A Critical Assessment of the Linear No-Threshold Hypothesis - What is the Evidence by John A. Shanahan

OPINION PAPER/COMMENTARY

A Critical Assessment of the Linear No-Threshold Hypothesis What Is the Evidence? Patrick M. Colletti, MD, FACNM, FSNMMI

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Abstract: The Linear No-Threshold (LNT) hypothesis regarding low-level radiation is based on expert opinion. As more experts critically evaluate the absence of convincing evidence supporting the LNT hypothesis, the more likely we will recognize that LNT may create more risk than it mitigates. Key Words: Linear No-Threshold, low dose, radiation, radiation protection (Clin Nucl Med 2019;44: 519–520)

n several occasions, I have received manuscripts containing statements in the form of: “The greatest risk for (medical imaging with radiation) is the induction of cancer.” The apparent linkage of medical imaging to cancer would seem to be an accepted medical fact. Are there published randomized controlled trials, systematic reviews, and meta-analyses? No. Are there case reports, case series, or cohort studies? No. So how do we know that medical imaging causes cancer? Well, there is the 2007 Recommendations of the International Commission on Radiological Protection: ICRP Publication 103.1 The International Commission on Radiological Protection experts proclaim the Linear No-Threshold (LNT) hypothesis to be “the best practical approach to managing risk from radiation exposure.” So, there is our evidence, reluctant expert opinion. Now what if a number of similar experts challenge the prevailing expert opinion?2–5 In this issue, Greenspan and colleagues6 further clarify a thoughtful challenge to the LNT hypothesis, concluding that “the evidence does not support the use of LNT either for risk assessment or radiation protection in the low-dose and dose-rate region.” They present the logical argument6: “The average annual natural background radiation dose on earth ranges from 1 to 260 mSv. Irrespective of the level of background exposure to a given population, no associated adverse health effects proportional to background dose have been documented anywhere in the world.” To further the argument against the LNT hypothesis, “epidemiologic studies of populations exposed to low levels of radiation have documented benefit (reduced cancer incidence and increased longevity), and not just absence of harm, from radiation exposures (6).” Thus, it appears that for every year we inhabit this earth exposed to 3 mSv of radiation, we in fact have lived another year! We should be very skeptical of the LNT hypothesis. Potential evidence is dubious at best.7–9 Expert opinion is under challenge.

CAN ADHERENCE TO THE LNT HYPOTHESIS LEAD TO UNINTENDED HARM? While the tsunami-related 2011 Fukushima Daiichi nuclear accident may have dispersed up to an additional 20 mSv of radiation to some local residents, a more reasonable estimate of 5 mSv/y may be correct.10 The tsunami resulted in nearly 15,000 deaths. Although no radiation-associated deaths were reported, 200,000 Fukushima residents were evacuated. An estimated 35,000 have not and perhaps may not ever return.10 “The number of disaster-related deaths resulting from the misguided LNT-based evacuation policy for nearby residents following the 2011 Fukushima Daiichi nuclear accident reached almost 2000, as of 2016. This number exceeds the number of Fukushima residents who were killed directly by the earthquake and tsunami.”6,11 “The evacuations did not go well. Evacuees, many elderly and frail, were moved repeatedly without any plans in place,” says Jan Beyea, a physicist with Consulting in the Public Interest who worked on a 2014 US National Academies of Sciences, Engineering and Medicine report about the accident. “Disrupted medical care and the trauma of moving were fatal to nearly 2000 people, according to the World Nuclear Association. Many of those who survived reportedly suffer from alcoholism and clinical depression.”10

Might there be a potential parallel situation in medicine, where exposures of 5 mSv may be avoided at the risk of misdiagnosis and mistreatment of discoverable conditions? The theoretical risk of cancer associated with CT pulmonary angiography (CTPA) for suspected pulmonary embolism is many orders of magnitude less than the risk of untreated PE or the bleeding associated with treatment for PE. It is especially illogical for experts to argue that the radiation associated with V/Q imaging is somehow superior to the radiation from CTPA. Will currently achievable submillisievert CTPA or ultralowdose CZT V/Q SPECT change this argument? In the end, both are sufficient examinations with other advantages and disadvantages. We are the patients' stewards of low-level medical radiation. We must manage this important role with respect and without fear. REFERENCES

Received for publication March 28, 2019; revision accepted March 29, 2019. From the Keck School of Medicine of USC, Los Angeles, CA. Conflicts of interest and sources of funding: none declared. Correspondence to: Patrick M. Colletti, MD, FACNM, FSNMMI, Keck School of Medicine of USC, 1500 San Pablo St, Los Angeles, CA 90033. E-mail: colletti@usc.edu. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0363-9762/19/4407–0519 DOI: 10.1097/RLU.0000000000002614

1. International Commission on Radiological Protection. The 2007 Recommendations of the International Commission on Radiological Protection: ICRP Publication 103. Maryland Heights, MO: Elsevier; 2007. 2. Marcus CS. Time to reject the linear-no threshold hypothesis and accept thresholds and hormesis: a petition to the U.S. Nuclear Regulatory Commission. Clin Nucl Med. 2015;40:617–619. 3. Doss M. Are we approaching the end of the linear no-threshold era? J Nucl Med. 2018;59:1786–1793. 4. Siegel JA, Welsh JS. Does imaging technology cause cancer? Debunking the linear no-threshold model of radiation carcinogenesis. Technol Cancer Res Treat. 2016;15:249–256.

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5. Siegel JA, Greenspan BS, Maurer AH, et al. The BEIR VII estimates of low-dose radiation health risks are based on faulty assumptions and data analyses: a call for reassessment. J Nucl Med. 2018;59: 1017–1019. 6. Greenspan BS, Siegel JA, Brooks AL, et al. A critical assessment of the linear no-threshold hypothesis: its validity and applicability for use in risk assessment and radiation protection. Clin Nucl Med. 2019. In press. 7. Pearce MS, Salotti J, Little MP, et al. Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study. Lancet. 2012;380:499–505.

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8. Mathews JD, Forsythe AV, Brady Z, et al. Cancer risk in 680,000 people exposed to computed tomography scans in childhood or adolescence: data linkage study of 11 million Australians. BMJ. 2013;346:f2360. 9. Journy N, Rehel JL, Ducou Le Pointe H, et al. Are the studies on cancer risk from CT scans biased by indication? Elements of answer from a large-scale cohort study in France. Br J Cancer. 2015;112:185–193. 10. Fukushima residents return despite radiation. Available at: https://www. scientificamerican.com/article/fukushima-residents-return-despiteradiation/. Accessed March 27, 2019. 11. Hayakawa M. Increase in disaster-related deaths: risks and social impacts of evacuation. Ann ICRP. 2016;45(Suppl 2):123–128.