APPENDIX B
Clarification of Cancer Groupings Used in Reporting Results, with Correspondence to NIOSH Cause-of-Death Codes and ICD Codes for Cancers

For Update 2006, the Department of Veterans Affairs (VA) requested two refinements in the system used in previous Veterans and Agent Orange (VAO) updates to present conclusions about the adequacy of evidence concerning associations between cancer types and exposure to the herbicides sprayed in Vietnam. First, conclusions should be provided for the full range of cancer types; that is, the cancer groupings for which conclusions are drawn should be exhaustive. Second, it should be apparent into which groupings specific cancer diagnosis falls.

The explicitly stated cancer grouping reviewed in prior updates left a few gaps in the full range of cancer types (as indicated in italics in Table B-1). Those gaps represent quite specific types of cancer on which no data compatible with review had been found; the endpoint by default was in the “inadequate or insufficient evidence” category. The major portion of evidence compiled for review in this series comes from cohort studies, primarily of mortality but some of incidence. Other data have been generated by case–control studies, which follow the only design amenable to studying very infrequent or very specific health outcomes. How researchers are able to group, analyze, and report their findings is influenced by the distribution of cases that they observe, so the data that VAO committees have had available for review reflect mortality experience at a level of specificity concordant with statistical analysis.

Previous updates have referred to the International Classification of Diseases (ICD) system, which is used by physicians and researchers around the world to group related diseases and procedures so that morbidity and mortality information can be classified for statistical purposes in a standard form amenable to data storage and retrieval. It is a comprehensive hierarchic system that permits great detail, but that can be collapsed into broad categories. Codes mentioned in VAO reports are stated in terms of ICD, Version 9 (ICD-9). ICD-7, ICD-8, and ICD-9 were



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APPENDIX B Clarification of Cancer Groupings Used in Reporting Results, with Correspondence to NIOSH Cause-of- Death Codes and ICD Codes for Cancers For Update 2006, the Department of Veterans Affairs (VA) requested two refinements in the system used in previous Veterans and Agent Orange (VAO) updates to present conclusions about the adequacy of evidence concerning asso- ciations between cancer types and exposure to the herbicides sprayed in Vietnam. First, conclusions should be provided for the full range of cancer types; that is, the cancer groupings for which conclusions are drawn should be exhaustive. Second, it should be apparent into which groupings specific cancer diagnosis falls. The explicitly stated cancer grouping reviewed in prior updates left a few gaps in the full range of cancer types (as indicated in italics in Table B-1). Those gaps represent quite specific types of cancer on which no data compatible with review had been found; the endpoint by default was in the “inadequate or insuf- ficient evidence” category. The major portion of evidence compiled for review in this series comes from cohort studies, primarily of mortality but some of incidence. Other data have been generated by case–control studies, which fol- low the only design amenable to studying very infrequent or very specific health outcomes. How researchers are able to group, analyze, and report their findings is influenced by the distribution of cases that they observe, so the data that VAO committees have had available for review reflect mortality experience at a level of specificity concordant with statistical analysis. Previous updates have referred to the International Classification of Diseases (ICD) system, which is used by physicians and researchers around the world to group related diseases and procedures so that morbidity and mortality information can be classified for statistical purposes in a standard form amenable to data stor- age and retrieval. It is a comprehensive hierarchic system that permits great detail, but that can be collapsed into broad categories. Codes mentioned in VAO reports are stated in terms of ICD, Version 9 (ICD-9). ICD-7, ICD-8, and ICD-9 were 707

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708 VETERANS AND AGENT ORANGE: UPDATE 2006 in effect for deaths that occurred in 1960–1967, 1968–1978, and 1979–1998, respectively; the differences among them are fairly subtle. Although ICD-10, which went into effect for coding causes of deaths that occurred from 1999 on, appears radically different from the earlier versions, it corresponds in large part to basically the same disease entities (see Table B-2). To date, most published epidemiologic studies have been related to health outcomes that occurred and were encoded before ICD-10 went into effect. Since 1983, the National Institute for Occupational Safety and Health (NIOSH) has maintained software for generating standardized expectations, as derived from US mortality data assembled by the National Center for Health Sta- tistics, for ICD-encoded mortality data sets. An article by Robinson et al. (2006) discusses revisions to that standard software to incorporate deaths coded accord- ing to ICD-10 and includes conversions and equivalencies between ICD-7, -8, -9, and -10 for 119 exhaustive categories for cause of death. Codes for malignant neoplasms span the ICD-9 range 140.0–208.9, NIOSH’s major categories 02–10, or NIOSH’s more specific minor categories 004–040. The NIOSH death codes for neoplasms provide comprehensive scaffold- ing for organizing the committee’s reviews and conclusions by cancer type that is somewhat simpler than ICD classifications, but maps completely to the ICD system as it has evolved. Because the NIOSH system has been used to mediate analysis of many sets of cohort data, its groupings correspond quite closely with the published research findings available for VAO review. In general cohort stud- ies, one is unlikely to encounter results on more specific groupings than NIOSH’s minor categories. As discussed in Chapter 2, this committee has not framed its conclusions strictly in terms of ICD codes, but the ICD system has been a valuable tool for the work of VAO committees. There can be coding errors on hospital records or death certificates, but when researchers present their results labeled with ICD codes, there can be little ambiguity about what they intended. When their most definitive indication is something like “respiratory cancers,” however, there can be uncertainty about where the evidence should be considered. In such cases, the committee has done its best to follow the hierarchy laid out in Table B-1. As indicated above, many of the studies reviewed by the committee use or were written at a time when ICD-9 was in place. Accordingly, ICD references in this report use that scheme. ICD-10 began to be implemented in the United States in 1999. It differs from ICD-9 in level of detail (about 8,000 categories versus about 5,000 in ICD-9) and nomenclature (alphanumeric versus the numeric codes of ICD-9); additions and modifications were also made with regard to some coding rules and the rules for selecting an underlying cause of death (Anderson et al., 2001). Table B-2 lists the ICD-9 and ICD-10 codes for the various forms of malignant neoplasm addressed in this report. In situ neoplasms, benign neo- plasms, neoplasms of uncertain behavior, and neoplasms of unspecified behavior have separate codes in both schemes.

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TABLE B-1 Mapping of Groupings of Malignant Neoplasms That Are the Subjects of Conclusions in Update 2004 with ICD-9 Codes NIOSH Category for Cause of Death Subsites “Update 2004 Characterization of Major Minor NIOSH Groupings of Cancer Sites Grouping”a ICD-9 Codes (Gapsb in Italics) “Oral, nasal, and pharyngeal” 02 Buccal cavity and pharynx 140 004 Lip 141 005 Tongue 006 Other parts of buccal cavity 142 Salivary glands 144 Floor of mouth 143, 145 Gum and other mouth 007 Pharynx 146 Oropharynx Tonsil 146.0–146.2 147 Nasopharynx 148 Hypopharynx Other buccal cavity and pharynx 149 (160 nasal below) “Gastrointestinal” 03 Digestive organs and peritoneum 150 008 Esophagus 151 009 Stomach 010 Intestine except rectum Small intestine 152 153 Colon (large intestine) 154 011 Rectum 709 continued

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TABLE B-1 Continued 710 NIOSH Category for Cause of Death Subsites “Update 2004 Characterization of Major Minor NIOSH Groupings of Cancer Sites Grouping”a ICD-9 Codes (Gapsb in Italics) “Hepatobiliary” 012 Biliary passages, liver, and gall bladder 155 Liver and intrahepatic bile ducts Gallbladder and extrahepatic bile ducts 156 013 Pancreas 157 Retroperitoneum and other and unspecified 158–159 014 digestive organs “Respiratory” 04 Respiratory system 161 015 Larynx 016 Trachea, bronchus, and lung 162 Trachea 162.0 (there is no ICD 162.1) 162.2–162.9 Lung and bronchus Pleura 163 017 Other respiratory 018 Nasal cavity, middle ear, and accessory sinuses (160, above with oral and pharyngeal) Thymus, heart, and mediastinum 164 (164.0, below with endocrine; 164.1, below with soft-tissue sarcoma) Other respiratory, unspecified 165 (discontinuity with ICD codes) “Breast” 174, 175 05 019 Breast (male and female) “Female reproductive” 06 Female genital organs 180 020 Cervix uteri 021 Other unspecified parts of uterus 179, 181, 182 Uterus, parts unspecified 179 Placenta 181 182 Body of uterus

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022 Ovary, fallopian tube, and broad ligament 183 Ovary 183.0 (there is no ICD 183.1) Fallopian tube and other uterine adnexa 183.2–183.9 Other female genital organs 184 023 07 Male genital system 185, 186 “Prostate” 185 024 Prostate “Testicular” 186 025 Testis Penis and other male genital organs [for NIOSH in minor group 036] 187 08 Urinary system “Renal” 189.0–189.2 026 Kidney (including renal pelvis and ureter) “Urinary bladder” 027 Bladder and other urinary organs 188, 189.3–189.9 188 Bladder 189.3–189.9 Urethra, paraurethral glands, other and unspecified urinary (discontinuity with ICD codes) 09 Other and unspecified sites “Bone and joint” 170 028 Bone (“and articular cartilage” in ICD nomenclature) “Skin” 172 029 Melanoma 173 030 Other malignant skin neoplasm Mesothelioma 031 No codes (new minor code) “Soft-tissue sarcoma” 171 032 Connective (“and other soft” in ICD nomenclature) tissue (164.1) (heart) “Brain” 191–192 033 Brain and other parts of nervous system (ICD “soft tissue” includes peripheral nerves and autonomic nervous system) Eye 190 034 Thyroid 193 035 (thymus) 164.0 711 continued

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712 TABLE B-1 Continued NIOSH Category for Cause of Death Subsites “Update 2004 Characterization of Major Minor NIOSH Groupings of Cancer Sites Grouping”a ICD-9 Codes (Gapsb in Italics) Other and unspecified sites Other endocrine cancers 194 036 Other and ill-defined sites 195 Stated or assumed to be secondary of specified 196–198 sites Site unspecified 199 10 Lymphatic and hematopoietic tissue Lymphoma Hodgkin’s disease 201 037 Non-Hodgkin’s lymphoma 038 200, 202 (excluding 202.4), 273.3 Multiple myeloma 039 203 (excluding 203.1)

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“Leukemia (other than CLL)” 040 Leukemia and aleukemia 204–208 Lymphocytic 204.0 Acute lymphocytic Chronic lymphocytic 204.1 202.4; 204.2–204.9 Other lymphocytic Myeloid (granulocytic) Acute myeloid 205.0 Acute 207.0 Acute erythremia and erythroleukemia 207.2 Megakaryocytic leukemia 205.1 Chronic myeloid 205.2–205.3, 205.8–205.9 Other myeloid Monocytic 206.0 Acute monocytic 206.1 Chronic monocytic 206.2–206.9 Other monocytic Other leukemia 208.0 Other acute 207.1, 208.1 Other chronic 203.1, 207.2, 207.8, 208.2–208.9 Aleukemic, subleukemia, and “not otherwise specified” a Boldface cancer (sub)site: most comprehensive grouping for which conclusion was drawn in Update 2004. b Italicized cancer (sub)site: prior gap in coverage of cancers (not explicitly addressed in text). 713

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714 VETERANS AND AGENT ORANGE: UPDATE 2006 TABLE B-2 Surveillance, Epidemiology, and End Results (SEER) Program Malignant Neoplasm Site Groupings for ICD-9 and ICD-10 Cancer Site ICD-9 Codes ICD-10 Codes Buccal cavity and pharynx Lip 140.0–140.9 C00.0–C00.9 Tongue 141.0–141.9 C01, C02.1–C02.9 Salivary glands 142.0–142.9 C07, C08.0–C08.9 Floor of mouth 144.0–144.9 C04.0–C04.9 Gum and other mouth 143.0–143.9, 145.0–145.6, C03.0–C03.9, C05.0–C05.9, 145.8–145.9 C06.0–C06.9 Nasopharynx 147.0–147.9 C11.1–C11.9 Tonsil 146.0–146.2 C09.0–C09.9 Oropharynx 146.3–146.9 C10.1–C10.9 Hypopharynx 148.0–148.9 C12, C13.0–C13.9 Other buccal cavity and pharynx 149.0–149.9 C14.0–C14.9 Digestive system Esophagus 150.0–150.9 C15.0–C15.9 Stomach 151.0–151.9 C16.0–C16.9 Small intestine 152.0–152.9 C17.0–C17.9 Colon excluding rectum 153.0–153.9, 159.0 C18.0–C18.9, C26.0 Rectum and rectosigmoid 154.0–154.1 C19, C20 junction Anus, anal canal, and anorectum 154.2–154.3, 154.8 C21.0–C21.9 Liver and intrahepatic bile duct Liver 155.0,155.2 C22.0, C22.2–C22.4, C22.7–C22.9 Intrahepatic bile duct 155.1 C22.1 Gallbladder 156.0 C23 Other biliary 156.1–156.9 C24.0–C24.9 Pancreas 157.0–157.9 C25.0–C25.9 Retroperitoneum 158.0 C48.0 Peritoneum, omentum, and 158.8–158.9 C48.1–C48.2 mesentery Other digestive organs 159.8–159.9 C26.8–26.9, C48.8 Respiratory system Nasal cavity, middle ear, and 160.0–160.9 C30.0, C30.1, C31.0–C31.9 accessory sinuses Larynx 161.0–161.9 C32.0–C32.9 Lung and bronchus 162.2–162.9 C34.0–C34.9 Pleura 163.0–163.9 C38.4 Trachea, mediastinum, and other 162.0, 164.2–165.9 C33, C38.1–C38.3, C38.8, respiratory organs C39 Bones and joints 170.0–170.9 C40.0–C40.9, C41.0–C41.9 Soft tissue (including heart) 171.0–171.9, 164.1 C38.0, C47.0–C47.9, C49.0–C49.9 Skin Malignant melanomas 172.0–172.9 C43.0–C43.9 Other malignant skin neoplasms 173.0–173.9 C44.0–C44.9 Breast (male and female) 174.0–174.9, 175 C50.0–C50.9

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715 APPENDIX B TABLE B-2 Continued Cancer Site ICD-9 Codes ICD-10 Codes Female genital system Cervix 180.0–180.9 C53.0–C53.9 Corpus 182.0–182.1, 182.8 C54.0–C54.9 Uterus, not otherwise specified 179 C55 Ovary 183.0 C56.0–C56.9 Vagina 184.0 C52 Vulva 184.1–184.4 C51.0–C51.9 Other female genital organs 181, 183.2–183.9, 184.8, C57.0–C57.9, C58 184.9 Male genital system Prostate 185 C61 Testis 186.0–186.9 C62.0–C62.9 Penis 187.1–187.4 C60.0–C60.9 Other male genital organs 187.5–187.9 C63.0–C63.9 Urinary system Urinary bladder 188.0–188.9 C67.0–C67.9 Kidney and renal pelvis 189.0, 189.1 C64.0–C64.9, C65.0–C65.9 Ureter 189.2 C66.0–C66.9 Other urinary organs 189.3–189.4, 189.8–189.9 C68.0–C68.9 Eye and orbit 190.0–190.9 C69.0–C69.9 Brain and other nervous system Brain 191.0–191.9 C71.0–C71.9 Meninges 192.1 C70.0–C70.9 Other nervous systema 192.0, 192.2–192.9 C72.0–C72.9 Endocrine system Thyroid 193 C73 Other endocrine (including 164.0, 194.0–194.9 C37, C74.00–C74.92, thymus) C75.0–C75.9 Lymphomas Hodgkin’s disease 201.0–201.9 C81.0–81.9 Non-Hodgkin’s lymphomas 200.0–200.8, 202.0–202.2, C82.0–C82.9, C83.0–C83.9, 202.8–202.9 C84.0–C84.5, C85.0–C85.9, C96.3 Multiple myeloma 203.0, 238.6 C90.0, C90.2 Leukemias Lymphocytic Acute lymphocytic 204.0 C91.0 Chronic lymphocytic 204.1 C91.1 Other lymphocytic 202.4, 204.2–204.9 C91.2-C91.4, C91.7, C91.9 Myeloid (granulocytic) Acute myeloid 205.0, 207.0, 207.2 C92.0, C92.4–C92.5, C94.0, C94.2 Chronic myeloid 205.1 C92.1 Other myeloid 205.2–205.3, 205.8–205.9 C92.2–C92.3, C92.7, C92.9 Monocytic Acute monocytic 206.0 C93.0 continued

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716 VETERANS AND AGENT ORANGE: UPDATE 2006 TABLE B-2 Continued Cancer Site ICD-9 Codes ICD-10 Codes Chronic monocytic 206.1 C93.1 Other monocytic 206.2–206.9 C93.2, C93.7, C93.9 Other leukemia Other acute 208.0 C94.4, C94.5, C95.0 Other chronic 207.1, 208.1 C94.1, C95.1 Aleukemic, subleukemic, and 203.1, 207.2, 207.8, C90.1, C91.5, C94.3, C94.7, “not otherwise specified” 208.2–208.9 C95.2, C95.7, C95.9 Miscellaneous malignant 159.1, 195.0–195.8, 196.0– C26.1, C76.0–C76.8, neoplasms 196.9, 199.0–199.1, C77.0–C77.9, C78.0–C78.8, 202.3, 202.5–202.6, C79.0–C79.8, C80, 203.8 C88.0–C88.9, C96.0–C96.2, C96.7, C96.9, C97 SOURCE: Adapted from Ries et al. (2003), Table A-4. a Cancers of the peripheral nerves and the autonomic nervous system are classified as “soft tissue” in ICD. REFERENCES Anderson RN, Minino AM, Hoyert DL, Rosenberg HM. 2001. Comparability of cause of death be- tween ICD-9 and ICD-10: preliminary estimates. National Vital Statistics Reports 49(2):1–32. Ries LAG, Eisner MP, Kosary CL, Hankey BF, Miller BA, Clegg L, Mariotto A, Fay MP, Feuer EJ, Edwards BK (eds). 2003. SEER Cancer Statistics Review, 1975–2000, National Cancer Institute. Bethesda, MD. Robinson CF, Schnorr TM, Cassinelli RT, Calvert GM, Steenland K, Gersic CM, Schubauer-Berigan MK. 2006. Tenth revision U.S. mortality rates for use with the NIOSH Life Table Analysis System. Journal of Occupational and Environmental Medicine 48(7):662–667.