Evolutionary Action Score of TP53 Analysis in Pathologically High-Risk Human Papillomavirus-Negative Head and Neck Cancer From a Phase 2 Clinical Trial: NRG Oncology Radiation Therapy Oncology Group 0234

Chieko Michikawa; Pedro A Torres-Saavedra; Natalie L Silver; Paul M Harari; Merrill S Kies; David I Rosenthal; Quynh-Thu Le; Richard C Jordan; Dzifa Y Duose; Saradhi Mallampati; Sanchit Trivedi; Rajyalakshmi Luthra; Ignacio I Wistuba; Abdullah A Osman; Olivier Lichtarge; Robert L Foote; Upendra Parvathaneni; D Neil Hayes; Curtis R Pickering; Jeffrey N Myers

doi:10.1016/j.adro.2022.100989

Evolutionary Action Score of TP53 Analysis in Pathologically High-Risk Human Papillomavirus-Negative Head and Neck Cancer From a Phase 2 Clinical Trial: NRG Oncology Radiation Therapy Oncology Group 0234

Adv Radiat Oncol. 2022 May 18;7(6):100989. doi: 10.1016/j.adro.2022.100989. eCollection 2022 Nov-Dec.

Authors

Chieko Michikawa^{1

2}, Pedro A Torres-Saavedra³, Natalie L Silver⁴, Paul M Harari⁵, Merrill S Kies⁶, David I Rosenthal⁷, Quynh-Thu Le⁸, Richard C Jordan⁹, Dzifa Y Duose¹⁰, Saradhi Mallampati¹⁰, Sanchit Trivedi¹, Rajyalakshmi Luthra¹¹, Ignacio I Wistuba¹⁰, Abdullah A Osman¹, Olivier Lichtarge¹², Robert L Foote¹³, Upendra Parvathaneni¹⁴, D Neil Hayes¹⁵, Curtis R Pickering¹, Jeffrey N Myers¹

Affiliations

¹ Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
² Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
³ NRG Oncology Statistics and Data Management Center, American College of Radiology, Philadelphia, Pennsylvania.
⁴ Cleveland Clinic, Head and Neck Institute/Lerner Research Institute, Cleveland, Ohio.
⁵ Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
⁶ Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
⁷ Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
⁸ Department of Radiation Oncology, Stanford University Medical Center, Stanford, California.
⁹ NRG Oncology Biospecimen Bank and University of California, San Francisco, San Francisco, California.
¹⁰ Department of Translational Molecular Pathology.
¹¹ Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
¹² Departments of Molecular and Human Genetics, Pharmacology, and Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas.
¹³ Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
¹⁴ Radiation Oncology Center, University of Washington Medical Center, Seattle, Washington.
¹⁵ Division of Medical Oncology, The University of Tennessee Health Science Center, Memphis, Tennessee.

Abstract

Purpose: An evolutionary action scoring algorithm (EAp53) based on phylogenetic sequence variations stratifies patients with head and neck squamous cell carcinoma (HNSCC) 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 patients with locally advanced HNSCC and explored its predictive value for treatment outcomes to adjuvant bio-chemoradiotherapy.

Methods and materials: 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 radiation therapy + cetuximab + cisplatin (cisplatin) or radiation therapy + cetuximab + docetaxel (docetaxel) as adjuvant treatment in a phase 2 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 2 EAp53 groups: (1) wild-type or low-risk; and (2) high-risk or other.

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

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

Abstract

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