Chapter 5: It’s All Very Evident – Other Evidence-Based Metrics

By sdavis | January 28, 2019 | Blog

The Long and Short of It Series

There is growing recognition and acceptance of volumetrics as a superior method for sizing tumors. At a minimum, quantitative measurements that leverage three-dimensional observations outperform traditional Long and Short measurements by more accurately detecting growth and reducing variability. While these advancements are good news for cancer treatment, greater potential exists to expand the reach and benefit of quantitative observations.

Radiologists know that three-dimensional simple lesion measurements represent only the tip of the iceberg in terms of the wealth of information available in imaging studies. In tandem, oncologists are also aware that a much deeper, more comprehensive base of quantitative information is available than what they are typically provided. With the right tools, both radiologists and oncologists can extract greater value from volumetrics by expanding their analysis to other evidenced-based metrics.

Image data used today is much like an iceberg. Only a small part of the iceberg is seen above the water line and represents the limited data we use today such as the Long and Short measures, but most of the iceberg lies under the water and represents the untapped volumetric data such as volume, density, mass and the full radiomic profile that are waiting to be discovered.

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Researchers in one study noted: “As therapeutic regimens continue to grow in complexity and precision, the current clinical methods of radiologic assessment of response will inevitably become inadequate. Emerging quantitative imaging methods are available for wide-scale deployment currently and will increase in the immediate future.”1 Some of these opportunities include:

Lung nodule mass and doubling time using CT.

One study revealed that growth measures that consider the change in mass of ground glass nodules (GGNs) allowed earlier detection of growth and less observer variability than lesion diameter or volume. Researchers noted that the “findings may have implications for early detection of malignancy in GGNs.”2

Another study evaluated the volume doubling time (VDT) and mass doubling time (MDT) of persistent pulmonary subsolid nodules as an innovative and sensitive measure increasingly used in lung cancer screening. 3 Defined as the number of days in which the volume or mass of the nodule doubles, VDT and MDT measurements are increasingly used for more accurate diagnosis of nodule changes—a critical component to the survival of lung cancer patients.

Volumetric data from an advanced quantitative imaging platform including Volume Doubling Time (VDT) and Mass Doubling Time (MDT)

Tumor cellularity measurements using diffusion-weighted imaging (DWI).

A form of MR imaging, clinicians currently look to DWI to determine cellularity—a measure of how densely packed the cells are within a region of the image. Multiple DWIs are used to determine an apparent diffusion coefficient (ADC) map. These findings then provide insights into the likelihood of malignancy or the nature of a tumor. For instance, lower ADC values suggest decreased diffusion, or more tightly packed cells, which helps distinguish a malignant lesion, or often correlates to a more aggressive tumor. Subsequently, ADC values can then be used to help stage disease after an initial cancer diagnosis.4 They can also be used to monitor treatment response, where an increase in ADC corresponds to a favorable treatment response.5

Tumor metabolism and proliferation using positron emission tomography (PET).

Uptake of the injected radiopharmaceutical 2-[(18)F]-fluoro-2-deoxy-D-glucose (FDG) is a hallmark of cancer. This is because FDG is a glucose analogue and consumed by tumors. Similarly, another compound, 18F-fluorothymidine (FLT), is taken up by proliferating cancer cells. Thus, measurements of the uptake of these compounds using PET can reveal information during diagnosis, staging and treatment follow up. Standardized uptake values (SUV) calculated from PET image pixel values are used to quantify concentration of a radiopharmaceutical in tissues.6

A whole-body PET scan Maximum Intensity Projection (MIP) using 18F-FDG shows liver metastases of a colorectal tumor from several different angles.)

Current Challenges to Deeper Volumetric Analysis

While greater potential exists to expand volumetrics, research suggests that uptake of these advanced evidence-based techniques remains low. A review of CT and MRI reports from two randomly selected weekdays in 2011 in a single-mixed academic practice found that 44 percent of all reports contained at least one quantitative metric, defined as any numerical descriptor of a physical property other than quantity. Yet, only 2 percent of reports contained an advanced quantitative metric, defined as a numerical parameter reporting on lesion function or composition, excluding simple size and distance measurements.7

Researchers found numerous reasons why only simple measurements are routinely made and incorporated into patient management decisions. First, extracting quantitative data beyond a simple diameter is technically challenging, time-consuming and often not possible with available tools. Traditional picture archiving and communication systems (PACS) routinely used by radiologists are not designed for quantitative analysis.

Today, quantitative image tools are primarily found in imaging laboratories and used for research and the small minority of patients enrolled in clinical trials. Even when quantitative imaging software exists, many radiologists consider the time required to extract a measurement such as a volume, percent ground-glass opacity and average diffusion coefficient unwarranted given lack of specific reimbursement for such activities.

In addition, there is still a fair amount of skepticism in the oncology community regarding use of advanced evidence-based metrics in diagnostic interpretation. Oncologists often rely on traditional measurements, such as tumor diameter, to help make decisions and are reluctant to use data that they consider has not been fully validated in real-world clinical settings. Consequently, radiologists provide only what is expected of them.

Finally, radiology is traditionally a qualitative discipline, and many radiologists consider their main value is in providing descriptive reports based on their knowledge and experience. They “paint a picture” for the oncologist, rather than provide definitive metrics. Indeed, many radiologists see the measurements they provide as a part of that qualitative picture, rather than as quantitative data that the oncologist will use objectively.

“Traditional picture archiving and communication systems (PACS) routinely used by radiologists are not designed for quantitative analysis.“

Advancing Evidence-Based Metrics

While adoption and use of advanced volumetric measurements has been slow to date, there remains consistent push from the academic radiology and oncology communities to make radiology reports more quantitative—not just in trial settings, but in routine care. Technology is an important enabler of this movement and must address the time and resource complexities that currently hinder forward momentum.

The good news is that solutions exist that drill deep into volumetrics, automating the process of extracting data and making calculations within the standard clinical workflow. Within seconds, radiologists can view details of volume, density, mass, solidity, doubling times, texture and other critical data and include these metrics in their reports to the multidisciplinary care team. Researchers who outlined challenges in the previously mentioned study noted that the “barriers are not insurmountable,” and the industry goal should be “to encourage and guide the oncology community to deploy standardized quantitative imaging techniques…to further personalize care for cancer patients and to provide a more efficient path for the development of improved targeted therapies.”8

Volumetric data from an advanced quantitative imaging platform including Volume Doubling Time (VDT) and Mass Doubling Time (MDT)

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Bibliography

  1. T. Yankeelov, D. Mankoff, L. Schwartz, F. Lieberman, J.Buatti, J. Mountz, et al. “Quantitative imaging in cancer clinical trials,” Clinical Cancer Research, 2016, 22(2):284–90.
  2. B. de Hoop, H. Gietema, S. van de Vorst, K. Murphy, R. van Klaveren, M. Prokop. “Pulmonary Ground-Glass Nodules: Increase in Mass as an Early Indicator of Growth,” Radiology, 2010, 255(1):199–206. Available from: http://pubs.rsna.org/doi/10.1148/radiol.09090571
  3. Y. Song, C. Park, S. Park, S. Lee, Y. Jeon, J. Goo. “Volume and Mass Doubling Times of Persistent Pulmonary Subsolid Nodules Detected in Patients without Known Malignancym,” Radiology, 2014, 273(1):276–84. Available from: http://pubs.rsna.org/doi/abs/10.1148/radiol.14132324%5Cnhttp://files/2218/Song et al_2014_Radiology_Volume and Mass Doubling Times of Persistent Pulmonary Subsolid Nodules.pdf%5Cnhttp://files/1303/radiol.html
  4. A. Rosenkrantz, M. Mendiratta-Lala, B. Bartholmai, D. Ganeshan, R. Abramson, K. Burton, et al. “Clinical Utility of Quantitative Imaging,” Academic Radiology, 2015, January; 22(1): 33–49.
  5. T. Yankeelov, et al. 2016.
  6. T. Yankeelov, et al. 2016.
  7. R. Abramson, P. Su, Y. Shyr. “Quantitative metrics in clinical radiology reporting: A snapshot perspective from a single mixed academic-community practice,” Magnetic Resonance Imaging, 2012, 30(9):1357–66.
  8. T. Yankeelov. 2016.