| Autor: |
Michikawa, Chieko, Torres-Saavedra, Pedro A, Silver, Natalie L, Harari, Paul M, Kies, Merrill S, Rosenthal, David I, Le, Quynh-Thu, Jordan, Richard C, Duose, Dzifa Y, Mallampati, Saradhi, Trivedi, Sanchit, Luthra, Rajyalakshmi, Wistuba, Ignacio I, Osman, Abdullah A, Lichtarge, Olivier, Foote, Robert L, Parvathaneni, Upendra, Hayes, D Neil, Pickering, Curtis R, Myers, Jeffrey N |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Advances in radiation oncology, vol 7, iss 6 |
| Popis: |
PurposeAn 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 materialsEighty-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.ResultsAt 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.ConclusionsThe 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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