Cochlea sparing optimized radiotherapy for nasopharyngeal carcinoma

Abstract

Background: Definitive chemoradiotherapy (CRT) is standard of care for nasopharyngeal carcinoma. Due to the tumor localization and concomitant platinum-based chemotherapy, hearing impairment is a frequent complication, without defined dose-threshold. In this study, we aimed to achieve the maximum possible cochleae sparing.

Materials and methods: Treatment plans of 20 patients, treated with CRT (6 IMRT and 14 VMAT) based on the QUANTEC organs-at-risk constraints were investigated. The cochleae were re-delineated independently by two radiation oncologists, whereas target volumes and other organs at risk (OARs) were not changed. The initial plans, aiming to a mean cochlea dose < 45 Gy, were re-optimized with VMAT, using 2-2.5 arcs without compromising the dose coverage of the target volume. Mean cochlea dose, PTV coverage, Homogeneity Index, Conformity Index and dose to other OAR were compared to the reference plans. Wilcoxon signed-rank test was used to evaluate differences, a p value < 0.05 was considered significant.

Results: The re-optimized plans achieved a statistically significant lower dose for both cochleae (median dose for left and right 14.97 Gy and 18.47 Gy vs. 24.09 Gy and 26.05 Gy respectively, p < 0.001) compared to the reference plans, without compromising other plan quality parameters. The median NTCP for tinnitus of the most exposed sites was 11.3% (range 3.52-91.1%) for the original plans, compared to 4.60% (range 1.46-90.1%) for the re-optimized plans (p < 0.001). For hearing loss, the median NTCP of the most exposed sites could be improved from 0.03% (range 0-99.0%) to 0.00% (range 0-98.5%, p < 0.001).

Conclusions: A significantly improved cochlea sparing beyond current QUANTEC constraints is feasible without compromising the PTV dose coverage in nasopharyngeal carcinoma patients treated with VMAT. As there appears to be no threshold for hearing toxicity after CRT, this should be considered for future treatment planning.

Keywords: Chemoradiotherapy; Cochlea sparing; Late toxicity; Nasopharyngeal carcinoma; VMAT.

Fig. 1

Exemplary comparison between original (a, c) and re-optimized plan (b, d)

Fig. 2

Boxplots for the cochlear mean and max doses of the original and optimized plans. Red lines indicate the patients that were originally planned with IMRT (n = 6). Stars indicate significance. ***p ≤ 0.001, ****p ≤ 0.0001

Fig. 3

Boxplots for the PTV dose parameters of the original and optimized plans. Red lines indicate the patients that were originally planned with IMRT (n = 6). Stars indicate significance. NS non-significant, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001