Oligometastatic Adenoid Cystic Carcinoma: Correlating Tumor Burden and Time to Treatment With Outcomes

Abstract

<h3>Purpose/Objective(s)</h3> : Ablation of oligometastases (OM) has demonstrated benefit in specific histologies such as non-small cell lung and prostate cancer, among other tumor types. Although local ablation is often employed in the treatment of patients with metastatic adenoid cystic carcinoma (ACC), there are limited data as to the detection and management of OM in this disease. We aimed to characterize the natural history of OM in patients with ACC and identify predictors of long-term outcomes. <h3>Materials/Methods</h3> : We identified 42 patients with metastatic ACC treated with systemic and/or locally ablative therapy between 2001 and 2019. Locally ablative treatments included surgical resection, radiation therapy, and radiofrequency ablation. Systemic treatments included chemotherapy, targeted therapy, or immunotherapy. Imaging studies were retrospectively analyzed to identify patients with OM (1-5 lesions) at any point during their follow-up. Number of metastases and tumor burden (sum of all measurable lesions > 2 mm) was recorded at three timepoints: when metastases were first visualizable on imaging, confirmed by biopsy, and treated. Long-term outcomes were analyzed using the Kaplan-Meier method. <h3>Results</h3> : There was evidence of OM in 33/42 (79%) patients. A majority of these patients had OM to the lungs (82%) while fewer patients had OM to the bone (9%) and liver (6%). The median time between initial ACC diagnosis and earliest detection of metastasis was 13.1 months (range 0-298). At the time of earliest detection, 15 patients had a single lesion, 7 patients had 2 lesions, 6 patients had 3 lesions, 2 patients had 4 lesions, 3 patients had 5 lesions, and 9 patients had polymetastases (PM, 6+ lesions). Median overall survival (OS) for patients with a solitary metastasis on first visualization was 36.0 years, compared to 11.7, 11.5, and 8.5 years for those presenting with 2-3, 4-5, and 6+ metastases, indicating a significant association between number of metastases and OS (<i>P</i> = 0.04). 18 patients still had OM when they first received local or systemic treatment for metastatic disease, and had significantly improved OS compared to 24 patients treated for PM (36.0 years vs. 9.2 years, HR 0.38; 95% CI, 0.14-0.89). Patients with OM who received earlier locally ablative treatment (median time from OM detection to local treatment 21.5 months) had improved OS (17.7 vs. 9.2 years, HR, 0.15; 95% CI 0.02-0.63). However, early systemic treatment of patients with OM did not impact survival. <h3>Conclusion</h3> : A significant proportion of patients with ACC will experience an oligometastatic state in the natural history of their cancer, for whom earlier ablative therapy may improve survival outcomes. To build upon these findings, we have since developed a clinical trial to investigate the benefit of treating oligometastatic ACC with early initiation of stereotactic body radiation therapy (SBRT). Future studies are needed to determine the potential role of early treatment of OM in patients with ACC.