open access

Vol 24, No 6 (2019)
Original research articles
Published online: 2019-11-01
Submitted: 2019-01-21
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Intrinsic radiosensitivity, genomic-based radiation dose and patterns of failure of penile cancer in response to adjuvant radiation therapy

Zhigang Yuan, G.Daniel Grass, Mounsif Azizi, Kamran A. Ahmed, G. Sean Yoder, Eric A. Welsh, William J. Fulp, Jasreman Dhillon, Javier F. Torres-Roca, Anna R. Giuliano, Philippe E. Spiess, Peter A. Johnstone
DOI: 10.1016/j.rpor.2019.09.006
·
Rep Pract Oncol Radiother 2019;24(6):593-599.

open access

Vol 24, No 6 (2019)
Original research articles
Published online: 2019-11-01
Submitted: 2019-01-21

Abstract

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 50Gy, in contrast to 84% benefit from GARD-modeled PORT of 66Gy. 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 50Gy, 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.

Abstract

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 50Gy, in contrast to 84% benefit from GARD-modeled PORT of 66Gy. 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 50Gy, 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.

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Keywords

Radiosensitivity; Penile cancer; Radiation therapy; GARD; Locoregional failure

About this article
Title

Intrinsic radiosensitivity, genomic-based radiation dose and patterns of failure of penile cancer in response to adjuvant radiation therapy

Journal

Reports of Practical Oncology and Radiotherapy

Issue

Vol 24, No 6 (2019)

Pages

593-599

Published online

2019-11-01

DOI

10.1016/j.rpor.2019.09.006

Bibliographic record

Rep Pract Oncol Radiother 2019;24(6):593-599.

Keywords

Radiosensitivity
Penile cancer
Radiation therapy
GARD
Locoregional failure

Authors

Zhigang Yuan
G.Daniel Grass
Mounsif Azizi
Kamran A. Ahmed
G. Sean Yoder
Eric A. Welsh
William J. Fulp
Jasreman Dhillon
Javier F. Torres-Roca
Anna R. Giuliano
Philippe E. Spiess
Peter A. Johnstone

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