Radical radiation alone versus radical radiation plus microwave hyperthermia for N3 (TNM-UICC) neck nodes: a prospective randomized clinical trial.

Between September 1985 and December 1986, 44 N3 (TNM-UICC) metastatic squamous cell cervical lymph-nodes were randomized to receive conventionally fractionated radical irradiation (RT) to a total dose of 64-70 Gy, or conventionally fractionated radical irradiation plus twice a week local microwave hyperthermia (Ht). The two major end points of this study were (a) local control rates evaluated at 3 months after the end of combined therapy and (b) incidence of acute local toxicity. Thirty-six nodes (82%) were evaluable as of December 1986, at which time there was a premature closure of this study due to ethical reasons. An interim analysis had revealed a statistically significant difference in complete response rates in favor of the combined arm (p = 0.0152). The complete response rates were 82.3% (14/17) for the combined treatment arm versus 36.8% (7/19) for the control irradiation arm, leading to an iso-dose thermal enhancement ratio (TER) value of 2.23. Both arms are comparable in average total RT dose delivered (RT: 67.05 Gy; RT + Ht: 67.85 Gy) and in average maximum node diameter (RT arm: 4.81 cm; RT + Ht: 4.88 cm). Acute local toxicities were similar in irradiated and heated plus irradiated neck regions; only one skin burn was observed. As possible treatment related death, one patient in the RT + Ht arm died 2 months after completion of therapy with a carotid rupture associated with extensive tumor necrosis. These results confirm previous non-randomized reports suggesting that hyperthermia in combination with full dose conventionally fractionated irradiation significantly enhances the chance of early local control of fixed N3 neck nodes without exhibiting an increase of acute local toxicity.