Temporal changes in childhood cancer incidence and survival by stage at diagnosis in Australia, 2000–2017

Figures & data

Table 1. Summary of the staging systems used in the Toronto Paediatric Cancer Stage Guidelines [1,2].

ICCC-3 Diagnostic group/subgroup	Staging system	Tier used^b
Acute lymphoblastic leukaemia	Children’s Oncology Group (COG) [13]	Tier 2
Hodgkin lymphoma	Ann Arbor [14]	Tier 2
Non-Hodgkin lymphoma^c	St Jude/Murphy [15]	Tier 2
Astrocytoma	Metastatic involvement	Tier 2
Ependymoma	M staging system [16]	Tier 2
Medulloblastoma	M staging system [16]	Tier 2
Neuroblastoma	International Neuroblastoma Risk Group Staging System (INRGSS) [17]	Tier 2
Retinoblastoma	International Retinoblastoma Staging System (IRSS) [18]	Tier 2
Renal tumours (except renal cell carcinomas)	Children’s Oncology Group/National Wilms Tumour Study Group (NWTSG) protocol^19 or International Society of Paediatric Oncology (SIOP) protocol^20	Tier 2
Hepatoblastoma	Metastatic involvement	Tier 1
Malignant bone tumours	Metastatic involvement	Tier 2
Rhabdomyosarcoma	Modified TNM [5]	Tier 2
Non-rhabdomyosarcoma soft tissue sarcoma	Modified TNM [5]	Tier 2
Testicular germ cell tumours	TNM [5]	Tier 1
Ovarian germ cell tumours	International Federation of Gynecology and Obstetrics (FIGO) [19]	Tier 2

(a) Classified according to the International Classification of Childhood Cancers, version 3 (ICCC-3) [6]. (b) Cases were staged using Tier 2 of the Toronto Paediatric Cancer Stage Guideline, unless otherwise specified (hepatoblastoma and testicular germ cell tumours). [1,7]. (c) Including Burkitt lymphoma.

Table 2. Study cohort by selected characteristics and period of diagnosis, Australia, 2000–2017.

	2000–2008		2009–2017
Characteristic	n	Col %	n	Col %
Sex	(p = 0.90)
Boys	2,010	55.5	2,561	55.4
Girls	1,609	44.5	2,062	44.6
Age group at diagnosis	(p = 0.62)
0–4 years	1,826	50.5	2,299	49.7
5–9 years	956	26.4	1,266	27.4
10–14 years	837	23.1	1,058	22.9
Type of cancer^a	(p = 0.73)
Acute lymphoblastic leukaemia	1,242	34.3	1,609	34.8
Hodgkin lymphoma	176	4.9	209	4.5
Non-Hodgkin lymphoma^b	249	6.9	300	6.5
Ependymoma	71	2.0	118	2.6
Astrocytoma	538	14.9	637	13.8
Medulloblastoma	147	4.1	191	4.1
Neuroblastoma	312	8.6	391	8.5
Retinoblastoma	135	3.7	162	3.5
Renal tumours^c	218	6.0	294	6.4
Hepatoblastoma	58	1.6	86	1.9
Malignant bone tumours	180	5.0	220	4.8
Rhabdomyosarcoma	142	3.9	185	4.0
Non-rhabdomyosarcoma soft tissue sarcoma	94	2.6	148	3.2
Testicular germ cell tumours	26	0.7	30	0.6
Ovarian germ cell tumours	31	0.9	43	0.9

(a) Classified according to the International Classification of Childhood Cancers, version 3 (ICCC-3). (b) Including Burkitt lymphoma. (c) Excluding renal cell carcinomas.

Figure 1. Incident distribution of stage at diagnosis by type of childhood cancer and period of diagnosis, Australia, 2000–2017^a,b,c,d. CNS: central nervous system; Local: localised; Met: metastatic; RCC: renal cell carcinoma; STS: soft tissue sarcoma. Staging categories: Ependymoma and medulloblastoma (M0 - no visible metastases on imaging and no tumour cells in the CSF; M1 - tumour cells in the cerebrospinal fluid; M2 - visible metastases in brain; M3 - visible metastases in spine; M4 - metastasis outside of CNS); Neuroblastoma (L1 - localised; L2 - locoregional; MS - metastases confined to skin, liver, and/or bone marrow for children younger than 18 months old at diagnosis); Renal tumours (y – denotes patients treated on the SIOP protocol); X – stage not assigned. (a). Type of cancer classified according to the International Classification of Childhood Cancers, version 3 (ICCC-3). (b). Cases were staged using the Toronto Paediatric Cancer Stage Guidelines. (c). P-values are for comparison of the stage distribution between the two diagnosis periods and were calculated after excluding cases with unknown stages at diagnosis. (d). Bars relating to cell counts of 5 or fewer patients are shown as missing to protect confidentiality.

Figure 2. Differences in adjusted survival curves from 2000–2008 to 2009–2017 for selected combinations of childhood cancer type and stage at diagnosis, Australia.^a,b,c ALL: acute lymphoblastic leukaemia; CNS: central nervous system. Staging categories: Acute lymphoblastic leukaemia (CNS1 - No clinical signs of central nervous system involvement and no blasts in the cerebrospinal fluid); Medulloblastoma (M3 - visible metastases in spine); Neuroblastoma (excludes stage MS - metastases confined to skin, liver, and/or bone marrow for children younger than 18 months old at diagnosis); Renal tumours (y – denotes patients treated on the SIOP protocol). (a) Survival was followed to 31 December 2020. Shaded areas denote the 95% confidence interval for the difference in survival. Positive values indicate survival has improved between the two diagnostic time periods. (b) Type of cancer classified according to the International Classification of Childhood Cancers, version 3 (ICCC-3). (c). The stage was defined by the Toronto Paediatric Cancer Stage Guidelines. d. Excludes renal cell carcinomas.

Table 3. Five-year observed survival by stage at diagnosis, type of childhood cancer and period of diagnosis, Australia, 2000-2017^a.

Type of cancer^b,c,d	Stage at diagnosis^e	2000–2008		2009–2017		Five–year adjusted mortality hazard ratio^f (95% CI)	p–value
		n	Five–year observed survival (95% CI)	n	Five–year observed survival (95% CI)
Acute lymphoblastic leukaemia	CNS1	1,087	91.0 (89.1–92.5)	1,399	95.1 (93.8–96.1)	0.54 (0.40–0.74)	<0.01
	CNS2	65	86.2 (75.1–92.5)	100	87.0 (78.7–92.2)	0.90 (0.38–2.12)	0.81
	CNS3	22	72.7 (49.1–86.7)	33	84.9 (67.4–93.4)	0.59 (0.17–2.02)	0.40
Non-Hodgkin lymphoma (including Burkitt lymphoma)	I/II	73	93.2 (84.3–97.1)	67	98.5 (89.9–99.8)	0.21 (0.03–1.83)	0.16
	III	120	88.3 (81.1–92.9)	160	88.7 (82.6–92.7)	0.99 (0.49–1.99)	0.98
	IV	44	86.4 (72.1–93.6)	69	84.1 (73.1–90.8)	1.34 (0.49–3.70)	0.56
Ependymoma	M0	61	70.5 (57.3–80.3)	101	78.8 (69.3–85.6)	0.68 (0.36–1.28)	0.23
Astrocytoma	Localised	526	80.8 (77.2–83.9)	618	87.6 (84.7–90.0)	0.60 (0.45–0.81)	<0.01
Medulloblastoma	M0	97	70.1 (59.9–78.2)	128	79.4 (71.3–85.5)	0.68 (0.40–1.16)	0.16
	M3	29	31.0 (15.6–47.9)	46	60.9 (45.3–73.3)	0.41 (0.21–0.79)	0.01
Neuroblastoma	L1	72	94.4 (85.9–97.9)	98	98.0 (92.1–99.5)	0.35 (0.06–1.95)	0.23
	L2	42	90.5 (76.6–96.3)	75	91.5 (82.0–96.1)	0.87 (0.24–3.07)	0.82
	MS	28	96.4 (77.2–99.5)	26	80.8 (59.8–91.5)	6.02 (0.70–51.7)	0.10
	Metastatic	159	46.2 (38.3–53.7)	185	61.6 (54.1–68.2)	0.61 (0.44–0.84)	<0.01
Renal tumours (excluding RCC)	I/yI	62	93.6 (83.7–97.5)	74	97.3 (89.6–99.3)	0.45 (0.08–2.46)	0.36
	II/yII	47	93.6 (81.5–97.9)	63	96.8 (87.9–99.2)	0.65 (0.10–4.24)	0.65
	III/yIII	64	89.1 (78.4–94.6)	98	99.0 (93.0–99.9)	0.10 (0.01–0.87)	0.04
	IV	36	80.6 (63.5–90.2)	50	86.0 (72.9–93.1)	0.70 (0.24–2.09)	0.53
Hepatoblastoma	Localised	43	83.3 (68.2–91.7)	52	92.3 (80.8–97.0)	0.40 (0.11–1.47)	0.17
Malignant bone tumours	Localised	128	88.3 (81.3–92.8)	154	84.0 (77.0–89.0)	1.34 (0.70–2.56)	0.38
	Metastatic	46	47.8 (32.9–61.3)	64	61.9 (48.6–72.6)	0.73 (0.41–1.31)	0.29
Rhabdomyosarcoma	I	44	81.8 (66.9–90.5)	60	90.0 (79.1–95.4)	0.52 (0.18–1.50)	0.22
	III	42	76.2 (60.3–86.4)	45	84.4 (70.1–92.3)	0.72 (0.27–1.90)	0.51
	IV	28	28.6 (13.5–45.6)	38	62.5 (45.0–75.9)	0.38 (0.19–0.77)	0.01
Non-rhabdomyosarcoma soft tissue sarcoma	I	49	83.7 (70.0–91.5)	66	90.9 (80.8–95.8)	0.50 (0.17–1.47)	0.21

CNS: central nervous system; RCC: renal cell carcinoma.

(a) Survival was followed up to 31 December 2020. (b) Type of cancer classified according to the International Classification of Childhood Cancers, version 3 (ICCC-3). (c) Includes combinations of type of cancer and stage category at diagnosis where there were a minimum of 20 cases for each period. (d) Comparisons over time were not included for Hodgkin lymphoma, retinoblastoma, testicular germ cell tumours or ovarian germ cell tumors as all, or nearly all, of these children survived for at least 5 years after diagnosis irrespective of time period. (e) The stage was defined by the Toronto Paediatric Cancer Stage Guidelines – see Supplementary Table 2 for definitions. (f) Mortality hazard ratio adjusted for age group at diagnosis and sex, using 2000–2008 as the reference group.

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Data availability statement

Unit record data that support the findings of this study are not publicly available through the Australian Childhood Cancer Registry due to privacy and ethical restrictions but may be requested directly from the data custodians at the state and territory cancer registries and treating hospitals (subject to all necessary ethics approvals). Please contact [email protected] for further details.