The JARC is coordinated by the Fondazione IRCCS Istituto ......Affordability across Europe is anticipated to be a major issue with new effective but expensive medicines for the treatment

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D33, D9.1 Report summarising the result of the survey on accessibility of standard treatment and recommendations to Member States and Europe to overcome bottlenecks The JARC is coordinated by the Fondazione IRCCS Istituto Nazionale dei Tumori of Milan

(Italy).

Work Package 9 is coordinated by SIOP Europe – the European Society for Paediatric

Oncology.

“This Deliverable is a part of the joint action “724161/JARC” which has received funding from the

European Union’s Health Programme (2014-2020)”.

“The content of this Deliverable represents the views of the authors only and they are sole

responsibility: it can not be considered to reflect the views of the European Commission and/or the

Country, Health, Agriculture and Food Executive Agency or any other body of the European Union.

The European Commission and the Agency do not accept any responsibility for use that may of the

information it contains”.

Ref. Ares(2019)2869557 - 29/04/2019

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Table of Contents

DELIVERABLE DESCRIPTION ............................................................................................. 3

ESSENTIAL MEDICINES REPORT ....................................................................................... 9

Introduction ................................................................................................................................ 9

Objectives ................................................................................................................................. 10

Methods .................................................................................................................................... 10

Results ...................................................................................................................................... 13

Discussion and Recommendations ........................................................................................... 25

Table 1: List of medicines ........................................................................................................ 32

Acknowledgements .................................................................................................................. 34

References ................................................................................................................................ 35

Annex 1: Country list ............................................................................................................... 37

Annex 2: Questionnaire for health professionals ..................................................................... 38

Annex 3: Questionnaire for parents ......................................................................................... 52

RADIOTHERAPY REPORT .................................................................................................. 54

Introduction .............................................................................................................................. 54

Objectives ................................................................................................................................. 55

Methods .................................................................................................................................... 55

Results ...................................................................................................................................... 57

Discussion ................................................................................................................................ 59

Acknowledgements .................................................................................................................. 60

References ................................................................................................................................ 62

Annex 1: Country list ............................................................................................................... 63

Annex 2: Questionnaire ............................................................................................................ 64

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DELIVERABLE DESCRIPTION

Joint Action on Rare Cancers (JARC) The Joint Action on Rare Cancers (JARC) is aimed to integrate and maximize efforts of the European Union (EU) Commission, EU Member States and all stakeholders to advance quality of care and research on rare cancers. The public health challenges posed by rare cancers include the limited professional expertise in the community, the difficulties in clinical research, the need of a timely and appropriate diagnosis and optimal treatment from the very beginning of the patient’s journey. An accurate clinical, pathologic and biological assessment of the disease of the individual patient is key to survival and cure, as well as an expert clinical decision provided by a multidisciplinary team. To this end, proper referral of patients and effective clinical networking are crucial in rare cancers. This is the main reason why JARC decided to shape its efforts around the new European Reference Networks (ERNs) with the following objectives: 1. Improving epidemiological surveillance of rare cancers in the EU 2. Identifying standards of care for all families of rare cancers to ensure sharing of

best practices and equality of care for rare cancers across Europe, particularly through clinical networking

3. Improving the implementation at local level and within ERNs of clinical practice guidelines on rare cancers

4. Promoting integration of translational research innovations into rare cancer care 5. Improving education on rare cancers for medical and non-medical experts to

ameliorate management of rare cancers and to improve rare cancer patients’ empowerment in the EU

6. Identifying core strategies to incorporate in National cancer plans and Rare disease plans to address the specific needs of rare cancers across EU MSs

The JARC is structured in 10 work packages (WPs). Three cross cutting WPs (WP1 coordination, WP2 dissemination, WP3 evaluation) and 7 specific WPs based on the JARC objectives: WP4 epidemiology, WP5 quality of care, WP6 clinical practice guidelines, WP7 innovation and access to innovation, WP8 medical education, WP9 childhood cancers and, WP10 rare cancers policy. Patients work across all work packages, driving the JARC efforts along the needs of the only end users of all what we can do, in care and research as well. Description of WP Work Package 9 – Childhood cancers contains actions to define evidence-informed recommendations for:

- Ensuring access to standard and innovative therapies for children with cancer - Addressing the research and clinical issues in young people with extremely

rare cancers and in survivors of childhood cancers.

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The aim and the purpose of the specific deliverable

Eighty percent (80%) of children and adolescents with cancer can be disease-free at 5 years by a combination of systemic agents, surgery and/or radiotherapy if they have access to standard of care multidisciplinary treatments. However, the essential therapies to cure, support and palliate children and adolescents with cancer are not consistently available and accessible across Europe. The aim of the deliverable was to explore the specific barriers and bottlenecks regarding access to essential medicines and radiotherapy resources used in the treatment of children and adolescents with cancer in each of the 28 EU Member States and other European countries and to make recommendations for improvements based on the generated evidence.

The purpose of this deliverable is to consolidate evidence on the state of access to essential medicines and high-quality radiation therapy for paediatric cancer and to

formulate recommendations to decision makers at the national and the European level on their basis.

The target group of the specific deliverable The recommendations are targeted to stakeholders involved in decision-making on healthcare organisation and delivery both at the national and at the EU level, the latter considering the value of cross-border collaboration in the field of paediatric cancers as a collection of rare diseases.

Summary of the main conclusions of the deliverable

Essential medicines

• 68 medicines with anticancer properties have been listed by experts from the

SIOP Clinical Research Council as used for the treatment of paediatric

malignancies. 24 of these medicines are included in the World Health

Organisation’s Model List of Essential Medicines for Children 2017 (WHO

EMLc).

• A survey on various aspects of medicines accessibility has been sent to

clinician, pharmacist and parents associations in up to 37 countries. Completed

answers from at least one stakeholder group – clinician, pharmacist, or parent

- were obtained from 34 countries: 27 Member States of the EU and 7 non-EU

countries, namely: Bosnia and Herzegovina, Israel, Montenegro, Norway,

Serbia, Switzerland, and Turkey.

• Parents and health professionals across Europe still experience issues of

access to the listed medicines for paediatric malignancies.

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• Countries that are particularly affected by access issues may be described as

those with a relatively low health expenditure rate.

• The medicines on the WHO EMLc have overall better accessibility compared to

the other medicines included in the list.

• Shortages of medicines are perceived as the most common reason for lack of

availability, with potentially critical implications for children’s lives.

• Budget limitations at the country or hospital level appear a less relevant reason

for lack of access but are still pronounced in some countries.

• Costs of treatments are an issue more in relation to the newer medicines.

Affordability across Europe is anticipated to be a major issue with new effective

but expensive medicines for the treatment of paediatric malignancies entering

the market.

• There are major differences in pain control accessibility for children undergoing

treatment for cancer among countries in Europe. Adequate supportive and

palliative care services are necessary for children, and opioids that manage

cancer pain are inexpensive and should be provided to avoid that children suffer

unnecessarily.

• The number of medicines available in child-friendly doses and formulations is

far below the needs.

- Recommendations to actors at the national level:

1. Reinforce the importance of access to essential medicines for paediatric

malignancies in national cancer plans or equivalent instruments guiding cancer

care at the national level;

2. Foster that all strategies and actions to improve access to medicines include

the agents used for the treatment and supportive care of childhood cancers,

with reference to the WHO essential medicines for children, the current survey

list, and their respective updates;

3. Foster national policy measures for manufacturers and other actors in the

supply chain to maintain adequate medicine stocks and exchange timely

information to avoid shortages;

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4. Allocate appropriate resources and facilities to enable availability of child-

friendly doses and formulations of essential anticancer medicines for the

paediatric population;

5. Ensure appropriate pricing and reimbursement strategies, in particular for new

anticancer medicines that are becoming available for the paediatric population,

with consideration for the life span gained through successful treatment in this

age group;

6. Set up appropriate pain control for 100% of children undergoing procedures as

an objective at the national level to be reached within 2 years.

- Recommendations to actors at the European level:

1. Consider including the list of medicines used for the current survey in European-

level reference lists of essential medicines, including the next revision of the

WHO Essential Medicines List for Children;

2. Set up a coordinated initiative with EU Member States and other European

countries to monitor and anticipate medicine shortages as well as to facilitate

and share the development of solutions;

3. Support policies, programmes and projects to overcome inequalities in access

to essential medicines used for the treatment and supportive/palliative care of

childhood cancers across Europe;

4. Improve the regulatory environment to foster paediatric medicine development

for childhood cancers, including issues related to the ‘EU Paediatric Regulation’

legislation and its implementation;

5. Facilitate international dialogue and cooperation regarding value-based

medicine pricing models for children cured of cancer, including the length of

their future life span compared to adults;

6. Support further research on access to medicines used for the treatment and

supportive/palliative care of paediatric malignancies across Europe;

7. Support outcome research projects, including economic data, to adequately

monitor the optimal use of medicines in both paediatric and adult cancers.

- Recommendation all stakeholders:

1. Engage in multi-stakeholder cooperation to ensure that safe, effective,

sustainable, and affordable quality cancer medicines defined as essential are

within reach for all children who require them across Europe.

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Radiotherapy

• National guidelines for paediatric radiotherapy are available in 3 European

countries.

• Based on available guidelines and expert opinion of stakeholders from SIOP

Europe and its QUARTET Committee, CCI Europe, ESTRO, and PROS,

recommendations for the organisation of care in paediatric radiotherapy across

Europe have been defined focusing on patient care, education, and research.

The take-home messages are summarised below.

• Over 250 paediatric radiotherapy centres and their representatives have been

mapped in the SIOP Europe region including all EU Member States.

• A survey focusing on the organisation of care for paediatric radiotherapy has

been sent to all centres to investigate the state of affairs in Europe.

- Recommendations on patient care

1. Ensure that all patients are discussed in appropriately documented and staffed

multi-disciplinary team meetings at diagnosis, treatment response evaluation,

and any suspicion of progression or relapse;

2. Foster the provision of information to the family and the patient in an age-

appropriate manner regarding the indication for radiation therapy, potential side-

effects, and the procedures and logistics involved in treatment preparation and

delivery;

3. Consider the use of highly-conformal radiation therapy as the standard of care;

4. Foster optimal daily reproducibility to maximise target dose coverage and

reduce the risk of late effects by emphasising:

o Specifically manufactured tools and technologies, o Specialised personnel with affinity for paediatric patients, o Access to a central review of treatment plans, o Personalised and age-specific approaches.

5. Facilitate referrals to specialised centres when the required techniques or

procedures are not available in-house, such as for advanced photon

techniques, proton beam therapy or brachytherapy.

6. Foster systematic registration of moderate to severe long-term side effects to

improve prevention and management of later toxicities in childhood cancer

survivors.

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- Recommendations on education

1. Ensure that the professional qualifications and development curricula of

relevant personnel foresee basic education in paediatric radiation oncology and

paediatric oncology, and regular courses and exchange at National, European

and International levels.

- Recommendations on clinical research

1. Foster centre participation and enrolment of patients in ongoing and therapy-

optimising studies, registries, and/or adherence to (inter)national guidelines.

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ESSENTIAL MEDICINES REPORT

Introduction Cancer remains the leading cause of children’s mortality by disease in Europe, with more than 6,000 young patients dying each year (International Agency for Research on Cancer, 2018). Eighty percent (80%) of children and adolescents with cancer can be disease-free at 5 years if they receive the appropriate standard treatments in a multidisciplinary setting. Significant progress has been achieved through academic clinical research that established optimal use of anticancer chemotherapy in combination with supportive modalities such as antibiotic, antifungal, antiviral, pain control medicines and blood transfusions required to deliver the right dosage and achieve remission. However, the essential therapies to cure, support and palliate young cancer patients are not equally available and accessible to all those who need them. These inequalities contribute to differences in childhood cancer survival rates of up to 20% across Europe (Gatta G, 2014). To foster equal access to the best paediatric cancer care and expertise is a major goal of the pan-European community, embedded in the European Standards of Care for Children with Cancer (Kowalczyk JR, 2014) and the SIOPE Strategic Plan (Vassal G, 2016). The equal access objective as described above is operationalised at the European level through the European Reference Network for Paediatric Oncology (ERN PaedCan), a virtual structure that involves healthcare providers across Europe to deliver high-quality, accessible and cost-effective cross-border healthcare to children and adolescents with cancer, regardless of where they live (ERN PaedCan, n.d.). Through the European Reference Network model, Member States cooperate to streamline the patient journey for conditions that require specialist expertise and tools not widely available due to low case volumes at the national level. Considering the Member States’ primary responsibility for healthcare organisation and delivery on their territories, understanding the specific realities in each country is highly important to foster the best standard care for children with cancer in Europe. Essential anticancer medicines are an indispensable component of any multidisciplinary treatment plan that should be available to children and adolescents with cancer. Within the JARC, SIOP Europe and partner organisations an European survey was undertaken on the availability and accessibility of essential medicines for paediatric malignancies, based on the World Health Organisation’s Model List of Essential Medicines for Children and supplemented with additional agents identified by paediatric cancer experts, with the aim to formulate recommendations to decision-makers at the national and European levels based on the findings.

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Objectives

The specific objectives of the JARC survey on the availability and accessibility of essential medicines for paediatric malignancies were:

• To assess the perceptions and experiences of health professionals and parents across Europe regarding:

o Availability of essential medicines used in the treatment of paediatric malignancies, including reasons for perceived non-availability;

o Out-of-pocket costs of essential medicines used in the treatment of paediatric malignancies;

o Suitability of formulation and dosage of the orally administered essential anticancer medicines for the paediatric population.

• To assess the perceptions of health professionals across Europe regarding the licensing and actual use of essential medicines used in the treatment of paediatric malignancies;

• To assess the perceptions of parents across Europe regarding the availability of medicines to control pain and other side-effects of core treatments for paediatric malignancies.

Methods

The survey was based on the questions and methodology developed by the European Society for Medical Oncology (ESMO) in its European and International Consortium Studies on the availability, out-of-pocket costs and accessibility of antineoplastic medicines (Cherny N, 2016) (Cherny N, 2017).

Project steering group A Core Working Group of the main stakeholders concerned with access to essential anticancer medicines in Europe was convened to steer the activities:

• The European Society for Paediatric Oncology (SIOP Europe, paediatric haematology oncology clinicians),

• Childhood Cancer International Europe (CCI Europe, parents),

• European Society of Oncology Pharmacy (ESOP, pharmacists),

• European Society for Medical Oncology (ESMO, medical oncologists).

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The Core Working Group was tasked to define the survey methodology and content, lead the analysis of the results, and formulate targeted recommendations on their basis. Experts met face-to-face on 14 September 2017 and held regular teleconferences throughout the project. The Core Working Group was supported by the SIOP Europe office for documenting group discussions, survey design and dissemination, and drafting the report. Target respondents It was agreed to collect information from associations of paediatric haemato-oncologists, pharmacists, and parents. These three groups correspond to the membership of SIOP Europe, ESOP and CCI Europe, respectively. The geographical scope of the survey included all EU Member States as well as additional countries covered by SIOP Europe as well as Montenegro, for a total of 37 countries (Annex 1). The membership of SIOP Europe and ESOP is represented mostly by national societies of paediatric haematology and oncology and hospital pharmacy, respectively. It was thus decided to collect national-level data from these health professionals. SIOP Europe and ESOP contacted their members with the request to nominate a lead rapporteur and a substitute rapporteur for the survey with an explanation regarding the initiative’s content and purpose. In the SIOP Europe approach, the chair of the national member society or institution was regarded as the rapporteur if no other expert was nominated. SIOP Europe respondents from 36 countries and ESOP respondents from 24 countries were identified. In line with the national-level focus, there was a maximum of one rapporteur from SIOP Europe and one rapporteur from ESOP in each country. The CCI Europe membership is represented by parent and patient organisations that may work at the hospital level. Data from parents was thus collected from all CCI Europe-affiliated organisations in the region covered by the survey. The number of CCI Europe respondents varied from one to up to seven per country and covered 32 countries. List of medicines The essential medicines in the scope of the survey were selected based on the World Health Organisation’s Model List of Essential Medicines (EML) (all specialities) for children (WHO EMLc) (World Health Organization, 2017) and the expertise of members of the SIOP Europe Clinical Research Council, composed of all disease-oriented European Clinical Trial Groups and national paediatric haematology and oncology societies. The final list of medicines was validated by the paediatric haematology and oncology experts in the Core Working Group (Table 1). European experts considered that 44 anticancer medicines, in addition to the 24 listed on the WHO EMLc, were needed for the treatment of paediatric malignancies. Thus, 68 medicines with anticancer properties have been listed by experts from the SIOP Europe Clinical Research Council as used for the treatment of paediatric malignancies: haematological malignancies, extracranial malignant solid tumours, and central nervous system (brain) tumours. 24 of these medicines are included in the WHO EMLc (World Health Organization, 2017). In addition, the WHO EMLc includes 4 medicines for supportive care, namely, allopurinol (for the treatment of tumour-lysis-

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induced hyperuricemia during the treatment of leukaemia, lymphoma and some solid tumours), calcium folinate (used as antidote with high dose methotrexate for the treatment of leukaemia, non-Hodgkin’s lymphoma, osteosarcoma and some brain tumours), filgastrim (prescribed to treat or prevent chemotherapy-induced neutropenia) and mesna (used to prevent ifosfamide- and high-dose-cyclophosphamide-induced haemorrhagic cystitis). These 4 medicines were not part of the JARC survey. The ESMO European Consortium Study on the availability, out-of-pocket costs and accessibility of antineoplastic medicines in Europe (Cherny N, 2016) concerned 49 medicines, but only for the treatment of adult solid tumours. The ESMO list did not contain any medicines for haematological malignancies. 25 medicines (51%) listed in the ESMO study for adult solid tumours are used in paediatric haematology and oncology. Survey components There were three (3) questionnaires as follows:

• Questionnaire on essential anticancer medicines for health professionals

(physicians and pharmacists);

• Questionnaire on palliative, supportive and pain control medicines for health

professionals (physicians and pharmacists);

• Questionnaire encompassing both anticancer and palliative, pain control, and

supportive medicines for parents.

The questionnaire on palliative, supportive and pain control medicines for health professionals was not analysed for the purposes of this deliverable; therefore, the report focuses on the questionnaire on essential anticancer medicines for health professionals and on the questionnaire for parents. Questionnaire for health professionals The questionnaire for health professionals was built around the validated list of anticancer medicines. There were 7 overarching questions, most requiring a separate response for every medicine on the list. The questions addressed the following topics: the regulatory approval of the medicines for use in children, their actual use in children, their availability in the past 2 years, any barriers to their prescription, their costs for the patient, and their formulations (Annex 2). Questionnaire for parents The questionnaire for parents contained 5 overarching questions on the following topics: perceived/experienced shortages of anticancer medicines in the past 2 years, out-of-pocket payments, the need to adjust the formulations for children, the availability of agents to control side-effects, and the availability of painkillers and anaesthesia/sedation (Annex 3).

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Survey design and dissemination Both questionnaires were designed in an online format using SurveyMonkey software and pre-tested. The survey was introduced at the annual face-to-face meetings of the respondent societies in 2018: the SIOP Europe Clinical Research Council meeting, the CCI European conference, and the ECOP (ESOP) Congress. SIOP Europe, ESOP and CCI Europe sent out invitations to respective national rapporteurs in April-May 2018, with the first deadline for responses on 30 June 2018. The official deadline was extended to 30 September 2018. A series of reminders were sent. The survey was closed in November 2018. Strategy of analysis Regarding the data from health professionals, results were presented for all 68 medicines (full survey list) as well as separately for the 24 medicines listed on the WHO EMLc. For countries where both the physician and pharmacist replied and provided divergent answers, these rapporteurs were contacted and asked to provide a common validated response. If no common response was obtained, the diverging answers were encoded as ‘Don’t know’. Where the responses provided by the rapporteur required further information, a teleconference with the respondent was held. The data from parents was analysed at the individual or hospital level without aggregation where more than one response per country was supplied.

Results

All responses Completed answers from at least one stakeholder group – clinician, pharmacist, or parent - were obtained from 34 countries: 27 Member States of the EU and 7 non-EU countries, namely: Bosnia and Herzegovina, Israel, Montenegro, Norway, Serbia, Switzerland, and Turkey. All three stakeholder groups provided a response for 7 countries: Belgium, Estonia, France, Lithuania, Spain, Sweden, and Switzerland. There was a response from at least one of the health professionals (pharmacist and/or paediatric haemato-oncologist) and parent for 16 countries: Austria, Belgium, Bulgaria, Croatia, Estonia, France, Ireland, Italy, Lithuania, Netherlands, Portugal, Romania, Serbia, Spain, Sweden, and Switzerland. No response was provided from 3 countries: Iceland, North Macedonia and UK. Data from Health Professionals Completed answers were obtained from 30 countries which are part of SIOP Europe: 25 members of the European Union (EU) and 5 non-EU countries, namely, Israel, Norway, Serbia, Switzerland, and Turkey. Complete data were missing from 7 countries: Bosnia & Herzegovina, Iceland, Luxembourg, Montenegro, North Macedonia, Slovakia and the UK.

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Responses were received from both rapporteurs (paediatric haemato-oncologist and pharmacist) and a joint validated response obtained for 8 countries: Czech Republic, Estonia, Hungary, Latvia, Poland, Slovenia, Switzerland, and Turkey. In addition, joint responses were obtained directly for 4 countries as the same rapporteur was nominated by SIOP Europe and ESOP: Belgium, Malta, Lithuania, and Spain. In 2 further countries, the response was coordinated by the nominated paediatric oncologist in cooperation with a pharmacist from their institution: France and Sweden. Therefore, input by both a paediatric oncologist and a pharmacist was obtained for a total of 14 countries. Data from the paediatric oncologist only was obtained for 12 countries: Bulgaria, Croatia, Cyprus, Denmark, Finland, Greece, Ireland, Israel, Italy, Norway, Portugal, and Romania. For 4 countries, the response was obtained only from the pharmacist: Austria, Germany, Netherlands and Serbia. - Use of medicines The 68 medicines are used in a median of 93% countries, ranging from 47% to 100% for each individual medicine. The 24 EMLc medicines are used in a median of 100% countries (13 out of 24 agents used in all counties), ranging from 63% to 100% for each. Figure 1: % of countries in which each of the 68 medicines is used (in red, EMLc medicines)

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The 30 countries use a median of 89% of the 68 medicines, ranging from 53% to 100% per country. 71% to 100% (median, 96%) of the 24 EMLc medicines are used in the 30 countries. Figure 2: % of the 68 medicines used in each country

Figure 3: % of the 24 EMLc medicines used per country

- Authorisation for use in children Responders reported that the 68 medicines are authorized for use in children in a median of 47% countries, ranging from 6.7% % to 100% for each individual medicine. The 24 EMLc medicines are reported as authorized in a median of 77% countries ranging from 23% to 97% for each. Figure 4: % of countries in which each of the 68 medicines is reported as authorized (in red, EMLc medicines)

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A median of 51% of the 68 medicines were reported as authorized in the 30 countries, ranging from 22% in Finland to 91% in Italy. The 24 EMLc medicines were reported as authorized in a median of 69% countries, ranging from 17% in Finland to 100%. For 7 countries, 23 to 24 EMLc medicines are reported as authorized. Figure 5: % of the 68 medicines authorised in each country

Figure 6: % of the 24 EMLc medicines authorised in each country

- Off label use Off-label use was estimated from the answers on use and authorization. As a median across the examined countries, 35% of the 68 medicines are reported as prescribed off- label. In 3 countries, namely, Austria, Cyprus and Portugal, none of the used medicines are reported as prescribed off-label. Only 24% (median) of the 24 EMLc medicines are reported as prescribed off-label. In 10 countries, namely, Austria, Belgium, Croatia, Cyprus, Czech Republic, Germany, Italy, Portugal, Israel and Turkey, none of the used EMLc medicines are reported as prescribed off-label. Figure 7: % of used medicines prescribed off-label in each country

Figure 8: % of used EMLc medicines prescribed off-label in each country

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- Availability of medicines For the purposes of the survey, availability was defined as follows: the medicine could be obtained as needed and in a timely manner over the last 24 months. 30 of the 68 medicines (44%) were reported as always available in 90% countries or more. 15 of the 24 EMLC medicines (63%) were reported as always available in 90% countries or more. Figure 9: % of countries in which each of the 68 medicines were always available (in red, EMLc medicines)

Importantly, 5 essential medicines used daily for the treatment of the most frequent paediatric malignancy, namely, acute lymphoblastic leukaemia (ALL), have been reported as always available in less than 60% of responding countries. This concerned the three asparaginase medicines (asparaginase – E Coli; Peg-asparaginase; asparaginase Erwinia) and corticosteroids (oral liquid dexamethasone and prednisone/prednisolone).

- Medicines shortages WHO provides the following core definition of shortage: “The supply of medicines, health products, and vaccines identified as essential by the health system is considered to be insufficient to meet public health and patient needs” (World Health Organization 2016). Over the last 24 months, medicine shortages were reported in at least one country for 49 of all the 68 medicines (72%) and 18 of the 24 EMLc medicines (75%). The three asparaginases used in the treatment of ALL had shortages reported in the most countries: asparaginase E Coli in 5 countries, PEG-asparaginase in 8 countries, and asparaginase Erwinia in 11 countries.

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Figure 10: Number of countries reporting medicine shortages over the last 24 months for each of the 68 medicines

Overall, only 12 countries (40%) did not directly report shortages as the reason for intermittent non-availability of medicines: Croatia, Cyprus, Finland, Hungary, Ireland, Israel, Lithuania, Malta, Norway, Poland, Portugal, and Switzerland. Lithuania indicated “Other” for one agent (Daunorubicin liposomal) and specified later in the survey that the reason was in fact production shortages. The top 5 countries with the largest number of medicines in shortage (more than 10 medicines over the last 24 months) were Bulgaria, Latvia, Romania, Spain and Turkey. Figure 11: Number of medicines reported with shortage over the last 24 months per country (in red, EMLc; in blue, all medicines)

-

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- Medicines not available due to budget limitations During the past 2 years, none of the 24 EMLc medicines was reported as unavailable due to budget limitations in any country. More than half of the remaining non-EMLc medicines (24 of 44), were reported as not available for this reason in at least one country. Figure 12: Number of countries reporting unavailability of at least one medicine due to budget limitations

Bulgaria, Germany, Lithuania and Romania reported the largest number of medicines (more than 5 medicines over the last 24 months) not available due to budget limitations. Figure 13: Number of medicines reported as usually or occasionally unavailable due to budget limitations per country

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- Out-of-pocket costs According to the health professionals, out-of-pocket cost was incurred by patients in 8 of the 30 countries for between 2 and 18% of the medicines used in each country. Figure 14: % of used medicines with out-of-pocket costs per country

Full costs for the patient were reported from Bulgaria, Latvia, Poland, Romania, and Turkey. In Finland and Spain, out-of-pocket costs ranged from 50% to full cost. In Estonia, only a small prescription fee was reported as payable by the patient. - Formulations Out of the 28 orally administered medicines on the survey list, a median of only 9% was reported as always available in child-friendly doses and formulations, but a median of 27% as never available in this format. For the 9 orally administered EMLc medicines, a median of only 22% were reported as always available in a child-friendly format. For the remaining 19 orally administered non-EMLc medicines, this figure was 5%. Availability of child-friendly formulations is thus a major issue for oral medicines used in Europe for the treatment of children with cancer.

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Figure 15: % of oral medicines reported as always available in the appropriate dose and formulation for children in all countries (in red, EMLc medicines)

All 28, including the 19 non-EMLc orally administered medicines, were reported as always available in a child-friendly format only in a median of 10% of the countries. The corresponding percentage for all 9 EMLc medicines was 30%. Figure 16: % of countries where all orally administrable medicines are always available in a child-friendly format

Figure 17: % of countries where orally administrable EMLc medicines are always available in a child-friendly format

Data from Parents 31 answers were obtained from 20 countries: 16 members of the EU and 4 non-EU countries, namely, Bosnia and Herzegovina, Montenegro, Serbia, and Switzerland. There was a median of one answer per country, ranging from 1 to 4. Data was missing from 12 countries: Czech Republic, Denmark, Finland, Germany, Greece, Hungary, Iceland, North Macedonia, Norway, Slovenia, Turkey, and the UK. One anonymous answer was not taken into account in the analysis.

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- Availability 14 answers (44%) from 11 countries (55%) reported issues of medicine shortages over the past 24 months. The 11 countries are: Bosnia and Herzegovina, Bulgaria, Croatia, Estonia, France, Lithuania, Montenegro, Portugal, Romania, Serbia, and Switzerland. The reported actions to address the issue were:

- Contacting local authorities in one’s country 12 85.7%

- Travel to another country 5 35.7%

- Requesting support from NGOs 6 42.9%

- Other (Please specify) 2 14.3%

Fundraising from individual donors

Asking other people who are travelling to get the missing medicines based on medical prescription, with costs covered by NGO

- Costs 10 answers (32%) from 7 countries (35%) reported that parents have been asked to pay for all or part of their child’s/adolescent’s treatment in the hospital(s) over the past 24 months. The 7 countries are: Belgium, Bosnia Herzegovina, Bulgaria, Estonia, Romania, Serbia, and Switzerland. The reported actions to address the issue were:

- Contacting local authorities in one’s country 6 60%

- Requesting funding from NGOs 9 90%

- Other (Please specify) 2 20%

Our organisation regularly helps families to cover such costs, but up to a certain limit - according to the organisation’s financial possibilities

Charity fundraising

- Formulations Most respondents described the frequency of adjusting the dose and format of a child’s medicine as ‘occasionally’ (10 responses, 32%) or ‘usually’ (8 responses, 26 percent) (Figure 15). Only the minority (2 responses, 6%, both from Bosnia and Herzegovina) reported never having to make such adjustments, while 3 (10%) respondents from Croatia, Lithuania and Serbia answered ‘always’.

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Figure 18: Frequency of the need to adjust dose and formulation of orally administered medicines according to parents

The reported actions to adjust the dose or format were crushing or cutting the pills (10 responses, or 32%), breaking pills in half (5 responses, or 16%), and diluting solid dose medications (2 responses, or 6%). The medicines adjusted in this manner were then mixed with food, apple sauce, yogurt, fruit juice, or other sweet liquid. 4 respondents (13%) highlighted that one of the aims was changing the taste of the medicine. One response described adjusting the formulation by dissolving the medicine and administering it via nasogastric tube. The respondent highlighted the inherent risks of this procedure, which includes potentially incomplete dosing and tube blockage. The latter necessitates tube replacement and can be traumatic for children. The same respondent provided a specific example of adjusting the dose of cis-Retinoic acid in neuroblastoma. It involves snipping hard capsules open, squeezing the contents out into a carrier for nasogastric administration or on a spoon of apple sauce or ice cream. This process was described as highly stressful due to the potentially harmful contents of the capsule for the parents manipulating it, and the difficulty of ensuring that the administered dose was as prescribed. Other actions reported by the respondents were producing the medicine at the hospital pharmacy as an oral solution. One response from Switzerland highlighted training programmes for parents offered by some hospitals.

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- Control of side-effects The percentage of answers reporting that medicines to control side-effects were always or usually available as needed ranged from 95% for nausea and vomiting to 50% for anxiety (Figure 16). Anxiety, pain from treatment, and pain during procedures were symptoms for which some parents reported that medicines were never available. Four respondents reported that medicines to control specific side-effects were never available. The concerned countries were Montenegro, Croatia, Switzerland, and Serbia. One respondent highlighted that the availability of equivalent medications for home use could prove complicated based on the availability of non-IV formats. Figure 19: % of responses in each category regarding availability of medicines to control the side-effects of anticancer treatments in children and adolescents

25

- Pain killers or anaesthesia/sedation during procedures Overall, pain during procedures was reported as always controlled with medicines in 48 to 61% of the answers. Pain control during lumbar puncture and bone marrow aspirates were reported as never used in Montenegro and Serbia. Figure 20: % of responses in each category regarding availability of pain killers or anaesthesia/sedation during procedures in children and adolescents

Discussion and Recommendations

The JARC survey on the accessibility of essential medicines for paediatric malignancies is the first of its kind and an initiative that examined the perceptions and experiences of health professionals and parents across Europe on this topic at the time of the survey. Responses were obtained from a total of 27 EU Member States and 7 non-EU countries: Bosnia and Herzegovina, Israel, Montenegro, Norway, Serbia, Switzerland, and Turkey. The survey for health professionals enabled differentiation of individual medicines including those on the WHO EMLc, and the aggregation of data at the national level. European experts considered that 44 anticancer medicines, in addition to the 24 listed on the WHO EMLc were needed for the treatment of paediatric malignancies according to best standards.

26

Off label use According to information provided by the respondents, off-label use was estimated for one-third of all medicines and one-fourth of those on the WHO EMLc. Verification of this figure would have necessitated consulting the ‘Summary of Product Characteristics (SmPC)’ of each of the 68 medicines in each of the 37 countries. This was neither feasible nor required. Indeed, off-label use is not a major concern for physicians in paediatric haematology and oncology, particularly in relation to WHO EMLc medicines. Dosing Guidelines Over the last 50 years, the international paediatric haematology and oncology community has established the efficacy, toxicity, dosage, and pharmacokinetics of essential medicines through academic prospective clinical trials that validated standard treatments to achieve an overall 80% disease-free survival rate at 5 years. However, the generated information on paediatric dosage has not been included in the SmPCs of the concerned medicines. As an example, all the SmPCs of carboplatin, including its generic form, still state in 2019 that “there is insufficient information to support a dosage recommendation in the paediatric population”. Interestingly, carboplatin is part of the validated standard treatment of several paediatric malignancies such as neuroblastoma, germ cell tumours, sarcomas, and low-grade gliomas, and its pharmacokinetic/pharmacodynamics properties have been well established in the paediatric population through many academic studies. A survey in PubMed with the terms “Carboplatin AND pediatric cancer” identified 687 articles on March 23, 2019. One of the oldest articles is a paediatric phase I trial of the Children’s Cancer Study Group published in 1987 (Gaynon PS, 1987) Thus, the goal is not to ask marketing authorisation holders to update their SmPCs of essential medicines regarding their use in the paediatric population, but rather to warrant that these medicines are always available across Europe for all children and adolescents with cancer. Availability The major finding of the survey for health professionals is that only 44% of medicines (63% of WHO EMLc medicines) were reported as available at all times over the last 24 months in 90% of countries. Shortages were the main reason of unavailability and were reported in at least one country for 72% of the 68 medicines and 75% of the 24 EMLc medicines. The questionnaire did not ask for details on the frequency and duration of shortages and it was therefore not possible to fully assess the extent of unavailability. In line with the findings from health professionals, parents reported experiencing shortages in over half of the examined countries. The most frequent shortages were reported for asparaginases and corticosteroids. These medicines are used daily in the treatment of ALL, which has a high cure rate, and is the most frequent paediatric malignancy with 5,000 newly diagnosed patients yearly in Europe (Orphanet, 2007). Shortages of essential medicines for treating ALL can thus have critical implications for children’s lives and exemplifies the severity of the issue.

27

Shortages Medicine shortages are a major concern in Europe. A recent report from ANSM, the French Competent Authority, showed that the number of medicines in shortage in France rose from 44 in 2008 to 538 in 2017, 14% of them being anticancer medicines (Les Entreprises du médicament, 2019). Shortages of oncology medicines are also identified as an issue by the survey undertaken by the European Association of Hospital Pharmacists (EAHP, 2018). In November 2018, the HMA and EMA held a workshop on the availability of authorised medicines (European Medicines Agency and Heads of Medicines Agencies, 2018), where the consequences of oncology medicine shortages were reported by ESMO and several policy recommendations have been made (Box 1).

Box 1: ESMO policy recommendations to address shortages of oncology medicines

• Introduce legislation for early notification requirements for medicines shortages

• Establish strategic plans for medicines shortages

• Develop catalogues of shortages

• Develop essential medicines lists and assess the risk for shortages

• Introduce incentives for production infrastructure improvements

• Establish procurement models designed to prevent medicines shortages

Source: 2017 ESMO-Economist Intelligence Report: Cancer medicines shortages in Europe: Policy Recommendations to prevent and manage shortages (European Society for Medical Oncology and the Economist Intelligence Unit, 2017)

Budgetary constraints on availability It was reassuring that no country reported budget limitations or out-of-pocket costs for any of the WHO EMLc medicines. Few countries reported cost issues for the non-EMLc medicines. Bulgaria, Romania, Latvia and Estonia were the four countries most affected by shortages, budget limitations, and out-of-pocket costs, as reported by health professionals. Issues with payments/applicability of out-of-pocket costs were reported by both parents and health professionals from Bulgaria, Estonia, Romania, and Spain. The survey showed more issues of cost for expensive innovative medicines. Affordability across Europe is anticipated to be a major issue with new effective but expensive medicines for the treatment of paediatric malignancies entering the market, such as CAR T-cells for relapsed ALL.

28

Child-friendly formulations

Another major finding of the survey for health professionals is that 27% of oral essential medicines are never available in an age-appropriate formulation to facilitate administration in young children. Parents confirmed this finding and provided detailed descriptions of their actions to give the child the medicine, and the distress that they often experience in this process. As an example, temozolomide is available only in large-size capsules, yet this medicine is used for the treatment of brain tumours even in children less than 3 years old. Lack of child-friendly formulations of orally administered essential anticancer medicines is an issue that needs to be addressed across Europe. Pharmacy departments in some countries are already preparing ad hoc liquid formulations of several concerned medicines for individual patients. At the European level, the ESOP Paediatric Working Group is running a project to share good practices and recommendations for the preparation of age-appropriate formulations of anticancer medicines for children. Supportive care Regarding supportive care, parents reported that the least well-controlled symptoms were anxiety, pain from treatment, and pain during procedures. There are obviously major differences in pain control accessibility among countries in Europe. This is important information to share with decision-makers and health professionals across Europe to foster the necessary changes. While pain control agents have been made available over the last years for the many procedures that children with cancer undergo (such as venous puncture, central line insertion, lumbar puncture, bone marrow sampling, and tumour biopsy), it is of major concern that many children across Europe don’t have access to this pain control as reported by parents. Strengths of this study The strength of this study lies in surveying for the first time paediatric haematology and oncology clinicians, oncology hospital pharmacists, and parents in the European Union and beyond, regarding the availability and accessibility of medicines needed to treat children and adolescents with cancer. The survey encompassed all medicines identified by European experts as essential and resulted in an enlarged list, compared with the WHO EMLc 2017. SIOP Europe will work to provide additional evidence and propose that the WHO expands its list of essential medicines for children during the next revision. Weaknesses of this study This was a perception survey, and the number of countries where all three respondent groups provided input was limited. In addition, responses from parents from the same country were not always concordant. Indeed, parents were reporting their experience at the level of the hospital(s) of their child’s treatment and/or activities of their organisation, rather than summarising the situation at the country level. The latter was not feasible for the parents’ respondent group. It was thus decided not to aggregate parents’ answers at the country level but to keep each individual answer in the analysis.

29

The data were not validated against official information provided by government authorities, such as in relation to the authorisation of medicines. As a result, the findings may not be generalisable to represent the situation in the examined countries. However, the survey results provide an interesting snapshot of the situation experienced daily by health professionals and parents across Europe. Conclusions

1. Overall, the findings on better accessibility of WHO EMLc medicines as

compared to non-EMLc medicines, higher costs of newer medicines, and

countries with low health expenditure rate being most affected by access

limitations, are in line with the conclusions of the ESMO European Consortium

Study on the availability, out-of-pocket costs and accessibility of antineoplastic

medicines in Europe (Cherny N, 2016).

2. Shortages of medicines are perceived as the most common underlying reason

for lack of availability. Budget limitations at the country or hospital level appear

less relevant in general but are still pronounced in some countries.

3. The number of medicines available in child-friendly doses and formulations is

far below the needs.

4. Adequate supportive and palliative care services are necessary for children, and

opioids that manage cancer pain are inexpensive and should be provided to

avoid that children suffer unnecessarily.

Recommendations The recommendations are based on the present survey results and build upon the other published reports on accessibility and shortage issues: (Cherny N, 2016), (The Economist Intelligence Unit and European Society for Medical Oncology 2017), (European Association of Hospital Pharmactists, 2018), and (European Medicines Agency and Heads of Medicines Agencies, 2018). Overall, the findings of this survey call for an European coordinated initiative with all Member States and other European countries to ensure availability and affordability of essential medicines for the treatment of children and adolescents with cancer. - Recommendations to actors at the national level:

1. Reinforce the importance of access to essential medicines for paediatric

malignancies in national cancer plans or equivalent instruments guiding cancer

care at the national level;

30

2. Foster that all strategies and actions to improve access to medicines include

the agents used for the treatment and supportive care of childhood cancers,

with reference to the WHO essential medicines for children, the current survey

list, and their respective updates;

3. Foster national policy measures for manufacturers and other actors in the

supply chain to maintain adequate medicine stocks and exchange timely

information to avoid shortages;

4. Allocate appropriate resources and facilities to enable availability of child-

friendly doses and formulations of essential anticancer medicines for the

paediatric population;

5. Ensure appropriate pricing and reimbursement strategies, in particular for new

anticancer medicines that are becoming available for the paediatric population,

with consideration for the life span gained through successful treatment in this

age group;

6. Set up appropriate pain control for all children undergoing procedures as an

objective at the national level to be reached within 2 years.

- Recommendations to actors at the European level:

1. Consider including the list of medicines used for the current survey in European-

level reference lists of essential medicines, including the next revision of the

WHO Essential Medicines List for Children;

2. Set up a coordinated initiative with EU Member States and other European

countries to monitor and anticipate medicine shortages as well as to facilitate

and share the development of solutions;

3. Support policies, programmes and projects to overcome inequalities in access

to essential medicines used for the treatment and supportive/palliative care of

childhood cancers across Europe;

4. Improve the regulatory environment to foster paediatric medicine development

for childhood cancers, including issues related to the ‘EU Paediatric Regulation’

legislation and its implementation;

5. Facilitate international dialogue and cooperation regarding value-based

medicine pricing models for children cured of cancer, including the length of

their future life span compared to adults;

31

6. Support further research on access to medicines used for the treatment and

supportive/palliative care of paediatric malignancies across Europe;

7. Support outcome research projects, including economic data, to adequately

monitor the optimal use of medicines in both paediatric and adult cancers.

- Recommendation all stakeholders:

1. Engage in multi-stakeholder cooperation to ensure that safe, effective,

sustainable, and affordable quality cancer medicines defined as essential are

within reach for all children who require them across Europe.

32

Table 1: List of medicines

Medicine JARC survey ESMO European Study

(Cherny N., 2016) WHO EMLc

2017

13 cis retinoic x

all-trans retinoic x

Asparaginase (PEG-aspa) x

asparaginase E Coli x x

asparaginase Erwinia x

bleomycin x x x

blinatumomab x

bortezomib x

busulfan injection x

busulfan oral tablet x

carboplatin x x x

cisplatin x x x

clofarabine x

crizotinib x x

cyclophosphamide x x

cytarabine x x

cytarabine liposomal x

dacarbazine x x x

dactinomycin x x

daunorubicin x x

daunorubicin liposomal x

dexamethasone injection x

dexamethasone oral liquid x x

dexamthesone oral tablet x

dinutuximab x

docetaxel x x

doxorubicin x x x

epirubicin x

etoposide IV x x x

etoposide phosphate x

etoposide tablets x x x

everolimus x x

fludarabine x

33

fluorouracil x x

gemcitabine x x

hydrocortisone injection x x

hydroxycarbamide x

idarubicin x

ifosfamide x x x

imatinib x

ipilimumab x x

irinotecan x x

lomustine oral tablet x

melphalan injection x

melphalan tablet x

mercaptopurine x x

methotrexate x x x

methylpredinosolome tablet x

methylprednisolone injection x x

mitoxantrone x

oxaliplatin x x

paclitaxel x x x

pamidronate x x

peginterferon alfa 2b x

prednisone oral liquid x x

prednisone oral tablet x x

procarbazine x

rituximab x

temozolomide x x

thioguanine x x

thiotepa x

topotecan x x

trofosfamide oral tablet x

vinblastine x x x

vincristine x x x

vindesine x

vinorelbine IV x x

zoledronate x x

ALL: 68 25 24

34

Acknowledgements

The European Society for Paediatric Oncology - SIOP Europe would like to thank the members

of the Core Working Group on Essential Medicines for Paediatric Malignancies:

- Frederic Arnold, Childhood Cancer International – Europe, France

- Gracemarie Bricalli, European Society for Medical Oncology – ESMO

- Nathan Cherny, Shaare Zedek Medical Centre, Jerusalem, Israel and European Society

for Medical Oncology – ESMO

- Svetlana Griskjane, Children's clinical university hospital, Riga, Latvia and European

Society of Oncology Pharmacy - ESOP

- Sherif Kamal, Children’s Cancer Hospital, Egypt and European Society of Oncology

Pharmacy - ESOP

- Lejla Kameric, Childhood Cancer International – Europe, Bosnia and Herzegovina

- Pamela Kearns, Institute of Cancer and Genomic Sciences, NIHR Birmingham

Biomedical Research Centre, University of Birmingham, Birmingham, United

Kingdom and European Society for Paediatric Oncology - SIOP Europe

- Anita Kienesberger, Childhood Cancer International – Europe, Austria

- Nicola Latino, European Society for Medical Oncology – ESMO

- Karsten Nysom, Department of Paediatrics and Adolescent Medicine, Rigshospitalet,

Copenhagen, Denmark and European Society for Paediatric Oncology - SIOP Europe

- Gilles Vassal, Department of Clinical Research, Gustave Roussy, Paris-Sud

University, Paris, France, European Society for Paediatric Oncology - SIOP Europe

35

References

Cherny N, Sullivan R, Torode J, Saar M, Eniu A. ESMO European Consortium Study on the

availability, out-of-pocket costs and accessibility of antineoplastic medicines in Europe. Ann

Oncol 2016; 27(8): 1423-1443. doi:10.1093/annonc/mdw213.

https://academic.oup.com/annonc/article/27/8/1423/2237392 (March 2019, date last accessed)

Cherny N, Sullivan R, Torode J, Saar M, Eniu A. ESMO International Consortium Study on

the availability, out-of-pocket costs and accessibility of antineoplastic medicines in countries

outside of Europe. Ann Oncol 2017; 28 (11): 2633-2647. doi:10.1093/annonc/mdx521.

https://academic.oup.com/annonc/article/28/11/2633/4110377 (March 2019, date last

accessed)

ERN PaedCan. European Reference Network for Paediatric Oncology. n.d.

http://paedcan.ern-net.eu/ (March 2019, date last accessed)

European Association of Hospital Pharmacists. Survey on medicines shortages to improve

patient outcomes. Brussels: European Association of Hospital Pharmacists 2018, 50.

http://www.eahp.eu/sites/default/files/report_medicines_shortages2018.pdf (March 2019, date

last accessed)

European Medicines Agency and Heads of Medicines Agencies. HMA/EMA workshop on

availability of authorised medicines. Report from a multi-stakeholder meeting. London:

European Medicines Agency 2018, 10.

https://www.ema.europa.eu/en/documents/report/report-multi-stakeholder-workshop-

hma/ema-task-force-availability-authorised-medicine_en.pdf (March 2019, date last accessed)

European Society for Medical Oncology and the Economist Intelligence Unit. Cancer

medicines shortages in Europe: Policy recommendations to prevent and manage shortages.

London: The Economist Intelligence Unit 2017, 32.

https://www.eiu.com/graphics/marketing/pdf/ESMO-Cancer-medicines-shortages.pdf (March

2019, date last accessed)

Gatta G, Botta L, Rossi S, et al. EUROCARE Working Group. Childhood cancer survival in

Europe 1999-2007: results of EUROCARE-5--a population-based study. Lancet Oncol 2014;

15(1): 35-47. doi:10.1016/S1470-2045(13)70548-5.

https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70548-5/fulltext

(March 2019, date last accessed)

Gaynon PS, Ettinger LJ, Moel D, et al. Pediatric phase I trial of carboplatin: a Childrens

Cancer Study Group report. Cancer Treat Rep 1987; 71(11): 1039-1042.

International Agency for Research on Cancer (Globocan). Cancer Today. 2018.

http://gco.iarc.fr/today/home (March 2019, date last accessed)

Kowalczyk JR, Samardakiewicz M, Fitzgerald E, et al. Towards reducing inequalities:

European Standards of Care for Children with Cancer. Eur J Cancer 2014; 50(3): 481-485.

doi:10.1016/j.ejca.2013.11.004.

https://www.ejcancer.com/article/S0959-8049%2813%2900999-4/fulltext

https://academic.oup.com/annonc/article/27/8/1423/2237392

https://academic.oup.com/annonc/article/28/11/2633/4110377

http://paedcan.ern-net.eu/

http://www.eahp.eu/sites/default/files/report_medicines_shortages2018.pdf

https://www.ema.europa.eu/en/documents/report/report-multi-stakeholder-workshop-hma/ema-task-force-availability-authorised-medicine_en.pdf

https://www.ema.europa.eu/en/documents/report/report-multi-stakeholder-workshop-hma/ema-task-force-availability-authorised-medicine_en.pdf

https://www.eiu.com/graphics/marketing/pdf/ESMO-Cancer-medicines-shortages.pdf


http://gco.iarc.fr/today/home


36

Les Entreprises du médicament. Ruptures de stocks et d'approvisionnement des médicaments:

plan d'actions. 2019

https://www.leem.org/presse/ruptures-de-stocks-et-dapprovisionnement-des-medicaments-

plan-dactions (March 2019, date last accessed)

Orphanet. Acute lymphoblastic leukemia. 2007.

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=513 (March 2019, date

last accessed)

SIOP Europe. European Standards of Care for Children with Cancer. 2009.

https://www.siope.eu/wp-content/uploads/2013/09/European_Standards_final_2011.pdf


Vassal G, Schrappe M, Ladenstein R, et al. The SIOPE strategic plan: A European cancer

plan for children and adolescents. Journal of Cancer Policy 2016; 8: 17-32.

doi:10.1016/j.jcpo.2016.03.007

https://www.sciencedirect.com/science/article/pii/S2213538316300017?via%3Dihub (March


World Health Organization. Meeting Report: Technical Definitions of Shortages and

Stockouts of Medicines and Vaccines. Geneva: World Health Organization 2016, 29.

https://www.who.int/medicines/areas/access/WHO_EMP_IAU_2017-03/en (March 2019,

date last accessed)

World Health Organization. WHO Model List of Essential Medicines for Children. 6th List.

2017.

https://www.who.int/medicines/publications/essentialmedicines/en/ (March 2019, date last

accessed)

https://www.leem.org/presse/ruptures-de-stocks-et-dapprovisionnement-des-medicaments-plan-dactions

https://www.leem.org/presse/ruptures-de-stocks-et-dapprovisionnement-des-medicaments-plan-dactions

https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=513

https://www.siope.eu/wp-content/uploads/2013/09/European_Standards_final_2011.pdf

https://www.sciencedirect.com/science/article/pii/S2213538316300017?via%3Dihub

https://www.who.int/medicines/areas/access/WHO_EMP_IAU_2017-03/en

https://www.who.int/medicines/publications/essentialmedicines/en/

37

Annex 1: Country list

Country EU Clinician

response

Pharmacist

response

Parent response

1. Austria X X X

2. Belgium X X X X

3. Bulgaria X X X

4. Croatia X X X

5. Cyprus X X

6. Czech Republic X X X

7. Denmark X X

8. Estonia X X X X

9. Finland X X

10. France X X X X

11. Germany X X

12. Greece X X

13. Hungary X X X

14. Ireland X X X

15. Italy X X X

16. Latvia X X X

17. Lithuania X X X X

18. Luxembourg X X

19. Malta X X X

20. Netherlands X X X

21. Poland X X X

22. Portugal X X X

23. Romania X X X

24. Slovakia X

25. Slovenia X X X

26. Spain X X X X

27. Sweden X X X X

28. UK X

29. Bosnia & Herzegovina X

30. Iceland

31. Israel X

32. Montenegro X

33. North Macedonia

34. Norway X

35. Serbia X X

36. Switzerland X X X

37. Turkey X X

Legend:

Response received from indicated stakeholder

Response not received from indicated stakeholder but at least one response

available for the country from other stakeholders

No response received from the country

38

Annex 2: Questionnaire for health professionals Q.1: Are the following medicines approved for use in the treatment of children in your

country? *

Terminology: For the purposes of the survey, ‘approved’ means that the medicine has

obtained an official Marketing Authorisation for use in children from the competent

authority/ies in the country

Yes No Don’t know

13 cis retinoic acid ☐ ☐ ☐

5-fluorouracil ☐ ☐ ☐

All-trans retinoic acid ☐ ☐ ☐

Asparaginase Erwinia ☐ ☐ ☐

Asparaginase (escherichia coli) ☐ ☐ ☐

Asparaginase (PEG-asparaginase) ☐ ☐ ☐

Bleomycin ☐ ☐ ☐

Blinatumomab ☐ ☐ ☐

Bortezomib ☐ ☐ ☐

Busulfan injection ☐ ☐ ☐

Busulfan oral tablet ☐ ☐ ☐

Carboplatin ☐ ☐ ☐

Cisplatin ☐ ☐ ☐

Clofarabine ☐ ☐ ☐

Crizotinib oral tablet ☐ ☐ ☐

Cyclophosphamide ☐ ☐ ☐

Cytarabine ☐ ☐ ☐

Cytarabine liposomal (DepoCyte) ☐ ☐ ☐

Dacarbazine ☐ ☐ ☐

Dactinomycin ☐ ☐ ☐

Daunorubicin ☐ ☐ ☐

Daunorubicin liposomal ☐ ☐ ☐

Dexamethasone injection ☐ ☐ ☐

Dexamethasone oral liquid ☐ ☐ ☐

Dexamethasone oral tablet ☐ ☐ ☐

Dinutuximab ☐ ☐ ☐

Docetaxel ☐ ☐ ☐

Doxorubicin ☐ ☐ ☐

Epirubicine ☐ ☐ ☐

Etoposide injection ☐ ☐ ☐

Etoposide phosphate ☐ ☐ ☐

Etoposide oral tablet ☐ ☐ ☐

Everollimus ☐ ☐ ☐

39

Yes No Don’t know

Fludarabine ☐ ☐ ☐

Gemcitabine ☐ ☐ ☐

Hydrocortisone injection ☐ ☐ ☐

Hydroxycarbamide/hydroxyurea ☐ ☐ ☐

Idarubicine ☐ ☐ ☐

Ifosfamide ☐ ☐ ☐

Imatinib ☐ ☐ ☐

Ipilimumab ☐ ☐ ☐

Irinotecan ☐ ☐ ☐

Lomustine oral tablet (CCNU) ☐ ☐ ☐

Melphalan injection ☐ ☐ ☐

Melphalan oral tablet ☐ ☐ ☐

Mercaptopurine ☐ ☐ ☐

Methotrexate ☐ ☐ ☐

Methylprednisolone oral tablet ☐ ☐ ☐

Methylprednisolone injection ☐ ☐ ☐

Mitoxantrone ☐ ☐ ☐

Oxaliplatin ☐ ☐ ☐

Paclitaxel ☐ ☐ ☐

Pamidronate ☐ ☐ ☐

Peginterferon alfa 2b ☐ ☐ ☐

Prednisone oral tablet ☐ ☐ ☐

Prednisone oral liquid ☐ ☐ ☐

Procarbazine ☐ ☐ ☐

Rituximab ☐ ☐ ☐

Temozolomide ☐ ☐ ☐

Thiotepa ☐ ☐ ☐

Tioguanine ☐ ☐ ☐

Topotecan ☐ ☐ ☐

Trofosfamide oral tablet ☐ ☐ ☐

Vinblastine ☐ ☐ ☐

Vincristine ☐ ☐ ☐

Vindesine ☐ ☐ ☐

Vinorelbine injection ☐ ☐ ☐

Zoledronate ☐ ☐ ☐

40

Q.2: Are the following medicines used in the treatment of children in your country? *

Terminology: For the purposes of the survey, ‘used in children’ means that the medicine is

used independently of its official indication, so including off-label use.

Yes No Don’t know






































41

Yes No Don’t know
































42

Q.3: Are the following medicines available in your country? *

Terminology: For the purposes of the survey, ‘available’ means that the medicine can be

obtained as needed and in a timely manner.

Always Usually Occasionally Never

Don’t

know

13 cis retinoic acid ☐ ☐ ☐ ☐ ☐

5-fluorouracil ☐ ☐ ☐ ☐ ☐

All-trans retinoic acid ☐ ☐ ☐ ☐ ☐

Asparaginase Erwinia ☐ ☐ ☐ ☐ ☐

Asparaginase (escherichia coli) ☐ ☐ ☐ ☐ ☐

Asparaginase (PEG-

asparaginase) ☐ ☐ ☐ ☐ ☐

Bleomycin ☐ ☐ ☐ ☐ ☐

Blinatumomab ☐ ☐ ☐ ☐ ☐

Bortezomib ☐ ☐ ☐ ☐ ☐

Busulfan injection ☐ ☐ ☐ ☐ ☐

Busulfan oral tablet ☐ ☐ ☐ ☐ ☐

Carboplatin ☐ ☐ ☐ ☐ ☐

Cisplatin ☐ ☐ ☐ ☐ ☐

Clofarabine ☐ ☐ ☐ ☐ ☐

Crizotinib oral tablet ☐ ☐ ☐ ☐ ☐

Cyclophosphamide ☐ ☐ ☐ ☐ ☐

Cytarabine ☐ ☐ ☐ ☐ ☐

Cytarabine liposomal

(DepoCyte) ☐ ☐ ☐ ☐ ☐

Dacarbazine ☐ ☐ ☐ ☐ ☐

Dactinomycin ☐ ☐ ☐ ☐ ☐

Daunorubicin ☐ ☐ ☐ ☐ ☐

Daunorubicin liposomal ☐ ☐ ☐ ☐ ☐

Dexamethasone injection ☐ ☐ ☐ ☐ ☐

Dexamethasone oral liquid ☐ ☐ ☐ ☐ ☐

Dexamethasone oral tablet ☐ ☐ ☐ ☐ ☐

Dinutuximab ☐ ☐ ☐ ☐ ☐

Docetaxel ☐ ☐ ☐ ☐ ☐

Doxorubicin ☐ ☐ ☐ ☐ ☐

Epirubicine ☐ ☐ ☐ ☐ ☐

Etoposide injection ☐ ☐ ☐ ☐ ☐

Etoposide phosphate ☐ ☐ ☐ ☐ ☐

Etoposide oral tablet ☐ ☐ ☐ ☐ ☐

Everollimus ☐ ☐ ☐ ☐ ☐

Fludarabine ☐ ☐ ☐ ☐ ☐

Gemcitabine ☐ ☐ ☐ ☐ ☐

43

Always Usually Occasionally Never

Don’t

know

Hydrocortisone injection ☐ ☐ ☐ ☐ ☐

Hydroxycarbamide/hydroxyurea ☐ ☐ ☐ ☐ ☐

Idarubicine ☐ ☐ ☐ ☐ ☐

Ifosfamide ☐ ☐ ☐ ☐ ☐

Imatinib ☐ ☐ ☐ ☐ ☐

Ipilimumab ☐ ☐ ☐ ☐ ☐

Irinotecan ☐ ☐ ☐ ☐ ☐

Lomustine oral tablet (CCNU) ☐ ☐ ☐ ☐ ☐

Melphalan injection ☐ ☐ ☐ ☐ ☐

Melphalan oral tablet ☐ ☐ ☐ ☐ ☐

Mercaptopurine ☐ ☐ ☐ ☐ ☐

Methotrexate ☐ ☐ ☐ ☐ ☐

Methylprednisolone oral tablet ☐ ☐ ☐ ☐ ☐

Methylprednisolone injection ☐ ☐ ☐ ☐ ☐

Mitoxantrone ☐ ☐ ☐ ☐ ☐

Oxaliplatin ☐ ☐ ☐ ☐ ☐

Paclitaxel ☐ ☐ ☐ ☐ ☐

Pamidronate ☐ ☐ ☐ ☐ ☐

Peginterferon alfa 2b ☐ ☐ ☐ ☐ ☐

Prednisone oral tablet ☐ ☐ ☐ ☐ ☐

Prednisone oral liquid ☐ ☐ ☐ ☐ ☐

Procarbazine ☐ ☐ ☐ ☐ ☐

Rituximab ☐ ☐ ☐ ☐ ☐

Temozolomide ☐ ☐ ☐ ☐ ☐

Thiotepa ☐ ☐ ☐ ☐ ☐

Tioguanine ☐ ☐ ☐ ☐ ☐

Topotecan ☐ ☐ ☐ ☐ ☐

Trofosfamide oral tablet ☐ ☐ ☐ ☐ ☐

Vinblastine ☐ ☐ ☐ ☐ ☐

Vincristine ☐ ☐ ☐ ☐ ☐

Vindesine ☐ ☐ ☐ ☐ ☐

Vinorelbine injection ☐ ☐ ☐ ☐ ☐

Zoledronate ☐ ☐ ☐ ☐ ☐

44

Q.3a: If in the previous question you answered ‘Never’ for the below listed medicines, please

define the reasons for non-availability over the past 24 months: *

Not licensed

in the

country

Not

procured in

the country

Budget

limitations

Don’t

know

Other*

(Specify

below)

[in this table

you will see the

medicines that

were selected

as ‘Never’]

Medicine

1_Never ☐ ☐ ☐ ☐ ☐

etc ☐ ☐ ☐ ☐ ☐

Other* (please specify the reasons for non-availability over the past 24 months)

[in this table you will see the medicines that

were selected as ‘Other*’]

Please specify reason

Medicine 1_Never_Other

Etc

Q.3b: If in question 3 you answered ‘Usually’ or ‘Occasionally’ for the below listed

medicines, please define the reasons for intermittent non-availability over the past 24

months: *

Shortages

(Go to

Q3b2)

Budget

limitations

Don’t know Other*

(Specify

below)

[in this table you will see the

medicines that were selected

as ‘Usually’ or

‘Occasionally’]

Medicine

1_Usually_Occasionally ☐ ☐ ☐ ☐

Etc ☐ ☐ ☐ ☐

Other* (please specify the reasons for intermittent non-availability over the past 24

months)

[in this table you will see the

medicines that were selected as

‘Other*’]

Please specify reason

Medicine

1_Usually_Occasionally_Other

etc

45

Q.3b2: If you indicated experiencing shortages of medicines in your country, please

indicate which options, if any, were available to overcome them: *

Using

substitutes

Borrowing

from other

countries

Using

another

protocol

Postponing

therapy

Obtaining

funding/support

from NGOs

Not able

to

overcome

shortages

Don’t

know Other*

[in this

table you

will see the

medicines

that were

selected as

‘Shortages’]

Med

1_Short ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐

etc ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐

Other* (please specify how you overcame the shortages)



Please specify how shortage was overcome

Med 1_Short_Other

Etc

Q.4: Did you face issues prescribing the following medicines to children in your country

in the past 24 months? *

Yes No

Not

applicable



















46

Yes No

Not

applicable









































47

Yes No

Not

applicable











Q.4a: If in the previous question you answered ‘Yes’ for the below listed medicines, how

were these barriers to prescribing overcome in your country? *

Obtaining

special

authorisation

from national

medicines

agency

Obtaining

special

authorisation

from

manufacturer

Obtaining

special

authorisation

from

wholesaler

Obtaining

insurance

pre-

approval

per

patient

Don’t

know

Other*

(Specify

below)

[in this table

you will see the

medicines that

were selected as

‘Yes’]

Medicine_1_Yes ☐ ☐ ☐ ☐ ☐ ☐

Etc ☐ ☐ ☐ ☐ ☐ ☐

Other* (please specify how were these barriers to prescribing overcome in your

country)



Please specify how barriers to prescribing

were overcome

Medicine_1_Yes_Other

Etc

48

Q.5: Do patients/parents have to incur out-of-pocket costs for the following medicines? *

Yes No Don’t know

























Dexamethasone tablet ☐ ☐ ☐















49

Yes No Don’t know






Melphalan tablet ☐ ☐ ☐
























Q5a: If In the previous question you answered Yes for the below listed medicines, please

select which proportion of out-of-pocket costs applies, approximately? *

25% of cost 50% of cost Full cost Don’t

know

Other*

[in this table you

will see the

medicines that

were selected as

‘Yes’]

Medicine 1_Yes ☐ ☐ ☐ ☐ ☐

Etc ☐ ☐ ☐ ☐ ☐

50

Other* (please specify which proportion of out-of-pocket costs applies)



Please specify the proportion

Medicine 1_Yes_Other

Etc

Q.6: Are the following orally administrable medicines available in child-friendly

formulations and doses? *

Always Usually Occasionally Never Don’t

know

Not

applicable

13 cis retinoic acid ☐ ☐ ☐ ☐ ☐ ☐

All-trans retinoic acid ☐ ☐ ☐ ☐ ☐ ☐

Busulfan oral tablet ☐ ☐ ☐ ☐ ☐ ☐

Crizotinib oral tablet ☐ ☐ ☐ ☐ ☐ ☐

Cyclophosphamide ☐ ☐ ☐ ☐ ☐ ☐

Dexamethasone oral liquid ☐ ☐ ☐ ☐ ☐ ☐

Dexamethasone oral tablet ☐ ☐ ☐ ☐ ☐ ☐

Etoposide oral tablet ☐ ☐ ☐ ☐ ☐ ☐

Everollimus ☐ ☐ ☐ ☐ ☐ ☐

Hydroxycarbamide/hydroxyurea ☐ ☐ ☐ ☐ ☐ ☐

Idarubicine ☐ ☐ ☐ ☐ ☐ ☐

Imatinib ☐ ☐ ☐ ☐ ☐ ☐

Lomustine oral tablet (CCNU) ☐ ☐ ☐ ☐ ☐ ☐

Melphalan oral tablet ☐ ☐ ☐ ☐ ☐ ☐

Mercaptopurine ☐ ☐ ☐ ☐ ☐ ☐

Methotrexate ☐ ☐ ☐ ☐ ☐ ☐

Methylprednisolone oral tablet ☐ ☐ ☐ ☐ ☐ ☐

Mitoxantrone ☐ ☐ ☐ ☐ ☐ ☐

Oxaliplatin ☐ ☐ ☐ ☐ ☐ ☐

Paclitaxel ☐ ☐ ☐ ☐ ☐ ☐

Pamidronate ☐ ☐ ☐ ☐ ☐ ☐

Peginterferon alfa 2b ☐ ☐ ☐ ☐ ☐ ☐

Prednisone oral tablet ☐ ☐ ☐ ☐ ☐ ☐

Prednisone oral liquid ☐ ☐ ☐ ☐ ☐ ☐

Procarbazine ☐ ☐ ☐ ☐ ☐ ☐

Temozolomide ☐ ☐ ☐ ☐ ☐ ☐

Tioguanine ☐ ☐ ☐ ☐ ☐ ☐

Trofosfamide oral tablet ☐ ☐ ☐ ☐ ☐ ☐

51

Q.7: When medicines are not available in a child-friendly dose or formulation, what

alternatives are available (in general/across agents covered)? *

☐ Preparation on the hospital ward by nurses

☐ Centralised preparation by hospital pharmacy only for in-patients

☐ Centralised preparation by hospital pharmacy for both in- and out- patients

☐ Preparation by any other pharmacy as additional service

☐ Don't know

☐ Other (please specify) Open text box

Q.8: Would you like your participation in the survey to be acknowledged? *

☐ Yes (Go to Q8a)

☐ No (Go to Q9)

Q.8a: If your answer is yes, please complete the below: *

First name: Open text box

Last name: Open text box

Q.9: Country* Open text box

52

Annex 3: Questionnaire for parents

Q.1: Over the course of treatment for children/adolescents in the hospital(s) where you

are active as an NGO, and did you encounter issues of medicine shortages over the past

24 months (e.g. may have resulted in treatment delay, treatment modification)? *

☐ Yes (Go to Q1a)

☐ No (Go to Q2)

☐ Do not know

Q.1a: If in the previous questions you answered Yes, please indicate which of the

below actions were taken? *

☐ Contacting local authorities in your country

☐ Travel to another country

☐ Requesting support from NGOs

☐ Don't know

☐ Other (Please specify) Open text box

Q.2: Have parents faced issues in paying for their child’s/adolescent’s treatment in the

hospital(s) where your NGO is active over the past 24 months? *

☐ Yes (Go to Q2a)

☐ No (Go to Q3)

☐ Do not know

Q.2a: If Yes, then which of the below actions were taken? *

☐ Contacting local authorities in your country

☐ Requesting funding from NGOs

☐ Don’t know

☐ Other (Please specify) Open text box

Q.3: How would you describe the frequency of adjusting the dose and format (e.g.

breaking pills in half, crushing pills, mixing pills’ content with apple sauce or similar) of

a child’s medicine for him or her to be able to take it as prescribed? *

☐ Always (Go to Q3a)

☐ Usually (Go to Q3a)

☐ Occasionally (Go to Q3a)

☐ Never (Go to Q4)

☐ Don’t know

Q.3a: If Always, Usually, or Occasionally, please provide details of what adjustments

to dose and format you have had to make to enable a child to take their medication as

prescribed. *

Open text box

53

Q.4: In the hospital(s) you are working with, how would you describe the frequency with

which medicines to control the following side-effects in children and adolescents are

available when needed? *


know

Nausea and vomiting ☐ ☐ ☐ ☐ ☐

Pain during

procedures ☐ ☐ ☐ ☐ ☐

Pain from disease or

complications ☐ ☐ ☐ ☐ ☐

Pain from treatments

(e.g. neuropathic

pain from

vincristine)

☐ ☐ ☐ ☐ ☐

Anxiety ☐ ☐ ☐ ☐ ☐

Constipation ☐ ☐ ☐ ☐ ☐

Diarrhoea ☐ ☐ ☐ ☐ ☐

Other*: Open text box

Q.5: In the hospital(s) you are working with, how would you describe the frequency with

which children/adolescents receive painkillers or anaesthesia/sedation during the

following procedures? *


know

Lumbar puncture ☐ ☐ ☐ ☐ ☐

Bone marrow

sampling ☐ ☐ ☐ ☐ ☐

Central venous line

insertion ☐ ☐ ☐ ☐ ☐

Tumour biopsy, e.g.

ultrasound guided ☐ ☐ ☐ ☐ ☐

Other*: Open text box

Q.6: Would you like your participation in the survey to be acknowledged? *

☐ Yes (Go to Q6a)

☐ No (Go to Q7)

Q.6a: If your answer is yes, please complete the below:

First name: Open text box

Last name: Open text box

Q.7: Country*

54

RADIOTHERAPY REPORT

Introduction Cancer remains the leading cause of children’s mortality by disease in Europe, with more than 6,000 young patients dying each year (International Agency for Research on Cancer, 2018). Eighty percent (80%) of children and adolescents with cancer can be disease-free at 5 years if they receive the appropriate standard treatments in a multidisciplinary setting. However, the essential therapies to cure, support, and palliate young cancer patients are not equally available and accessible to all those who need them. These inequalities contribute to differences in childhood cancer survival rates of up to 20% across Europe (Gatta G, 2014). To foster equal access to the best paediatric cancer care and expertise is a major goal of the pan-European community, embedded in the European Standards of Care for Children with Cancer (Kowalczyk JR, 2014) and the SIOPE Strategic Plan (Vassal G, 2016). The equal access objective as described above is operationalised at the European level through the European Reference Network for Paediatric Oncology (ERN PaedCan), a virtual structure that involves healthcare providers across Europe to deliver high-quality, accessible and cost-effective cross-border healthcare to children and adolescents with cancer, regardless of where they live (ERN PaedCan, n.d.). Through the European Reference Network model, Member States cooperate to streamline the patient journey for conditions that require specialist expertise and tools not widely available due to low case volumes at the national level. Considering the Member States’ primary responsibility for healthcare organisation and delivery on their territories, understanding the specific realities in each country is highly important to foster the best standard care for children with cancer in Europe. Paediatric radiation oncologists are core medical members of the childhood cancer treatment team. Historically, radiotherapy was delivered to children following a standard one-size-fits-all approach. The individual risk adaption of cancer therapy plus the growing availability of novel modalities and techniques today means that radiotherapy for children is gaining complexity. Individual approaches are increasingly required. There has also been a marked increase in the understanding of the molecular biology of paediatric cancers, which may be relevant for radiotherapy too. In addition, the potential late effects of radiotherapy on normal organ structure and function are increasingly being recognised and quantified in relation to the specific treatment given. In order to achieve the best possible outcomes for children, treatment centres delivering radiotherapy should meet an appropriate level of standards and have access to continuously updated ‘best practice’ information. (Janssens GO, 2019)

55

Objectives

1. Map existing national-level guidelines regarding the delivery of paediatric

radiation oncology across Europe;

2. Define overarching European recommendations on the organisation of

paediatric radiotherapy;

3. Map all centres delivering radiation therapy to children with cancer in the EU

and other countries in the SIOP Europe region;

4. Initiate a pan-European survey to the centres regarding existing set-up and

capacities in relation to the overarching criteria defined in Point 2.

Methods Project steering group A Core Working Group with stakeholders representing different radiation oncology groups in Europe, as listed below, was convened to steer the activities.

• SIOPE (European Society for Paediatric Oncology) representing paediatric

haematology oncology clinicians,

• QUARTET (Quality and Excellence in Radiotherapy and Imaging for Children

and Adolescents with Cancer across Europe in Clinical Trials) as the SIOP

Europe committee reviewing the quality of radiotherapy target volume

delineations and dose distributions,

• CCI Europe (Childhood Cancer International Europe) representing parents,

• ESTRO (European SocieTy for Radiotherapy & Oncology) as radiation

oncology professionals,

• PROS (Paediatric Radiation Oncology Society) as worldwide radiation

oncologists and allied professionals involved in paediatric oncology.

The Core Working Group was tasked to define the project methodology, oversee its implementation, and formulate recommendations on their basis. Experts held regular teleconferences and were supported by the SIOP Europe and ESTRO offices for documenting discussions, outreach activities, and drafting the content.

56

Mapping national-level guidelines on paediatric radiation oncology Experts in 37 countries (Annex 1) were contacted by email asking to indicate whether national radiation oncology guidelines for the paediatric population were in place and to provide the corresponding document(s). The geographic scope included all EU Member States, other SIOP Europe affiliated countries, as well as Albania and Montenegro. Respondents were specialists in paediatric radiotherapy active in the SIOP Europe QUARTET network, which covers 18 countries, and representatives of national radiation oncology societies in the ESTRO network in the remaining 19 countries. Defining recommendations on the organisation of paediatric radiotherapy

The recommendations were consolidated based on the identified national guidelines and the joint expertise of the Core Working Group. It was agreed to organise the document in a step-by-step manner reflecting the patient pathway: intake, tumour board discussion, delineation and dose calculation, treatment delivery, and follow up. In addition, recommendations would address the expert network surrounding the patient pathway, professional education, and clinical research activities. To guide the development of the recommendations, a table with specific items in each focus area was created. Items were subdivided into requirements on equipment and those on personnel. Aspects of specific relevance to paediatric as opposed to general or adult radiotherapy were emphasised. To foster an inclusive approach while accepting different levels of chances and standard in care within Europe, the recommendations for each item were also subdivided into standard/mandatory and optional. The recommendations were finalised after several rounds of comments from the Core Working Group. The outcome position paper translated and detailed the items in the table into a set of standards of care. The tables themselves were also included in the manuscript (Janssens GO, 2019). Mapping centres delivering radiation therapy to children with cancer Experts in 38 countries (with the addition of Israel relative to the national guideline mapping exercise in Annex 1) were contacted by email asking for information on centres delivering radiation therapy to children with cancer in their country. The questionnaire included a standardised form where the required details could be filled in: location of centre(s), name of centre(s), key person responsible for paediatric radiation oncology per centre, and their email address. In the same manner as the mapping of national guidelines, target respondents were members of the SIOP Europe QUARTET network and of the ESTRO network. In case of non-response, input was sought from the SIOP E Europe Clinical Research Council members and personal contacts of the Core Working Group. The list of centres was received from 34 countries. Children in 2 countries are referred abroad for radiotherapy: Luxemburg and Montenegro. No information was obtained for 2 further countries: Malta and Albania. Information on selected countries was verified

57

with additional respondents at the national level. The compiled list of centres was validated by the Core Working Group. European survey on the organisation of care in paediatric radiation oncology The Core Working Group developed a questionnaire (Annex 2) based on the agreed European recommendations on the organisation of paediatric radiotherapy. The aim is to investigate the extent to which centres across Europe meet the formulated criteria. Target respondents are representatives of all centres known to irradiate children with cancer in Europe. Only one response per centre/hospital is required, ideally by the person in charge of paediatric radiation oncology. The list of respondents was obtained through the mapping of centres as described above. An online pilot survey was developed, tested and sent to all respondents at the end of February 2019 with the first deadline on 28 March 2019. A reminder was circulated one week prior to the deadline.

Results

National guidelines

Guidelines for paediatric radiation oncology were available in three (3) out of 30 European countries that responded to the enquiry: France, Germany, and United Kingdom. Although different on detailed level, these guidelines covered the same broad topic areas, had no fundamental differences, and thus provided a solid basis for defining the overarching European criteria. European recommendations The European criteria were consolidated in a manuscript which is accepted for publication in the European Journal of Cancer by March 2019 and foreseen to be available in open access mid-April (Janssens GO, 2019).

- Position paper: Recommendations for the Organisation of Care in Paediatric

Radiation Oncology across Europe: a SIOP Europe – ESTRO – PROS – CCI

Europe collaborative project in the framework of the JARC.

The recommendations are summarised below. - Patient pathway

- Ensure that all patients are discussed in appropriately documented and staffed

multi-disciplinary team meetings at diagnosis, treatment response evaluation,

and any suspicion of progression or relapse;

- Foster the provision of information to the family and the patient in an age-

appropriate manner regarding the indication for radiation therapy, potential side-

effects, and the procedures and logistics involved in treatment preparation and

delivery;

58

- Consider the use of highly-conformal radiation therapy as the standard of care;

- Foster optimal daily reproducibility to maximise target dose coverage and

reduce the risk of late effects by emphasising:

▪ Specifically manufactured tools and technologies, ▪ Specialised personnel with affinity for paediatric patients, ▪ Access to a central review of treatment plans, ▪ Personalised and age-specific approaches.

- Facilitate referrals to specialised centres when the required techniques or

procedures are not available in-house, such as for advanced photon

techniques, proton beam therapy or brachytherapy.

- Foster systematic registration of moderate to severe long-term side effects to

improve prevention and management of later toxicities in childhood cancer

survivors.

- Education

- Ensure that the professional qualifications and development curricula of

relevant personnel foresee basic education in paediatric radiation oncology and

paediatric oncology, and regular courses and exchange at National, European

and International levels.

- Clinical research

- Foster centre participation and enrolment of patients in ongoing and therapy-

optimising studies, registries, and/or adherence to (inter)national guidelines.

Mapping of national centres and survey initiation Over 250 paediatric radiotherapy centres across the SIOP Europe-affiliated countries have been mapped and received the survey to document alignment with the above criteria. Approximately 50% of the centres provided their response as of 25 April 2019. A manuscript detailing outcome of the survey is planned after data collection and analysis.

59

Discussion

There are significant disparities in survival and the severity of long-term side effects across countries affiliated with SIOP Europe (Gatta G, 2014) (Kowalczyk JR, 2014). Differences in the organisation of complex multi-disciplinary care and education on rare diseases, like paediatric cancers, are probably amongst the most important explanations (Janssens GO, 2019). Radiotherapy is an essential component of multi-disciplinary cancer care for the paediatric population. It is becoming increasingly complex due to current highly risk-adapted, individualized treatments, the growing availability of new techniques and the evolution of molecular biology. These added challenges have the potential to increase disparities in survival and side-effects between countries and also between centres in the same country. Establishing appropriate processes and structures is crucial to reduce disparities in survival rates and the severity of long-term side-effects for children and adolescents with cancer across Europe. (Janssens GO, 2019) To tackle the issue of disparities related to radiotherapy, SIOP Europe, PROS, ESTRO and CCI-Europe defined the European recommendations on the structures and processes related to patient care, education, and clinical research that are needed to create an appropriate environment for children receiving radiation therapy. In addition, a comprehensive list of centres delivering radiation therapy in 35 European countries has been consolidated, and a questionnaire sent to representatives to understand the centres’ alignment with the formulated criteria. Thus, the JARC made substantial progress in formulating the current needs and developing a transparent picture of the available resources and expertise for paediatric radiation therapy across Europe. A specific consideration concerns the caseload/yearly patient number indicators per centre. As most paediatric cancer clinics in Europe diagnose less than 100 new patients annually, an associated radiation oncologist will treat an average of 1 or maybe 2 or 3 similar cases per year (Janssens GO, 2019). Although there is currently no consensus on a minimum number of patients, there are benefits for centres that treat higher numbers. Indeed, high-volume centres may have the opportunity to generate better techniques for challenging scenarios and to establish a dedicated team that can participate in specialist meetings and educational activities (Janssens, GO 2019). The presented recommendations are not meant to be binding but rather aim to provide guidance that can be used as a reference by national authorities, individual centres, and clinical trial sponsors in the absence of existing national guidelines. The outcome of the mapping of centres can in addition be highly relevant for European Reference Networks in terms of visibility of collaboration pathways and referrals in paediatric radiotherapy.

60

Acknowledgements

The European Society for Paediatric Oncology - SIOP Europe would like to thank the

members of the Core Working Group on Paediatric radiation oncology:

- Tom Boterberg, Department of Radiation Oncology, Ghent University Hospital,

Ghent, Belgium; European Society for Paediatric Oncology – SIOP Europe; Quality

and Excellence in Radiotherapy and Imaging for Children and Adolescents with

Cancer across Europe in Clinical Trials – QUARTET

- Melanie Brunhofer, Childhood Cancer International – Europe, Austria

- Cyrus Chargari, Department of Radiation Oncology, Gustave Roussy, Villejuif,

France and European SocieTy for Radiotherapy and Oncology – ESTRO

- Chiara Gasparotto, European SocieTy for Radiotherapy and Oncology – ESTRO

- Geert Janssens, Department of Radiation Oncology, University Medical Centre

Utrecht, The Netherlands; Princess Maxima Centre for Paediatric Oncology,

Utrecht, The Netherlands; Quality and Excellence in Radiotherapy and Imaging for

Children and Adolescents with Cancer across Europe in Clinical Trials –

QUARTET; Paediatric Radiation Oncology Society - PROS

- Neige Journy, INSERM Unit 1018, Centre for Research in Epidemiology and

Population Health (CESP), Cancer and Radiations group, Gustave Roussy, Villejuif,

France

- Lejla Kameric, Childhood Cancer International – Europe, Bosnia and Herzegovina

- Pamela Kearns, Institute of Cancer and Genomic Sciences, NIHR Birmingham

Biomedical Research Centre, University of Birmingham, Birmingham, United

Kingdom, and European Society for Paediatric Oncology - SIOP Europe

- Anita Kienesberger, Childhood Cancer International – Europe, Austria

- Anne Laprie, Department of Radiation Oncology, Institut Claudius Regaud, Institut

Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France and Toulouse

NeuroImaging Center, ToNIC, INSERM Université Toulouse III Paul Sabatier,

Toulouse, France

- Yolande Lievens, Department of Radiation Oncology, Ghent University Hospital,

Ghent, Belgium and European SocieTy for Radiotherapy and Oncology – ESTRO

61

- Henry Mandeville, Department of Radiotherapy, The Royal Marsden Hospital and

The Institute of Cancer Research, Sutton, United Kingdom, and Quality and

Excellence in Radiotherapy and Imaging for Children and Adolescents with Cancer

across Europe in Clinical Trials – QUARTET

- Laetitia Padovani, Department of Radiation Oncology, Assistance Publique

Hôpitaux de Marseille, Marseille, France

- Beate Timmermann, Department of Particle Therapy, University Hospital Essen,

West German Proton Therapy Centre Essen (WPE), West German Cancer Centre

(WTZ), German Cancer Consortium (DKTK) and European SocieTy for

Radiotherapy and Oncology – ESTRO

- Gilles Vassal, Department of Clinical Research, Gustave Roussy, Paris-Sud

University, Paris, France and European Society for Paediatric Oncology – SIOP

Europe

62

References

ERN PaedCan. European Reference Network for Paediatric Oncology. n.d.

http://paedcan.ern-net.eu/ (March 2019, date last accessed)

Gatta G, Botta L, Rossi S, et al. EUROCARE Working Group. Childhood cancer survival in

Europe 1999-2007: results of EUROCARE-5--a population-based study.” Lancet Oncol 2014;

15(1): 35-47. doi:10.1016/S1470-2045(13)70548-5.



International Agency for Research on Cancer (Globocan). Cancer Today. 2018.

http://gco.iarc.fr/today/home (March 2019, date last accessed)

Janssens GO, Timmermann B, Vassal G, et al. Recommendations for the Organisation of

Care in Paediatric Radiation Oncology across Europe: a SIOP Europe – ESTRO – PROS –

CCI Europe collaborative project in the framework of the JARC. Eur J Cancer 2019

(Accepted for publication).

Kowalczyk JR, Samardakiewicz M, Fitzgerald E, et al. Towards reducing inequalities:

European Standards of Care for Children with Cancer. Eur J Cancer 2014; 50(3): 481-485.

doi:10.1016/j.ejca.2013.11.004.


Vassal G, Schrappe M, Ladenstein R, et al. The SIOPE strategic plan: A European cancer

plan for children and adolescents. Journal of Cancer Policy 2016; 8: 17-32.

doi:10.1016/j.jcpo.2016.03.007

https://www.sciencedirect.com/science/article/pii/S2213538316300017?via%3Dihub (March


http://paedcan.ern-net.eu/


http://gco.iarc.fr/today/home


https://www.sciencedirect.com/science/article/pii/S2213538316300017?via%3Dihub

63

Annex 1: Country list

Country EU National guidelines available?

List of centres available?

1. Austria X X

2. Belgium X X

3. Bulgaria X X

4. Croatia X X

5. Cyprus X X

6. Czech Republic X X

7. Denmark X X

8. Estonia X X

9. Finland X X

10. France X X X

11. Germany X X X

12. Greece X X

13. Hungary X X

14. Ireland X X

15. Italy X X

16. Latvia X X

17. Lithuania X X

18. Luxembourg X (RT delivered abroad)

19. Malta X TBC

20. Netherlands X X

21. Poland X X

22. Portugal X X

23. Romania X X

24. Slovakia X X

25. Slovenia X X

26. Spain X X

27. Sweden X X

28. UK X X X

29. Albania TBC

30. Bosnia & Herzegovina X

31. Iceland X

32. Israel X

33. Montenegro (RT delivered abroad)

34. North Macedonia X

35. Norway X

36. Serbia X

37. Switzerland X

38. Turkey X

64

Annex 2: Questionnaire

GENERAL QUESTIONS FOR THE PAEDIATRIC RADIATION ONCOLOGIST

Q1: Name of your centre or hospital*: Open comment box

Q2: City*: Open comment box

Q3: Country*: Open comment box

Q.4: Is your radiotherapy department part of a comprehensive paediatric cancer centre?

*(NB: For the purposes of this survey, a comprehensive paediatric cancer centre offers all

medical disciplines involved in the treatment of paediatric cancer in one hospital/campus)

o Yes (Go to Q4a)

o No (Go to Q5)

o Other (Please specify) Open comment box

Q.4a: Approximately how many new patients are diagnosed in your comprehensive

paediatric cancer centre per year? *

Please select one

o 0-10

o 11-25

o 26-50

o 51-75

o 76-100

o 101-150

o 151-200

o 201-300

o 301-400

o 401-500

o 501+

Q.5: How many radiation oncologists in your department routinely treat patients with

paediatric cancer? *

Please select one

o 1

o 2

o 3

o 4

o 5

o Other (Please specify): Open comment box

65

Q.6: How many years of clinical experience in GENERAL radiation oncology do the

members of your department treating children have (training or residency period

excluded)? *

To be filled in for each person in the department

Person 1* o 0-5

o 6-10

o 11-15

o 16-20

o 21-25

o 26-30

o 31-35

o 36-40

o Other (Please specify): Open

comment

Q.7: How many years of clinical experience in PAEDIATRIC radiation oncology do you

have (training or residency period excluded)? *

To be filled in for each person in the department, rows can be added

Person 1* o 0-5

o 6-10

o 11-15

o 16-20

o 21-25

o 26-30

o 31-35

o 36-40

o Other (Please specify): Open

comment

etc

Q.8: Approximately how many paediatric patients (age 0-18 years) are irradiated within

your department annually? *

(NB: Patients referred to other centres, e.g. for proton therapy, if not available in your

department, are excluded)

Please select one

o 0-10

o 11-25

o 26-50

o 51-100

o 101-150

o 151-200

o 201-250


66

Q.9: Approximately how many paediatric patients (age 0-18 years) do you refer to another

radiotherapy department annually (e.g. proton therapy, brachytherapy, advanced photon

techniques)? *

Please select one

o 0-10

o 11-25

o 26-50

o 51-100

o 101-150

o 151-200

o 201-250


Q.10: What categories of paediatric tumours are irradiated in your department? *

Select all that apply

o Neuro-oncology

o Solid tumours

o Haemato-oncology

67

PART 1: QUESTIONS ON DAILY ACTIVITIES RELATED TO PATIENT CARE

Q.11: As a radiation oncologist involved in paediatric oncology, do you also participate in

paediatric oncology-specific tumour boards? * (NB: A tumour board involves a

multidisciplinary patient discussion)

o Yes (go to Q11a)

o No (go to Q12)

Q.11a: Please indicate all medical specialists, who participate in paediatric oncology

tumour boards on a regular basis*:


o Paediatric Oncologist

o General surgeon

o Paediatric surgeon

o Neurosurgeon

o Paediatric neurosurgeon

o Radiation oncologist

o Radiologist

o Nuclear medicine physician

o Pathologist

o Neurologist

o Ophthalmologist

o Endocrinologist

o Clinical geneticist


Q.11b: What is the frequency of these paediatric oncology tumour board meetings? *

Please select one

o 2x per week

o 1x per week

o 1x per 2 weeks

o 1x per 3 weeks

o 1x per 4 weeks

o On indication only


Q.11c: What technical options are available during the paediatric tumour boards in your

hospital? *


o Showing radiology and nuclear medicine data

o Showing pathology data

o Remote telephone connections allowing colleagues from other hospitals to join

o Remote video conference connections allowing colleagues from other hospitals to

join


68

Q.12: Outside of paediatric tumour boards, how do you exchange information on patients

with paediatric cancers referred for radiotherapy? *


o Referral letter and imaging

o Case by case, by telephone

o Case by case, by email


Q.13: Is your department equipped with child-friendly corners (locations and equipment

designed especially for children)? *

o Yes (Go to Q 13a)

o No (Go to Q 14)

Q.13a: Which child-friendly locations and equipment are available? *


o Waiting room(s)

o Doctor’s office

o Treatment machine(s)


Q.14: What kind of educational or information tools are available to prepare children for

radiotherapy? *


o No specific information for children is available

o A booklet or textbook is available

o A movie or digital application (APP) for children is available

o A mini-CT-scan, mini-LINAC is available for children


Q.15: Who prepares the child for radiotherapy? *


o Parents

o Play specialists (or equivalent personnel)

o Nurses

o Radiation therapy technologists (RTT)

o Paediatric oncologist



69

Q.16: In case of an emergency or any urgent question related to radiotherapy from

parents outside of working hours, how can parents or those who care for the children

reach the department? *


o 24-hour on-call service organised by the radiotherapy department

o Parents have to contact the paediatric oncologist first

o Not possible to contact the radiation oncologist after working hours


Q.17: Is anaesthesiology (or equivalent option) for treatment preparation or during

radiotherapy available in your department? *

Please select one

o No, I have to refer to another hospital in case of anaesthesia

o Yes, I have easy access

o Yes, anaesthesia is available but often leads to a treatment onset delay of > 2 weeks


Q.18: Do you refer patients for fertility preservation when indicated in the context of

radiotherapy? *

Please select one

o Yes

o No


Q.19: Please indicate which statements are applicable for your department: *


o RTT’s (radiation therapy technologists or equivalent) dedicated to paediatric patients

are available for mould-room applications

o RTT’s dedicated to paediatric patients are available for (PET-) CT and/or MRI

applications

o Treatment plans are generated by RTT’s, dosimetrists or clinical physicists with specific

interest in paediatric oncology.

o RTT’s dedicated for paediatric patients are available on the machines

Q.20: Indicate what equipment is AVAILABLE and - when indicated – is also USED for

children in your department. *

Equipment AVAILABLE USED Don’t know Not applicable

Head+/-neck fixation

(mask)

Body fixation (cast)

Vacuum mattress

(fixation/comfort)

70


3D-CT-scan

4D-CT-scan

3D-PET-CT-scan

4D-PET-CT-scan

3D-MRI-scan

4D-MRI-scan

2D-manual calculations

3D-treatment planning

system

Photons

Electrons

Protons

Brachytherapy PDR

Brachytherapy HDR

(rotational) IMRT

Stereotactic radiotherapy

or radiosurgery

IMPT

EPID (electronic portal

imaging devices)

KV-Cone Beam CT

MV-Cone Beam CT

MRI (MR-Linac)

Offline imaging

protocols

71


Online imaging

protocols

Q.21: Do you refer patients to other centres for advanced photon techniques if they are

not available in your own department? *

Please select one

o Yes (Go to Q21a)

o No (Go to Q22)

Q.21a: Please indicate the details about the referrals to other centres for advanced photon

techniques: *


o National referral

o International referral

Q.21b: Please indicate the name of the centre(s) of reference*: Open text box

Q.21c: Approximately how many paediatric patients do you refer to another radiotherapy

department for advanced photon techniques per year?

o 0 – 5

o 6 – 10

o 11 – 15

o 16 – 20

o Other: Open comment box

Q.22: Do you refer patients to other centres for proton therapy if it is not available in your

own department? *

Please select one

o Yes (Go to Q22a)

o No (Go to Q23)

Q22a: Please indicate the details about the referrals to other centres for proton therapy: *


o National referral


Q22b: Please indicate the name of the centre(s) of reference*: Open text box

72

Q21c: Approximately how many paediatric patients do you refer to another radiotherapy

department for proton therapy per year?

o 0 – 5

o 6 – 10

o 11 – 15

o 16 – 20


Q.23: Do you refer patients to other centres for brachytherapy if it is not available in your

own department? *

Please select one

o Yes (Go to Q23a)

o No (Go to Q24)

Q.23a: Please indicate the details about the referrals to other centres for brachytherapy: *


o National referral


Q.23b: Please indicate the name of the centre(s) of reference*: Open text box

Q.23c: Approximately how many paediatric patients do you refer to another radiotherapy

department for brachytherapy per year?

o 0 – 5

o 6 – 10

o 11 – 15

o 16 – 20


Q.24: Are late-effect outpatient clinics organised in your hospital/centre?

o Yes (Go to Q24a)

o No (Go to Q25)

Q.24a: Are you involved in late-effect outpatient clinics? *

o Yes (Go to Q24b)

o No (Go to Q24c)

Q.24b: How often you participate in the late-effect outpatient clinic? *

Please select one

o 2x per week

o 1x per week

o 1x per 2 weeks

o 1x per 3 weeks

o 1x per 4 weeks

73

o On indication only

o Other (Please specify): Open text box

Q.24c: Which specialists routinely participate in the late effect outpatient clinic? *


o Paediatric Oncologist

o (Paediatric) (neuro)surgeons


o Neurologist

o Ophthalmologist

o Endocrinologist

o Cardiologist

o Clinical genetics


Q.25: Do you have further comments regarding Survey Part 1: Daily Activities Related to

Patient Care?

Open text box

74

PART 2: EDUCATION AND TRAINING

Q.26: Which training in paediatric oncology did you receive before exercising paediatric

radiotherapy? *


o A paediatric oncology course dedicated to radiation oncologists

o Specify which course:

o A paediatric radiation oncology course


o A paediatric oncology course dedicated to any speciality related to paediatric oncology

(e.g. paediatrician, surgeon, radiation oncologist)


o I spent at least X months in a reference* centre for paediatric radiotherapy (NB: a centre

that irradiates at least 100 children per year)

o Indicate the number of months:

o Specify the centre(s) you mention:

o I spent at least X months in a reference* centre for paediatric oncology

o Indicate the number of months:

o Specify the centre(s) you mention:

o Other options? please specify

Q.27: When did you last participate in an educational course/session on paediatric

radiotherapy (e.g. at PROS; at ESTRO/SIOPE; at ASTRO)? *

Please select one

o I never participated

o 1-5 years ago

o 6-10 years ago

o 11-15 years ago


Q.28: How do you update/refresh your knowledge on paediatric radiotherapy oncology

or paediatric oncology? *


o National conferences on paediatric oncology & radiotherapy

o Meetings of the PROS-society

o Meetings of SIOP(E)

o Meetings of ESTRO

o Meetings of ASTRO

o Paediatric tumour group meetings (e.g. SIOPEN, SIOP-BTG,…)

o Via literature only


75

Q.29: Where do you discuss individual patient-related problems with radiotherapy? *


o I don’t have a forum/colleague to discuss my problem

o I contact my colleague within the department

o I contact a colleague in my country/the national representative of the relevant study

o I contact ‘my’ international network

o There is a (web) conference system in the country to discuss difficult patients


Q.30: Do you have access to recent protocols, defining the ‘gold standard’ of paediatric

radiotherapy? *

Please select one

o Yes

o No

o Don’t know

Q.31: Do you believe a European network of paediatric radiation oncologists could be

helpful for your daily practice? *

Please select one

o No

o Yes


Q.32: Do you have further comments regarding Survey Part 2: Education and Training?

Open text box

76

PART 3: CLINICAL RESEARCH

Q.33: Does your radiotherapy department participate or run prospective clinical trials

(not limited to paediatric oncology)? *

Please select one

o Yes (Go to Q 33a)

o No (Go to Q33b)

o Don’t know

Q.33a: Please specify how your department is involved in prospective clinical trials*


o My department participates in prospective clinical trials

o My department runs prospective clinical trials

o Q.33b: Please specify the major reason for non-involvement in prospective clinical

trials

Open text box

Q.34: Does your radiotherapy department participate in prospective clinical trials in

paediatric oncology? *

Please select one

o Yes (Go to Q34a)

o No (Go to Q34b)

o Don’t know

Q.34a: Please specify what prospective trials in paediatric oncology is your department

involved in. *


o SIOPE

o COG


Q.34b: Please specify the reasons for non-involvement in prospective clinical trials in

paediatric oncology

Open text box

Q.35: Outside of clinical trials, do you systematically register your radiotherapy data (e.g.

prescription dose, dose to organs at risk, images, etc…) in a data-registration platform? *

Please select one

o Yes (Go to Q35a)

o No (Go to Q36)

77

Q.35a: At what level do you register your radiotherapy data? *


o Hospital (or department) level

o National level*

o International level*

*If yes, please specify the name of the project Open text box

Q.36: Outside of clinical trials, do you systematically register outcome (e.g. local failure,

distant failure, survival, late toxicity) in a database? *

o Yes (Go to Q36a)

o No (Go to Q37)

Q.36a: At what level do you register outcome data?


o Hospital (or department) level

o National level*

o International level*

*If yes, please specify the name of the project Open text box

Q.37: Do you have further comments regarding Survey Part 3: Clinical Research?

Open text box

78

FINAL PART

Q.38: Can your name be listed, as reference radiation oncologist for your centre, in

future reports/publications? *

- Yes (Go to Q 39-40)

- No (Go to end of survey)

Q.39: Your name and last name Open text box

Q.40: Your email address Open text box

Documents

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