rafael Molina Porto, MD, Universitat de Barcelona, Spain, explained the role of biomarkers in the early diagnosis and histological diagnosis of lung cancer. Biomarkers can be used in atrisk patients to help with early treatment, leading to increased surgical probabilities and increased survival. When using biomarkers, one must look at the sensitivity and specificity of the test and not rely on just one biomarker, but rather use a combination of biomarkers. 3 Carolyn Greig, PhD, University of Edinburgh, Scotland, discussed the importance of assessing skeletal muscle mass and function in patients with cancer cachexia. She presented data on the difference in quadricep muscle mass between men and women showing that men with cancer cachexia experience an 18% decline compared to controls and men with cancer without cachexia in contrast to women with and without cancer cachexia where muscle mass was preserved. There was also no significant difference in hand grip strength in men and women with or without cachexia, which may suggest that hand grip strength may not be a sensitive functional marker of cachexia. Paula Ravasco, PhD, University of Lisbon, Portugal, reviewed the impact of nutritional status on quality of life. She reviewed a number of studies that looked at nutrition and dietary counselling on outcomes in patients with cancer undergoing radiotherapy.13, Individualized nutrition counseling and education was found to improve nutritional, clinical, functional, and QoL outcomes. The ESPEN guidelines16 have a Grade A recommendation for GI and head and neck cancer patients undergoing radiation therapy or chemotherapy that recommends intensive dietary counseling with regular food and/or oral nutritional supplements to increase dietary intake, prevent therapy-associated weight loss, and prevent treatment interruption.15 Early nutrition intervention should be an adjuvant to treatment in order to have an impact on nutritional status, QoL, and the potential to impact tolerance to treatment and affect prognosis. MULTIMODAL INTERVENTION Annemie Schols, PhD, Maastricht University Medical Centre, The Netherlands, described the role of nutritional intervention in multimodal management of chronic wasting disease. She compared how lung cancer and chronic obstructive pulmonary disease (COPD) are both chronic wasting diseases in that both involve skeletal muscle weakness and cachexia,

4 systemic inflammation (IL-6, TNF-α), and acute phase proteins (CRP), which lead to decreased quality of life and increased mortality. included in the survey, malnutrition was significantly higher in the patients with cancer (44%) compared to those without (32%).17 Neil MacDonald, MD, Founding Director, McGill Cancer Nutrition-Rehabilitation Program, Montreal, Canada, introduced The McGill Cancer NutritionRehabilitation Program. This program is privately funded and involves an interdisciplinary team that includes a physician, physiotherapist, dietitian, nurse, psychologist, occupational therapist, and social worker, who work with the patient and family. Patients are screened for nutritional and functional deficits. If a patient is found to be at risk, he or she receives a personalized care plan that includes nutritional counseling, an exercise program, psychological support, nursing intervention, and pharmaceutical therapy. Nutritional interventions included in this program are highlighted in the table below. Mladen Solarić, MD, University Hospital Centre Sisters of Charity, Zagreb, Croatia, gave a presentation on Screening and Assessment for Early Intervention. He noted that malnutrition occurs in 38%-66% of hospitalized oncology patients.18, 19 Malnutrition increases morbidity, mortality, and cost while decreasing quality of life.20 Nutritional Interventions of the McGill Cancer Nutrition-Rehabilitation Program The A.S.P.E.N. Guidelines recommend that patients with cancer undergo nutrition screening.21 The Malnutrition Screening Tool (MST) assesses involuntary weight loss and appetite. An MST score of 2-5 indicates that the patient should undergo a nutrition assessment using the Subjective Global Assessment (SGA).22 In Croatia, cancer patients are screened using the MST and assessed with the SGA. Patients who are identified as moderately malnourished or severely malnourished are recommended enteral nutrition plus 2.2 g EPA plus an appetite stimulant. This recommendation is included in the Croatian guidelines.23 Remove dietary restrictions g protein/kg body weight 2 g EPA (omega-3 fatty acid) if there is evidence of inflammation IU of Vitamin D Multivitamins if there is evidence of malnutrition PRESENTATIONS FROM AROUND THE WORLD Nada Rotovnik Kozjek, MD, Institute of Oncology, Ljubljana, Slovenia, reviewed results of the British Association for Parenteral and Enteral Nutrition Winter Nutrition Screening Week survey that identified that 34% of patients admitted to the hospital are at risk for malnutrition.17 Of the 13% of patients with cancer 4 CLINICAL PRACTICE IN VARIOUS CANCER TREATMENTS AND NUTRITIONAL IMPLICATIONS Diclehan Kiliç, MD, Gazi University Hospital, Ankara, Turkey, discussed the role of nutrition intervention during chemoradiotherapy. In a study of 40 patients with rectal cancer receiving chemo-radiotherapy (CRT), patients who consumed an oral nutritional supplement (ONS) with EPA experienced less GIrelated side effects of CRT (diarrhea) than patients who did not consume the ONS.24 She also presented unpublished data on 30 patients with inoperable pancreatic cancer who were undergoing CRT while receiving an ONS with EPA and a diabetic ONS. After 13 weeks of supplementation, 83% of the patients had a reduction in the rate of weight loss and 33% experienced a median 1.2 kg/month weight gain.

5 John V Reynolds, MA, MB, BCh, FRCSI, Trinity College, Dublin, Ireland, discussed complex cancer surgery. He noted that the prevalence of malnutrition in patients with GI cancer in the UK is 59%.17 In a study by Stephens et al,25 survival in gastroesophageal cancer patients was predicted based on CRP levels. Gut barrier function is altered in malnourished patients leading to increased intestinal permeability that correlates with acute phase proteins (CRP, IL-6). Atila Tanyeli, MD, Univeristy of Çukuruva, Adana, Turkey, presented results of a study using ProSure in pediatric oncology patients receiving chemothearpy.26 Fifty-two children were enrolled in this prospective, randomized trial. Children with leukemia in the treatment group had significantly less body weight loss (5.6% versus 54.5%; P = 0.006) and less loss of body mass index (BMI) (11.1% versus 54.5%; P = 0.018) compared to the control group. No significant difference was noted in weight loss or BMI in the children with solid tumors. However, at 3 months the remission rate was greater in the treatment group compared to the control group, (87.9% vs. 63.2%; P = 0.036). This study also demonstrated that ProSure is safe and well-tolerated in children with cancer. THE BIOCHEMICAL SOCIETY POSTER SESSION This year, to support investigators and their research, the conference included an abstract submission and poster presentation. Thirteen abstracts were submitted and included research in basic and translational science and clinical nutrition. Two of the abstracts included studies conducted with ProSure. 5 Jacqueline A.E. Langius, RD, VU University Medical Center Amsterdam, The Netherlands, pictured below, presented data on her study on resting energy expenditure (REE) in head and neck cancer patients during radiotherapy (RT). Seventy-one patients were enrolled who were expected to receive primary or postoperative RT for greater than 4 weeks. The control group included 40 healthy subjects. REE was measured at 4 time points by indirect calorimetry-before RT, week 3 of RT, at the end of RT (week 6), and week 18 (3 months) after RT. Before RT, there was no difference in REE between the patients and controls. During the 18 weeks of the study, weight and fat-free mass were found to decrease by 6% and 5%, respectively. REE also decreased by 9% during RT.

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