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Reirradiation plus EGFR inhibition in locally recurrent and unresectable head and neck cancer

Final results from a single institution

Rebestrahlung und EGFR-Inhibition beim lokal rezidivierten, nichtresektablen Kopf-Hals-Karzinom

Abschließende Ergebnisse einer monozentrischen Studie

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Abstract

Purpose

For some patients with recurrent, unresectable, and previously irradiated head and neck squamous cell carcinoma (HNSCC), reirradiation (re-RT) may be a curative option. Chemotherapy with epidermal growth factor receptor (EGFR) inhibition is established as palliative management. This retrospective single-institutional study investigates feasibility, toxicity, and outcome of reirradiation (re-RT) combined with EGFR blockade for these patients.

Patients and methods

Between June 2008 and June 2012, 23 patients with inoperable and previously irradiated HNSCC were reirradiated. Concomitant EGFR blockade (cetuximab) was given initially at 400 mg/m2 two days prior to re-RT and weekly (250 mg/m2) thereafter. PET/CT imaging was fused with planning CT in 8 patients.

Results

One patient died of anaphylactic shock during the first cetuximab administration; two discontinued treatment on their own request. In all, 20 patients completed re-RT (50.4–66.6 Gy) and received cetuximab as prescribed. Grade 3 acute side effects were documented for dermatitis (35 %), dysphagia (30 %), acneiform rash (30 %), and mucositis (15 %). The 1-year overall survival rate was 34.8 %. Median overall and progression-free survival times were 9 and 4.3 months, respectively. A multivariable analysis using the Cox regression model showed significant positive impact of acneiform rash (hazard ratio [HR] 0.1531, 95 % confidence interval [CI] 0.0383–0.6111), while a period from first radiation to re-RT longer than 120 months negatively (HR 0.1633, 95 % CI 0.0305–0.8734) influenced patient survival.

Conclusion

re-RT with concurrent cetuximab was feasible. Compared to platinum-based chemotherapy with fluorouracil and cetuximab, this therapeutic approach did not demonstrate survival benefit. Prolonged intervals from first treatment to re-RT seem to be unfavorable.

Zusammenfassung

Hintergrund

Eine erneute Bestrahlung (Re-RT) kann für Patienten mit rezidiviertem, nichtresektablem Kopf-, Hals-Karzinom (HNSCC) eine kurative Option darstellen, während Chemotherapie und Inhibition des epidermalen Wachstumsfaktorrezeptors (EGFR) nur eine palliative Rolle spielen. Diese retrospektive und monozentrische Studie untersucht bei diesen Patienten die Durchführbarkeit, Toxizität und Effektivität einer Re-RT mit simultaner EGFR-Inhibition mit Cetuximab.

Methoden

Von Juni 2008 bis Juni 2012 wurden 23 nichtselektierte Patienten mit rezidiviertem, histologisch gesichertem und nichtresektablem, vorbestrahltem HNSCC erneut bestrahlt. Sie erhielten zusätzlich 2 Tage vor der Re-RT 400 mg/m2 Cetuximab (EGFR-Blockade), gefolgt von 6 wöchentlichen Gaben à 250 mg/m2. Bei 8 Patienten erfolgte die Bestrahlungsplanung aufgrund der PET/CT-Bildgebung.

Ergebnisse

Ein Patient verstarb an einem anaphylaktischen Schock nach der ersten Cetuximabgabe, zwei weitere brachen die Behandlung auf eigenen Wunsch ab. Insgesamt 20 Patienten wurden mit 59,4 Gy (50,4–66,6 Gy) und Cetuximab behandelt. Akute Grad-3-Nebenwirkungen wurden für Dermatitis (35 %), Dysphagie (30 %), akneiformes Exanthem (30 %) und Mukositis (15 %) beobachtet. Die 1-Jahres-Überlebensrate lag bei 34,8 %. Medianes und progressionsfreies Überleben betrugen 9 und 4,3 Monate. In der multivariaten Cox-Analyse waren akneiformes Exanthem positiv (Hazard Ratio [HR] 0,1531; 95 %-Konfidenzintervall [CI] 0,0383–0,6111) und mehr als 120 Monate zwischen erster und Re-RT negativ (HR 0,1633; 95 % CI 0,0305–0,8734) zum Überleben korreliert.

Schlussfolgerung

Eine Re-RT mit simultaner Cetuximabgabe ist bei Patienten mit rezidiviertem HNSCC durchführbar. Tumorkontrolle und Überleben entsprechen allerdings Berichten nach alleiniger Cisplatin-, 5-Fluorouracil- und Cetuximab-Gabe. Ein prolongiertes Intervall zwischen erster Bestrahlung und Re-RT erscheint eher ungünstig.

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References

  1. Adelstein DJ, Li Y, Adams GL et al (2003) An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol 21:92–98

    Article  PubMed  Google Scholar 

  2. Balermpas P, Keller C, Hambek M et al (2012) Reirradiation with cetuximab in locoregional recurrent and inoperable squamous cell carcinoma of the head and neck: feasibility and first efficacy results. Int J Radiat Oncol Biol Phys 83:377–383

    Article  Google Scholar 

  3. Baselga J (2001) The EGFR as a target for anticancer therapy-focus on cetuximab. Eur J Cancer 37(Suppl 4):S16–S22

    Article  PubMed  CAS  Google Scholar 

  4. Bernier J, Domenge C, Ozsahin M et al (2004) European Organization for Research and Treatment of Cancer Trial 22931. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350:1945–1952

    Article  PubMed  CAS  Google Scholar 

  5. Bonner JA, Harari PM, Giralt J et al (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354:567–578

    Article  PubMed  CAS  Google Scholar 

  6. Bonner JA, Raisch KP, Trummell HQ et al (2000) Enhanced apoptosis with combination C225/radiation treatment serves as the impetus for clinical investigation in head and neck cancers. J Clin Oncol 18:47S–53S

    PubMed  CAS  Google Scholar 

  7. Coatesworth AP, Tsikoudas A, MacLennan K (2002) The cause of death in patients with head and neck squamous cell carcinoma. J Laryngol Otol 116:269–271

    PubMed  CAS  Google Scholar 

  8. Comet B, Kramar A, Faivre-Pierret M et al (2012) Salvage stereotactic reirradiation with or without cetuximab for locally recurrent head-and-neck cancer: a feasibility study. Int J Radiat Oncol Biol Phys 84:203–209

    Article  PubMed  Google Scholar 

  9. Cooper JS, Zhang Q, Pajak TF et al (2012) Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 84:1198–1205

    Article  PubMed  Google Scholar 

  10. De Crevoisier R, Bourhis J, Domenge C et al (1998) Full-dose reirradiation for unresectable head and neck carcinoma: experience at the Gustave-Roussy Institute in a series of 169 patients. J Clin Oncol 16:3556–3562

    Google Scholar 

  11. Dittmann K, Mayer C, Fehrenbacher B et al (2005) Radiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase. J Biol Chem 280:31182–31189

    Article  PubMed  CAS  Google Scholar 

  12. Forastiere AA, Leong T, Rowinsky E et al (2001) Phase III comparison of high-dose paclitaxel + cisplatin + granulocyte colony-stimulating factor versus low-dose paclitaxel + cisplatin in advanced head and neck cancer: Eastern Cooperative Oncology Group Study E1393. J Clin Oncol 19:1088–1095

    PubMed  CAS  Google Scholar 

  13. Gibson MK, Li Y, Murphy B et al (2005) Eastern Cooperative Oncology Group. Randomized phase III evaluation of cisplatin plus fluorouracil versus cisplatin plus paclitaxel in advanced head and neck cancer (E1395): an intergroup trial of the Eastern Cooperative Oncology Group. J Clin Oncol 23:3562–3567

    Article  PubMed  CAS  Google Scholar 

  14. Haddad RI, Shin DM (2008) Recent advances in head and neck cancer. N Engl J Med 359:1143–1154

    Article  PubMed  CAS  Google Scholar 

  15. Harari PM, Huang SM (2001) Radiation response modification following molecular inhibition of epidermal growth factor receptor signaling. Semin Radiat Oncol 11:281–289

    Article  PubMed  CAS  Google Scholar 

  16. Hoebers F, Heemsbergen W, Moor S et al (2011) Reirradiation for head-and-neck cancer: delicate balance between effectiveness and toxicity. Int J Radiat Oncol Biol Phys 81:e111–e118

    Article  PubMed  Google Scholar 

  17. Jeremic B, Shibamoto Y, Milicic B et al (2000) Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. J Clin Oncol 18:1458–1464

    PubMed  CAS  Google Scholar 

  18. Jeremic B, Shibamato Y, Stanisavljevic B et al (1997) Radiation therapy alone or with concurrent low-dose daily either cisplatin or carboplatin in locally advanced unresectable squamous cell carcinoma of the head and neck: a prospective randomized trial. Radiother Oncol 43:29–37

    Article  PubMed  CAS  Google Scholar 

  19. Langer CJ, Harris J, Horwitz EM et al (2007) Phase II study of low-dose paclitaxel and cisplatin in combination with split-course concomitant twice-daily reirradiation in recurrent squamous cell carcinoma of the head and neck: results of Radiation Therapy Oncology Group Protocol 9911. J Clin Oncol 25:4800–4805

    Article  PubMed  CAS  Google Scholar 

  20. Leemans CR, Braakhuis BJ, Brakenhoff RH (2011) The molecular biology of head and neck cancer. Nat Rev Cancer 11:9–22

    Article  PubMed  CAS  Google Scholar 

  21. Licitra L, Störkel S, Kerr KM et al (2013) Predictive value of epidermal growth factor receptor expression for first-line chemotherapy plus cetuximab in patients with head and neck and colorectal cancer: analysis of data from the EXTREME and CRYSTAL studies. Eur J Cancer 49:1161–1168

    Article  PubMed  CAS  Google Scholar 

  22. Milanovic D, Jeremic B, Kayser G et al (2012) Relapsing high grade mucoepidermoid carcinoma. Long-lasting complete response following reirradiation and EGFR blockade. Strahlenther Onkol 188:518–522

    Article  PubMed  CAS  Google Scholar 

  23. Milas L, Fan Z, Andratschke NH, Ang KK (2004) Epidermal growth factor receptor and tumorresponse to radiation: in vivo preclinical studies. Int J Radiat Oncol Biol Phys 58:966–971

    Article  PubMed  CAS  Google Scholar 

  24. Petrelli F, Borgonovo K, Barni S (2013) The predictive role of skin rash with cetuximab and panitumumab in colorectal cancer patients: a systematic review and meta-analysis of published trials. Target Oncol

  25. Pignon JP, le Maître A, Maillard E, Bourhis J (2009) MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 92:4–14

    Article  PubMed  Google Scholar 

  26. R Development Core Team (2009) A language and environment for statistical computing. R Foundation for Statistical Computing. http://www.R-project.org ISBN 3-900051-07-0

  27. Salomon DS, Brandt R, Ciardiello F, Normanno N (1995) Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 19:183–232

    Article  PubMed  CAS  Google Scholar 

  28. Spencer SA, Harris J, Wheeler RH et al (2008) Final report of RTOG 9610, a multi-institutional trial of reirradiation and chemotherapy for unresectable recurrent squamous cell carcinoma of the head and neck. Head Neck 30:281–288

    Article  PubMed  Google Scholar 

  29. Trotti A, Colevas AD, Setser A et al (2003) CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 13:176–181

    Article  PubMed  Google Scholar 

  30. Tsuchihashi Z, Khambata-Ford S, Hanna N, Jänne PA (2005) Responsiveness to cetuximab without mutations in EGFR. N Engl J Med 353:208–209

    Article  PubMed  CAS  Google Scholar 

  31. Vermorken JB, Mesia R, Rivera F et al (2008) Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 359:1116–1127

    Article  PubMed  CAS  Google Scholar 

  32. Vormittag L, Lemaire C, Radonjic D et al (2012) Re-irradiation combined with capecitabine in locally recurrent squamous cell carcinoma of the head and neck. A prospective phase II trial. Strahlenther Onkol 188:235–242

    Article  PubMed  CAS  Google Scholar 

  33. Wong LY, Wei WI, Lam LK, Yuen AP (2003) Salvage of recurrent head and neck squamous cell carcinoma after primary curative surgery. Head Neck 25:953–959

    Article  PubMed  Google Scholar 

  34. Wong SJ, Machtay M, Li Y (2006) Locally recurrent, previously irradiated head and neck cancer: concurrent re-irradiation and chemotherapy, or chemotherapy alone? J Clin Oncol 24:2653–2658

    Article  PubMed  Google Scholar 

  35. Wong SJ, Bourhis J, Langer CJ (2012) Retreatment of recurrent head and neck cancer in a previously irradiated field. Semin Radiat Oncol 22:214–219

    Article  PubMed  Google Scholar 

  36. Zwicker F, Roeder F, Thieke C et al (2011) IMRT reirradiation with concurrent cetuximab immunotherapy in recurrent head and neck cancer. Strahlenther Onkol 187:32–38

    Article  PubMed  Google Scholar 

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Conflict of interest

On behalf of all authors, the corresponding author states that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Radiation Oncology, University Medical Center Freiburg, Robert Koch Str. 3, 79106, Freiburg, Germany

    D. Milanović M.D., A.L. Grosu M.D. & M. Henke M.D.

  2. Division of Radiation Oncology, University of Stellenbosch Medical School and Tygerberg, Hospital, Gene Louw Building, 7505, Cape Town, Republic of South Africa

    B. Jeremić M.D., Ph.D.

  3. Institute of Medical Biometry and Medical Informatics, University Medical Center Freiburg, Stefan-Meier-Str. 26, 79104, Freiburg, Germany

    G. Rücker Ph.D.

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  1. D. Milanović M.D.
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  2. B. Jeremić M.D., Ph.D.
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  3. A.L. Grosu M.D.
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Correspondence to D. Milanović M.D..

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Milanović, D., Jeremić, B., Grosu, A. et al. Reirradiation plus EGFR inhibition in locally recurrent and unresectable head and neck cancer. Strahlenther Onkol 189, 842–848 (2013). https://doi.org/10.1007/s00066-013-0402-6

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