Evaluating Radiation-Related Risk Factors for Pneumonitis in Patients with Stage III NSCLC Receiving Durvalumab after Definitive Chemoradiation

Abstract

<h3>Purpose/Objective(s)</h3> Concurrent chemoradiotherapy (CCRT) followed by durvalumab consolidation up to 12 mo became the standard of care for patients (pts) with stage III NSCLC after the publication of the PACIFIC trial. Both radiation pneumonitis (RP) and immune checkpoint inhibitor pneumonitis (ICI-p) are serious toxicities that can occur in this population, and radiation and ICI modality individually is known to contribute to pneumonitis risk; when combined, they could work synergistically or additively to increase this risk. We set out to evaluate radiation treatment specific risk factors for symptomatic pneumonitis in pts receiving CCRT followed by durvalumab. We hypothesize that adjuvant ICI (durvalumab) will increase the pneumonitis risk from CCRT predicted by current consensus guidelines. <h3>Materials/Methods</h3> We conducted a retrospective study of pts with stage III NSCLC treated with CCRT followed by durvalumab from 2018 -21. Median follow up time was 18.8 mo from the last day of RT to last contact. RT dose parameters were extracted from each treatment plan. Normal lung volume (NLV) was defined as total lung volume minus clinical target volume (Lung -CTV). Percentage of NLV receiving more than 5, 10, or 20 Gy (V5, V10, V20), and mean lung dose (MLD) were calculated. The primary endpoint was development of symptomatic pneumonitis (≥gr 2), assessed via clinical presentation and available imaging. The association between the % NLV of radiation and the probability of developing pneumonitis was analyzed using logistic regression, and odds ratios (OR) were estimated. <h3>Results</h3> Of the 80 patients included in this study, 21 (26.3%) developed symptomatic pneumonitis following durvalumab initiation. 69 (86.3%) received carboplatin-paclitaxel and 11 (13.8%) received cisplatin-etoposide chemotherapy. 73 (91.2%) had received standard RT dose of 60 Gy, while 7 (8.8%) received an additional 12-16 Gy SBRT boost to the primary tumor on a separate study. We found no significant association between symptomatic pneumonitis and RT dose or type of chemotherapy. However, smaller treatment volumes receiving 5 or 10 Gy were associated with lower pneumonitis risk: V10 < 40%, vs ≥ 40% (OR = 0.347, 95% CI 0.11-1.07, P=0.067) and V5 <65% vs ≥65% (OR = 0.42, 95% CI: 0.15-1.17, P = 0.096). Mean MLD was 14.9 Gy (3.9-21.9 Gy), Mean V20 was 25.7% (4.5-40.1%), both well below current consensus guidelines. We did not identify a notable association between pneumonitis and other known clinical risk factors. <h3>Conclusion</h3> This data is from our institution's first cohort of pts treated as in the PACIFIC study after durvalumab was approved by FDA for this indication. Our data suggest pts with a lower radiation treatment volume at 5 or 10 Gy (V5/V10) prior to durvalumab may have a lower risk of developing pneumonitis when other parameters (MLD, V20) are kept under the current recommended radiation tolerance without adjuvant ICI. Further research with larger study populations is needed to confirm this and inform guideline development.