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The Cancer Genetics Tissue of Origin Test is an in vitro diagnostic intended to measure the degree of similarity between the RNA expression patterns in a patient's formalin-fixed, paraffin-embedded (FFPE) tumor and the RNA expression patterns in a database of fifteen tumor types (poorly differentiated, undifferentiated and metastatic cases) that were diagnosed acording to then current clinical and pathological practice. This test should be evaluated by a qualified physician in the context of the patient's clinical history and other diagnostic test results.

Limitations: The Cancer Genetics Tissue of Origin Test is not intended to establish the origin of tumors (e.g., cancer of unknown primary) that cannot be diagnosed according to current clinical and pathological practice. It is not intended to subclassify or modify the classification of tumors that can be diagnosed by current clinical and pathological practice, nor to predict disease course or survival or treatment efficacy, nor to distinguish primary from metastatic tumor. Tumor types not in the Cancer Genetics Tissue of Origin Test database may have RNA expression patterns that are similar to patterns in the database. Therefore, results cannot be used to distinguish tumor types in the database from tumor types not in the database.

The modified and the predicate devices (K092967 and K120489) are all in vitro diagnostic product consisting of a reagent kit and instructions, plus a microchip and software, for the comparison of the RNA expression pattern of a patient's tumor sample to a database of expression patterns of 15 known tumor tissues. Equipment required but not provided are an Affymetrix GeneChip Fluidics Station FS450Dx v2 and an Affymetrix GeneChip Scanner GCS3000Dx, attached to an Affymetrix Workstation with GeneChip Operating System (GCOS). Additional equipment required but not provided is commonly available laboratory equipment.

Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text.

It's important to note that this document is a 510(k) summary, which often focuses on demonstrating substantial equivalence to an existing device rather than presenting a full, de novo validation study. Therefore, some of the requested information, particularly regarding initial clinical validation or ground truth establishment for the original device, might not be explicitly detailed. The acceptance criteria described here pertain to demonstrating performance after modifications to an already cleared device.

Acceptance Criteria and Device Performance for Modified Tissue of Origin Test Kit-FFPE

The acceptance criteria here refer to the demonstration that two specific modifications (reagent change and software update) to an already cleared device (Pathwork Tissue of Origin Test Kit FFPE, K120489) did not negatively impact its performance. The primary metric used is concordance with the previous, validated method.

1. Table of Acceptance Criteria and Reported Device Performance

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

• Test Set Sample Size:
  • Reagent Comparison: 142 specimens
  • Software Comparison: 20 specimens
• Data Provenance: The specimens were "randomly selected from FFPE tumor specimens employed for assessment of performance during development of the original TOO-FFPE kit." This indicates the data is retrospective, using archived samples. The country of origin is not specified, but the context of an FDA submission implies commercial use in the US, suggesting data likely from US/North American sources, though not explicitly stated.

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

• This information is not provided in the document. The studies assess concordance between the modified and original methods, implying the "truth" is established by the original method's result for the sample. The original device's clearance (K092967, K120489) would have involved establishing its ground truth based on clinical and pathological practice, but the details are not replicated here for this 510(k) summary focused on modifications.

4. Adjudication Method for the Test Set

• This information is not applicable in the context of these specific studies. The studies are comparing the output of a modified process against the output of the original, previously cleared process for the same samples. Discrepancies are noted as "discordance" rather than requiring expert adjudication of a "ground truth" difference, as the reference is the prior method's output.

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

• No, an MRMC comparative effectiveness study was not conducted. This device is an in vitro diagnostic (IVD) test measuring molecular expression patterns, not an imaging AI designed to assist human readers. The outputs are numerical similarities to pre-defined tumor types, not interpretations for human review.

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

• Yes, the performance described is standalone (algorithm only). The device, the "Tissue of Origin Test Kit-FFPE," measures RNA expression patterns and provides a similarity score. The studies assess the consistency of these scores between modified and original methods, which is a direct output of the algorithm and associated lab processes without human interpretation as part of the core performance evaluation.

7. The Type of Ground Truth Used

• For the purpose of these modification studies, the "ground truth" for each sample's classification is implicitly the result obtained from the original, previously cleared and validated method. The studies aim to show that the new modifications yield the same result as the established method. The ultimate ground truth for the original validation of the TOO-FFPE test, as stated in its Indications for Use, was based on "diagnosed according to then current clinical and pathological practice" for the 15 tumor types in its database. This would typically involve expert consensus diagnostics (e.g., pathology reports, clinical history).

8. The Sample Size for the Training Set

• The sample size for the training set is not specified in this document. This 510(k) summary pertains to modifications of an already developed and trained device. The original development and validation of the "Tissue of Origin Test Kit-FFPE" (K092967 / K120489) would have involved a training set, but its details are not part of this summary for a modified device. The document mentions the "database of fifteen tumor types" against which patient samples are compared, which serves as the trained model/reference.

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

• How the ground truth for the original training set was established is not detailed in this document.
  • However, the Indications for Use states that the database samples were "diagnosed according to then current clinical and pathological practice." This typically means that the ground truth for the 15 tumor types in the database was established by expert consensus diagnoses based on a combination of clinical history, pathological findings (histology, immunohistochemistry), and potentially other diagnostic tests. This implies a rigorous, multi-modal diagnostic approach by qualified medical professionals (e.g., pathologists, oncologists).

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