(P 140) CIRCULATING TUMOR DNA AS A TOOL OF SURVEILLANCE AND EARLY INDICATOR OF RELAPSE IN SARCOMA PATIENTS

Objective: The use of circulating tumor DNA (ctDNA) has been increasingly explored to monitor treatment response and surveillance for recurrence in cancer patients. Given the minimally-invasive method of measurement via blood samples and its accuracy compared to traditional tools of monitoring with imaging studies, this method shows promise for implementation as part of patient monitoring following their primary treatment. Currently, the role of ctDNA monitoring is being explored in sarcoma patients. We report our experience in a retrospective series of sarcoma patients where ctDNA was measured in the context of clinical care.

Methods: Retrospective review of medical records from four sarcoma patients who were monitored with a tumor-informed ctDNA assay (SignateraTM) and conventional imaging studies after completing primary treatment for underlying sarcoma was carried out . Each patient’s ctDNA results and overall clinical course were recorded. CtDNA was measured every two months following completion of treatment.

Results: Patient A: A 36 year-old female was initially diagnosed with left breast angiosarcoma with liver metastasis. Patient was on pazopanib after initial treatment with surgery and chemotherapy, and there was no tumor evidence. Patient was followed with ctDNA, and 37 days later, ctDNA measurements yielded a positive result (1.25 MTM/mL). Abdomen MRI two months later revealed a liver lesion suspicious for metastasis. Patient was then referred for Cryoablation.
Patient B: A 43 year-old female was initially diagnosed with metastatic undifferentiated pleomorphic sarcoma. Patient was in remission for almost one year after metastatectomies of lung lesions and was on pazopanib. Chest CT of abdomen and pelvis during remission revealed no evidence of obvious recurrence. CtDNA measurements first yielded a positive result (1.31 MTM/mL plasma) 14 days before CT results. Given that the patient's CT scans did not show any obvious metastatic disease but ctDNA was positive, a PET scan was done, which showed multiple hypermetabolic lesions in the left paravertebral, left hilar, left cardiophrenic, and fifth intercostal space, indicating recurrence. Patient was started on systemic chemotherapy. Positive ctDNA levels with negative CT scans led us to an additional PET study, which enabled earlier treatment redirection.
Patient C: A 49 year-old female was initially diagnosed with left breast angiosarcoma. She finished initial treatment and was followed closely. A ctDNA assay yielded a positive result (1.69 MTM/mL). A CT chest, abdomen, and pelvis one month later showed no recurrent disease. A second ctDNA 17 days after CT scan showed further ctDNA increase (8.9 MTM/mL). This ctDNA levels increase and negative CT scans led us to order a PET scan, which revealed new bone lesions in the sternum, right sacrum/ilium, and left femur, all indicating metastasis. Patient was started on systemic therapy.
Patient D: A 34 year-old male was initially diagnosed with dedifferentiated chondrosarcoma of the right fibula. The patient completed treatment with surgery and chemotherapy, and ctDNA measurements were routinely obtained and were negative. Subsequently, patient had a right knee MRI showing a small lesion in the resection bed. A core biopsy revealed dedifferentiated chondrosarcoma. Subsequently, ctDNA assay was performed and found to be positive, and radiation was implemented. Follow-up ctDNA became negative, likely in response to radiation therapy. Patient ultimately underwent resection.

Conclusion: Given each sarcoma patient’s unique initial disease, remission, and recurrence, the use of ctDNA testing demonstrated promising use compared to traditional imaging studies in the sarcoma patients reported, appearing to indicate evidence of disease recurrence and progression. The patient cases analyzed here hold promise for ctDNA as an additional tool to traditional surveillance methods, given the assay’s ability to correlate precisely to disease recurrence or progression. In three of four patients, positive ctDNA results were obtained before imaging studies and revealed signs of recurrence. Early recurrence detection made possible by using a tumor-informed ctDNA assay may ultimately improve patient outcomes by starting them on treatment after early detection of recurrence.