Postoperative irradiation for squamous cell carcinoma of head and neck: Retrospective comparison of accelerated radiochemotherapy and standard radiotherapy

Background: Comparison of accelerated radiochemotherapy (aRCT) and standard radiotherapy (sRT) in postoperative treatment after macroscopically complete resection of squamous cell cancers of head and neck. Material and Methods: 229 patients treated within the same period had either (no randomization) postoperative radiotherapy with conventional fractionation (60-70 Gy, 2.0 Gy per day) or received 2 fractions of 2.1 Gy per day, 8 times/week, up to a total dose of 56.7 Gy with a treatment split after 2 weeks and simultaneous low dose cisplatin or carboplatin on treatment days (cumulative dose >66 mg/m² or 550 mg/m² in 83% of patients). Results: 65 patients completed their course of twice-daily irradiations within a maximum of 35 days and therefore had aRCT; their 3-year locoregional tumor control (Kaplan-Meier estimate) was 86%, whereas that of 42 patients with prolonged twice-daily radiochemotherapy was 65% (p=0.0509). After sRT, i.e. 1 fraction daily and treatment time up to 45 days, locoregional tumor control was 67%, this result being significantly inferior to that after aRCT (p=0.0282). In multivariate analysis, pN stage, tumor site oral cavity/floor of mouth, high/moderate differentiation of squamous cell carcinoma and conventional surgery (versus CO₂-laser surgery) were significantly predictive of locoregional failure. Whereas nodal status, the strongest prognostic factor, was evenly distributed among aRCT and sRT patients, there was a misbalance of 3 risk factors favoring the aRCT collective. Superior tumor control after aRCT was confirmed unilaterally for nearly each subgroup (significant for recurrent tumors, close margins, pN 1/2 a-b). For pN2c/pN3 nodal stage, the results after aRCT were by tendency worse than after sRT, possibly due to a particularly long interval between surgery and start of radio(chemo)therapy for the patients with aRCT (mean 58.0 days vs. 43.8 days, p =0.037). Among the total of patients the 3-year hazard for late toxicity III-IV was 31% after twice-daily treatment and 17% after conventionally fractionated radiotherapy (p=0.083). Conclusions: This retrospective analysis provides some evidence that accelerated radiotherapy with simultaneous chemotherapy is more potent than standard radiotherapy. However, as multivariate analysis misses significance and the influence of misbalance of some prognostic factors among aRCT and sRT patients remains unclear, only a randomized trial with stratification according to risk factors as well as a defined interval between surgery and initiation of RT can provide more evidence.