Ethos Treatment Management is a software product designed to help radiation therapy medical professionals manage treatments for patients with malignant or benign diseases for whom radiation therapy is indicated. It allows the physician to create and communicate radiation treatment intent (RT intent) to the treatment planner, review and approve candidate plans, and monitor treatment progress. It is intended to be used with a treatment planning system to treat or alleviate disease in humans by streamlining the treatment management and monitoring processes.

Ethos Treatment Planning is a standalone software device designed to generate and modify radiation therapy treatment plans and manage treatment sessions. The device supports the traditional and adapted treatments, in which the scheduled plan is adapted to the patient's anatomy at the time of treatment.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the AI segmentation models within the Ethos Treatment Management 3.0 and Ethos Treatment Planning 2.0 devices, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance (AI Model Validation for Contouring)

Validation Characteristic	Acceptance Criteria (Implied)	Reported Device Performance
Contour Quality	Minor or no adjustments needed in at least 80% of test cases.	Consistently produced contours that needed minor or no adjustments in at least 80% of the test cases.
Quantitative Metric (DICE coefficient)	Comparison benchmark against references published in the literature.	Used as a comparison benchmark, especially when introducing a model for a new organ.
Model Type	Not explicitly stated as acceptance criteria, but a characteristic of the model.	Convolutional neural networks with static weights; do not continuously learn.
Image Resolution Handling	Not explicitly stated as acceptance criteria, but a characteristic of the model's operation.	Operates on suitable image resolutions, patient images are resampled before inference, and label maps are sampled back onto the patient image grid.

2. Sample Size Used for the Test Set and Data Provenance

Test Set Sample Size: 1045 scans from various body sites.
- Full body: (part of 179 total patients)
- Head and Neck: (part of 1173 total patients)
- Thorax: (part of 600 total patients)
- Abdomen: (part of 527 total patients)
- Bowel: (part of 507 total patients)
- Pelvis: (part of 1192 total patients)
Data Provenance: The largest number and percentage proportionally of scans originated from patients in the United States. Other country origins are not specified but implied to be varied due to "various healthcare facilities worldwide" mentioned for expert evaluation. The data appears to be retrospective, collected from patients with existing treatment indications for various cancers.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

Number of Experts: Not explicitly stated, but referred to as "Experts" (plural).
Qualifications of Experts: Radiation oncologists, dosimetrists, and physicists from various healthcare facilities worldwide, with "significant clinical experience in segmentation of CT imaging for the different disease sites covered by the AI models."

4. Adjudication Method for the Test Set

Adjudication Method: Not explicitly stated as a formal adjudication method (like 2+1 or 3+1). The text mentions that "Experts... evaluated the quality of the contours across test sets to assess the need and the type of contour adjustments." This suggests a consensus-based or individual expert assessment of the AI-generated contours against their clinical judgment, but not a specific multi-reader adjudication protocol for the initial ground truth creation for the test set. For the model validation of contour quality, experts assessed the AI output.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

A formal MRMC comparative effectiveness study comparing human readers with AI vs. without AI assistance was not explicitly described in the provided text. The validation process involved experts evaluating the AI-generated contours to assess "the time saved on contouring tasks," which hints at an indirect measure of assistive benefit, but not a direct MRMC study.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, a standalone performance assessment was done. The "Contouring performance undergoes rigorous evaluation through verification and validation processes." This included quantitative metrics like the DICE similarity coefficient. The validation also focused on the AI models producing contours that required "minor or no adjustments in at least 80% of the test cases," which is a metric of the AI's standalone output quality observed by experts.

7. The Type of Ground Truth Used

Ground Truth Type: Expert consensus based on "human anatomy experts" following "RTOG and DAHANCA clinical guidelines." Pathology or outcomes data were not mentioned as ground truth for segmentation.

8. The Sample Size for the Training Set

Training Set Sample Size: 4769 scans from various body sites.
- Full body: (part of 179 total patients)
- Head and Neck: (part of 1173 total patients)
- Thorax: (part of 600 total patients)
- Abdomen: (part of 527 total patients)
- Bowel: (part of 507 total patients)
- Pelvis: (part of 1192 total patients)

9. How the Ground Truth for the Training Set Was Established

Ground Truth Establishment for Training Set: "Ground truth annotations were established by human anatomy experts as part of the algorithm development following RTOG and DAHANCA clinical guidelines. A single set of contours was produced for each training image. These clinical experts have significant clinical experience in segmentation of CT imaging for the different disease sites covered by the AI models. To ensure accuracy, contour definitions available in contouring guidelines are established prior to contouring tasks."

Summary

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April 30, 2024

Image /page/0/Picture/1 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA acronym and name on the right. The Department of Health & Human Services logo is a stylized depiction of a human figure, while the FDA acronym and name are written in blue, with the acronym in a square and the name in a sans-serif font.

Varian Medical Systems Inc. % Lynn Allman Sr. Director Regulatory Affairs Varian Medical Systems, Inc 3100 Hansen Way PALO ALTO, CA 94304

Re: K232923

Trade/Device Name: Ethos Treatment Management 3.0, Ethos Treatment Planning 2.0 Regulation Number: 21 CFR 892.5050 Regulation Name: Medical Charged-Particle Radiation Therapy System Regulatory Class: Class II Product Code: IYE, MUJ Dated: April 1, 2024 Received: September 20, 2023

Dear Lynn Allman:

We have reviewed your section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

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Your device is also subject to, among other requirements, the Quality System (OS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Loca Weidner

Lora D. Weidner, Ph.D. Assistant Director Radiation Therapy Team DHT8C: Division of Radiological Imaging and Radiation Therapy Devices OHT8: Office of Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

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Indications for Use

Submission Number (if known)

K232923

Device Name

Ethos Treatment Management (3.0);

Ethos Treatment Planning (2.0)

Indications for Use (Describe)

Ethos Treatment Management is indicated for use in managing and monitoring radiation therapy treatment plans and sessions.

Ethos Treatment Planning is indicated for use in generating and modifying radiation therapy treatment plans.

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

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Image /page/3/Picture/0 description: The image shows three gray circles in a horizontal line. To the right of the circles is the text "K232923". The text is in a sans-serif font and is black. The background of the image is white.

Image /page/3/Picture/1 description: The image displays the logo for Varian, a Siemens Healthineers Company. The word "Varian" is written in a bold, sans-serif font, with each letter in uppercase except for the "a", which is lowercase. Below the logo, in a smaller font size, is the text "A Siemens Healthineers Company", indicating Varian's affiliation with Siemens Healthineers. The logo is simple and modern, with a focus on the company name and its connection to Siemens Healthineers.

Varian Medical Systems

3100 Hansen Way Palo Alto, CA 94304

650.493.4000 800.544.4636

varian.com

SUBMITTER CONTACT DETAILS l.

510(k) Summary

Applicant Name	Varian Medical Systems, Inc.
Applicant Address	3100 Hansen WayPalo Alto, CA 94304
Applicant Contact Telephone	+1 (650) 424 5369 (phone) +1 (650) 646 9200 (fax)
Applicant Contact	Dr. Lynn Allman Sr. Director, Regulatory Affairs
Applicant Contact Email	submissions.support@varian.com
Date	12 January 2024

DEVICE NAME II.

This is a bundled 510(k) for two devices: Ethos Treatment Management and Ethos Treatment Planning. The devices are submitted together to ensure that the shared scientific and regulatory considerations they raise are addressed within one review.

Device Trade name:	Ethos Treatment Management, version 3.0	Ethos Treatment Planning, version 2.0
Common name:	Treatment plan and image managementapplication	Treatment planning system
Classification name:	Medical charged particle radiation therapysystem(21 CFR 892.5050)	Medical charged particle radiation therapysystem(21 CFR 892.5050)
Regulatory class:	Class II	Class II
Product code:	IYE	MUJ

III. LEGALLY MARKETED PREDICATE DEVICES

Predicate device:
Ethos Treatment Management, version 2.1(K212294)	Ethos Treatment Planning, version 1.1(K212294)

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Image /page/4/Picture/0 description: The image shows the logo for Varian, a Siemens Healthineers Company. The word "varian" is written in a bold, sans-serif font. Below the word "varian" is the text "A Siemens Healthineers Company" in a smaller, sans-serif font. The logo is in grayscale.

IV. DEVICE DESCRIPTION SUMMARY

Device Description:	Ethos Treatment Management is a software product designed to help radiation therapy medical professionals manage treatments for patients with malignant or benign diseases for whom radiation therapy is indicated. It allows the physician to create and communicate radiation treatment intent (RT intent) to the treatment planner, review and approve candidate plans, and monitor treatment progress. It is intended to be used with a treatment planning system to treat or alleviate disease in humans by streamlining the treatment management and monitoring processes.	Ethos Treatment Planning is a standalone software device designed to generate and modify radiation therapy treatment plans and manage treatment sessions. The device supports the traditional and adapted treatments, in which the scheduled plan is adapted to the patient's anatomy at the time of treatment.
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V. INTENDED USE AND INDICATIONS FOR USE

Intended Use:	Ethos Treatment Management is used tomanage and monitor radiation therapytreatment plans and sessions; it is intended tobe used with a treatment planning system.(Same as predicate)	Ethos Treatment Planning is used to generateand modify radiation therapy treatment plans.(Same as predicate)
Indications forUse:	Ethos Treatment Management is indicated foruse in managing and monitoring treatmentplans and sessions.(Same as predicate)	Ethos Treatment Planning is indicated for use ingenerating and modifying radiation therapytreatment plans.(Same as predicate)

TECHNOLOGICAL COMPARISON VI.

Ethos Treatment Management:

There are identical technological characteristics and features that apply to the subject device and predicate. Both the subject device and the predicate device provide tools for qualified medical professionals to do initial planning, review and approve candidate plans, and monitor ongoing treatments for patients to be treated with radiation therapy. The significant differences between the subject device and predicate device are the following:

o High fidelity mode support
. Al segmentation deep learning algorithms added to contouring
Hypersight images supported as planning images
. Handling of image only sessions
. Ethos – ARIA Coexistence in ARIA connected mode

These modifications do not raise different questions of safety and effectiveness. The verification and validation demonstrate that the device is as safe and effective as the predicate.

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Image /page/5/Picture/0 description: The image shows the logo for Varian, a Siemens Healthineers Company. The word "Varian" is in a bold, sans-serif font. Below the logo is the text "A Siemens Healthineers Company" in a smaller, sans-serif font. The logo is simple and modern.

Ethos Treatment Planning:

Both the new device and the predicate device perform treatment planning, provide tools for gesissionals to manage treatment sessions and adapt plans for patients to be treated with radiation therapy. A subset of features is different. The significant differences in design for Ethos Treatment Planning 2.0 when compared to the predicate are:

Enhanced Intelligent Optimizer Engine (IOE)
High Fidelity Mode on IOE
New Beam Geometry Optimizer
o Al segmentation – additional anatomical site support
Enhancement of target propagation
o Support HyperSight CBCT - direct CBCT dose calculation

These differences are all considered by Varian to be minor enhancements of the predicate. There are no changes in the principle of operation of the device. The verification demonstrate that the device is as safe and effective as the predicate.

VII. NON-CLINICAL AND/OR CILINICAL TESTS SUMMARY & CONCLUSIONS

The following performance data were provided in support of the substantial equivalence determination.

Ethos Treatment Management 3.0 and Ethos Treatment Planning 2.0 has undergone formal design validation testing. Design verification and design validation testing demonstrates that Ethos Treatment 3.0 and Ethos Treatment Planning 2.0 performs as intended and meets its essential performance. The subject device is considered to have a "major" level of concern, since a failure or latent flaw in the software could directly result in serious injury or death to the patient or operator.

Software Verification and Validation Testing

Software design verification and design vas performed according to the FDA Quality System Regulation (21 CFR §820), ISO 13485 Quality Management System Standard, ISO 14971 Risk Management Standard, and IEC 62304 Software Life Cycle Process standard. Test results demonstrate conformance to applicable requirements specifications and assure hazard safeguards function properly. Software design validation testing was conducted, and documentation is provided as recommended by FDA's Guidance for Industry and FDA Staff, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices" (June 2023).

No animal studies or clinical tests have been included in this submission.

Al Model Validation

The following are details on the validation charatseristics for the Al models:

Validation Characteristic	As applied in the Subject Device:
Characterization of ModelPerformance	Organs are detected on the patient image via artificial intelligence(AI) segmentation models. These models consist of convolutionalneural networks, the weights of which are static. They are notadapted during the operation of the product. That means, themodels do not continuously learn and thus do not alter theirbehavior over time based on user input.
	The AI models operate on image resolutions that are suitable forrepresentation of the organs they were trained for. Patient imagesare re sampled before inference (running the detection network).After inference, the resulting label maps are sampled back onto thepatient image grid.
	Contouring performance undergoes rigorous evaluation throughverification and validation processes. The verification process aimsto identify eligible models for subsequent validation. This initialstage relies on quantitative metrics such as the DICE similaritycoefficient. The DICE coefficient serves as a comparison benchmarkagainst references published in the literature, especially whenintroducing a model for a new organ. In cases of model replacement,
	The validation process emulates the usage of the auto contouringsolution in clinical practice. Experts, including radiation oncologists,dosimetrists, and physicists from various healthcare facilitiesworldwide, evaluated the quality of the contours across test sets toassess the need and the type of contour adjustments, whichconsequently gives an estimate of the time saved on contouringtasks. Models were only considered eligible for production if theyconsistently produced contours that needed minor or noadjustments in at least 80% of the test cases.
Number of Patients andSamples in Dataset	For the training datasets, a variety of subjects and scans were usedaccording to the body site of interest. The overall total number oftraining scans used was 4769, while the total for testing scans was1045. These scans consisted of the following body sites with therespective patient count (#, inclusive of training and testingsubjects): full body (179), head and neck (1173), thorax (600),abdomen (527), bowel (507), and pelvis (1192).
Demographic, clinicalsubgroups, and confoundingdetails	The scans are obtained from different patient subgroups which areprimarily comprised of those with treatment indications for cancers(assorted tumors, brain cancer, lung cancer, breast cancer, livercancer, pancreatic cancer, stomach cancer, adrenal cancer, bladdercancer, prostate cancer, cervical cancer, vaginal cancer, uteruscancer, rectal cancer, anal cancer, and/or spinal cancer). Some scanscame from post prostatectomy or post hysterectomy sourcing.Patient demographics from a large portion of the scans areanonymized, but the largest number and percentage proportionallyof scans originated from patients in the United States.Other confounding details in the images used to train and testmodels would include contrasting agents, catheters, radioactiveseeds, compression devices, external devices (tracheostomy tubes),breast implants, teeth implants, and/or radiotherapy masks.

Equipment and protocolsused to collect images	The scans are comprised of CBCT (734 training, 398 testing) and CT(4035 training, 647 testing) image types; these were obtained on avariety of scanner manufacturers and models, including systemsfrom GE Medical Systems (553 total), Phillips (1194), Siemens (274),Varian Medical Systems (1973), and others. The patient position formost of the scans (~90%) was head first supine (HFS).
Development of GroundTruth	Ground truth annotations were established by human anatomyexperts as part of the algorithm development following RTOG andDAHANCA clinical guidelines. A single set of contours was producedfor each training image. These clinical experts have significantclinical experience in segmentation of CT imaging for the differentdisease sites covered by the Al models. To ensure accuracy, contourdefinitions available in contouring guidelines are established prior tocontouring tasks.
Data Independence forTraining and Test Sets	The partitioning of training and test sets was done at the patientlevel, such that no scans from a patient could be used within boththe training set and the test set.

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CONCLUSIONS VIII.

The intended use and indications for use are the predicate device. The overall verification and validation testing for Ethos Treatment Management and Ethos Treatment Planning demonstrates that the device requirements and risk control measures perform as intended at a level similar to the predicate. The subject device and the predicate device have the same intended use, and the significant differences do not result in a new intended use. Varian, therefore, believes that Ethos Treatment Management 3.0 and Ethos Treatment Planning 2.1 are substantially equivalent to their respective predicate devices.

Regulation Number and Section

§ 892.5050 Medical charged-particle radiation therapy system.

(a)
Identification. A medical charged-particle radiation therapy system is a device that produces by acceleration high energy charged particles (e.g., electrons and protons) intended for use in radiation therapy. This generic type of device may include signal analysis and display equipment, patient and equipment supports, treatment planning computer programs, component parts, and accessories.(b)
Classification. Class II. When intended for use as a quality control system, the film dosimetry system (film scanning system) included as an accessory to the device described in paragraph (a) of this section, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 892.9.