Australian Childhood Cancer Registry Research Articles

Population-level 5-year event-free survival for children with cancer in Australia.

Event-free survival (EFS) considers other adverse events in addition to mortality. It therefore provides a more complete understanding of the effectiveness and consequences of treatment than standard survival measures, but is rarely reported at the population level for childhood cancer. Our study cohort (n=7067) was obtained from the Australian Childhood Cancer Registry, including children aged under 15 diagnosed with cancer between 2006 and 2015, with follow-up potentially available to 31 December 2020. The events of interest were relapse following remission, progressive disease, diagnosis of a second primary cancer or death from any cause. Five-year EFS and all-cause observed survival were both calculated, stratified by type of childhood cancer, remoteness of residence and stage at diagnosis. Differences in EFS were assessed using multivariable flexible parametric models. Approximately one quarter of patients (n=1605 of 7067, 23%) experienced at least one of the events of interest within 5years of diagnosis. Relapse was twice as common for children with metastatic/advanced disease (22%) versus children with localised/limited cancers (11%). Overall 5-year EFS was 75.0% (95% confidence interval [CI]: 73.9%-76.0%), compared to 85.8% observed survival (95% CI: 85.0%-86.6%). Patients with other gliomas had the lowest EFS (35.4%, 95% CI: 27.8%-43.1%). EFS was significantly lower among children with acute myeloid leukaemia in outer regional/remote areas compared to major cities (adjusted hazard ratio [HR]=1.90, 95% CI: 1.20-3.00). Reporting EFS at a population level provides further insight on a wider range of impacts apart from mortality alone, contributing towards efforts to improve the management and outcomes of childhood cancer.

Incidence and survival for childhood cancer by endorsed non-stage prognostic indicators in Australia.

An international expert panel recently recommended 15 'non-stage prognostic indicators' (NSPIs) across eight childhood cancers, classified as essential or additional, for collection in population-based cancer registries. We aimed to describe the incidence distribution and survival of each of these NSPIs. Cases were extracted from the Australian Childhood Cancer Registry. The study cohort (n=4187) comprised all children aged under 15years diagnosed with an eligible cancer between 2010 and 2018, with follow-up until 31 December 2020. NSPI data were collected directly from each patient's medical records. Differences in 5-year relative survival were assessed using multivariable flexible parametric models, adjusted for sex and age group at diagnosis. The availability of data varied, exceeding 85% for all essential NSPIs apart from histologic subtype for Wilms tumours (69%) and lineage for acute lymphoblastic leukaemia (78%). Information on additional NSPIs tended to be recorded less often, particularly cytogenetic subtype for non-alveolar rhabdomyosarcoma (28%) and astrocytoma (4%). Eight NSPIs exhibited a significant difference in survival, with the largest disparity occurring among children with astrocytoma according to tumour grade (5-year relative survival of 18% for grade IV disease compared with 99% for grade I disease; p<.001). Our findings demonstrate that most of the recommended NSPIs can be retrieved from medical records in Australia in recent years, allowing the capability of assessing survival within patient subgroups of clinical interest. Reporting of NSPI data has the capability to inform local and global understanding of population-level disparities in childhood cancer survival.

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

Background The Toronto Paediatric Cancer Stage Guidelines are a compendium of staging systems developed to facilitate collection of consistent and comparable data on stage at diagnosis for childhood cancers by cancer registries. Material and Methods This retrospective, observational cohort study investigated changes in stage-specific incidence and survival for children diagnosed between 2000-2008 compared to 2009-2017 using the population-based Australian Childhood Cancer Registry. Information on mortality for each patient was available to 31st December 2020. Shifts in incidence by stage were evaluated using chi-square tests, and differences in stage-specific five-year observed survival for all causes of death over time were assessed using flexible parametric models. Results Stage was assigned according to the Toronto Guidelines for 96% (n = 7944) of the total study cohort (n = 8292). Changes in the distribution of incidence by stage between the two diagnosis periods were observed for retinoblastoma, with stage 0 increasing from 26% to 37% of cases (p = 0.02), and hepatoblastoma, with metastatic disease increasing from 22% to 39% of cases (p = 0.04). There were large gains in stage-specific survival over time for stage IV rhabdomyosarcoma (five-year adjusted mortality hazard ratio for 2009–2017 compared to 2000–2008 of 0.38, 95% CI 0.19–0.77; p = 0.01), stage M3 for medulloblastoma (HR = 0.41, 95% CI 0.21–0.79; p = 0.01) and metastatic neuroblastoma excluding stage MS (HR = 0.61, 95% CI 0.44-0.84; p < 0.01). Conclusion These results indicate that improvements in childhood cancer survival in Australia are most likely due to refined management rather than changes in stage at diagnosis, particularly for metastatic solid tumours. Wide international uptake of the Toronto Guidelines will allow comprehensive evaluation of differences in survival between countries.

The growing prevalence of childhood cancer survivors in Australia.

Survivors of childhood cancer have an increased risk of long-term health issues arising mostly from the side effects of treatment. Using population-based data from the Australian Childhood Cancer Registry (ACCR) for children aged 0-14 at diagnosis between 1983 and 2018, there were a total of 17,468 prevalent cases of childhood cancer survivors on 31 December 2018. We also found an 80% increase in the number of 5-year prevalent cases, from 1979 in 1988 to 3566 in 2018. Both short- and long-term prevalence estimates are important for monitoring childhood cancer survivorship and planning for the specific needs of this expanding cohort.

Long-term childhood cancer survival in Australia using period estimation.

Estimates of childhood cancer survival are usually reported at 5years after diagnosis only. Using cases prevalent between 2014 and 2018 from the population-based Australian Childhood Cancer Registry, we used the period method to calculate relative survival up to 20years post diagnosis by cancer type. Twenty-year relative survival for all childhood cancers combined (n=14,353) was 83.8% (95% confidence interval [CI]=82.6%-85.0%). Survival decreased only slightly after 10years for most childhood cancers, except for some types of brain and liver tumours. These contemporary estimates of long-term survival provide valuable information to assist childhood cancer patients and their families in planning for the future.

If we build it, will they come? Modeling of public hospital care requirements for the Australian Bragg Centre for Proton Therapy and Research.

The Australian Bragg Centre for Proton Therapy and Research (ABCPTR) will be Australia's first proton beam therapy (PBT) facility. A model was developed to predict associated public hospital care requirements for patients during PBT, to facilitate resource planning for pediatric, adolescent and young adult (AYA), and adult public hospitals in South Australia. National incidence rates for specific cancer indications were obtained from the Australian Childhood Cancer Registry, Australian Institute of Health and Welfare and published data. Australian Bureau of Statistics national population projections were used to estimate new cases in 2025 and beyond. Radiation oncologists and pediatric oncologists from the Central Adelaide Local and Women's and Children's Health Network, along with international colleagues, provided guidance on chemotherapy utilization and inpatient admission estimates. It was estimated 180 patients (40.4%) within the adult population (≥25 years) and 265 patients (59.6%) within the pediatric/AYA population (<25 years) would be eligible for PBT in 2025. There was no indication adult cancers would require concurrent outpatient/inpatient chemotherapy, in contrast with pediatric and AYA patients (59.5% and 62.8% outpatient and 18.9% and 41.9% inpatient, respectively). It was estimated 53% and 29% of pediatric and AYA patients could require inpatient admission for toxicity related to disease, concurrent chemotherapy or PBT. Associated public hospital care requirements related to the delivery of a national PBT service were estimated. This has particular implications for planning of the new Women's and Children's hospital, co-located with the ABCPTR. True data accuracy will be determined on future data generation and analysis.

Childhood cancer survival and avoided deaths in Australia, 1983-2016.

Large improvements in childhood cancer survival have been reported over recent decades. Data from cancer registries have the advantage of providing a 'whole of population' approach to gauge the success of cancer control efforts. The aim of this study was to investigate recent survival estimates for children diagnosed with cancer Australia and to examine the extent of changes in survival over the last 35 years. For the first time, we also estimated the number of deaths among Australian children that were potentially avoided due to improvements in survival. A retrospective, population-based cohort study design was used. Case information was extracted from the Australian Childhood Cancer Registry for 1983-2016, with follow-up to 31 December 2017. Eligible children were aged 0-14 with a basis of diagnosis other than autopsy or death certificate only. Five-year relative survival was calculated using the semi-complete cohort method for three diagnosis periods (1983-1994, 1995-2006 and 2007-2016), and changes in survival over time were assessed via flexible parametric models. Avoided deaths within 5 years for those diagnosed between 1995 and 2016 were estimated under the assumption that survival rates remained the same as for 1983-1994. Overall 5-year survival within the study cohort (n=20,871) increased from 72.8% between 1983 and1994 to 86.1% between 2007 and 2016, equating to an adjusted excess mortality hazard ratio of 1.82 (95% confidence interval 1.67, 1.97). Most cancers showed improvements in survival; other gliomas, hepatoblastoma and osteosarcoma were exceptions. Among children diagnosed between 1995 and 2016, 38.7% of expected deaths within 5 years of diagnosis (n=1537 of 3970) were avoided due to temporal improvements in survival. Survival for childhood cancer has continued to improve over recent years, thanks mainly to ongoing progress in treatment development combined with improved supportive care. Providing innovative measures of survival, such as avoided deaths, may assist with understanding outcome data produced by cancer registries.

Changes in cancer incidence and survival among Aboriginal and Torres Strait Islander children in Australia, 1997-2016.

This study reports cancer incidence and survival among Aboriginal and Torres Strait Islander children and other Australian children, and assesses changes over time. Data were from the population-based Australian Childhood Cancer Registry. The study comprised children aged under 15 diagnosed between 1997 and 2016 and with mortality follow-up until 31 December 2017. Incidence trends were analysed using JoinPoint regression. Five-year cancer-specific survival was calculated using the semi-complete approach with survival comparisons made using multivariable flexible parametric models. Aboriginal and Torres Strait Islander children accounted for 506 of 13,299 eligible cases (3.8%). Incidence rates for Aboriginal and Torres Strait Islander children across the study period increased by 2.3% annually (95% confidence interval [CI]: +0.6% to +4.0%) and for other Australian children increased by 0.6% annually (95% CI: +0.3% to +0.9%; p = .05). Nonetheless, cancer incidence was consistently lower for Aboriginal and Torres Strait Islander children, with an incidence rate ratio of 0.73 (95% CI: 0.62-0.85; p<.01) between 2012 and 2016. Survival for Aboriginal and Torres Strait Islander children with solid tumours was 70.6% (95% CI: 62.5%-77.3%) and for other Australian children was 83.5% (95% CI: 82.3%-84.7%; p < .01), with indications of this difference diminishing in recent years. Improvements in identification, particularly in urban areas, most likely accounts for the greater increase in cancer incidence rates among Aboriginal and Torres Strait Islander children. Examination of data on stage at diagnosis and treatment may provide important insights into survival for children with solid tumours.

Incidence and survival for childhood central nervous system tumours in Australia, 1983-2016.

To investigate incidence and survival of childhood tumours of the central nervous system (CNS) by histological subtype, tumour behaviour and tumour grade. National, population-based data on all children under 15years old diagnosed with a CNS tumour between 1983 and 2016 were sourced from the Australian Childhood Cancer Registry. Incidence rate trends were calculated using Joinpoint regression. Relative survival was calculated using the cohort method, with changes in survival over time by cancer type and tumour grade assessed by multivariable flexible parametric survival modelling. The study cohort included 4914 patients, with astrocytoma (n = 2181, 44%) and embryonal tumours (n = 931, 19%) the most common diagnostic subgroups. Almost half (n = 2181, 44%) of all tumours were classified as high grade (III or IV). Incidence rates increased by 29% between 1983 and 2016, with high grade tumours rising by an annual average of + 1.1% (95% CI = + 0.7%, + 1.5%, p < 0.001). 5-year survival for all patients combined was 72% (95% CI = 71-74%), ranging from 50% (46-54%) for those with other gliomas to 81% (79-83%) for astrocytoma (p < 0.001). Survival improved over time for grade II and III ependymomas but not for patients with astrocytoma irrespective of grade. Improvements in diagnostic technology leading to more precise tumour classification are likely to explain some of the differences in incidence rate trends by histological type and grade. While improvements in survival over time were noted for some tumours, outcomes remained poor among patients with high-grade astrocytoma.

Late mortality from other diseases following childhood cancer in Australia and the impact of intensity of treatment.

People who receive treatment for cancer during childhood often experience subsequent complications of therapy, known as late effects, which can lead to an increased risk of death. Using deidentified population-based data from the Australian Childhood Cancer Registry for children aged 0-14 diagnosed with cancer during the period 1983-2011 and who survived for a minimum of 5years, we examined disease-related deaths (other than cancer recurrence or second primary cancers) that occurred up to 31 December 2016. Risk of death relative to the general population was approximated using standardised mortality ratios (SMRs). Treatment received was stratified according to the intensity of treatment rating, version 3 (ITR-3). During the study period, 82 noncancer disease-related deaths were recorded among 13432 childhood cancer survivors, four times higher than expected (SMR=4.43, 95% CI=3.57-5.50). A clear link to treatment intensity was observed, with the relative risk of noncancer disease-related mortality being twice as high for children who underwent 'most intensive' treatment (SMR=5.94, 95% CI=3.69-9.55) compared to the 'least intensive' treatment group (SMR=2.98, 95% CI=1.42-6.24; Ptrend =.01). Thirty-year cumulative mortality from noncancer disease-related deaths was estimated at 1.4% (95% CI=1.1-1.9) after adjusting for competing causes of death such as cancer, accidents, or injuries. Although childhood cancer survivors are at increased relative risk of death from noncancer diseases, particularly those who undergo more intensive treatment, the cumulative mortality within 30years of diagnosis remains small. Knowledge of late effects can guide surveillance of survivors and treatment modification, without wanting to compromise the high rates of survival.

Renal tumours in Australian children: 30 years of incidence, outcome and second primary malignancy data from the Australian Childhood Cancer Registry.

This paper describes the incidence and outcomes of childhood renal malignancies in Australia using national population-based data from the Australian Childhood Cancer Registry. De-identified data for children (0-14 years) diagnosed with renal malignancies from 1983 to 2015 inclusive were extracted. Cause-specific (CSS) and event-free survival up to 20 years from diagnosis were estimated using the cohort method. Adjusted excess mortality hazard ratios were calculated using a multivariable flexible parametric survival model. Details relating to second primary malignancies (SPMs) were also examined. There were 1046 children diagnosed with renal malignancies in Australia between 1983 and 2015 (91% nephroblastoma), generating an annual age-standardised incidence rate of 8 per million children, which remained constant over the study period. CSS was 89% (95% confidence interval = 87-91%) and 88% (86-90%) at 5 and 20 years, respectively, and 5-year event-free survival was 82% (80-84%). Five-year CSS did not change over the study period and was highest for nephroblastoma (91%). Of the 94% of patients achieving remission, 15% relapsed and subsequent 5-year CSS was 49% (40%-58%). Eleven children were diagnosed with SPM (standardised incidence ratio = 2.9, 95% confidence interval = 1.6-5.3, P < 0.001), and five of them (45%) died within 5 years of the second diagnosis. Children treated for renal malignancies in Australia have excellent long-term survival, which is unchanged since 1983. SPMs are uncommon following treatment for childhood renal cancer but carry a poor prognosis. Relapse carries a similarly poor prognosis to SPM but is more common. These data are comparable to registry outcomes in similarly developed nations.

Primary malignant lung tumors in children: A report from the Australian Childhood Cancer Registry, 1983-2015.

Lung cancers in children under the age of 15 are very uncommon, with a scarcity of literature describing patient characteristics and survival. This study assessed first primary malignant cancers occurring in the trachea, bronchus, or lung (International Classification of Diseases for Oncology, 3rd edition [ICD-O-3] codes C33-C34) for the period 1983-2015, using data from the population-based Australian Childhood Cancer Registry. Variables of interest included morphology, sex, age group, and metastatic status at diagnosis. Mode of treatment was also assessed where possible. The Kaplan-Meier method was used to calculate 5-year observed survival. Of the 53 in-scope patients, almost half (n = 23, 43%) were diagnosed with pleuropulmonary blastoma and a further 8 (15%) had a carcinoid tumor. Few of the patients with details available on stage at diagnosis (n = 7 of 43, 16%) presented with metastatic disease. Surgical excision was the most common treatment (30 of 37 children, 81%), with two-thirds (n = 28 of 43, 65%) receiving chemotherapy. Five-year observed survival was estimated to be 74% (95% CI = 61%-85%). Our results represent one of the largest and most complete population-based cohorts of children with primary malignant lung cancers available to date. Detection of childhood lung cancer can be difficult due to the rarity of this disease and symptoms that are typically nonspecific.

The incidence of childhood cancer in Australia, 1983-2015, and projections to 2035.

ObjectivesTo describe changes in childhood cancer incidence in Australia, 1983–2015, and to estimate projected incidence to 2035.Design, settingPopulation‐based study; analysis of Australian Childhood Cancer Registry data for the 20 547 children under 15 years of age diagnosed with cancer in Australia between 1983 and 2015.Main outcome measuresIncidence rate changes during 1983–2015 were assessed by joinpoint regression, with rates age‐standardised to the 2001 Australian standard population. Incidence projections to 2035 were estimated by age‐period‐cohort modelling.ResultsThe overall age‐standardised incidence rate of childhood cancer increased by 34% between 1983 and 2015, increasing by 1.2% (95% CI, +0.5% to +1.9%) per annum between 2005 and 2015. During 2011–2015, the mean annual number of children diagnosed with cancer in Australia was 770, an incidence rate of 174 cases (95% CI, 169–180 cases) per million children per year. The incidence of hepatoblastoma (annual percentage change [APC], +2.3%; 95% CI, +0.8% to +3.8%), Burkitt lymphoma (APC, +1.6%; 95% CI, +0.4% to +2.8%), osteosarcoma (APC, +1.1%; 95%, +0.0% to +2.3%), intracranial and intraspinal embryonal tumours (APC, +0.9%; 95% CI, +0.4% to +1.5%), and lymphoid leukaemia (APC, +0.5%; 95% CI, +0.2% to +0.8%) increased significantly across the period 1983–2015. The incidence rate of childhood melanoma fell sharply between 1996 and 2015 (APC, –7.7%; 95% CI, –10% to –4.8%). The overall annual cancer incidence rate is conservatively projected to rise to about 186 cases (95% CI, 175–197 cases) per million children by 2035 (1060 cases per year).ConclusionsThe incidence rates of several childhood cancer types steadily increased during 1983–2015. Although the reasons for these rises are largely unknown, our findings provide a foundation for health service planning for meeting the needs of children who will be diagnosed with cancer until 2035.

Second primary cancers in people who had cancer as children: an Australian Childhood Cancer Registry population-based study.

To investigate the incidence of second primary cancers in people diagnosed with cancer during childhood. Retrospective, population-based study; analysis of Australian Childhood Cancer Registry data. People alive at least two months after being diagnosed before the age of 15 years with a primary cancer, 1983-2013, followed until 31 December 2015 (2-33 years' follow-up). Risks of second primary cancer compared with the general population, expressed as standardised incidence ratios (SIRs). Among 18230 people diagnosed with cancer during childhood, 388 (2%) were later diagnosed with second primary cancers; the estimated 30-year cumulative incidence of second cancers was 4.4% (95% CI, 3.8-5.0%). The risk of a new primary cancer was five times as high as for the general population (SIR, 5.13; 95% CI, 4.65-5.67). Relative risk of a second primary cancer was greatest for people who had childhood rhabdomyosarcoma (SIR, 19.9; 95% CI, 14.4-27.6). Relative risk was particularly high for children who had undergone both chemotherapy and radiotherapy (SIR, 9.80; 95% CI, 8.35-11.5). Relative risk peaked during the 5 years following the first diagnosis (2 to less than 5 years: SIR, 10.3; 95% CI, 8.20-13.0), but was still significant at 20-33 years (SIR, 2.58; 95% CI, 2.02-3.30). The most frequent second primary cancers were thyroid carcinomas (65 of 388, 17%) and acute myeloid leukaemias (57, 15%). Survivors of childhood cancer remain at increased risk of a second primary cancer well into adulthood. As the late effects of cancer treatment probably contribute to this risk, treatments need to be refined and their toxicity reduced, without reducing their benefit for survival.

Stage at diagnosis for childhood solid cancers in Australia: A population-based study

BackgroundStage of cancer at diagnosis is one of the strongest predictors of survival and is essential for population cancer surveillance, comparison of cancer outcomes and to guide national cancer control strategies. Our aim was to describe, for the first time, the distribution of cases by stage at diagnosis and differences in stage-specific survival on a population basis for a range of childhood solid cancers in Australia. MethodsThe study cohort was drawn from the population-based Australian Childhood Cancer Registry and comprised children (<15 years) diagnosed with one of 12 solid malignancies between 2006 and 2014. Stage at diagnosis was assigned according to the Toronto Paediatric Cancer Stage Guidelines. Observed (all cause) survival was calculated using the Kaplan-Meier method, with follow-up on mortality available to 31 December 2015. ResultsAlmost three-quarters (1256 of 1760 cases, 71%) of children in the study had localised or regional disease at diagnosis, varying from 43% for neuroblastoma to 99% for retinoblastoma. Differences in 5-year observed survival by stage were greatest for osteosarcoma (localised 85% (95% CI = 72%–93%) versus metastatic 37% (15%–59%)), neuroblastoma (localised 98% (91%–99%) versus metastatic 60% (52%–67%)), rhabdomyosarcoma (localised 85% (71%–93%) versus metastatic 53% (34%–69%)), and medulloblastoma (localised 69% (61%–75%) versus metastases to spine 42% (27%–57%)). ConclusionThe stage-specific information presented here provides a basis for comparison with other international population cancer registries. Understanding variations in survival by stage at diagnosis will help with the targeted formation of initiatives to improve outcomes for children with cancer.

Stage at diagnosis for children with blood cancers in Australia: Application of the Toronto Paediatric Cancer Stage Guidelines in a population-based national childhood cancer registry.

Information on stage at diagnosis for childhood blood cancers is essential for surveillance but is not available on a population basis in most countries. Our aim was to apply the internationally endorsed Toronto Paediatric Cancer Stage Guidelines to children (<15 years) with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma (HL), or non-Hodgkin lymphoma (NHL) and to assess differences in survival by stage at diagnosis. Stage was defined by extent of involvement of the central nervous system (CNS) for ALL and AML and using the Ann Arbor and St Jude-Murphy systems for HL and NHL, respectively. The study cohort was drawn from the population-based Australian Childhood Cancer Registry, consisting of children diagnosed with one of these four blood cancers between 2006 and 2014 with follow-up to 2015. Five-year observed survival was estimated from the Kaplan-Meier method. Stage was assigned to 2201 of 2351 eligible patients (94%), ranging from 85% for AML to 95% for ALL, HL, and NHL. Survival following ALL varied from 94% (95% CI=93%-95%) for CNS1 disease to 89% (95% CI=79%-94%) for CNS2 (P=0.07), whereas for AML there was essentially no difference in survival between CNS- (77%) and CNS+ disease (78%; P=0.94). Nearly all children with HL survived for five years. There was a trend (P=0.04) toward worsening survival with higher stage for NHL. These results provide the first population-wide picture of the distribution and outcomes for childhood blood cancers in Australia by extent of disease at diagnosis and provide a baseline for future comparisons.

Therapy-related acute myeloid leukemia following treatment for cancer in childhood: A population-based registry study.

Therapy-related acute myeloid leukemia (t-AML) is defined as AML that develops after exposure to cytotoxic chemotherapy and/or radiation therapy. There is a paucity of available literature, particularly in regard to t-AML following childhood cancer. Our aim was to describe the risk of t-AML among children treated for other cancers and their subsequent survival. We utilized data from the population-based Australian Childhood Cancer Registry to examine all childhood patients (<15 years at diagnosis) treated with chemotherapy and/or radiotherapy for cancers other than AML who received a subsequent diagnosis of AML between 1983 and 2014. Standardized incidence ratios (SIRs) were calculated to approximate the relative risk of being diagnosed with AML compared to the general population. Estimates of 5-year observed survival were obtained using the Kaplan-Meier method, with differences determined by the log-rank test. Fifty-eight of 11,753 patients in the study cohort (0.5%) were diagnosed with t-AML, an almost 50-fold higher risk than expected (SIR=45.6, 95% confidence interval [CI]=35.3-59.0). Five-year observed survival from the date of t-AML diagnosis was 31.2% (95% CI=19.6-43.5%). A significant survival advantage was found for patients who underwent hematopoietic stem cell transplantation (HSCT) following diagnosis of t-AML, with a 5-year survival of 52.4% (29.7-70.9%) compared to 5.7% (0.4-22.6%) for those who did not have HSCT (P<0.001). Although rare, t-AML is an important potential late effect of childhood cancer therapy. Prognosis is generally poor, with HSCT offering some survival benefit.

Assessing the feasibility and validity of the Toronto Childhood Cancer Stage Guidelines: a population-based registry study

Cancer stage at diagnosis is crucial for assessing global efforts to increase awareness of childhood cancer and improve outcomes. However, consistent information on childhood cancer stage is absent from population cancer registries worldwide. The Toronto Childhood Cancer Stage Guidelines, compiled through an international consensus process, were designed to provide a standard framework for collection of information on stage at diagnosis of childhood cancers. We aimed to assess the feasibility of implementing the Toronto Guidelines within a national population cancer registry. We did a population-based registry study using data from the Australian Childhood Cancer Registry and included data from children aged 0-14 years diagnosed between Jan 1, 2006, and Dec 31, 2010 with one of 16 childhood cancers listed in the Toronto Guidelines (acute lymphoblastic leukaemia, acute myeloid leukaemia, Hodgkin's lymphoma, non-Hodgkin lymphoma, neuroblastoma, Wilms' tumour, rhabdomyosarcoma, non-rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, Ewing's sarcoma, retinoblastoma, hepatoblastoma, testicular cancer, ovarian cancer, medulloblastoma, and ependymoma). We extracted data from medical records, and assigned stage according to the Tier 1 criteria (basic) and Tier 2 criteria (more detailed, requiring data from cytology, imaging, and other diagnostic tests, where available) using computer algorithms derived from the Toronto Guidelines. Additionally, expert reviewers independently assigned Tier 2 stage to a random subsample of 160 cases (ten per malignancy type). Feasibility of the guidelines was assessed on the percentage of cases that could be staged, agreement between stage assigned by the algorithms and the expert reviewers, and the mean time (min) taken to collect the required data. We obtained data for 1412 eligible children. Stage could be assigned according to Tier 2 criteria for 1318 (93%) cases, ranging from 48 (84%) of 57 cases of non-rhabdomyosarcoma soft tissue sarcoma to 46 (100%) cases of hepatoblastoma. According to Tier 1 criteria, stage could be assigned for 1329 (94%) cases, ranging from 131 (87%) of 151 cases of acute myeloid leukaemia to 46 (100%) cases of hepatoblastoma. By contrast, stage at diagnosis was recorded by the treating physician for 555 (39%) of the 1412 cases. The computer algorithm assigned the same stage as did one or more independent expert reviewers in 155 (97%) of the 160 cases assessed. The mean time taken to review medical records and extract the required data was 18·0 min (SD 9·5 per case). The Toronto Guidelines provide a highly functional framework that can be used to assign cancer stage at diagnosis using data routinely available in medical records for most childhood cancers. Data on staging have the potential to inform interventions targeting improved diagnosis and survival. Cancer Australia.