Clinical utility of circulating cell-free DNA in advanced colorectal cancer

<div><p>Background</p><p>Circulating cell-free DNA (cfDNA) isolated from the plasma of cancer patients (pts) has been shown to reflect the genomic mutation profile of the tumor. However, physician and patient assessment of clinical utility of these assays in patients with metastatic colorectal cancer (mCRC) has not been previously described.</p><p>Methods</p><p>Patients were prospectively consented to a prospective genomic matching protocol (Assessment of Targeted Therapies Against Colorectal Cancer [ATTACC]), with collection of blood for cfDNA extraction and sequencing of a 54-gene panel in a CLIA-certified lab. Formalin-fixed, paraffin-embedded (FFPE) tissue from prior resections or biopsies underwent 50-gene sequencing. Results from both assays were returned to the treating physicians for patient care and clinical trial selection. Follow-up surveys of treating physicians and chart reviews assessed clinical utility.</p><p>Results</p><p>128 mCRC pts were enrolled between 6/2014 and 1/2015. Results were returned in median of 13 and 26 days for cfDNA and FFPE sequencing, respectively. With cfDNA sequencing, 78% (100/128) of samples had a detectable somatic genomic alteration. 50% of cfDNA cases had potentially actionable alterations, and 60% of these could be genomically matched to at least one clinical trial in our institution. 50% (15/30) of these pts enrolled onto an identified matched trial. Physicians reported that the cfDNA testing improved the quality of care they could provide in 73% of the cases, and that 89% of pts reported greater satisfaction with the efforts to personalize experimental therapeutic agents.</p><p>Conclusions</p><p>cfDNA sequencing can provide timely information on potentially actionable mutations and amplifications, thereby facilitating clinical trial enrollment and improving the perceived quality of care.</p></div

Patient demographic characteristics.

<p>Patient demographic characteristics.</p

Clinical utility of cfDNA sequencing results.

<p><b>(A)</b> Detectable mutations and/or amplification were present in 78% of patients. <b>(B)</b> 50% of these patients (N = 50) had “potentially actionable” mutations and/or amplifications. <b>(C)</b> Among these, 60% (N = 30) patients had a clinical trial identified based on the matched biomarker detected from the cfDNA (D) 15 patients ultimately enrolled on a biomarker-based clinical trial. Pt = patient; MDACC = MD Anderson Cancer Center.</p

Provider survery results.

<p>Physician preference for convenience (A) and clinical utility (B) according to the sample detection method and a stated desire to incorporate sequencing results into clinical decisions. FFPE = formalin-fixed, paraffin-embedded tissue; cfDNA = cell-free DNA.</p

The impact of the use of cfDNA in (A) quality of care and (B) patient satisfaction.

<p>The impact of the use of cfDNA in (A) quality of care and (B) patient satisfaction.</p

Number of patients with genomic alterations detected by both FFPE and cfDNA analysis.

<p>FFPE = formalin-fixed, paraffin-embedded tissue; cfDNA = cell-free DNA; Amplif = amplification.</p

Additional findings noted in sequencing of historic FFPE specimens compared to cfDNA sequencing.

<p>FFPE = formalin-fixed, paraffin-embedded tissue; cfDNA = cell-free DNA.</p

The Mid-infrared Instrument for JWST and Its In-flight Performance

The Mid-Infrared Instrument (MIRI) extends the reach of the James Webb Space Telescope (JWST) to 28.5 μm. It provides subarcsecond-resolution imaging, high sensitivity coronagraphy, and spectroscopy at resolutions of λ/Δλ ∼ 100–3500, with the high-resolution mode employing an integral field unit to provide spatial data cubes. The resulting broad suite of capabilities will enable huge advances in studies over this wavelength range. This overview describes the history of acquiring this capability for JWST. It discusses the basic attributes of the instrument optics, the detector arrays, and the cryocooler that keeps everything at approximately 7 K. It gives a short description of the data pipeline and of the instrument performance demonstrated during JWST commissioning. The bottom line is that the telescope and MIRI are both operating to the standards set by pre-launch predictions, and all of the MIRI capabilities are operating at, or even a bit better than, the level that had been expected. The paper is also designed to act as a roadmap to more detailed papers on different aspects of MIRI.</p