George Cernile, Manager A.I. Technology Group Artificial Intelligence In Medicine Inc. Advancements in Automated Synoptic Reporting

Synoptex technologyPerformance measuresSynoptex enhancementsUses of synoptic dataCAP checklists Slide 2

11 June Synoptic Report CLINICAL HISTORY/MACROSCOPY Right mastectomy and axillary tissue. A right mastectomy specimen with overlying skin measuring 220mm x 85mm and underlying breast tissue measuring 220mm x 100mm x 70mm. The axillary tail measures 125 x 60mm. The nipple is slightly retracted and located centrally. The superior margin is painted red, the inferior margin painted green and the deep cut margin is painted blue. Cut sections of the underlying breast tissue shows an ill-defined grey white yellow lesion with patchy areas of haemorrhage measuring 35 x 35 x 35mm located immediately below the nipple, 20mm from the inferior margin, 45mm from the deep cut margin, 50mm from the superior margin, 85mm from the medial margin and 100mm from the lateral cut margin. A1 - nipple, B1 - upper outer quadrant, C1 - upper inner quadrant, D1 - lower outer quadrant, E1 - lower inner quadrant, F1, G1 - tumour composite blocks, H1, I1 - tumour composite blocks, J1 - deep cut margin, K1 - superior margin, L1 – inferior margin, M4 - lymph nodes, N4 - lymph nodes, O - 3 serial slices, lymph node, P - 3 lymph nodes. MICROSCOPY This right mastectomy specimen demonstrates an invasive ductal carcinoma with the following pathological features: TUMOUR HISTOLOGY & GRADE The tumour is of an infiltrating poorly differentiated ductal carcinoma of non-otherwise specified type. The tumour is poorly defined and extremely infiltrative, comprising poorly-formed tubules, nests or strands of cuboidal tumour cells displaying high grade nuclei. The tumour cells are set within fibrotic desmoplastic stroma. Many lactiferous ducts are entrapped within the tumour. Frequent tumour mitoses are seen. Microcalcification is seen in some neoplastic tubules. Tumour grade (Modified Bloom-Richardson Scoring System): Tubular formation: 3 Nuclear atypia: 3 Tumour mitoses: 2 Total score: 8 (Grade III) TUMOUR LOCATION, SIZE AND EXTENT The tumour is located 5mm below the nipple and has a macroscopic size of 35mm across. The border of the tumour is poorly circumscribed and infiltrative. INTRA-LYMPHOVASCULAR OR PERINEURAL TUMOUR PERMEATION Focal intralymphatic tumour permeation is noted. No perineural tumour invasion is seen in sections submitted.

11 June CLINICAL HISTORY/MACROSCOPY Right mastectomy and axillary tissue. A right mastectomy specimen with overlying skin measuring 220mm x 85mm and underlying breast tissue measuring 220mm x 100mm x 70mm. The axillary tail measures 125 x 60mm. The nipple is slightly retracted and located centrally. The superior margin is painted red, the inferior margin painted green and the deep cut margin is painted blue. Cut sections of the underlying breast tissue shows an ill-defined grey white yellow lesion with patchy areas of haemorrhage measuring 35 x 35 x 35mm located immediately below the nipple, 20mm from the inferior margin, 45mm from the deep cut margin, 50mm from the superior margin, 85mm from the medial margin and 100mm from the lateral cut margin. A1 - nipple, B1 - upper outer quadrant, C1 - upper inner quadrant, D1 - lower outer quadrant, E1 - lower inner quadrant, F1, G1 - tumour composite blocks, H1, I1 - tumour composite blocks, J1 - deep cut margin, K1 - superior margin, L1 – inferior margin, M4 - lymph nodes, N4 - lymph nodes, O - 3 serial slices, lymph node, P - 3 lymph nodes. MICROSCOPY This right mastectomy specimen demonstrates an invasive ductal carcinoma with the following pathological features: TUMOUR HISTOLOGY & GRADE The tumour is of an infiltrating poorly differentiated ductal carcinoma of non-otherwise specified type. The tumour is poorly defined and extremely infiltrative, comprising poorly-formed tubules, nests or strands of cuboidal tumour cells displaying high grade nuclei. The tumour cells are set within fibrotic desmoplastic stroma. Many lactiferous ducts are entrapped within the tumour. Frequent tumour mitoses are seen. Microcalcification is seen in some neoplastic tubules. Tumour grade (Modified Bloom-Richardson Scoring System): Tubular formation: 3 Nuclear atypia: 3 Tumour mitoses: 2 Total score: 8 (Grade III) TUMOUR LOCATION, SIZE AND EXTENT The tumour is located 5mm below the nipple and has a macroscopic size of 35mm across. The border of the tumour is poorly circumscribed and infiltrative. INTRA-LYMPHOVASCULAR OR PERINEURAL TUMOUR PERMEATION Focal intralymphatic tumour permeation is noted. No perineural tumour invasion is seen in sections submitted. Synoptic Report

Manual extraction of Synoptic data from text min. per report Manual extraction with Synoptex Assist 2 min. per report Fully automated extraction 2 – 3 seconds per report Slide 5

Data can be found in many formats Data aggregate detection Pattern matching Heuristics for logical consistency Language processing Slide 6 Specimen type : Hemicolectomy, right, partial excision of urinary bladder, and salpingo-oophorectomy, right Orientation Clinical information : Colon, right Anatomical landmarks : Ileum = proximal Surgical markings : Absent Pathlogy markings : Ink = margins of urinary bladder wall Ileum, terminal Length : 8 cm Serosa : Unremarkable Wall : Thickness: 0.4 cm Mucosa : Slightly edematous Vermiform appendix : Absent Colon, right Length : 22 cm Serosa : Cecum: Puckering and attached portion of urinary bladder wall and right adnexa (see below) Otherwise: Unremarkable Wall : Thickness: 0.4 cm Mucosa : Tumour: - Location: Ileocecal valve - Configuration: Fungating - Size: - Length: 7 cm - Width: 12 cm - Thickness: 7 cm - Extent of invasion: Urinary bladder - Margins: - Proximal: 8 cm - Distal: 15 cm - Radial: 0.1 cm` Non-neoplastic colon: Unremarkable Specimen type : Hemicolectomy, right, partial excision of urinary bladder, and salpingo-oophorectomy, right Orientation Clinical information : Colon, right Anatomical landmarks : Ileum = proximal Surgical markings : Absent Pathlogy markings : Ink = margins of urinary bladder wall Ileum, terminal Length : 8 cm Serosa : Unremarkable Wall : Thickness: 0.4 cm Mucosa : Slightly edematous Vermiform appendix : Absent Colon, right Length : 22 cm Serosa : Cecum: Puckering and attached portion of urinary bladder wall and right adnexa (see below) Otherwise: Unremarkable Wall : Thickness: 0.4 cm Mucosa : Tumour: - Location: Ileocecal valve - Configuration: Fungating - Size: - Length: 7 cm - Width: 12 cm - Thickness: 7 cm - Extent of invasion: Urinary bladder - Margins: - Proximal: 8 cm - Distal: 15 cm - Radial: 0.1 cm` Non-neoplastic colon: Unremarkable

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Synoptex technologyPerformance measuresSynoptex enhancementsUses of synoptic dataCAP checklists Slide 9

How often does Synoptex return the expected value? How often does Synoptex return a non-expected value? Is there a tradeoff between completeness and accuracy? How does Synoptex improve with new iterations? Slide 10

Sensitivity and Specificity measure the performance of a binary classification system  Present/Not present  True/False In the Synoptex case, this could only be applied to a single value, for example histologic type Need a new method to evaluate Synoptex that is analogous to Sensitivity and Specificity Sensitivity and Specificity? Synoptex has many variables and many checklists Slide 11

Build a manual reference data set Define three measures from the manually reviewed reference data Slide 12 C= Correct: Sum of correctly returned values by Synoptex. ∑ (all correctly found values) I= Incorrect: Sum of incorrectly returned values by Synoptex ∑ (all incorrect values) M= Missed: Sum of values the were missed by Synoptex ∑ (all missed values)

Define two new concepts with the variables Slide 13 Required Correct + Missed = C + M Returned Correct + Incorrect = C + I C = Correct (all correct values) I = Incorrect (all incorrect values) M = Missed (all missed values)

Completeness Correct / Required= C / (C + M) The ability to find the correct data when it is in the path report. Accuracy Correct / Returned= C / (C + I) The ability to find only the correct data when it is in the path report. Accuracy can be seen as a measure of exactness or fidelity. C = Correct I = Incorrect M = Missed Sensitivity Specificity

Completeness 81.2% average Accuracy 82.0% average

Completeness 93.4% average Accuracy 93.8% average

Synoptex technologyPerformance measuresSynoptex enhancementsUses of synoptic dataCAP checklists Slide 17

Add new elements, e.g.: HER2, ER, PR New template definitions Expand or modify Sites / Templates Concepts / data items Expressions Synonyms Modify standard expressions for data items How do we expand capabilities of Synoptex system Slide 18

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Synoptex technologyPerformance measuresSynoptex enhancementsUses of synoptic dataCAP checklists Slide 23

Standardization of Pathology Reports for Registries Data Quality Assessments Audits Mining of Current and Legacy Data Export of Indexed Data for Statistical Processing Annotated Datasets for Biospecimen Repositories Data for Automated Record Matching –Clinical Trials –Case Control Studies Slide 24

Slide 25 Range % ReportsWeighted Data Site: Breast Reports Sample Size: Date Range: No. Of Cancer Reports: 8422 No. Of Breast Cancers: 1678 Element Analysis Data Element Report CountWeight Specimen Type Lymph Node Sampling895 1 Specimen Size Tumor Laterality Tumor Site775 0 Tumor Size996 1 Histologic Type Grading System779 0 Pathologic Staging (pTNM)511 0 Margins901 1 Lymphatic Invasion838 0 Microcalcifications759 0 Additional Pathologic Findings885 0 Tubule Formation741 1 Nuclear Pleomorphism Mitotic Count792 1 Histologic Grade Extent of Margin Involvement for Invasive Ca Extent of Margin Involvement for DCIS10 0 HER2 Status570 0 ER Status PR Status Lymph Nodes Positive449 1 Lymph Nodes Examined618 1

Slide ER + - HER (61%) 148 (68%) (61%) ER Positive %

Synoptex technologyPerformance measuresSynoptex enhancementsUses of synoptic dataCAP checklists Slide 27

CAP Checklists version updates Slide 28 How frequently are they updated? How do we manage updates/versions? How can systems be maintained ? How can custom additions be kept across versions?

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Interoperability Synoptex output same format as Manual checklists  SNOMED codes  CKEYS Synoptex data can be viewed with STS checklist system Slide 31

Export Synoptic Database Synoptic Database Export

Import Export Synoptic Database Checklist Converter

Renders Pathology Reports Machine Readable – Facilitates Research Identifies Some Collaborative Stage Elements Saves Labor in Deriving Synoptic Reports – both manually and fully automated Verifies Report Content (Audits) Compare reporting accuracy hospital-to-hospital Apply Synoptex to other data sources – Surgical reports – Medical records – Radiology reports – Hematology reports Slide 34

Thank You Slide 35