Circulating tumor DNA and magnetic resonance imaging to predict neoadjuvant chemotherapy response and recurrence risk.
Mark Jesus M MagbanuaWen LiDenise M WolfChristina YauGillian L HirstLamorna Brown SwigartDavid C NewittJessica GibbsAmy L DelsonEkaterina KalashnikovaAlexey AleshinBernhard ZimmermannA Jo ChienDebasish TripathyLaura J EssermanNola M HyltonLaura van 't VeerPublished in: NPJ breast cancer (2021)
We investigated whether serial measurements of circulating tumor DNA (ctDNA) and functional tumor volume (FTV) by magnetic resonance imaging (MRI) can be combined to improve prediction of pathologic complete response (pCR) and estimation of recurrence risk in early breast cancer patients treated with neoadjuvant chemotherapy (NAC). We examined correlations between ctDNA and FTV, evaluated the additive value of ctDNA to FTV-based predictors of pCR using area under the curve (AUC) analysis, and analyzed the impact of FTV and ctDNA on distant recurrence-free survival (DRFS) using Cox regressions. The levels of ctDNA (mean tumor molecules/mL plasma) were significantly correlated with FTV at all time points (p < 0.05). Median FTV in ctDNA-positive patients was significantly higher compared to those who were ctDNA-negative (p < 0.05). FTV and ctDNA trajectories in individual patients showed a general decrease during NAC. Exploratory analysis showed that adding ctDNA information early during treatment to FTV-based predictors resulted in numerical but not statistically significant improvements in performance for pCR prediction (e.g., AUC 0.59 vs. 0.69, p = 0.25). In contrast, ctDNA-positivity after NAC provided significant additive value to FTV in identifying patients with increased risk of metastatic recurrence and death (p = 0.004). In this pilot study, we demonstrate that ctDNA and FTV were correlated measures of tumor burden. Our preliminary findings based on a limited cohort suggest that ctDNA at surgery improves FTV as a predictor of metastatic recurrence and death. Validation in larger studies is warranted.
Keyphrases
- circulating tumor
- neoadjuvant chemotherapy
- free survival
- cell free
- circulating tumor cells
- magnetic resonance imaging
- locally advanced
- lymph node
- end stage renal disease
- transcription factor
- squamous cell carcinoma
- newly diagnosed
- computed tomography
- contrast enhanced
- healthcare
- depressive symptoms
- peritoneal dialysis
- early breast cancer
- coronary artery disease
- mass spectrometry
- rectal cancer
- health information
- diffusion weighted imaging
- percutaneous coronary intervention
- real time pcr
- breast cancer risk