Advertisement

A Prospective Phase 2 Trial of Reirradiation With Stereotactic Body Radiation Therapy Plus Cetuximab in Patients With Previously Irradiated Recurrent Squamous Cell Carcinoma of the Head and Neck

      Purpose

      Salvage options for unresectable locally recurrent, previously irradiated squamous cell carcinoma of the head and neck (rSCCHN) are limited. Although the addition of reirradiation may improve outcomes compared to chemotherapy alone, significant toxicities limit salvage reirradiation strategies, leading to suboptimal outcomes. We therefore designed a phase 2 protocol to evaluate the efficacy of stereotactic body radiation therapy (SBRT) plus cetuximab for rSCCHN.

      Methods and Materials

      From July 2007 to March 2013, 50 patients >18 years of age with inoperable locoregionally confined rSCCHN within a previously irradiated field receiving ≥60 Gy, with a Zubrod performance status of 0 to 2, and normal hepatic and renal function were enrolled. Patients received concurrent cetuximab (400 mg/m2 on day −7 and then 250 mg/m2 on days 0 and +8) plus SBRT (40-44 Gy in 5 fractions on alternating days over 1-2 weeks). Primary endpoints were 1-year locoregional progression-free survival and National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 graded toxicity.

      Results

      Median follow-up for surviving patients was 18 months (range: 10-70). The 1-year local PFS rate was 60% (95% confidence interval [CI]: 44%-75%), locoregional PFS was 37% (95% CI: 23%-53%), distant PFS was 71% (95% CI: 54%-85%), and PFS was 33% (95% CI: 20%-49%). The median overall survival was 10 months (95% CI: 7-16), with a 1-year overall survival of 40% (95% CI: 26%-54%). At last follow-up, 69% died of disease, 4% died with disease, 15% died without progression, 10% were alive without progression, and 2% were alive with progression. Acute and late grade 3 toxicity was observed in 6% of patients respectively.

      Conclusions

      SBRT with concurrent cetuximab appears to be a safe salvage treatment for rSCCHN of short overall treatment time.
      To read this article in full you will need to make a payment
      ASTRO Member Login
      ASTRO Members, full access to the journal is a member benefit. Use your society credentials to access all journal content and features.
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Forastiere A.A.
        • Goepfert H.
        • Maor M.
        • et al.
        Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer.
        N Engl J Med. 2003; 349: 2091-2098
        • Cooper J.S.
        • Pajak T.F.
        • Forastiere A.A.
        • et al.
        Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck.
        N Engl J Med. 2004; 350: 1937-1944
        • Fakhry C.
        • Zhang Q.
        • Nguyen-Tan P.F.
        • et al.
        Human papillomavirus and overall survival after progression of oropharyngeal squamous cell carcinoma [e-pub ahead of print].
        J Clin Oncol. 2014; 32: 3365-3373
        • Cooper J.S.
        • Pajak T.F.
        • Rubin P.
        • et al.
        Second malignancies in patients who have head and neck cancer: Incidence, effect on survival and implications based on the RTOG experience.
        Int J Radiat Oncol Biol Phys. 1989; 17: 449-456
        • Coatesworth A.P.
        • Tsikoudas A.
        • MacLennan K.
        The cause of death in patients with head and neck squamous cell carcinoma.
        J Laryngol Otol. 2002; 116: 269-271
        • McDonald M.W.
        • Lawson J.
        • Garg M.K.
        • et al.
        ACR appropriateness criteria retreatment of recurrent head and neck cancer after prior definitive radiation.
        Int J Radiat Oncol Biol Phys. 2011; 80: 1292-1298
        • Clavel M.
        • Vermorken J.B.
        • Cognetti F.
        • et al.
        Randomized comparison of cisplatin, methotrexate, bleomycin and vincristine (CABO) versus cisplatin and 5-fluorouracil (CF) versus cisplatin (C) in recurrent or metastatic squamous cell carcinoma of the head and neck: A phase III study of the EORTC Head and Neck Cancer Cooperative Group.
        Ann Oncol. 1994; 5: 521-526
        • Argiris A.
        • Li Y.
        • Forastiere A.
        • et al.
        Prognostic factors and long-term survivorship in patients with recurrent or metastatic carcinoma of the head and neck.
        Cancer. 2004; 101: 2222-2229
        • Spencer S.A.
        • Harris J.
        • Wheeler R.H.
        • et al.
        Final report of RTOG 9610, a multi-institutional trial of re-irradiation and chemotherapy for unresectable recurrence squamous cell carcinoma of the head and neck.
        Head Neck. 2008; 30: 281-288
        • Langer C.J.
        • Harris J.
        • Horwitz E.M.
        • et al.
        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 RT oncology group protocol 9911.
        J Clin Oncol. 2007; 25: 4800-4805
        • Sulman E.P.
        • Schwartz D.L.
        • Le T.T.
        • et al.
        IMRT reirradiation of head and neck cancer—Disease control and morbidity outcomes.
        Int J Radiat Oncol Biol Phys. 2009; 73: 399-409
        • Salama J.K.
        • Vokes E.E.
        • Chmura S.J.
        • et al.
        Long-term outcome of concurrent chemotherapy and reirradiation for recurrent and second primary head and neck squamous cell carcinoma.
        Int J Radiat Oncol Biol Phys. 2006; 64: 382-391
        • Heron D.E.
        • Ferris R.L.
        • Karmouzis M.
        • et al.
        Stereotactic body radiotherapy for recurrent squamous cell carcinoma of the head and neck: Results of a phase I dose-escalation trial.
        Int J Radiat Oncol Biol Phys. 2009; 75: 1493-1500
        • Vermorken J.B.
        • Mesia R.
        • Rivera F.
        • et al.
        Platinum-based chemotherapy plus cetuximab in head and neck cancer.
        N Engl J Med. 2008; 359: 1116-1127
        • Bonner J.A.
        • Harari P.M.
        • Giralt J.
        • et al.
        Radiotherapy plus cetuximab for squamous-cell carcinoma of head and neck.
        N Engl J Med. 2006; 354: 567-578
        • Heron D.E.
        • Rwigema J.C.
        • Gibson M.K.
        • et al.
        Concurrent cetuximab with stereotactic body radiotherapy for recurrent squamous cell carcinoma of the head and neck: a single institution matched case-control study.
        Am J Clin Oncol. 2011; 34: 165-172
        • Wang K.
        • Heron D.E.
        • Clump D.A.
        • et al.
        Target delineation in stereotactic body radiation therapy for recurrent head and neck cancer: a retrospective analysis of the impact of margins and automated PET-CT segmentation.
        Radiother Oncol. 2013; 106: 90-95
        • Rwigema J.C.
        • Heron D.E.
        • Ferris R.L.
        • et al.
        The impact of tumor volume and radiotherapy dose on outcome in previously irradiated recurrent squamous cell carcinoma of the head and neck treated with stereotactic body radiation therapy.
        Am J Clin Oncol. 2011; 34: 372-379
        • Weymuller E.A.
        • Alsarraf R.
        • Yueh B.
        • et al.
        Analysis of the performance characteristics of the University of Washington Quality of Life instrument and its modification (UW-QOL-R).
        Arch Otolaryngol Head Neck Surg. 2001; 127: 489-493
        • Warren S.
        • Gates O.
        Multiple primary malignant tumors. A survey of the literature and a statistical study.
        Am J Cancer. 1932; 16: 1358-1414
        • Lartigau E.F.
        • Tresch E.
        • Thariat J.
        • et al.
        Multi institutional phase II study of concomitant stereotactic reirradiation and cetuximab for recurrent head and neck cancer.
        Radiother Oncol. 2013; 109: 281-285
        • Vargo J.A.
        • Heron D.E.
        • Ferris R.L.
        • et al.
        Prospective evaluation of patient-reported quality-of-life outcomes following SBRT ± cetuximab for locally-recurrent, previously-irradiated head and neck cancer.
        Radiother Oncol. 2012; 104: 91-95
        • Zwicker F.
        • Roeder F.
        • Thieke C.
        • et al.
        IMRT reirradiation with concurrent cetuximab immunotherapy in recurrent head and neck cancer.
        Strahlenther Onkol. 2011; 187: 32-38
        • Balermpas P.
        • Keller C.
        • Hambek M.
        • et al.
        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. 2012; 83: e377-383
        • Duprez F.
        • Mandani I.
        • Bonte K.
        • et al.
        High-dose reirradiation with intensity-modulated radiotherapy for recurrent head and neck cancer: Disease control, survival and toxicity.
        Radiother Oncol. 2014; 111: 388-392
        • Roh K.W.
        • Jang J.S.
        • Kim M.S.
        • et al.
        Fractionated stereotactic radiotherapy as reirradiation for locally recurrent head and neck cancer.
        Int J Radiat Oncol Biol Phys. 2009; 74: 1348-1355
        • Cengiz M.
        • Ozyigit G.
        • Yazici G.
        • et al.
        Salvage reirradiation with stereotactic body radiotherapy for locally recurrent head and neck tumors.
        Int J Radiat Oncol Biol Phys. 2011; 81: 104-109
        • Comet B.
        • Kramar A.
        • Faivre-Pierret M.
        • et al.
        Salvage stereotactic reirradiation with or without cetuximab for locally recurrent head and neck cancer: A feasibility study.
        Int J Radiat Oncol Biol Phys. 2012; 84: 203-209
        • Yazici G.
        • Snli T.Y.
        • Cengiz M.
        • et al.
        A simple strategy to decrease fatal carotid blowout syndrome after stereotactic body reirradiation for recurrent head and neck cancers.
        Radiat Oncol. 2013; 8: 242
        • Vargo J.A.
        • Heron D.E.
        • Ferris R.L.
        • et al.
        Examining tumor control and toxicity after stereotactic body radiotherapy in locally recurrent previously irradiated head and neck cancers: Implications of treatment duration and tumor volume.
        Head Neck. 2014; 36: 1349-1355
        • Yamazaki H.
        • Ogita M.
        • Kodani N.
        • et al.
        Frequency, outcome and prognostic factors of carotid blowout syndrome after hypofractionated reirradiation of head and neck cancer using CyberKnife: A multi-institutional study.
        Radiother Oncol. 2013; 107: 305-309
        • Popovtzer A.
        • Gluck I.
        • Chepeha D.B.
        • et al.
        The pattern of failure after reirradiation of recurrent squamous cell head and neck cancer: Implications for defining the targets.
        Int J Radiat Oncol Biol Phys. 2009; 74: 1342-1347
        • Rusthoven K.E.
        • Feigenberg S.J.
        • Raben D.
        • et al.
        Initial results of a Phase I dose-escalation trial of concurrent and maintenance erlotinib and reirradiation for recurrent and new primary head and neck cancer.
        Int J Radiat Oncol Biol Phys. 2010; 15: 1020-1025
        • Seiwert T.Y.
        • Darga T.
        • Haraf D.
        • et al.
        A phase I dose escalation study of Ad GV.EGR.TNF.11D (TNFerade biologic) with concurrent chemoradiotherapy in patients with recurrent head and neck cancer undergoing reirradiation.
        Ann Oncol. 2013; 24: 769-776

      Comments

      Commenting Guidelines

      To submit a comment for a journal article, please use the space above and note the following:

      • We will review submitted comments as soon as possible, striving for within two business days.
      • This forum is intended for constructive dialogue. Comments that are commercial or promotional in nature, pertain to specific medical cases, are not relevant to the article for which they have been submitted, or are otherwise inappropriate will not be posted.
      • We require that commenters identify themselves with names and affiliations.
      • Comments must be in compliance with our Terms & Conditions.
      • Comments are not peer-reviewed.