Interstitial Lung Change in Pre-radiation Therapy Computed Tomography Is a Risk Factor for Severe Radiation Pneumonitis

Yun Hee Lee, Yeon Sil Kim, Sang Nam Lee, Hyo Chun Lee, Se Jin Oh, Seoung Joon Kim, Young Kyoon Kim, Dae Hee Han, Ie Ryung Yoo, Jin Hyung Kang, Suk Hee Hong, Yun Hee Lee, Yeon Sil Kim, Sang Nam Lee, Hyo Chun Lee, Se Jin Oh, Seoung Joon Kim, Young Kyoon Kim, Dae Hee Han, Ie Ryung Yoo, Jin Hyung Kang, Suk Hee Hong

Abstract

Purpose: We examined clinical and dosimetric factors as predictors of symptomatic radiation pneumonitis (RP) in lung cancer patients and evaluated the relationship between interstitial lung changes in the pre-radiotherapy (RT) computed tomography (CT) and symptomatic RP.

Materials and methods: Medical records and dose volume histogram data of 60 lung cancer patients from August 2005 to July 2006 were analyzed. All patients were treated with three dimensional (3D) conformal RT of median 56.9 Gy. We assessed the association of symptomatic RP with clinical and dosimetric factors.

Results: With a median follow-up of 15.5 months (range, 6.1 to 40.9 months), Radiation Therapy Oncology Group grade ≥ 2 RP was observed in 14 patients (23.3%). Five patients (8.3%) died from RP. The interstitial changes in the pre-RT chest CT, mean lung dose (MLD), and V30 significantly predicted RP in multivariable analysis (p=0.009, p < 0.001, and p < 0.001, respectively). MLD, V20, V30, and normal tissue complication probability normal tissue complication probability (NTCP) were associated with the RP grade but less so for grade 5 RP. The risk of RP grade ≥ 2, ≥ 3, or ≥ 4 was higher in the patients with interstitial lung change (grade 2, 15.6% to 46.7%, p=0.03; grade 3, 4.4% to 40%, p=0.002; grade 4, 4.4% to 33.3%, p=0.008). Four of the grade 5 RP patients had diffuse interstitial change in pre-RT CT and received chemoradiotherapy.

Conclusion: Our study identified diffuse interstitial disease as a significant clinical risk for RP, particularly fatal RP. We showed the usefulness of MLD, V20, V30, and NTCP in predicting the incidence and severity of RP.

Keywords: Interstitial lung diseases; Lung neoplasms; Radiation pneumonitis; Radiotherapy.

Conflict of interest statement

Conflict of interest relevant to this article was not reported.

Figures

Fig. 1.
Fig. 1.
Cumulative curves of the development of RP, which were stratified by MLD (A), V20 (B), V30 (C), and NTCP (D). There were consistencies in that the higher RP rates were associated with higher MLD, V20, V30, and NTCP. Maintaining a MLD less than 15 Gy, V20 < 25%, and V30 < 20% could reduce the incidence of RP. RP, radiation pneumonitis; MLD, mean lung dose; V20 and V30, percent lung volume receiving more than 20 Gy and 30 Gy; NTCP, normal tissue complication probability.
Fig. 2.
Fig. 2.
The distribution of RP grade stratified by MLD (A), V20 (B), V30 (C), and NTCP (D). A MLD, V20, V30, V40, and NTCP also were strongly associated with RP grade. However, all dosimetric parameters were even lower in grade 5 fatal RP. RP, radiation pneumonitis; MLD, mean lung dose; V20 and V30, percent lung volume receiving more than 20 Gy and 30 Gy; NTCP, normal tissue complication probability.
Fig. 3.
Fig. 3.
Representative of grade 5 fatal radiation pneumonitis patient. This patient was a 65 year-old male with non-small cell lung cancer, T2N2M0 (2.2-cm-sized fluorodeoxyglucose avid mass in right lower lobe (arrow) with metastatic lymphadenopathies in right interlobar and subcarina/right paraesophageal area) (A) treated with weekly docetaxel (20 mg/m2)+cisplatin (20 mg/m2) concurrent chemoradiotherapy (CCRT). Although, he had a history of interstitial lung disease diagnosed 2 years ago, he was in a clinically stable condition with acceptable pulmonary function (forced expiratory volume in 1 second, 2.2 L; carbon monoxide lung diffusion capacity, 74%). Initial chest computed tomography showed diffuse involvement of reticular opacity, subpleural ground glass opacity (arrows) (B), traction bronchiectasis (arrow) (C), and honeycombing (arrow) (D). One month after completing CCRT (59.4 Gy/33 fractions) (E), he achieved excellent partial response. The malignant tumor in right upper lobe showed partial metabolic response (arrow) (F) and minimal haziness was noted in the computed tomography (arrow) (G). However, he developed coughing, progressive dyspnea, and fever with newly developed diffuse interstitial infiltration and consolidation extending beyond radiation field 3 months after completion of radiation therapy (H, I). No specific infectious cause was identified. He died despite 2 weeks of intensive care.

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