BACKGROUND. A key objective in managing HPV+ oropharyngeal squamous cell carcinoma (OPSCC) is reducing radiation therapy (RT) doses without compromising cure rates. A recent phase II/III HN005 trial revealed that clinical factors alone are insufficient to guide safe RT dose de-escalation. Our prior research demonstrated that the genomic adjusted radiation dose (GARD) predicts RT benefit and may inform dose selection. We hypothesize that GARD can guide personalized RT deescalation in HPV+ OPSCC patients. METHODS. Gene expression profiles were analyzed in 191 HPV+ OPSCC patients enrolled in an international, multi-institutional observational study (AJCC Eighth Edition, stages I–III). Most patients received 70 Gy in 35 fractions or 69.96 Gy in 33 fractions (median dose: 70 Gy; range: 51.0–74.0 Gy). Overall survival (OS) was 94.1% at 36 months and 87.3% at 60 months. A Cox proportional hazards model assessed association between GARD and OS, and time-dependent receiver operating characteristic analyses compared GARD with traditional clinical predictors. RESULTS. Despite uniform RT dosing, GARD showed wide heterogeneity, ranging from 15.4 to 71.7. Higher GARD values were significantly associated with improved OS in univariate (HR = 0.941, P = 0.041) and multivariable analyses (HR = 0.943, P = 0.046), while T and N stages were not. GARD demonstrated superior predictive performance at 36 months (AUC = 78.26) versus clinical variables (AUC = 71.20). Two GARD-based RT de-escalation strategies were identified, offering potential survival benefits while reducing radiation exposure. CONCLUSION. GARD predicts OS and outperforms clinical variables, supporting its integration into the diagnostic workflow for personalized RT in HPV+ OPSCC.
Personalized treatment in HPV+ oropharynx cancer using genomic adjusted radiation dose / Ho, E., De Cecco, L., Eschrich, S.A., Cavalieri, S., Sedor, G., Hoebers, F., Brakenhoff, R.H., Scheckenbach, K., Poli, T., Yang, K., Scarborough, J.A., Nellore, S., Campbell, S., Woody, N., Chan, T., Miller, J., Silver, N., Koyfman, S., Bates, J., Caudell, J.J., et al.. - In: THE JOURNAL OF CLINICAL INVESTIGATION. - ISSN 0021-9738. - 135:24(2025), pp. e194073.1-e194073.9. [10.1172/JCI194490]
Personalized treatment in HPV+ oropharynx cancer using genomic adjusted radiation dose
Poli T.Investigation
;
2025-01-01
Abstract
BACKGROUND. A key objective in managing HPV+ oropharyngeal squamous cell carcinoma (OPSCC) is reducing radiation therapy (RT) doses without compromising cure rates. A recent phase II/III HN005 trial revealed that clinical factors alone are insufficient to guide safe RT dose de-escalation. Our prior research demonstrated that the genomic adjusted radiation dose (GARD) predicts RT benefit and may inform dose selection. We hypothesize that GARD can guide personalized RT deescalation in HPV+ OPSCC patients. METHODS. Gene expression profiles were analyzed in 191 HPV+ OPSCC patients enrolled in an international, multi-institutional observational study (AJCC Eighth Edition, stages I–III). Most patients received 70 Gy in 35 fractions or 69.96 Gy in 33 fractions (median dose: 70 Gy; range: 51.0–74.0 Gy). Overall survival (OS) was 94.1% at 36 months and 87.3% at 60 months. A Cox proportional hazards model assessed association between GARD and OS, and time-dependent receiver operating characteristic analyses compared GARD with traditional clinical predictors. RESULTS. Despite uniform RT dosing, GARD showed wide heterogeneity, ranging from 15.4 to 71.7. Higher GARD values were significantly associated with improved OS in univariate (HR = 0.941, P = 0.041) and multivariable analyses (HR = 0.943, P = 0.046), while T and N stages were not. GARD demonstrated superior predictive performance at 36 months (AUC = 78.26) versus clinical variables (AUC = 71.20). Two GARD-based RT de-escalation strategies were identified, offering potential survival benefits while reducing radiation exposure. CONCLUSION. GARD predicts OS and outperforms clinical variables, supporting its integration into the diagnostic workflow for personalized RT in HPV+ OPSCC.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
