ORAUT-OTIB-0082

Dose Reconstruction Method for Chronic 

Lymphocytic Leukemia

Report from the Subcommittee for Procedure Reviews (SCPR)

Presented to the

Advisory Board on Radiation and Worker Health

Oakland, California 

December 11, 2019

1
ORAUT-OTIB-0082, “Dose Reconstruction Method for Chronic 

Lymphocytic Leukemia”

ORAUT-OTIB-0082 is a new document initiated to describe the use of the 

chronic lymphocytic leukemia (CLL) model and to provide guidance to dose 

reconstructors on its application.

• Revision 00: Issued December 04, 2012.

• Revision 00 PC-1: Issued December 20, 2012, to add clarification on the use of 

ORAUT-OTIB-0017, “Interpretation of Dosimetry Data for Assignment of Shallow 

Dose,” and a description of the blended electron dose conversion factor to be 

used for assigning dose due to electrons.

• SC&A’s review of Rev. 00 PC-1 was submitted October 6, 2014. SC&A was not 

tasked with reviewing the CLL risk model developed under contract by SENES Oak 

Ridge, Inc., which was used as the basis for ORAUT-OTIB-0088. The review did not 

identify any findings or observations. Even though there were no findings, this 

presentation aims to provide the Board a better understanding of the dose 

reconstruction methods associated with the complex CLL model.

2
Overview of OTIB-0082, Rev. 00 PC-1

Of all cancers assessed under EEOICPA, estimating radiation dose to cells 

suspected of giving rise to CLL is by far the most complex and challenging, as 

explained in the following statements from OTIB-0082:

• “CLL originates in the B lymphocytes rather than in a well-defined organ as with other cancers. These lymphocytes are distributed throughout the 

lymph system and . . . they can travel throughout the body and their 

inventories in various compartments of the body can change significantly 

with age, gender, health status and other factors” (p. 5). 

• “Estimation of dose to the cancer site for CLL cases requires the calculation 

of the radiation dose to this population of CLL precursor cells” (p. 5).

• “In the development of the CLL dosimetric model, information was 

analyzed to derive compartment-specific weights based on relative sizes of 

B-lymphocyte . . . pools to be used in estimating a weighted average radiation dose. Because of the variability and uncertainty in the 

distribution of these cells, probability distribution functions were assigned 

to the number of lymphocytes and to the fraction that represent B cells for 

each organ of interest” (p. 6).

3
Overview of OTIB-0082, Rev. 00 PC-1 (continued)

• “The final model consists of an average dose (and its uncertainty) obtained 

using weights based on the fractional distribution of B-lymphocyte precursors across 30 compartments for CLL” (p. 6). 

• For external dose calculation, the B lymphocytes compartments 

corresponding to 15 organs must be assessed (Section 4.3)

• For internal dose calculation, the B lymphocytes compartments 

corresponding to a total of 28 organs must be assessed (Section 4.2).

• For medical x-ray dose calculation, the B lymphocytes compartments correspond to 18 organs (Section 4.1).

• The corresponding ICRP-modeled organs to be assessed for each compartment of the CLL model are shown in OTIB-0082, Table 3-1 

(reproduced here in Slide 5).

4
Correspondence of CLL model to ICRP-modeled organs (OTIB-0082, Table 3-1)

Compartment of CLL

dosimetry model X-ray dose organ Internal dose organ External dose organ

Lymph nodes 

Extrathoracic Thyroid LN(ET) Thyroid 

Thoracic Lung LN(TH) Lung 

Remainder Ovaries HNM Stomach

Spleen Spleen (lung or ovaries) Spleen Stomach 

Peyer's Patches Colon (ovaries) SI Stomach

Thymus Thymus (lung) Thymus Thymus 

Red bone marrow Bone marrow RBM RBM 

Tonsils Esophagus (lung) LN(ET) Esophagus 

Blood Remainder HNM Stomach 

Intestinal mucosa 

Small intestinal wall Ovary SI Stomach 

Upper intestinal wall Colon (ovaries) ULI Colon 

Lower large intestinal wall Colon (ovaries) LLI Colon

Respiratory mucosa 

Extrathoracic airways Esophagus (lung) ET2 Esophagus 

Lung Lung Lung Lung 

Skin Skin Skin Skin 

Liver Liver (lung or ovary) Liver Liver

Vermiform appendix Colon (Ovaries) ULI Colon 

Residual soft tissue 

Muscle Remainder Muscle Remainder 

Breast Breast Breast Breast 

Kidneys Remainder Kidney Liver 

ST wall Stomach (lung or ovaries) Stomach Stomach 

Pancreas Pancreas (lung or ovaries) Pancreas Stomach 

Uterus Uterus Uterus Uterus 

Urinary bladder wall Urinary bladder (ovaries) Bladder Bladder 

Esophagus Esophagus (lung) Esophagus Esophagus 

Testes Testes Testes Testes 

Thyroid Thyroid Thyroid Thyroid 

Prostate Prostate (ovaries) HNM Bladder 

Adrenals Remainder Adrenals Remainder 

Ovaries Ovaries Ovaries Ovaries 

5
External Dose

• To account for the correlation of external dose between dosimeter 

measurements and the individual organs listed in OTIB-0082, Table 3-1, a 

special dose conversion factor (DCF) was derived and is used to determine the 

dose to the appropriate CLL compartments.

• This blended CLL DCF, which is described in DCAS-RPT-004, “Chronic 

Lymphocytic Leukemia (CLL) Dose Conversion Factors,” is composed of the 

weighted fractions of the DCF values associated with the 15 organs listed in 

Table 3-1.

• Blended DCFs are based on previously assessed DCF values cited in OCAS-IG001, “External Dose Reconstruction Implementation Guide,” for selected 

radiation types, energies, and exposure geometries using Monte Carlo 

techniques.

6
External Dose (continued)

• For each CLL DCF, NIOSH employed a total of 50,000 iterations, which were 

fitted to five standard probability distributions that included normal, 

lognormal-3 parameter, lognormal-2 parameter, Weibull-3 parameter, and Weibull-2 parameter.

• NIOSH determined the best fit of the data among the five distributions 

using the Akaike Information Criterion (AIC) and selected the fit(s) with the lowest AIC score.

• To properly apply the blended DCF values in dose reconstruction, NIOSH 

added a “CLL DCF” tab/spreadsheet with these CLL DCFs to all site-specific external dose calculation workbooks.

• SC&A’s review: 

• Critically reviewed the statistical approach described in DCAS-RPT-004.

• Verified that the site-specific external dose calculation workbooks had been 

updated with the “CLL DCF” tab, and that the data entered into the spreadsheet 

associated with this tab were consistent with data given in DCAS-RPT-004. 

• SC&A concurred with the methodology used to derive blended CLL DCF 

values.

7
Internal Dose

• Given the complexity of deriving weighted organ/tissue doses, 

NIOSH developed the CLL Simulator Tool, which allows the 

Integrated Modules for Bioassay Analysis (IMBA) and Chronic Annual 

Dose Workbook (CADW) files to be imported for calculating internal 

doses to all CLL organs simultaneously.

• The CADW was also modified to create a separate file for each of the 

28 organs/tissues, which can be used in the CLL Simulator Tool.

8
Internal Dose (continued)

• CLL-specific guidance was added to the following list of applicable 

documents to address the complexity of the CLL risk model:

• ORAUT-OTIB-0018, “Internal Dose Overestimates for Facilities with Air 

Sampling Programs” 

• ORAUT-OTIB-0054, “Fission and Activation Product Assignment for Internal 

Dose-Related Gross Beta and Gross Gamma Analyses” 

• ORAUT-OTIB-0049, “Estimating Doses for Plutonium Strongly Retained in the 

Lung” 

• ORAUT-OTIB-0011, “Technical Information Bulletin: Tritium Calculated and 

Missed Dose Estimates” 

• Site-specific radionuclide chooser tools

• Site-specific internal environmental tools

9
Internal Dose (continued)

• SC&A was provided training on running the CLL Simulator Tool. 

Subsequently, SC&A generated both IMBA and CADW files for a CLL 

claim, imported these files into the CLL Simulator Tool, and evaluated 

the internal doses generated by the tool.

• SC&A assessed the changes made to tools and to dose reconstruction 

guidance for performing internal dose estimates.

• SC&A’s evaluation of internal dose tools confirmed that appropriate 

changes have been incorporated into these tools, and that the tools 

generated internal doses that included the weighted organs/tissues 

specified in OTIB-0082. 

• SC&A’s evaluation of the technical guidance verified that appropriate 

changes were incorporated for performing best estimates for CLL 

claims. 

10
Medical X-ray Dose

• For occupational medical radiation associated with either a chest or 

lumbar spine x-ray examination, dose estimates to each CLL 

compartment are defined by the product of the incident air kerma 

and the compartment-specific DCFs assigned to organs shown in the 

second column of Table 3-1.

• For the CLL compartment involving the skin, an entrance and exit skin 

dose is defined, as well as the fraction of exposed skin, which varies 

from 0.19 for a properly collimated beam to 0.38 for a poorly 

collimated beam.

• The effective organ dose to CLL precursor cells from occupational 

medical exposure is the sum of the weighted organ doses that takes 

into consideration uncertainties associated with each organ-specific 

DCF value and the weighted fraction of CLL cells.

11
Medical X-ray Dose (continued)

• For estimates of CLL medical x-ray doses, NIOSH developed CLL xray doses that were facility specific, view specific (e.g., PA or LAT), 

and facility specific to given time periods. 

• Variables among time periods included assigned organ doses and 

whether beams were properly or poorly collimated. 

• A lookup table containing these values has been incorporated 

into each site-specific external dose calculation workbook as a 

single tab (“CLL X-ray Data”).

12
Medical X-ray Dose (continued)

• SC&A’s review consisted of: 

• Evaluating NIOSH’s methodology and guidance pertaining to the 

assignment of medical x-ray dose to compartments. These 

indicated that they are consistent with existing models and, when 

properly adjusted to account for the distribution of CLL precursor 

cells among compartments, comply with the CLL risk model. 

• Examining all site-specific external dose calculation workbooks to 

ensure that the ‘CLL X-ray Data” tab had been added and the data 

were consistent with technical basis document guidance.

13
Validation of Guidance in ORAUT-OTIB-0082 by 

Dose Reconstruction

• To assess the functionality of the guidance in OTIB-0082, SC&A 

conducted a preliminary review of a CLL case assigned as part of our 

audit of the 19th set of dose reconstructions.

• The CLL case review included evaluation of (1) photon/neutron doses, 

(2) occupational medical exposure, (3) bioassay data, (4) IMBA inputs 

and results, and (5) the CLL Simulator Tool.

• From this preliminary evaluation and a spot check of calculations, 

doses, etc., it appears that, for this case, the dose reconstructor used 

the proper procedures and assigned the correct doses.

14
Questions?

15