Evolutionary Action Score of TP53 Analysis in Pathologically High-Risk HPV-Negative Head and Neck Cancer from a Phase II Clinical Trial: NRG Oncology RTOG 0234

ABSTRACT

PURPOSE

An evolutionary action scoring algorithm (EAp53) based on phylogenetic sequence variations stratifies head and neck squamous cell carcinoma (HNSCC) patients bearing TP53 missense mutations as high-risk, associated with poor outcomes, or low-risk, with similar outcomes as TP53 wild-type, and has been validated as a reliable prognostic marker. We performed this study to further validate prior findings demonstrating that EAp53 is a prognostic marker for locally advanced HNSCC patients, and explore its predictive value for treatment outcomes to adjuvant bio-chemoradiotherapy.

METHODS

Eighty-one resection samples from patients treated surgically for stage III or IV human papillomavirus-negative HNSCC with high-risk pathologic features, who received either radiotherapy+cetuximab+cisplatin (cisplatin) or radiotherapy+cetuximab+docetaxel (docetaxel), as adjuvant treatment in a phase II study were subjected to TP53 targeted sequencing and EAp53 scoring to correlate with clinical outcomes. Due to the limited sample size, patients were combined into two EAp53 groups: wild-type/low-risk and high-risk/other.

RESULTS

At a median follow-up of 9.8 years, there was a significant interaction between EAp53 group and treatment for overall survival (OS) (P =.008), disease-free survival (DFS) (P = .05) and distant metastasis (DM) (P = .004). In wild-type/low-risk group, the docetaxel arm showed significantly better OS [HR 0.11 (0.03-0.36)]. DFS [HR 0.24 (0.09-0.61)], and less DM [HR 0.04 (0.01-0.31)] than the cisplatin arm. In high-risk/other group, differences between treatments were not statistically significant.

CONCLUSION

The docetaxel arm was associated with better survival than the cisplatin arm for patients with wild-type/low-risk EAp53. These benefits appear to be largely driven by a reduction in DM.