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Childhood Cancer Registry of the Province of Torino, Italy Survival, Incidence, and Mortality Over 20 Years Maria Luisa Mosso, MD, Renata Colombo, MD, Livia Giordano, MD, Guido Pastore, MD, Benedetto Terracini, MD, and Corrado Magnani, M D
Incident childhood cancers in the Province of Torino, Italy (populationaged 0 to 14 years averaging 0.5 million) have been registered since 1967. Four population-based exhaustive surveys have been done to collect cases diagnosed during the periods 1967 to 1969,1970 to 1975,1976 to 1981, and 1982 to 1986. For each registered child, vital status on June 30,1988 was assessed. This article reports incidence, mortality, and survival rates over a 20-year period. A statistically significant trend toward an increased incidence of soft tissue sarcomas was identified. Statistically insignificant trends included an increased incidence of brain tumors (probably reflecting improved diagnostic procedures) and a decreased incidence of thyroid tumors. Incidence rates of leukemias in the first year of life tended to decrease. As expected, survival rates of some childhood cancers dramatically improved throughout the 2O-year period this occurred in leukemias, brain tumors, soft tissue sarcomas, and renal tumors. Survival rates are compared with observations in comparable population-based series. Cancer 1992; 69:1300-1306.
The population-based Registry of Childhood Cancer of the Province of Torino (Registro Tumori Infantili della Provincia di Torino, RTIPT) was begun in 1967. At the From the Service of Cancer Epidemiology, University of ToMo and Local Health Unit Torino 8, Torino, Italy. The Childhood Cancer Registry was supported by the Italian National Research Council (Progetto Finalizzato Oncologia, grants 84.00722.44, 85.02221.44, 86.00677.44, 87.01547.44, and 88.00727.44); Associazione Italiana per la Ricerca sul Cancro, Milano; and Sezione Provinciale di Torino della Lega Italiana per la Lotta contro i Tumori, Torino, Italy. Computer facilities provided in part by CSI Piemonte, Torino, Italy. The authors thank Ms. Rita Giacometti for secretarialhelp at the Registry, the heads of the hospital units where cases were sought, and their medical and nonmedical co-workers. Address for reprints: Benedetto Terracini, MD, Servizio di Epidemiologia dei Tumori, Ente Convenzionato Universit; di Torino, USL Torino 8, via Santena 7, 10126 Torino, Italy. Accepted for publication June 1, 1991.
1981 National Census, the total population of the province was 2,345,771; those 0 to 14 years of age were 19% of this number. Nearly 80% lived in the metropolitan area of Torino. In 1976, registration was extended to the other provinces of Piemonte. However, our report is limited to the Province of Torino, where registration currently includes a 20-year period. The incidence and mortality rates and survival patterns up to 1981 were reported previously.' We describe incidence and mortality data up to 1986 and cumulative survival probabilities updated to June 1988.
Materials and Methods At intervals, the RTIPT staff actively does a retrospective survey of files of clinical records of children (age, 0 to 14 years) hospitalized in pediatric units and in the major departments of medicine, hematology, and neurosurgery operating in the Piemonte region and in five Italian outstanding centers located outside the region (Istituto Nazionale Tumori and Istituto Neurologico C. Besta in Milano, Istituto Giannina Gaslini in Genova, and University Servicesof Paediatricsin Milano-Monza and Pavia). In some hospitals of the region with a pediatric unit, the files of the services of pathology and radiation therapy also are surveyed. The registry is notified of bone cancers in children living in Piemonte histologically diagnosed in the Istituto Ortopedico Rizzoli in Bologna by its pathology service. On the occasion of the most recent surveys, the Institute Gustave-Roussy of Villejuif (France) and the Cancer Registry of Geneva (Switzerland)provided the list of children living in Piemonte included in their files. Finally, the RTIPT files were cross checked with those of hospital discharges in Piemonte and Lombardia and with the file of residents (of any age) in Piemonte dying of cancer kept by the regional cancer registry. Four retrospective surveys
Childhood Cancer Registry in Torino/Mosso et al.
1301
have been done, collecting cases diagnosed during the periods 1967 to 1979,1970 to 1975,1976 to 1981, and 1982 to 1986. In addition to all cancers (International Classification of Diseases, Ninth Revision, categories 140 to 208), the RTIPT records angiomas of the central nervous system (CNS), but histiocytosis X is not recorded. Data collection procedures were reported elsewhere.' Individual records include identification data (name, surname, date of birth, and town of residence) and cancer type, date of diagnosis, diagnostic procedures, and some major clinical information. "DCO' cases, ix., those identified only through the report of a malignant neoplasm as the leading cause of death on the death certificate (3.6% during 1967 to 1969, decreasing progressively to 0.0% in 1982 to 1986) were considered as diagnosed on the date of death. Cases registered under the same surname and name were reviewed manually, and double cancers were accepted only if both cancers were verified histologically. Cancer cases were coded both with an ad hoc code originally developed by the RTIPT and according to standard International Classificationof Diseases for Oncology morphologic and topographic codes.' A case was considered to be histologically verified when a histologic report was identified during the registration procedures. In the computation of histologically verified cases, bone marrow aspiration cytology for leukemia was considered equivalent to histologic confirmation.
For each child registered since 1967, vital status on June 30, 1988 was assessed through the Anagrafe (the Italian equivalent to Registrars of Births, Marriages, and Deaths in the United Kingdom) of the town of residence. The rates were computed on the basis of the age (1-year age classes) structure of the population during the 1971 and 1981 census and between-census estimates provided since 1972 by the Istituto per le Ricerche Economiche e Sociali of the Piemonte region. All rates in this report are annual per million; the 1971population of the province was used as standard for age adjustment (using four age classes: 0 , l to 4,5 to 9, and 10 to 14 years). Survival analyses were done with the KaplanMeier3 method, and the statistical significance of the differences between survival curves was assessed using the long-rank test.4 Time-related differences in incidence and mortality rates were analyzed with the chisquare test for trend with one degree of freedom. Results
During 1967 to 1986, 1321 cases of childhood cancers were recorded, corresponding to an annual rate of 144.3 per million children. Table 1 reports incidence rates by tumor type, age, sex ratios, and proportion of cases for which a histologic confirmation was available. Among cases diagnosed in 1982 to 1986, there was his-
Table 1. Incidence Rates (Annual per Million) of Childhood Cancer in the Province of Torino (1967-86) by Age, Male to Female Ratio, Percentage of Cases Histologically Verified, and Absolute Number of Cases Age-specific rates (yr) 0
Leukemias (all types) ALL ANLL Others and unspecified CNS neoplasms Neuroblastoma Hodgkin's lymphoma Non-Hodgkin's lymphoma Soft tissue sarcomas Bone sarcomas Renal tumors Retinoblastoma Thyroid tumors Others All cancers No. of patients
1-4
5-9
10-14
47.1 16.3 7.3 23.6 23.6 36.3 3.6 1.8 18.1 3.6 23.6 14.5 0.0 32.7 204.9
77.0 56.3 5.9 14.8 32.1 22.0 2.5 5.9 9.7 0.8 19.0 7.8 0.0 11.0 187.8
42.4 26.0 5.6 10.8 33.7 4.3 5.9 11.8 8.0 6.8 2.2 0.9 1.2 9.0 126.2
26.2 15.1 4.6 6.5 29.2 2.2 11.2 7.1 5.2 15.1 0.6 0.0 2.8 10.1 109.6
113
444
408
356
Male to female ratio
0-14*
47.8 30.3 5.9 11.6 31.2 11.0 6.3 8.0 8.4 7.3 8.0
3.5 1.3 11.6 144.3
1.2 1.3 1.2 1.0 1.2 1.5 1.6 3.3 1.4 0.9 0.8 1.0 0.8 1.o 1.2
1321
HV: histologic verification; ALL acute lymphocytic leukemia; ANLL acute nonlyrnphocytic leukemia; CNS: central nervous system. * Age-standardized on the age structure of the population of the province in 1971.
HV /%) 97
71 94 98 93 96 91 90 72 92 82 88
No. of cases
430 275 51 104 293 93 63 76 76 75 67 29 13 106 1321
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CANCER March 1,1992, Volume 69, No. 5
Table 2. Incidence Rates of Childhood Cancer in the Province of Torino (1967-86) by Period of Diagnosis 1967-69
Rate Leukemias (all types) ALL ANLL Others and unspecified CNS neoplasms Neuroblastoma Hodgkin’s lymphoma Non-Hodgkin’s lymphoma Soft tissue sarcomas Bone sarcomas Renal tumors Retinoblastoma Thyroid tumors Others Unspecified Total
46.9 8.0 0.0 38.9 27.5 14.7 6.0 7.4 6.7 6.0 8.7 5.4 2.7 11.4 6.0 149.5
1970-75
(No. of cases) (70) (12) (0) (58) (41) (22) (9) (11)
Rate
1976-81
(No. of cases)
1982-86
(No. of cases)
Rate
(No. of
Rate
cases) (83) (69) (12) (2) (66) (20) (11) (15) (19) (20) (17) (2) (1) (15) (0) (269)
(146) (93) (19) (34) (91) (23) (20) (21) (21) (21) (16) (8) (4) (31) (6)
46.8 37.0 6.5 3.4 32.4 11.5 7.1 9.7 9.5 7.4 8.4 4.8 1.2 9.3 0.8
(131) (101)
(9) (13) (8) (4) (17) (9)
48.3 30.9 6.2 11.1 29.8 7.7 6.5 6.9 6.9 6.8 5.4 2.7 1.3 10.2 2.0
(11) (4) (26) (2)
47.5 39.3 7.5 0.7 34.5 13.1 4.6 6.9 11.0 8.4 11.4 1.4 0.4 7.9 0.0
(223)
134.3
(408)
149.1
(421)
147.2
(10)
(20)
(10) (95) (28) (23) (29) (26) (25) (21)
ALL acute lymphocytic leukemia; ANLL acute nonlymphocytic leukemia; CNS central nervous system. Rates are annual per million, age-standardized on the structure of the population of the province in 1971.
tologic c o n h a t i o n in 100% of cases for leukemias, 82% for CNS neoplasms, and 97% for other tumors. Time-trendsin incidence are shown in Table 2. This reports rates during the periods covered by each of the four surveys done over the 20-year period. Only the trend toward an increased incidence of soft tissue sarcomas was statistically significant (chi-square, 9.01). During 1982 to 1986, the rate for CNS neoplasms was increased 25% over that estimated during 1967to 1969, but the trend was not statistically significant (chisquare, 1.48). Additional (not tabulated) trend analyses were limited to the first year of life. In this age group, there was a statistically significant (chi-squarefor trend, 7.80) monotonic decrease of leukemias; the rates in the four periods were 86.9, 58.1, 27.4, and 10.5, respectively, based on 9, 12,4, and 1cases, respectively. Only two of these cases were ”DCO,” and in none was the presence of Down syndrome reported. Corresponding rates for CNS tumors and soft tissue sarcomas were 19.3, 9.7, 34.2, and 42.0 (based on two, two, five, and four cases) and 19.3, 4.8, 13.7 and 52.4 (based on two, one, two, and five cases), respectively. These trends were not statistically significant. Up to 1976, leukemia typing was not always done, and its registration was unsatisfactory. The 187 cases recorded during the subsequent 10 years included 153 of acute lymphatic leukemia (47% not otherwise specified, 7% specified as acute lymphatic leukemia of T-cell origin, and 46% as non-T-cell non-B-cell), and 27 of nonlymphatic acute leukemias ( i e . , 12 M1 to M2,3 pro-
myelocytic M3, 4 myelomonocytic M4, 3 monocytic M5, and 5 nonlymphatic leukemias with no further specification). Of the remaining seven cases, four were myelocytic leukemias, and three were recorded as ”acute leukemias.” Tables 3, 4, and 5 report respectively the distribution of histologic types of neoplasms of the CNS, soft tissue sarcomas, and ”other” cancers. As expected, carcinomas were rare. One of the two liver adenocarci-
Table 3. Distribution of Neoplasms of the Central Nervous System by Subtype, Male to Female Ratio, Percentage of Cases With Histologic Verification, and Incidence Rates (Age-Standardized,Annual per Million) Male to female ratio
HV (%)
Rate
56 80 14 16 21 26 80
1.8 1.6 0.6 1.2 0.9 0.8 1.0
98 99 100 100 71 85 8
6.0 8.6 1.5 1.7 2.1 2.8 8.4
293
1.2
71
31.2
No. of cases Medulloblastomas Astrocytomas Ependymomas Craniopharyngiomas Hemangiomas* Otherst Not otherwise specified Total
HV: histologic verification. * Nineteen benign angiomas, one hemangiopericytoma, and one hemangioblastoma. t Reported as follows: 15 gliomas, 2 neurinomas, 2 pinealomas, 1 pituitary adenoma, 1 chordoma, 3 meningiomas, 1 cerebral ganglioneuroma, and 1neuroeuhithelioma.
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Childhood Cancer Registry in Torino/Mosso et al. Table 4. Distribution of Histologic Diagnoses of Soft Tissue Sarcomas Rhabdomyosarcoma Fibrosarcoma Liposarcoma Leiomyosarcoma Synovial sarcoma Chondrosarcoma Malignant mesenchymoma Malignant schwannoma Myxosarcoma Hemangiopericytoma Soft tissue sarcoma, no further specification Histologic report untraced Total
34 13 9 3 2
2 1 1 1 1 6 3 76
nomas occurred in a child previously diagnosed as having a neuroblastoma. Among bone cancers, 62% and 34% were specified respectively as osteosarcomas and Ewing’s sarcomas. All renal tumors were reported as Wilms’ tumor (two were specified as bilateral) except for two diagnosed as dear cell cancers. Among the 29 retinoblastomas recorded over the entire period, only 6 were identified as bilateral. However, this is an underestimate because no systematic effort was made to identify metachronous bilateral retinoblastomas. During 1967 to 1986, a total of 731 deaths from cancer in patients aged 0 to 14 years were recorded (these included cases diagnosed before 1967).Mortality rates by period of death are reported in Table 6. The trend was statistically significant (P < 0.01) for leukeTable 5. Distribution of Cases Included Under Others in Tables 1 and 2 by Histologic Diagnosis Primary liver tumor Malignant reticulohistiocytosis Ovarian tumor Extragonadal immature teratoma Yolk sac tumors Testicular tumor Melanoma Nasopharyngeal undifferentiated carcinoma Pheochromocytoma Thymoma Adrenocortical tumor Adenocarcinoma in the liver, no further specification Others, with histologic diagnosis Histologic report untraced Total
12 10 10 10 7 6 6 6 2 2 2 2 9’ 22 106
* One each of the following: carcinoid of the appendix, chorionepithelioma, adenocarcinoma of the colon, basalioma of the skin, adenocarcinoma of the pancreas, adenocarcinoma of the salivary glands, dermoid, undifferentiated carcinoma in lymph node, undifferentiated carcinoma in the connective tissue of the abdomen.
Table 6. Mortality Rates of Childhood Cancer in the Province of Torino (1967-86)
Leukemias (all types) ALL ANLL Others and unspecified CNS neoplasms Neuroblastoma Hodgkin’s lymphoma Non-Hodgkin‘s lymphoma Soft tissue sarcomas Bone sarcomas Renal tumors Retinoblastoma Others and unspecified Total No. of uatients
1967-69
1970-75
1976-81
1982-86
33.5 2.7 0.0 30.8 19.4 8.0 1.3 4.0 2.7 4.0 4.7 0.0 6.0 83.8 125
36.4 17.7 4.9 13.8 17.9 8.6 2.3 4.6 4.2 4.5 3.4 1.3 6.6 89.9 274
24.4 16.4 4.0 3.9 17.8 8.0 1.2 5.6 2.9 3.8 2.2 0.8 8.0 74.7 215
21.1 15.7 4.7 0.7 13.1 5.9 0.9 4.7 5.4 2.9 2.3 1.4 2.9 60.8 117
~
ALL acute lymphocytic leukemia; ANLL acute nonlymphocytic leukemia; CNS: central nervous system. Rates are annual per million, age-standardized on the structureof the population of the province in 1971.
mias considered as a whole, CNS neoplasms, and all tumors. Finally, Table 7 reports cumulative survival at 3 and 5 years after diagnosis, over six 3-year periods of diagnosis. Survival for leukemias and CNS neoplasms is described in greater detail in Figures 1 and 2. In the log-rank test, differences were significant for both leukemias (chi-square, 80.27; df, 3; P < 0.0001) and CNS neoplasms (chi-square, 16.98; df, 3 df; P < 0.001). Discussion
Over 20 years, the RTIPT has maintained uniform criteria of registration of incidence, mortality, and survival. Thus, time-related trends are unlikely to be biased. However, changes in incidence rates may reflect improvements in diagnostic procedures. The dramatic increase in efficacy of therapeutic protocols for several childhood cancer types largely explains the corresponding changes in mortality and survival rates. Two statistically significant time-related trends in incidence were found. Assessing whether the increase in time of incidence rates of soft tissue sarcomas was real or reflected diagnostic improvement requires conh a t i o n during subsequent periods of registration. In addition, in the first year of life, there was a downward trend in incidence rates of leukemias, which was not determined by cases either exclusively registered through the death certificate or associated with Down syndrome. A similar time-related trend in chil-
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CANCER March 1, 1992, Volume 69, No. 5
Table 7. Cumulative Survival Percentages and Standard Error at 3 and 5 Years Since Diagnosis by Period of Diagnosis 1967-69
Leukemias (all types) ALL ANLL Other leukemias CNS neoplasms Neuroblastoma Hodgkin's lymphoma Non-Hodgkin's lymphoma Soft tissue sarcomas Bone sarcomas Renal tumors Others
All neoplasms
3 Y' 5Yr 3 Y' 5Yr 3 Y' 5Yr 3 Y' 5Yr 3Yr 5 Y' 3Yr 5Yr 3 Y' 5Yr 3Yr 5Yr 3Yr 5Yr 3 Y' 5Yr 3Yr 5 Y' 3 Y' 5Yr 3Yr 5 vr
1970-72
1973-75
1976-78
1979-81
1982-84
%
SE
%
SE
Yo
SE
%
SE
%
SE
%
SE
19 11 50 17 -
4.9 3.9 14.4 10.8 -
5.6 4.4 7.3 5.8 -
6.1 5.7 7.2 6.9 10.5 10.5 13.9 13.9 6.9 6.8 8.7 -
63 57 72 65 33 33 0 0 45 39 36 29 93 93 38 38 65 65 29 29 82 82 88 88 57 53
5.9 6.1 6.1 6.5 15.7 15.7 -
58 45 70 57 18 9 25 0 57 55 29 21 89 89 60 53 67 67 45 27 67 67 33 33 56 49
6.3 6.3 6.7 7.2 11.6 8.7 21.6
6.9 7.3
4.4 4.0 7.6 7.3 10.4 9.4 10.5 13.9 13.4 11.6 17.1 17.1 18.8 18.8 14.4 14.4 11.7 11.7 3.4 3.3
44 30 54 35 11 11 22 22 40 36 9 0 73 73 36 36 56 56 13 0 38 38 75 75 42 35
58 -
12 10 35 29 34 24 89 78 27 18 63 63 44 44 50 50 88 88 41 36
29 15 36 18 0 0 23 15 47 41 8 8 78 67 21 0 27 27 27 27 29 29 50 50 36 29
-
-
7.2 7.3 12.1 11.0 10.5 10.5 12.7 12.9 19.3 19.3 15.0 13.4 15.7 15.7 27.2 27.2 3.6 3.6
72 69 80
11.7 10.1 8.8 8.7 8.0 8.0 13.9 15.7 18.4 13.4 13.4 13.4 13.4 17.1 17.1 25.0 25.0 3.6 3.4
13.4 13.4 12.8 12.8 16.6 16.6 11.7 -
17.1 17.1 21.7 21.7 3.5 3.4
7.5 7.3 12.8 12.1 6.9 6.9 13.5 13.5 10.7 10.7 12.1 12.2 11.6 11.6 11.7 11.7 3.3 3.3
67 25 0
-
15.3 -
6.8 12.8 -
12.7 -
-
16.6 -
56 83 80
10.8 -
12.7 -
-
86 100 -
9.4 0.0 -
68 -
3.5 ~~
SE standard error; ALL acute lymphocytic leukemia; ANLL acute nonlymphocytic leukemia; CNS central nervous system.
dren younger than 1 year of age, but not in older children, was found for acute lymphatic leukemia in a cumulative sum analysis covering a 24-year period of activity of the Manchester Children's Tumour Regi~try.~ The upward trend in time of incidence rates of CNS neoplasms we observed-although not statistically significant-reproduces findings described in other registries in Europe and North AmericaG8and probably reflects improved diagnostic procedures.6 Although statistically not significant and based on only 13 cases, the downward trend of incidence rates (Table 2) of thyroid tumors was interesting because it paralleled the dilution of radioactive pollution from nuclear tests done in the early 1960s. The affectedchildren included 6 boys and 7 girls, all of whom were 9+ years of age. No case was observed among children born after 1972. The 13 cases included 11carcinomas (7 papillary, 1follicular, 2 papillary and follicular, and 1medullary) and 2 adenomas. The case of medullary carcinoma also had a pheochromocytoma, as in the Sipple syndrome. The time trends for survival rates should be mentioned, although some estimates reported in Table 7 are
based on small absolute numbers. In particular, 3-year and 5-year survival rates of children with leukemia increased sharply for diagnosis up to the late 1970s and remained constant in subsequent periods. For Wilms' tumors, there was a marked difference between those diagnosed before and after 1976. A trend toward improved prognosis was suggested for CNS neoplasms and non-Hodgkin's lymphomas. The prognosis of children with Hodgkin's disease was good throughout the whole period. There was no prognostic improvement for neuroblastomas, with the exception of those diagnosed after 1982. (This observation requires confirmation over a longer period of registration and observation.) In comparison with similar population-based estimates on white children in the United States diagnosed after 1980: 5-year survival rates of children living in the Province of Torino diagnosed in 1979 to 1981 were lower for acute lymphatic leukemia (57% versus 71%), neuroblastomas (21% versus %YO), renal tumors (67% versus 81%),and bone sarcomas (27% versus 47%). The rates were similar for Hodgkin's lymphoma (89% ver-
Childhood Cancer Registry in Torino/Mosso et al.
1305
(3
z
2
$ 0.8 3 v,
z
g2
0.6
-
8330
1W-98 .............
0 0.4
W
2
4
23
0.2
0 Figure 1. Survival for children with leukemias (all types).
0
I
I
I
500
1,000
1,500
sus 89%) and non-Hodgkin's lymphoma (53% versus
50%). The survival of children with soft tissue sarcomas was similar in the two series." Survival from childhood brain tumors diagnosed during the 1970s was similar in our registry and in the Manchester Children's Tumor Registry," but the comparison was biased by the different criteria of registration. In our series, with the exception of acute lymphatic leukemia, standard errors of survival rates exceeded
I
I
I
I
I
2,000 2.500 3,000 3,500 4,000 DAYS AFTER DIAGNOSIS
I
I
i
4,500
5,000
5,506
10%. Given the rarity of childhood cancer, this is to be expected even in a relatively large pediatric population, such as that of the Province of Torino. However, for an overall evaluation of effectiveness of childhood cancer care, population-based studies are more informative than hospital-based series. Although current etiologic investigations on cancer in children are based mainly on understanding biologic mechanisms, we believe that maintenance of popula-
CASES UNDER OBSERVATION YEARS AFTER DIAGNOSIS RRlOD
196740
-..-..-...
1
0 41
3
13 11
$ 0.8 3 v, Z
f 0.6
1982-86
.............
2
88M
0 0.4
W
1
4 3
0.2
50 0
Figure 2. Survival of children with CNS tumors.
1 0
500 1,006 1,500 2,060 2,500 3,0003,5004,000 4,500 5,000 5,500 6,0006,500 7.000 7,500
DAYS AFTER DIAGNOSIS
5
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CANCER March 2,1992, Volume 69, No. 5
tion-based childhood cancer registries is important to monitor-at a population level-both incidence rates and therapeutic success, in a domain where cancer therapy has been promising.
References Pastore G, Magnani C, Ghisetti V, Terracini B, Mosso ML, Zanetti R. Childhood Cancer Registry of the Province of Torino: Survival patterns since 1967 and update of incidence rates. Pediatric Hematology and Oncology 1986; 3:195-204. International Classification of Diseases for Oncology. Geneva: World Health Organization, 1976; 1-131. Kaplan EL, Meier P. Non-parametric estimation from incomplete observations. ] A m Stat Assoc 1958; 53:457-481. Peto R, Pike MC, Armitage P et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient: Part 11. Analysis and examples. Br J Cancer 1977; 35:l39.
5. Birch JM, Swindell R, Marsden HB, Moms-Jones PH. Childhood leukaemia in northwest England 1954-77 Epidemiology, incidence and survival. Br J Cancer 1981; 43:324-329. 6. Breslow NE, Langholz B. Childhood cancer incidence: Geographical and temporal variations. Int J Cancer 1983; 32:703716. 7. Ericsson JLE, Karnstrom L, Mattsson B. Childhood cancer in Sweden 1958-1974: I. Incidence and mortality. Acta Paediatr Scand 1978; 67425-432. 8. Teppo L, Salonen T, Hakulinen T. Incidence of childhood cancer in Finland. J Null Cancer lnst 1975; 55:1065-1067. 9. National Cancer Institute, Division of Cancer Prevention and Control Surveillance Program. Cancer Statistics Review 197386. Bethesda, MD: National Institutes of Health, 1989. 10. Myers MH, Gloeckler Ries LA. Cancer patient survival rates: SEER program results for 10 years of follow-up. In: Cancer Statistics. Atlanta: American Cancer Society, 1989; 19-31. 11. Birch JM, Marsden HB, Moms-Jones PH, Pearson D. Improvements in survival from childhood cancer: Results of a population based survey over 30 years. Br Med J 1988; 296:1372-1376.
Childhood Cancer Registry of the Province of Torino, Italy Survival, Incidence, and Mortality Over 20 Years Maria Luisa Mosso, MD, Renata Colombo, MD, Livia Giordano, MD, Guido Pastore, MD, Benedetto Terracini, MD, and Corrado Magnani, M D
Incident childhood cancers in the Province of Torino, Italy (populationaged 0 to 14 years averaging 0.5 million) have been registered since 1967. Four population-based exhaustive surveys have been done to collect cases diagnosed during the periods 1967 to 1969,1970 to 1975,1976 to 1981, and 1982 to 1986. For each registered child, vital status on June 30,1988 was assessed. This article reports incidence, mortality, and survival rates over a 20-year period. A statistically significant trend toward an increased incidence of soft tissue sarcomas was identified. Statistically insignificant trends included an increased incidence of brain tumors (probably reflecting improved diagnostic procedures) and a decreased incidence of thyroid tumors. Incidence rates of leukemias in the first year of life tended to decrease. As expected, survival rates of some childhood cancers dramatically improved throughout the 2O-year period this occurred in leukemias, brain tumors, soft tissue sarcomas, and renal tumors. Survival rates are compared with observations in comparable population-based series. Cancer 1992; 69:1300-1306.
The population-based Registry of Childhood Cancer of the Province of Torino (Registro Tumori Infantili della Provincia di Torino, RTIPT) was begun in 1967. At the From the Service of Cancer Epidemiology, University of ToMo and Local Health Unit Torino 8, Torino, Italy. The Childhood Cancer Registry was supported by the Italian National Research Council (Progetto Finalizzato Oncologia, grants 84.00722.44, 85.02221.44, 86.00677.44, 87.01547.44, and 88.00727.44); Associazione Italiana per la Ricerca sul Cancro, Milano; and Sezione Provinciale di Torino della Lega Italiana per la Lotta contro i Tumori, Torino, Italy. Computer facilities provided in part by CSI Piemonte, Torino, Italy. The authors thank Ms. Rita Giacometti for secretarialhelp at the Registry, the heads of the hospital units where cases were sought, and their medical and nonmedical co-workers. Address for reprints: Benedetto Terracini, MD, Servizio di Epidemiologia dei Tumori, Ente Convenzionato Universit; di Torino, USL Torino 8, via Santena 7, 10126 Torino, Italy. Accepted for publication June 1, 1991.
1981 National Census, the total population of the province was 2,345,771; those 0 to 14 years of age were 19% of this number. Nearly 80% lived in the metropolitan area of Torino. In 1976, registration was extended to the other provinces of Piemonte. However, our report is limited to the Province of Torino, where registration currently includes a 20-year period. The incidence and mortality rates and survival patterns up to 1981 were reported previously.' We describe incidence and mortality data up to 1986 and cumulative survival probabilities updated to June 1988.
Materials and Methods At intervals, the RTIPT staff actively does a retrospective survey of files of clinical records of children (age, 0 to 14 years) hospitalized in pediatric units and in the major departments of medicine, hematology, and neurosurgery operating in the Piemonte region and in five Italian outstanding centers located outside the region (Istituto Nazionale Tumori and Istituto Neurologico C. Besta in Milano, Istituto Giannina Gaslini in Genova, and University Servicesof Paediatricsin Milano-Monza and Pavia). In some hospitals of the region with a pediatric unit, the files of the services of pathology and radiation therapy also are surveyed. The registry is notified of bone cancers in children living in Piemonte histologically diagnosed in the Istituto Ortopedico Rizzoli in Bologna by its pathology service. On the occasion of the most recent surveys, the Institute Gustave-Roussy of Villejuif (France) and the Cancer Registry of Geneva (Switzerland)provided the list of children living in Piemonte included in their files. Finally, the RTIPT files were cross checked with those of hospital discharges in Piemonte and Lombardia and with the file of residents (of any age) in Piemonte dying of cancer kept by the regional cancer registry. Four retrospective surveys
Childhood Cancer Registry in Torino/Mosso et al.
1301
have been done, collecting cases diagnosed during the periods 1967 to 1979,1970 to 1975,1976 to 1981, and 1982 to 1986. In addition to all cancers (International Classification of Diseases, Ninth Revision, categories 140 to 208), the RTIPT records angiomas of the central nervous system (CNS), but histiocytosis X is not recorded. Data collection procedures were reported elsewhere.' Individual records include identification data (name, surname, date of birth, and town of residence) and cancer type, date of diagnosis, diagnostic procedures, and some major clinical information. "DCO' cases, ix., those identified only through the report of a malignant neoplasm as the leading cause of death on the death certificate (3.6% during 1967 to 1969, decreasing progressively to 0.0% in 1982 to 1986) were considered as diagnosed on the date of death. Cases registered under the same surname and name were reviewed manually, and double cancers were accepted only if both cancers were verified histologically. Cancer cases were coded both with an ad hoc code originally developed by the RTIPT and according to standard International Classificationof Diseases for Oncology morphologic and topographic codes.' A case was considered to be histologically verified when a histologic report was identified during the registration procedures. In the computation of histologically verified cases, bone marrow aspiration cytology for leukemia was considered equivalent to histologic confirmation.
For each child registered since 1967, vital status on June 30, 1988 was assessed through the Anagrafe (the Italian equivalent to Registrars of Births, Marriages, and Deaths in the United Kingdom) of the town of residence. The rates were computed on the basis of the age (1-year age classes) structure of the population during the 1971 and 1981 census and between-census estimates provided since 1972 by the Istituto per le Ricerche Economiche e Sociali of the Piemonte region. All rates in this report are annual per million; the 1971population of the province was used as standard for age adjustment (using four age classes: 0 , l to 4,5 to 9, and 10 to 14 years). Survival analyses were done with the KaplanMeier3 method, and the statistical significance of the differences between survival curves was assessed using the long-rank test.4 Time-related differences in incidence and mortality rates were analyzed with the chisquare test for trend with one degree of freedom. Results
During 1967 to 1986, 1321 cases of childhood cancers were recorded, corresponding to an annual rate of 144.3 per million children. Table 1 reports incidence rates by tumor type, age, sex ratios, and proportion of cases for which a histologic confirmation was available. Among cases diagnosed in 1982 to 1986, there was his-
Table 1. Incidence Rates (Annual per Million) of Childhood Cancer in the Province of Torino (1967-86) by Age, Male to Female Ratio, Percentage of Cases Histologically Verified, and Absolute Number of Cases Age-specific rates (yr) 0
Leukemias (all types) ALL ANLL Others and unspecified CNS neoplasms Neuroblastoma Hodgkin's lymphoma Non-Hodgkin's lymphoma Soft tissue sarcomas Bone sarcomas Renal tumors Retinoblastoma Thyroid tumors Others All cancers No. of patients
1-4
5-9
10-14
47.1 16.3 7.3 23.6 23.6 36.3 3.6 1.8 18.1 3.6 23.6 14.5 0.0 32.7 204.9
77.0 56.3 5.9 14.8 32.1 22.0 2.5 5.9 9.7 0.8 19.0 7.8 0.0 11.0 187.8
42.4 26.0 5.6 10.8 33.7 4.3 5.9 11.8 8.0 6.8 2.2 0.9 1.2 9.0 126.2
26.2 15.1 4.6 6.5 29.2 2.2 11.2 7.1 5.2 15.1 0.6 0.0 2.8 10.1 109.6
113
444
408
356
Male to female ratio
0-14*
47.8 30.3 5.9 11.6 31.2 11.0 6.3 8.0 8.4 7.3 8.0
3.5 1.3 11.6 144.3
1.2 1.3 1.2 1.0 1.2 1.5 1.6 3.3 1.4 0.9 0.8 1.0 0.8 1.o 1.2
1321
HV: histologic verification; ALL acute lymphocytic leukemia; ANLL acute nonlyrnphocytic leukemia; CNS: central nervous system. * Age-standardized on the age structure of the population of the province in 1971.
HV /%) 97
71 94 98 93 96 91 90 72 92 82 88
No. of cases
430 275 51 104 293 93 63 76 76 75 67 29 13 106 1321
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CANCER March 1,1992, Volume 69, No. 5
Table 2. Incidence Rates of Childhood Cancer in the Province of Torino (1967-86) by Period of Diagnosis 1967-69
Rate Leukemias (all types) ALL ANLL Others and unspecified CNS neoplasms Neuroblastoma Hodgkin’s lymphoma Non-Hodgkin’s lymphoma Soft tissue sarcomas Bone sarcomas Renal tumors Retinoblastoma Thyroid tumors Others Unspecified Total
46.9 8.0 0.0 38.9 27.5 14.7 6.0 7.4 6.7 6.0 8.7 5.4 2.7 11.4 6.0 149.5
1970-75
(No. of cases) (70) (12) (0) (58) (41) (22) (9) (11)
Rate
1976-81
(No. of cases)
1982-86
(No. of cases)
Rate
(No. of
Rate
cases) (83) (69) (12) (2) (66) (20) (11) (15) (19) (20) (17) (2) (1) (15) (0) (269)
(146) (93) (19) (34) (91) (23) (20) (21) (21) (21) (16) (8) (4) (31) (6)
46.8 37.0 6.5 3.4 32.4 11.5 7.1 9.7 9.5 7.4 8.4 4.8 1.2 9.3 0.8
(131) (101)
(9) (13) (8) (4) (17) (9)
48.3 30.9 6.2 11.1 29.8 7.7 6.5 6.9 6.9 6.8 5.4 2.7 1.3 10.2 2.0
(11) (4) (26) (2)
47.5 39.3 7.5 0.7 34.5 13.1 4.6 6.9 11.0 8.4 11.4 1.4 0.4 7.9 0.0
(223)
134.3
(408)
149.1
(421)
147.2
(10)
(20)
(10) (95) (28) (23) (29) (26) (25) (21)
ALL acute lymphocytic leukemia; ANLL acute nonlymphocytic leukemia; CNS central nervous system. Rates are annual per million, age-standardized on the structure of the population of the province in 1971.
tologic c o n h a t i o n in 100% of cases for leukemias, 82% for CNS neoplasms, and 97% for other tumors. Time-trendsin incidence are shown in Table 2. This reports rates during the periods covered by each of the four surveys done over the 20-year period. Only the trend toward an increased incidence of soft tissue sarcomas was statistically significant (chi-square, 9.01). During 1982 to 1986, the rate for CNS neoplasms was increased 25% over that estimated during 1967to 1969, but the trend was not statistically significant (chisquare, 1.48). Additional (not tabulated) trend analyses were limited to the first year of life. In this age group, there was a statistically significant (chi-squarefor trend, 7.80) monotonic decrease of leukemias; the rates in the four periods were 86.9, 58.1, 27.4, and 10.5, respectively, based on 9, 12,4, and 1cases, respectively. Only two of these cases were ”DCO,” and in none was the presence of Down syndrome reported. Corresponding rates for CNS tumors and soft tissue sarcomas were 19.3, 9.7, 34.2, and 42.0 (based on two, two, five, and four cases) and 19.3, 4.8, 13.7 and 52.4 (based on two, one, two, and five cases), respectively. These trends were not statistically significant. Up to 1976, leukemia typing was not always done, and its registration was unsatisfactory. The 187 cases recorded during the subsequent 10 years included 153 of acute lymphatic leukemia (47% not otherwise specified, 7% specified as acute lymphatic leukemia of T-cell origin, and 46% as non-T-cell non-B-cell), and 27 of nonlymphatic acute leukemias ( i e . , 12 M1 to M2,3 pro-
myelocytic M3, 4 myelomonocytic M4, 3 monocytic M5, and 5 nonlymphatic leukemias with no further specification). Of the remaining seven cases, four were myelocytic leukemias, and three were recorded as ”acute leukemias.” Tables 3, 4, and 5 report respectively the distribution of histologic types of neoplasms of the CNS, soft tissue sarcomas, and ”other” cancers. As expected, carcinomas were rare. One of the two liver adenocarci-
Table 3. Distribution of Neoplasms of the Central Nervous System by Subtype, Male to Female Ratio, Percentage of Cases With Histologic Verification, and Incidence Rates (Age-Standardized,Annual per Million) Male to female ratio
HV (%)
Rate
56 80 14 16 21 26 80
1.8 1.6 0.6 1.2 0.9 0.8 1.0
98 99 100 100 71 85 8
6.0 8.6 1.5 1.7 2.1 2.8 8.4
293
1.2
71
31.2
No. of cases Medulloblastomas Astrocytomas Ependymomas Craniopharyngiomas Hemangiomas* Otherst Not otherwise specified Total
HV: histologic verification. * Nineteen benign angiomas, one hemangiopericytoma, and one hemangioblastoma. t Reported as follows: 15 gliomas, 2 neurinomas, 2 pinealomas, 1 pituitary adenoma, 1 chordoma, 3 meningiomas, 1 cerebral ganglioneuroma, and 1neuroeuhithelioma.
1303
Childhood Cancer Registry in Torino/Mosso et al. Table 4. Distribution of Histologic Diagnoses of Soft Tissue Sarcomas Rhabdomyosarcoma Fibrosarcoma Liposarcoma Leiomyosarcoma Synovial sarcoma Chondrosarcoma Malignant mesenchymoma Malignant schwannoma Myxosarcoma Hemangiopericytoma Soft tissue sarcoma, no further specification Histologic report untraced Total
34 13 9 3 2
2 1 1 1 1 6 3 76
nomas occurred in a child previously diagnosed as having a neuroblastoma. Among bone cancers, 62% and 34% were specified respectively as osteosarcomas and Ewing’s sarcomas. All renal tumors were reported as Wilms’ tumor (two were specified as bilateral) except for two diagnosed as dear cell cancers. Among the 29 retinoblastomas recorded over the entire period, only 6 were identified as bilateral. However, this is an underestimate because no systematic effort was made to identify metachronous bilateral retinoblastomas. During 1967 to 1986, a total of 731 deaths from cancer in patients aged 0 to 14 years were recorded (these included cases diagnosed before 1967).Mortality rates by period of death are reported in Table 6. The trend was statistically significant (P < 0.01) for leukeTable 5. Distribution of Cases Included Under Others in Tables 1 and 2 by Histologic Diagnosis Primary liver tumor Malignant reticulohistiocytosis Ovarian tumor Extragonadal immature teratoma Yolk sac tumors Testicular tumor Melanoma Nasopharyngeal undifferentiated carcinoma Pheochromocytoma Thymoma Adrenocortical tumor Adenocarcinoma in the liver, no further specification Others, with histologic diagnosis Histologic report untraced Total
12 10 10 10 7 6 6 6 2 2 2 2 9’ 22 106
* One each of the following: carcinoid of the appendix, chorionepithelioma, adenocarcinoma of the colon, basalioma of the skin, adenocarcinoma of the pancreas, adenocarcinoma of the salivary glands, dermoid, undifferentiated carcinoma in lymph node, undifferentiated carcinoma in the connective tissue of the abdomen.
Table 6. Mortality Rates of Childhood Cancer in the Province of Torino (1967-86)
Leukemias (all types) ALL ANLL Others and unspecified CNS neoplasms Neuroblastoma Hodgkin’s lymphoma Non-Hodgkin‘s lymphoma Soft tissue sarcomas Bone sarcomas Renal tumors Retinoblastoma Others and unspecified Total No. of uatients
1967-69
1970-75
1976-81
1982-86
33.5 2.7 0.0 30.8 19.4 8.0 1.3 4.0 2.7 4.0 4.7 0.0 6.0 83.8 125
36.4 17.7 4.9 13.8 17.9 8.6 2.3 4.6 4.2 4.5 3.4 1.3 6.6 89.9 274
24.4 16.4 4.0 3.9 17.8 8.0 1.2 5.6 2.9 3.8 2.2 0.8 8.0 74.7 215
21.1 15.7 4.7 0.7 13.1 5.9 0.9 4.7 5.4 2.9 2.3 1.4 2.9 60.8 117
~
ALL acute lymphocytic leukemia; ANLL acute nonlymphocytic leukemia; CNS: central nervous system. Rates are annual per million, age-standardized on the structureof the population of the province in 1971.
mias considered as a whole, CNS neoplasms, and all tumors. Finally, Table 7 reports cumulative survival at 3 and 5 years after diagnosis, over six 3-year periods of diagnosis. Survival for leukemias and CNS neoplasms is described in greater detail in Figures 1 and 2. In the log-rank test, differences were significant for both leukemias (chi-square, 80.27; df, 3; P < 0.0001) and CNS neoplasms (chi-square, 16.98; df, 3 df; P < 0.001). Discussion
Over 20 years, the RTIPT has maintained uniform criteria of registration of incidence, mortality, and survival. Thus, time-related trends are unlikely to be biased. However, changes in incidence rates may reflect improvements in diagnostic procedures. The dramatic increase in efficacy of therapeutic protocols for several childhood cancer types largely explains the corresponding changes in mortality and survival rates. Two statistically significant time-related trends in incidence were found. Assessing whether the increase in time of incidence rates of soft tissue sarcomas was real or reflected diagnostic improvement requires conh a t i o n during subsequent periods of registration. In addition, in the first year of life, there was a downward trend in incidence rates of leukemias, which was not determined by cases either exclusively registered through the death certificate or associated with Down syndrome. A similar time-related trend in chil-
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CANCER March 1, 1992, Volume 69, No. 5
Table 7. Cumulative Survival Percentages and Standard Error at 3 and 5 Years Since Diagnosis by Period of Diagnosis 1967-69
Leukemias (all types) ALL ANLL Other leukemias CNS neoplasms Neuroblastoma Hodgkin's lymphoma Non-Hodgkin's lymphoma Soft tissue sarcomas Bone sarcomas Renal tumors Others
All neoplasms
3 Y' 5Yr 3 Y' 5Yr 3 Y' 5Yr 3 Y' 5Yr 3Yr 5 Y' 3Yr 5Yr 3 Y' 5Yr 3Yr 5Yr 3Yr 5Yr 3 Y' 5Yr 3Yr 5 Y' 3 Y' 5Yr 3Yr 5 vr
1970-72
1973-75
1976-78
1979-81
1982-84
%
SE
%
SE
Yo
SE
%
SE
%
SE
%
SE
19 11 50 17 -
4.9 3.9 14.4 10.8 -
5.6 4.4 7.3 5.8 -
6.1 5.7 7.2 6.9 10.5 10.5 13.9 13.9 6.9 6.8 8.7 -
63 57 72 65 33 33 0 0 45 39 36 29 93 93 38 38 65 65 29 29 82 82 88 88 57 53
5.9 6.1 6.1 6.5 15.7 15.7 -
58 45 70 57 18 9 25 0 57 55 29 21 89 89 60 53 67 67 45 27 67 67 33 33 56 49
6.3 6.3 6.7 7.2 11.6 8.7 21.6
6.9 7.3
4.4 4.0 7.6 7.3 10.4 9.4 10.5 13.9 13.4 11.6 17.1 17.1 18.8 18.8 14.4 14.4 11.7 11.7 3.4 3.3
44 30 54 35 11 11 22 22 40 36 9 0 73 73 36 36 56 56 13 0 38 38 75 75 42 35
58 -
12 10 35 29 34 24 89 78 27 18 63 63 44 44 50 50 88 88 41 36
29 15 36 18 0 0 23 15 47 41 8 8 78 67 21 0 27 27 27 27 29 29 50 50 36 29
-
-
7.2 7.3 12.1 11.0 10.5 10.5 12.7 12.9 19.3 19.3 15.0 13.4 15.7 15.7 27.2 27.2 3.6 3.6
72 69 80
11.7 10.1 8.8 8.7 8.0 8.0 13.9 15.7 18.4 13.4 13.4 13.4 13.4 17.1 17.1 25.0 25.0 3.6 3.4
13.4 13.4 12.8 12.8 16.6 16.6 11.7 -
17.1 17.1 21.7 21.7 3.5 3.4
7.5 7.3 12.8 12.1 6.9 6.9 13.5 13.5 10.7 10.7 12.1 12.2 11.6 11.6 11.7 11.7 3.3 3.3
67 25 0
-
15.3 -
6.8 12.8 -
12.7 -
-
16.6 -
56 83 80
10.8 -
12.7 -
-
86 100 -
9.4 0.0 -
68 -
3.5 ~~
SE standard error; ALL acute lymphocytic leukemia; ANLL acute nonlymphocytic leukemia; CNS central nervous system.
dren younger than 1 year of age, but not in older children, was found for acute lymphatic leukemia in a cumulative sum analysis covering a 24-year period of activity of the Manchester Children's Tumour Regi~try.~ The upward trend in time of incidence rates of CNS neoplasms we observed-although not statistically significant-reproduces findings described in other registries in Europe and North AmericaG8and probably reflects improved diagnostic procedures.6 Although statistically not significant and based on only 13 cases, the downward trend of incidence rates (Table 2) of thyroid tumors was interesting because it paralleled the dilution of radioactive pollution from nuclear tests done in the early 1960s. The affectedchildren included 6 boys and 7 girls, all of whom were 9+ years of age. No case was observed among children born after 1972. The 13 cases included 11carcinomas (7 papillary, 1follicular, 2 papillary and follicular, and 1medullary) and 2 adenomas. The case of medullary carcinoma also had a pheochromocytoma, as in the Sipple syndrome. The time trends for survival rates should be mentioned, although some estimates reported in Table 7 are
based on small absolute numbers. In particular, 3-year and 5-year survival rates of children with leukemia increased sharply for diagnosis up to the late 1970s and remained constant in subsequent periods. For Wilms' tumors, there was a marked difference between those diagnosed before and after 1976. A trend toward improved prognosis was suggested for CNS neoplasms and non-Hodgkin's lymphomas. The prognosis of children with Hodgkin's disease was good throughout the whole period. There was no prognostic improvement for neuroblastomas, with the exception of those diagnosed after 1982. (This observation requires confirmation over a longer period of registration and observation.) In comparison with similar population-based estimates on white children in the United States diagnosed after 1980: 5-year survival rates of children living in the Province of Torino diagnosed in 1979 to 1981 were lower for acute lymphatic leukemia (57% versus 71%), neuroblastomas (21% versus %YO), renal tumors (67% versus 81%),and bone sarcomas (27% versus 47%). The rates were similar for Hodgkin's lymphoma (89% ver-
Childhood Cancer Registry in Torino/Mosso et al.
1305
(3
z
2
$ 0.8 3 v,
z
g2
0.6
-
8330
1W-98 .............
0 0.4
W
2
4
23
0.2
0 Figure 1. Survival for children with leukemias (all types).
0
I
I
I
500
1,000
1,500
sus 89%) and non-Hodgkin's lymphoma (53% versus
50%). The survival of children with soft tissue sarcomas was similar in the two series." Survival from childhood brain tumors diagnosed during the 1970s was similar in our registry and in the Manchester Children's Tumor Registry," but the comparison was biased by the different criteria of registration. In our series, with the exception of acute lymphatic leukemia, standard errors of survival rates exceeded
I
I
I
I
I
2,000 2.500 3,000 3,500 4,000 DAYS AFTER DIAGNOSIS
I
I
i
4,500
5,000
5,506
10%. Given the rarity of childhood cancer, this is to be expected even in a relatively large pediatric population, such as that of the Province of Torino. However, for an overall evaluation of effectiveness of childhood cancer care, population-based studies are more informative than hospital-based series. Although current etiologic investigations on cancer in children are based mainly on understanding biologic mechanisms, we believe that maintenance of popula-
CASES UNDER OBSERVATION YEARS AFTER DIAGNOSIS RRlOD
196740
-..-..-...
1
0 41
3
13 11
$ 0.8 3 v, Z
f 0.6
1982-86
.............
2
88M
0 0.4
W
1
4 3
0.2
50 0
Figure 2. Survival of children with CNS tumors.
1 0
500 1,006 1,500 2,060 2,500 3,0003,5004,000 4,500 5,000 5,500 6,0006,500 7.000 7,500
DAYS AFTER DIAGNOSIS
5
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CANCER March 2,1992, Volume 69, No. 5
tion-based childhood cancer registries is important to monitor-at a population level-both incidence rates and therapeutic success, in a domain where cancer therapy has been promising.
References Pastore G, Magnani C, Ghisetti V, Terracini B, Mosso ML, Zanetti R. Childhood Cancer Registry of the Province of Torino: Survival patterns since 1967 and update of incidence rates. Pediatric Hematology and Oncology 1986; 3:195-204. International Classification of Diseases for Oncology. Geneva: World Health Organization, 1976; 1-131. Kaplan EL, Meier P. Non-parametric estimation from incomplete observations. ] A m Stat Assoc 1958; 53:457-481. Peto R, Pike MC, Armitage P et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient: Part 11. Analysis and examples. Br J Cancer 1977; 35:l39.
5. Birch JM, Swindell R, Marsden HB, Moms-Jones PH. Childhood leukaemia in northwest England 1954-77 Epidemiology, incidence and survival. Br J Cancer 1981; 43:324-329. 6. Breslow NE, Langholz B. Childhood cancer incidence: Geographical and temporal variations. Int J Cancer 1983; 32:703716. 7. Ericsson JLE, Karnstrom L, Mattsson B. Childhood cancer in Sweden 1958-1974: I. Incidence and mortality. Acta Paediatr Scand 1978; 67425-432. 8. Teppo L, Salonen T, Hakulinen T. Incidence of childhood cancer in Finland. J Null Cancer lnst 1975; 55:1065-1067. 9. National Cancer Institute, Division of Cancer Prevention and Control Surveillance Program. Cancer Statistics Review 197386. Bethesda, MD: National Institutes of Health, 1989. 10. Myers MH, Gloeckler Ries LA. Cancer patient survival rates: SEER program results for 10 years of follow-up. In: Cancer Statistics. Atlanta: American Cancer Society, 1989; 19-31. 11. Birch JM, Marsden HB, Moms-Jones PH, Pearson D. Improvements in survival from childhood cancer: Results of a population based survey over 30 years. Br Med J 1988; 296:1372-1376.
