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

Advances in Radiation Oncology (Nov 2022)

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

Affiliations

Chieko Michikawa, DDS, PhD: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
Pedro A. Torres-Saavedra, PhD: NRG Oncology Statistics and Data Management Center, American College of Radiology, Philadelphia, Pennsylvania
Natalie L. Silver, MD, MS: Cleveland Clinic, Head and Neck Institute/Lerner Research Institute, Cleveland, Ohio
Paul M. Harari, MD: Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Merrill S. Kies, MD: Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
David I. Rosenthal, MD: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Quynh-Thu Le, MD: Department of Radiation Oncology, Stanford University Medical Center, Stanford, California
Richard C. Jordan, DDS, PhD: NRG Oncology Biospecimen Bank and University of California, San Francisco, San Francisco, California
Dzifa Y. Duose, PhD: Department of Translational Molecular Pathology
Saradhi Mallampati, DVM, PhD: Department of Translational Molecular Pathology
Sanchit Trivedi, MS: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
Rajyalakshmi Luthra, PhD: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Ignacio I. Wistuba, MD: Department of Translational Molecular Pathology
Abdullah A. Osman, PhD: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
Olivier Lichtarge, MD, PhD: Departments of Molecular and Human Genetics, Pharmacology, and Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas
Robert L. Foote, MD: Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
Upendra Parvathaneni, MBBS: Radiation Oncology Center, University of Washington Medical Center, Seattle, Washington
D. Neil Hayes, MD, MPH: Division of Medical Oncology, The University of Tennessee Health Science Center, Memphis, Tennessee
Curtis R. Pickering, PhD: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
Jeffrey N. Myers, MD, PhD: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas; Corresponding author: Jeffrey N. Myers, MD, PhD

Journal volume & issue: Vol. 7, no. 6
p. 100989

Abstract

Read online

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.

Published in Advances in Radiation Oncology

ISSN: 2452-1094 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Medicine (General): Medical physics. Medical radiology. Nuclear medicine; Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.journals.elsevier.com/advances-in-radiation-oncology/

About the journal