Randomized clinical trial on reduction of radiotherapy dose to the elective neck in head and neck squamous cell carcinoma; update of the long-term tumor outcome

Abstract

Background and purpose: A multicenter prospective randomized controlled trial was performed to investigate whether dose reduction to the elective nodal volume (PTVelect) in head and neck carcinoma reduces radiation-induced dysphagia, primary endpoint, without compromising tumor control, secondary endpoint. Here, we report on the long-term follow-up of the secondary endpoint (NCT01812486). Materials and methods: Two hundred patients treated with primary (chemo)radiotherapy (RT) were randomized (1:1) between the standard arm, irradiation to PTVelect up to an equivalent dose (EQD2) of 50 Gy and the experimental arm, irradiation to PTVelect up to EQD2 of 40 Gy. The primary tumor and involved nodes were treated according to the standard of care, EQD2 70 Gy (PTVhigh). Regional recurrences (RR) were projected on the initial RT planning-CT to identify the recurrence localization. Results: The 5-year (5Y) RR was 14.0% (CI95% 7.9; 21.8) in the 40 Gy arm versus 7.5% (CI95% 3.3; 14.0) in the 50 Gy arm (p = 0.10). Majority of RR in the 40 Gy arm (9/13) were projected in PTVhigh and 2 RR were seen outside the treated RT volume. Only 2 RR occurred in PTVelect irradiated up to 40 Gy which was the same number as RR occurring in the 50 Gy PTVelect.The 5Y-overall survival (OS) was 56.5% (CI95% 45.7; 65.9) in the 40 Gy arm versus 49.6% (CI95% 39.0; 59.2) in the 50 Gy arm (p = 0.56). Conclusion: At 5-years, no statistically significant differences regarding OS, local recurrence, RR nor distant metastases were observed between both treatment arms. This study is underpowered to undoubtedly demonstrate non-inferiority. However, since in both arms only two RR in the PTVelect were observed, reducing the dose to PTVelect appears safe and should be further investigated.

Contemporary management of the neck in nasopharyngeal carcinoma

“…Furthermore, in a randomized study consisting of 200 HNSCC patients comparing ENI of 40 Gy versus 50 Gy, no statistically significant differences in treatment outcome were observed. Although the study was underpowered to undoubtedly detect non‐inferiority, it appears safe to reduce the dose of ENI to subclinical disease 69 . This is in accordance with the fact that patients historically received 50 Gy in 25 fractions specified at the maximum dose ( D max ) to the low neck with Co‐60 and thus, the LNs received approximately 80%–85% of the given dose.…”

“…Clinical studies in HNSCC using lower ENI to the neck of less than 50 Gy have been reported 68,69 . Salama et al compared three different dose schemes of ENI (45, 39, and 36 Gy) in treating patients with head and neck cancer after induction chemotherapy in a multi‐institutional phase II trial and found that locoregional control and OS were not different among the groups 68 .…”

Prophylactic gastrostomy in locally advanced head and neck cancer: results of a national survey among radiation oncologists

“…Advanced tumour stage (T3-T4), oropharyngeal and nasopharyngeal tumour site, primary and bilateral neck irradiation, weight loss at baseline, and treatment modality (accelerated RT or CCRT) were identified as independent factors predicting swallowing dysfunction. In Belgium, such studies are focussing on reduction of the elective dose and on volume individualisation of the prophylactic nodal target irradiated zone using the identification of the sentinel node [ 33 , 35 ].…”

Prophylactic Gastrostomy in Locally Advanced Head and Neck Cancer: Results of A National Survey Among Radiation Oncologists

“…(25)(26)(27)(28)(29)(30)(31). Subsequently, several studies are currently focusing on reducing the elective radiation dose and the irradiated volume in order to decrease acute and late swallowing dysfunction (32)(33)(34)(35). Langendijk et al developed a predictive model to identify patients at high risk of radio-induced dysphagia (14).…”

“…Advanced tumour stage (T3-T4), oropharyngeal and nasopharyngeal tumour site, primary and bilateral neck irradiation, weight loss at baseline, and treatment modality (accelerated RT or CCRT) were identi ed as independent factors predicting swallowing dysfunction. In Belgium, such studies are focussing on reduction of the elective dose and on volume individualisation of the prophylactic nodal target irradiated zone using the identi cation of the sentinel node (33,35).…”