key: cord-0020502-wxeose87 authors: Welsh, James S.; Bevelacqua, Joe; Mortazavi, S.M.J.; Sacks, Bill title: In Regard to Shuryak et al. date: 2021-10-01 journal: Int J Radiat Oncol Biol Phys DOI: 10.1016/j.ijrobp.2021.05.117 sha: 2b528a65ee057f00f5e57eef8a140682b3392c3c doc_id: 20502 cord_uid: wxeose87 nan physician payment data, is possible to assess whether there is an association between physician payments and treatment selection; such data were not used for our study. 3 To continue this conversation about impacts of financial payments to physicians, here we provide a summary of Open Payments data on inflation-adjusted 4 general and research payments 5 made to radiation oncologists and teaching hospitals for proton therapy equipment from 2014 to 2019. Of known proton equipment manufacturers, ProTom International and Hitachi did not report to Open Payments. Varian Medical Systems paid $426,158 in general payments to physicians, as well as $527,482 in general payments and $960,874 in research payments to teaching hospitals. Ion Beam Applications paid $169,290 to physicians and $19,800 to teaching hospitals as general payments. Finally, Mevion Medical Systems paid $76,797 in general payments to physicians and $6360 in research payments to teaching hospitals. A substantial limitation of these data is that names of the associated products or research studies are often nonspecific. Therefore, these numbers likely underestimate the extent of relationships. Specifically, Varian payments exclude general payments ($1,436,332) and research payments (eg, Master Research Agreements; Total: $14,757,058) that did not identify the product or research project. Halperin's inquiry as to whether Open Payments can confirm data demonstrating lower likelihood of physician-industry interactions among Veterans Health Administration (VHA) physicians is important when considering effectiveness of system policies. The VHA obliges physicians to follow Federal and Executive Branch laws, which include prohibiting use of one's position for private gain. Because Open Payments is regulated by the Centers for Medicare & Medicaid Services 6 and the VHA does not accept Medicare reimbursement, Open Payments does not statutorily include VHA physicians or hospitals. To address this question, assessment of journal or professional society data on reported financial conflicts of interest and author affiliation may provide additional, potentially confirmatory insight into associations of reported financial conflicts of interest and VHA policies. I look forward to continued dialogue on this important topic. In Regard to Shuryak et al. 1 The authors aim to evaluate the benefit−risk balance of low-dose radiation therapy (LDRT) for COVID-19. To do so, they estimated the lifetime risk of radiation-induced lung cancer and heart disease for patients with different background risks (e.g., sex, age, and the existence of other risk factors such as smoking and heart disease) by using what the authors call "state-of-the-art radiation risk models" for lung cancer and heart disease. Shuryak et al. suggest that in such evaluations, the background risk factors, and in particular cigarette smoking, should be precisely considered, and they conclude that the predicted risks are lowest in older nonsmoking patients and those with lower cardiac risk factors. Despite some strengths, their report has some major shortcomings, as follows: 12 and 131 (2015) 13 have addressed the increased resistance of cells or tissues to radiation after a priming dose. However, these ICRP publications are based on the linear no-threshold (LNT) hypothesis, which fails to account for the immune system and the body's effective repair mechanisms at low doses. The LNT approach also significantly overestimates the radiation risks of these doses and discounts the possibility of hormesis. Moreover, the National Aeronautics and Space Administration, in a report published in 2016, supported the protective role of adaptive response against cancer. 14 4. Shuryak et al are fully aware of the life-threatening outcomes of COVID-19, such as the "cytokine storm" and thrombosis and state that Current evidence suggests that the most serious symptoms and death from COVID-19 result from an ineffective immune response in some patients, where a proinflammatory feedback loop is created. 15 This process leads to accumulation of immune cells in the lungs and the overproduction of proinflammatory cytokines ("cytokine storm") which damages the lungs and multiple other organs. 15, 16 However, they ignore the cardinal advantages of LDRT regarding inhibition of cytokine storm and thrombosis and reducing the risk of adaptive mutations as a response to selective pressure-exerting treatments such as antiviral drugs or steroids (Fig. 1) . Given these considerations, in contrast with what is claimed by Shuryak et al, the effectiveness of LDRT for COVID-19 is not limited to older patients with low baseline risk factors, and more realistic evidence-based risk estimates are needed. Fig. 1 . Low-dose radiation therapy for COVID-19 is based on some key properties of low-dose radiation, such as anti-inflammatory and antithrombosis effects, optimization of the immune system and inhibition of cytokine storm, and reducing the risk of viral mutations that can lead to the emergence of new variants with higher transmissibility and virulence. To the Editor: We appreciate the comments 1 regarding our article "Lung Cancer and Heart Disease Risks Associated with Low-Dose Pulmonary Radiotherapy to COVID-19 Patients With Different Background Risks." 2 It is indeed true that the effects of very low radiation doses are uncertain, and epidemiologic evidence at these very low doses is limited. However, the pulmonary and cardiac doses relevant to pulmonary radiation therapy for patients with COVID-19 are not in that "very low" dose range. Specifically, the pulmonary and cardiac doses are very similar to the prescription dose, typically in the range from 0.5 to 1.5 Gy 2 -and we summarize here evidence that these values are in the organ dose range where we have significant epidemiologic data. Considering first radiation-induced cancer, at very low doses it is true that potential risks remain uncertain. The dose above which there is clear epidemiologic evidence of increased risk is often termed the "minimal significant dose" (MSD). 3 Among atomic bomb survivors, the estimated MSD, both for cancer incidence and for cancer mortality, is 0.15 Gy. 3 Of course, there are uncertainties associated with risk estimates derived from atomic bomb survivors, but the fact that the risk estimates for both radiation-induced cancer incidence and radiation-induced cancer mortality-which derive from entirely different databases -are very similar suggests that these MSD estimates are realistic. Recent data from a large study (N = 259,350) of nuclear workers also yields a similar estimated MSD of »0.2 Gy for radiation-induced cancer. 4 Turning to radiation-induced circulatory disease, as recently summarized, 5 there has long been statistically significant evidence for increased risks in the 0.5 to 1.5 Gy (and Disclosures: none. Open data on industry payments to healthcare providers reveal potential hidden costs to the public Trends in financial relationships between industry and radiation oncologists versus other physicians in the United States from Consumer Price Index for All Urban Consumers (CPI-U) U.S. city average series for all items, not seasonally adjusted Open payments data. Available at: openpaymentsdata.cms.gov Children's Health Insurance Programs: Transparency reports and reporting of physician ownership or investment interests Lung cancer and heart disease risks associated with low-dose pulmonary radiotherapy to COVID-19 patients with different background risks The risk of induced cancer and ischemic heart disease following low dose lung irradiation for COVID-19: Estimation based on a virtual case Regarding Mortazavi S. The risk of induced cancer and ischemic heart disease following low dose lung irradiation for COVID-19: Estimation based on a virtual case Reply to: Regarding: "The risk of induced cancer and ischemic heart disease following low dose lung irradiation for COVID-19: Estimation based on a virtual case COVID-19 tragic pandemic: Concerns over unintentional "directed accelerated evolution" of novel Coronavirus (SARS-CoV-2) and introducing a modified treatment method for ARDS Immunomodulatory low-dose whole-lung radiation for patients with coronavirus disease 2019-related pneumonia Low-dose whole-lung irradiation for COVID-19 pneumonia: Short course results Low-dose whole-lung irradiation for COVID-19 pneumonia: Final results of a pilot study Low-dose radiation therapy in the management of coronavirus disease 2019 (COVID-19) pneumonia (LOWRAD-Cov19): Preliminary report Low dose radiation therapy for COVID-19 pneumonia: A pilot study The 2007 Recommendations of the International Commission on Radiological Protection. ICRP Publication 103. ICRP publication 103 ICRP publication 118: ICRP statement on tissue reactions and early and late effects of radiation in normal tissues and organs-threshold doses for tissue reactions in a radiation protection context Stem Cell Biology with Respect to Carcinogenesis Aspects of Radiological Protection Evidence report: Risk of radiation carcinogenesis Low dose radiation therapy for COVID-19 pneumonia: A double-edged sword Low dose radiation therapy for COVID-19 pneumonia: A double-edged sword