Cancer et Nutrition Genève 2015 C. Pichard, MD, PhD Unité Didac. Geneve de lac Nutrition, HUG, Genève
1. Cancer : prévalence croissante 2. Prévention : complexe! 3. Croissance tumorale : nutri- modulation 4. Nutriments : adjuvants thérapeutiques
CANCER - WHO http://www.who.int/mediacentre/factsheets/fs297/en/2015 2004 7.4 * 10 6 deaths 2012 8.2 * 10 6 deaths 2032 increase by 70%
Cancer prévalence croissante
CANCER - WHO http://www.who.int/mediacentre/factsheets/fs297/en/2015 Cancer is a leading cause of death worldwide Most common causes (x 10 3 /year): lung 1590 liver 745 stomach 723 colorectal 694 breast 521 oesophageal 400
CANCER - WHO http://www.who.int/mediacentre/factsheets/fs297/en/2015 5 most common sites : MEN : lung, prostate, colorectum, stomach, liver WOMEN : breast, colorectum, lung, cervix, stomach 1/3 cancer deaths due to the 5 leading behavioural and dietary risks: High BMI, low fruit & vegetable intake, lack of physical activity, tobacco use, alcohol use Tobacco : most important risk factor for cancer causing 20% cancer deaths
The Cancer Burden World Cancer Research Fund / American Institute for Cancer Research: Policy & Action for Cancer Prevention. Washington DC: AICR, 2009
Increase across all age-groups Children and adolescents Steliarova-Foucher E, Lancet, 2004
incidence > 65 years: 60% cancer 80% death by cancer mortality
Cancer Et Environnement
Observational evidence: migrant studies WCRF/AICR. Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective, Washington DC: AICR, 2007
Cancer : Number of cases Treatment duration
CANCER - Financial Costs 2005 (USA) http://www.cdc.gov/cancer/dcpc/research/articles/costs.htm Billions 200 150 100 50 43 48 0 US Overall Education Direct medical Worker productivity Premature death
Cancer Prévention complexe
1981 1997 2007 Cancer is preventable
CANCER - WHO http://www.who.int/mediacentre/factsheets/fs297/en/2015 World Cancer Report provides clear evidence that action on smoking, diet, infections can prevent 1/3 of cancers.
CANCER - W.H.O. http://www.who.int/mediacentre/releases/2003/pr27/en/print.html GI cancer European Prospective Investigation into Cancer & Nutrition (EPIC) : n= 65 000 (Publ Health Nutr 2003) 500 g / d fruits - vegetables -> incidence: - 25 % GI
FOLIC ACID
Observational evidence: folic acid supplementation and colorectal cancer risk folate fortification : mandatory USA: Canada : 140 µg/100 g flour 150 µg /100 g flour Start: 1996 USA, Canada : 1997 Mason, JB, Cancer Epidemiol Biomarkers Prev, 2007
Observational evidence: folic acid supplementation and colorectal cancer risk Mason, JB, Cancer Epidemiol Biomarkers Prev, 2007
Observational evidence: folic acid supplementation and colorectal cancer risk In 2000, folate fortification became mandatory in Chile 2001 2004: after mandatory flour fortification program with 220 µg/100 g flour, colon cancer rates increased by 162 % in 45-64 yrs 190 % in 65-79 yrs Hirsch S, Eur J Gastroenterol Hepatol. 2009
ACIDE FOLIQUE: à pas bon pour tous, critique durant la grossesse
Des nutriments précieux Vitamine D
Observational evidence vitamin D status & cancer risk A predicted of 25 nmol/l in 25(OH)D status : - 17 % total cancer incidence - 29 % total cancer mortality - 45 % GI tract cancer mortality Intake of 1000 IU/day is projected to reduce cancer mortality in men and women in the US by 7% and 9%, and in European countries with low UVB irradiance of 14 and 20% 1. Giovannucci E, JNCI, 2006 2. Grant WB, Recent Results Cancer Res. 2007
Vitamin D Increased intake favourable for Cancer AND Osteoporosis
Cancer prevention? A global action
When more is better 10 yrs follow-up: Survival function according to health behaviours in 20244 men & women, 45-79 ys w/o known Smoking PA OH Vit C CV disease or cancer Khaw KT, PLoS Med, 2008
1. Lutte contre surpoids et obésité WCRF recommendations 2. Réaliser une activité physique dans le cadre de la vie quotidienne 3. Limiter la consommation d aliments >250 kcal/100g 4. Consommer > 600 g/ j légumes (hors féculents) et fruits, > 25 g/j fibres 5. Limiter la consommation de viande rouge et toutes préparées 6. Limiter la consommation d alcool 7. Limiter la consommation de sel, des moisissures de céréales ou de légumes secs 8. Assurer les besoins nutritionnels par la seule alimentation 9. Promouvoir l allaitement maternel exclusif > 6 mois Further Implementation With Normalized Vitamin D status? 10. Promouvoir l application de ces recommandations chez les patients survivants de cancer, en dehors des périodes de traitement oncologique
NUTRITION Santé Cancer Santé Prévention I Traitement Prévention II
Croissance tumorale nutri- modulation
Tumor : Anabolism > Catabolism Host : Catabolism > Anabolism
Matt Seymour, MRC Colorectal Cancer Group Cancer cell number 10 12 10 9 10 6 10 3 10 0 lethal symptomatic detectable no chemotherapy survival med 6-9 mths 1st line 5-FU survival med 6 months 2nd line new drug survival med 3 months Nutrition : how much benefit? 0 6 12 18 24 months
Nourrir la tumeur? NON, mais...
Metastatic Liver Tumors in Mice TJ. Yeatman et al. Arch Surg 1991, 26: 1376 300 200 (177-313) (median, range) * p<0.05 100 0 n=8 ARGININE repleted (29-168) * n=10 ARGININE depleted
L-arginine on the growth of 3 human colorectal adenocarcinoma cell lines Dupertuis Y et al. Clin Nutr 23, 887-8, 2004 Cell number / ml 1.8x10 6 1.4x10 6 1x10 6 6x10 5 2x10 5 0 µm Arg 10 µm Arg 100 µm Arg 1000 µm Arg 0 1 2 3 4 5 6 Number of days of treatment
Nutrients Stimulate Cancer Cells Growth 6x10 5 LS174T Cell number / ml 3x10 5 Immunonutrition (1/1000) Cell culture medium 0 0 3 6 12 18 Nb of days of treatment
Jeûner pour affamer le cancer
Toxicity in Chemotherapy When Less Is More Laviano A Rossi Fanelli F. N Engl J Med 2012, 366; 2319-20
Nutriments Adjuvants thérapeutiques
Stimulation Griffini P & al. Cancer Res, 58:3312-9 (1998) Meterissian SH & al. Cancer Lett, 89:145-52 (1995) Ω6-PUFAs AA Arachidonic Acid Ω3-PUFAs EPA Eicosapentaenoic Acid Inhibition Latham P & al. Carcinogenesis, 20:645-50 (1999) Rao C & al. Cancer Res, 61:1927-33 (2001)
Cancer Cells Culture & PUFAs LS174T 600'000 500'000 0 µm EPA 30 µm EPA N cells / ml 400'000 300'000 200'000 100'000 50 µm EPA 100 µm EPA Incubation 4 d X ± 1 SD, triplicate /condition 0 0 1 2 3 4 5 Treatment days
Tumor-modulating nutrition: OncoNutritionMixture n-3 fatty acids Arginine Glutamine Vitamins Extracellular Intracellular DNA RNA Protein precursors Cell Division Nucleus
Cell Irradiation Linear beam accelerator X-rays 6MV Linear accelerator Xrays 6MV Dose: 2-4 Gy 5 cm 2 cm Polystyrene (water equivalent) Air Cells 5 cm Treatment couch (no beam attenuation) Beam direction - field limits Field size : 15 cm x 20 cm
Interaction between Nutrients : CAUTION! Survival fraction (S/So %) 160 140 120 100 80 60 40 20 0 0 0 0 Gy 4 Gy ** RADIOSENSITIVE HT-29 0 10 ns 80 ns ** ** 60 ** 50 0 50 10 160 140 120 100 40 20 0 0 0 RADIORESISTANT CO112 Different from controls, t-test * P < 0.05, ** P < 0.01 Supra-additive effect (Multivariable linear regression analysis), P < 0.05 0 10 50 0 50 10 DHA Vit E µm
Pour le moment: Assurer l équilibre en énergie et protéines
Nutrition lors de cancer : Bénéfices?
Diagnosis & Prevalence (%) of weight loss % weight loss n 0 < 5 10-30 Favorable non-hodgkin s lymphoma 290 69 8 10 Breast 289 64 8 6 Acute nonlymphocytic lymphoma 129 61 8 4 Sarcoma 189 60 11 7 Unfavorable n-hodgkin s lymphoma 311 52 13 15 Colon 307 46 14 14 Prostate 78 44 18 10 Lung, small cell 436 43 20 14 Lung, non-small cell 590 39 21 15 Pancreas (2 months!) 111 17 28 26 Estomac 138 13 29 38 DeWyss WD. Am J Med 1980
Body weight loss & Survival De Wys et al. Am J Med 1980 --> No weight loss: better survival
CANCER chimiothérapie radiothérapie chirurgie Dépression Douleur Hypophagie Aphtes, mycose, Nausées, vomissements, Aversion alimentaire, dysgeusie, dysosmie, Cachexie Anorexie, satiété précoce
CANCER - Body weight Pre diagnostic Treatments - complications
PATIENT A SM = 31.66 cm2 AT = 575.5 cm2 Homme 68 ans Cancer Intestin grêle IMC 24.4 kg/m² Surface musculare = 31.66 cm² Surface tissu adipeux = 575.5 cm² BMI = 24.4 kg/m2 BBBBBB PATIENT B Homme 54 ans Adénocarcinome pancréas BMI 24.2 kg/m² SM = 177.0 cm2 AT= 303.1 cm2 Surface musculaire = 177.0 cm² Surface tissu adipeux = 303.1 cm² Antoun S
Prevalence and clinical implications of sarcopenic obesity in 250 patients with solid tumours of the respiratory and GI tracts Prado CM et al. Lancet Oncol 2008, 9: 605-607 Sarcopenic obesity is an independent predictor of survival (HR 4.2 [2.4 7.2], p<0,0001) links body composition, especially sarcopenic obesity, to clinical parameters (functional status, survival, and potentially, chemotherapy toxicity
Sarcopenia as a determinant of chemotherapy toxicity and time to tumor progression in Toxicity metastatic breast cancer patients receiving capecitabine treatment Prado CM, et al. Clin Cancer Res 2009, 15: 2920-2926 Sarcopenic n = 14 Nonsarcopenic n = 41 p- value Present 7 (50.0%)* 8 (20%)* 0.03 Absent 7 (50.0%)* 33 (80%)* Weight (kg) 65.6 (11.4) 71.4 (16.7) 0.23 BMI (kg/m 2 ) 24.6 (4.0) 27.8 (5.7) 0.06 BSA (m 2 ) 1.7 (0.2) 1.8 (0.2) 0.42 Lumbar skeletal muscle index (cm 2 /m 2 ) 35.0 (3.3) 47.4 (5.0) <0.0001 Whole body lean mass (kg) 34.0 (3.3) 42.5 (5.0) <0.0001 Mg capecitabine / kg FFM 104.2 (16.1) 86.9 (13.7) <0.0001
Le patient doit manger...
Nutrition therapy in cachectic cancer patients The Tight Caloric Control (TiCaCo) pilot trial De Waele E, Appetite 2015, 91: 298-301 10 patients receiving nutrition therapy and 10 controls Endpoints Primary : recovery of body composition after nutrition therapy Secondary : declined in morbidity and mortality with nutrition therapy
Cancer wasting & QoL react to early individualized nutritional counselling! Ravasco P et al. Clin Nutr 2007; 26: 7-15 Nutritional counselling Oral Nutrition Supplem. Ad Libitum Nutritional counselling Oral Nutrition Supplem. Ad Libitum
Pourquoi nourrir les patients cancéreux? - Optimiser la tolérance / l efficacité des traitements - Optimiser la survie
Oncology ESPEN Guidelines on Parenteral Nutrition: Non-surgical oncology F. Bozzetti et al. Clin Nutr 2009, 28: 445-454 *** Free at: www.espen.org
Optimisation de l état nutritionnel : qualité de vie
Cancer : disease and nutrition are key determinants of 271 patients quality of life Ravasco P et al. Support Care Cancer 2004; 12: 246-252
Conclusion
le temps d agir
CANCER approche multidisciplinaire longitudinale, incluant la nutrition Prévention Traitements aigus chroniques Guérison / prévention II ou décès Nutrition adaptée aux besoins métaboliques, cliniques, éthiques spécifiques de chaques phases
PREVENTION: Fruits, Légumes Activité physique
CANCER et NUTRITION Lors de traitements aigus ou chroniques, 1: Nutrition pour: Maintenir la masse et les fonctions corporelles Préserver la qualité de vie Optimiser la tolérance au traitement 2. Pas de nutrition (?) si pas de bénéfices pour le patient
Itinéraire Clinique Ethique PATIENT Proches Soignants Savoir Information Pathologie
OncoNut Optimisation de la prise en charge OncoNut nutritionnelle des patients atteints de cancer
alimentation.3000