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. 2021 Mar;23(3):543-553.
doi: 10.1007/s12094-020-02447-y. Epub 2020 Jul 15.

Decrease in treatment intensity predicts worse outcome in patients with locally advanced head and neck squamous cell carcinoma undergoing radiochemotherapy

S Mollnar  1 , P Pondorfer  2 , A-K Kasparek  1 , S Reinisch  2 , F Moik  1 , M Stotz  1 , M Halm  1 , J Szkandera  1 , A Terbuch  1 , F Eisner  1 , A Gerger  1   3 , K S Kapp  4 , R Partl  4 , S Vasicek  2 , T Weiland  2 , M Pichler  1   5   6 , H Stöger  1 , D Thurnher  2 , F Posch  7
Affiliations

Decrease in treatment intensity predicts worse outcome in patients with locally advanced head and neck squamous cell carcinoma undergoing radiochemotherapy

S Mollnar et al. Clin Transl Oncol. 2021 Mar.

Abstract

Purpose: Radiochemotherapy (RCT) is an effective standard therapy for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Nonetheless, toxicity is common, with patients often requiring dose modifications.

Methods: To investigate associations of RCT toxicities according to CTCAE version 5.0 and subsequent therapy modifications with short- and long-term treatment outcomes, we studied all 193 patients with HNSCC who received RCT (70 Gy + platinum agent) at an academic center between 03/2010 and 04/2018.

Results: During RCT, 77 (41%, 95% CI 34-49) patients developed at least one ≥ grade 3 toxicity, including seven grade 4 and 3 fatal grade 5 toxicities. The most frequent any-grade toxicities were xerostomia (n = 187), stomatitis (n = 181), dermatitis (n = 174), and leucopenia (n = 98). Eleven patients (6%) had their radiotherapy schedule modified (mean radiotherapy dose reduction = 12 Gy), and 120 patients (64%) had chemotherapy modifications (permanent discontinuation: n = 67, pause: n = 34, dose reduction: n = 7, change to other chemotherapy: n = 10). Objective response rates to RCT were 55% and 88% in patients with and without radiotherapy modifications (p = 0.003), and 84% and 88% in patients with and without chemotherapy modifications (p = 0.468), respectively. Five-year progression-free survival estimates were 20% and 50% in patients with and without radiotherapy modifications (p = < 0.001), and 53% and 40% in patients with and without chemotherapy modifications (p = 0.88), respectively.

Conclusions: Reductions of radiotherapy dose were associated with impaired long-term outcomes, whereas reductions in chemotherapy intensity were not. This suggests that toxicities during RCT should be primarily managed by modifying chemotherapy rather than radiotherapy.

Keywords: HNSCC; Radiochemotherapy; Toxicity; Treatment modification.

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Conflict of interest statement

All authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Kaplan–Meier Progression-free (PFS) and Overall Survival (OS) estimates according to concomitant radiotherapy schedule modifications. RTx Radiotherapy. Five-year PFS estimates from start of RCT were 20% and 50% in patients with and without radiotherapy modifications (p < 0.001) and 53% and 40% in patients with and without chemotherapy modifications (p = 0.88). Corresponding 5-year OS estimates were 12% and 53% in patients with and without radiotherapy modifications (p < 0.001), and 47% and 54% in patients with and without chemotherapy modifications (p = 0.19), respectively
Fig. 2
Fig. 2
Evolution of kidney function during radiochemotherapy. “Week 0” represents kidney function data immediately before treatment initiation. *p < 0.1, **p < 0.01, ***p < 0.001. eGFR Estimated Glomerular Filtration Rate. RCT was associated with a highly significant decline in kidney function. Median eGFR at baseline was 94.7 ml/min/1.73m2, 79.1 ml/min/1.73m2 after 9 weeks of treatment and did not fully recover over the first 12 weeks after treatment initiation
See this image and copyright information in PMC

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