Association between lung density changes and radiation pneumonitis after IMRT for lung cancer.
Ghanem, AI, Qixue W, Al Feghali K, Khalil R, Liu C, Ajlouni M, Movsas B, and Chetty I. Association between lung density changes and radiation pneumonitis after IMRT for lung cancer. Radiother Oncol 2018; 127:S386.
Purpose or Objective Definitive chemoradiotherapy (CRT) is potentially curative for locally advanced bronchogenic carcinoma and non-surgical candidates. However, radiation induced pneumonitis (RP) constitutes a major threat to the quality of life. The aim of our work is to investigate the impact of lung density changes as well as other risk factors in predicting RP in patients with lung cancer undergoing CRT using IMRT technique. Material and Methods After IRB approval we queried lung cancer cases treated definitively using CRT with available follow up CT chest datasets. We excluded all patients with prior chest RT, incomplete treatment and cases lacking post-RT images. All patients underwent 4D-CT simulation and the treatment plan was prescribed to cover PTV with 60-66 Gy in 2 Gy fractions using IMRT. Planning CT images with dose distribution were mapped to follow up CT using deformable registration to assess Hounsfield Unit (HU) changes after RT as portrayed in figure (1) excluding any tumor specific changes. Radiation oncologists graded RP by reviewing surveillance encounters using CTCAE v4.03 scale and were blinded to HU changes. Spearman's correlation was plotted for post-RT HU changes against all RP grades. Chi-square and Fisher's exact test were used to study factors associated with RP ≥2. Results After a median follow up of 17 months (2-57) we were able to identify 118 patients who met our inclusion criteria. All had a smoking history with mean pack years (46±29), 51% were males and median age was 70 (45-88). Stage III were the majority (64%) and adenocarcinoma was present in 52.5% followed by squamous and small cell carcinoma (40 & 7.5%). Carboplatin/taxol was the most utilized regimen (54%) followed by platinum/pemetrexed or eteposide (26% & 15%).Grade 1 (G1), a radiological finding; RP was detected in 42 cases (35.6%); grade 2 (G2) & 3 (G3) in 22(18.6%) and 7(5.9%) respectively. The mean corresponding density increases for both lungs - CTV were 10, 26.7, 29.3 & 58.1 HU for G0-3 RP respectively that resulted in a significant Spearman's correlation (r=0.43, p<0.0001) as shown in figure (2). Similar outcomes were depicted for ipsilateral lung - CTV as well as the V20 volumes (p<0.001). Another significant correlation was observed between increasing mean lung dose (MLD) (r=0.26, p=0.01) and V20 (r=0.22, p=0.02) with RP grades, although both were within normal constraints (V20: 21.3±3.9 % and MLD: 13.1±3.9 Gy). All baseline metrics were balanced among RP groups with no significant differences, except that symptomatic RP requiring medical intervention (G2 & 3) had significantly more chronic obstructive lung disease (COPD) (93% vs 67% for G2+ vs G0-1; p=0.006). Conclusion Deformable registration and quantification of HU changes between baseline and follow up CT is strongly predictive for RP and can be integrated in regular follow up protocols after validation in a prospective trial setting. More robust dose constraints need to be tailored for cases with baseline COPD as they are at increased risk for RP. (Figure Presented) .