Optimal postoperative radiation therapy (PORT) dose is unclear in penile squamous cell carcinoma (PeSCC). Herein, we characterized the radiosensitivity index (RSI) and genomic-adjusted radiation dose (GARD) profiles in a cohort of patients with PeSCC, and assessed the application of GARD to personalize PORT.
A total of 25 PeSCC samples were identified for transcriptomic profiling. The RSI score and GARD were derived for each sample. A cohort of 34 patients was reviewed for clinical correlation.
The median RSI for PeSCC was 0.482 (range 0.215-0.682). The majority (n = 21; 84%) of cases were classified as radioresistant. PeSCC GARD ranged from 9.56 to 38.39 (median 18.25), suggesting variable therapeutic effects from PORT. We further determined the optimal GARD-based RT doses to improve locoregional control. We found that therapeutic benefit was only achieved in 52% of PeSCC lesions with PORT of 50 Gy, in contrast to 84% benefit from GARD-modeled PORT of 66 Gy. In the clinical cohort, the majority of patients presented with pathological N2 or N3 disease (n = 31; 91%) and was treated with adjuvant concurrent platinum-based chemoradiotherapy (CRT, n = 30; 88%). Fourteen of the 34 patients (41%) had locoregional recurrence (LRR), of which half had LRR within six months of completion of PORT.
The majority of PeSCC are intrinsically radioresistant with a low GARD-based therapeutic effect from PORT dose of 50 Gy, consistent with the observed high rate of LRR in the clinical cohort. A GARD-based strategy will allow personalizing PORT dose prescription to individual tumor biology and improve outcomes.
Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology. 2019 Nov 01 [Epub]
Zhigang Yuan, G Daniel Grass, Mounsif Azizi, Kamran A Ahmed, G Sean J Yoder, Eric A Welsh, William J Fulp, Jasreman Dhillon, Javier F Torres-Roca, Anna R Giuliano, Philippe E Spiess, Peter A Johnstone
Department of Radiation Oncology, H Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr, Tampa, FL 33612, USA., Department of Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr, Tampa, FL 33612, USA., Moffitt Genomics core, H Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr, Tampa, FL 33612, USA., Department of Biostatistics and Bioinformatics, H Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr, Tampa, FL 33612, USA., Department of Anatomic Pathology, H Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr, Tampa, FL 33612, USA., Department of Cancer Epidemiology, H Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr, Tampa, FL 33612, USA.