Cardiac catheterization real-time dynamic radiation dose measurement to estimate lifetime attributable risk of cancer.

Cardiac catheterization procedure is the gold standard to diagnose and treat cardiovascular disease. However, radiation safety and cancer risk remain major concerns. This study aimed to real-time dynamic radiation dose measurement to estimate lifetime attributable risk (LAR) of cancer incidence and mortality in operators. Coronary angiography (CA) with percutaneous coronary intervention (PCI), CA, and others (radiofrequency ablation, pacemaker and defibrillator implantation) procedures with different beam directions, were undertaken on x-ray angiography system. A real-time electronic personal dosimeter (EPD) system was used to measure the radiation dose of staff during all procedures. We followed the Biological Effects of Ionizing Radiation (BEIR) VII report to estimate the LAR of all cancer incidence and mortality. Primary operators received radiation dose in CA with PCI, CA, and others procedures were 59.33 ± 95.03 μSv, 39.81 ± 103.85 μSv, and 21.92 ± 37.04 μSv, respectively. As to the assistant operators were 30.03 ± 55.67 μSv, 14.67 ± 14.88 μSv, and 4 μSv, respectively. LAR of all cancer incidences for staffs aged from 18 to 65 are varied from 0.40% for males to 1.50% for females. LAR of all cancer mortality for staffs aged from 18 to 65 are varied from 0.22% for males to 0.83% for females. Our study provided an easy, real-time and dynamic radiation dose measurement to estimate LAR of cancer for staff during the cardiac catheterization procedures. The LAR for all cancer incidence is about twice that for cancer mortality. Although the radiation doses of staff are lower during each procedure, the increased years of service leads to greater radiation risk to the staff.

Introduction

Cardiac catheterization is an ionizing radiation procedure used to diagnose heart conditions or treat cardiovascular diseases. The procedures are well recognized to facilitate early and accurate diagnosis of the disease, improve treatment planning to save patient’s life [1]. Nevertheless, the procedures usually perform with longer fluoroscopy time and may cause radiation exposure to staff [2-5]. Due to the correlation between exposure to ionizing radiation and cancer risk is related [6-11], staff are becoming increasingly aware of the potential damaging effects of ionizing radiation during the procedures. Thus, estimation of radiation dose and cancer risk in staff during the procedures is a major issue regarding the public health significance.

Although a number of studies had examined the radiation exposure during the interventional procedures in recent years, most of studies were performed on a phantom to simulate the radiation exposure to staff [12-17]. These phantom studies did not evaluate the dynamic changes in staff positions, beam orientation and movement, exposure parameters, and so on; moreover, in clinical procedures are often complex. Accordingly, the purpose of this study was real-time dynamics measurement of medical radiation dose to estimate the lifetime attributable risk (LAR) of cancer incidence and mortality in staff.

Materials and methods

Study design

The study was approved by the Mackay Memorial Hospital Institutional Review Board on June 22, 2017 and valid till June 21, 2018 (approval number: 17MMHIS075e). The constitution and operation of this review board are according to the guidelines of ICH-GCP, the records/information were anonymized and de-identified prior to analysis. All procedures were Data were collected for 3 different types of procedures: Coronary angiography (CA) with percutaneous coronary intervention (PCI), CA, and others (radiofrequency ablation, pacemaker and defibrillator implantation). Procedural details including types of procedure, fluoroscopy time, fluoroscopy tube voltage, fluoroscopy tube current, cine acquisition tube voltage, cine acquisition tube current, cine acquisition time, cine acquisition runs, dose area product (DAP), beam directions, staff (primary and assistant operator) age and radiation dose were recorded.

Radiation dose measurement

Experimental measurements were used three x-ray angiography systems(one was Philips Allura FD20, the others were Philips Allura FD 10) with similar cardiac catheterization protocols. All protocols followed standard technical characteristics of image acquisition and quality control. Collimation and magnification were used during the procedures according to the clinical requirements. The operational protocols evaluated were fluoroscopy (15 pulses/s and 0.9 mm Cu as additional filtration) and cine acquisition (15 pulses/s without Cu filtration) modes. All staff adhered to standard radiation protection procedures. Each staff wore a lead apron, a thyroid collar, and leaded glasses. Because the thyroid is known to be radiosensitive and makes a significant contribution to the radiation dose [18-21], a real-time electronic personal dosimeter (EPD) system (i2, Raysafe) was placed over the left side of staff’s thyroid collar to measure the radiation dose at various locations. EPD system has store instantaneous dose rate and cumulative dose values at the beginning to the end of each procedure. In addition, the system is design to measure the personal dose equivalent at depth of 10 mm (Hp(10)) for x-ray, and is considered to be the dose to the whole body [22].

Cancer risk estimation

Currently, the linear no-threshold model is widely used to estimate the LAR of cancer from exposure to low levels of ionizing radiation. The LAR of cancer incidence and mortality, which are defined as additional cancer risk above and beyond baseline cancer risk. In this study, the LAR of all cancer incidence and mortality were calculated based on the Biological Effects of Ionizing Radiation (BEIR) VII report [9]. Average radiation doses for each of the 3 procedure types were used to estimate the LAR of all cancer incidence and mortality. The LAR of all cancer incidence and mortality were estimated as follows: Where (e) is the age at exposure, (s) is the sex specific excess relative risk (ERR), (D) is the dose of radiation received, (a) is the specific cancer site at attained age, the summation is from a = e + L to l00, where a denotes attained age (years) and L is a risk-free latent period (L = 5 for solid cancers; L = 2 for leukemia), ERR (e, s, D, a) is the risk model in the equation, m (s, a) is the baseline risk, S(s, a) is the probability of surviving until age (a), S(s, a)/S(s, e) is the probability of surviving to age (a) conditional on survival to age (e). This study estimated the cancer risk under the assumption that the operators were continuously exposed to radiation from the age of 18 to 65.

Statistical analysis

Beam directions distribution of cardiac catheterization procedures was presented as percentage. Procedural details were presented as means and standard deviations by descriptive analyses. Multiple linear regression analysis was performed to DAP versus staff radiation dose. The p value < 0.05 was considered significant. LAR of cancer incidence and mortality for staff were expressed as line graphs.

Results

There were 71 procedures were included in our study, 43 CA with PCI, 16 CA and 12 others. The beam directions distribution in CA with PCI, CA, and others procedures are illustrated in Fig 1. In CA with PCI procedure, the beam directions distribution of fluoroscopy and acquisition were most complexity. The procedural details in CA with PCI, CA, and others are listed in Table 1. Primary operators doses were measured under 43 CA with PCI, 16 CA, and 12 others procedures, respectively. As to the assistant operators doses were 38 CA with PCI, 6 CA, and 1 others procedures, respectively. Primary operators radiation dose in CA with PCI, CA, and others procedures were 59.33 ± 95.03 μSv, 39.81 ± 103.85 μSv, and 21.92 ± 37.04 μSv, respectively. As to the assistant operators were 30.03 ± 55.67 μSv, 14.67 ± 14.88 μSv, and 4 μSv, respectively. The fluoroscopy tube voltage of CA with PCI procedure (98.54±16.55 kV) was significantly higher than other two procedures, while the acquisition tube voltage was the same situation. The fluoroscopy time was longest in CA with PCI procedure (14.67±12.83 mins), followed by others procedure (14.21±12.73 mins) and CA procedure (6.10±3.49 mins). The acquisition time was also longest in CA with PCI procedure (53.16 ± 10.33 s), followed by CA procedure and others procedure. However, the fluoroscopy and acquisition tube current in others procedure were significantly lower than in the other two procedures. Correlation between DAP and staff radiation dose from all procedures are illustrated in Fig 2. Scatter graph of DAP versus primary operator (p = 0.004, R2 = 0.11) and assistant operator radiation dose (p < 0.001, R2 = 0.46) demonstrated weak positive correlations.

Fig 1

Beam directions distribution of cardiac catheterization procedures in (a) CA with PCI, (b) CA, and (c) Others. (LAO: left anterior oblique, RAO: right anterior oblique, AP: anterior posterior, CRAN: cranial, CAU: caudal, F: fluoroscopy, A: acquisition).

Table 1

The procedural details in CA with PCI, CA, and others.

	CA with PCI	CA	Others
Procedural details
Number of procedures (n = 71)	43	16	12
Radial approach (%)	100	100	0
Fluoroscopy time (mins)	14.67 ± 12.83	6.10 ± 3.49	14.21 ± 12.73
Fluoroscopy tube voltage (kV)	98.54 ± 16.55	87.23 ± 15.06	93.61 ± 15.31
Fluoroscopy tube current (mA)	12.31 ± 4.93	15.62 ± 4.21	6.12 ± 2.93
Acquisition tube voltage (kV)	85.60 ± 14.94	80.84 ± 13.91	83.40 ± 20.61
Acquisition tube current (mA)	784.75 ± 107.18	733.46 ± 157.42	505.70 ± 300.73
Acquisition time (s)	53.16 ± 10.33	41.31 ± 11.56	4.42 ± 5.23
Dose area product (Gy-cm2)	238.67 ± 201.51	119.30 ± 54.40	49.82 ± 126.27
Primary operators (n = 6)
Number of primary operators	5	4	3
Age (years)	49.25 ± 6.99	43.75 ± 3.30	42.33 ± 2.08
Male (%)	100	100	100
Case volumes	43	16	12
EPD radiation dose (μSv)	59.33 ± 95.03	39.81 ± 103.85	21.92 ± 37.04
Assistant operators (n = 5)
Number of assistant operators	5	3	1
Age (years)	32.6 ± 3.58	33.00 ± 4.58	32
Male (%)	44.74	83.33	100
Case volumes	38	6	1
EPD radiation dose (μSv)	30.03 ± 55.67	14.67 ± 14.88	4

Fig 2

Correlation of DAP versus staff radiation dose.

(a) DAP versus primary operator. (b) DAP versus assistant operator.

We used a 12 month average for the preceding year to estimate the 1 year occupational radiation exposure to the operators is presented in Fig 3. The annual average radiation dose per primary operator from all procedures was 3.49 mSv. As to the assistant operator was 1.30 mSv. Estimated LAR of all cancer incidence and mortality from cardiac catheterization procedures for operators are presented in Table 2. LAR of all cancer incidence and mortality for male primary operators aged from 18 to 65 were 1.07%, and 0.59%, respectively. As to the female primary operators aged from 18 to 65 were 1.50%, and 0.83%, respectively. In contrast, the LAR of all cancer incidence and mortality were significantly lower in assistant operators. The LAR of all cancer incidence and mortality for females were significantly higher than for males.

Fig 3

The 1 year occupational radiation exposure to the operators.

Table 2

Estimated LAR of all cancer incidence and mortality from cardiac catheterization procedures for operators.

Operators	Primary operators		Assistant operators
LAR	All cancer incidence aged from 18 to 65	All cancer mortality aged from 18 to 65	All cancer incidence aged from 18 to 65	All cancer mortality aged from 18 to 65
Male	1.07%	0.59%	0.40%	0.22%
Female	1.50%	0.83%	0.56%	0.31%

Discussion

Many previous important phantom studies for similar cardiac catheterization procedures are listed in Table 3. However, our study was real-time dynamics measurement of medical radiation to estimate the link between medical radiation exposure and LAR of cancer in staff from cardiac catheterization procedures. Indeed, we analyzed the beam directions distribution complexity during the different procedures in this study. We have demonstrated the more complex procedures are associated with increasing the radiation doses. Estimation of the radiation doses in staff have a wide variation across the literatures as a result of the levels of complexity of the procedures [1, 3, 23–25]. This phenomenon is comparable with our staff radiation doses. Nevertheless, the assistant operators radiation doses were significantly lower than primary operators is observed in all procedures. This result is caused by many factors during the procedures such as equipment set-up, operator technique, use of radiation reducing techniques, workload and procedural complexity [26-29].

Table 3

Previous phantom studies for similar cardiac catheterization procedures.

Author	Location of dosimeter	Measurement tool	Dose unit	No of projections
Panetta et al.[32]	Wrist	EPD	Dose rate	4
Patet et al.[33]	Chest	EPD	Equivalent dose	_
Etzel et al.[34]	Eye/ Neck/ Chest/ Gonads/ Lower leg	Ion chamber	Dose rate	3
Jia et al.[35]	Eye/ Neck/ Chest/ Epigastrium/ Hypogastrium/ Thigh/ Lower leg/ Ankle	EPD	Dose rate	8
Haga et al.[36]	Eye/ Neck	EPD/ Eye dosimeter	Equivalent dose	-
Alnewaini et al.[37]	Eye/ Neck	TLD	Radiation dose	14
Oliveira da Silva et al.[38]	Eye/ Chest	EPD	Equivalent dose	6
Perisinakis et al.[39]	Eye/ Waist	Ion chamber	Dose rate	17
Ordiales et al.[15]	Neck	EPD	Equivalent dose	7
Sciahbasi et al.[40]	Head/ Chest/ Wrist/ Hip	EPD	Equivalent dose	8
Vano et al.[41]	Chest/ Eye	EPD	Dose rate	13
Principi et al.[42]	Neck/ Chest/ Shoulder	EPD/ TLD	Equivalent dose	2
Liu et al.[43]	Chest	TLD	Effective dose	6
Farah et al.[44]	Eye/Neck/Chest/Waist	EPD/ TLD	Equivalent dose	10
Ertel et al.[45]	Chest	Ion chamber	Radiation dose	7
Chida et al.[46]	Neck/ Chest/ Knee	EPD	Dose rate	-
Boetticher et al.[47]	Eye/ Neck/ Chest/ Gonads/ Knee/ Lower leg/ Foot	TLD	Effective dose	3
Mesbahi et al.[48]	From head to foot (for every 10 cm)	Ion chamber	Dose rate	-
Schultz et al.[49]	Trunk	EPD	Effective dose	2
Koichi et al.[50]	Neck/ Chest	OSLD*	Dose rate	4
Kuon et al.[51]	Chest	Ion chamber	Dose rate	163
Balter et al.[52]	Neck/ Chest/ Knee	Ion chamber	Dose rate	6

*OSLD: optically stimulated luminescence dosimeter.

There have been many studies[1, 30, 31] to estimate effective dose or effective dose equivalent using personal monitors. The information from these studies could be used in evaluating likely dose levels. The modified Niklason algorithm provided a measure of the exposure of sensitive organs in the trunk: where E is effective dose, Hos is Hp (0.07) measured over shield on thyroid level, and Hu is Hp (10) measured under apron. The Hp (10) over shield on thyroid level is converted to Hp (0.07) by adding 3% to the measurement dose. For a single dosimeter worn at the thyroid collar, again assuming HU ≈ 0.01 Hos, the conversion algorithm as follows:

Martin et al.[31] is recommended for estimating the eye dose from a measurement with an unshielded neck dosimeter, the equation:

Cardiac catheterization procedures provide great diagnostic and treatment benefit to patients. Unfortunately, the radiation doses of these procedures are imposed on staff. The radiation dose to staff during the procedure is due to Compton scatter in the patient which is the dominant interaction in tissue at diagnostic x-ray energies [28, 53]. Modern angiography system provides DAP values to monitor the radiation dose for patient during the procedures. From some literatures reported a positive correlation between DAP and staff radiation dose during the procedures [22, 29, 54]. This means that DAP values can be represented the relative radiation dose of the staff. Nevertheless, our results demonstrated a weak correlation. This could be due to several factors: first, the quantity of radiation varies significantly depending on the position of staff relative to the x-ray source and patient; second, the staff used a ceiling-mounted radiation shielding screen for radiation protection; third, the staff might leave the cardiac catheterization lab during the acquisition. This implies that the radiation dose to staff during the procedures might be reduced by improving radiation protection practices.

Although our study demonstrates that the radiation doses of staff are lower during each procedure, the increased years of service leads to greater radiation risk to the operators. In fact, the radiation risks are mainly stochastic effects at low radiation exposure levels. These effects with the probability of occurrence increasing with the absorbed dose [28, 55]. Therefore, lead aprons and thyroidal collars and leaded glasses allow staff to achieve As Low As Reasonably Achievable (ALARA) during the procedures. As was shown in an earlier report [28], lead aprons of 0.25 or 0.5 mm absorb 85–92% 100 kV of energy and 93–97% of 100 kV of energy, respectively. All operators wear lead aprons, thyroid collars, and leaded glasses to protect themselves, during long-term performance of the procedures, it is still impossible to completely avoid radiation exposure and its effects. If operators fail to use protective gear or adjust the exposure time properly, within a few years operators may have increased the LAR of cancer. Optimizing the fluoroscopy or cine acquisition dose rate to reduce staff radiation dose and long-term risk is much more efficient. Ishibashi et al. [56] reported the fluoroscopy dose rates in Japan were 7.5 pulses/s at 44% of CA, 7.5 pulses/s at 43% of PCI, and 7.5 pulses/s at 54% of radiofrequency catheter ablationpulses, respectively. As to the cine acquisition dose rates were 15 pulses/s at 93% of CA, 15 pulses/s at 90% of PCI, and 7.5 pulses/s at 55% of radiofrequency catheter ablationpulses, respectively. van Dijk et al. [57] reported the fluoroscopy dose rate in pacemaker and defibrillator implantation was 7.5 pulses/s. As to the cine acquisition dose rates were 3.75–15 pulses/s. In our study, the default pulse rates (15 pulses/s) both fluoroscopy and cine acquisition dose rates were used in other procedures. Consequently, the fluoroscopy and cine acquisition dose rates would be optimized to ensure that the radiation dose would be reduced to an acceptable level.

There are a few limitations in our study. First of all, due to the characteristics of equipment and method of radiation dose measurement which lead to each beam direction and field size variation were not straightforward determined during the procedure. Our study did not analyze the correlation between each beam direction, field size variation and radiation dose. Second, the presented exposure levels reflected the procedure types were most often performed at two hospitals. This certainly did not cover the all types of procedures and which was affected the sample size. Third, the hand doses may be much greater than doses at the neck, eye, or trunk during the procedures. There is no conversion algorithm to estimate the hand dose from the doses at neck. The dosimeter should be worn towards on the hand adjacent to the x-ray tube if a meaningful result is to be obtained. Fourth, BEIR VII report was based on a linear no-threshold (LNT) model to assess the correlation between radiation exposure and biological risk. The principal source was the effect of whole body acute exposure to high radiation dose. Whether the principal source can be extrapolated to the partial body exposure at a much lower radiation dose. In addition, our study did not estimate the yearly of radiation exposure exactly and job tenure of operators. However, according to the BEIR VII report, when exposed continuously to 10 mSv on a yearly basis from ages 18 to 65 years old, cancer incidence was 3,059 for male and 4,295 for female. That data was directly applied to the calculation of cancer risk to medical staff in many studies [10, 58–60]. Although the LNT model for low-dose (<100mSv) is characterized by a great deal of uncertainty, there is no direct evidence to estimate the cancer risks for staff during the cardiac catheterization procedures. Currently BEIR VII report offers the most accurate estimates of cancer incidence and mortality from medical radiation dose.

Conclusion

The radiation dose to staff mainly depend on the large number of acquisition and longer fluoroscopy time during the procedures. The present study provided an easy, real-time and dynamic radiation dose measurement to estimate LAR of cancer for staff in the cardiac catheterization procedures. Although the radiation doses of staff are lower during each procedure, the increased years of service leads to greater radiation risk to the staff. In addition, the LAR for all cancer incidence is about twice that for cancer mortality. Given the limits of the correlation between each beam direction, field size variation and staff radiation dose of this study. In our future studies will be of value to validate these findings.

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6 Feb 2020

PONE-D-19-29699

Cardiac Catheterization Real-time Dynamic Radiation Dose Measurement to Estimate Lifetime Attributable Risk of Cancer

PLOS ONE

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Reviewer #1: 1. please provide a table (in discussion) listing all important phantom studies for similar cardiac procedures.

2. How many personnale were included for dosimetric measurements ? Please list the number of each staff-e.g. How many primary operators, how many assistant operators etc. How many women and what age ?

3. The EPD was worn around the collar, what about the chest, hands, ovaries or pelvis in women. Even if there were no EPD measurements in these body sites, an estimate should be given and discussed.

4. Line 231-232 is incomplete, please fix grammar throughout the document.

5. Its not clear if the EPD measurements listed are an average exposure of each individual or average of the entire group. There is a need for a major clarification- are the measured doses from one or an average of all personnel

6. How many such procedures are done in a year and how much cumulative exposure does a person get exposed to in a year? that estimate has to be provided.

7. How does the exposure differ between various machine models?

Reviewer #2: 1. Line 50 -- Cardiac catheterization should not be described as a "radiologic" procedure. Rather, it is ionizing radiation-based.

2. "other procedures" often use frame rates of 4/s or 7.5/s, considerably lower than the 15 fps listed here. Please acknowledge this in the Discussion.

3. The manuscript leaves very unclear what is being calculated. Is it the radiation dose per case, per year, or per career. This is crucial to the manuscript's conclusions. For example, calculating the LAR of a 60 year old interventional cardiologist based on one year's exposure isn't meaningful, since that individual has likely had exposures beginning 30 years previously. Complicating factors even further, exposure times were likely longer when the individual was younger and less experienced, and the yearly case load may have been lower as the individual was building a career and reputation. Exactly what is being calculated is critical here.

4. The first table should include the ages and case volumes of the operators under study.

5. How was the volume of 450 cases/year obtained?

6. How was continual and correct placement of the dosimeter assured?

7. Are approaches to PCI predominantly femoral or radial?

8. The beam angles in Fig 1 add up to more than 100%.

9. One assumes that he dose-area products recorded are those for the patient. Is this correct?

10. The fluoroscopy and acquisition times for PCI seem very short. Please double check.

11. How many procedures were used for the measurements?

12. Was there a specific protocol for edge-to edge collimation?

13. Lines 175-176 seem to be erroneous. This study didn't report relations between beam angles and radiation dose. Was this from a previous publication.

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Reviewer #1: No

Reviewer #2: No

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20 Mar 2020

Dear Editor, Dear reviewers

We thank the reviewers for the helpful comments. They are all very important points and definitely improve the quality of this manuscript. The following is a point-by-point response to each comment:

Reviewer #1:

1. please provide a table (in discussion) listing all important phantom studies for similar cardiac procedures.

Author response:

Thank you for the instructions. We have rephrased the statement in line 171-174 as “Many previous important phantom studies for similar cardiac catheterization procedures are listed in Table 3. However, our study was real-time dynamics measurement of medical radiation to estimate the link between medical radiation exposure and LAR of cancer in staff from cardiac catheterization procedures.”

We have added a table in the main manuscript (in discussion) as follows:

Table 3 Previous phantom studies for similar cardiac catheterization procedures

Newly added references:

30. Padovani R, Rodella C. Staff dosimetry in interventional cardiology. Radiation protection dosimetry. 2001;94(1-2):99-103.

31. Martin C. Personal dosimetry for interventional operators: when and how should monitoring be done? The British journal of radiology. 2011;84(1003):639-48.

32. Panetta CJ, Galbraith EM, Yanavitski M, Koller PK, Shah B, Iqbal S, et al. Reduced radiation exposure in the cardiac catheterization laboratory with a novel vertical radiation shield. Catheterization and Cardiovascular Interventions. 2020;95(1):7-12.

33. Patet C, Ryckx N, Arroyo D, Cook S, Goy JJ. Efficacy of the SEPARPROCATH® radiation drape to reduce radiation exposure during cardiac catheterization: A pilot comparative study. Catheterization and Cardiovascular Interventions. 2019;94(3):387-91.

34. Etzel R, König AM, Keil B, Fiebich M, Mahnken AH. Effectiveness of a new radiation protection system in the interventional radiology setting. European journal of radiology. 2018;106:56-61.

35. Jia Q, Chen Z, Jiang X, Zhao Z, Huang M, Li J, et al. Operator Radiation and the Efficacy of Ceiling-Suspended Lead Screen Shielding during Coronary Angiography: An Anthropomorphic Phantom Study Using Real-Time Dosimeters. Scientific reports. 2017;7:42077.

36. Haga Y, Chida K, Kaga Y, Sota M, Meguro T, Zuguchi M. Occupational eye dose in interventional cardiology procedures. Scientific reports. 2017;7(1):1-7.

37. Alnewaini Z, Langer E, Schaber P, David M, Kretz D, Steil V, et al. Real‐time, ray casting‐based scatter dose estimation for c‐arm x‐ray system. Journal of applied clinical medical physics. 2017;18(2):144-53.

38. Oliveira da Silva M, Canevaro L, Hunt J, Rodrigues B. Comparing Measured and Calculated Doses in Interventional Cardiology Procedures. Radiation protection dosimetry. 2017;176(4):439-43.

39. Perisinakis K, Solomou G, Stratakis J, Damilakis J. Data and methods to assess occupational exposure to personnel involved in cardiac catheterization procedures. Physica Medica. 2016;32(2):386-92.

40. Sciahbasi A, Rigattieri S, Sarandrea A, Cera M, Di Russo C, Fedele S, et al. Operator radiation exposure during right or left transradial coronary angiography: a phantom study. Cardiovascular Revascularization Medicine. 2015;16(7):386-90.

41. Vano E, Sanchez R, Fernandez J, Bartal G, Canevaro L, Lykawka R, et al. A set of patient and staff dose data for validation of Monte Carlo calculations in interventional cardiology. Radiation protection dosimetry. 2015;165(1-4):235-9.

42. Principi S, Ginjaume M, Duch MA, Sánchez RM, Fernández JM, Vano E. Influence of dosemeter position for the assessment of eye lens dose during interventional cardiology. Radiation protection dosimetry. 2015;164(1-2):79-83.

43. Liu H, Jin Z, Jing L. Comparison of radiation dose to operator between transradial and transfemoral coronary angiography with optimised radiation protection: a phantom study. Radiation protection dosimetry. 2014;158(4):412-20.

44. Farah J, Struelens L, Dabin J, Koukorava C, Donadille L, Jacob S, et al. A correlation study of eye lens dose and personal dose equivalent for interventional cardiologists. Radiation protection dosimetry. 2013;157(4):561-9.

45. Ertel A, Nadelson J, Shroff AR, Sweis R, Ferrera D, Vidovich MI. Radiation Dose Reduction during Radial Cardiac Catheterization: Evaluation of a Dedicated Radial Angiography Absorption Shielding Drape. ISRN Cardiol. 2012;2012:769167. Epub 2012/09/19. doi: 10.5402/2012/769167. PubMed PMID: 22988525; PubMed Central PMCID: PMCPMC3439952.

46. Chida K, Morishima Y, Inaba Y, Taura M, Ebata A, Takeda K, et al. Physician-received scatter radiation with angiography systems used for interventional radiology: comparison among many X-ray systems. Radiation protection dosimetry. 2012;149(4):410-6.

47. von Boetticher H, Lachmund J, Hoffmann W. Cardiac catheterization: impact of face and neck shielding on new estimates of effective dose. Health Physics. 2009;97(6):622-7.

48. Mesbahi A, Mehnati P, Keshtkar A, Aslanabadi N. Comparison of radiation dose to patient and staff for two interventional cardiology units: a phantom study. Radiation protection dosimetry. 2008;131(3):399-403.

49. Schultz F, Zoetelief J. Dosemeter readings and effective dose to the cardiologist with protective clothing in a simulated interventional procedure. Radiation protection dosimetry. 2008;129(1-3):311-5.

2. How many personnale were included for dosimetric measurements ? Please list the number of each staff-e.g. How many primary operators, how many assistant operators etc. How many women and what age ?

Author response:

Thank you for the correction. We have added more specific details about the operators characteristics in the Table 1 as follows:

Table 1 The procedural details in CA with PCI, CA, and others

3. The EPD was worn around the collar, what about the chest, hands, ovaries or pelvis in women. Even if there were no EPD measurements in these body sites, an estimate should be given and discussed.

Author response:

Thank you for pointing this out. We have added more specific details about the radiation doses of the different body sites in discussion as follows:

We have rephrased the statement in line 185-198 as “There have been many studies[1, 30, 31] to estimate effective dose or effective dose equivalent using personal monitors. The information from these studies could be used in evaluating likely dose levels. The modified Niklason algorithm provided a measure of the exposure of sensitive organs in the trunk:

E = 0.02 (HOS − HU) + HU (with a thyroid collar)

where E is effective dose, Hos is Hp (0.07) measured over shield on thyroid level, and Hu is Hp (10) measured under apron. The Hp (10) over shield on thyroid level is converted to Hp (0.07) by adding 3% to the measurement dose. For a single dosimeter worn at the thyroid collar, again assuming HU ≈ 0.01 Hos, the conversion algorithm as follows:

E = 0.03 HOS

Martin et al.[31] is recommended for estimating the eye dose from a measurement with an unshielded neck dosemeter, the equation:

Eye dose = 0.75 × neck dose”

Newly added references:

30. Padovani R, Rodella C. Staff dosimetry in interventional cardiology. Radiation protection dosimetry. 2001;94(1-2):99-103.

31. Martin C. Personal dosimetry for interventional operators: when and how should monitoring be done? The British journal of radiology. 2011;84(1003):639-48.

We have rephrased the statement in line 192-205 as” Third, the hand doses may be much greater than doses at the neck, eye, or trunk during the procedures. There is no conversion algorithm to estimate the hand dose from the doses at neck. The dosimeter should be worn towards on the hand adjacent to the x-ray tube if a meaningful result is to be obtained.”

4. Line 231-232 is incomplete, please fix grammar throughout the document.

Author response:

Thank you for the correction. We have rephrased the statement in line 253-255 as “Although the LNT model for low-dose (<100mSv) is characterized by a great deal of uncertainty. As it for cardiac imagines, there is no direct evidence to estimate the cancer risks.”

5. Its not clear if the EPD measurements listed are an average exposure of each individual or average of the entire group. There is a need for a major clarification- are the measured doses from one or an average of all personnel

Author response:

Thank you for your valuable opinions. We have rephrased the statement in line 130-133 as “Primary operators doses were measured under 43 CA with PCI, 16 CA, and 12 others procedures, respectively. As to the assistant operators doses were 38 CA with PCI, 6 CA, and 1 others procedures, respectively.”

We also have added more details about the case volumes of the operators under this study in the Table 1 as follows:

Table 1 The procedural details in CA with PCI, CA, and others

6. How many such procedures are done in a year and how much cumulative exposure does a person get exposed to in a year? that estimate has to be provided.

Author response:

Thank you for your valuable opinions. We have rephrased the statement in line 155-158 as “We used the data from 71 procedures within 2 months to estimate the 1 year occupational radiation exposure to the operators is presented in Fig. 3. The annual average radiation dose per primary operator from all procedures was 3.28 mSv. As to the assistant operator was 1.59 mSv.”

7. How does the exposure differ between various machine models?

Author response:

Thank you for the correction. We have added more details about the exposure differ between various machine models in materials and methods as follows:

We have rephrased the statement in line 83-87 as “Experimental measurements were used three x-ray angiography systems(one was Philips Allura FD20, the others were Philips Allura FD 10) with similar cardiac catheterization protocols. All protocols followed standard technical characteristics of image acquisition and quality control. Collimation and magnification were used during the procedures according to the clinical requirements.”

Reviewer #2:

1. Line 50 -- Cardiac catheterization should not be described as a "radiologic" procedure. Rather, it is ionizing radiation-based.

Author response:

Thank you for your valuable opinions. We have rephrased the statement in line 50-51 as “Cardiac catheterization is an ionizing radiation procedure used to diagnose heart conditions or treat cardiovascular diseases.”

2. "other procedures" often use frame rates of 4/s or 7.5/s, considerably lower than the 15 fps listed here. Please acknowledge this in the Discussion.

Author response:

Thank you for pointing this out. We have added more details about the frame rates of other procedures in discussion as follows:

We have rephrased the statement in line 227-238 as “Optimizing the fluoroscopy or cine acquisition dose rate to reduce staff radiation dose and long-term risk is much more efficient. Ishibashi et al. [56] reported the fluoroscopy dose rates in Japan were 7.5 pulses/s at 44 % of CA, 7.5 pulses/s at 43 % of PCI, and 7.5 pulses/s at 54 % of radiofrequency catheter ablationpulses, respectively. As to the cine acquisition dose rates were 15 pulses/s at 93 % of CA, 15 pulses/s at 90 % of PCI, and 7.5 pulses/s at 55 % of radiofrequency catheter ablationpulses, respectively. van Dijk et al. [57] reported the fluoroscopy dose rate in pacemaker and defibrillator implantation was 7.5 pulses/s. As to the cine acquisition dose rates were 3.75-15 pulses/s. In our study, the default pulse rates (15 pulses/s) both fluoroscopy and cine acquisition dose rates were used in other procedures. Consequently, the fluoroscopy and cine acquisition dose rates must be optimized to ensure that the radiation dose be reduced to an acceptable level.”

Newly added references:

56. Ishibashi T, Takei Y, Sakamoto H, Yamashita Y, Kato M, Tsukamoto A, et al. Nationwide Survey of Medical Radiation Exposure on Cardiovascular Examinations in Japan. Nihon Hoshasen Gijutsu Gakkai zasshi. 2020;76(1):64.

57. van Dijk JD, Ottervanger JP, Delnoy PPH, Lagerweij MC, Knollema S, Slump CH, et al. Impact of new X-ray technology on patient dose in pacemaker and implantable cardioverter defibrillator (ICD) implantations. Journal of Interventional Cardiac Electrophysiology. 2017;48(1):105-10.

3. The manuscript leaves very unclear what is being calculated. Is it the radiation dose per case, per year, or per career. This is crucial to the manuscript's conclusions. For example, calculating the LAR of a 60 year old interventional cardiologist based on one year's exposure isn't meaningful, since that individual has likely had exposures beginning 30 years previously. Complicating factors even further, exposure times were likely longer when the individual was younger and less experienced, and the yearly case load may have been lower as the individual was building a career and reputation. Exactly what is being calculated is critical here.

Author response:

Thank you for pointing this out. We have added more details about the cancer risk estimation in abstract, materials and methods, results, discussion and conclusion as follows:

We have rephrased the statement in line 32-39 (abstract) as” LAR of all cancer incidences for staffs aged from 18 to 65 are varied from 0.49 % for males to 1.41 % for females. LAR of all cancer mortality for staffs aged from 18 to 65 are varied from 0.27 % for males to 0.78 % for females. Our study provided an easy, real-time and dynamic radiation dose measurement to estimate LAR of cancer for staff during the cardiac catheterization procedures. The LAR for all cancer incidence is about twice that for cancer mortality. Although the radiation doses of staff are lower during each procedure, the increased years of service leads to greater radiation risk to the staff.”

We have rephrased the statement in line 115-117 (materials and methods) as “This study estimated the cancer risk under the assumption that the operators were continuously exposed to radiation from the age of 18 to 65.”

We have rephrased the statement in line 158-165 (results) as “Estimated LAR of all cancer incidence and mortality from cardiac catheterization procedures for operators are presented in Table 2. LAR of all cancer incidence and mortality for male primary operators aged from 18 to 65 were 1.00 %, and 0.56 %, respectively. As to the female primary operators aged from 18 to 65 were 1.41 % and 0.78 %, respectively. In contrast, the LAR of all cancer incidence and mortality were significantly lower in assistant operators. The LAR of all cancer incidence and mortality for females were significantly higher than for males.”

Table 2 Estimated LAR of all cancer incidence and mortality from cardiac catheterization procedures for operators

We have rephrased the statement in line 215-227 (discussion) as “Although our study demonstrates that the radiation doses of staff are lower during each procedure, the increased years of service leads to greater radiation risk to the operators. In fact, the radiation risks are mainly stochastic effects at low radiation exposure levels. These effects with the probability of occurrence increasing with the absorbed dose [28, 55]. Therefore, lead aprons and thyroidal collars and leaded glasses allow staff to achieve As Low As Reasonably Achievable (ALARA) during the procedures. As was shown in an earlier report [28], lead aprons of 0.25 or 0.5 mm absorb 85-92 % 100 kV of energy and 93-97 % of 100 kV of energy, respectively. All operators wear lead aprons, thyroid collars, and leaded glasses to protect themselves, during long-term performance of the procedures, it is still impossible to completely avoid radiation exposure and its effects. If operators fail to use protective gear or adjust the exposure time properly, within a few years operators may have increased the LAR of cancer.”

We have rephrased the statement in line 261-265 (conclusion) as “The present study provided an easy, real-time and dynamic radiation dose measurement to estimate LAR of cancer for staff in the cardiac catheterization procedures. Although the radiation doses of staff are lower during each procedure, the increased years of service leads to greater radiation risk to the staff.”

4. The first table should include the ages and case volumes of the operators under study.

Author response:

Thank you for your valuable opinions. We have added more details about the ages and case volumes of the operators under this study in the Table 1 as follows:

Table 1 The procedural details in CA with PCI, CA, and others

5. How was the volume of 450 cases/year obtained?

Author response:

Thank you for pointing this out. We have added more details about the cumulative exposure does a person get exposed to in a year as follows:

We have rephrased the statement in line 155-158 as “We used the data from 71 procedures within 2 months to estimate the 1 year occupational radiation exposure to the operators is presented in Fig. 3. The annual average radiation dose per primary operator from all procedures was 3.28 mSv. As to the assistant operator was 1.59 mSv.”

6. How was continual and correct placement of the dosimeter assured?

Author response:

Before the all measurements, the dosimeter was attached over the operator’s thyroid collar at a fixed position (left side) and marked it. For every procedure, all operators used the same thyroid collar with dosimeter.

7. Are approaches to PCI predominantly femoral or radial?

Author response:

Yes, approaches to PCI are predominantly radial in this study. Radial approach has lower vascular and bleeding complications, improved patient comfort and early ambulation. We have added more details about the arterial approach in the Table 1 as follows:

Table 1 The procedural details in CA with PCI, CA, and others

8. The beam angles in Fig 1 add up to more than 100%.

Author response:

Thank you for the correction. We have modified the Figure 1:

9. One assumes that he dose-area products recorded are those for the patient. Is this correct?

Author response:

That's right. The dose area product (DAP) is obtained by DAP meters. DAP is a product of the surface area of the patient that is exposed to radiation at the skin entrance (in square centimeters or square meters) multiplied by the radiation dose at this surface (in grays). DAP is the best overall measurement of total patient dose and risks due to stochastic effects, such as DNA damage and future cancer. In clinical practice, tabular data of the conversion factors (in millisieverts per grays-centimeters squared) for DAP can yield the effective dose.

10. The fluoroscopy and acquisition times for PCI seem very short. Please double check.

Author response:

Thank you for being patient and helping me improve. We reconfirmed the fluoroscopy and acquisition times for all procedures. The acquisition time for all procedures including data conversion errors are rephrased as following:

We have rephrased the statement in line 140-141 as “The acquisition time was also longest in CA with PCI procedure (53.16 ± 10.33 s)”

Table 1 The procedural details in CA with PCI, CA, and others

11. How many procedures were used for the measurements?

Author response:

Thank you. There were 71 procedures were used for the measurements in our study. We have added more details about the number of procedures as follows:

In line 126-127 : “There were 71 procedures were included in our study, 43 CA with PCI, 16 CA and 12 others.”

12. Was there a specific protocol for edge-to edge collimation?

Author response:

Yes, we utilized standard imaging capture protocols in the study. We used a collimation when the size of heart is greater than 2 cm in the diastolic phases to limit the images field size exposed.

13. Lines 175-176 seem to be erroneous. This study didn't report relations between beam angles and radiation dose. Was this from a previous publication.

Author response:

Thank you for the correction. We have rephrased the statement in line 174-176 as “Indeed, we analyzed the beam directions distribution complexity during the different procedures in this study.”

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

22 Apr 2020

PONE-D-19-29699R1

Cardiac Catheterization Real-time Dynamic Radiation Dose Measurement to Estimate Lifetime Attributable Risk of Cancer

PLOS ONE

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Reviewer #1: All questions that were raised have been addressed, the grammar is corrected, additional table and additional information about personal exposure has been added.

Reviewer #2: The operator exposure still needs to be more detailed.

What specific assumptions have the authors make about LAR? -a)-Constant yearly exposure from age 18 through 65? Probably not an entirely valid assumption since Cardiologist don't start at age 18, and probably don't do as many cases when starting, also have longer exposure per case when they are learning. b) -- Do operators continue through age 65 or does the LAR assume that they have stopped at the time of the study? c) is it possible to produce a survival analysis curve of the LAR?

Using a two month average is subject to determine case volume is subject to a good deal of error as there are seasonal variations in catheterization lab volume. Is it possible to use a 12 month average for the preceding year?

The quality y of Figure 1 need to be improved. It is very difficult to read the figures.

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26 May 2020

Dear Editor, Dear reviewers

We thank the reviewers again for the helpful comments. The following is a point-by-point response to each comment:

Reviewer #2: The operator exposure still needs to be more detailed.

1. What specific assumptions have the authors make about LAR?

-a)-Constant yearly exposure from age 18 through 65? Probably not an entirely valid assumption since Cardiologist don't start at age 18, and probably don't do as many cases when starting, also have longer exposure per case when they are learning.

b) -- Do operators continue through age 65 or does the LAR assume that they have stopped at the time of the study?

c) is it possible to produce a survival analysis curve of the LAR?

Author response:

For question a and b

Thank you for pointing this out. In our study, the LAR of all cancer incidence and mortality at the radiation dose for operators were calculated by BEIR VII Report. The BEIR VII report is based on a wide enough range of exposure to support meaningful statistical modeling. However, according to the LNT model adopted in BEIR VII, 10 mSv on a yearly basis from ages 18 to 65 years old, cancer incidence was 3,059 for male and 4,295 for female. That data was directly applied to the calculation of cancer risk to medical staff, so there is limitation for generalization in our results.

We have added more specific details in discussion as follows:

We have rephrased the statement in line 253-260 as “In addition, our study did not estimate the yearly of radiation exposure exactly and job tenure of operators. However, according to the BEIR VII report, when exposed continuously to 10 mSv on a yearly basis from ages 18 to 65 years old, cancer incidence was 3,059 for male and 4,295 for female. That data was directly applied to the calculation of cancer risk to medical staff in many studies [10, 58-60]. Although the LNT model for low-dose (<100mSv) is characterized by a great deal of uncertainty, there is no direct evidence to estimate the cancer risks for staff during the cardiac catheterization procedures.”

Newly added references:

58. Cho H-O, Park H-S, Choi H-C, Cho Y-K, Yoon H-J, Kim H-S, et al. Radiation dose and cancer risk of cardiac electrophysiology procedures. International Journal of Arrhythmia. 2015;16(1):4-10.

59. Mehta S. Health risks of low level radiation exposures: a review. Ind J Nucl Med. 2005;20:29-41.

60. Kim JB, Lee J, Park K. Radiation hazards to vascular surgeon and scrub nurse in mobile fluoroscopy equipped hybrid vascular room. Annals of surgical treatment and research. 2017;92(3):156-63.

For question c

Thank you for your kind advice. However, a survival analysis curve requires prolonged observation and studies to rule out many potentially personal, mechanical, and environmental factors. We really appreciate your precious advice and useful suggestions for our future studies.

2. Using a two month average is subject to determine case volume is subject to a good deal of error as there are seasonal variations in catheterization lab volume. Is it possible to use a 12 month average for the preceding year?

Author response:

Thank you for being patient and helping me improve.

We have modified the case volume of 1 year occupational radiation exposure to the operators in abstract and results as follows:

We have rephrased the statement in line 32-35 (abstract) as LAR of all cancer incidences for staffs aged from 18 to 65 are varied from “0.40 %” for males to “1.50 %” for females. LAR of all cancer mortality for staffs aged from 18 to 65 are varied from “0.22 %” for males to “0.83 %” for females.

We have rephrased the statement in line 155-158 (results) as “We used a 12 month average for the preceding year to estimate the 1 year occupational radiation exposure to the operators is presented in Fig. 3. The annual average radiation dose per primary operator from all procedures was 3.49 mSv. As to the assistant operator was 1.30 mSv.”

We have rephrased the statement in line 160-162 (results) as LAR of all cancer incidence and mortality for male primary operators aged from 18 to 65 were “1.07 %”, and “0.59 %”, respectively. As to the female primary operators aged from 18 to 65 were “1.50 %”, and “0.83 %”, respectively.

We have modified the Table 2 as follows:

Table 2 Estimated LAR of all cancer incidence and mortality from cardiac catheterization procedures for operators

Operators Primary operators Assistant operators

LAR All cancer incidence aged from 18 to 65 All cancer mortality aged from 18 to 65 All cancer incidence aged from 18 to 65 All cancer mortality aged from 18 to 65

Male 1.07 % 0.59% 0.40 % 0.22 %

Female 1.50 % 0.83 % 0.56 % 0.31 %

3. The quality y of Figure 1 need to be improved. It is very difficult to read the figures.

Author response:

Thank you for the correction. We have modified the Figure 1:

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

28 May 2020

Cardiac Catheterization Real-time Dynamic Radiation Dose Measurement to Estimate Lifetime Attributable Risk of Cancer

PONE-D-19-29699R2

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2 Jun 2020

PONE-D-19-29699R2

Cardiac Catheterization Real-time Dynamic Radiation Dose Measurement to Estimate Lifetime Attributable Risk of Cancer

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