Diagnostic Testing Basics

Diagnostic Testing

• A diagnostic test aims to identify a disease or condition to enable its clinical management
• The performance of a diagnostic test is characterized by two key concepts: Sensitivity and Specificity

Sensitivity and Specificity

• Sensitivity: the probability that a diagnostic test will identify disease when disease is present
• Specificity: the probability that a diagnostic test will identify healthy tissue when healthy tissue is present

MarginProbe

• MarginProbe is a diagnostic test that seeks to identify cancerous tissue
• The test can produce four possible outcomes: True Positive, False Positive, True Negative, and False Negative
• Sensitivity and Specificity are calculated using the following formulas:
  • Sensitivity: TP/(TP+FN)
  • Specificity: TN/(TN+FP)

False Positive and False Negative Rates

• False Positive Rate: the probability that a diagnostic test will incorrectly identify healthy tissue as cancerous
• False Negative Rate: the probability that a diagnostic test will incorrectly identify cancerous tissue as healthy
• False Positive Rate = 1-Specificity
• False Negative Rate = 1-Sensitivity

PPV and NPV

• PPV (Positive Predictive Value): the probability that a positive test result is a true positive
• NPV (Negative Predictive Value): the probability that a negative test result is a true negative

Pathology

• Pathology is the study and diagnosis of disease through the examination of surgically removed organs, tissues, bodily fluids, or autopsy
• Surgical Pathology involves macroscopic and microscopic tissue analysis
• Cytopathology examines free cells or tissue fragments
• Molecular Pathology studies and diagnoses disease through examination of molecules within organs, tissues, or bodily fluids

Evaluation of Lumpectomy Margins

• Lumpectomy margins are evaluated to achieve a pathologically clear margin
• The Gold Standard for assessing MarginProbe performance is final histopathology

Diagnostic Testing Concepts

• A diagnostic test seeks to identify a disease or condition to enable its clinical management.
• The performance of a diagnostic test is characterized by its accuracy, sensitivity, and specificity.

Sensitivity and Specificity

• Sensitivity is the probability that a diagnostic test will identify disease when disease is present.
• It measures the proportion of true positives (correctly identified disease cases) among all actual disease cases.
• Example: In a patient with a positive margin, what is the probability that MarginProbe will call it positive?

Specificity

• Specificity is the probability that a diagnostic test will identify healthy tissue when healthy tissue is present.
• It measures the proportion of true negatives (correctly identified healthy tissue cases) among all actual healthy tissue cases.
• Example: In a patient with a clear margin, what is the probability that MarginProbe will call it negative?

MarginProbe Performance

• MarginProbe performance is evaluated by comparing its results to the Gold Standard (final histopathology).
• The Gold Standard is the accepted true description of tissue and margin.
• MarginProbe's sensitivity and specificity can be calculated using formulas: TP/(TP+FN) for sensitivity, and TN/(TN+FP) for specificity.

Pathology

• Pathology is the study and diagnosis of disease through the examination of surgically removed organs, tissues, bodily fluids, or autopsy.
• Surgical Pathology involves macroscopic and microscopic tissue analysis.
• Cytopathology studies and diagnoses disease on a cellular level, while Molecular Pathology identifies mutations or alterations in the genetic code of a patient.

Lumpectomy Margins

• Successful lumpectomy is predicated on achieving a pathologically clear margin.
• Pathologic processing of a breast specimen involves orientation, specimen inking, gross assessment, paraffin embedding, and slicing for microscopic examination.

Breast Conservation Therapy

• Positive margins in breast-conserving surgery (BCS) are associated with patient discomfort, increased costs, and poorer cosmetic outcomes.
• Up to 50% of BCS cases may require reoperation due to positive margins.

Standard of Care (SOC)

• SOC intraoperative methods to evaluate margin status include palpation, specimen imaging, and intraoperative gross and/or microscopic pathology assessment.

Margin Definition

• There is no consensus on the required distance of tumor from the cut edge to define a positive margin.
• Positive/close margins may be defined anywhere between tumor at the inked margin to tumor within 5 mm of the inked margin.

Surgical Margin and Re-excision

• Patients not amenable to margin-free lumpectomy should undergo mastectomy.
• Up to 54% of main lumpectomy specimens may have positive or close margins, requiring re-excision.

MarginProbe Study

• A prospective, randomized, controlled, multicenter study evaluated the use of a real-time, intraoperative probe for positive margin detection in breast-conserving surgery.
• Surgeons were allowed to use any standard of care (SOC) intraoperative methods to evaluate margin status.
• Pathology data were collected for the primary lumpectomy and all repeat ipsilateral surgical procedures within 6 months.

Cosmetic Evaluation

• Cosmetic evaluation was performed at baseline, 7-30 days, and 3-6 months following surgery by an observer unaware of the patient's randomization assignment.
• A symmetry-based scale was used for assessment.

Study Results

• The study demonstrated a significant and consistent reduction in positive margins and re-excision rates.
• A relative reduction of 23% re-excision rates and 62% margins were observed.
• Cosmesis was maintained or improved in the study group.