Elsevier

Radiotherapy and Oncology

Volume 122, Issue 2, February 2017, Pages 171-177
Radiotherapy and Oncology

Phase III randomised trial
Reduction of the dose of radiotherapy to the elective neck in head and neck squamous cell carcinoma; a randomized clinical trial. Effect on late toxicity and tumor control

https://doi.org/10.1016/j.radonc.2016.08.009Get rights and content

Abstract

Background and purpose

A multi-center prospective randomized clinical trial has been performed investigating whether a reduction of the dose to the elective nodal sites in head and neck cancer delivered by intensity modulated radiotherapy (IMRT) would result in a reduction of late side effects without compromising tumor control.

Materials and methods

Two hundred patients were included. The prescription dose to the elective nodal volumes was a normalized iso-effective dose in 2 Gy fractions (NID2Gy) of 50 Gy in the standard arm and of 40 Gy in the experimental arm. Late toxicity was scored at 6, 12, 18 and 24 months using the RTOG scoring system.

Results

We observed a trend toward less dysphagia at 6 months in the experimental arm, however this was not confirmed after longitudinal analysis. Regarding moderate salivary gland toxicity we observed lower incidence of salivary gland toxicity ⩾grade 1, at 6 (p = 0.01) and 18 months (p = 0.03).

After two years of follow up, we did not observe significant differences in estimated local failure rate (14.1% in the 40 Gy arm vs 14.4% in the 50 Gy arm), estimated regional failure rate (13.0% vs 5.5% in the 40 and the 50 Gy arm respectively), estimated metastatic recurrence (13.4% vs 18.5% in the 40 and the 50 Gy arm respectively), estimated disease-free survival (57.9% vs 65.3% in the 40 and the 50 Gy arm respectively) nor estimated overall survival (72.0% vs 73.2% in the 40 and the 50 Gy arm respectively).

Conclusions

In our study population there was no statistically significant difference regarding survival and estimated recurrence rates between both arms of this study. We found a trend toward less dysphagia at 6 months (however not significant after longitudinal analysis) and found a significant reduction of any salivary gland toxicity at 6 and 18 months in the 40 Gy arm.

Section snippets

Material and methods

A prospective randomized multicenter non-inferiority phase III study was set up between 6 centers. Inclusion criteria were previously untreated, histologically proven squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, larynx or cervical lymph node metastases of unknown primary cancer (CUP). Patient work-up was done according to institutional guidelines. T1–T2N0 were allowed, if prophylactic neck irradiation was performed. Patients were older than 18 years with a Karnofsky

Patients

Between May 2008 and May 2011, 200 patients were included and randomized. Treatment characteristics of 7 patients could not be retrieved before close-out date of this analysis, yielding 193 patients for analysis (96 in the experimental arm and 97 in control arm). Patient characteristics are depicted in Table 1.

The study included 83 patients with an oropharyngeal tumor; 41 in the 40 Gy and 42 in the 50 Gy arm. 17 patients (20,5%) of these 83 patients had an HPV positive tumor; 60 patients (72,5%)

Discussion

In this paper we describe the late toxicity and outcome of a multicenter randomized controlled trial reducing the dose to the elective lymph nodes in patients treated for head and neck cancer.

The primary endpoint of this study was late dysphagia as this is the most important quality of life compromising toxicity after curative treatment of HNC [2]. Altered fractionation schedules, concomitant chemotherapy and oropharyngeal tumor location are associated with more dysphagia [6]. With the

Conclusions

Dose de-escalation to the elective nodal volume in HNC from a 50 to a 40 Gy-equivalent dose results in a trend toward less dysphagia at 6 months and less moderate salivary gland toxicity without significant differences in disease control or survival.

Conflict of interest

None of the authors has a conflict of interest in connection with the paper and the material is not under publication or consideration for publication elsewhere.

Acknowledgments

The project was funded by Kom Op Tegen Kanker. Study organization and data collection were performed by Rita Aerts.

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