Minimal Residual Disease Detection using a Plasma-only Circulating Tumor DNA Assay in Patients with Colorectal Cancer.

PURPOSE: Detection of persistent circulating tumor DNA (ctDNA) after curative-intent surgery can identify patients with minimal residual disease (MRD) who will ultimately recur. Most ctDNA MRD assays require tumor sequencing to identify tumor-derived mutations to facilitate ctDNA detection, requiring tumor and blood. We evaluated a plasma-only ctDNA assay integrating genomic and epigenomic cancer signatures to enable tumor-uninformed MRD detection. EXPERIMENTAL DESIGN: A total of 252 prospective serial plasma specimens from 103 patients with colorectal cancer undergoing curative-intent surgery were analyzed and correlated with recurrence. RESULTS: Of 103 patients, 84 [stage I (9.5%), II (23.8%), III (47.6%), IV (19%)] had evaluable plasma drawn after completion of definitive therapy, defined as surgery only (n = 39) or completion of adjuvant therapy (n = 45). In "landmark" plasma drawn 1-month (median, 31.5 days) after definitive therapy and >1 year follow-up, 15 patients had detectable ctDNA, and all 15 recurred [positive predictive value (PPV), 100%; HR, 11.28 (P < 0.0001)]. Of 49 patients without detectable ctDNA at the landmark timepoint, 12 (24.5%) recurred. Landmark recurrence sensitivity and specificity were 55.6% and 100%. Incorporating serial longitudinal and surveillance (drawn within 4 months of recurrence) samples, sensitivity improved to 69% and 91%. Integrating epigenomic signatures increased sensitivity by 25%-36% versus genomic alterations alone. Notably, standard serum carcinoembryonic antigen levels did not predict recurrence [HR, 1.84 (P = 0.18); PPV = 53.9%]. CONCLUSIONS: Plasma-only MRD detection demonstrated favorable sensitivity and specificity for recurrence, comparable with tumor-informed approaches. Integrating analysis of epigenomic and genomic alterations enhanced sensitivity. These findings support the potential clinical utility of plasma-only ctDNA MRD detection.See related commentary by Bent and Kopetz, p. 5449.

Minimally invasive evacuation of intraventricular hemorrhage with the Apollo vibration/suction device.

Intraventricular hemorrhages (IVH) can occur as a consequence of spontaneous intracerebral hemorrhage, aneurysm rupture, arteriovenous malformation hemorrhage, trauma, or coagulopathy. IVH is a known risk factor for poor clinical outcome with up to 80% mortality. The current standard treatment strategy for IVH consists of the placement of an external ventricular drain. We report our early experience with using the Apollo suction/vibration aspiration system (Penumbra, Alameda, CA, USA) for minimally invasive evacuation of IVH with a review of the pertinent literature. Medical records of patients with IVH who were admitted to Rush University Medical Center, USA, from July to November 2014 were queried from the electronic database. Patients with Graeb Scores (GS) >6 were selected for minimally invasive IVH evacuation with the Apollo aspiration system. Patient demographics, pre- and post-operative GS, pre- and post-operative modified Graeb Score (mGS), as well procedure related complications were analyzed and recorded. A total of eight patients (five men) were identified during the study period. The average age was 55.5years. The mean GS was 9.6 pre-operatively and decreased to 4.9 post-operatively (p=0.0002). The mean mGS was 22.9 pre-operatively and decreased to 11.4 post-operatively (p=0.0001). Most of the IVH reduction occurred in the frontal horn and atrium of the lateral ventricle, as well the third ventricle. One (1/8) procedure-related complication occurred consisted of a tract hemorrhage. The Apollo system can be used for minimally invasive IVH evacuation to achieve significant blood clot volume reduction with minimal procedure-related complication.