Risk Factors and Incidence of Pneumonitis in NSCLC Patient Treated with ChemoRadiotherapy and Durvalumab: A Comparative Analysis with a Non-Durvalumab Cohort (PraDa) - 12/09/26

Doi : 10.1016/j.resmer.2026.101325

Julien SWIDERSKI ^1,^2,^⁎ , Cécile EVIN ³, François DURAND-HARDY ⁴, Thomas DUROY ⁴, Emilie LANOY ⁴, Sabrina AZIEZ ⁵, Oulimata DIENG ⁶, Mickael ANDRAUD ⁷, Sophie GUILLERM ⁵, Anthony CANELLAS ⁸, Baptiste ABBAR ⁹, Elisabeth FABRE ¹⁰, Valérie GOUNANT ¹¹, Etienne GIROUX-LEPRIEUR ¹², Guillaume CHASSAGNON ¹³, Catherine DURDUX ³, Marie WISLEZ ^1,²

¹ Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, Institut du cancer Paris CARPEM, Team Inflammation, Complement and Cancer, Paris, France

² Department of Pneumology, Cochin Hospital, AP-HP.centre, Université Paris Cité, Paris, France

³ Service d’Oncologie-Radiothérapie, Hôpital Européen Georges-Pompidou, 20 rue Leblanc, Paris, France

⁴ Unité de Recherche Clinique, INSERM CIC-EC1418, Hôpital Européen Georges-Pompidou, Paris, France

⁵ Service de Cancérologie-Radiothérapie, Hôpital Saint-Louis, 1 avenue Claude-Vellefaux, Paris, France

⁶ Service d’Oncologie-Radiothérapie, Hôpital Tenon, 4 rue de la Chine, Paris, France

⁷ AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service de Radiothérapie, Paris, France.

⁸ Service de Pneumologie, Sorbonne Université, Hôpital Tenon, 4 rue de la Chine, Paris, France

⁹ Service d’Oncologie médicale, Hôpital Pitié-Salpêtrière, Sorbonne Université, 47-83 boulevard de l’Hôpital, Paris, France

¹⁰ Service d’Oncologie médicale, Hôpital Européen Georges-Pompidou HEGP, 20 rue Leblanc, Paris, France

¹¹ Service d’Oncologie thoracique, Hôpital Bichat Claude-Bernard, 46 rue Huchard, Paris, France

¹² Service de Pneumologie et oncologie thoracique, Hôpital Ambroise-Paré, 9 avenue Charles-de-Gaulle, Boulogne-Billancourt, France

¹³ Service de Radiologie, Hôpital Cochin, 27 rue du Faubourg Saint-Jacques, Paris, France

^⁎ Corresponding author: Julien SWIDERSKI, Service de Pneumologie, Hôpital Cochin, 27 rue du Faubourg Saint-Jacques, Paris, France Service de Pneumologie Hôpital Cochin 27 rue du Faubourg Saint-Jacques Paris France

Sous presse. Manuscrit accepté. Disponible en ligne depuis le Saturday 12 September 2026

Highlights

•	91 NSCLC patients included in the ambispective multicenter PRADA study.
•	G2+ pneumonitis rates similar with or without Durvalumab consolidation.
•	Female sex, total RT dose, heart dose associated with G2+ pneumonitis.
•	Centralized CT scan review ensured robust pneumonitis assessment.
•	Detailed dosimetric data reinforced validity of observed associations.

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Abstract

Background

Concurrent chemoradiotherapy is the standard treatment for unresectable, locally advanced non-small cell lung cancer (NSCLC). In patients without progression, adjuvant Durvalumab, an anti–PD-L1 antibody, improves survival but raises concerns about iatrogenic pneumonitis (radiation-induced or immune-mediated). This study aimed to assess the incidence and identify predictive factors of grade ≥2 (G2+) iatrogenic pneumonitis in patients treated with or without Durvalumab.

Materials and Methods

We conducted an ambispective cohort study across five hospitals between January 2019 and December 2020. Patients with unresectable, locally advanced NSCLC treated with concurrent chemoradiotherapy with or without Durvalumab were included. Iatrogenic pneumonitis was diagnosed based on clinical and radiological criteria, excluding alternative causes. The primary endpoint was the 2-year cumulative incidence of G2+ iatrogenic pneumonitis after radiotherapy.

Results

Ninety-one patients were included: 57 in the Durvalumab group and 34 in the control group. Grade ≥ 2 iatrogenic pneumonitis occurred in 30% of patients receiving Durvalumab and 24% of those without (p = 0.5). In the complete cohort, significant interactions between durvalumab treatment and female sex (p = 0.05), total radiotherapy dose (p = 0.03), and mean heart dose (p = 0.04) were observed for the risk of pneumonitis.

Conclusion

The addition of Durvalumab to chemoradiotherapy did not significantly increase the incidence of G2+ iatrogenic pneumonitis. However, the identification of female sex, total radiation dose, and mean heart dose as potential risk factors highlights the need for personalized monitoring. Prospective validation is warranted.

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Keywords : Non-small cell lung cancer, Durvalumab, Chemoradiotherapy, Iatrogenic pneumonitis, Radiation-induced pneumonitis, Immune-related toxicity, Predictive factors