"First, do no harm" (Hippocratic Oath)

By Antonio M.C. Reis, M.D.
and Maria de Lurdes F.V. Queimado, M.D., Ph.D.

Introduction

We started this investigation suspecting that the long-term risks associated to CTs (computed tomography) would deserve attention, and that replacing CTs by MRIs (magnetic resonance imaging) would be an acceptable general rule. What we never suspected in the beginning was that our investigation would leave us terrified when we extrapolated the high risk associated with a few CTs. 

Fortunately, we were relieved when we found that MRIs are acceptable and recommended for the follow-up of lymphoma patients by several experts, including the European radiology and nuclear medicine in conjunction with the UK Royal College of Radiologists. Importantly, among most medical procedures associated with radioactive exposure, CTs represent the highest risk due to the highest radiation exposure. 

Paradoxically, many cancer patients are at higher risk because they repeatedly receive CTs and other radiological evaluations. Obviously, this chronic exposure leads to a significant increase in the cumulative risk (already high for a single CT scan). At the molecular level, this cumulative exposure has a great potential to lead either to the progressive accumulation of mutations in pre-existing cancer cells or to the generation of a second cancer in a matter of years. For example, it is not easy to rule out that transformation (a stage of more malignant phenotype, to which low-grade follicular non-Hodgkin lymphoma commonly evolves) could be (in some patients) linked to the radiation exposure during medical evaluations. Hence, since the deleterious effects of radiation has the potential to compromise the evaluation and/or efficacy of promising new therapies, the avoidance of radiation exposure is of major interest, not only to patients who are monitored routinely, but also to doctors, scientists, and companies conducting clinical trials in which participants can receive head-to-pelvis exposures every few months.  It is well known that MRIs, PET (or Gallium) scans, as well as other diagnostic procedures, can be used as an alternative (or sometimes in a complementary fashion) to CTs. Even a decrease in the frequency of CTs has the potential to have a significant benefit for the patient in the long term. More importantly, patients should be evaluated in the safest way possible. The use of safer monitoring alternatives may deserve financial considerations, but the patient should have the right to avoid relevant risks and to choose the safest way in concert with his or her medical staff.

The Risks of CTs

      In effective doses, one CT scan of the abdomen is equivalent to 500 chest rays. It’s estimated that the risk of a CT scan of the abdomen causing fatal cancer is up to 1 in 2,000 (http://europa.eu.int/comm/environment/radprot/118/rp-118-en.pdf). However, considering that cancer patients are often subjected to at least 2 CTs per year, the risk of transformation in a previously established cancer, as well as the risk of developing a new cancer (or both) could be even much more dramatic. Furthermore, it has been calculated that patients are routinely exposed to more radiation than nuclear workers and Japanese survivors of atomic bombs (http://www.ratical.org/radiation/CNR/XHP/NTP.html#Gofm99)! Consistent with these shocking findings and terrifying predictions, regulators at the Food and Drug Administration reported recently their concerns about the extensive use of CT scans. Dr. Thomas B. Shope, a special assistant at FDA's Center for Devices and Radiological Health, told the panel that the average whole-body CT scan delivers 0.2 to 2.0 rads of radiation. Studies of Japanese survivors of the US atomic attacks on Hiroshima and Nagasaki in World War II linked an increased risk of cancer to lifetime cumulative exposures of 5 to 20 rads. "At 2 rads per exam, we're not far from potentially dangerous radiation doses", Dr. Shope said.

      John W. Gofman, M.D., Ph.D., (a distinguished medical and nuclear scientist), has come to the shocking conclusion that the exposure to radiation from medical procedures is a highly important (probably principal) cause of cancer and ischemic heart disease in America. We also wish to note that radiation damage to the DNA is never completely repaired. The first-ever report on the effects of one single particle of radiation shot through one single cell (Zhou et al., 2000), creating one single track, claims that the lowest possible dose of radiation is not safe, and does more damage than previously thought. In this work, it is described that a single particle hit in the nucleus, which kills only 20% of the cells, is indeed mutagenic. Hence, no amount of radiation, no matter how small, is safe.

Unfortunately, we come to the conclusion that the acceptance of radiation as safe by medical professionals has to be challenged. The uncritical acceptance of the safety of “routine” radiation exposure is dangerous.

For more information about risks related with radiation exposure see
http://www.x-raysandhealth.org/ and http://www.physics.isu.edu/radinf/risk.htm.

Are  MRIs  appropriate  to  replace CTs as a general rule?

       As indicated in the Introduction, the European Commission of the European Union (following experts representing the European radiology and nuclear medicine in conjunction with the UK Royal College of Radiologists) recommends MRIs for the follow-up of lymphoma patients (http://europa.eu.int/comm/environment/radprot/118/rp-118-en.pdf, page 108).

MRIs have been already used to follow up patients with low-grade follicular non-Hodgkin lymphoma receiving standard treatments or enrolled in clinical trials.  For example, MRIs are used at SKCC to follow up NHL patients receiving vaccine therapy.

      There are many examples showing that MRIs are appropriate to replace CT scans when monitoring cancer patients. However, we will mention only a few references that discuss the general evaluation of thorax, abdomen and bone marrow.

• Jung et al. (2000) concludes that in the staging of abdominal lymphomas, MR imaging with a T2-weighted TSE sequence can be regarded as equal to spiral CT in the detection of lymph adenopathy and the demonstration of focal organ lesions.

• In addition to the absence of ionizing radiation, Jung et al. (2000) claims that the advantage of MR imaging for the abdominal region is that there is no necessity for oral or intravenous administration of contrast agent. 

• Looking at chest tumors, Wyttenbach et al. (1998) conclude that “magnetic resonance imaging is preferred for posterior mediastinal lesions, whereas CT should be used for pulmonary lesions.

• For the residual locations, both modalities are complementary.” Ozguroglu et al. (1999) concludes that MRI of bone marrow is a fairly sensitive, noninvasive modality and might be of potential value in detecting bone marrow infiltration in malignant lymphoid neoplasms which can be utilized as a useful adjunct to standard staging procedures.

In conclusion, it appears that MRIs can be used to safely and effectively monitor patients with specific cancers.  In fact,  MRIs are recommended by several experts for the follow-up of lymphoma patients.  In this regard, please contact Karl Schwartz at [email protected].

 Conclusions

 “First, do no harm” should always be the basis of care, particularly in the practice of medicine. Established misconceptions have led to the general acceptance that exposure to some radioactive sources, often used in medical practice, can be classified as safe (or relatively safe). However, recent data shows that just one CT scan is associated with potentially dangerous effects in the long-term. This concept is very much underestimated or unknown in current medical practice.  Unfortunately, we know that repeated CTs in the same individual are associated with terrifying risks in just a matter of years. Altogether, we conclude that the avoidance of radiation exposure, particularly repeated exposure during medical procedures should be a major interest for all doctors, scientists, and companies conducting clinical trials because the deleterious effects of radiation might compromise the potential of some promising therapies. Fortunately, the existence of some non-radioactive alternatives, which are able to produce similar (or at least acceptable) results, make their use practical—sometimes, in a complementary or alternate fashion. The appropriate exploration of these safer alternatives may deserve financial considerations, but the patient should have the right to avoid relevant risks and choose the safest way to monitor disease in concert with his or her medical staff. Finally, in order to shift from regular CTs to regular MRIs, in patients that have been regularly evaluated by CTs, we propose that in future evaluations, an MRI (or an MRI and a CT scan on the same date) should be performed for comparison purposes, followed (as much as possible) by regular MRIs only—or MRIs in combination with other procedures to clarify a doubtful image as needed.

Acknowledge

We thank the Lymphoma Vaccine Group for extensive help, inspiration and contributions. Particularly, we thank Karl Schwartz, Bob Ulfik and Sue Gallant for their extensive contributions and help.

References

• European Commission guidelines on radiation imaging (go to http://europa.eu.int, or go directly to http://europa.eu.int/comm/environment/radprot/118/rp-118-en.pdf).

• Life Extension journal (www.lef.org); issue of November 2001.

• Jung G, Heindel W, von Bergwelt-Baildon M, Bredenfeld H, Gossmann A, Zahringer M, Tesch H.
  Abdominal lymphoma staging: is MR imaging with T2-weighted turbo-spin-echo sequence a diagnostic alternative to contrast-enhanced spiral CT. J Comput Assist Tomogr. 2000 Sep-Oct;24(5):783-7.

• Ozguroglu M, Esen Ersavasti G, Demir G, Aki H, Demirelli F, Kanberoglu K, Mandel N, Buyukunal E, Serdengecti S, Berkarda B. Magnetic resonance imaging of bone marrow versus bone marrow biopsy in malignant lymphoma. Pathol Oncol Res 1999;5(2):123-8.

• Zhou H, et al 2000. Induction of bystander mutagenic effect of alpha particles in mammalian cells. Proc Natl Acad Sci 97:2099-104.

• Wyttenbach R, Vock P, Tschappeler H. Cross-sectional imaging with CT and/or MRI of pediatric chest tumors. Eur Radiol 1998;8(6):1040-6.