Does Suppressing Inflammation Response In Lung Radiotherapy Protect the Lung Cancer Cells?
Abstract
Purpose
Radiation-induced lung injury, characterized by chronic inflammation and fibrosis, limits the dose we can give in lung cancer radiotherapy. Drugs that block this response have been shown to protect normal lung tissues from radiation. In this study, we wish to determine if one of these drugs also protect the cancer cells.
Methods
To initiate this study, we developed and validated a protocol to irradiate cell cultures in 12 well plates with an orthovoltage x-ray unit. This is followed by employing clonogenic survival assays to assess the effects of a peptide that blocks fibrosis response in a non-small cell lung cancer (NSCLC) cell line A549. Dosimetric accuracy of the irradiation setup was verified using GAFchromic films after calibration. Cell survival was quantified using clonogenic assays after optimization of seeding density across preliminary trials. We obtained the radiation cell survival curve by radiating between 2-10 Gy in 2Gy increments. NSCLC cells were then pre-treated with peptide concentrations of 0.5, 5, and 50 μM prior to 4Gy irradiation.
Results
The GAF film exponential curve fit had an value of 0.996 and a mean difference of 3.1% in a test trial. Dose profiles underneath the wells had a 95.6% flatness and a mean difference of 5.5%. Across two independent peptide trials, no statistically significant difference between peptide-treated and control was observed. At 4 Gy, SER values were 1.17 (0.5 μM, p=0.68), 1.15 (5.0 μM, p=0.72), and 1.18 (50.0 μM, p=0.60).
Conclusion
Preliminary results indicate that peptide pre-treatment did not alter radiation response under the test conditions. Ongoing work includes adding the peptide after radiation, using higher doses, and better modelling using spheroids. This study assessed a novel anti-fibrosis drug for use in lung cancer cells. We integrated biological assays with physics dosimetry to provide foundational data to increase therapeutic ratios for lung radiotherapy.