Radiation-induced lung damage in rats: The influence of fraction spacing on effect per fraction

Haston, Christina K.; Hill, Richard P.; Newcomb, C.; Dyk, Jake Van

doi:10.1016/0360-3016(94)90188-0

Cited by 9 publications

(6 citation statements)

References 20 publications

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“…Also different irradiation facilities were used in the two studies (due to the decommissioning of the Co-60 treatment facility) with different dose rates and different expected relative biological effectiveness. The difference in the doses delivered was designed to address these latter two issues based on our previous experience (Newcomb et al 1993, Haston et al 1994) but the accommodation may not have been exact. Regardless, the difference in the results from these two experiments could be very important, since it suggests the possibility that the mitigation of radiation-induced pneumonitis and functional lung damage may be more effective at lower levels of overall lung damage.…”

Section: Discussionmentioning

confidence: 99%

Mitigation of radiation-induced lung injury by genistein and EUK-207

Mahmood

Jelveh

Calveley

et al. 2011

International Journal of Radiation Biology

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Purpose We examined the effects of genistein and/or Eukarion (EUK)-207 on radiation-induced lung damage and investigated whether treatment for 0–14 weeks (wks) post-irradiation (PI) would mitigate late lung injury. Materials and Methods The lungs of female Sprague-Dawley (SD) rats were irradiated with 10 Gy. EUK-207 was delivered by infusion and genistein was delivered as a dietary supplement starting immediately after irradiation (PI) and continuing until 14 wks PI. Rats were sacrificed at 0, 4, 8, 14 and 28 wks PI. Breathing rate was monitored and lung fibrosis assessed by lung hydroxyproline content at 28 wks. DNA damage was assessed by micronucleus (MN) assay and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels. The expression of the cytokines Interleukin (IL)-1α, IL-1β, IL-6, Tumor necrotic factor (TNF)-α and Transforming growth factor (TGF)-β1, and macrophage activation were analysed by immunohistochemistry. Results Increases in breathing rate observed in the irradiated rats were significantly reduced by both drug treatments during the pneumonitis phase and the later fibrosis phase. The drug treatments decreased micronuclei (MN) formation from 4–14 wks but by 28 wks the MN levels had increased again. The 8-OHdG levels were lower in the drug treated animals at all time points. Hydroxyproline content and levels of activated macrophages were decreased at 28 wks in all drug treated rats. The treatments had limited effects on the expression of the cytokines. Conclusion Genistein, and EUK-207 can provide partial mitigation of radiation-induced lung damage out to at least 28 wks PI even after cessation of treatment at 14 wks PI.

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Section: Discussionmentioning

confidence: 99%

Mitigation of radiation-induced lung injury by genistein and EUK-207

Mahmood

Jelveh

Calveley

et al. 2011

International Journal of Radiation Biology

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“…A dose of 18 Gy (dose rate approximately 0.5 Gy/min) was given to all animals, which were irradiated in groups of four. It was anticipated from previous studies (23, 28, 29) that, at the dose rate used, this dose of 18 Gy would be approximately equivalent to 14 Gy at a dose rate above 1 Gy/min.…”

Section: Methodsmentioning

confidence: 97%

Genistein Can Mitigate the Effect of Radiation on Rat Lung Tissue

et al. 2010

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We investigated whether genistein could protect the lung from radiation-induced injury. We hypothesized that genistein would reduce the levels of inflammatory cytokines and ROS after irradiation and therefore lead to reduced DNA damage and functional deficits. Whole lungs of Sprague-Dawley rats were irradiated with 18 Gy at ~0.5 Gy/min. At 28 weeks a micronucleus assay was used to examine DNA damage and, using immunohistochemical analysis, expression of IL-1α, IL-1β, IL-6, TNF-α and TGF-β, macrophage activation, oxidative stress (8-OHdG) and collagen levels were measured. A TBARS assay was used to measure the level of malondialdehyde. Functional damage was assessed by measuring the breathing rate of the rats over the course of the experiment. The increase in breathing rate after irradiation was damped in rats receiving genistein during the phase of pneumonitis (6–10 weeks), and there was a 50–80-day delay in lethality in this group. Genistein treatment also decreased the levels of the inflammatory cytokines TNF-α, IL-1β and TGF-β and led to a reduction in collagen content, a reduction in 8-OHdG levels, and complete protection against DNA damage measured in surviving rats at 28 weeks after irradiation. These results demonstrates that genistein treatment can provide partial protection against the early (pneumonitis) effects of lung irradiation and reduce the extent of fibrosis, although not sufficiently to prevent lethality at the radiation dose used in this study.

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“…In the past, efforts to escalate the dose for treatment of lung cancer have been limited by early esophageal and late pulmonary, spinal cord, cardiac, and esophageal toxicity. Radiation-induced pulmonary toxicity is well established, and its severity is increased in direct correlation with dose, volume, and fraction size [5][6][7][8][9][10][11][12][13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Results of multifield conformal radiation therapy of nonsmall-cell lung carcinoma using multileaf collimation beams

Bahri¹,

Flickinger²,

Kalend³

et al. 1999

Radiat. Oncol. Investig.

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A five‐field conformal technique with three‐dimensional radiation therapy treatment planning (3‐DRTP) has been shown to permit better definition of the target volume for lung cancer, while minimizing the normal tissue volume receiving greater than 50% of the target dose. In an initial study to confirm the safety of conventional doses, we used the five‐field conformal 3‐DRTP technique. We then used the technique in a second study, enhancing the therapeutic index in a series of 42 patients, as well as to evaluate feasibility, survival outcome, and treatment toxicity. Forty‐two consecutive patients with nonsmall‐cell lung carcinoma (NSCLC) were evaluated during the years 1993–1997. The median age was 60 years (range 34–80). The median radiation therapy (RT) dose to the gross tumor volume was 6,300 cGy (range 5,000–6,840 cGy) delivered over 6 to 6.5 weeks in 180–275 cGy daily fractions, 5 days per week. There were three patients who received a split course treatment of 5,500 cGy in 20 fractions, delivering 275 cGy daily with a 2‐week break built into the treatment course after 10 fractions. The stages of disease were II in 2%, IIIA in 40%, IIIB in 42.9%, and recurrent disease in 14.3% of the patients. The mean tumor volume was 324.14 cc (range 88.3–773.7 cc); 57.1% of the patients received combined chemoradiotherapy, while the others were treated with radiation therapy alone. Of the 42 patients, 7 were excluded from the final analysis because of diagnosis of distant metastasis during treatment. Two of the patients had their histology reinterpreted as being other than NSCLC, 2 patients did not complete RT at the time of analysis, and 1 patient voluntarily discontinued treatment because of progressive deterioration. Median follow‐up was 11.2 months (range 3–32.5 months). Survival for patients with Stage III disease was 70.2% at 1 year and 51.5% at 2 years, with median survival not yet reached. Local control for the entire series was 23.3 ± 11.4% at 2 years. However, for Stage III patients, local control was 50% at 1 year and 30% at 2 years. Patients who received concurrent chemotherapy had significantly improved survival (P = 0.002) and local control (P = 0.004), compared with RT alone. Late esophageal toxicity of ≥Grade 3 occurred in 14.1 ± 9.3% of patients (3 of 20) receiving combined chemoradiotherapy, but in none of the 15 patients treated with RT alone. Pulmonary toxicity limited to Grades 1–2 occurred in 6.8% of the patients, and none developed ≥Grade 3 pulmonary toxicity. Patients with locally advanced NSCLC, who commonly have tumor volumes in excess of 200 cc, present a challenge for adequate dose delivery without significant toxicity. Our five‐field conformal 3‐DRTP technique, which incorporates treatment planning by dose/volume histogram (DVH) was associated with minimal toxicity and may facilitate dose escalation to the gross tumor. Radiat. Oncol. Invest. 7:297–308, 1999. © 1999 Wiley‐Liss, Inc.

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Radiation-induced lung damage in rats: The influence of fraction spacing on effect per fraction

Cited by 9 publications

References 20 publications

Mitigation of radiation-induced lung injury by genistein and EUK-207

Mitigation of radiation-induced lung injury by genistein and EUK-207

Genistein Can Mitigate the Effect of Radiation on Rat Lung Tissue

Results of multifield conformal radiation therapy of nonsmall-cell lung carcinoma using multileaf collimation beams

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