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TGF?1 Genetic Variants Predict Clinical Outcomes of HPV-Positive Oropharyngeal Cancer Patients after Definitive Radiotherapy.

ABSTRACT: Purpose: TGF?1 plays a critical role in inflammation and immune responses and treatment response and survival. TGF?1 variants may affect its expression level or functional efficiency, thus modifying tumor status and survival in human papillomavirus (HPV)-positive squamous cell carcinoma of the oropharynx (SCCOP).Experimental Design: We determined tumor HPV16 status and genotyped three TGF?1 polymorphisms in 564 incident SCCOP patients treated with radiotherapy or chemoradiation. Univariate and multivariable Cox models were used to evaluate the associations between the three polymorphisms and survival.Results: Overall, 85% of patients (482 of 564) had HPV16-positive SCCOP. We found that TGF?1 rs1982073 had statistically significant associations with survival, whereas TGF?1 rs1800469 and TGF?1 rs1800471 did not. Patients with TGF?1 rs1982073 CT/CC variant genotypes had significantly better overall, disease-specific, and disease-free survival compared with those with the corresponding common homozygous TT genotype (all log-rank: P < 0.001). Furthermore, these genotypes were significantly associated with an approximately 5 times reduced risk of overall death, death owing to disease, and recurrence after multivariable adjustment. Moreover, the stratified analyses by tumor HPV status indicated that the significant effects of TGF?1 rs1982073 polymorphism on survival were found among HPV16-positive SCCOP patients only. Finally, the functional relevance of these variants was further characterized.Conclusions: Our findings support that the TGF?1 rs1982073 polymorphism plays a significant role in the prognosis of SCCOP, especially in HPV16-positive SCCOP patients treated with chemoradiation. Prospective studies with larger sample sizes are needed to confirm these findings. Clin Cancer Res; 24(9); 2225-33. ©2018 AACR.

SUBMITTER: Tao Y

PROVIDER: S-EPMC5932112 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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TGFβ1 Genetic Variants Predict Clinical Outcomes of HPV-Positive Oropharyngeal Cancer Patients after Definitive Radiotherapy.

Tao Ye Y Sturgis Erich M EM Huang Zhigang Z Wang Ying Y Wei Peng P Wang Jennifer Rui JR Wei Qingyi Q Li Guojun G

Clinical cancer research : an official journal of the American Association for Cancer Research 20180220 9

Purpose: TGFβ1 plays a critical role in inflammation and immune responses and treatment response and survival. TGFβ1 variants may affect its expression level or functional efficiency, thus modifying tumor status and survival in human papillomavirus (HPV)-positive squamous cell carcinoma of the oropharynx (SCCOP).Experimental Design: We determined tumor HPV16 status and genotyped three TGFβ1 polymorphisms in 564 incident SCCOP patients treated with radiotherapy or chem ...[more]

PMID: 29463556

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Project description:Purpose: HPV-positive oropharyngeal carcinoma (HPV-OPC) is increasingly treated with primary surgery. The National Comprehensive Cancer Network (NCCN) recommends adjuvant therapy for surgically treated HPV-OPC displaying adverse pathological features (AF). We evaluated adjuvant radiotherapy patterns and outcomes in surgically treated AF-positive HPV-OPC (AF-HPV-OPC). Methods: The National Cancer Database was interrogated for patients ≥ 18 years with early-stage HPV-OPC from 2010 to 2017 who underwent definitive resection. Patients that had an NCCN-defined AF indication for adjuvant radiotherapy were assessed, including positive surgical margins (PSM), extranodal extension (ENE), lymphovascular invasion, and level 4/5 cervical lymph nodes. Overall survival (OS) was evaluated using Cox proportional hazards models and Kaplan−Meier analysis in whole and propensity score matched (PM) cohorts. Results: Of 15,036 patients meeting inclusion criteria, 55.7% were positive for at least one AF. Presence of any AF was associated with worse OS (hazard ratio (HR) = 1.56, p < 0.001). In isolation, each AF was associated with worse OS. On PM analysis, insurance status, T2 category, Charlson-Deyo comorbidity score, ENE (HR = 1.81, p < 0.001), and PSM (HR = 1.58, p = 0.002) were associated with worse OS. Median 3-year OS was 92.0% among AF-HPV-OPC patients undergoing adjuvant radiotherapy and 84.2% for those who did not receive adjuvant radiotherapy (p < 0.001, n = 1678). The overall rate of patients with AF-HPV-OPC who did not receive adjuvant radiotherapy was 13% and increased from 10% in 2010 to 17% in 2017 (ptrend = 0.007). Conclusions: In patients with AF-HPV-OPC, adjuvant radiotherapy is associated with improved survival. In the era of de-escalation therapy for HPV-OPC, our findings demonstrate the persistent prognostic benefit of post-operative radiotherapy in the setting of commonly identified adverse features. Ongoing clinical trials will better elucidate optimized patient selection for de-escalated therapy.

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TGF?1 Genetic Variants Predict Clinical Outcomes of HPV-Positive Oropharyngeal Cancer Patients after Definitive Radiotherapy.

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<i>TGFβ1</i> Genetic Variants Predict Clinical Outcomes of HPV-Positive Oropharyngeal Cancer Patients after Definitive Radiotherapy.

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