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Summary Background & aims Metastatic non-small cell lung cancer (NSCLC) is the first cause of cancer death worldwide. Increased resting energy expenditure (REE) is frequent among cancer patients and may contribute to cancer cachexia. The aim of this study was to examine the prognostic value of increased REE in metastatic NSCLC patients. Methods This observational study was conducted between June 2012 and November 2017 in the outpatient unit of the oncology department of Cochin hospital, Paris. Consecutive patients with newly diagnosed stage IV NSCLC underwent measurement of REE by indirect calorimetry before treatment initiation. Uni- and multivariate analysis of overall survival (OS, Cox models) included age, sex, smoking habit, histological subtype, performance status, body mass index, weight loss, albumin and CRP levels and the ratio of measured REE to the REE predicted by the Harris Benedict formula (mREE/pREE). Results 144 patients were enrolled: mean age 64 years, 63% male, 90% non-squamous carcinoma, including 17% with ALK/EGFR alteration. In univariate analysis, tobacco consumption (p = 0.007), histo-molecular subtype (p vs ≤ 120%: HR = 2.16, p and ≤120%, respectively. In multivariate analysis, histo-molecular subtype (non-squamous ALK/EGFR mutated vs squamous carcinoma: HR = 0.25, p = 0.006), weight loss (>vs ≤ 5%: HR = 1.98, p = 0.004), albumin (≥vs vs ≤120%: HR = 1.90, p = 0.004) were identified as independent prognostic factors. Conclusions Elevated resting energy expenditure emerges as an independent prognostic factor in metastatic NSCLC.

Alterations of nutritional and performance status (PS) are associated with higher risk of chemotherapy toxicity. Increased resting energy expenditure (REE) is frequent in cancer patients and may contribute to cachexia. We investigated whether abnormal energetic metabolism could predict early acute limiting toxicities (ELT) of anticancer treatments.In this observational monocentric study, REE was measured by indirect calorimetry before treatment initiation. Based on the ratio of measured REE to REE predicted by the Harris-Benedict formula, patients were classified as hypometabolic (90%), normometabolic (90-110%) or hypermetabolic (110%). Body mass index, weight loss, PS, albumin, transthyretin, C-reactive protein (CRP) and muscle mass (CT-scan) were studied. Were defined as ELT any unplanned hospitalization or any adverse event leading to dose reduction or discontinuation during the first cycle of treatment.We enrolled 277 patients: 76% had metastatic disease; 89% received chemotherapy and 11% targeted therapy; 29% were normometabolic, 51% hypermetabolic and 20% hypometabolic. Fifty-nine patients (21%) experienced an ELT. Toxicity was associated with abnormal metabolism (vs normal: OR = 2.37 [1.13-4.94], p = 0.023), PS (2-3 vs 0-1: OR = 2.04 [1.12-3.74], p = 0.023), albumin (35 vs ≥35 g/l: OR = 2.39 [1.03-5.54], p = 0.048), and inflammation (CRP ≥10 vs10 mg/l: OR = 2.43 [1.35-4.38], p = 0.004). To predict toxicity, the most sensitive parameter was the REE (83%) followed by PINI (63%), GPS (59%), CRP (55%), PS (41%), NRI (37%), and albumin (16%). In multivariate analysis, elevated CRP was an independent predictor of toxicity (p = 0.047).Abnormal basal energy metabolism identifies patients at higher risk of treatment-related acute complications.

Background: Cachexia is a major cause of death in cancer patients. The role of hypermetabolism in cancer cachexia remains unclear.Objective: We studied the relation between resting energy expenditure (REE), the estimated energy balance, clinical and biological markers of cachexia, and survival.Design: REE was measured with the use of indirect calorimetry in cancer patients before the initiation of anticancer therapies. Hypermetabolic, normometabolic, and hypometabolic patients were identified with the use of Boothby's standard. Weight loss, performance status (PS), C-reactive protein (CRP), albumin, the nutritional risk index, daily energy intake, energy balance (equal to daily energy intakes minus the REE), and survival were recorded.Results: Of 390 enrolled patients, 49% of subjects were hypermetabolic, 30% of subjects were normometabolic, and 21% of subjects were hypometabolic. Mean daily energy intakes did not differ significantly between the 3 groups. Hypermetabolic patients, compared with normometabolic patients, were more likely to have a negative energy balance [45% compared with 32%, respectively; OR: 1.74 (95% CI: 1.05, 2.91); P = 0.024], weight loss >5% [48% compared with 34%, respectively; OR: 1.83 (95% CI: 1.11, 3.04); P = 0.013], PS ≥2 [40% compared with 29%, respectively; OR: 1.70 (95% CI: 1.01, 2.88); P = 0.038], and CRP concentrations ≥10 mg/L [52% compared with 33%, respectively; OR: 2.2 (95% CI: 1.33, 3.66); P = 0.001]. In metastatic patients, compared with normometabolism, hypermetabolism was associated with a reduced median survival [14.6 compared with 21.4 mo, respectively; OR: 1.48 (95% CI: 1.01, 2.17); P = 0.044].Conclusions: Hypermetabolism is correlated with clinical and biological markers of cancer cachexia and is associated with a shorter survival in metastatic cancer patients. The development of therapeutic strategies that aim to blunt hypermetabolism appears warranted. This trial was registered at www.controlled-trials.com as ISRCTN46152275.

Resume Contexte Depuis la loi du 4 mars 2002 le medecin doit a son patient une information claire, loyale et appropriee. En cancerologie, face a l’annonce d’un mauvais pronostic, le devoir d’information loyale au patient pour faire valoir et respecter son autonomie peut entrer en contradiction avec le principe de non-malfaisance. Objectif Cette etude visait a identifier et comprendre les attentes d’information pronostique des patients atteints de cancer metastatique incurable ainsi que l’impact et le sens de ces informations. Patients et methodes Cette etude qualitative prospective se basait sur neuf entretiens semi-directifs conduits chez les patients atteints de cancer incurable suivis a l’hopital Cochin et qui avaient recu une mauvaise nouvelle liee au pronostic par leur medecin referent dans le mois precedent et il y a plus de 6 jours. Le guide d’entretien suivi visait a identifier le sens des informations recues ou manquantes selon qu’elles etaient desirees ou non. Resultats L’analyse des themes et sous-themes a permis de mettre en evidence sept themes qui se declinent differemment selon que le patient esperait la guerison et rejetait les autres possibilites, esperait la guerison mais envisageait qu’elle ne soit pas possible, ou avait fait le deuil de la guerison. Le caractere utile et acceptable de l’information pronostique ne dependait pas de criteres precis mais d’un faisceau d’arguments correspondant a des axes : la nature des objectifs qui passaient de la guerison a la qualite de vie, la demande de verite et de reassurance qui devenait de moins en moins pregnante, le rapport a l’incertitude qui d’angoissante devenait source d’espoir, l’espoir centre sur la guerison se centrait ensuite sur la qualite de vie, les manifestations d’angoisse qui s’estompaient au cours du cheminement, la temporalite qui se reduisait et le rapport a la mort qui entrait dans le champs des possibles. Conclusion L’identification de ces axes est un prealable a l’amelioration des pratiques d’annonce pronostique en cancerologie mais des etudes complementaires sont necessaires afin de determiner une facon adaptee de les utiliser en pratique clinique.

Background: Immune evasion and deregulation of energy metabolism play a pivotal role in cancer progression. Immunosuppression in the tumor microenvironment can be based on the mutual metabolic requirements of immune and tumor cells. We evaluated the value of resting energy expenditure (REE) as a predictor of outcome, in mNSCLC patients under Nivolumab, an immune checkpoint inhibitor. Methods: We studied the relation between REE, clinical and biological markers of cachexia and inflammation, and response to Nivolumab in 82 consecutive mNSCLC patients. Efficacy was assessed every 2 months according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria. REE was measured using indirect calorimetry, before the initiation of Nivolumab. According to their REE and with the use of Boothby's standard, patients were categorized as hypermetabolic, normometabolic and hypometabolic. Body mass index (BMI), performance status (PS), C-reactive protein (CRP), albumin, Neutrophil Lymphocyte R Ratio (NLR) and PD-L1 tumor expression were also recorded. Results: Patients characteristics were: 62% males, median age of 65 years (range 37-78), 61% PS 0-1, median BMI of 24 kg.m-² (range 17-39), 78% nonsquamous NSCLC. The analysis of REE was available for 69 out of 82 consecutive pts: 37.7% were hypermetabolic, 47.8% were normometabolic, and 14.5% were hypometabolic. In univariate analysis, hypometabolism was a strong predictive marker of disease progression (Table 1), with positive and negative predictive values of 0.80 and 0.52 respectively. In multivariate analysis, independent parameters associated with disease progression were baseline hypometabolism (vs normometabolism: OR 1.77 [1.31-2.39] p= 0.0004) and albumin (per 1pt increase: OR 0.96 [0.94-0.99] p= 0.005). Conclusion: Rest energy expenditure assessed by calorimetry appears as a biomarker of nivolumab clinical activity independently of PD1/PDL1 status. Table 1Disease control (best response) n (%)115% calculated REE n=26 (37.7%) Hypermetabolicunivariate OR (Hypometabolic vs normometabolic)pProgression8 (80%)11 (33%)17 (65%)8 [1.4-44.2]0.0007Disease control rate2 (20%)22 (67%)9 (35%) Citation Format: Claire Gervais, Pascaline Boudou-Rouquette, Anne Jouinot, Jeanne Chapron, Jennifer Arrondeau, Marco Alifano, Frédérique Giraud, Olivier Huillard, Jérôme Alexandre, Clara Vazeille, Jean-Philippe Durand, Karen Leroy, Marie-Pierre Revel, Jean-Pascal de Bandt, Luc Cynober, Diane Damotte, Audrey Lupo-Mansuet, François Goldwasser. Prediction of the efficacy of nivolumab using resting energy expenditure in metastatic non-small cell lung cancer (mNSCLC) patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1693.

Aim: The WHO Performance Status (PS) of cancer patients (pts) correlates with survival and with anticancer treatments tolerability. However, PS is subject to inter-observer variability and is not sensitive to detect pts with high-risk of treatment toxicity. We studied the relationship between Rest Metabolic Rate (RMR) and PS. Methods: A prospective observational, monocentric study was conducted. Before treatment initiation, RMR was measured using indirect calorimetry (Fitmate®, Cosmed srl) and compared to estimated RMR obtained by the modified Harris and Benedict equation. Hypermetabolics (Hm) pts were defined as having measured RMR ≥110% of calculated RMR and Not Hypermetabolics (NoHm) pts Results: A total of 161 consecutive pts were analyzed : 58% males, median age : 64 years (20-94). Primary tumor: genito-urinary (23%) gastro-intestinal (20%), lung (17%); 10% were PS ≥3; median weight loss : 4.1% (-14.9–+18.5); mean energetic gap: +80 kcal/d; mean RMR : 1676 kcal/d; 60% of the pts were Hm with mean RMR= 1815 kcal/d vs 1433 kcal/d in NoHm pts (P 5% in 52% vs 32% of the pts (p = 0.03). Hm pts had more inflammation: a1-GP 1.5 vs 1.1 g/L (t=3.41, p Conclusions: Hypermetabolism may account for cancer-induced asthenia and development of cachexia. The measurement of RMR allows to detect pts at high-risk of malnutrition amongst pts with PS Disclosure: All authors have declared no conflicts of interest.

PP090-SUN SYNERGISTIC EFFECTS OF COMBINED PHYTOCHEMICALS IN DIMINISHING BREAST CANCER CELL GROWTH AND METASTASIS M.E.E. Abdraboh1,2, R. Gaur3, A. Ouhtit4, A. Hollenbach5, A. El-hadidy6, M. Raj7. 1Zoology, Faculty of Science, Mansoura University, Mansoura, Egypt; 2Pathology, Louisiana State University, New Orleans, 3Pathology, Stanford University, California, United States; 4Genetics, Sultan Qaboos University, Muscat, Oman; 5Genetics, Louisiana State University, New Orleans, United States; 6Basic Science, Delta University, Gamasa, Egypt; 7Obstetrics and Gynecology, Louisiana State University, New Orleans, United States

9620 Background: Alterations of performance status (PS) and of nutritional status are predictors of acute toxicity following anticancer treatment. Resting energy expenditure (REE) is often increase...