Chest computed tomography of trastuzumab-deruxtecan (T-DXd)-related interstitial lung disease: Key points for radiologists

Trastuzumab-deruxtecan (T-DXd) is an antibody-drug conjugate targeting HER2, increasingly used to treat advanced HER2-positive tumors, including breast, gastric, lung, and colorectal cancers. Like other anticancer agents, T-DXd carries a risk of pneumotoxicity, with interstitial lung disease (ILD) occurring in 10-12% of patients. Early identification, accurate diagnosis, and appropriate management of T-DXd-related ILD are essential to optimize patient outcomes. Radiologists are key in detecting, characterizing, and monitoring ILD on chest computed tomography (CT) within a multidisciplinary care team. This review aims to familiarize radiologists with the chest CT imaging features of T-DXd-related ILD, drawing from clinical trials and real-world data. Practical guidance is provided for image interpretation and differential diagnosis, with a focus on recognizing key patterns. To support this, the review also outlines the mechanism of action of T-DXd, its clinical indications, and associated adverse events, particularly pneumotoxicity. Given the expanding use of T-DXd, radiologists must recognize ILD patterns on CT, namely organizing pneumonia (the most common), diffuse alveolar damage, hypersensitivity pneumonitis, and nonspecific interstitial pneumonia, while remaining alert to less frequent findings and differential diagnoses. When available, prior imaging for comparison is essential to differentiate disease progression, infection, and other conditions. CT imaging also supports the assessment of patient eligibility for T-DXd, proactive monitoring during treatment, and ILD reassessment. Close collaboration between radiologists and oncologists is critical for early ILD detection, accurate diagnosis, and optimal patient management.