Connor, Dana

e18064 Background: Cell-free circulating tumor DNA (ctDNA)-based test has emerged as a promising tool in informing treatment modification in solid tumors. The clinical applications of ctDNA in head and neck squamous cell carcinoma (HNSCC) has been explored and here we report the clinical utilities of ctDNA in disease monitoring in HNSCC. Methods: HNSCC patients treated at our institution with available ctDNA test (Signatera) results between 2022 and 2024 were identified. Clinical information including disease site, stage and imaging results were collected and analyzed. Results: A total of 59 patients were identified. 21 (36%) patients had P16 + oropharyngeal cancer, 16 (27%) had oral cavity cancer, 9 (15%) patients had laryngeal cancer, 7 (12%) had P16-oropharyngeal cancer, 6 (10%) had perinasal sinus, hypopharyngeal or nasopharyngeal cancers. At the time of ctDNA test, 22 (36%) patients completed curative-intent treatment and had no radiographic evidence of disease (NED), 16 (26%) patients were treatment-naïve and had local/regional (LR) disease only, and 22 (36%) patients completed definitive treatment and developed radiographic evidence of LR recurrence or distant (D) metastatic disease. ctDNA was detectable in less than half (44%) of the treatment-naïve patients and the detection rate was even lower (14%) in the subgroup of p16+ oropharyngeal cancer. However, among patients with LR recurrent and distant metastatic disease, majority (77%) had positive ctDNA. ctDNA was undetectable in most of the patients (80%) who completed definitive treatment and were NED radiographically. Among the 3 patients who had detectable ctDNA, 2 were subsequently found to have recurrent disease on images and 1 is still on surveillance (table). Conclusions: Positive ctDNA was detected in most of the HNSCC with LR recurrent or distant metastatic disease, supporting its potential role in treatment response monitoring in this group of patients. Detectable ctDNA preceded radiographic evidence of recurrent disease in a small number of patients, suggesting the possibility of minimal residual disease detection using ctDNA in a subgroup of patients. Treatment history S/P definitive treatment Treatment naive S/P definitive treatment Radiographic evidence of disease (patient number) No (21) Yes (16; LR only) Yes (21; LR only: 10, distant: 11) ctDNA negative 18 9 4 ctDNA positive 3 (recurrence confirmed on subsequent imaging in 2 patients) 7 17

e15046 Background: ctDNA assays can be used to assess molecular residual disease, and the value of ctDNA monitoring in disease surveillance and treatment response assessment has been demonstrated in colon, breast, lung, and bladder cancers. However, the data of ctDNA in rare cancers has been lacking. We conducted this retrospective study to investigate the potential roles of ctDNA monitoring in rare tumors in both surveillance and response evaluation. Methods: ctDNA assay results of 12 patients (pts) with rare cancers including adrenocortical carcinoma (ACC) (4 pts), salivary gland cancers (3 pts), pleural or peritoneal malignant mesothelioma (4 pts), and anaplastic thyroid cancer (ATC) (1pt) undergoing treatment or surveillance in 2023 at Mayo Clinic Florida were analyzed. The trends of ctDNA levels were correlated with radiographic images findings. Results: Among the 12 patients, ctDNA was detected in at least one time point in 9 (75%) pts, including 1 (100%) ATC pt, 2 (66%) salivary gland pts, 3 (75%) malignant mesothelioma pts, and 3 (75%) ACC pts. Among these 9 pts, 5 pts had ctDNA collected at more than one timepoints, and the trends of ctDNA levels were consistent with image findings in all 5 pts. Among these 5 pts, one pt received definitive surgery for ACC with clearance of ctDNA after the surgery and one salivary gland cancer pt was undergoing surveillance and later developed disease progression. The other 3 pts were undergoing palliative systemic therapy and had responded to treatments. Conclusions: ctDNA was detectable in majority of the patients with rare malignancies reviewed in this study, including ACC, ATC, pleural or peritoneal malignant mesothelioma, and salivary gland cancers. Further study is warranted to investigate the role of ctDNA monitoring in surveillance and treatment response evaluation in rare malignancies.