Predicting the risk of symptomatic radiation-induced lung injury using both the physical and biologic parameters V30 and transforming growth factor β

Fu, Xiao; Huang, Hong; Bentel, Gunilla C.; Clough, Robert; Jirtle, Randy L.; Kong, Feng-Ming; Marks, Lawrence B.; Anscher, Mitchell S.

doi:10.1016/s0360-3016(01)01524-3

Cited by 153 publications

(95 citation statements)

References 40 publications

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“…Inflammatory cytokines have been implicated in the development and perpetuation of post-irradiation injury in various tissues, including the lung [27]. Serum levels of cytokines, in particular, interleukin-6 (IL-6) and transforming growth factor-β (TGF-β), are inconclusive in predicting radiation pneumonitis [28][29][30][31][32].…”

Section: Discussionmentioning

confidence: 99%

High superoxide dismutase and low glutathione peroxidase activities in red blood cells predict susceptibility of lung cancer patients to radiation pneumonitis

Park

Ramnath

Yang

et al. 2007

Free Radical Biology and Medicine

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Radiation pneumonitis is an unpredictable complication of radiotherapy for lung cancer and a condition which can cause significant morbidity. The ability to identify patients at a high risk of developing pneumonitis is critical, since it will enable the individualization of the treatment plan. Because the cytotoxic effect of radiation is propagated through ROS and ROS-driven oxidative stress, the role of anti-oxidant defense systems in radiation pneumonitis was investigated. Using the pneumonitis-sensitive C3H/HeN mice as a model, we demonstrated that the anti-oxidant response of the lung correlated well with that of RBC. We then proceeded to test whether differences of RBC anti-oxidant response would predict the pneumonitis development in patients. SOD, GPX, CAT activities and glutathione in RBC were measured at baseline and then weekly for 6 weeks of treatment in fifteen eligible patients receiving concurrent chemo-radiotherapy for unresectable stage III NSCLC. Striking differences were found in the anti-oxidant activities of RBC with respect to the pneumonitis development. Those who developed pneumonitis showed higher SOD and lower GPX activities at baseline compared to those who did not (3.7 vs. 6.8 unit/mg for median SOD, 16.5 vs. 10.7 nmol/min/mg for median GPX). The functional imbalance of SOD and GPX was displayed consistently throughout the treatment period. The sensitivity and specificity of pneumonitis prediction were further increased when the GPX/SOD ratio was analyzed (pre-treatment P = 0.0046). Our results provide a strong rationale to monitor SOD and GPX activities of RBC to identify patients who are at risk of developing pneumonitis, and to implement a strategy of increasing the GPX/SOD ratio in order to lower the risk.

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Section: Discussionmentioning

confidence: 99%

High superoxide dismutase and low glutathione peroxidase activities in red blood cells predict susceptibility of lung cancer patients to radiation pneumonitis

Park

Ramnath

Yang

et al. 2007

Free Radical Biology and Medicine

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“…For patients treated for lung cancer, approximately 5% to 20% develop symptomatic lung injury, 50% to 100% develop radiologic evidence of regional injury, and 50% to 90% experience declines in pulmonary function [1][2][3][4][5][6]. Identification of the dosimetric and biologic determinants of RTinduced lung injury would be useful in developing risk profiles for individual patients; thereby tailoring treatment to maximize efficacy and minimize toxicity [1].…”

Section: Introductionmentioning

confidence: 99%

“…Several recent studies have investigated transforming growth factor-beta-1 (TGF-β1) as a predictor for RT-induced lung injury [1,3,7,[12][13][14][15]. TGF-β1 is a cytokine that has been suggested to play an important role in both tumor progression and normal tissue damage by suppressing antitumor immune responses, enhancing extracellular matrix production, and augmenting angiogenesis [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

“…Fu et al [3] showed that plasma TGF-β1 levels at the end of RT relative to pre-RT TGF-β1 levels seemed to be an independent risk factor for developing symptomatic RT-induced lung injury, and that combining plasma TGF-β1 levels with V30 appeared to facilitate stratification of patients into low-, intermediate-, and high-risk groups.…”

Section: Introductionmentioning

confidence: 99%

“…Since our last publication [3], we have enrolled additional patients onto our studies. The goal of the present analysis is to reassess the utility of TGF-β1 together with dosimetric and tumor parameters as a predictor for RP, in the context of a prospective clinical trial.…”

Section: Introductionmentioning

confidence: 99%

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Does transforming growth factor-β1 predict for radiation-induced pneumonitis in patients treated for lung cancer?

et al. 2006

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The purpose of the study was to reassess the utility of transforming growth factor-beta-1 (TGF-β1) together with dosimetric and tumor parameters as a predictor for radiation pneumonitis (RP). Of the 121 patients studied, 32 (26.4%) developed grade ≥ 1 RP, and 27 (22.3%) developed grade ≥ 2 RP. For the endpoint of grade ≥ 1 RP, those with V30 > 30% and an end-RT/baseline TGF-β1 ratio ≥ 1 had a significantly higher incidence of RP than did those with V30 > 30% and an end-RT/baseline TGF-β1 ratio < 1. For most other patient groups, there were no clear associations between TGF-β1 values and rates of RP. These findings suggest that TGF-β1 is generally not predictive for RP except for the group of patients with a high V30.

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Association of Radiation Therapy With Risk of Adverse Events in Patients Receiving Immunotherapy

et al. 2022

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IMPORTANCE Immune checkpoint inhibitors (ICIs) and radiation therapy (RT) are widely used to treat various cancers, but little data are available to guide clinicians on ICI use sequentially with RT. OBJECTIVE To assess whether there is an increased risk of serious adverse events (AEs) associated with RT given within 90 days prior to an ICI. DESIGN, SETTING, AND PARTICIPANTS Individual patient data were pooled from 68 prospective trials of ICIs submitted in initial or supplemental licensing applications in the US Food and Drug Administration (FDA) databases through December 2019. Two cohorts were generated: (1) patients who received RT within the 90 days prior to beginning ICI therapy and (2) those who did not receive RT within the 90 days prior to beginning ICI therapy, and AE frequencies were determined. A 1:1 propensity score-matched analysis was performed.INTERVENTIONS All patients received an ICI (atezolizumab, avelumab, cemiplimab, durvalumab, ipilimumab, nivolumab, or pembrolizumab); 1733 received RT within the 90 days prior to starting ICI therapy, and 13 956 did not. MAIN OUTCOMES AND MEASURESThe primary outcome was frequency and severity of AEs. Incidence of AEs was compared descriptively between participants who did vs did not receive RT in the propensity score-matched set. Because all analyses are exploratory (ie, not preplanned and no alpha allocated), assessment for statistical significance of the differences between groups was not considered appropriate.RESULTS A total of 25 469 patients were identified; 8634 were excluded because they lacked comparators who had received RT (n = 976), did not receive an ICI (n = 4949), received RT outside of the target window (n = 2338), or had missing data in 1 or more variables used in the propensity analysis (n = 371), leaving 16 835 patients included in the analysis. The majority were younger than 65 years (9447 [56.1%]), male (10 459 [62.1%]), and White (13 422 [79.7%]). Patients receiving RT had generally similar rates of AEs overall to those patients who did not receive RT. The average absolute difference in rates across the AEs was 1.2%, and the difference ranged from 0% for neurologic AEs to 8% for fatigue. No difference in grade 3 to 4 AEs was observed between the 2 groups (absolute difference ranged from 0.01% to 2%). These findings persisted after propensity score matching. CONCLUSIONS AND RELEVANCEIn this pooled analysis, administration of an ICI within 90 days following RT did not appear to be associated with an increased risk of serious AEs. Thus, it would appear to be safe to administer an ICI within 90 days of receiving RT. These findings should be confirmed in future prospective trials.

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Predicting the risk of symptomatic radiation-induced lung injury using both the physical and biologic parameters V30 and transforming growth factor β

Cited by 153 publications

References 40 publications

High superoxide dismutase and low glutathione peroxidase activities in red blood cells predict susceptibility of lung cancer patients to radiation pneumonitis

High superoxide dismutase and low glutathione peroxidase activities in red blood cells predict susceptibility of lung cancer patients to radiation pneumonitis

Does transforming growth factor-β1 predict for radiation-induced pneumonitis in patients treated for lung cancer?

Association of Radiation Therapy With Risk of Adverse Events in Patients Receiving Immunotherapy

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