Management of severe bio-radiation dermatitis induced by radiotherapy and cetuximab in patients with head and neck cancer: emphasizing the role of calcium alginate dressings

  • Pierluigi BonomoEmail author
  • Isacco Desideri
  • Mauro Loi
  • Lucia Pia Ciccone
  • Monica Lo Russo
  • Carlotta Becherini
  • Daniela Greto
  • Gabriele Simontacchi
  • Nicola Pimpinelli
  • Lorenzo Livi
Original Article



Severe bio-radiation dermatitis may develop in patients treated with concurrent radiotherapy and cetuximab for head and neck squamous cell carcinoma. The aim of our work was to report on the impact of a grade-specific management approach on treatment tolerability.


Concomitant radiotherapy and cetuximab was prescribed for patients deemed ineligible for cisplatin-based chemoradiation. Since 2014, an advanced wound care nursing team was established in our clinic to implement a standardized policy for skin toxicity. A central role of calcium alginate dressings was defined in our management algorithm. The correlation between patient, disease, and treatment features with severe bio-radiation dermatitis and treatment tolerability was evaluated.


Between 2007 and 2018, 51 patients were treated at our center with radiotherapy and cetuximab. The incidence of G3/G4 bio-radiation dermatitis was 43.1%. Comparing two consecutive cohorts of 26 and 25 patients treated before and after January 2014, respectively, the adoption of a grade-specific dermatitis management allowed to improve treatment tolerability. A mean radiation treatment interruption of 8.42 days (SD, 6.73; 95% CI 5.7–11.1) was reduced to 0.86 days (SD, 2.66; 95% CI − 0.28–2.02) in the more recent group (p < 0.0001). Mean relative dose intensity of cetuximab was also significantly higher (86.3% vs 74.5%, p = 0.0226).


Routine involvement of an advanced wound care management team and early consideration for calcium alginate dressings in case of moist desquamation should be warranted to ensure high compliance to radiotherapy and cetuximab in patients with head and neck cancer.


Head and neck cancer Radiotherapy Cetuximab Bio-radiation dermatitis Skin toxicity 



The authors wish to thank the advanced wound care nursing team (Mrs. Vincenza Capalbo, Beatrice Formigli, Flavia Picone, and Susanna Targioni) for the excellent work.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

The authors have full control of all primary data and agree to allow the journal to review the data if requested

Supplementary material

520_2018_4606_MOESM1_ESM.docx (20 kb)
Supplementary material : p value: differences reported according to cohort 2014-2018 vs cohort 2007-2013 (t test and log rank test) (DOCX 20 kb)


  1. 1.
    Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354:567–578. CrossRefPubMedGoogle Scholar
  2. 2.
    Bolderston A, Lloyd NS, Wong RKS, Holden L, Robb-Blenderman L, and the Supportive Care Guidelines Group of Cancer Care Ontario Program in Evidence-based Care (2006) The prevention and management of acute skin reactions related to radiation therapy: a systematic review and practice guideline. Support Care Cancer 14:802–817. CrossRefPubMedGoogle Scholar
  3. 3.
    Ferreira EB, Vasques CI, Gadia R, Chan RJ, Guerra ENS, Mezzomo LA, de Luca Canto G, dos Reis PED (2017) Topical interventions to prevent acute radiation dermatitis in head and neck cancer patients: a systematic review. Support Care Cancer 25:1001–1011. CrossRefPubMedGoogle Scholar
  4. 4.
    Gregoire V, De Neve W, Eisbruch A et al (2007) Intensity-modulated radiation therapy for head and neck carcinoma. Oncologist 12(5):555–564. CrossRefPubMedGoogle Scholar
  5. 5.
    Russi EG, Bensadoun RJ, Merlano MC, Bourhis J, Ricardi U, Giralt J, Pinto C, Budach W, Corvo R, Lacouture ME, Bernier J (2013) Bio-radiation dermatitis: the need of a new grading: in regard to Bernier et al. Ann Oncol 2011 22(10):2191–2200. Ann Oncol 24(9):2463–5. CrossRefGoogle Scholar
  6. 6.
    Pinto C, Barone CA, Girolomoni G, Russi EG, Merlano MC, Ferrari D, Maiello E (2016) Management of skin reactions during cetuximab treatment in association with chemotherapy or radiotherapy: update of the Italian expert recommendations. Am J Clin Oncol 39(4):407–415. CrossRefPubMedGoogle Scholar
  7. 7.
    Russi EG, Merlano MC, Numico G, Corvò R, Benasso M, Vigna-Taglianti R, Melano A, Denaro N, Pergolizzi S, Colantonio I, Lucio F, Brizio R, Ricardi U (2012) The effects on pain and activity of daily living caused by crusted exudation in patients with head and neck cancer treated with cetuximab and radiotherapy. Support Care Cancer 20(9):2141–2147. CrossRefPubMedGoogle Scholar
  8. 8.
    Eilers RE Jr, Gandhi M, Patel JD, Mulcahy MF, Agulnik M, Hensing T, Lacouture ME (2010) Dermatologic infections in cancer patients treated with epidermal growth factor receptor inhibitor therapy. J Natl Cancer Inst 102(1):47–53. CrossRefPubMedGoogle Scholar
  9. 9.
    Mirabile A, Numico G, Russi EG, Bossi P, Crippa F, Bacigalupo A, de Sanctis V, Musso S, Merlotti A, Ghi MG, Merlano MC, Licitra L, Moretto F, Denaro N, Caspiani O, Buglione M, Pergolizzi S, Cascio A, Bernier J, Raber-Durlacher J, Vermorken JB, Murphy B, Ranieri MV, Dellinger RP (2015) Sepsis in head and neck cancer patients treated with chemotherapy and radiation: literature review and consensus. Crit Rev Oncol Hematol 95(2):191–213. CrossRefPubMedGoogle Scholar
  10. 10.
    Budach W, Bölke E, Homey B (2007) Severe cutaneous reaction during radiation therapy with concurrent cetuximab. N Engl J Med 357(5):514–515CrossRefGoogle Scholar
  11. 11.
    Giro C, Berger B, Bölke E, Ciernik IF, Duprez F, Locati L, Maillard S, Ozsahin M, Pfeffer R, Robertson AG, Langendijk JA, Budach W (2009) High rate of severe radiation dermatitis during radiation therapy with concurrent cetuximab in head and neck cancer: results of a survey in EORTC institutes. Radiother Oncol 90:166–171. CrossRefPubMedGoogle Scholar
  12. 12.
    Pryor DI, Porceddu SV, Burmeister BH, Guminski A, Thomson DB, Shepherdson K, Poulsen M (2009) Enhanced toxicity with concurrent cetuximab and radiotherapy in head and neck cancer. Radiother Oncol 90:172–176. CrossRefPubMedGoogle Scholar
  13. 13.
    McKloskey SA, Jaggernauth W, Rigual NR et al (2009) Radiation treatment interruptions greater than one week and low hemoglobin levels (12 g/dL) are predictors of local regional failure after definitive concurrent chemotherapy and intensity-modulated radiation therapy for squamous cell carcinoma of the head and neck. Am J Clin Oncol 32(6):587–591. CrossRefGoogle Scholar
  14. 14.
    Bernier J, Bonner J, Vermorken JB, Bensadoun RJ, Dummer R, Giralt J, Kornek G, Hartley A, Mesia R, Robert C, Segaert S, Ang KK (2008) Consensus guidelines for the management of radiation dermatitis and coexisting acne-like rash in patients receiving radiotherapy plus EGFR inhibitors for the treatment of squamous cell carcinoma of the head and neck. Ann Oncol 19(1):142–149CrossRefGoogle Scholar
  15. 15.
    Bernier J, Russi EG, Homey B, Merlano MC, Mesía R, Peyrade F, Budach W (2011) Management of radiation dermatitis in patients receiving cetuximab and radiotherapy for locally advanced squamous cell carcinoma of the head and neck: proposals for a revised grading system and consensus management guidelines. Ann Oncol 22:2191–2200. CrossRefPubMedGoogle Scholar
  16. 16.
    Pinto C, Barone CA, Girolomoni G, Russi EG, Merlano MC, Ferrari D, Maiello E (2011) Management of skin toxicity associated with cetuximab treatment in combination with chemotherapy or radiotherapy. Oncologist 16(2):228–238. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Bonomo P, Loi M, Desideri I, Olmetto E, Delli Paoli C, Terziani F, Greto D, Mangoni M, Scoccianti S, Simontacchi G, Francolini G, Meattini I, Caini S, Livi L (2017) Incidence of skin toxicity in squamous cell carcinoma of the head and neck treated with radiotherapy and cetuximab: a systematic review. Crit Rev Oncol Hematol 120:98–110. CrossRefPubMedGoogle Scholar
  18. 18.
    Deutsch C, Edwards D, Myers S (2017) Wound dressings. Br J Hosp Med 78:C103–C109. CrossRefGoogle Scholar
  19. 19.
    NCCN guidelines: Head and Neck Cancers, version 1. 2018. Available at:
  20. 20.
    National Cancer Institute (2009). Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. 2009 May. Available at:
  21. 21.
    Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373–383CrossRefGoogle Scholar
  22. 22.
    Tao Y, Auperin A, Sire C et al (2017) Multicenter Randomized Double-Blind, Placebo-Controlled Trial GORTEC (Groupe Oncologie Radiotherapie Tete et Cou) 2009-01 Evaluating the Effect of the Regenerating Agent on Radiodermatitis of Head and Neck Cancer Patients. Int J Radiat Oncol Biol Phys 99:590–595. CrossRefPubMedGoogle Scholar
  23. 23.
    Iacovelli NA, Galaverni M, Cavallo A et al (2018) Prevention and treatment of radiation-induced acute dermatitis in head and neck cancer patients: A systematic review. Futur Oncol 14.
  24. 24.
    Macmillan MS, Wells M, MacBride S et al (2007) Randomized Comparison of Dry Dressings Versus Hydrogel in Management of Radiation-Induced Moist Desquamation. Int J Radiat Oncol Biol Phys 68:864–872. CrossRefPubMedGoogle Scholar
  25. 25.
    Herst P, Bennet N, Sutherland A et al (2014) Prophylactic use of mepitel film completely prevents radiation-induced moist desquamation in an intra-patient controlled RCT of 78 breast cancer patients in New Zealand. Radiother Oncol 110:137–143CrossRefGoogle Scholar
  26. 26.
    Wooding H, Yan J, Yuan L et al (2018) The effect of mepitel film on acute radiation-induced skin reactions in head and neck cancer patients: A feasibility study. Br J Radiol 91.
  27. 27.
    Narvaez C, Doemer C, Idel C et al (2018) Radiotherapy related skin toxicity (RAREST-01): Mepitel® film versus standard care in patients with locally advanced head-and-neck cancer. BMC Cancer 18:1–5. CrossRefGoogle Scholar
  28. 28.
    Pastore S, Mascia F, Mariani V, Girolomoni G (2008) The epidermal growth factor receptor system in skin repair and inflammation. J Invest Dermatol 128:1365–1374. CrossRefPubMedGoogle Scholar
  29. 29.
    Harris R, Probst H, Beardmore C et al (2012) Radiotherapy skin care: A survey of practice in the UK. Radiography 18:21–27. CrossRefGoogle Scholar
  30. 30.
    Tischer B, Huber R, Kraemer M, Lacouture ME (2017) Dermatologic events from EGFR inhibitors: the issue of the missing patient voice. Support Care Cancer 25:651–660. CrossRefPubMedGoogle Scholar
  31. 31.
    Tischer B, Bilang M, Kraemer M et al (2018) A survey of patient and physician acceptance of skin toxicities from anti-epidermal growth factor receptor therapies. Support Care Cancer 26:1169–1179. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Pierluigi Bonomo
    • 1
    Email author
  • Isacco Desideri
    • 1
  • Mauro Loi
    • 1
  • Lucia Pia Ciccone
    • 1
  • Monica Lo Russo
    • 1
  • Carlotta Becherini
    • 1
  • Daniela Greto
    • 1
  • Gabriele Simontacchi
    • 1
  • Nicola Pimpinelli
    • 2
  • Lorenzo Livi
    • 1
  1. 1.Radiation OncologyAzienda Ospedaliero – Universitaria Careggi, University of FlorenceFlorenceItaly
  2. 2.Division Dermatology, Department Surgery and Translational MedicineUniversity of FlorenceFlorenceItaly

Personalised recommendations