Overweight is associated to a better prognosis in metastatic colorectal cancer: A pooled analysis of FFCD trials

Aparicio, Thomas; Ducreux, Michel; Faroux, Roger; Barbier, E.; Manfrédi, Sylvain; Lecomte, Thierry; Etienne, Pierre-Luc; Bedenne, Laurent; Bennouna, Jaafar; Phélip, Jean-Marc; François, Ετιεννε; Michel, Pierre; Legoux, Jean-Louis; Gasmi, Mohamed; Breysacher, Gilles; Rougier, Philippe; Gramont, Aimery de; Lepage, Côme; Bouché, Olivier; Seitz, Jean‐François; Adenis, Antoine; Aghemo, Alessio; Aouakli, A.; Azzedine, A.; Bedjaoui, Ahmed; Bidault, Anne Thirot; Blanchi, A.; Botton, A.; Cadier-Lagnes, A.; Fatisse, Abdelaziz; Gagnaire, Alice; Gilbert, Alexandra; Gueye, A.; Hollebecque, Antoine; Lemaire, A; Mahamat, Abakar; Marre, A.; Patenotte, Arnaud; Rotenberg, Alexander; Roussel, A; Thirot-Bidault, Anne; Votte, A.; Weber, Ana Paula; Zaanan, Aziz; Dupont-Gossart, Anne-Claire; Villing, Anne-Laure; Queuniet, A M; Coudert, Bruno; Denis, Bernard; Garcia, Bruno; Lafforgue, B; Landi, Bruno; Leduc, Bernard; Linot, Benjamin; Paillot, B; Rhein, B.; Winkfield, Betsy; Barberis, Claudia; Becht, Catherine; Belletier, Christine; Berger, C.; Bineau, Catherine; Borel, Christian; Brézault, Catherine; Buffet, C; Cornila, Corina; Couffon, Caroline; Fouchardière, Christelle De La; Giraud, Claire; Lecaille, Cédric; Lepère, Céline; Lobry, Céline; Locher, Christophe; Lombard‐Bohas, Catherine; Paoletti, Costanza; Platini, Christian; Rebischung, Christine; Sarda, Corinne; Vilain, Claire; Briac-Levaché, C.; Auby, Dominique; Baudet-Klepping, D.; Béchade, Dominique; Besson, Dominique; Cléau, D.; Festin, D; Gargot, D.; Genet, Dominique; Goldfain, D; Luet, Dominique; Malka, David; Péré-Vergé, Denis; Pillon, D.; Sevin-Robiche, D.; Smith, Deborah A.; Soubrane, D.; Tougeron, David; Zylberait, D; Carola, Élisabeth; Cuillerier, Emmanuel; Danquechin, E. Dorval; Echinard, E.; Janssen, Emiel A. M.; Maillard, E.; Mitry, Emmanuel; Norguet-Monnereau, Emmanuelle; Suc, Etienne; Terrebonne, Éric; Zrihen, E; Pariente, E. A.; Almaric, Françoise; Audemar, Franck; Bonnetain, Franck; Desseigne, Françoise; Dewaele, François; Fiore, Frédéric Di; Ghiringhelli, François; Husseini, F.; Khemissa, Faïza; Kikolski, F.; Morvan, F.; Petit-Laurent, Fabien; Riot, François; Subtil, Fabien; Zerouala-Boussaha, F.; Caroli-Bosc, François-Xavier; Boilleau-Jolimoy, G.; Bordes, Gilbert; Cavaglione, Gérard; Coulanjon, G.; Deplanque, Gaël; Gatineau-Saillant, G.; Goujon, Gaël; Medinger, G.; Roquin, Guillaume; Brixi-Benmansour, Hedia; Castanie, Hélène; Lacroix, Hendrik; Maechel, H; Perrier, H.; Salloum, Hatem; Senellart, Hélène; Baumgaertner, Isabelle; Cumin, Isabelle; Graber, I. G.; Trouilloud, Isabelle; Boutin, JM; Butel, J; Charneau, J; Crétin, J; Dauba, Jérôme; Deguiral, J.; Egreteau, Joëlle; Ezenfis, J.; Forestier, Julien; Goineau, J.; Lacourt, J; Lafon, J; Martin, J. M. Artigas; Meunier, Jérôme; Moreau, Johanna; Provençal, J.; Taı̈eb, Julien; Thaury, J.; Tuaillon, J; Vergniol, Julien; Villand, J; Vincent, Jeroen; Volet, Julien; Bachet, Jean Baptiste; Barbare, Jean‐Claude; Souquet, J. C.; Grangé, J.D.; Dor, Jehoshua; Paitel, J.F.; Jouve, Jean-Louis; Raoul, Jean‐Luc; Cheula, J.M.; Gornet, Jean–Marc; Sabaté, Jean‐Marc; Vantelon, J; Vaillant, Jean-Nicolas; Aucouturier, J.P.; Barbieux, Jean-Pierre; Herr, Jean-Philippe; Lafargue, J.P.; Lagasse, Jean-Paul; Latrive, Jean-Paul; Plachot, J. P.; Ramain, Julie; J, Robin; Spano, J.P.; Douillard, Jean Yves; Beerblock, K.; Bouhier-Leporrier, Karine; Fawzi, K. Slimane; Cany, Laurent; Choné, Laurence; Dahan, L.; Gasnault, Laurent; Rob, Lynn; Stefani, Laëtitia; Wander, L.; Baconnier, Mathieu; Abdelghani, Méher Ben; Benchalal, M.; Blasquez, M.; Carreiro, M.; Charbit, Marina; Combe, M.; Duluc, Muriel; Fayolle, M.; Gignoux, M; Giovannini, Marc; Glikmanas, M; Mabro, May; Mignot, M.H.; Mornet, M.; Mousseau, M; Mozer, M.; Pauwels, Martine; Pelletier, M; Porneuf, M.; Ramdani, Mohamed; Schnee, Matthieu; Tissot, M.; Zawadi, Mohamed-Ayman; Clavero-Fabri, Marie-Christine; Gouttebel, M. C.; Kaminsky, Marie Christine; Galais, Marie-Pierre; Abdelli, Naceur; Barrière, Nicolas M.; Bouaria, N.; Bouarioua, Nadia; Delas, Nicolas; Gérardin, N.; Hess-Laurens, N.; Stremsdoerfer, N; Berthelet, Olivier; Boulat, Olivier; Capitain, Olivier; Favre, Olivier; Amoyal, P.; Bergerault, P.; Burtin, Pascal; Cassan, P; Chatrenet, P; Chiappa, Pascale; Claudé, Pierre; Couzigou, Patrice; Feydy, P; Follana, Philippe; Geoffroy, Patrick; Godeau, P; Hammel, Pascal; Laplaige, P.; Lehair, P; Martin, Petra; Novello, P.; Pantioni, P.; Pienkowski, P.; Pouderoux, Philippe; Prost, Patricia; Ruszniewski, P.; P, Souillac; Texereau, Patrick; Thévenet, P; Haineaux, P.A.; Benoit, R.; Coriat, Romain; Lamy, R.; Mackiewicz, R; Beorchia, S.; Chaussade, Stanislas; Hiret, Sandrine; Jacquot, S.; Denes, S. Lavau; Montembault, Sarah; Nahon, Sophie; Nasca, S; Nguyen, Sa; Oddou-Lagranière, S.; Pesque-Penaud, S.; Fratté, S.; Chatellier, Thierry; Mansourbakht, T.; Morin, Thierry; Walter, Thomas; Boige, Valérie; Bourgeois, Vincent; Derias, V.; Guerin‐Meyer, Véronique; Hautefeuille, Vincent; Tallec, V. Jestin Le; Lorgis, Véronique; Quentin, V.; Sebbagh, Virginie; Veuillez, Véronique; Adhoute, Xavier; Coulaud, X.; Bécouarn, Y.; Coscas, Yvan; Courouble, Y; Bricquir, Y. Le; Molin, Yann; Rinaldi, Yves; Lam, You-Heng; Ladhib, Z.

doi:10.1016/j.ejca.2018.03.031

Cited by 33 publications

(21 citation statements)

References 35 publications

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“…BMI is another important metabolic index; the present study reported that patients with an overweight BMI classification had a favorable prognosis compared with that of patients with a normal or obese BMI classification, which was consistent with the results demonstrated in other studies (47,48).…”

Section: Cut-off No Of Patients In the -----------------------------supporting

confidence: 93%

Prognostic significance of high triglyceride and apolipoprotein B levels in patients with stage III and high-risk stage II colorectal cancer undergoing curative surgery

Chen

Liu

et al. 2020

Oncol Lett

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Although epidemiologic studies suggest that dyslipidemia increases the risk of colorectal cancer (CRC), the prognostic value of blood lipid and apolipoprotein levels in CRC remains unclear. The aim of the present study was to investigate the impact of blood lipid and apolipoprotein levels on the prognosis of patients with stage III and high-risk stage II CRC undergoing curative surgery. Preoperative levels of total cholesterol, triglycerides (TG), high-density lipoprotein, low-density lipoprotein, very-low-density lipoprotein, apolipoprotein A1 and apolipoprotein B (APO-B) in patients with CRC undergoing surgery were evaluated. The cutoff values of these factors were determined by the maximal x 2 method and were used to classify patients into two prognostic groups: Poor and good prognosis groups. The patients' prognostic values were assessed using the Kaplan-Meier curve and Cox regression analysis. In addition, the impact of these parameters on the prognosis and their predictive accuracy were evaluated using nomograms and Harrell's concordance index, respectively. In total, 246 patients were included in this evaluation. Based on the cutoff points for TG (1.53 mmol/l in men and 1.58 mmol/l in women) and APO-B (0.73 mmol/l in men and women), the present study determined that both TG and APO-B were predictors of disease-free survival (DFS) and overall survival (OS). Multivariate analysis demonstrated that high TG (men, ≥1.53 mmol/l; women, ≥1.58 mmol/l) and high APO-B (≥0.73 mmol/l) levels were significantly associated with decreased DFS and OS. Nomograms that included values for TG and APO-B levels demonstrated higher predictive accuracy compared with that of nomograms without these values. These results indicated that TG and APO-B levels may be good independent prognostic biomarkers after radical CRC surgery. Therefore, adjusting these parameters to moderate levels may be beneficial.

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Section: Cut-off No Of Patients In the -----------------------------supporting

confidence: 93%

Prognostic significance of high triglyceride and apolipoprotein B levels in patients with stage III and high-risk stage II colorectal cancer undergoing curative surgery

Chen

Liu

et al. 2020

Oncol Lett

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“…[1][2][3][4] Cancer patients with excess weight may also have a worse overall prognosis compared to patients with normal Body Mass Index (BMI), [5][6][7][8][9][10][11] and some studies have suggested that excess weight may be related to a worse response to conventional therapies, [12][13][14] although this has not always been confirmed. 6,[15][16][17][18] A recent report has suggested that there is a paradoxical effect of obesity on immunotherapy-treated cancer, because there is an improved antitumor efficacy after checkpoint blockade. 19 The authors suggested that this might be related to a direct targeting of some of the pathways activated in obesity.…”

Section: Introductionmentioning

confidence: 99%

Effect of excess weight and immune-related adverse events on the efficacy of cancer immunotherapy with anti-PD-1 antibodies

et al. 2020

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Immunotherapy is an effective treatment in advanced cancer, although predictors of response are limited. We studied whether excess weight influences the efficacy outcomes of immunotherapy. We have also evaluated the combined prognostic effect of excess weight and immune-related adverse events (irAEs). Efficacy of anti-PD-1 treatment was evaluated with both objective radiological response (ORR) rate and progression-free survival (PFS), and toxicity with irAEs. We studied the association between excess weight and ORR, PFS or irAEs. 132 patients diagnosed with advanced cancer were included. Median body mass index (BMI) was 24.9 kg/ m2. 64 patients had normal weight (BMI<25 kg/m2), and 64 patients had excess weight (BMI≥25 kg/m2). Four patients had underweight and were excluded from further analysis. ORR was achieved in 50 patients (38.0%), median PFS was 6 months. 44 patients developed irAEs (33.3%). ORR was higher in excess weight patients than in patients with normal weight (51.6% vs 25.0%; OR 3.45, p = .0009). PFS was improved in patients with excess weight (7.25 months vs 4 months, HR 1.72, p = .01). The incidence of IrAEs was not different in patients with excess weight (54.5% vs 43.2%, p = .21). When high BMI and irAEs were combined, we observed a marked prognostic trend in ORR rate (87.5% vs 6.2%; OR 161.0, p < .00001), and in PFS (14 months vs 3 months; HR 5.89, p < .0001). Excess weight patients with advanced cancer that receive single-agent anti-PD-1 antibody therapy exhibit a significantly improved clinical outcome compared with normal BMI patients. This association was especially marked when BMI and irAEs were considered combined.

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“…This association is strong and has been shown in multiple cohort studies (Murphy et al, 2000;Jochem and Leitzmann, 2016). Nevertheless, although higher BMI is associated with higher CRC risk, the survival rate of these patients tends to be better than patients with lower BMI (Aparicio et al, 2018;Shahjehan et al, 2018;Tran et al, 2018). Nevertheless, studies show that BMI did not affect any chemotherapy-based side effects or benefit (Meyerhardt et al, 2003;Sinicrope et al, 2013).…”

Section: Introductionmentioning

confidence: 77%

Extracellular Vesicles Derived From Colorectal Cancer Affects CD8 T Cells: An Analysis Based on Body Mass Index

Abu

Othman

Razak

et al. 2020

Front. Cell Dev. Biol.

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Colorectal cancer (CRC) is one of the most widely diagnosed cancers worldwide. It has been shown that the body-mass index (BMI) of the patients could influence the tumor microenvironment, treatment response, and overall survival rates. Nevertheless, the mechanism on how BMI affects the tumorigenesis process, particularly the tumor microenvironment is still elusive. Herein, we postulate that extracellular vesicles (EVs) from CRC patients and non-CRC volunteers with different BMI could affect immune cells differently, in CD8 T cells particularly. We isolated the EVs from the archived serum of CRC patients with high and low BMI, as well as healthy controls with similar BMI status. The EVs were further characterized via electron microscopy, western blot and dynamic light scattering. Then, functional analysis was performed on CD8 T cells including apoptosis, cell proliferation, gene expression profiling and cytokine release upon co-incubation with the different EVs. Our results suggest that CRC-derived EVs were able to regulate the CD8 T cells. In some assays, low BMI EVs were functionally different than high BMI EVs. This study highlights the possible difference in the regulatory mechanism of cancer patients-derived EVs, especially on CD8 T cells.

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Overweight is associated to a better prognosis in metastatic colorectal cancer: A pooled analysis of FFCD trials

Abstract: Overweight patients had a prolonged OS compared with normal weight patients with mCRC. The association of overweight with better OS was only observed in men. The pejorative prognosis of BMI <18.5 was confirmed.

Cited by 33 publications

References 35 publications

Prognostic significance of high triglyceride and apolipoprotein B levels in patients with stage III and high-risk stage II colorectal cancer undergoing curative surgery

Prognostic significance of high triglyceride and apolipoprotein B levels in patients with stage III and high-risk stage II colorectal cancer undergoing curative surgery

Effect of excess weight and immune-related adverse events on the efficacy of cancer immunotherapy with anti-PD-1 antibodies

Extracellular Vesicles Derived From Colorectal Cancer Affects CD8 T Cells: An Analysis Based on Body Mass Index

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