Profile: CT Lung Nodule - Small Nodule in Neoadjuvant Setting

Section 1: Title Page

The Radiological Society of North America (RSNA) Quantitative Imaging Biomarker Alliance (QIBA) Volumetric Computed Tomography (v-CT) Technical Committee: Profile Claims for Quantifying the Volumes of Lung Nodules in Patients Undergoing Neoadjuvant Treatment for Cancer

Running Title: "v-CT neo Rx" key words: nodule; lung nodules; neoadjuvant therapy

Proffered by the Volumetric CT Technical Committee (in alphabetical order)

James L. Mulshine (Subgroup Chair)

Table of Contents Page

Section 2: Executive Summary, Introduction and Background Information

The v-CT technical committee is composed of scientists representing the imaging device manufacturers, image analysis software developers, image analysis laboratories, biopharmaceutical industry, academia, government research organizations, professional societies, and regulatory agencies, among others. All work is classified as pre-competitive. A more detailed description of the v-CT group and its work can be found at the following web link: http://qibawiki.rsna.org/index.php?title=Volumetric_CT

The long-term goal of the v-CT committee is to qualify the quantification of anatomical volumes of interest with x-ray computed tomography (CT) as biomarkers. The v-CT group selected solid tumors of the chest in patients with lung cancer as its first case-in-point. This Profile Claims document extends that work into neoadjuvant settings.

The primary problem, or clinical use case, is that past attempts to quantify the volumes of small lung nodules has been highly imprecise. While both intra- and inter-rater reliability has been consistently less than 1% for static images, coffee break designs have shown that confidence intervals surrounding volume measurements have been greater than 30%. This level of variability makes it difficult to suggest using volumetric image analysis as a biomarker of response in neoadjuvant settings.

The specific aim of this image acquisition and processing protocol is to describe procedures that seem sufficient for quantifying the volumes of small neoplastic masses in the chest.

The Profile describes, in predominantly chronological order, procedures that are required to achieve high levels of precision. At each step in the process, key terms include procedures that are (1) "acceptable", by which it is meant that anything less rigorous will likely fail to meet minimum criteria for precision and accuracy; (2) "targets", by which it is meant parameters that are most likely to meet or exceed specifications; and (3) "ideal", by which it is meant parameters that are probably the best fit-for-purpose currently available, regardless of the effort required to implement them.

The protocol describes procedures that should be universally followed in neoadjuvant settings, regardless of the instrument that is used to acquire the data. It also provides links to tables that list specific settings on various makes-and-models of CT scanners.

This Profile should be considered fit for purpose in the care of individual patients in conventional medical settings, as well as in clinical trials of new neoadjuvant therapies for lung cancer. Some of these clinical settings are described in Table 1.

Table 1: Summary of Image Processing Issues Relative to Stage of Lung Cancer

Stage	% of Cases	5-year Survival %	Imaging Focus / Therapy Focus	Imaging Tool	Issues	Thoracic Segmentation	Hi-Res
I	16	49	Primary tumor / Neo and adjuvant RX	sCT	Small cancers surrounded by air	Can be straightforward	Needed
II/III	35	15.2	Primary, hilar and mediastinal lymph nodes / Combined modality	sCT, PET	Larger tumors and nodes abut other structures	Often challenging	Optional
IV	41	3	Primary/regional nodes and metastatic sites / Chemotherapy	sCT, PET, Bone, Brain scans	Tumor response often determined outside of the chest	Often challenging	Optional

Table 1; Summary of how staging relates to lung cancer drug therapy approaches, the imaging approaches used in those stages and issues relative to the image requirements.

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Profile Claims (what users will be able to achieve)

Claim #1:

• Precursor:

Claim #2:

• Precursor:

Claim #3:

• Precursor:

Appendices

• Appendix 1. Definitions of Terms and Abbreviations
• Appendix 2: Acquisition Parameters and Settings for Specific Makes & Models
• Appendix 3. Risks of the Imaging Procedures
• Appendix 4. Reader Training
• Appendix 5. Site Selection