Abstract
PurposeRadiochemotherapy (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.MethodsTo 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.ResultsDuring 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.ConclusionsReductions 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.
Highlights
MethodsPlatinum-based concomitant radiochemotherapy (RCT) is the current standard of care for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) [1]
The most frequent induction chemotherapy (ICT) regimen was docetaxel, cisplatin, and 5-fluorouracil [TPF, n = 62 (84%)], and the objective response rate (ORR) to ICT was 43% with only one patient developing progressive disease during ICT
Experiencing any ≥ G3 toxicity was not associated with worse ORR during ICT
Summary
MethodsPlatinum-based concomitant radiochemotherapy (RCT) is the current standard of care for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) [1]. Randomized controlled trials have shown that ICT leads to an increased risk of hematologic toxicity, especially neutropenia and leucopenia, with prolonged neutropenia often being responsible for treatment-associated delays [3, 4]. Randomized data suggest favorable effects of ICT on distant metastatic risk and organ preservation rates, but whether ICT + RCT consistently prolongs progression-free (PFS) and overall survival (OS) as compared to RCT alone is still debated [5, 6]. Optimal treatment indication for LA-HNSCC poses a clinical challenge for treating physicians who have to weigh potential oncologic benefits against increased toxicity. It can be hypothesized that a better understanding of acute ICT and RCT toxicities including their frequency, predictors and impact on long-term treatment outcome may allow physicians a refined treatment indication in this setting
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