Hot Spot · 2020-07-01 · Visiopharm A/S – Agern Allé 24, DK-2970 Hørsholm Phone: +45 88 20 20...

Visiopharm A/S – Agern Allé 24, DK-2970 Hørsholm

Phone: +45 88 20 20 88 – Fax: +45 88 20 20 99 - Mail: [email protected]

Hot Spot

ID: 20114 1st edition

The Hot Spot APP is an image analysis application designed to conduct automated and objective analysis of

digital images acquired by scanning tissue sections stained with immunohistochemistry (IHC).

The Hot Spot APP is an accessory IVD APP compatible with various analytical biomarker APPs, e.g. the

Visiopharm IVD Ki-67 APP for breast cancer, when used with VirtualDoubleStaining™ (VDS™) supported Region

of Interest (ROI) identification.

In such cases, the APP enables analysis of the analytical biomarker expression within one or more hot spots.

Hot Spot – Package Insert – 1st Edition, Revision 20181121 2

TABLE OF CONTENTS

TABLE OF CONTENTS ........................................................................................................................................ 2

INTENDED USE ................................................................................................................................................. 3

SUMMARY AND EXPLANATION........................................................................................................................ 3

PRINCIPLE OF PROCEDURE ............................................................................................................................... 3

SOFTWARE AND HARDWARE ........................................................................................................................... 5

SOFTWARE PROVIDED ................................................................................................................................................ 5

SOFTWARE REQUIRED AND AVAILABLE FROM VISIOPHARM ................................................................................................ 5

SOFTWARE CHARACTERISTICS...................................................................................................................................... 5

HARDWARE REQUIRED ............................................................................................................................................... 6

Whole slide scanner ......................................................................................................................................... 6

Computer requirements................................................................................................................................... 6

PRECAUTIONS .................................................................................................................................................. 6

INSTALLATION, CONFIGURATION & CALIBRATION ........................................................................................... 7

INSTALLATION .......................................................................................................................................................... 7

CONFIGURATION ...................................................................................................................................................... 7

CALIBRATION ........................................................................................................................................................... 7

LICENSE ............................................................................................................................................................ 7

IMAGE COLLECTION ......................................................................................................................................... 7

OPERATING PROCEDURE ................................................................................................................................. 7

MANUAL REVIEW ............................................................................................................................................ 7

PROCEDURAL NOTES ....................................................................................................................................... 8

QUALITY CONTROL .......................................................................................................................................... 8

WHOLE SLIDE SCANNER ............................................................................................................................................. 8

IHC MARKER ASSAY CONTROLS .................................................................................................................................... 8

CONTROL IMAGE ....................................................................................................................................................... 8

LIMITATIONS ................................................................................................................................................... 8

ANALYTICAL PERFORMANCE CHARACTERISTICS .............................................................................................. 9

REPEATABILITY ....................................................................................................................................................... 10

REPRODUCIBILITY ................................................................................................................................................... 11

CLINICAL PERFORMANCE CHARACTERISTICS ...................................................................................................13

APP, SOFTWARE, AND PACKAGE INSERT VERSIONS ........................................................................................16

TROUBLESHOOTING ........................................................................................................................................17

SERIOUS INCIDENTS ........................................................................................................................................17

BIBLIOGRAPHY ................................................................................................................................................17

TECHNICAL ADVICE AND CUSTOMER SERVICE.................................................................................................17


INTENDED USE

EU: For in vitro diagnostics use.

The Hot Spot APP is intended for use with digital images as an accessory to in vitro diagnostic test for the

purpose of identifying one or more hot spots in formalin-fixed, paraffin-embedded tissue sections. The APP

supports Ki-67 assessment restricted to hot spots in combination with the Visiopharm APP Ki-67 APP, Breast

Cancer (ID: 90004). In such cases, the APP is indicated as an aid to the pathologist in the assessment of breast

cancer patients (but is not the sole basis for treatment).

SUMMARY AND EXPLANATION

Cancer has the ability to rapidly mutate and adapt, potentially creating heterogenous tumors with diverse cell

populations. In histopathology, depending on the immunohistochemical (IHC) test, it can be important to

evaluate a specimen in different regions such as the invasive front or hot spots where the tumor cells show

increased activity. This is for example the case for Ki-67 IHC, where one of the more recent approaches to Ki-67

scoring is the hot spot scoring method, that has been implemented in several scoring guidelines, e.g. the

Swedish guidelines for mamma-cancer (1) and the Danish guidelines for mamma-cancer (2). However, the hot

spot scoring method is often found to be subjective and prone to both intra- and inter-observer variability (3).

Using the Hot Spot APP a standardized and objective method for hot spot scoring can be obtained.

The Hot Spot APP is an image analysis application, that offers automated and objective analysis of whole slide

digital images acquired by scanning tissue sections stained with relevant biomarker immunohistochemistry.

The APP offers automated identification of one or more hot spots and reports the score for each hot spot. The

identified hot spot(s) are outlined as separate Regions of Interest (ROIs) on the digital image.

The APP is an accessory IVD APP compatible with different analytical biomarker APPs, e.g. Ki-67 APP, Breast

Cancer (ID: 90004), when used with VirtualDoubleStaining™ (VDS™) supported Region of Interest (ROI)

identification. In such cases, the APP enables assessment of the analytical biomarker expression within a hot

spot or hot spots rather than a global whole slide assessment.

The Hot Spot APP in combination with an analytical biomarker APP, e.g. Ki-67 APP, Breast Cancer (ID: 90004),

provides a supplement to manual and subjective scoring. The hot spot(s) identified by the Hot Spot APP and the

score calculated within the hot spot(s) must be confirmed by manual review of the results by a qualified

pathologist.

PRINCIPLE OF PROCEDURE

The Hot Spot APP is a software analysis protocol package which requires installation of Oncotopix® Diagnostics.

The APP should be used in combination with VDS™ and the module Tissuealign™. The principle of procedure

for the Hot Spot APP and the necessary configuration of Oncotopix® Diagnostics is described below.


Workflow:

1. Open the serial whole slide image set stained with analytical biomarker IHC (e.g. Ki-67) and a tumor marker

(e.g. p63+CK7/19)

2. Link and align the images

3. Manually outline general area of interest (optional)

4. Run tumor marker APP to automatically create tumor ROIs

5. Run analytical biomarker APP within tumor ROIs

6. Run Hot Spot APP to identify hot spot(s) and compute score within hot spot(s).

7. Review result

Required software:

• Hot Spot (ID: 20114)

• APP for analytical biomarker (e.g. Ki-67 APP, Breast Cancer, ID: 90004)

• APP for tumor marker (e.g. Invasive Tumor Detection (PDS), ID: 20101)

• Oncotopix® Diagnostics with:

o Engine™

o Viewer

o Viewer+

o Tissuealign™ incl. VirtualDoubleStaining™

The Hot Spot APP consists of two protocols that:

1. Generates an Object Heatmap showing where the highest number of objects (e.g. Ki-67 positive

nuclei) are located. The method for generating heatmaps can be tailored to the customer’s needs before delivery, e.g. a ratio heatmap can be used to show where the highest percentage of objects

are. Hot spot regions-of-interest (ROIs) are placed based on the heatmap.

2. Calculates the appropriate object parameters within the hot spot(s), as defined by the analytical

biomarker APP that identified the objects. This is typically the number or percentage of objects within

the hot spot(s).

Note that the Hot Spot APP only performs mathematical operations on objects already identified with another

APP (referred to as the analytical biomarker APP). Thus, the Hot Spot APP must always be used in combination

with an analytical biomarker APP to function.

Fundamentally, the following configuration options are available for the Hot Spot APP:

• A square or circular ROI with a fixed size is placed where the highest number or percentage of objects

(e.g. Ki-67 positive nuclei) is found.

• An adaptive ROI that follows the heatmap contours is grown from where the highest number or

percentage of objects is found.

For all configuration options a minimum object requirement can be specified to ensure sufficient cells are

included in the hot spot. Any countable object (nuclei, cells, RNA etc.) can be used to generate heatmaps and

hot spots.

The configuration of the Hot Spot APP may depend on the type of tissue and staining, the analytical biomarker

APP used for identifying objects and user preferences.


A configuration example for the Hot Spot APP is given below.

Heatmap type: Object Count

Hot spot shape: Circle

Hot spot size: 0.25mm radius

Minimum # of objects: 500

# of hot spots: 1

SOFTWARE AND HARDWARE

SOFTWARE PROVIDED

Hot Spot, ID: 20114, ver. 1.0

SOFTWARE REQUIRED AND AVAILABLE FROM VISIOPHARM

Required:

Oncotopix® Diagnostics, VIS ver. 2018.4 or later, with:

• Engine™

• Viewer

• Viewer+

• Tissuealign™ incl. VirtualDoubleStaining™

• APP for analytical biomarker quantification (e.g. Ki-67 APP, Breast Cancer, ID: 90004)

• APP for tumor marker quantification (e.g. Invasive Tumor Detection (PDS), ID: 20101 or PCK VDS,

Tumor Detection, ID: 20002)

The listed modules are available as components of different software configurations. If in doubt, please contact

Visiopharm to understand what is needed for your application.

SOFTWARE CHARACTERISTICS

Software solutions intended as a Client/Server based solution:

Permissions and user rights are based on Microsoft active directory or equivalent user access control. Rights

should always be granted through a user access control system with ability to monitor failed and succeeded

logons.

Software solutions intended to be deployed locally:

Solution can be deployed locally to a client with equivalent safeguards as defined in previous section.

Network characteristics:

Standard TCP/UDP traffic occurring in ethernet networks. Security measures should always be based on

customer requirements though antivirus and antimalware systems must be configured with exceptions for

APPs and software.


HARDWARE REQUIRED

WHOLE SLIDE SCANNER

Whole slide scanners capable of acquiring 24 bit RGB whole slide images using bright field illumination at 20x

or 40x scan mode (min. resolution 1650 pixels/mm).

COMPUTER REQUIREMENTS

Use of the APP requires Oncotopix® Diagnostics, VIS ver. 2018.4 or later, with appropriate software additions

and introduces no additional requirements.

Table 1. Computer requirements for Oncotopix® Diagnostics, VIS ver. 2018.4 or later

Recommended Minimum recommended

Operative system Windows 7/10, 64 bit Windows 7/10, 64 bit

Processor Intel Core i7 or better Intel Core i3 or better

RAM 8 GB 4 GB

Hard drive SSD with 256 GB of free space before

installation 10 GB of free space before installation

Graphics Graphics with 512 MB and output for two

screens

Graphics with 256 MB and output for two

screens

Screens Two 27” screens Two 20” screens

PRECAUTIONS

EU: For in vitro diagnostics use.

Rest of World, incl. US: Research Use Only.

For professional users.

The accuracy of the test result depends upon the quality of the analytical biomarker and tumor marker

staining. It is recommended, that the clinical laboratory participates in regular external quality assessments to

ensure optimal performance of their IHC testing.

The number of objects in the identified hot spot might be slightly lower than requested by the user. It is the

responsibility of the qualified pathologist, during the final review of the image and the results produced by the

Hot Spot APP, to decide whether a hot spot, with a lower number of objects than requested, can be accepted

or not, or if re-analysis of the image, in accordance with the APP Review Operating Procedure, should be

conducted.


INSTALLATION, CONFIGURATION & CALIBRATION

INSTALLATION

Installation of Oncotopix® Diagnostics and the Hot Spot APP is performed by Visiopharm in collaboration with

the customer’s IT department. Updates to third party software components (e.g. drivers), that are introduced after installation has been

performed, can introduce changes to how images are perceived by VIS and may require re-calibration of the

analytical biomarker and tumor marker APPs that are used in combination with the Hot Spot APP. Re-

calibration must be performed by Visiopharm.

CONFIGURATION

The Hot Spot APP must be configured prior to installation to ensure compatibility with the intended use case.

The configuration is performed by Visiopharm based on input from the user.

CALIBRATION

The Hot Spot APP only performs mathematical operations on objects identified with an analytical biomarker

APP. Hence, the Hot Spot APP is not dependent on the laboratory’s tissue preparation, IHC staining protocol or

slide scanning system, and does not require calibration to these parameters.

However, changes to the laboratory’s tissue preparation, IHC staining protocol, or slide scanning system may

affect the analytical biomarker APP and the tumor marker APP that are used in combination with the Hot Spot

APP and may require re-calibration of these APPs by Visiopharm.

LICENSE

A license for running the software is required. Do not use the APP without a valid service agreement.

IMAGE COLLECTION

Whole slide images of specimens stained for the presence of relevant IHC markers are acquired using a single

in-focus Z-plane at 20x or 40x scanning mode in 24 bit RGB using bright field illumination.

All data obtained by analysis with the Hot Spot APP is saved, linking them to the original digital image, thereby

allowing subsequent reviews and new analysis if required.

OPERATING PROCEDURE

See separately available APP Operating Procedure.

MANUAL REVIEW

The results obtained with the Hot Spot APP in combination with an analytical biomarker APP must be

confirmed by manual review of the images by a qualified pathologist. See separately available APP Review

Operating Procedure.


PROCEDURAL NOTES

Oncotopix® Diagnostics can integrate with a laboratory’s existing LIS/LIMS, PACS, IMS or VNA systems. Hence,

the Hot Spot APP can integrate with CGI’s Pathology System and other LIS systems, which may be used instead

of Oncotopix® Diagnostics for the “Open Image” and “Save in Database” steps.

Please contact Visiopharm for more information about what LIS/LIMS, PACS, IMS and VNA systems Oncotopix®

Diagnostics and the APP can integrate with.

QUALITY CONTROL

WHOLE SLIDE SCANNER

The responsible operator must ensure that the whole slide scanner is calibrated, and if needed adjust the

instrument settings in order to ensure sufficient image quality.

IHC MARKER ASSAY CONTROLS

Staining quality must be assessed for each run of the analytical IHC test that is used in combination with the

Hot Spot APP. The staining quality must be assessed in accordance with the reagent manufacturer’s recommendation. This may involve staining and scoring of control slides and can be facilitated by the APP.

CONTROL IMAGE

Correct installation and operation of the Hot Spot APP can be assured by analysis of one or more control

images representing samples with known results by the APP.

LIMITATIONS

The Hot Spot APP must be used in combination with an analytical biomarker APP.

The APP has been validated for use with the Visiopharm IVD APP Ki-67 APP, Breast Cancer (ID: 90004). Use of

the APP in combination with other analytical biomarker APPs must be clinically validated by the user.

The APP has been validated for use on whole slide breast cancer tissue sections (resection specimens). Use of

the APP on other types of material must be clinically validated by the user.


ANALYTICAL PERFORMANCE CHARACTERISTICS

The analytical performance characteristics of the Hot Spot APP were investigated in the study outlined in Table

2. Because the Hot Spot APP does not analyze the digital image, but the objects created by an analytical

biomarker APP that are overlaid the image, the analytical performance was evaluated by comparison with the

IVD APP Ki-67 APP, Breast Cancer (ID: 90004).

Three TMAs containing breast cancer specimens stained for Ki-67 with reagents from Dako, Leica and Ventana,

respectively, were analyzed together with serial sections stained for PCK aligned to the images for automated

tumor detection. Each TMA was scanned three times on a Hamamatsu NanoZoomer HT 2.0 (20x scanning

mode) and analyzed using the accessory IVD APP PCK VDS, Tumor Detection (ID: 20002), the IVD Ki-67 APP and

the Hot Spot APP to verify that nuclei were accurately identified. The three TMAs contained a total of 37 cores,

providing a total of 111 images of TMA cores by including the multiple scans.

The objects identified by the Ki-67 APP were compared to the objects identified by the Hot Spot APP and the

results showed they were identical, providing the following parameters:

Sensitivity = 100%

Specificity = 100%

Bias = 0

Accuracy = 100%

On Figure 1, the proliferation indexes (PI) calculated within the hot spot by both APPs are shown for all the

scans for each reagent.

Figure 1. Scatter plots showing the proliferation indexes calculated by both APPs on all the scanned cores

for each reagent against each other, showing perfect correlation.

R² = 1

0

20

40

60

80

100

0 20 40 60 80 100

Ki-

67

PI

[%]

Hot Spot PI [%]

Dako

R² = 1

0

20

40

60

80

100

0 20 40 60 80 100

Hot Spot PI [%]

Leica

R² = 1

0

20

40

60

80

100

0 20 40 60 80 100

Hot Spot PI [%]

Ventana


Table 2. Outline of Analytical Performance Study

Material 37 TMA cores obtained from whole slide images of formalin-fixed, paraffin-embedded

breast cancer specimens stained for Ki-67, aligned to serial sections stained for PCK.

Reagents

Ki-67 (clone MIB1, Dako)

Ki-67 (clone 30-9, Ventana)

Ki-67 (clone MM1, Leica)

PCK (clone AE1/AE3, Dako)

Scanner Hamamatsu NanoZoomer 2.0HT (20x scanning mode)

Reference scoring

method IVD APP Ki-67 APP, Breast Cancer (ID: 90004)

Reporting

parameter Number and location of negative and positive nuclei.

REPEATABILITY

Repeatability of the Hot Spot APP was investigated in two studies, (1) where the same operator analyzed a

TMA slide three times and (2) where three different operators analyzed the same TMA slide. The TMA

contained 13 cores of breast cancer specimens stained for Ki-67 viable for analysis and was scanned using a

Hamamatsu NanoZoomer HT 2.0 (20x scanning mode). The analysis workflow consisted of de-arraying the slide

using Tissuearray™, aligning it to the serial slide stained for PCK, and analyzing the de-arrayed cores with the

accessory IVD APP PCK VDS, Tumor Detection (ID: 20002), the IVD Ki-67 APP and the Hot Spot APP.

Results were reported as center X/Y coordinate of the hot spot identified, and the proliferation index (PI)

calculated within the hot spot for each sample. Results are summarized in the figures and tables below.

Figure 2. Intra-operator repeatability on 13 TMA cores where the same operator analyzed the same scanned

slide three times. Error bars show standard deviation.

Table 3. Average pair-wise agreement for intra-operator repeatability. The agreement is based on how well

the placement of the hot spots and the proliferation index calculated matched each other.

Pair-wise agreement

Run 1 vs. Run 2 100%



Average pair-wise agreement 100%

0

20

40

60

80

100

0 4 8 12

PI

[%]

Sample

Hot Spot Proliferation Index


Figure 3. Inter-operator repeatability on 13 TMA cores where 3 different operators analyzed the same

scanned slide. Error bars show standard deviation.

Table 4. Average pair-wise agreement for inter-operator repeatability. The agreement is based on how well

the placement of the hot spots and the proliferation index calculated matched each other.

Pair-wise agreement

Operator 1 vs. Operator 2 92.3%



Average pair-wise agreement 92.3%

REPRODUCIBILITY

Reproducibility of the Hot Spot APP was investigated by analyzing TMAs containing breast cancer specimens,

stained for Ki-67 with reagents from Dako, Leica and Ventana, respectively. The three TMAs contained a total

of 37 cores and were scanned three times on a Hamamatsu NanoZoomer HT 2.0 (20x scanning mode) scanner,

providing 111 images of TMA cores by including the multiple scans. Serial sections of the TMAs stained for PCK

were aligned to the images for automated tumor detection. The images were analyzed using the accessory IVD

APP PCK VDS, Tumor Detection (ID: 20002), IVD APP Ki-67 APP, Breast Cancer (ID: 90004) and the Hot Spot APP.

Results were reported as center X/Y coordinate of the hot spot identified, and the proliferation index

calculated within the hot spot for each sample. Results are summarized in the figures and tables below.

0

20

40

60

80

100

0 4 8 12

PI

[%]

Sample

Hot Spot Proliferation Index


Pair-wise agreement




Average pair-wise

agreement 100%

Pair-wise agreement




Average pair-wise

agreement 100%

Pair-wise agreement




Average pair-wise

agreement 100%

0

20

40

60

80

100

0 4 8 12

PI

[%]

Sample

Hot Spot Proliferation Index - Dako

0

20

40

60

80

100

0 4 8 12

PI

[%]

Sample

Hot Spot Proliferation Index - Leica

0

20

40

60

80

100

0 4 8 12

PI

[%]

Sample

Hot Spot Proliferation Index -

Ventana


CLINICAL PERFORMANCE CHARACTERISTICS

The Hot Spot APP does not provide results for diagnosis, but it may be used in combination with an analytical

biomarker APP that does. In such cases the contribution of the hot spot APP to the diagnostic workflow is the

identification of one or more hot spots. Thus, the clinical performance characteristics of the APP have been

determined by comparing hot spots identified with the APP to hot spots identified with an established

reference method for hot spot identification at the participating sites on Ki-67 stained breast cancer resection

specimens.

In each conducted study the assessing pathologist was asked to place a hot spot on at least 30 whole slide

images. Afterwards, the pathologist was presented with the hot spots identified with the APP on the same

whole slide images and was asked to compare his/her hot spot to the APP hot spot. The pathologist also had

access to the Ki-67 proliferation index for each hot spot as computed with the analytical biomarker APP Ki-67

APP, Breast Cancer (ID: 90004). The comparison of the hot spots could then have one out of four outcomes:

• Match (M): The pathologist hot spot and the APP hot spot match w.r.t. the location of the hot spots.

• Equivalent (E): The pathologist hot spot and the APP hot spot are equivalent w.r.t. to the Ki-67

proliferation index.

• XM – Pathologist: The pathologist hot spot and the APP hot spot are neither matching nor equivalent,

and the pathologist prefers the pathologist hot spot.

• XM – APP: The pathologist hot spot and the APP hot spot are neither matching nor equivalent, but

the pathologist prefers the APP hot spot.

The following tables and figures provide an overview of the conducted studies and the achieved results.

Table 5. Overview of clinical performance study on 34 samples conducted at Pathology Diagnostics Jarutat

with samples provided by Odense University Hospital.

Clinical site Pathology Diagnostics Jarutat, Germany

Data provided by Odense University Hospital, Denmark

Number of samples 34

Whole slide scanner Hamamatsu NanoZoomer HT 2.0 (C9600-12) at 20x

Analytical Stain Ki-67: clone 30-9, Dako

Tumor Stain

P63+CK7/19 double stain

P63: clone 4A4, Zeta

CK7: clone OV-TL12/30, Dako

CK19: clone A53-B/A2.26, Roche Ventana

Sample type Whole slide images of FFPE breast cancer resection specimens

Hot spot configuration

Object heatmap based on ratio of Ki-67 positive nuclei to total

number of nuclei. Circular hot spot with a radius of 0.45mm

and a minimum of 1000 cells within the hot spot.

Reference method Digital reading

Output method used for comparison Hot spot placement

Table 6. Agreement between pathologist hot spots and APP hot spots

Category: M E XM – Pathologist XM - APP Total in agreement Total

Quantity: 2 27 1 4 33 34

Agreement: 97.1 %

Lower 95% confidence interval (CI): 83.8 %


Figure 4. Proliferation index in the pathologist hot spot and APP hot spot as quantitated with the analytical

biomarker APP Ki-67 APP, Breast Cancer (ID: 90004).

Table 7. Overview of clinical performance study on 40 samples conducted at Karolinska Institutet

Clinical site Karolinska Institutet, Sweden


Whole slide scanner Hamamatsu NanoZoomer HT 2.0 (C9600-12) at 20x

Analytical Stain Ki-67: clone 30-9, Roche Ventana

Tumor Stain Cytokeratin: clone MNF 116, Dako



Object heatmap based on ratio of Ki-67 positive nuclei to total

number of nuclei. Circular hot spot with a radius of 0.25mm

and a minimum of 500 cells within the hot spot.





Quantity: 15 18 1 6 39 40

Agreement: 97.5 %


0

20

40

60

80

100

0 10 20 30P

I [%

]

Sample

Proliferation Index in Hot Spot

APP Pathologist




Table 9. Overview of clinical performance study on 38 samples conducted at Nap Pathology Consultance,

with samples provided by University Medical Center Groningen.

Clinical site

Nap Pathology Consultance, The Netherlands

Data provided by University Medical Center Groningen, The

Netherlands


Whole slide scanner Hamamatsu S360 at 20x

Analytical Stain Ki-67: clone 30-9, Roche Ventana

Tumor Stain

P63+CK7/19 double stain

P63: clone 4A4, Roche Ventana

CK7: clone OV-TL12/30, Dako

CK19: clone A53-B/A2.26, Cell Marque



Object heatmap based on count of Ki-67 positive nuclei.

Circular hot spot with a radius of 0.25mm and a minimum of

200 cells within the hot spot.





Quantity: 14 18 2 4 36 38

Agreement: 94.7 %


0

20

40

60

80

100

0 10 20 30 40P

I [%

]

Sample


APP Pathologist




A summary of the three conducted studies can be found in the table below. The table includes the number of

samples in agreement, the percent agreement and lower 95% CI for each site as well as a total for all three

studies. Please refer to Table 11 for details.

Table 11. Overview of clinical studies

Site Samples

(n)

Samples in

agreement (n) Agreement (%) Lower 95% CI

Pathology Diagnostics Jarutat 34 33 97.1% 83.8%

Karolinska Institutet 40 39 97.5% 86.0%

Nap Pathology Consultance 38 36 94.7% 81.8%

Total 112 108 96.4% 90.9%

APP, SOFTWARE, AND PACKAGE INSERT VERSIONS

The current package insert (1st edition) is to be used as a reference when version 1.0 of the Hot Spot APP is run

on VIS ver. 2018.4 or later as outlined in Table 12.

Table 12. Relationship between APP, software and package insert versions.

APP version VIS version Package Insert version

1.0 2018.4 - 1st edition

0

20

40

60

80

100

0 10 20 30 40P

I [%

]

Sample


APP Pathologist


TROUBLESHOOTING

Please contact Visiopharm in case of device not working as expected.

SERIOUS INCIDENTS

If any serious incident occurs in relation to the device, immediately contact Visiopharm and the competent

authority of your country.

BIBLIOGRAPHY

1. DBCG, Patologi, May 2017, URL:

http://www.dbcg.dk/PDF%20Filer/Kap_3_Patologi_22_juni_2017.pdf, Accessed 2018-07-19

2. Svensk Förening för Patologi – Svensk Förening för klinisk Cytologi, KVAST bröstcancer (2018), URL:

http://www.svfp.se/foreningar/uploads/L15178/kvast/brostpatologi/KVASTbrostcancer2018.pdf,

Accessed 2018-07-19

3. Jang, Min Hye et al., A Comparison of Ki-67 Counting Methods in Luminal Breast Cancer: The Average

Method vs. the Hot Spot Method, Ed. William B. Coleman. PLoS ONE 12.2 (2017): e0172031. PMC.

doi:10.1371/journal.pone.0172031. Accessed 2018-07-19.

TECHNICAL ADVICE AND CUSTOMER SERVICE

For all inquiries, please contact Visiopharm or your local distributor.

Visiopharm A/S

Agern Allé 24

DK-2970 Hoersholm

Denmark

Telephone: +45 88 20 20 88

Fax: +45 88 20 20 99

E-mail: [email protected]

Visiopharm Integrator System™ (VIS™) is a trademark of Visiopharm A/S.

Oncotopix® is a registered trademark of Visiopharm A/S.

VirtualDoubleStaining™ (VDS™) is a trademark of Visiopharm A/S.

US 8,229,194. Feature-based registration of sectional images

EP 2,095,332. Feature-based registration of sectional images

http://www.dbcg.dk/PDF%20Filer/Kap_3_Patologi_22_juni_2017.pdf

http://www.svfp.se/foreningar/uploads/L15178/kvast/brostpatologi/KVASTbrostcancer2018.pdf

Hot Spot · 2020-07-01 · Visiopharm A/S – Agern Allé 24, DK-2970 Hørsholm Phone: +45 88 20 20...

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Transcript of Hot Spot · 2020-07-01 · Visiopharm A/S – Agern Allé 24, DK-2970 Hørsholm Phone: +45 88 20 20...