[CANCER RESEARCH (SUPPL.) 52, 5432s-5440s, October I, 1992]

Non-Hodgkin's Lymphoma Time Trends: United States and International Data1

Susan S. Devesa2 and Thomas Fears

Epidemiology and Biostalistics Program, Division of Cancer Etiology, National Cancer Institute, Bethesda, Maryland 20892

Abstract

Incidence data from the Surveillance, Epidemiology, and End ResultsProgram of the National Cancer Institute, earlier incidence surveys, andthe International Agency for Research on Cancer, mortality data fromthe National Center for Health Statistics, and population data from theCensus Bureau were used to assess rates of non-Hodgkin's lymphoma.

Mortality and incidence rates have been increasing for many years.Larger increases among older persons suggest a role for improvingdiagnosis, particularly during the 1950s and 1960s. Urban/rural andsocioeconomic differences have diminished over time. Since the early1970s, incidence rates increased at 3-4%/year, more rapidly than for all

other cancers except melanoma of the skin and lung cancer amongwomen. Incidence rates increased over all ages except the very young,among whites and blacks, in geographic areas both in the United Statesand internationally, and both sexes. During the 1980s, the impact ofAIDS is apparent among young and middle-aged men. Differences innon-Hodgkin's lymphoma rates persist between races and sexes. In

creases have been more marked for extranodal disease, particularlythose arising in the brain, and for high-grade tumors. Explanations

accounting for all the increases in rates are not readily available.

More than 37,000 cases of non-Hodgkin's lymphoma will be

diagnosed in the United States during 1991, and almost 19,000deaths will be attributed to this cancer (1). Since the early1970s, based on data from the SEER3 program of the NCI,

incidence rates increased at almost 4%/year among men and3%/year among women, which is more rapidly than for all othercancers except melanoma of the skin and lung cancer amongwomen (2). In spite of some improvements in 5-year relativesurvival rates, currently about 50%, United States mortalityrates are increasing at almost 2%/year.

Based on updated age-adjusted (1970 United States standard) incidence data from four geographic areas in the UnitedStates (Atlanta, Detroit, San Francisco-Oakland, and Connecticut) (3), incidence increased 150% among white men andwomen from the late 1940s to the late 1980s (Fig. 1). Meanwhile, mortality rates in the total United States increased 85-100% among whites, nonwhites, males, and females, with aplateau during the late 1960s through the late 1970s. Thecurves for white males, white females, nonwhite males, andnonwhite females are remarkably parallel, with rates consistently higher among men than women, and whites than non-

whites.Age-specific mortality rates among white men during this

time did not change greatly among those in the middle agegroups 25-54 years (Fig. 2). Rates increased in each age group55 years and older, with the rate of increase larger among eachsuccessively older age group. The rate among men 85 years and

1 Presented at the National Cancer Institute Workshop. "The Emerging Epidemic of Non-Hodgkin's Lymphoma: Current Knowledge Regarding EtiologicalFactors," October 22-23, 1991, Bethesda. MD.

2 To whom requests for reprints should be addressed, at Epidemiology andBiostatistics Program, Division of Cancer Etiology. National Cancer Institute,Executive Plaza North, Room 415, Bethesda, MD 20892.

3 The abbreviations used are: NCI, National Cancer Institute; SEER, Surveillance, Epidemiology, and End Results; AAPC, average annual percentage change;AIDS, acquired immunodeficiency syndrome.

older increased from less than those for ages 65-84 years to

become the highest rate in recent years. Mortality declinedsubstantially during the 1960s and 1970s among young persons.

Fig. 3 presents the same curves as the previous figure but withcohort year of birth on the abscissa. Striking increases are apparent among older persons, i.e., those born prior to the early1900s. Some peaks are suggested among those aged 25-54

years, but they are not consistent by birth cohort.Age-specific mortality curves among white men by decade of

death are presented in Fig. 4. Again, rates hardly changedamong the middle age groups, increased substantially amongthe older age groups, and declined at younger ages. Age-specificmortality patterns among women generally mirror those amongmen (not shown).

Age-specific incidence trends in the four geographic areas are

similar to the mortality trends in that rates increased substantially among the older age groups (Fig. 5/1). An unknown proportion of these increases may be due to improving diagnosis;environmental exposures also may have increased at greaterrates many years ago and subsequently less rapidly. Amongwhite men aged 75 years and older, incidence increased 300-

400% during the entire time. Among those in each age groupolder than 45 years, rates went up at least 2.5%/year. Since theearly 1980s, striking increases occurred among those aged25-44 years and to a lesser extent among those 45-54 years,

most likely related to the AIDS epidemic. Rates among youngerpersons have not changed greatly, suggesting that the substantial declines in mortality reflect improvements in survival.Among women, the patterns were generally similar, with ratesincreasing among older persons and only modestly among middle-aged persons, but without sudden increases in the mid-

1980s (Fig. 5B).Based on United States mortality data by "state economic

area," NCI produced cancer atlases for deaths during 1950-

1980 (4, 5). Rates among white men for the decade 1970-1980generally were low across the south and elevated in the northand midwest. Non-Hodgkin's lymphoma mortality rates among

white men during the period 1950-1980 increased mostly in theeastern half of the country, both north and south. The generalpattern was similar for white women and men, but there waslittle exact geographic correspondence. The atlases present datathrough 1980, whereas the recent mortality increases have beenmostly since the late 1970s. Thus, it will be of interest to evaluate non-Hodgkin's lymphoma mortality patterns during the

1980s.Analysis of 1950-1969 mortality revealed that rates in purely

urban counties were about 40% higher than those in purelyrural areas among both white men and women (6). Urban-rural

gradients diminished from the early 1950s to the early 1970s,because rates increased more rapidly in rural than urban areas(7). These gradients continued through the 1980s (Table 1),with rates 15-25% higher in urban than rural areas. The patterns were similar among men and women, except for a surgeamong men in the most urban category during the last periodshown.

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COce

oCO io

LUCL

SOo"o

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-O- WHITE MALE. INCIDENCE

-O- WHITE MALES. MORTALITY

•¿�NON-WHITE MALES. MORTALITY

-O- WHITE FEMALE, INCIDENCE

-O- WHITE FEMALES. MORTALITY

--•-•NON-WHITE FEMALES,MORTALITY

11945 1950 1955 1960 1965 1970 1975 1980 1985 1990

YEARFig. 1. Trends in age-adjusted (1970 United States standard) non-Hodgkin's

lymphoma incidence rates in four United States geographic areas (Atlanta, Connecticut, Detroit. San Francisco-Oakland), 1947-1950 to 1985-1988. and mortality rates in the total United States, 1950-1954 to 1985-1988. by race and sex.

o

•¿�15-24 •¿�•¿�•••35-44 -O- 55-64 -O- 7564

•¿�25-34 -*«-45-54 -û- 65 74 -O- 85»

1950 1955 1960 1965 1970 1975 1980 1985 1990

YEAR

Fig. 2. Age-specific non-Hodgkin's lymphoma mortality trends among whitemales in the total United States, 1950-1954 to 1985-1988. by year of death (ratesage adjusted within 10-year age groups).

W YEARS -t- 45-54 YEARS

5-14 YEARS 4> 55-64 YEARS

15-24 YEARS -O- 66 74 YEARS

25-34 YEARS * 75-84 YEARS

35-44 YEARS -O- K «YEARS

18601870188018901900191019201930194019501960197019801990

COHORT YEAR OF BIRTH

Fig. 3. Age-specific non-Hodgkin's lymphoma mortality trends among whitemales in the total United States, 1950-1954 to 1985-1988, by cohort year ofbirth.

O 51015 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90

AGE

Fig. 4. Decade-specific non-Hodgkin's lymphoma mortality rates among whitemales in the total United States, 1950-1959 to 1980-1988, by age at death.

Excluding the purely rural counties, the 1950-1969 data alsorevealed non-Hodgkin's lymphoma mortality rates 40-50%

higher in counties with populations having median years ofschooling in the top 10% compared to the lowest 10% (6).Based on 1969-1988 data, non-Hodgkin's lymphoma mortality

rates generally were higher among counties with higher medianeducation within each urban category (Table 2). In the moreurban areas, rates increased more rapidly among counties withlower median education, narrowing the socioeconomic differentials. Similar comments pertain to counties when rankedby percentage below poverty level (Table 3). However, in counties 50-<95% urban, the largest increases occurred in areaswith the fewest persons below poverty level. In Tables 2 and 3,increases ranged from 14.6%, or 1.0%/year, in highly urbanizedcounties with relatively little poverty to 37.2%, or 2.2%/year,in moderately urbanized counties with relatively few years of

schooling. Therefore, some modest socioeconomic differentialsin non-Hodgkin's lymphoma mortality at the county level have

existed, but the patterns have not been regular and rates increased in every category, suggesting that diagnostic or medicalcare differences do not entirely account for the increase in non-Hodgkin's lymphoma during the past two decades.

Other population-based studies have been inconsistent in thesocioeconomic associations observed. Table 4 presents databased on incidence at the census tract level in urban areas included in the 1969-1971 Third National Cancer Survey (8).Tracts with moderate median years of education had low ratesamong white men and women, contrasted with high ratesamong black women; the pattern was positive among blackmen. The association with median family income was somewhat positive among white men but inconsistent for whitewomen, and tracts with moderate median family income hadelevated rates among black men and women.

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100

I -X- <M •¿�••••15-24 •¿�••••35-M -O- 5M4 -u- 75-Õ4

- •¿�••••5-14 •¿�-*--25-34 -*- 45-54 -O- 65-74 -O- 85» —¿�

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1945 1950 1955 1960 1965 1970 1975 1980 1985 1990

YEAR

B

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•¿�•«••5-14 •¿�•*••25J4 -*- 45-54 -O- 65-74 -O- I

1945 1950 1955 1960 1965 1970 1975 1980 1985 1990

YEAR

Fig. 5. Age-specific non-Hodgkin's lymphoma incidence trends among whitesin four geographic areas, 1947-1950 to 1985-1988, by year of diagnosis (rates ageadjusted within 10-year age groups): A, males; /'. females.

By about 1980, based on SEER incidence data from threeareas, an inverse pattern with education was indicated amongwhite women but not white men or blacks (Table 5). The trendwith income was positive among men but not women. There

fore, it appears that factors associated with socioeconomic status have not been playing major roles in the development ordiagnosis of non-Hodgkin's lymphoma, at least in recent years.

Geographic variation and trends in non-Hodgkin's lym

phoma incidence among whites are presented in Table 6. Thenumbers of cases for 1974-1978, shown in the first column,were all substantial except those for Hawaii. The areas areordered by the 1984-1988 rates. Among men, rates were highest in San Francisco, where the largest absolute increase, overallrelative change, and annual relative change occurred. Rates inthe other SEER areas generally increased almost 50%, or 3%/year. Exceptions include Atlanta and Hawaii, where the initialrates were relatively high. If one excludes New Mexico, wherethe inclusion of Hispanics has lowered the rate, the recent rangein rates was from about 14 to 17/100,000. Overall, non-Hodgkin's lymphoma incidence among white men increased

47%, or 2.8%/year, from the mid-1970s to the mid-1980s. Ifone excludes the data for San Francisco, where the impact ofAIDS-related non-Hodgkin's lymphoma most likely is the

greatest, rates still increased 43%, or 2.6%/year.Among women, rates in 1984-1988 were high in Detroit and

Connecticut, where they had increased >2%/year. The largeapparent increase in Atlanta was due to a relatively low rate inearlier years. Rates were somewhat lower in New Mexico, Hawaii, and Utah; excluding these three areas, the range in rateswas fairly narrow: from 11.1 to 11.9/100,000. Overall, ratesincreased 32%, or about 2%/year.

Although trend data among most minority groups generallyare not available, there is racial/ethnic variation in non-Hodgkin's lymphoma incidence within the SEER program,

which is shown in Table 7 for 1977-1983 (9). The groups arelisted in descending order of rate ratios relative to geographically comparable whites. Rates among all minority groups wereless than those for whites. Among men, rates among Hawaiiansand Chinese were 80% those of whites; Filipinos, blacks, andHispanics were about 70%; Puerto Rican and American Indianrates were <50%. Patterns among women were generally similar, and the ranking was virtually the same. Explanations forthese racial/ethnic variations are not known.

Internationally, non-Hodgkin's lymphoma incidence has var

ied 8-to 10-fold around the world (10-12). However, some ofthe low rates were from small registries with relatively few

Table 1 Non-Hodgkin's lymphoma mortality trends among United States whites by 1970 county-level percentage urban population

%urbanMales0

(rural)>0-<5050-<7575-<95>95

urbanTotalUrban/rural

x100Females0

(rural)>0-<5050-<7575-<95>95

urbanTotalUrban/rural

x 100Deaths

(1969-1973)1,1195,1395,0287.0076,23624,5298484,0834,2696,1035,56020,8631969-19735.35.65.86.06.66.01253.63.74.04.14.44.0122Ral1974-19785.35.75.96.16.46.01213.63.94.04.24.44.1122es"1979-19835.96.36.36.66.86.41154.14.44.44.54.74.51151984-19886.57.07.07.58.07.31234.54.95.05.05.25.0116%change22.625.020.725.021.221.725.032.425.022.018.225.0AAPC.5.6.4.6.41.41.82.01.71.41.21.5

' Per 10,000 person-years, age adjusted using 1970 United States standard.

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Table 2 Non-Hodgkin's lymphoma mortality trends among United States whites living in counties at least 50% urban in 1970 by degree urban and median years of

schooling

Rates"

Deaths (1969-1973) 1969-1973 1974-1978 1979-1983 1984-1988 % change AAPC

Median yr of schooling among counties 50-<75%urban<12.012.0-12.3>12.4Median

yr of schooling among counties 75-<95%urban<12.012.0-12.3>I2.4Median

yr of schooling among counties >95%urban<12.012.0-12.3>12.4214364576971256919526593022691918554.64.94.64.35.05.15.25.45.64.74.95.24.65.15.35.15.25.65.15.35.25.45.45.45.65.65.95.75.96.15.96.16.16.86.26.723.920.432.637.222.019.630.814.819.61.61.41.82.21.41.21.81.11.3

" Per 100.000 person-years, age adjusted using 1970 United States standard.

Table 3 Non-Hodgkin 's lymphoma mortality trends among United Slates whites living in counties at least 50% urban in 1970 by degree urban and percentage below

poverty level

Rates"

Deaths (1969-1973) 1969-1973 1974-1978 1979-1983 1984-1988 % change AAPC

% below poverty level among counties 50-75%urban>8.05.0-7.9<5.0%

below poverty level among counties 75-<95%urban>8.05.0-7.9<5.0%

below poverty level among counties a95%urban>8.05.0-7.9<5.0"

Per 100.000 person-years, age adjusted using 1970 United439936221276230363784429312744844185Statesstandard.4.64.94.94.65.04.95.35.25.54.75.05.04.75.15.15.25.35.25.05.45.75.25.35.65.45.75.75.76.06.25.66.16.36.66.46.323.922.426.521.722.028.624.523.114.61.41.51.71.41.41.71.41.41.0

Table 4 Socioeconomic variation" in non-Hodgkin 's lymphoma incidence inmetropolitan areas of the Third National Cancer Survey. 1969-1971

Whites Blacks

Males Females Males Females

MedianeducationLow234HighMedian

familyincomeLow234High0.900.840.770.901.000.750.860.870.831.001.091.070.911.021.001.001.030.991.091.000.930.991.000.821.201.000.921.231.001.441.471.00

1Rate ratios using the rate for the highest Socioeconomic status group as referent.

cases. Based on data from about 20 registries with adequatenumbers of cases, the rates varied 4-to 6-fold around 1970,decreasing to 3-to 4.4-fold around 1980. Fig. 6 presents rates,age adjusted to the world standard, from the three most recentvolumes of Cancer Incidence in Five Continents and the UnitedStates four geographic areas for around 1970, 1975, and 1980.All are shown on the same log scale 1:10, so the absolute magnitude of the rates as well as the secular trends are comparable.The highest rate in the world in recent years among men wasamong United States whites in the four geographic areas (Fig.

Table 5 Socioeconomic variation in non-Hodgkin 's lymphoma incidence" in SanFrancisco, Atlanta, and Detroit, 1978-1982

Source: J. W. Horm, personal communication.

WhitesMedian

education(vr)<121213+Median

family income($)<15,00015,000-24,999>25,000Males12.912.713.211.712.613.2Females11.19.89.59.910.09.8BlacksMales8.89.38.68.89.39.5Females5.45.27.15.45.05.6

" Rates per 100,000 person-years, age adjusted using 1970 United States standard.

6/1). Incidence among United States blacks was somewhatlower but increasing as rapidly. Rates in three of the Canadianprovinces also increased, converging over time, and were intermediate between those for United States whites and blacks.Rates in the United Kingdom and New Zealand were somewhatlower, increasing as rapidly in Oxford as in North America butless rapidly in Birmingham and New Zealand. In Europe, incidence in Denmark, Finland, Norway, and Sweden has beenfairly similar to that in the United Kingdom, with predominantly upward trends. Rates in Hamburg, Germany, and Warsaw, Poland, were lower and have not increased greatly. Ratesamong Jews in Israel were the highest in the past and increasedonly modestly, while increases among Jews born in Israel have

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Table 6 Geographic variation in non-Hodgkin's lymphoma incidence among whiles, SEER program, 1974-1978 lo 1984-I988

MalesSanFranciscoSeattleDetroitIowaConnecticutAtlantaUtahHawaiiNew

MexicoTotalTotal

excluding SanFranciscoFemalesDetroitConnecticutSan

FranciscoAtlantaIowaSeattleUtahHawaiiNew

MexicoTotalTotal

excluding San FranciscoCases

(1974-1978)806612836818712204227622014478367277475572317583556521536197427535521974-197813.011.611.411.410.312.09.812.19.111.311.08.58.38.97.58.98.78.07.57.78.58.4Rates"1979-198313.513.513.714.113.111.912.012.110.713.213.110.19.710.28.910.39.79.07.48.09.79.7%

change1984-198821.517.316.716.315.215.114.613.911.216.615.711.911.611.511.411.211.110.19.68.811.211.1Absolute

change8.55.75.34.94.93.14.81.82.15.34.73.43.32.63.92.32.42.12.11.12.72.7Total65494643482649152347434040295226282628143232Peryr3.72.92.82.62.81.72.91.01.52.82.62.42.41.83.11.61.71.71.80.91.92.0

' Per 100.000 person-years, age adjusted using 1970 United States standard.

Table 7 Racial/ethnic variation in non-Hodgkin 's lymphoma incidence,SEER program, 1977-1983

Source: J. W. Horrn et al. (9).

Table 8 Percentage of non-Hodgkin's lymphoma cases withmicroscopic confirmation of the diagnosis, SEER, 1974-1988

Minoritygroup"MalesHawaiiansChineseFilipinosBlacksHispanicsJapanesePuerto

RicansAmericanIndiansFemalesHawaiiansFilipinosChineseBlacksJapaneseHispanicsPuerto

RicansAmericanIndiansNo.357575419909456414243750363856747816Rate10.410.39.38.77.88.56.02.66.67.06.86.06.25.64.83.2Rate

ratio* x10085797267676546228574727065635636

" Data are for blacks in Atlanta, Detroit, San Francisco, Connecticut; for Chinese, Japanese, and Filipinos in San Francisco and Hawaii; Hispanics and American Indians in New Mexico; Puerto Ricans in Puerto Rico; and Hawaiians inHawaii.

* Relative to geographically comparable whites.

been more marked. Although incidence was consistently lowerin Bombay, Japan, and Chinese in Singapore, the rates of increase were similar to those in North America and Scandinavia.Rates in South America were intermediate between those inAsia and Israel or North America, with generally increasingtrends. Overall, incidence appears to be increasing across virtually all registries, although the rates of increase vary. In noregistry were consistent declines suggested.

Among women, incidence generally increased across all registries except Hamburg, Germany; Warsaw, Poland; all Jews inIsrael; and Cali, Colombia (Fig. 6B). Within North America,rates for whites were the highest and those among blacks the

Race,sexWhitemalesWhitefemalesBlackmalesBlack

femalesAmong

white males(yr)0-1415-3435-5455-74S751974-197898.297.797.497.798.698.599.298.596.21979-198398.497.698.097.7100.097.799.298.896.71984-198897.997.997.596.099.298.198.098.696.1

lowest, with intermediate rates in Canada. Although the incidence was lower than among men, the international patternswere generally similar.

In the United States, the proportion of lymphoma cases reported only via a death certificate declined from about 10%around 1950 to 1.6% in 1970 and <1% thereafter (13-15).About 83% of the non-Hodgkin's lymphoma cases had micro

scopic confirmation of the diagnosis in the early years, whichincreased to 95% by 1970. These figures suggest improvementover time in case identification, accuracy of diagnosis, and completeness of registration.

During the SEER program in 1974-1988, 96% or more ofnon-Hodgkin's lymphoma cases were microscopically con

firmed, with little variation over time, by sex or by race (Table8). Virtually all cases younger than age 75 years, shown here forwhite men, had confirmation rates of at least 98%, but ratesdeclined to 96% among those aged 75 years and older. Therewas little change over time, and the patterns were consistentacross all SEER geographic areas.

Focusing on recent incidence among whites, Table 9 compares the trends for non-Hodgkin's lymphoma with those forHodgkin's disease, multiple myeloma, and lymphocytic leuke-mias. Non-Hodgkin's lymphoma incidence increased 5.3 and

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NON-HODGKIN'S LYMPHOMA TIME TRENDS

Table 9 Comparison of incidence trends for non-Hodgkin's lymphoma, Hodgkin's disease, and lymphocytic leukemias, SEER program, 1974-1978 to 1984-1988

Rates"Cases

(1974- 1978) 1974-1978 1979-1983 1984-1988 AbsolutechangeWhite

malesNon-Hodgkin's lymphoma 4478 11.3 13.2 16.6 5.3Hodgkin's disease 1544 3.5 3.5 3.5 0.0

Multiple myeloma 1764 4.6 4.5 4.7 0.1Lymphocytic leukemia 2525 6.6 6.4 6.1 -0.5

Acute 575 1.5 1.6 1.8 0.3Chronic 1853 4.9 4.7 4.2-0.7White

femalesNon-Hodgkin's lymphoma 4275 8.5 9.7 11.2 2.7Hodgkin's disease 1220 2.6 2.5 2.6 0.0

Multiple myeloma 1604 3.1 3.1 3.2 0.1Lymphocytic leukemia 1846 3.7 3.6 3.3 -0.4

Acute 403 1.0 1.2 1.2 0.2Chronic 1362 2.6 2.3 2.0-0.6"

Per 100,000 person-years, age adjusted using 1970 United Statesstandard.RACE-WHITE

RACE-BIACKA«H» -1 400-1-

.si*^*^^ i.v-r'* - °"io°-*« ,1^^^ a..-i>--*- * «itf^&£

...ÃŽ--Ç-̂ C -, r Olii—•¿�—'—¿�"*~*~rTt ...l-r*-^%..,.-9* ?:-*rí?

?gX1W1-VEAR

YEARF

g. 7. Annual race- and sex-specific age-adjusted (1970 United States standard) non-Hodgkin's lymphoma incidence rates in the nine SEER areas, 1973-1988, and fitted regression lines. (Data not available for Atlanta 1973-1974 orSeattle 1975). Symbols, observed age-adjusted rates; lines, fitted values.1

;

2.7/100,000 among men and women, respectively. RatesforHodgkin'sdisease did not change, those for multiple myeloma 0.4

increased minimally, and those for lymphocytic leukemia declined slightly, due to decreases in the chronic form. Patternsamong blacks were very similar. Increases in non-Hodgkin's B

lymphoma, therefore, are not explainable by changing categorization of these diseases.

Fig. 7 presents the annual age-adjusted (1970 United Statesstandard) incidence rates in the nine SEER areas from 1973- 100-1988 by race and sex, along with regression lines fitted using thelog of the rates weighted by the number of cases. Rates increased 3-4%/year in each of the race/sex groups. The 3.8%rate of increase among white men was significantly greater than -the 2.8%/year increase among white women; the difference §among blacks was not significant. 2 10

Fig. SA presents the trends among whites by age group. In- <creases in all age groups were significant, and among both menand women were about 4%/year among the oldest and about3%/year among those aged 55-74 years. Among those aged15-54 years, increases of 2%/year among women contrastedwith 5%/year among men. Notice the change in slope during 1

the early 1980s among men younger than age 55 years, suggesting that two separate lines should be fitted. If a change in 0Aslope is assumed after 1982 (16), rates among men aged 15-34and 35-54 years increased at 1.5 and 3.7%/year prior to 1983,respectively, and at 8-10%/year thereafter. Fig.8.

The same age-specific trends, but excluding San Francisco fi,â„¢^â„¢

from the calculations, are presented in Fig. SB. Increases in all observedaMALE•*•**''"*

KjJOt)m-mm"

..-mr'•---"

•¿�»

;1

1 1 i l l 1 12 74 76 78 80 82 84 86 88 7

YEARMALE„w----**"r*0.0-00"°

°FEMALEAGE

GROUP•

275O 55-74•¿�35-54D15-34OO

O2

74 76 78 80 82 84 86 88YEARFEMALE

AGEGROUP•

275O 55-74•¿�3554D15-3472

74 76 78 80 82 84 86 88 72 74 76 78 80 82 84 86 88

YEARYEAR\nnualage-specific (age adjusted within age group) non-Hodgkin's

incidence rates among whites older than age 14 years, 1973-1 988, andssion lines: A, nine SEER areas; //. excluding San Francisco. Symbols,ge-specific rates; lines, fitted values.

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Table 10 Nodal versus extranodal site of non-Hodgkin's lymphoma Incidence, SEER program, 1974-1978 to 1984-1988

WhitemalesNodalExtranodalWhite

femalesNodalExtranodalBlack

malesNodalExtranodalBlack

femalesNodalExtranodalCases

(1974-1978)3521957339388218747150271974-19788.92.46.81.75.61.43.80.6Rates"1979-198310.52.77.81.96.72.64.91.5%

change1984-198812.54.18.62.67.62.95.21.7Absolute

change3.61.71.80.92.01.51.41.1Total407126533610737183Peryr2.53.71.73.02.25.02.26.9

1Per 100,000 person-years, age adjusted using 1970 United States standard.

Table 11 Trends in extranodal non-Hodgkin's lymphomas by site of origin, SEER program, 1974-1978 to 1984-1988

Rates" Change

StomachSkinBrain

and other nervoussystemSmallintestineColon

andrectumOral»Soft

tissueEyeThyroidSalivary

glandsLungAll

sitesCases

(1984-1988)69961236731418414914013213011911136401974-19780.410.330.090.180.100.080.080.050.070.060.071.981979-19830.420.490.150.200.090.090.090.060.100.070.082.251984-19880.610.550.310.280.160.120.120.120.120.100.103.20Absolute0.200.220.220.100.060.040.040.070.050.040.031.22%49672445660505014071674362

" Per 100,000 person-years, age adjusted using 1970 United States standard.'•Excludes lip, salivary glands, nasopharynx.

Table 12 Variation in non-Hodgkin's lymphoma incidence trends, SEER program, 1978-1981 to 1986-1988

Rates" % change

NodularDiffuseOtherTotalCases

(1978-1981)1959

690629491591978-19812.3

7.90.310.51982-19852.5

9.10.412.01986-19882.6

10.30.513.4Absolute

change0.3

2.40.22.9Total1330 6728Per

yr1.93.6

5.23.4

" Per 100,000 person-years, age adjusted using 1970 United States standard.

Table 13 Variation in non-Hodgkin's lymphoma incidence trends by working formulation, SEER program, 1978-1981 to ¡986-1988

Rates"

" Per 100,000 person-years, age adjusted using 1970 United States standard.'' Small cleaved and large cell.

% change

Cases (1978-1981)Low

gradeA:small,lymphocyticB:follicular, smallcleavedC:follicular,mixed*IntermediateD:

follicular, largecellE:diffuse, smallcleavedF:diffuse,mixedG:diffuse, largecellHigh

gradeH:large cell,immunoblasticI:

lymphoblasticJ:small noncleaved;Burkitt'sUnclassifiedTotal2398859113940046261691506564238744716875204168891591978-19812.81.01.30.55.30.21.70.62.70.50.20.10.21.910.51982-19853.11.11.40.65.60.31.20.93.21.10.60.20.42.112.01986-19883.41.31.30.76.10.40.90.94.01.60.80.20.62.313.4Absolute

change0.60.30.00.20.80.2-0.80.31.31.10.60.10.40.42.9Total213004015100-4750482203001002002128Peryr2.84.0—6.32.08.3-8.24.45.214.818.112.211.62.63.4

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NON-HODGKIN'S LYMPHOMA TIME TRENDS

age groups were still significant and were similar to those seenon the previous figure except among men 15-54 years of age,for whom rates increased at 4% rather than 5%/year, due to lessrapid increases during the 1980s. Within each age group, theslope was steeper among men than women.

The majority of non-Hodgkin's lymphomas arise in lymph

nodes, but extranodal cases do occur, shown by race and sex inTable 10. Whereas the absolute increases in nodal disease exceeded those of extranodal origin, the proportional increaseswere greater for the extranodal cases. Rates increased 1.7-2.5%/year for nodal cases, compared to 3.0-6.9%/year for extra-nodal cases.

Table 11 presents the trends in extranodal cases by site oforigin. Shown are those sites with >100 cases among all racesand sexes combined during the recent period 1984-1988, listedin descending order. These sites accounted for about 81% of allextranodal cases. The most frequent sites were stomach andskin. The largest increases were for those arising in the brainand other areas of the nervous system, with acceleration overtime in that rates increased 50% during the first period shownand 100% during the last. Increases in the skin and many othersites were more uniform over time, whereas most of the increaseoccurred in recent years for those of the stomach, intestines,and eye.

Since the late 1970s when use of the International Classification of Diseases (17) commenced, we can consider severalother variables. More than 75% of all non-Hodgkin's lym-

phoma were diffuse and about 21% were nodular (Table 12).Rates increased in each group, with the largest absolute increasein the diffuse type, which also showed larger proportional increases than the nodular type.

The patterns of non-Hodgkin's lymphoma by the workingformulation (18) are shown in Table 13. Most non-Hodgkin's

lymphomas were of intermediate grade, followed by low grade,with relatively few high grade, which includes those associatedwith AIDS. The most frequent type was the intermediate-gradediffuse large cell, accounting for 30% of all non-Hodgkin's

lymphoma during the late 1980s and increasing about 5%/yearduring the time shown. The largest proportional increases werein high-grade tumors, with the immunoblastic type increasingabout 18%/year. Rates increased for most low and intermediatetypes, except low-grade follicular small cleaved cell and intermediate-grade diffuse small cleaved cell, the latter decliningalmost 50%.

In summary, mortality and incidence rates for non-Hodgkin's

lymphoma have been increasing for many years. Part of theincreases, particularly in the 1950s and 1960s, were due tochanges in rates primarily among older persons, suggesting arole for improving diagnosis. Urban/rural and socioeconomicdifferences have diminished over time. Since 1970, incidence

rates have increased over all ages except the very young, allraces, geographic areas both in the United States and internationally, and both sexes. Differences in rates persist, however,between races and sexes. Increases have been more marked forextranodal disease, particularly those arising in the brain, andfor high-grade tumors.

Acknowledgments

We thank Scott Gaetjen and Kathy Robinson of Information Management Services, Inc., for computer and graphics support.

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