Intrinsic radiosensitivity, genomic-based radiation dose and patterns of failure of penile cancer in response to adjuvant radiation therapy
| Autor: | G. Daniel Grass, Peter A.S. Johnstone, Kamran Ahmed, Javier F. Torres-Roca, Mounsif Azizi, Zhigang Yuan, Eric A. Welsh, Philippe E. Spiess, G. Sean J. Yoder, Anna R. Giuliano, William J. Fulp, Jasreman Dhillon |
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| Rok vydání: | 2019 |
| Předmět: |
Oncology
medicine.medical_specialty business.industry medicine.medical_treatment Therapeutic effect Original research article medicine.disease 030218 nuclear medicine & medical imaging Radiation therapy 03 medical and health sciences 0302 clinical medicine Port (medical) 030220 oncology & carcinogenesis Internal medicine Cohort Medicine Penile cancer Radiology Nuclear Medicine and imaging Radiosensitivity business Adjuvant Chemoradiotherapy |
| Zdroj: | Rep Pract Oncol Radiother |
| ISSN: | 1507-1367 |
| DOI: | 10.1016/j.rpor.2019.09.006 |
| Popis: | Purpose 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. Methods 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. Results 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. Conclusions 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. |
| Databáze: | OpenAIRE |
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