Tumor control probability predictions for genetic radiotherapy.
OBJECTIVE
Genetic radiotherapy, the combination of gene therapy and radiation therapy, for cancer treatment is evolving from laboratory studies to clinical trials. Genetic radiotherapy involves the viral infection of cells that change the sensitivity of transduced cells to radiation. Because there is no patient outcome data for genetic radiotherapy, prospective models are needed to determine the expected benefit of this new modality. Such a prospective model has been developed in this work.


METHODS
An existing tumor control probability (TCP) calculation model developed for external beam radiotherapy was modified for genetic radiotherapy. Specifically, the (1) transduced fraction and (2) enhancement factor of the transduced cells were included in the model. Parametric studies of the effects of these two variables on TCP for head-and-neck cancer were performed.


RESULTS
Using reasonable transduction fraction and enhancement factor values (0.8 and 1.4, respectively), the model predicts an increase in the TCP for genetic radiotherapy over radiotherapy alone by up to 15% for the same radiotherapy dose. The theoretical limit of TCP increase was calculated to be near 70%, which may occur with improved techniques that increase the transduced fraction or because of a strong bystander effect. To maintain existing TCP, dose reductions from 5 Gy (reasonable values) to >30 Gy (ideal case) are predicted for genetic radiotherapy over radiotherapy alone.


CONCLUSIONS
Our results indicate that genetic radiotherapy has the potential to significantly improve tumor control over radiotherapy alone.
Keall
Paul J
PJ
Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA 23298-0058, USA. pjkeall@vcu.edu
Lammering
Guido
G
Lin
Peck-Sun
PS
Winter
David S
DS
Chung
Theodore D
TD
Mohan
Radhe
R
Schmidt-Ullrich
Rupert K
RK
D003131:Combined Modality Therapy / Q000379:methods; D003198:Computer Simulation; D004307:Dose-Response Relationship, Radiation; D015316:Genetic Therapy / Q000379:methods*; D006258:Head and Neck Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D008954:Models, Biological; D015233:Models, Statistical; D011836:Radiation Tolerance / Q000235:genetics; D011878:Radiotherapy / Q000379:methods; D011879:Radiotherapy Dosage; D012680:Sensitivity and Specificity; D014161:Transduction, Genetic / Q000379:methods*; D016896:Treatment Outcome