The DecisionDx-EC test has completed extensive technical and clinical validation in localized esophageal adenocarcinoma with initial phases done in the research laboratories of The University of Texas MD Anderson Cancer Center (MD Anderson) and final clinical validation completed in a CLIA certified clinical laboratory under the direction of Castle Biosciences.
Development study results and data from the first clinical validation study were presented at the American Society of Clinical Oncology in 2011 (Ajani, 2011). This study was a single-center, prospectively planned study using archival tissue samples.
A multi-center, prospectively planned study using archival tissue samples was recently completed, which constitutes a second, independent clinical validation study. Importantly, the response to CTRT was re-confirmed under blinded conditions. Data from this second study, and additional ongoing studies, are expected to be presented at an upcoming scientific meeting.
The development program includes Discovery, Development and Clinical Validation studies.
Data from the MD Anderson development and validation studies were presented at the annual meeting of the American Society of Clinical Oncology in 2011 (Ajani, JCO 2011). Patients received CTRT followed by surgery. For these studies, researchers defined extreme resistance to chemoradiation therapy as patients having greater than 50% residual tumor upon surgical resection per the Rohatgi research tool. In clinical practice physicians often use a grading tool developed and approved by the College of American Pathologists (CAP). The CAP tool uses Treatment Response Grades (TRG) of 0, 1, 2, and 3. TRG grade 0 is defined as complete response with no residual tumor cells, grade 1 is defined as “moderate” response with minimal residual tumor cells, grade 2 is minimal response, and grade 3 is defined as no or poor response.
In the first DecisionDx-EC clinical validation study, biostatistical analysis of the logistic regression model used to classify extreme resistance samples yielded an uncorrected area under the receiver operating curve, or AUC, of 0.96 and corrected AUC of 0.95. This statistical measure is used to assess new tests on a scale where 0.5 means the result is similar to chance, and 1.0 means that the test perfectly predicts the known outcome.
Castle Biosciences completed technical requirements for DecisionDx-EC analytical validation by processing more than 250 sample runs of archival esophageal adenocarcinoma tumor tissue. Two clinical experts (a pathologist and a doctorate-level clinical scientist) who were blinded to patient outcome scored each sample during development and optimization studies. A 94% concordance was achieved between these two assessors indicating high proficiency and consistency.
The second clinical validation study was a multi-center, prospectively planned and blinded study that was initiated and completed following finalization of the CLIA standard operating procedures. This study achieved several important objectives:
- Confirmed the concordance between the research grading tool used by
MD Anderson and the College of American Pathologists (CAP)
Treatment Response Grading (TRG) tool used clinically for esophageal
cancer. This study employed centralized blinded pathology scoring of
paired post-treatment resection tissue. Each specimen was graded
according to both tools. Blinded scoring showed the following:
|Pathologic complete response||Grade 0||0% residual tumor||100%|
|Partial response||Grade 1 or 2||>0% and ≤50%||100%|
- Maintained the high level of test scoring concordance between the two
clinical scientists established in the first clinical validation study.
The concordance between the two clinical scientists in the second study
- Established the positive predictive value (PPV) of the DecisionDx-EC
test under CLIA conditions. The PPV was found to be 92%, meaning
that when the assay predicts likelihood of ex-CTRT, it is highly accurate.
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