Genève C. Pichard, MD, PhD

Transcription

1 Cancer et Nutrition Genève 2015 C. Pichard, MD, PhD Unité Didac. Geneve de lac Nutrition, HUG, Genève

2 1. Cancer : prévalence croissante 2. Prévention : complexe! 3. Croissance tumorale : nutri- modulation 4. Nutriments : adjuvants thérapeutiques

3 CANCER - WHO * 10 6 deaths * 10 6 deaths 2032 increase by 70%

4 Cancer prévalence croissante

5 CANCER - WHO 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

6 CANCER - WHO 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

7 The Cancer Burden World Cancer Research Fund / American Institute for Cancer Research: Policy & Action for Cancer Prevention. Washington DC: AICR, 2009

8 Increase across all age-groups Children and adolescents Steliarova-Foucher E, Lancet, 2004

9 incidence > 65 years: 60% cancer 80% death by cancer mortality

10 Cancer Et Environnement

11 Observational evidence: migrant studies WCRF/AICR. Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective, Washington DC: AICR, 2007

12 Cancer : Number of cases Treatment duration

13 CANCER - Financial Costs 2005 (USA) Billions US Overall Education Direct medical Worker productivity Premature death

14 Cancer Prévention complexe

15 Cancer is preventable

16 CANCER - WHO World Cancer Report provides clear evidence that action on smoking, diet, infections can prevent 1/3 of cancers.

17 CANCER - W.H.O. GI cancer European Prospective Investigation into Cancer & Nutrition (EPIC) : n= (Publ Health Nutr 2003) 500 g / d fruits - vegetables -> incidence: - 25 % GI

18 FOLIC ACID

19 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

20 Observational evidence: folic acid supplementation and colorectal cancer risk Mason, JB, Cancer Epidemiol Biomarkers Prev, 2007

21 Observational evidence: folic acid supplementation and colorectal cancer risk In 2000, folate fortification became mandatory in Chile : after mandatory flour fortification program with 220 µg/100 g flour, colon cancer rates increased by 162 % in yrs 190 % in yrs Hirsch S, Eur J Gastroenterol Hepatol. 2009

22 ACIDE FOLIQUE: à pas bon pour tous, critique durant la grossesse

23 Des nutriments précieux Vitamine D

24 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, Grant WB, Recent Results Cancer Res. 2007

25 Vitamin D Increased intake favourable for Cancer AND Osteoporosis

26 Cancer prevention? A global action

27 When more is better 10 yrs follow-up: Survival function according to health behaviours in men & women, ys w/o known Smoking PA OH Vit C CV disease or cancer Khaw KT, PLoS Med, 2008

28 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

29 NUTRITION Santé Cancer Santé Prévention I Traitement Prévention II

30 Croissance tumorale nutri- modulation

31 Tumor : Anabolism > Catabolism Host : Catabolism > Anabolism

32 Matt Seymour, MRC Colorectal Cancer Group Cancer cell number 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? months

33 Nourrir la tumeur? NON, mais...

34 Metastatic Liver Tumors in Mice TJ. Yeatman et al. Arch Surg 1991, 26: ( ) (median, range) * p< n=8 ARGININE repleted (29-168) * n=10 ARGININE depleted

35 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 1.8x x10 6 1x10 6 6x10 5 2x µm Arg 10 µm Arg 100 µm Arg 1000 µm Arg Number of days of treatment

36 Nutrients Stimulate Cancer Cells Growth 6x10 5 LS174T Cell number / ml 3x10 5 Immunonutrition (1/1000) Cell culture medium Nb of days of treatment

37 Jeûner pour affamer le cancer

38 Toxicity in Chemotherapy When Less Is More Laviano A Rossi Fanelli F. N Engl J Med 2012, 366;

39 Nutriments Adjuvants thérapeutiques

40 Stimulation Griffini P & al. Cancer Res, 58: (1998) Meterissian SH & al. Cancer Lett, 89: (1995) Ω6-PUFAs AA Arachidonic Acid Ω3-PUFAs EPA Eicosapentaenoic Acid Inhibition Latham P & al. Carcinogenesis, 20: (1999) Rao C & al. Cancer Res, 61: (2001)

41 Cancer Cells Culture & PUFAs LS174T 600' '000 0 µm EPA 30 µm EPA N cells / ml 400' ' ' ' µm EPA 100 µm EPA Incubation 4 d X ± 1 SD, triplicate /condition Treatment days

42 Tumor-modulating nutrition: OncoNutritionMixture n-3 fatty acids Arginine Glutamine Vitamins Extracellular Intracellular DNA RNA Protein precursors Cell Division Nucleus

43 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

44 Interaction between Nutrients : CAUTION! Survival fraction (S/So %) Gy 4 Gy ** RADIOSENSITIVE HT ns 80 ns ** ** 60 ** RADIORESISTANT CO112 Different from controls, t-test * P < 0.05, ** P < 0.01 Supra-additive effect (Multivariable linear regression analysis), P < DHA Vit E µm

45 Pour le moment: Assurer l équilibre en énergie et protéines

46 Nutrition lors de cancer : Bénéfices?

47 Diagnosis & Prevalence (%) of weight loss % weight loss n 0 < Favorable non-hodgkin s lymphoma Breast Acute nonlymphocytic lymphoma Sarcoma Unfavorable n-hodgkin s lymphoma Colon Prostate Lung, small cell Lung, non-small cell Pancreas (2 months!) Estomac DeWyss WD. Am J Med 1980

48 Body weight loss & Survival De Wys et al. Am J Med > No weight loss: better survival

49 CANCER chimiothérapie radiothérapie chirurgie Dépression Douleur Hypophagie Aphtes, mycose, Nausées, vomissements, Aversion alimentaire, dysgeusie, dysosmie, Cachexie Anorexie, satiété précoce

50 CANCER - Body weight Pre diagnostic Treatments - complications

51 PATIENT A SM = cm2 AT = cm2 Homme 68 ans Cancer Intestin grêle IMC 24.4 kg/m² Surface musculare = cm² Surface tissu adipeux = cm² BMI = 24.4 kg/m2 BBBBBB PATIENT B Homme 54 ans Adénocarcinome pancréas BMI 24.2 kg/m² SM = cm2 AT= cm2 Surface musculaire = cm² Surface tissu adipeux = cm² Antoun S

52 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: Sarcopenic obesity is an independent predictor of survival (HR 4.2 [ ], p<0,0001) links body composition, especially sarcopenic obesity, to clinical parameters (functional status, survival, and potentially, chemotherapy toxicity

53 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: 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) < Whole body lean mass (kg) 34.0 (3.3) 42.5 (5.0) < Mg capecitabine / kg FFM (16.1) 86.9 (13.7) <0.0001

54 Le patient doit manger...

55 Nutrition therapy in cachectic cancer patients The Tight Caloric Control (TiCaCo) pilot trial De Waele E, Appetite 2015, 91: 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

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57 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

58 Pourquoi nourrir les patients cancéreux? - Optimiser la tolérance / l efficacité des traitements - Optimiser la survie

59 Oncology ESPEN Guidelines on Parenteral Nutrition: Non-surgical oncology F. Bozzetti et al. Clin Nutr 2009, 28: *** Free at:

60 Optimisation de l état nutritionnel : qualité de vie

61 Cancer : disease and nutrition are key determinants of 271 patients quality of life Ravasco P et al. Support Care Cancer 2004; 12:

62 Conclusion

63 le temps d agir

64 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

65 PREVENTION: Fruits, Légumes Activité physique

66 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

67 Itinéraire Clinique Ethique PATIENT Proches Soignants Savoir Information Pathologie

68 OncoNut Optimisation de la prise en charge OncoNut nutritionnelle des patients atteints de cancer

69 alimentation.3000