Accelerated vs. conventionally fractionated adjuvant radiotherapy in high-risk head and neck cancer: a meta-analysis

Abstract

BackgroundAdjuvant radiotherapy in advanced head and neck squamous cell cancer (HNSCC) reduces the risk of local-regional failure and most likely increases the survival rate. Patients at high risk for tumor recurrence may benefit from more aggressive altered fractionation schedules in order to reduce the overall time from surgery to completion of radiotherapy. Here, we reviewed the results of six randomized trials addressing the above hypothesis.MethodsIn the six trials of interest, a total of 988 patients with locally advanced HNSCC were randomly assigned to receive either accelerated or conventionally fractionated adjuvant radiotherapy. Hazard ratios (HR) were extracted from available publications for local-regional control, distant metastasis as well as overall-, cancer specific- and disease-free survival. Meta-analysis of the effect sizes was performed using fixed and random effect models. Acute and late side effects were categorized and summarized for comparison.ResultsAccelerated radiotherapy did not improve the loco-regional control (n = 988, HR = 0.740, CI = 0.48–1.13, p = 0.162), progression-free survival (HR = 0.89, CI = 0.76–1.04, p = 0.132) or overall survival (HR = 0.88, CI = 0.75–1.04, p = 0.148) significantly. Acute confluent mucositis occurred with significant higher frequency with accelerated radiotherapy. Late side effects did not differ significantly in either group.ConclusionAccelerated radiotherapy does not result in a significant improvement of loco-regional control or overall survival in high-risk patients. Acute but not late radiation toxicity were more frequent with the accelerated RT technique. In clinical practice accelerated postoperative radiation therapy might be a suitable option only for a subset of patients.

Definitive chemoradiotherapy in patients with squamous cell cancers of the head and neck - results from an unselected cohort of the clinical cooperation group “Personalized Radiotherapy in Head and Neck Cancer”

“…Depending on tumor localization the absolute survival advantage is between four to 9 % [2]. Beyond that, additional induction chemotherapy prior to concurrent CRT or acceleration of radiotherapy did not improve outcome [11–13].…”

Systematic review of postoperative therapy for resected squamous cell carcinoma of the head and neck: Executive summary of the American Radium Society appropriate use criteria

“…An additional five eligible studies were added, including four that were published after the cut-off date of 01/10/2019 [15][16][17][18] and one randomized trial that was not identified through the literature search. 19 Studies with primary oncologic endpoints are shown in Table S1 and included 11 systematic reviews, [20][21][22][23][24][25][26][27][28][29][30] 24 randomized trials with four long-term updates, 19,31-57 29 nonrandomized clinical trials, [15][16][17][18] and nine post hoc analyses of randomized trials. [83][84][85][86][87][88][89][90][91] The randomized trials are presented in Table 4.…”

“…Single‐arm prospective 76,79,81 and randomized studies 23,24,51 demonstrated that altered fractionation increases acute toxicities, such as mucositis, dermatitis and feeding‐tube use during treatment. The effects on late toxicity have varied, but at least one study showed an increase in late toxicity 23,24,34 …”

Postoperative Combined Modality Treatment in High Risk Resected Locally Advanced Squamous Cell Carcinomas of the Head and Neck (HNSCC)

“…A Phase III study comparing accelerated versus fractionated postoperative radiotherapy for advanced head and neck cancer did show a trend for improved locoregional control for patients who had a delay in starting radiation, but otherwise no significant differences were seen between the control and experimental arms (30). One meta-analysis of six trials involving more than 900 patients with locally advanced HNSCC found that accelerated radiation therapy did not improve loco-regional control, progression-free survival, or overall survival (32). In fact, the meta-analysis found that accelerated radiation therapy schedules were associated with higher rates of acute mucositis.…”