Purpose: This work investigates the radiation response of conventional radiotherapy (CRT) and pulsed low-dose-rate (PLDR) radiotherapy using in vivo small cell lung cancer murine tumor models.
Methods: Lung cell line KP1 (murine small cell lung cancer) was prepared for inoculation of ~20 gram C57BL/6 mice (The Jackson Laboratory). Exponentially growing cells were harvested and suspended in serum-free medium, and 5x10⁵ cells were injected subcutaneously into the right hind leg of 6 mice. Tumors were allowed to develop to a diameter of 5-7 mm before being separated into CRT and PLDR groups. A Varian Clinac iX machine was used to deliver 20Gy (4Gy/fraction) to the tumor using a SSD set-up, while the mice were under general anesthesia by way of isoflurane vapor with oxygen used as a carrier gas. The novelty of using isoflurane is that it safely allows for repeated and prolonged administration, which lends itself well to fractionated treatments and extended intra-fraction PLDR treatments. The dose rate for the CRT group was 500 cGy/min, while the effective dose rates (EDR) for PLDR was 8.3 cGy/min (a train of radiation pulses, each 0.25Gy, delivered in 3 minute intervals). After each fraction, mice were revived and tumors were measured with a caliper.
Results: Radiation responses of tumors in the CRT and PLDR groups were statistically indistinguishable, while both showing tumor control.
Conclusion: PLDR effect is comparable to that of CRT against KP1 murine tumors. This result adds to the body of research showing PLDR’s clinical efficacy, due its equivalent tumor control and reduced normal tissue toxicity with decreased EDRs. Further studies are underway to replicate a standard treatment protocol for lung cancer using stereotactic body radiotherapy. PLDR may be developed into a clinically viable alternative for treating large tumor masses and/or recurrent cancers with decreased normal tissue tolerances.