Salvage Stereotactic Reirradiation With or Without Cetuximab for Locally Recurrent Head-and-Neck Cancer: A Feasibility Study

Purpose

Normal tissues tolerance limits the use of reirradiation for recurrent head-and-neck cancers (HNC). Stereotactic body radiotherapy (SBRT) could offer precise irradiation while sparing healthy tissues. Results of a feasibility study using SBRT with or without cetuximab are reported for reirradiation of recurrent primary HNC.

Methods and Materials

Patients with inoperable recurrent, or new primary tumor, in a previously irradiated area were included. Reirradiation dose was 36 Gy in six fractions of 6 Gy to the 85% isodose line covering 95% of the planning target volume. Patients with squamous cell carcinoma received concomitant cetuximab.

Results

Between June 2007 and January 2010, 40 patients were prospectively treated for 43 lesions. Median age was 60 and median tumor size was 29 mm. Fifteen patients received concomitant cetuximab and 1 received concomitant cisplatin. Median follow-up was 25.6 months with 34 patients evaluable for tumor response. Median overall survival was 13.6 months and response rate was 79.4% (15 complete and 12 partial responses). Grade 3 toxicity occurred in 4 patients.

Conclusion

These results suggest that short SBRT with or without cetuximab is an effective salvage treatment with good response rate in this poor prognosis population with previously irradiated HNC. Treatment is feasible and, with appropriate care to limiting critical structure, acute toxicities are acceptable. A prospective multicenter Phase II trial of SRT and concomitant cetuximab in recurrent HNC squamous cell carcinoma is ongoing.

Introduction

Treatment of advanced, Stage III–IV, head-and-neck cancers (HNC) usually involves a combination of surgery, chemotherapy, and radiotherapy. Yet nearly 50% of patients present with a local relapse or second primary in previously irradiated tissues 1, 2, 3, 4. For these patients, surgery remains the treatment of choice 5, 6, but is very often difficult to perform with curative intent (<15% of patients). Consequently, these patients receive palliative treatment such as best possible supportive care or chemotherapy, resulting in a median survival time of less than 1 year. Reirradiation is another option, but the applicability of curative-intent reirradiation has been limited by the dose tolerance of nearby critical structures (e.g., bone, spinal cord). Developments in the field of radiation oncology, such as three-dimensional treatment planning and intensity-modulated radiation therapy, now make it possible to reirradiate these patients with limited toxicity and greater precision. However, these treatments are mostly delivered with conventional fractionation schedules (2 Gy/fraction) resulting in long overall treatment times and, in some cases, ethical issues for these patients with limited life expectancy.

Stereotactic body radiotherapy (SBRT) is an attractive treatment modality for HNC reirradiation because it is delivered with a very high precision. One potential advantage with SBRT is the ability to deliver the dose with multiple small beams (>150 per treatment) with good skin tolerance and smaller irradiated volumes, and may allow the use of a hypofractionated scheme. Even if there is no demonstrated biological advantage using hypofractionation in recurrent HNC, there is a major clinical advantage in keeping the overall treatment time short in a population with a poor clinical prognosis. Altogether, we considered that the combination of precision, small irradiated volumes with multiple small beans, and short overall treatment time might significantly increase the therapeutic ratio (local control/morbidity) in this patient population.

Another consideration in the treatment of recurrent HNC is the use of combined chemotherapy and radiotherapy. Recently, the role of targeted therapies has been demonstrated in the treatment of advanced tumors combined with radiation or as a single treatment modality in the palliation of advanced recurrent or metastatic head-and-neck disease 7, 8. Furthermore, there is a strong preclinical background to consider the use of anti epidermal growth factor receptor molecules when treating tumors growing that are growing in already irradiated tissues (tumor bed effect) (9).

Combining radiation-based treatment with targeted therapies has the advantage of minimal acute toxicity, with the exception of an acceptable skin rash for patients with short life expectancy.

In 2007, a feasibility study using SRT reirradiation (combined with targeted therapy using cetuximab) was undertaken in 40 patients with the intent of offering a short, nontoxic, intensive treatment for local control of recurrent head-and-neck tumors.