Jens Kondrup Professor, senior physician, dr med sci

Transcription

1 Jens Kondrup Professor, senior physician, dr med sci Conflicts of interest: honoraria and grants from Fresenius-Kabi, Nutricia, Nestle Rigshospitalet University of Copenhagen

2 Hvorfor taber kræftpatienter sig? Hvad betyder vægttab for kræftpatienter? Evidens: hvad hjælper det at ernære kræftpatienter? Forslag til indsats

3 Cytokines and weight loss in pancreatic cancer Falconer et al Ann Surg 219: editorial: Mullen Ann Surg 219: Pos Acute Phase proteins Neg Acute Phase Proteins CRP, mg/l 72 <10 Albumin, g/l REE, kcal/kg BW Weight, kg Weight loss (months?), % Fat free mass (BIA), kg Body cell mass (BIA), kg Ex vivo PBMC + endotoxin, TNF-, pg/ml Ex vivo PBMC + endotoxin, Il-6, ng/ml 12 4 Energy deficit calculated from weight loss Excess REE compared to healthy controls Expected wt loss in e.g. 6 months 80, ,000 Kcal 120 Kcal/day 3 kg versus 13 kg observed Editor s conclusion: other factors, such as reduced food intake, must play a major role

4 Monitoring: Clinical database at Rigshospitalet Nutrition therapy for 3.9 weeks (Benign) or 3.2 weeks (Malignant) Patients weighed, without edema. Pt group Initial BW, kg BMI Recent wt- loss, % Energy goal, MJ Energy intake, MJ Final BW, kg. < 75% req, % >5% wt loss, % Benign (524) Malignant (459)

5 Associations with 5% wt loss within 3 months % with YES no loss, or <5% N= 759 5% wt loss N=292 Male * Diagnosis other than breast cancer * Eaten less in the last week? * Reduced appetite in the last week? * Changed dietary habits in the last week? * Difficulty in light carrying? * Difficulty in walking >1 km * Difficulty in walking 100 m? * Difficulty in bathing or dressing? * Had fever in last month? 7 20 * BW is too low? 8 45 * * P < Kondrup et al 2001 upubliceret P

6 Supplementary questionnaire if any weight loss % with YES <5% (96) 5% (292) nausea/vomiting reduced food intake phys hindrance reduced food intake * taste alterations reduced food intake * smell alterations reduced food intake * wt loss bothered you? * wt loss a problem? * wt loss impaired daily living? 5 25 * wt loss impaired mood? wt loss impaired physical activity? 7 22 * wt loss impaired social activity? 4 21 * feel more ill because of wt loss? look more ill because of wt loss? * *P< P Kondrup et al 2001 upubliceret

7 Logistic regression analysis: Odds ratios for weight loss Odds ratios for 5% weight loss (N=292) OR (95% CI) P Diagnosis breast c. 2.2 ( ) * Eaten less 2.8 ( ) * Changed dietary habits 1.8 ( ) * Decreased appetite 2.9 ( ) * Low physical activity 2.5 ( ) * Odds ratios for 5% weight loss defined as problematic 1) (N=155) Male versus female 3.5 ( ) * Relapse 2.7 ( ) Usual BMI< ( ) 0.01 Decreased appetite 5.1 ( ) * Low physical activity 3.2 ( ) * 1) one of the following: impaired mood, impaired social activity, feel more ill *P< Kondrup et al 2001 upubliceret

8 Hvorfor taber kræftpatienter sig? Hvad betyder vægttab for kræftpatienter? Evidens: hvad hjælper det at ernære kræftpatienter? Forslag til indsats

9 American Gastroenterological Association: technical review on parenteral nutrition Koretz, R. L., T. O. Lipman, et al. (2001). Gastroenterology 121: Oncology RCTs

10 American Gastroenterological Association: technical review on parenteral nutrition Koretz, R. L., T. O. Lipman, et al. (2001). Gastroenterology 121:

11 Does Enteral Nutrition Affect Clinical Outcome? A Systematic Review of the Randomized Trials Koretz et al Am J Gastroenterol. 102: Nonsurgical Cancer Treatment Tube feeding Two RCTs (162 patients) failed to find any significant, or even trends for, benefit Liquid supplements Meta-analysis of four RCTs found no difference in mortality Grade D: limited data could not support the intervention

12 multi Stratton et al. Combined Analysis of the Effects of Oral Nutritional Supplements and Enteral Tube Feeding. In: Disease-related Malnutrition: an evidence-based approach to treatment. Wallingford: CABI Publishing; p

13 Multi_mort

14 Multi compl

15 N RCT Fra NRS 2002 Diagnostic groups PN, EN or ON 40 GI surg 35 Pos No Cancer Misc 10 Cirrhosis COPD Trauma ATIN Femur 5 0 < 3 >= 3 < 3 >= 3 < 3 >= 3 < 3 >= 3 < 3 >= 3 < 3 >= 3 < 3 >= 3 < 3 >= 3 Kondrup et al. Clin Nutr 2003; 22:

16 Clinical effect, if present: Cancer tolerance/on (2) tolerance/pn (39) tolerance/pn (40) tolerance/on (41) QoL/EN (35) survival/pn (44) survival/pn (91) Acute Renal Failure survival/pn (89) survival/pn (90) Femoral fracture LOS/ON (3) LOS/ON (4) survival/en (5) Geriatry ADL/ON (34) ADL/ON (85) survival/on (45) ( ) = References in Kondrup et al. Clin Nutr 2003; 22: Cirrhosis Clin Index/PN (36) encephalopathy/en (42) infection/en (81) LOS/PN (88) survival/on (93) Misc. Trauma infection/en (18) LOS/EN (29) survival/pn (30) infection/burns/en (28) survival/bmt/pn (31) survival/stroke/on (92)

17 State of the art: Most RCTs in cancer patients have been performed in patiens in whom there was no indication for nutrition support The intervention was inefficient (oral), or added to adequate intake (oral & PN) The conclusion that PN in cancer patients is useless and probably harmful is valid only if PN is used as an adjunct to patients who are not malnourished/hypophagic The major end-points investigated (survival, reponse to therapy) may not be sensitive to nutrition support Some RCTs show an effect on minor end-points incl QoL

18 g protein, or Kcal energy, or Global QoL Nutitional counselling in head & neck cancer 3 x N = 75 Ravasco et al. Head Neck 2005;27: RT 2400 Counsel Energy Supplement Energy Paula H&N *Sign change form baseline * * Months Control Energy Counsel QoL Counsel Protein Supplement QoL Supplement Protein Control QoL Control Protein

19 g p ro te in, o r K c a l e n e rg y, o r G lo b a l Q o L Nutitional counselling in colorectal cancer 3 x N = 111 Ravasco et al. J Clin Oncol Mar 1;23(7): RT C o u n s e l E n e rg y S u p p le m e n t E n e rg y C o n tro l E n e rg y * * C o u n s e l Q o L C o u n s e l P ro te in S u p p le m e n t Q o L S u p p le m e n t P ro te in C o n tro l P ro te in C o n tro l Q o L Paula colorectal *Sign change form baseline M o n th s

20 QoL: oral nutritional interventions in malnourished patients with cancer (active treatment or palliative care). Baldwin et al. J Natl Cancer Inst 2012;104:371-85

21 QoL: oral nutritional interventions in malnourished patients with cancer (active treatment or palliative care). Without heterogeneity. Baldwin et al. J Natl Cancer Inst 2012;104:371-85

22 Long-term follow-up of a randomized controlled trial of nutritional therapy in colo-rectal patients Ravasco et al. Am J Clin Nutr 2012;96: Counselling Supplement Control

23 Long-term follow-up of a randomized controlled trial of nutritional therapy in colo-rectal patients Ravasco et al. Am J Clin Nutr 2012;96: Control 26 Supplement 29 Counsel 34 Median disease-specific survival, yrs Local recurrence, N (%) 9 (30) - 7 (19) Liver metastases, N (%) 6 (20) 3 (9) - Positive lymph nodes, N (%) - 6 (16) - Event frequency (P < 0.01) > >

24 Perioperative arginine-supplemented nutrition in malnourished patients with head and neck cancer improves long-term survival. Buijs et al. Am J Clin Nutr 2010;92:

25 Perioperative arginine-supplemented nutrition in malnourished patients with head and neck cancer improves long-term survival. Buijs et al. Am J Clin Nutr 2010;92:

26 Perioperative arginine-supplemented nutrition in malnourished patients with head and neck cancer improves long-term survival. Buijs et al. Am J Clin Nutr 2010;92:1151-6

27 Effect of arginine? Proliferating remnant malignant cells attacked by arginineinduced improved T cells? Arginine-derived NO activates the p53 genes and switch on the immune system to clear pre-malignant cells from the residual normal-appearing cells? etc etc Buijs et al. Am J Clin Nutr 2010;92:1151-6

28 12 mths PN in palliative chemotherapy of advanced colon or rectal carcinoma. 67% with liver metastasis. 2N = 82. Malnourished: BMI 20 or 5% wt loss in 3 mths. BW: 67 kg; BMI: 23.0; 3 mths wt loss: 7 kg. Hasenberg et al Colorectal Dis 12: e190-e199 Total energy, kcal/d Total protein/aa, g/d PN energy, kcal/d PN AA, g/d 28 - Nausea (%) ) Vomiting (%) ) Abdominal pain (%) ) Diarrhoea (%) ) Mucositis (%) ) Survival (%) ) QoL, EORTC QLQ-C ) 1) P<0.001; 2) P<0.02; 3) P<0.05 PN Ctr

29 Konklusioner Metaanalyser af dårlige studier giver statistisk sikker dårlig evidens. NRS 2002 litteratur-analyse tyder på effekt på minor endpoints Nye studier tyder på effekt på QoL - hos underernærede og/eller småtspisende kræftpatienter. 3 studier tyder nu på effekt på overlevelse. Status: gøre mere end ingenting

30 Hvorfor taber kræftpatienter sig? Hvad betyder vægttab for kræftpatienter? Evidens: hvad hjælper det at ernære kræftpatienter? Forslag til indsats

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