Validation of temporal optimization effects for a single fraction of radiation in vitro.
OBJECTIVE
To experimentally validate how temporal modification of the applied dose pattern within a single fraction of radiation therapy affects cell survival.


METHODS
Using the linear-quadratic model, we have previously demonstrated that the greatest difference in cell survival results from comparing a temporal dose pattern delivering the highest doses during the middle of a fraction and the lowest at the beginning and end ("Triangle") to one with the lowest doses at the middle and the highest at the beginning and end ("V-shaped"). Also, these differences would be greatest in situations with low alpha/beta and large dose/fraction and fraction length. Two low (WiDr, PC-3) and one high (SQ-20B) alpha/beta cell lines were irradiated in six-well plates with 900 cGy over 20 min (900 cGy/20 min), one each with a Triangle and V-shaped dose pattern. WiDr cells were subjected to the same experiments with first 180 cGy/20 min, then 900 cGy/5 min. Cell survival was assessed using the clonogenic assay.


RESULTS
At 900 cGy/20 min, irradiation with a V-shaped pattern resulted in an increased survival compared with use of a Triangle pattern of 21.2% for WiDr (p < 0.01), 18.6% for PC-3 (p < 0.025), and 4.7% for SQ-20B cells (p > 0.05). For WiDr cells at 180 cGy/20 min, this increase reduced to 2.7% (p > 0.05) and to -0.8% (p > 0.05) at 900 cGy/5 min.


CONCLUSIONS
These results verify the assertions of the modeling study in vitro, and imply that the temporal pattern of applied dose should be considered in treatment planning and delivery.
Altman
Michael B
MB
Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60657, USA. mbaltman@uchicago.edu
Stinauer
Michelle A
MA
Javier
Desler
D
Smith
Brett D
BD
Herman
Lauren C
LC
Pytynia
Matthew L
ML
Aydogan
Bulent
B
Pelizzari
Charles A
CA
Chmura
Steven J
SJ
Roeske
John C
JC
D000230:Adenocarcinoma / Q000532:radiotherapy; D000465:Algorithms; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy; D045744:Cell Line, Tumor / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects*; D003110:Colonic Neoplasms / Q000532:radiotherapy; D019583:Dose Fractionation, Radiation; D006258:Head and Neck Neoplasms / Q000532:radiotherapy; D006801:Humans; D016014:Linear Models; D008297:Male; D011471:Prostatic Neoplasms / Q000532:radiotherapy; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods; D013997:Time Factors; D014410:Tumor Stem Cell Assay / Q000379:methods*