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Whole-body imaging as cancer screening tool; answering an unmet clinical need?

Author: Dror Nir, PhD

Sometimes technologies that were developed to answer clinical needs in a certain area are migrated to perform in a totally inappropriate area. A good example which I discussed several times in my posts is PSA.

Cancer patients’ prognoses, strongly depend on accurate tumor staging. It is also a prerequisite for therapy choice and planning. Whole-body imaging is frequently used in patients with advanced malignant diseases including presence of metastases as these may occur in any anatomic region. It is important to note that classifying a patient as harboring a potentially advanced disease is based on biopsy results of Sentinel Lymph-Nodes and not on imaging. Moreover, referring a patient to a whole-body imaging is a choice of the treating practitioner! Clearly, when the choice of treatment includes administration of drugs, the type of drugs to be used is determined by the characteristics of the primary tumor.

To date, the use of whole-body imaging for post treatment follow-up can be considered as anecdotal.

The most-used technologies for whole-body imaging are computed tomography (CT), positron emission tomography (PET) and MRI. The performance of these systems in detection of cancer metastases of more than 1cm in diameter is very similar and in general quite good, dependent on the primary disease and the body locations of the metastases. Alas, each of these modalities has its strengths and weakness in different cancer and different body locations. Therefore, in the last decade, combined modalities such as PET-CT and recently PET/MRI were introduced. In some cases [1-6] these are reported to show sensitivity of more than 90%.

To demonstrate the level of information produced during whole-body imaging procedure here is an example (taken from Whole-body MRI and PET-CT in the management of cancer patients). This resource includes additional, educating examples:

Fig. 1

From multimodality to single-step examination. Restaging in a 29-year-old woman treated for breast cancer and with newly elevated tumor markers and bone pain. 1a, 1b Radiograms of the skeleton were normal, but bone scintigraphy showed a pathological tracer uptake in the right pubic bone (arrow). Abdominal ultrasound exhibited a suspicious mass. 1c, 1d CT revealed tumor recurrence in the right breast and confirmed hepatic metastasis. 2a, 2b T1-weighted whole-body MRI depicted a metastasis in the right pubic bone (circle). 2c, 2d HASTE images of the thorax showed the tumor recurrence in the right breast (arrow) and dynamic contrast enhanced studies of the abdomen unmasked the liver metastasis

Before addressing the issue of using whole-body imaging as a screening tool I would like to draw attention to existence of other methods for screening and post treatment follow-up of cancer patients; e.g. detecting levels of cancer-specific bio-markers in the blood or urine or, in case of advanced disease, detecting the level of tumor cells circulating in the blood as presented in: Circulating Tumor Cells versus Imaging—Predicting Overall Survival in Metastatic Breast Cancer by G. Thomas Budd et.al.

“Abstract

Purpose: The presence of ≥5 circulating tumor cells (CTC) in 7.5 mL blood from patients with measurable metastatic breast cancer before and/or after initiation of therapy is associated with shorter progression-free and overall survival. In this report, we compared the use of CTCs to radiology for prediction of overall survival.

Experimental Design: One hundred thirty-eight metastatic breast cancer patients had imaging studies done before and a median of 10 weeks after the initiation of therapy. All scans were centrally reviewed by two independent radiologists using WHO criteria to determine radiologic response. CTC counts were determined ∼4 weeks after initiation of therapy. Specimens were analyzed at one of seven laboratories and reviewed by a central laboratory.

Results: Inter-reader variability for radiologic responses and CTC counts were 15.2% and 0.7%, respectively. The median overall survival of 13 (9%) patients with radiologic nonprogression and ≥5 CTCs was significantly shorter than that of the 83 (60%) patients with radiologic nonprogression and <5 CTCs (15.3 versus 26.9 months; P = 0.0389). The median overall survival of the 20 (14%) patients with radiologic progression and <5 CTCs was significantly longer than the 22 (16%) patients with ≥5 CTCs that showed progression by radiology (19.9 versus 6.4 months; P = 0.0039).

Conclusions: Assessment of CTCs is an earlier, more reproducible indication of disease status than current imaging methods. CTCs may be a superior surrogate end point, as they are highly reproducible and correlate better with overall survival than do changes determined by traditional radiology. “

I would like first to present the following publication that could explain why people can easily be drawn why whole-body screening is an effective way to detect early cancers:

Enthusiasm for cancer screening in the United States by Schwartz LM, Woloshin S, Fowler FJ Jr, Welch HG SO, JAMA. 2004; 291(1):71.:

“ CONTEXT: Public health officials, physicians, and disease advocacy groups have worked hard to educate individuals living in the United States about the importance of cancer screening.

OBJECTIVE: To determine the public’s enthusiasm for early cancer detection.

DESIGN, SETTING, AND PARTICIPANTS: Survey using a national telephone interview of adults selected by random digit dialing, conducted from December 2001 through July 2002. Five hundred individuals participated (women aged>or =40 years and men aged>or =50 years; without a history of cancer).

MAIN OUTCOME MEASURES: Responses to a survey with 5 modules: a general screening module (eg, value of early detection, total-body computed tomography); and 4 screening test modules: Papanicolaou test; mammography; prostate-specific antigen (PSA) test; and sigmoidoscopy or colonoscopy.

RESULTS: Most adults (87%) believe routine cancer screening is almost always agood idea and that finding cancer early saves lives (74% said most or all the time). Less than one third believe that there will be a time when they will stop undergoing routine screening. A substantial proportion believe that an 80-year-old who chose not to be tested was irresponsible: ranging from 41% with regard to mammography to 32% for colonoscopy. Thirty-eight percent of respondents had experienced at least 1 false-positive screening test; more than 40% of these individuals characterized that experience as “very scary” or the “scariest time of my life.” Yet, looking back, 98% were glad they had had the initial screening test. Most had a strong desire to know about the presence of cancer regardless of its implications: two thirds said they would want to be tested for cancer even if nothing could be done; and 56% said they would want to be tested for what is sometimes termed pseudodisease (cancers growing so slowly that they would never cause problems during the person’s lifetime even if untreated). Seventy-three percent of respondents would prefer to receive a total-body computed tomographic scan instead of receiving 1000 dollars in cash.

CONCLUSIONS: The public is enthusiastic about cancer screening. This commitment is not dampened by false-positive test results or the possibility that testing could lead to unnecessary treatment. This enthusiasm creates an environment ripe for the premature diffusion of technologies such as total-body computed tomographic scanning, placing the public at risk of over testing and overtreatment.”

Whole-body screening is promoted as a one-stop shop for painlessly detecting hidden cancer and preventing cancer-related deaths. It is big business in the United States and in Canada where private clinics have begun offering full-body diagnostic procedures for a fee. The tests and procedures are often marketed to healthy people as a way to scan for hidden abnormalities or cancers, affording people the peace of mind that they are in good health [7 – 9].

When used in this manner, the evidence shows that whole-body cancer screening offers no proven health benefits and that it, in fact, exposes people to a number of unnecessary health risks. The problem I see is that the public is not exposed to “scientific publications” but is exposed to commercial ones!

 

References

1. FDG PET and PET/CT: EANM procedure guidelines for tumor PET imaging: version 1.0
2. Cancer of the Prostate, Testicles and Penis
3. Gynecologic Cancers
4. Malignant Melanoma
5. Molecular Imaging in Cancer
6. Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and applications
7. Full body CT scan for screening
8. Screening for Cancer with PET and PET/CT: Potential and Limitations 
9. http://www.privatescan.nl/total-bodyscan

Written by: Dror Nir, PhD