Supportive Care in Cancer

, Volume 20, Issue 12, pp 3129–3135 | Cite as

Immunonutrition before and during radiochemotherapy: improvement of inflammatory parameters in head and neck cancer patients

  • Christelle Machon
  • Simon Thezenas
  • Anne-Marie Dupuy
  • Eric Assenat
  • Françoise Michel
  • Emilie Mas
  • Pierre Senesse
  • Jean-Paul Cristol
Original Article



Inflammatory, angiogenic and oxidative stress markers have been explored in head and neck squamous cell carcinoma (HNSCC) patients before and during radiochemotherapy. Furthermore, the effects of an oral supplementation containing amino acids, ω-3 fatty acids, ribonucleic acids, vitamins, and antioxidants on biological markers and acute toxicities were investigated.


Thirty-one patients with non-metastatic stage III or IV HNSCC treated with concomitant radiochemotherapy were recruited. A nutritional support (Oral Impact®) was given during 5 days before each cycle of chemotherapy. Biological samples were collected at baseline, after 5 days of oral supplementation and before the last cycle of chemotherapy. Acute phase proteins levels, proteomic cytokines determination and urinary isoprostanes levels were used as inflammatory and oxidative stress biomarkers. Toxicities were followed up during radiochemotherapy.


At baseline, median levels of inflammatory (CRP 9.8 mg/l [0.8–130.1], IL-6 4.2 pg/ml [0.7–126.5]), pro-angiogenic (VEGF 229.5 pg/ml [13.1–595.9]) and pro-oxidative stress (urinary isoprostanes 118 pmol/mmol creatinine [51–299]) markers were increased. Decrease in CRP (p = 0.002) and α-1 acid glycoprotein (p = 0.020) levels were observed after 5 days of oral supplementation. During radiochemotherapy, no significant variation of inflammatory markers was reported, and a low incidence of severe acute mucositis was noted.


Stage III or IV HNSCC patients are characterised by a pro-inflammatory, pro-angiogenic and pro-oxidative status. Nutritional support could improve this inflammatory state and could prevent severe acute mucositis.


Head and neck cancer Radiochemotherapy-induced toxicities Inflammation Immunonutrition 



The authors wish to thank M. Delage for her precious help, Biochemistry Lapeyronie’s technicians and Val d’Aurelle Cancer Institute’s dieticians. This work was supported in part by APARD and Novartis Consumer Health.

Conflict of interest

Nutritional support has been generously provided by Novartis France.


  1. 1.
    Argiris A, Karamouzis MV, Raben D, Ferris RL (2008) Head and neck cancer. Lancet 371:1695–1709PubMedCrossRefGoogle Scholar
  2. 2.
    IARC (2008) World cancer report 2008. International Agency for Research on Cancer, LyonGoogle Scholar
  3. 3.
    Pivot X, Felip E, On behalf of the ESMO Guidelines Working Group (2008) Squamous cell carcinoma of the head and neck: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 19(Suppl 2):ii79–ii80PubMedCrossRefGoogle Scholar
  4. 4.
    Cooper JS, Pajak TF, Forastiere AA, for the Radiation Therapy Oncology Group 9501/Intergroup et al (2004) Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 350:1937–1944PubMedCrossRefGoogle Scholar
  5. 5.
    Bernier J, Domenge C, Ozsahin M, for the European Organization for Research and Treatment of Cancer Trial 22931 et al (2004) Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350:1945–1952PubMedCrossRefGoogle Scholar
  6. 6.
    Trotti A, Byhardt R, Stetz J, for the Radiation Therapy Oncology Group et al (2000) Common toxicity criteria: version 2.0. An improved reference for grading the acute effects of cancer treatment: impact on radiotherapy. Int J Radiat Oncol Biol Phys 47(1):13–47PubMedCrossRefGoogle Scholar
  7. 7.
    Trotti A (2000) Toxicity in head and neck cancer: a review of trends and issues. Int J Radiat Oncol Biol Phys 47(1):1–12PubMedCrossRefGoogle Scholar
  8. 8.
    Langendijk JA, de Jong MA, Leemans CR et al (2002) Postoperative radiotherapy in squamous cell carcinoma of the oral cavity: the importance of the overall treatment time. Int J Radiat Oncol Biol Phys 54:229–236Google Scholar
  9. 9.
    Assenat E, Thezenas S, Flori N et al (2011) Prophylactic percutaneous endoscopic gastrostomy in patients with advanced head and neck tumors treated by combined chemoradiotherapy. J Pain Symptom Manage 42(4):548–556PubMedCrossRefGoogle Scholar
  10. 10.
    Braga M, Gianotti L, Radaelli G et al (1999) Perioperative immunonutrition in patients undergoing cancer surgery: results of a randomized double-blind phase 3 trial. Arch Surg 134:428–433PubMedCrossRefGoogle Scholar
  11. 11.
    Gianotti L, Braga M, Nespoli L, Radaelli G, Beneduce A, Di Carlo V (2002) A randomized controlled trial of preoperative oral supplementation with a specialized diet in patients with gastrointestinal cancer. Gastroenterology 122:1763–1770PubMedCrossRefGoogle Scholar
  12. 12.
    Stableforth WD, Thomas S, Lewis SJ (2009) A systematic review of the role of immunonutrition in patients undergoing surgery for head and neck cancer. Int J Oral Maxillofac Surg 38:103–110PubMedCrossRefGoogle Scholar
  13. 13.
    Paccagnella A, Morello M, Da Mosto MC et al (2010) Early nutritional intervention improves treatment tolerance and outcomes in head and neck cancer patients undergoing concurrent chemoradiotherapy. Support Care Cancer 18:837–845PubMedCrossRefGoogle Scholar
  14. 14.
    Kemen M, Senkal M, Homann HH et al (1995) Early postoperative enteral nutrition with arginine-omega-3 fatty acids and ribonucleic acid-supplemented diet versus placebo in cancer patients: an immunologic evaluation of Impact. Crit Care Med 23(4):652–659PubMedCrossRefGoogle Scholar
  15. 15.
    Weimann A, Bastian L, Bischoff et al (1998) Influence of arginine, omega-3 fatty acids and nucleotide-supplemented enteral support on systemic inflammatory response syndrome and multiple organ failure in patients after severe trauma. Nutrition 14(2):165–172PubMedCrossRefGoogle Scholar
  16. 16.
    Sorensen D, McCarthy M, Baumgartner B, Demars S (2009) Perioperative immunonutrition in head and neck cancer. Laryngoscope 119:1358–1364PubMedCrossRefGoogle Scholar
  17. 17.
    Portales F, Assenat E, Latournerie M et al (2008) Phase II clinical trial assessing the impact of an oral immunonutrition during concomitant chemoradiotherapy in advanced local-regional squamous cell carcinomas of the head and neck. J Clin Oncol 26(20 supp;abstract:9629)Google Scholar
  18. 18.
    Haute Autorité de Santé (2007) Recommandations professionnelles. Stratégie de prise en charge en cas de dénutrition protéino-énergétique chez la personne âgée. Avril 2007. Accessed 22 June 2011
  19. 19.
    Buzby GP, Knox LS, Crosby LO et al (1988) Study protocol: a randomized clinical trial of total parenteral nutrition in malnourished surgical patients. Am J Clin Nutr 47:366–381PubMedGoogle Scholar
  20. 20.
    Badiou S, Cristol JP, Jaussent I et al (2008) Fine-tuning of the prediction of mortality in hemodialysis patients by use of cytokine proteomic determination. Clin J Am Soc Nephrol 3(2):423–430PubMedCrossRefGoogle Scholar
  21. 21.
    Dupuy AM, Lehmann S, Cristol JP (2005) Protein biochip systems for the clinical laboratory. Clin Chem Lab Med 43(12):1291–1302PubMedGoogle Scholar
  22. 22.
    Mas E, Michel F, Guy A et al (2008) Quantification of urinary F2-isoprostanes with 4(RS)-F4t-neuroprostane as an internal standard using gas chromatography–mass spectrometry: application to polytraumatized patients. J Chrom B 872:133–140CrossRefGoogle Scholar
  23. 23.
    Monnier L, Mas E, Ginet C et al (2006) Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 295:1681–1687PubMedCrossRefGoogle Scholar
  24. 24.
    Wang F, Arun P, Friedman J, Chen Z, Van Waes C (2009) Current and potential inflammation targeted therapies in head and neck cancer. Curr Opin Pharmacol 9(4):389–395PubMedCrossRefGoogle Scholar
  25. 25.
    Woods RV, El-Naggar A, Clayman GL, Grimm E (1998) Variable expression of cytokines in human head and neck squamous cell carcinoma cell lines and consistent expression in surgical specimens. Cancer Res 58(14):3132–3141PubMedGoogle Scholar
  26. 26.
    Chen Z, Malhotra PS, Thomas GR et al (1999) Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer. Clin Cancer Res 5:1369–1379PubMedGoogle Scholar
  27. 27.
    Allin KH, Bojesen SE, Nordestgaard BG (2009) Baseline C-reactive protein is associated with incident cancer and survival in patients with cancer. J Clin Oncol 27(13):2217–2224PubMedCrossRefGoogle Scholar
  28. 28.
    Shang ZJ, Li JR, Li ZB (2002) Circulating levels of VEGF in patients with oral squamous cell carcinoma. Int J Oral Maxillofac Surg 31:495–498PubMedCrossRefGoogle Scholar
  29. 29.
    Prawan A, Buranrat B, Kukongviriyapan U, Sripa B, Kukongviriyapan V (2009) Inflammatory cytokines suppress NAD(P)H:quinone oxidoreductase-1 and induce oxidative stress in cholangiocarcinoma cells. J Cancer Res Clin Oncol 135(4):515–522PubMedCrossRefGoogle Scholar
  30. 30.
    Rasheed MH, Beevi SS, Geetha A (2007) Enhanced lipid peroxidation and nitric oxide products with deranged antioxidant status in patients with head and neck squamous cell carcinoma. Oral Oncol 43:333–338PubMedCrossRefGoogle Scholar
  31. 31.
    Nagini S, Manoharan S, Ramachandran CR (1998) Lipid peroxidation and antioxidants in oral squamous cell carcinoma. Clin Chim Acta 273:95–98PubMedCrossRefGoogle Scholar
  32. 32.
    Liu W, Morrow JD, Yin H (2009) Quantification of F2-isoprostanes as a reliable index of oxidative stress in vivo using gas chromatography–mass spectrometry (GC-MS) method. Free Radic Biol Med 47:1101–1107PubMedCrossRefGoogle Scholar
  33. 33.
    Dalaveris E, Kerenidi T, Katsabeki-Katsafli A et al (2009) VEGF, TNF-alpha and 8-isoprostane levels in exhaled breath condensate and serum of patients with lung cancer. Lung Cancer 64(2):219–225PubMedCrossRefGoogle Scholar
  34. 34.
    Rossner P, Gammon MD, Terry MB et al (2006) Relationship between urinary 15-F2t-isoprostane and 8-oxodeoxyguanosine levels and breast cancer risk. Cancer Epidemiol Biomarkers Prev 15(4):639–644PubMedCrossRefGoogle Scholar
  35. 35.
    Cengiz M, Akbulut S, Atahan IL, Grigsby PW (2001) Acute phase response during radiotherapy. Int Radiat Oncol Biol Phys 49(4):1093–1096CrossRefGoogle Scholar
  36. 36.
    Ki Y, Kim W, Nam J, Kim D, Park D, Kim D (2009) C-reactive protein levels and radiation-induced mucositis in patients with head and neck cancer. Int J Radiat Oncol Biol Phys 75(2):393–398PubMedCrossRefGoogle Scholar
  37. 37.
    De Luis DA, Arranz M, Aller R, Izaola O, Cuellar L, Terroba MC (2005) Immunoenhanced enteral nutrition, effect on inflammatory markers in head and neck cancer patients. EJCN 59:145–147PubMedGoogle Scholar
  38. 38.
    De Luis DA, Aller R, Izaola O, Cuellar L, Terroba MC (2002) Postsurgery enteral nutrition in head and neck cancer patients. EJCN 56:1126–1129PubMedGoogle Scholar
  39. 39.
    Riso S, Aluffi P, Brugnani M, Farinetti F, Pia F, D’Andrea F (2000) Postoperative enteral immunonutrition in head and neck cancer patients. Clin Nutr 19(6):407–412PubMedCrossRefGoogle Scholar
  40. 40.
    Snyderman CH, Kachman K, Molseed L et al (1999) Reduced postoperative infections with an immune-enhancing nutritional supplement. Laryngoscope 109(6):915–921PubMedCrossRefGoogle Scholar
  41. 41.
    Caparrós T, Lopez J, Grau T (2001) Early enteral nutrition in critically ill patients with a high-protein diet enriched with arginine, fiber, and antioxidants compared with a standard high-protein diet. The effect on nosocomial infections and outcome. J Parenter Enter Nut 25(6):299–308CrossRefGoogle Scholar
  42. 42.
    Bensadoun RJ, Le Page F, Darcourt V et al (2006) Mucite radio-induite des voies aérodigestives: prévention et prise en charge. Recommandations du groupe Mucites MASCC/ISOO. Bull Cancer 93(2):201–211PubMedGoogle Scholar
  43. 43.
    Meirovitz A, Kuten M, Billan S et al (2010) Cytokines levels, severity of acute mucositis and the need of PEG tube installation during chemo-radiation for head and neck cancer—a prospective pilot study. Radiat Oncol 5:16PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Christelle Machon
    • 1
  • Simon Thezenas
    • 2
  • Anne-Marie Dupuy
    • 1
  • Eric Assenat
    • 3
  • Françoise Michel
    • 1
  • Emilie Mas
    • 1
  • Pierre Senesse
    • 3
  • Jean-Paul Cristol
    • 1
  1. 1.Department of BiochemistryLapeyronie HospitalMontpellier Cedex 5France
  2. 2.Biostatistics UnitVal d’Aurelle Cancer InstituteMontpellierFrance
  3. 3.Department of Medical and Digestive OncologyVal d’Aurelle Cancer InstituteMontpellierFrance

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