The role of circulating tumor DNA (ctDNA), tumor markers (TMs), and patient-reported outcomes (PROs) in predicting treatment response in patients with metastatic gastrointestinal (GI) cancer.

Abstract

833 Background: Changes in ctDNA and serum TMs (CEA and CA19-9) can serve as predictors of response to systemic therapy in GI cancer patients (pts). Similarly, PROs correlate with survival and treatment response. We present a preliminary analysis of ctDNA, TMs, and PROs in predicting treatment response. Methods: We are enrolling 200 pts in a prospective study with metastatic pancreatic (PDAC), colorectal (CRC), gastroesophageal (GE), and biliary cancers. We are collecting ctDNA, TMs (CEA for all tumor types; CA19-9 for PDAC, GE, biliary), and PROs (FACT-G for QOL [higher scores indicate better QOL]; ESAS-r and PRO-CTCAE for symptoms; and PHQ-4 [consists of GAD-2 and PHQ-2 for anxiety and depression]; higher ESAS-r, PRO-CTCAE, and PHQ-4 scores reflect greater symptom burden) at baseline and 4 weeks. ctDNA is benchmarked against somatic tissue alterations, and serially assessed by digital droplet PCR. We correlated median percent change from baseline to 4 weeks for ctDNA, TMs, and PROs with treatment response (clinical benefit [CB], progressive disease [PD]). Results: From April to August 2019, we have enrolled 38/45 (84.4%) eligible pts (median age = 64 years; 36.8% female). Among these 38 pts, tumor types are PDAC (36.8%), CRC (31.6%), GE (28.9%), and biliary (2.6%). 18/38 pts were evaluable for ctDNA. Change in ctDNA was -94.5% in pts with CB (n = 10) and -19.5% in pts with PD (n = 8; p = 0.025). No correlation was observed between CEA and treatment response (p = 0.367). Change in CA19-9 was -1.5% for pts with CB and +47% for pts with PD (p = 0.019). Changes in PRO-CTCAE (p = 0.345), GAD-2 (p = 0.697), and ESAS scores (p = 0.743) did not differ between pts with CB and PD. However, changes in PHQ-2 (CB 0% v. PD +22.5%; p < 0.001), PHQ-4 (CB -8.5% v. PD +5%; p = 0.015), and FACT-G (CB +30% v. PD +5%; p = 0.049) were significant. Conclusions: Preliminary analysis suggests that ctDNA and PROs demonstrate promising utility for early prediction of treatment response, with favorable performance relative to standard TMs. Further analyses of larger pt numbers in this ongoing study may clarify the use and integration of these measures to better predict pt outcomes.