Glenn J Hanna1, Ji Eun Bae2, Jochen H Lorch2, Jonathan D Schoenfeld3, Danielle N Margalit3, Roy B Tishler3, Robert I Haddad2, Nicole G Chau4. 1. Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. Electronic address: glenn_hanna@dfci.harvard.edu. 2. Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. 3. Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham & Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. 4. Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; BC Cancer, Vancouver Centre, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada.
Abstract
BACKGROUND: Little is known about the long-term impact of local and systemic therapies for recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC), or the clinical significance of molecular alterations. METHODS: We identified 72 R/M cases among 123 ACC patients from our institution. We report long-term outcomes, predictors of recurrence and survival, and the impact of sequential cancer-directed therapy among R/M patients. We integrate genomic data for 36 sequenced ACC patients. RESULTS: Median overall survival (OS) from initial diagnosis was 35.1 ys (95%CI: 25.8-37.3) for R/M ACC patients. 10-y OS among R/M patients was 84.7%, worse for patients with extra-pulmonary metastatic disease (p = 0.02). Only initial disease stage predicted recurrence (OR 1.69, p = 0.03). Longer time to first R/M treatment predicted improved survival (p < 0.01); those treated ≤ 3 years from their R/M diagnosis had poor outcomes (p = 0.01). R/M patients who received systemic therapy vs. active surveillance had similar survival (p = 0.35). Molecular findings predicted outcomes: 10-y OS: 100% MYB, 53.3% PI3K, 32.1% NOTCH1 and others, p = 0.03. PI3K mutations predicted a longer disease-free interval (p = 0.04). CONCLUSIONS: Underlying disease biology remains the strongest predictor of outcomes in R/M ACC. Shorter time to R/M therapy predicts poor outcomes. Molecular alterations are prognostic, and PI3K mutations identify an intermediate-risk ACC subgroup.
BACKGROUND: Little is known about the long-term impact of local and systemic therapies for recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC), or the clinical significance of molecular alterations. METHODS: We identified 72 R/M cases among 123 ACCpatients from our institution. We report long-term outcomes, predictors of recurrence and survival, and the impact of sequential cancer-directed therapy among R/M patients. We integrate genomic data for 36 sequenced ACCpatients. RESULTS: Median overall survival (OS) from initial diagnosis was 35.1 ys (95%CI: 25.8-37.3) for R/M ACCpatients. 10-y OS among R/M patients was 84.7%, worse for patients with extra-pulmonary metastatic disease (p = 0.02). Only initial disease stage predicted recurrence (OR 1.69, p = 0.03). Longer time to first R/M treatment predicted improved survival (p < 0.01); those treated ≤ 3 years from their R/M diagnosis had poor outcomes (p = 0.01). R/M patients who received systemic therapy vs. active surveillance had similar survival (p = 0.35). Molecular findings predicted outcomes: 10-y OS: 100% MYB, 53.3% PI3K, 32.1% NOTCH1 and others, p = 0.03. PI3K mutations predicted a longer disease-free interval (p = 0.04). CONCLUSIONS: Underlying disease biology remains the strongest predictor of outcomes in R/M ACC. Shorter time to R/M therapy predicts poor outcomes. Molecular alterations are prognostic, and PI3K mutations identify an intermediate-risk ACC subgroup.
Authors: Lauren E Miller; Vivienne Au; Tara E Mokhtari; Deborah Goss; Daniel L Faden; Mark A Varvares Journal: Cancers (Basel) Date: 2022-02-16 Impact factor: 6.639