The Long and Short of It Series
If you or someone you know has been diagnosed with cancer, or if you are a clinician that performs diagnoses, the chances are pretty high that the diagnosis was made from information in an image. It may have been an X-ray, mammogram, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), or even a combination of these, but most cancer patient’s stories start with that image and the diagnosis made from it.
In 1979, the World Health Organization, in an attempt to standardize the way that the details and results of patients being treated for cancer are reported, and in cooperation with the world’s leading cancer organizations, published the WHO Handbook for Reporting Results of Cancer Treatment. Their intention was to “develop a ‘common language’ to describe cancer treatment and to agree on internationally acceptable general principles for evaluating data.” 1 As part of the recommendations, WHO describes a minimum desirable dataset for describing the tumor. This includes information about the location, histopathology, anatomical extent, clinical stage, and most importantly for this discussion, describes how to measure the tumor or lesion in order to evaluate the results of therapy. Specifically, they state to “give, in centimeters, the maximum diameter(s) and second transverse diameter(s), at a right angle to the first and in the same plane.” Almost 40 years later, this is still the standard for determining therapy results and is commonly referred to as the Long and Short measurements.
Most of today’s most common therapy response assessment protocols like RECIST 1.1 use these measurements and some form of WHO’s definitions of response such as ‘Complete Response’ meaning, “the disappearance of all known disease, determined by 2 observations not less than 4 weeks apart,” or ‘Partial Response’ meaning, “50% or more decrease in total tumor size of the lesions which have been measured to determine the effect of therapy by 2 observations not less than 4 weeks apart.”
The use of the Long and Short measurements was designed to provide a simple method to approximate the volume of a tumor as volume is known to be an accurate biomarker of response but can be very difficult to determine quickly and accurately. Unfortunately, there are issues with using diameter measurements to approximate volume.
The first is getting measurements to begin with. The American Journal of Radiology (AJR) published a two-part series titled “Quantitative Imaging in Oncology Patients” in which they surveyed both radiologists and oncologists regarding their views on quantitative, objective imaging data. While 93% of oncologists felt that having tumor measurements affected their ability to manage their patient’s disease, only 7% of radiologists reported providing those measurements on the first clinical interpretation. 2, 3
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Part of this stems from the fact that many radiologists feel that subjective information such as “the lesion is noticeably larger” is sufficient, but much of it is caused by the fact that the tools that are available to radiologists for making measurements are cumbersome, adding time they don’t have to the read. The tools are also prone to introducing errors, bringing us to the second issue.
Inter- and even intra-reader variability is a well-known fact in the world of radiology. There is hardly a clinician practicing that will disagree. Some of the problem is caused by the tools themselves. The digital calipers available in today’s Picture Archiving and Communication Systems (PACS) are not designed for precision, although much of the variability comes from the fact that the human eye cannot easily discern, especially consistently, what the widest point of an irregularly shaped lesion is. In a recent conversation with a radiologist regarding this variability, they laughed and told a story of how they recently opened a case with a prior study and while looking at the measurements provided by the previous radiologist wondered “what in the heck were they thinking?” Then they noticed that in fact they were the one who did the read and it was their own measurements they were critiquing!
Even if the measurements could be accurate, it doesn’t solve all of the problems. Long and Short diameters are used as a surrogate for volume, a well-known biomarker for response. But, diametric measurements can give inaccurate estimates of the true volume. Frenette, et al determined just that, and in fact their results do not paint a very good picture. They found that on average, the estimated volume from diameter measurements in their experiments varied by 88.03% from the actual measured volumes. 4 Their conclusion was that their “results suggest that diametric measurements cannot be correlated to actual tumor size.”
There are some intriguing questions that are raised based on this information. If we have been using these values for almost 40 years, and there is evidence that these values haven’t been very accurate or consistent, what does that mean for the treatments based on them? Of course, the big question is, is there anything we can do about it?
The good news is that yes, there is. We now know the why and the what of the problems. The next chapters will attempt to answer the how in regard to achieving more accuracy, more consistency, and maybe most importantly providing better evidence-based metrics to ensure that patients who are fighting cancer receive optimum care.
Figure 1: On average, there was an 88.03% variance between the estimated and actual measured volumes with one lesion showing a greater than 500% difference
- World Health Organization, "WHO Handbook for Reporting Results of Cancer Treatment," World Health Organization, Geneva .
- T. A. Jaffe, N. W. Wickersham and D. C. Sullivan, "Quantitative Imaging in Oncology Patients: Part 1, Radiology Practice Patterns at Major U.S. Cancer Centers," AJR, vol. 195, pp. 101-106, July 2010.
- T. A. Jaffe, N. W. Wickersham and D. C. Sullivan, "Quantitative Imaging in Oncology Patients: Part 2, Oncologists’ Opinions and Expectations at Major U.S. Cancer Centers," AJR, vol. 195, pp. W19-W30, July 2010.
- A. Frenette, J. Morrell, K. Bjella, E. Fogarty, J. Beal and V. Chaudhary, "Do Diametric Measurements Provide Sufficient and Reliable Tumor Assessment? An Evaluation of Diametric, Areametric, and Volumetric Variability of Lung Lesion Measurements on Computerized Tomography Scans," Journal of Oncology, 2015.