Clinical features and risk factors for interstitial lung disease spreading in low-dose irradiated areas after definitive radiotherapy with or without durvalumab consolidation therapy for patients with non-small cell lung cancer

Background: The current standard of care for patients with unresectable locally advanced non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) combined with durvalumab consolidation therapy. However, radiotherapy (RT) always carries the risk of radiation pneumonitis (RP), which can preclude durvalumab continuation. In particular, the spread of interstitial lung disease (ILD) in low-dose areas or extending beyond the RT field often makes it difficult to determine the safety of continuation or rechallenging of durvalumab. Thus, we retrospectively analyzed ILD/RP after definitive RT with and without durvalumab, with assessment of radiologic features and dose distribution in RT. Methods: : We retrospectively evaluated the clinical records, CT imaging, and radiotherapy planning data of 74 patients with NSCLC who underwent definitive RT at our institution between July 2016 and July 2020. Univariate analysis and propensity score analysis were performed to assess the risk factors for recurrence within one year and occurrence of ILD/RP. Results: : In 68 patients followed up for more than one year, propensity score analysis showed that ≥7 cycles of durvalumab significantly reduced the risk of recurrence within one year (odds ratio: 0.232). Nineteen patients (26%) were diagnosed with ≥ Grade 2 and 7 (9.5%) with ≥ Grade 3 ILD/RP after completing RT. Propensity score analysis showed no significant correlation between durvalumab administration and ≥ Grade 2 ILD/RP. Twelve patients (16%) developed ILD/RP that spread outside the high-dose (>40 Gy) area, of whom 8 (67%) had ≥ Grade 2 and 3 (25%) had Grade 3 symptoms. Univariate analysis showed that high HbA1c level (>6.2%) was significantly associated with the ILD/RP distribution pattern. In propensity score analysis adjusted for risk factors for diabetes mellitus, high HbA1c level was also significantly correlated with ILD/RP pattern spreading outside the high-dose area (odds ratio: 9.865). Conclusions: : Durvalumab improves 1-year progression-free survival without increasing the risk of ILD/RP. High HbA1c level was associated with ILD/RP distribution pattern spreading in the lower dose area or outside RT fields, with a high rate of symptoms. Further study of the clinical background of patients including diabetes is needed to safely increase the number of durvalumab doses after CRT.