This action might not be possible to undo. Are you sure you want to continue?
Improving cancer care for children and young people 1 Sustaining innovation and improvement in the treatment of childhood cancer: lessons from high-income countries
Kathy Pritchard-Jones, Rob Pieters, Gregory H Reaman, Lars Hjorth, Peter Downie, Gabriele Calaminus, Marianne C Naafs-Wilstra, Eva Steliarova-Foucher
Cancer in children and adolescents is rare and biologically very different from cancer in adults. It accounts for 1·4% of all cancers worldwide, although this proportion ranges from 0·5% in Europe to 4·8% in Africa, largely because of differences in age composition and life expectancy. In high-income countries, survival from childhood cancer has reached 80% through a continuous focus on the integration of clinical research into front-line care for nearly all children affected by malignant disease. However, further improvement must entail new biology-driven approaches, since optimisation of conventional treatments has in many cases reached its limits. In many instances, such approaches can only be achieved through international collaborative research, since rare cancers are being subdivided into increasingly smaller subgroups on the basis of their molecular characteristics. The long-term effect of anticancer treatment on quality of life must also be taken into account because more than one in 1000 adults in high-income countries are thought to be survivors of cancer in childhood or adolescence. The introduction of drugs that are less toxic and more targeted than those currently used necessitates a partnership between clinical and translational researchers, the pharmaceutical industry, drug regulators, and patients and their families. This therapeutic alliance will ensure that efforts are focused on the unmet clinical needs of young people with cancer. Most children with cancer live in low-income and middle-income countries, and these countries account for 94% of all deaths from cancer in people aged 0–14 years. The immediate priority for these children is to improve access to an affordable, best standard of care in each country. Every country should have a national cancer plan that recognises the unique demographic characteristics and care needs of young people with cancer. Centralisation of the complex components of treatment of these rare diseases is essential to improve survival, accelerate research, and train the future specialist workforce. Referral routes and care pathways must take account of the large geographical distances between many patients’ homes and treatment centres, and the economic, cultural, and linguistic diversity of the populations served.
Published Online February 20, 2013 http://dx.doi.org/10.1016/ S1470-2045(13)70010-X See Online/Comment http://dx.doi.org/10.1016/ S1470-2045(13)70043-3 This is the ﬁrst in a Series of four papers about improving cancer care for children and young people Institute of Child Health, University College London, London, UK (Prof K Pritchard-Jones PhD); Department of Oncology/ Haematology, Erasmus MC Sophia Children’s Hospital, Rotterdam, Netherlands (Prof R Pieters PhD); Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA (Prof G H Reaman MD); Department of Paediatrics, Skåne University Hospital, Clinical Sciences Lund University, Lund, Sweden (L Hjorth PhD); Monash Children’s Cancer Centre and Department of Paediatrics, Monash University, Clayton,
Since systemic treatment for cancer ﬁrst became available in the 1950s, the treatment of childhood cancer has become the benchmark for the achievement of successful outcomes for patients. In high-income countries, 5-year survival has improved from 30% in the 1960s to 80% in the 2000s,1,2 with the expectation that most children with cancer can now be cured (ﬁgure 1). This rapid progress was made possible by collaborative work between paediatric cancer specialists within and across national boundaries, who were able to implement clinical trials in these individually very rare diseases. Indeed, for many decades, a comprehensive portfolio of national or international phase 3 clinical trials was available for most newly diagnosed children with cancer, and these trials have underpinned the continuous improvement in survival.3 Progress has depended on sustained international collaborative research to generate the evidence that has set the standards of care, which in turn give both professionals and patients and their families the reassurance that care for children with cancer follows an evidence-based, quality controlled diagnostic and treatment protocol. Enrolment in a clinical trial is viewed as consistent with best practice in many countries, and this contributes to the knowledge base for further improvements in management of these
life-threatening diseases.4,5 However, the historical rate of improvement is unsustainable for several reasons (panel 1). In high-income countries, we have nearly reached optimisation of present anticancer treatments—the rate of decrease in mortality has slowed substantially since
Figure 1: More children than ever before are surviving cancer
www.thelancet.com/oncology Published online February 20, 2013 http://dx.doi.org/10.1016/S1470-2045(13)70010-X
Louie Psihoyos/Science Faction/Corbis
This inequality is seen both within well-resourced continents such as Europe. France (E Steliarova-Foucher PhD) Correspondence to: Prof Kathy Pritchard-Jones. London WC1N 1EH. The introduction of biologically targeted agents into frontline treatment faces several challenges. cancer is the most common cause of death from disease in childhood beyond infancy (second only to accidents) and accounts for more than 5000 potentially avoidable deaths every year www.1016/S1470-2045(13)70010-X . and International Agency for Research on Cancer. International Society of Paediatric Oncology. Netherlands (M C Naafs-Wilstra MA). Survivors face major risks. Department of Paediatric Haematology and Oncology.6. targeted drugs for children with cancer • Insufficient resources to maintain a full portfolio of research to address the unmet clinical needs of patients the early 2000s (ﬁgure 2). and the psychosocial effects of their disease and treatment on both the patients and their families. or nihilistic beliefs about its curability. Even when symptoms clearly show that a child has a tumour. which can sometimes take many years to manifest in the growing child. 30 Guilford Street. International Confederation of Childhood Cancer Parents’ Organisations. where survival can vary by as much as 20% (ﬁgure 3).9 additional challenges exist in childhood cancers because these diseases are already rare. University Children’ s Hospital Münster.ac. Cure at the least cost is what our patients demand of us and what we must strive to deliver. In highincome countries. can delay or prevent referral for appropriate medical help. The ultimate ambition for our patients is to maximise their chances of survival while minimising the side-effects of treatment. and provision of free drugs should recognise the widespread oﬀ-label use of some drugs in regimens that are regarded as standard of care Insuﬃcient commercial interest from pharmaceutical companies • Poor access to new.12 Lifelong follow-up is imperative to prevent or attenuate some of these known risks. The cured childhood cancer survivor has many years ahead of them. a major research aim should be to minimise the use of treatments that carry these risks and thus maximise lifelong health and functioning. neurocognitive defects. two-thirds of which occur in children younger than 15 years. second primary neoplasms. These risks include a continuing excess risk of mortality. Although such an approach has been established for the common adult cancers. With the growing recognition of the total cost to the individual and society of long-term health problems. where the vast majority of the global burden of death from childhood cancer now exists and where it is predicted to remain (ﬁgure 4). particularly those in which primary care for children is of variable quality or is delivered by non-specialists. requirements for insurance. Münster. University College London. Institute of Child Health. because of the pivotal roles of signalling pathways in normal human growth and development. consideration of appropriate tests might be delayed in some countries.Series VIC. and survivors should be empowered to self-manage their health needs as they move into adulthood and often lose contact with their initial treatment centre. Geneva.org/10. UK k. Nieuwegein. Lyon. despite excellent survival. which contribute to whether prompt diagnosis and uniform access to speciﬁed standards of multidisciplinary expert care are available.uk Panel 1: Challenges for continued clinical research into childhood cancers Increasing complexity of risk stratiﬁcation • Smaller therapeutic subgroups need a new approach to trial design and expansion of international collaboration to achieve suﬃcient recruitment • Preclinical and biomarker research needs international tissue sharing and pooled analyses of individual clinical data Optimisation of intensive use of present treatments has reached its limits • New biology-driven approaches are needed to improve survival and quality of life.thelancet. especially for the highest-risk subgroups Unaﬀordable and unnecessarily complex regulatory bureaucracy for international investigator-led clinical trials • Sponsor obligations need to be adapted to the additional risk posed by trial participation rather than the inherent risk of standard treatment. substantial inequality exists in survival from childhood cancers between countries.pritchard-jones@ucl. the community’s attitudes about non-disclosure of cancer in the family. with recognition of the track records for patient safety achieved by long-established academic international collaborative trial groups • Policies for pharmacovigilance reporting.com/oncology Published online February 20. Switzerland (G Calaminus). as much due to sequelae of their treatment as to the risk of recurrence of their original cancer.6. during which they wish to achieve 2 their full potential.doi. other organ dysfunction. Second.11 These differences are caused not only by differences in health-care resources. These issues need to be seen in the context of the global challenge of 263 000 new cases of cancer estimated to affect people younger than 20 years annually. Australia (P Downie MD). and biological subgroups might constitute only a handful of patients per year in each country. Germany (G Calaminus MD). 2013 http://dx. and to a much greater extent in less-developed regions. but also by differences in the organisation of care. The planned incorporation of molecularly targeted agents unfortunately does not preclude the need for long-term follow-up. First. Because the signs and symptoms of childhood cancer are often non-speciﬁc.8 These include the need to identify and validate targets and to develop a new biology-driven approach for the early assessment of novel agents by use of enriched populations of patients selected for the likely molecular drivers of their tumours. Substantial innovation in therapeutic approaches in the coming decades will be needed to achieve this goal. the long-term risks of cancer treatment given during childhood and adolescence are increasingly being recognised.7 New approaches now need to be tested if we are to ﬁnd effective treatments for the highest risk subgroups of childhood cancers.10 This aim emphasises two further challenges for sustaining improvements in cancer treatment for children and young people around the world. cardiovascular disease.
20 In Europe. Finland. become much less common and biologically diverse with age. adolescents (aged 15–19 years) and young adults (aged 20–24 years) with cancer are being regarded as groups that need special consideration because of their unique composition of cancer types (ﬁgure 6) and their speciﬁc health-care needs. by this deﬁnition. neuroblastoma.org/10.1016/S1470-2045(13)70010-X 20 0 2005–09 5– 07 /0 9 in people younger than 15 years (ﬁgure 5). 80 Mortality (per million person-years) Former socialist economies Other European countries 60 40 20 0 1970–74 1975–79 1980–84 1985–89 1990–94 Years 1995–99 2000–04 Figure 3: Child cancer mortality (aged 0–14 years) in former socialist economies compared with other European countries Data are from the UN6 and WHO.15 we discuss the policies and approaches needed to improve cancer care for children and adolescents. embryonal tumours. Embryonal tumours such as retinoblastoma. The individual rarity of each childhood cancer and the particular challenges of treating life-threatening diseases in young children necessitates speciﬁc management strategies and wide collaboration. the overall incidence of childhood cancer has been increasing by about 1% per year during the three For more on RARECARE see http://www. Ireland. Slovenia. Italy. and sarcomas. Norway. Russia. Sweden.doi. 2013 http://dx. cancer incidence ranges from about 90 to 300 cases per million people in young men and from 88 to 270 cases per million people in young women. and nephroblastoma (Wilms’ tumour) very rarely occur later in life. Large proportions of patients have haema tological malignancies.rarecare. France.11 All childhood cancers are individually rare. Croatia. along with three others in this Series. Czech Republic. Denmark. the most common histological type in adults. Luxembourg. Spain. and even effective palliative care is poor. with incidences that vary from 1·2 cases per million people for very rare cancers such as hepatoblastoma to 35 cases per million people for the most common malignant disease—acute lymphoblastic leukaemia. the Netherlands. Portugal. Latvia. All data are from the UN6 and WHO. Cancers in young people are histologically very diverse (ﬁgure 6). treatment.7 Mean age-standardised mortality was weighted by country-speciﬁc and sex-speciﬁc standard errors. and Ukraine. as is testiﬁed by the long-standing missions and successes of the childhood cancer study groups such as the International Society of Paediatric Oncology (Société Internationale d’Oncologie Pédia. Belgium. and the UK. which presents substantial challenges for the improvement of care. about 1 in 400 children in the USA are affected by cancer. Switzerland. Czechoslovakia.19 In adolescents. and where access to appropriate specialist diagnosis. As such.com/oncology Published online February 20. central nervous system tumours. respectively. according to data for a large population. the European Union (EU)-funded RARECARE project has deﬁned rare as a disease with an incidence of fewer than six cases per 100 000 people. represent less than 5% of all childhood cancer. Iceland. even childhood acute lymphoblastic leukaemia can be classiﬁed as rare. at least for paediatric-like cancers such as acute lymphoblastic leukaemia.Series 80 – 85 – 70 50 55 75 60 90 65 95 0– 19 19 19 19 19 19 20 0 19 19 19 19 Burden of cancer in children and adolescents The term childhood cancer is usually used to describe cancers that arise before age 15 years. Not all countries were included for all time periods. Romania. Germany. The characteristic morphological appearances imply distinct developmental origins and causes for tumours in childhood.eu/ www. Greece. Other European countries are Austria. the incidence was 186 cases per million person-years in the period 1988–97.8. Slovakia.14 In this paper. Because of age proximity. Netherlands.thelancet.trique.13 However. Carcinomas. and UK (combined) USA 80 60 40 20 0 4 4 4 84 04 9 9 9 9 –6 89 4 –6 –9 –5 –7 –9 –5 –7 * 3 . Lithuania. In Europe. almost 90% of the world’s children live in parts of the world (low-income and some middle-income countries) where their cancer is often detected too late for effective treatment or not diagnosed at all. Macedonia. SIOP)18 and the Children’s Oncology Group.17 By this deﬁnition. adolescent patients are often managed within or in close association with paediatric oncology services. Indeed.7 Age-standardised mortality measures were weighted by their country-speciﬁc and sex-speciﬁc standard errors.16 Cancer in children represents about 2% and 0·5% of all cancers in the populations of developing and developed countries. Bulgaria. The former socialist economies are Albania. Estonia.21 Increasingly. and the need for a very sensitive approach. Belarus. and others. such as acute lymphoblastic leukaemia. Malta.14. Poland. and the UK. Hungary. similarity of the tumour range. Netherlands. adolescents might beneﬁt from inclusion in paediatric therapeutic protocols rather than those developed for adults. about 91 000 deaths from childhood cancer (94% of the global mortality) occur in less-developed countries (ﬁgure 4). Serbia. *Data for the European countries are for 1950–2009 and data for the USA are for 1950–2007. Years Figure 2: Child cancer mortality (aged 0–14 years) in three European countries and the USA Data for the European countries are combined from Ireland. 100 Mortality (per million person-years) Ireland.22 According to data from population-based cancer registries.
thelancet. and children with acute lymphoblastic leukaemia were some of the earliest participants in studies of new drugs for cancer. which tends to be higher in high-income countries. whereby they work closely with multi disciplinary specialists in the diagnosis. made available from the War Department. albeit transient. In the EU. Two initial groups were formed—the Acute Leukemia Chemotherapy Study Group A (later to become the Children’s Cancer Study Group and then the Children’s Cancer Group) and the Cancer and Leukemia Group B (of which the Figure 5: Disease-related causes of death in children (aged 5–14 years) and young adults (aged 15–29 years) in high-income countries13 4 www.11 Projection is based on an assumption of medium population growth and stable incidence. The timing coincides with the report of successful. the high survival from childhood cancer in recent years has resulted in a fairly low estimated mortality rate in 2008 of 27 per million person-years in people aged 0–14 years. Australia.23–26 Cancer incidence in adolescents has also increased during the same period.org/10. close monitoring of incidence trends in the young population remains a public health priority. For example. Cancers Cardiovascular diseases Neuropsychiatric disorders Infectious and parasitic diseases Endocrine disorders Congenital abnormalities Digestive diseases Respiratory diseases (non-infectious) Respiratory infections Maternal disorders Diabetes mellitus Musculoskeletal diseases Genitourinary diseases Benign tumours Skin diseases Nutritional deﬁciencies Perinatal disorders Oral disorders Sense organ diseases 0 10 20 30 40 Mortality (per million person-years) 50 15–29 years 5–14 years 60 rate. but the effects of changes in exposures and lifestyles during the same period cannot be excluded.1016/S1470-2045(13)70010-X . despite a reduction in the geographical differences in the period 2005–09. a cancer chemotherapy national committee met to form the Cancer Chemotherapy National Service Centre of the National Institutes of Health.28 as industrial development continues worldwide. remission induction in acute lymphoblastic leukaemia with the antifolate aminopterin. treatment.Series decades from the early 1970s in Europe. and elsewhere.27 These temporal trends might be partly caused by improved reporting of childhood cancers. The geographical differences in survival and mortality seen between more-developed and less-developed countries are another major challenge (ﬁgure 5). which was charged to support voluntary cooperative research in chemotherapy for acute leukaemia and other cancers. at a slightly faster 200 000 175 000 150 000 125 000 Number 100 000 75 000 50 000 25 000 0 World More-developed regions Less-developed regions Total cases in 2008 Projected cases in 2030 Total deaths in 2008 Projected deaths in 2030 Figure 4: Projected incidence and mortality of childhood cancer (aged 0–14 years) in 2030 compared with estimates for 2008 Data are from the UN6 and GLOBOCAN. Although the future burden of cancer in children is not projected to change substantially (ﬁgure 4). Before Sidney Farber’s ﬁndings on aminopterin were reported. on leukaemia in mice. and long-term follow-up of successfully treated children with cancer. Childhood cancer in North America The long-established model of practice for paediatric oncologists.doi. although the rate of increase seems to have slowed since the turn of the millennium. the former socialist economies still have roughly 20% excess mortality from cancer in children compared with the rest of Europe (ﬁgure 3).11 Cancer mortality trends in children for the past 60 years in Europe and North America clearly show that the rate at which mortality has been falling has slowed down in the past 10–15 years (ﬁgure 2).1. Major new breakthroughs in treatments are therefore needed to accelerate the present rate of improvement in survival.23.1. dates back to the early 1950s. 2013 http://dx. North America. Because future changes in incidence are difficult to predict. an increase might be expected in the incidence of acute lymphoblastic leukaemia.29 Focused efforts on drug development for cancer in the USA had its origin in the search for effective treatment for acute leukaemia.30 By 1954.com/oncology Published online February 20.29 Joseph Burchenal and colleagues reported on the effect of nitrogen mustard compounds.
outcomes.doi. combined with radio therapy and surgery when appropriate. treatment planning. neuroblastoma. nephroblastoma. 12 member institutions were involved in ﬁve combination antimetabolite treatment protocols that had enrolled more than 500 patients. To support the diffusion of effective infrastructures to deliver best-practice care for national populations. By the early 1970s. despite differences in ethical review systems and regulatory requirements. in which specialist centres that are responsible for accurate diagnosis. designed and ran sequential clinical trials. through study protocols that provided detailed guidance on delivery and appropriate dose modiﬁcation in response to excessive toxicity from these complex treatments. and survivorship research. disease-speciﬁc paediatric cooperative groups were formed to focus on clinical trials in rhabdomyosarcoma and Wilms’ tumour. and simple chemotherapy closer to most patients’ homes. planners have built on these standards and expectations of multidisciplinary teamwork. epidemiological. the results of which set the standards of care for the diagnosis and management of childhood cancers in the USA and Canada. and incorporated six children’s hospitals or university paediatric programmes. monitoring.Series paediatric division would later merge with other groups to become the Pediatric Oncology Group). 5 years later. SIOP Europe has published standards of care that were developed in conjunction with childhood cancer parents’ associations (panel 2). The institutional members of this paediatric cancer clinical trials network were responsible for the care of more than 90% of children with cancer younger than 15 years in the two countries. they need to be accompanied by a quality assurance process. lymphomas.1016/S1470-2045(13)70010-X . which continues the clinical trials mission augmented by active programmes in basic. MD. During the 1980s and 1990s. drove a culture of multidisciplinary teamwork that raised the standard of care for all patients. and brain tumours. 2013 http://dx. By 1959. almost 1500 children had been enrolled into clinical trials. The Children’s Cancer Study Group expanded its scientiﬁc agenda to include common solid tumours. under the auspices of the US National Cancer Institute. and complex treatments liaise with designated shared-care local hospitals that provide less complex components of supportive care. The particular needs of adolescents and young people with cancer have also been recognised in recent years. In the absence of industry support.thelancet.18 Under the SIOP umbrella. the shared goal of addressing the unmet clinical needs of children with cancer allowed collaborative. supported by a small amount of charitable funding and relying on each country’s health service framework to deliver the basic standard of care. risk stratiﬁcation. although many countries are only now starting to take speciﬁc actions to address these. All of these trials were led by academic investigators and were designed to optimise the use of conventional cytotoxic drugs. 10 years later. so treatments could be intensiﬁed more safely. and soft-tissue sarcomas) and substantial improvements in survival and reductions in treatment morbidity were achieved. A national clinical trials infrastructure. into which most newly diagnosed children with cancer were enrolled. 100 90 80 70 Proportion (%) 60 50 40 30 20 10 0 0 1–4 5–9 10–14 Age group (years) 15–19 Other and not otherwise speciﬁed Carcinomas Germ-cell tumours Soft-tissue sarcomas Bone tumours Hepatic tumours Renal tumours Retinoblastomas Sympathetic nervous system tumours Central nervous system tumours Lymphomas Leukaemias Figure 6: Proportions of the 12 main tumour groups in children and adolescents in Europe1 Childhood cancer in Europe A similar structured approach to cooperation for the beneﬁt of patients was developed in Europe by early pioneers such as Odile Schweisguth and others who founded SIOP in 1969. neuroblastomas. The ﬁrst was formed in 1955.com/oncology Published online February 20. This process is now underway in several countries. formal collaborative clinical research was initially undertaken across Europe in common childhood cancers (eg. As national cancer plans have been formulated in many European countries during the past decade. whether enrolled in a clinical trial or not. translational.org/10. patient-centred research to thrive across national boundaries. As supportive care improved. The national network has been strengthened in the past decade as the result of the uniﬁcation of the four legacy cooperative groups into the Children’s Oncology Group. headed by Joseph Burchenal at Memorial Hospital (Baltimore. The skills needed to deliver the standardised methods of diagnosis.19 The link between care and research remains stronger than ever. and response assessment mandated by these late-phase trials. USA). every common childhood cancer was being studied collaboratively by clinical investigators at children’s hospitals and academic medical centres nationwide. Many plans have included recommendations for a so-called hub-and-spoke model.4 These standards focus on 5 www. such trials were only possible through the efforts of national childhood cancer organisations. which consisted of four separate groups and encompassed more than 200 academic paediatric cancer programmes.5 Once standards are deﬁned.
roughly 550 cases of cancer are newly diagnosed in people aged 0–18 years annually. all tumour types occur in fewer than 30 patients per year. of course. In the Netherlands. Indeed.thelancet. and early response to treatment. and in specialised hospitals leads to improved outcomes. where excessive travel distances would put additional burdens on patients and families. Additionally. in patients with breast cancer an improved outcome has been shown if clinicians treat at least 30 patients per year.org/10.39 bone tumours40. the association between treatment in high-volume hospitals or by high-casevolume clinicians and better outcomes for patients is clear. in the Netherlands. such analyses are more difficult to undertake because all types of childhood cancer are rare. extended to include adolescent cases and international comparative studies Access to specialists Deﬁned referral pathways should exist so that every patient is managed at an age-appropriate specialist treatment centre and can access innovative treatments if appropriate Multidisciplinary teams Every child and adolescent with cancer should be treated by a multiprofessional team who treat sufficient numbers of patients with the same disease to maintain the necessary skills and who participate in audit and accreditation schemes Specialist training Specialist training in paediatric haemato-oncology should be recognised in every country Family support Recognition that parental or other family support is crucial to treatment outcome and survival of young people with cancer Research A national strategy is needed to ensure support for investigator-led clinical and translational research. with patients treated in one of seven childhood cancer centres. does not immediately lead to a substantial increase in survival. with the recognition that participation in clinical trials is integral to delivery of best-practice care for young people with cancer effect. With the exception of acute lymphoblastic leukaemia. even multi disciplinary teams have great difficulty developing and maintaining the knowledge and skills necessary for the treatment of all types of childhood cancer.41 and those receiving allogeneic bone marrow transplantation.doi. such high case numbers per clinician are almost never met. Improving care In many adult cancers. which leads to better value care (deﬁned as patient outcomes per resource expended).com/oncology Published online February 20. but evidence that centralisation improves outcomes does exist. A disadvantage is potentially increased travel time and expense for parents and patients. by high-case volume clinicians. which has a population of 17 million people. The small geographical size of the Netherlands makes provision in a single centre feasible. Concentration of services in itself. genetics.1016/S1470-2045(13)70010-X . For example. and that opportunities for training and education are improved.Series organisation of care to maximise equitable access to appropriate specialist services and on embedding data collection and research into routine care. The evidence is strongest for children with brain tumours. concentration of care will need more than one such centre. but it does create the optimum conditions for progress. but outcomes might improve still further with a higher number of patients per clinician. since both involve complex processes delivered through multidisciplinary teamwork. For example. a recent systematic review lends support to the conclusion that treatment of children with cancer in high-volume hospitals. for which large numbers of patients can be studied. 6 www. Therefore. Additionally. low-volume treatment will rely on con centration of care services and skilled clinicians to ensure that the best possible care is provided as safely as possible and to support effective research that can change clinical practice.42. but most families are willing to travel to get the best available care for their child.35 All included studies of sufficient quality reported either a signiﬁcant or a non-signiﬁcant positive association for the effect of increased volume of patients treated on outcome. 2013 http://dx. concen tration of care means that bureaucratic procedures for the implementation of new treatment protocols can be minimised.44 In childhood cancer. histology. Concentration of services increases accessibility to new treatments and ensures that every patient is able to have a mutually supportive interaction with researchers. the same volume-tooutcome relation reported in adult cancers can also be assumed for paediatric cancers. As such.34 Logically. and no study showed a negative Panel 2: SIOP Europe’s proposed seven key elements for a national cancer strategy Cancer plans Every country should have a national cancer plan that contains speciﬁc standards for age-appropriate treatment and care for children and young people with cancer Cancer registration Every country should support national prospective registration and follow-up of all cases with the international childhood cancer classiﬁcation scheme. further improvement in highly complex.31–33 In paediatric oncology. In larger countries. within each tumour type several different protocols exist for subclasses based on staging. with the aim of improving evidence for outcomes that are important to patients and driving continuous improvements.36–38 acute lymphoblastic leukaemia. Good facilities should be organised for patients and families while away from home.43 No clear threshold can be established for the number of treated cases above which the positive relation plateaus. and those components of patient care that can be effectively delivered outside the specialist centre should be provided closer to patients’ homes. professionals and parents are working together to concentrate care into one national childhood cancer centre.
Parents.45 one person in 1000 in the general population in high-income countries is a survivor of childhood cancer.12 Despite this issue. the focus has shifted from a cure at any cost approach to cure at a reasonable cost. and advocacy groups are also increasingly involved in deﬁning the aims of clinical trials and helping to design information for trial participants and their families.47 More than 60% of all cancer survivors have at least one chronic health problem. who are culturally and linguistically diverse. 2013 http://dx. to ensure continued innovation that meets the needs of children and young people with cancer. promote earlier diagnosis and the understanding that childhood cancer is curable.encca. web-accessible survivorship passport that supports patients to take proactive responsibility for their follow-up and that encourages mobility of young childhood cancer survivors is being tested as a way to improve quality of life.10 The number of survivors after cancer in childhood and adolescence is substantial.49 to quantify the substantial health risks associated with present treatments.1016/S1470-2045(13)70010-X 7 . population-based childhood cancer registries and ensure that childhood cancer is a notiﬁable disease in all countries • Ensure high-quality training and education of health professionals who treat and care for children with cancer • Support research to develop care (protocols. The support provided by national parent and patient groups to address local issues ranges from practical help with accommodation and peer support groups to enable centralised specialist care services to function well. The aim now is to provide cure with the least possible cost to patients. in many countries the focus on survivorship issues and late effects is fragmented or absent. despite the good intentions of paediatric medical regulations that have come into force in North America and Europe. accessibility. the therapeutic alliance between patients and parents. This development presents speciﬁc challenges in terms of clinical trial participation and delivery of care in partnership with families. more than 20–25% of childhood cancer survivors are aged 40 years or older. however. through PanCare SurFup and the European Network for Cancer Research in Children and Adolescents. For example.doi.15 Only in this way will the clinical needs of patients be given appropriate priority over ﬁnancial incentives. and on society is evident. many high-income countries still do not have a coherent national plan for children and young people with cancer. Panel 3: Key policies to improve care for children with cancer51 • Guarantee the availability.com/oncology Published online February 20.eu For more on the European Network for Cancer Research in Children and Adolescents see http://www. Comprehensive studies in survivors of childhood cancers have taken place both in the USA12 and in some European countries48. and end the stigma and myths attached to the illness • Secure (through legislation. or one that recognises these patients’ unique demographic characteristics and care needs. However. and almost 30% have a severe or life-threatening illness. and the number in Europe is estimated to be between 300 000 and 500 000. This strong link between quality of care and research activity is dependent on national resources and healthcare priorities being aligned to support the improvement of care for children with cancer. guidelines) that is adapted to local resources and needs • Support the establishment of specialist late effect clinics and empower survivors of childhood cancers Conclusions The single biggest contributing factor to the substantial improvements in survival of children with cancer seen in the past few decades is the longstanding integration of clinical research into front-line care in paediatric oncology.Series Survivorship and late eﬀects As care and treatment in paediatric oncology has evolved during the past 40–50 years. and clinician-led research needs to be extended to include relevant pharmaceutical companies and drug regulators.pancaresurfup.eu Parent organisations The International Confederation of Childhood Cancer Parents’ Organisations (ICCCPO) is an increasingly inﬂuential voice in driving improvements in cancer care for children worldwide.org/10.thelancet.51 For more on ICCCPO see http:// icccpo. The policy of involving parents and children in strategic thinking is another major factor that has also contributed to increasing quality of care. Several such actions have been supported by the European Commission. The other key issue around national planning is the increasing complexity of For more on PanCare SurFup see http://www. if necessary) availability and access to aﬀordable essential drugs and technologies for children with cancer. Increasing numbers of children are being born in highincome countries to ﬁrst-generation and secondgeneration migrants. The speciﬁc needs of the patients and their families vary widely around the world.50 SIOP and ICCCPO have identiﬁed and proposed several key policy issues to be addressed to achieve the aim of improving access to care for children with cancer globally (panel 3). their families. irrespective of where they live • Support the establishment of effective. Despite improvements in the development of national cancer control plans. and affordability of health services for the early detection and treatment of childhood cancer • Provide effective information campaigns with a broad societal reach to create awareness of the early warning signs of childhood cancer. to strategic policy work with politicians and regulators to ensure that resources are focused on innovation that addresses the major unmet clinical needs of children and young people with cancer. According to one estimate. such as the UK and the Nordic countries. the burden on individuals.46 In countries with long periods of follow-up. older patients.org www. Now is the time to act to empower patients and their families to reduce this risk and to proactively manage their anticipated health problems. The number of survivors of childhood cancer in the USA is estimated to be 328 000 people. creation of a personalised.
1016/S14702045(13)70008-1. et al. 8 Vassal G. Oxford: Oxford University Press. 2005.doi. An appropriate search strategy to explore the topics covered in this paper would be: “paediatric” OR “pediatric” OR “child” OR “children” AND “oncology” OR “cancer” OR “malignancy” OR “leukemia” OR “leukaemia” AND “care” OR “pathways” OR “systems” OR “treatment”. London: National Institute for Health and Clinical Excellence. http://www.siop-online.1016/S1470-2045(13)70010-X . We also used data from the UN. For every child with cancer whose life is saved as a result of adequate care. 2013 http://dx.eu/ rarecancers/Rare_Cancers_list_March2011. The Erice Statement. published online Feb 20. Shin HR. 2013). Acknowledgments This work has received funding from the European Union’s Seventh Framework Programme (FP7/2007–13) under the European Network for Cancer Research in Children and Adolescents project (grant number 261474). 7 WHO. Paediatric cancer in low-income and middle-income countries. http:// www. 355: 1572–82.doi. 2012). Bethesda: National Cancer Institute.cancer. what is often seen as the small problem of childhood cancer is actually an important public health issue. Kroll ME. 2009. 364: 2097–105. References 1 Steliarova-Foucher E. WHO. 2012).int/whosis/mort/download/en/ index. Stiller C. 11: 201–14. org/10.who. 5 NICE.rarecare. Long term survivors of childhood cancer: cure and care. Parkin DM. 23: 2464–69. Geneva: World Health Organization. Zwaan CM.xls (accessed June 12. et al. 14 Magrath I. Sigman CC. especially the section about survivorship. New York: United Nations. WHO mortality database. http://dx. et al. et al.org/10. LH contributed content about long term follow-up and survivorship. RP. 12 Oeffinger KC. 17 RARECARE rare cancers list. Cancer in children and young people is only a small proportion of the global cancer burden. Lancet Oncol 2013.iarc.eu/ binarydata.siope. ed. both socially and economically. summary tables. and the large cancer databases (GLOBOCAN. Sklar CA. In: Stiller C. childrensoncologygroup. 18 International Society of Paediatric Oncology.org/page/about-siop-0 (accessed Jan 16. Nat Rev Drug Discov 2012. 43: 1778–80. eds. et al.Series Search strategy and selection criteria Papers published in English since January. 2012. Ann Oncol 2012. the infrastructure will not be in place to deal with what will have become the most common disease-related cause of death in childhood. Lancet Oncol 2013. 2012). 2007. http://seer. 2011. 2 Stiller CA. Kroll ME. Population Division. 2010.uk/nicemedia/ live/10899/28876/28876. Now is the time to put the infrastructure in place. Spinetta JJ. Edwards B. collaborative clinical trials and other research. 13 WHO. March 2011. http://www. Ban I. Department of Economic and Social Affairs. 2013). Lyon: International Agency for Research on Cancer. IARC Scientiﬁc Publications No 160. Kowalczyk JR. 4 European standards of care for children with cancer.org.org/index. Cancer incidence in ﬁve continents. http://globocan. 8 www. many years of productive life can be preserved. N Engl J Med 2006. Krapcho M. LH. and GC contributed content based on their personal experiences in running international.html (accessed Nov 25.1016/S1470-2045(13)70013-5 9 Kelloff GJ.aspx?type=doc/European_Standards_ﬁnal_2011(1). World population prospects: the 2010 revision. Warsaw: European Society of Paediatric Oncology. Mertens AC. 2011. whereas for every 70-year-old individual whose cancer is cured or controlled.php/history (accessed Jan 16. SEER). http://www. Conﬂicts of interest We declare that we have no conﬂicts of interest. 10 Haupt R. MCN-W contributed most of the section about parent organisations and commented on the ﬁnal manuscript. All authors reviewed and approved the ﬁnal submitted version of the report.pdf (accessed Sept 7. Noone AM. particularly in terms of training and resources for high-quality care and research to sustain innovation.doi. Kaatsch P. ES-F contributed most of the content about epidemiology. Geneva: World Health Organization. Agarwal B. 20 Curado MP. This number is staggering in view of the fact that 80% of all childhood cancers are potentially curable with present treatments. when infant mortality and mortality in children younger than 5 years have fallen. 6 United Nations.doi. the potential in terms of the years of life that might be saved is substantial. Our history. Every day roughly 250 children around the world lose their lives to cancer. Shin HR. Lancet Oncol 2013. managing the rare and heterogeneous types of cancers that affect children and young people.fr (accessed May 11. If policy makers continue to fail to pay attention to this issue then in 10 years. 1970 were considered relevant for this Series paper. Eur J Cancer 2007. 15 Sullivan R. 19 Children’s Oncology Group.org/10. This difficulty makes the need for specialised centres of excellence and referral pathways important components of care planning.gov/csr/1975_2009_pops09/results_ merged/sect_29_childhood_cancer_iccc. http://dx. Contributors KP-J ﬁrst conceived of the report and coordinated the speciﬁc contributions of each author. Steliarova-Foucher E.pdf (accessed Dec 12. www. 2013). Chronic health conditions in adult survivors of childhood cancer.int/gho/mortality_ burden_disease/global_burden_disease_DTH6_2008. Cancer biomarkers: selecting the right drug for the right patient.com/oncology Published online February 20. Improving outcomes in children and young people with cancer. and analysed global data to produce all of the ﬁgures. 16 Howlader N. New policies to address the global burden of childhood cancers. maybe only another 5 years of additional survival can be expected. Childhood cancer in Britain. Epelman S. but for children with cancer and their families access to treatment is the difference between life and death. Ashley D. 11 Ferlay J. Eatock EM. PD. 2007: 131–204. Survival from childhood cancer. Viewed through this prism. 2012).thelancet. http://www.pdf (accessed Dec 21. 2012). et al. 2011). Mathers C.xls (accessed Jan 5. Lancet 2004. http://www. Lyon: International Agency for Research on Cancer. ACCIS. Population survival from childhood cancer in Britain during 1978–2005 by eras of entry to clinical trials. Geographical patterns and time trends of cancer incidence and survival among children and adolescents in Europe since the 1970s (the ACCIS project): an epidemiological study. GHR. vol IX.org/10. et al. http://dx.1016/S14702045(13)70007-X.who. Pritchard-Jones K. 3 Stiller CA.nice. published online Feb 20. SEER cancer statistics review 1975–2009. hope and despair. Cited references are illustrative of the authors’ major points and are not meant to be exhaustive. published online Feb 20. Bray F. et al. GLOBOCAN 2008 v1.2—cancer incidence and mortality worldwide: IARC CancerBase No 10. Although the number of children with cancer is much smaller than the number of adults. About SIOP. Causes of death 2008. New drugs for children and adolescents with cancer: the need for novel development pathways. KP-J. Forman D.
population structure. Ioka A. Japan. 28 Parkin DM. Brownbill PA. a report from the Children’s Oncology Group. Am J Hematol 2012. 44 Sainsbury R. Winter DL. Green S. Desch CE. et al. Przepiorka D. for the British Childhood Cancer Survivor Study Steering Group. Yabroff KR. Blood 2010. Draper GJ. 2012. Adolescents and young adults with acute lymphoblastic leukemia have a better outcome when treated with pediatric-inspired regimens: systematic review and metaanalysis. Craft AW. Childhood medulloblastoma in Ontario. Cancer incidence and survival in European adolescents (1978–1997). et al. Craniotomy for resection of pediatric brain tumors in the United States. 54: 553–63. et al. Barker FG 2nd. N Engl J Med 1948. Labopin M. 1980–1994. International Confederation of Childhood Cancer Parent Organizations and International Society of Paediatric Oncology. 34 Stiller CA. et al. Möller T. ICCCPO–SIOP response to WHO discussion paper on non-communicable diseases. Ann Oncol 2013. Haward B. 137: 511–20. Lyon: International Agency for Research on Cancer. et al. Wallis JC. Jenkin RD. J Natl Cancer Inst 2009. 33 Hillner BE. www. Pitt V. 238: 787–93. Dirksen U. 87: 472–78. Anderson H. adolescents and adult patients. The volume effect in paediatric oncology: a systematic review. 115: 3437–46. 1998. 2012). 22 Ram R. Improving recruitment to clinical trials for cancer in childhood. et al. et al. Wagget J. 101: 787–92. Cancer Sci 2010.com/oncology Published online February 20. McCarthy BJ.onlinebase. 25 Baba S. 23 Kohler BA. 79: 2771–74. Temporary remissions in acute leukemia in children produced by folic acid antagonist. Cancer Epidemiol Biomarkers Prev 2009. 18: 1033–40. CMAJ 2009 180: 422–24. et al. JAMA 2007. Passmore SJ. 42 Klingebiel T. Should HLA-identical sibling bone marrow transplants for leukemia be restricted to large centers? Blood 1992. Holmes E. 26 Ellison LF. Cancer Treat Rev 2007. Br J Cancer 2010. Canadian Cancer Society’s Steering Committee for Canadian Cancer Statistics. response rates and initial descriptive information. Long-terms survivors of childhood cancer in the United States. Naafs-Wilstra M. 1977–1987: population-based results. 29 Farber S. The British childhood cancer survivor study: objectives. 18: 2327–40. 26: 1–9. vol II. Johnston C. Ewing tumours: outcome in children. eds. Noda H. What needs to be done to improve cancer pathways? Arch Dis Child 1988. Kroll ME. 47: 879–85. Lancet Oncol 2008. Sposto R. Butler WE. Ranft A. Scott JE. et al. Br J Cancer 1987. Annual report to the nation on the status of cancer. International patterns of cancer incidence in adolescents. 56: 853–58. The effect of provider case volume on cancer mortality: systematic review and meta-analysis. 1973–2001. Ann Intern Med 2002. Br J Cancer 2006. Lancashire ER. Ajiki W. Jolley D.doi. 4-aminopteroyl-glutamic acid (aminopterin). Smith TJ. Chassin MR.thelancet. Long-term cause-speciﬁc mortality among survivors of childhood cancer. JAMA 2010. Population-based survival estimates for childhood cancer in Australia during the period 1997–2006. 38 Danjoux CE. Progress in childhood cancer: 50 years of research collaboration. 63: 23–30. pdf (accessed Dec 9. Lee C. 45 Olsen JH. 101: 806–13. Tsukuma H. Semin Oncol 2008. Is volume related to outcome in health care? A systematic review and methodologic critique of the literature. Rowland JH. Krailo M. SIOP.Series 21 Stiller CA. The Northern Region children’s malignant disease registry 1968–82: incidence and survival.org/10. Winter DL. Hospital and physician volume or specialization and outcomes in cancer treatment: importance in quality of cancer care. Inﬂuence of clinician workload and patterns of treatment on survival from breast cancer. 1988 to 2000: effects of provider caseloads and progressive centralization and specialization of care. 345: 1265–70. 50 Pritchard-Jones K. CA Cancer J Clin 2009. 31 Gruen RL. Danon SE. 297: 2705–15. 35 Knops RRG. Cornish J. Pediatr Blood Cancer 2008. McLaughlin J. International incidence of childhood cancer. Diamond LK. Neurosurgery 2004. Neurosurgery 2000. J Clin Oncol 2000. et al. Eur J Cancer 2007. Rider L. Amineddine HA. Campbell D. Canadian cancer statistics at a glance: cancer in children. 35: 484–93. methods. 2013 http://dx. 48 Reulen RC. Kremer LC. Vidal L. 103: 714–36. Iso H. 1975–2007. Jurgens H. 47 Hawkins MM. et al. 40 Stiller CA. Kramárová E. Incidence and survival trends for childhood cancer in Osaka. 94: 22–29. Lancet 1995. 50: 1018–25. 103: 1663–70. 59: 192–211. 5 (suppl): 209–15. Mercer RD. Report from the Automated Childhood Cancer Information System project. 30 O’Leary M. 32 Halm EA. et al. Ward E. Youlden DR. http://cms. J Natl Cancer Inst 2011. 43 Horowitz MM. Med Pediatr Oncol 1996. Frobisher C. 27 Stiller CA. 304: 172–79.1016/S1470-2045(13)70010-X 9 . Wolff JA. IARC Scientiﬁc Publications No 144. Valsecchi MG. Eur J Cancer 2006. DOI:10. 51 ICCCPO. Mulder RL. Cardous-Ubbink MC. Lifelong cancer incidence in 47 697 patients treated for childhood cancer in the Nordic countries. Desandes E. 24 Baade PD. Mery LS. et al. 33: 631–45. published online Feb 1. Reaman GH. 46 Mariotto AB. 39 Craft AW. van Dalen EC. Dixon-Woods M. Anderson JR. Medical assessment of adverse health outcomes in long-term survivors of childhood cancer. 9: 392–99. Parkhill A. Sylvester RF. De P. et al. featuring tumors of the brain and other nervous system. 41 Paulussen M. 42: 2006–18. Patterns of care and survival for patients aged under 40 years with bone sarcoma in Britain. Results and factors inﬂuencing outcome after fully haploidentical hematopoietic stem cell transplantation in children with very high-risk acute lymphoblastic leukemia: impact of center size: an analysis on behalf of the Acute Leukemia and Pediatric Disease Working Parties of the European Blood and Marrow Transplant group.1093/annonc/mds656. Round C. 49 Geenen MM. Champlin RE. Valery PC. 36 Albright AL. 37 Smith ER. Grundy PE. et al. Correlation of neurosurgical subspecialization with outcomes in children with malignant brain tumors. Wolach O.nl/ userﬁles/c1icccpo/ﬁle/ICCCPO-SIOP_Response_to_WHO_120419.
This action might not be possible to undo. Are you sure you want to continue?
We've moved you to where you read on your other device.
Get the full title to continue reading from where you left off, or restart the preview.