Using benchmarked lung radiation dose constraints to predict pneumonitis risk: Developing a nomogram for patients with mediastinal lymphoma

Abstract

Purpose: We identified lung dosimetric constraints to assist in predicting the radiation pneumonitis (RP) risk in patients with mediastinal lymphoma and then identified the clinical prognostic factors that were associated with the achievement of key dosimetric constraints.

Methods and materials: In 190 patients who received mediastinal intensity modulated radiation therapy, we used univariate χ² and multivariate logistic models to identify the predictors of RP and achievement of lung dose-volume histogram (DVH) constraints and build a predictive nomogram for RP.

Results: An increased risk of RP was strongly associated with mean lung dose (MLD) > 13.5 Gy (odds ratio [OR]: 8.13; 95% confidence interval [CI], 3.01-21.93; P < .001) and the percent of lung volume receiving ≥5 Gy (V5) > 55% (OR: 7.01; 95% CI, 2.94-16.72; P < .001). Therefore, patients had low RP risk (8%) if both MLD ≤13.5 and V5 ≤55 constraints were achieved, moderate risk (24%) if only MLD was achieved, and the highest risk (48%) if MLD was not achieved. Deep-inspiration breath-hold (DIBH) technique during treatment strongly prognosticated achieving MLD and V5 DVH constraints (OR,3.88; 95% CI, 1.84-8.19; P < .001). Specifically, 86% of patients who were treated with DIBH versus 63% without DIBH achieved DVH constraints (P < .001). This translated into a "number needed to treat" with DIBH of 4 patients to enable 1 additional patient to achieve both constraints. In comparison, the clinical characteristics were marginal prognosticators: DVH constraints were more likely achieved in nonbulky disease (OR: 3.01; 95% CI, 0.89-4.53; P = .09) and patients who had not previously received salvage chemotherapy (OR, 2.44; 95% CI, 0.98-6.11; P = .06). Nomogram-predicted risks of RP ranged from 4% to 60% on the basis of MLD and V5, total radiation dose, and use of salvage chemotherapy.

Conclusions: Achieving mean lung and V5 DVH constraints is critical to reduce RP risk in patients with lymphoma who receive mediastinal intensity modulated radiation therapy. The use of the DIBH technique is a promising risk-modifying treatment approach in patients with mediastinal lymphoma and especially in patients with a history of nonmodifiable risk factors for RP such as bulky disease and salvage chemotherapy.

Figure 1

Mean lung dose, percent of lung volume receiving ≥5 Gy, and grades 1 to 3 radiation pneumonitis.

Figure 2

Derivation of lung dose volume (LDV) score on the basis of optimal goodness-of-fit for percent of lung volume receiving ≥5 Gy and mean lung dose dosimetric constraints to predict radiation pneumonitis.

Figure 3

Nomogram to predict risk of radiation pneumonitis for patients with mediastinal lymphoma who were treated with intensity modulated radiation therapy. (A) All patients. Fit characteristics: For the above multivariate model, Hosmer-Lemeshow test P = .18 and Akaike Information Criteria 142.59 compared with a model including only lung dose volume score as a covariate, Hosmer-Lemeshow P = 1.0, and Akaike Information Criteria 140.34. (B) Patients treated with deep-inspiration breath-hold technique. Fit characteristics: For the above multivariate model, Hosmer-Lemeshow test P = .69 and Akaike Information Criteria 93.19 compared with a model including only lung dose volume score as a covariate, Hosmer-Lemeshow P = 1.0, and Akaike Information Criteria 90.45. (C) Example patient: A patient was treated without deep-inspiration breath-hold to 30 Gy. The plan achieved mean lung dose constraint but not percent of lung volume receiving ≥5 Gy constraint. The patient did not have relapsed mediastinal lymphoma. To calculate total points: 88, calculate the sum of points that are associated with the 1) patient's dose of 30 Gy: 23 points; 2) Lung dose volume score of moderate: 65 points; and 3) No relapse status: 0 points. Draw a straight line from total points calculated to find the risk of pneumonitis (eg, total points of 188 correlates with risk of 0.21 or 21%).