Original Research

# Impact of COVID-19 pandemic on childhood cancer incidence and stage in France – A national registry-based study

<figure><img src="image_1.png" /></figure>

Maud Gédor<sup>a, b</sup>, Brigitte Lacour<sup>a, c, e</sup>, Sandra Guissou<sup>a</sup>, Laure Faure<sup>b, c</sup>, Claire Poulalhon<sup>b, c</sup>, François Doz<sup>d</sup>, Arnaud Petit<sup>e</sup>, Jérémie Rouger<sup>f</sup>, Virginie Gandemer<sup>g</sup>, Emmanuel Désandes<sup>a, c, i</sup>, Jacqueline Clavel<sup>b, c, j</sup>

ARTICLE INFO

Keywords:

Childhood cancer

COVID-19 pandemic

French Childhood Cancer Registry

Stage at diagnosis

Time to diagnosis

ABSTRACT

COVID-19 pandemic has considerably affected access to healthcare resources with global decline in cancer care activities in 2020. This national study aimed to assess a possible impact of the pandemic on the management of pediatric cancer cases.

**Methods:** The study was based on the French National Childhood Cancer Registry and included all cases of cancer under 18 years of age diagnosed between January 1, 2016 and December 31, 2020. We estimated incidence rates, the proportion of advanced/metastatic stages (Toronto Pediatric Cancer Stage Guidelines) and the distribution of treatment initiation time during the 2020 pandemic period compared to the 2016–2019 reference period.

**Results:** Age-standardized incidence rates of overall pediatric cancer were similar in 2020 (161.4 cases per million person-years; 2250 cases) and in 2016–2019 (162.4 cases per million person-years; 9208 cases). They were also similar by sex, age group, region, and cancer type. We did not observe any significant differences in stage at diagnosis or median time to treatment.

**Conclusion:** Our nationwide population-based study suggests that pediatric cancer management was not substantially altered in 2020, despite the challenges induced by the COVID-19 pandemic and associated lockdown.

1. Introduction

The outbreak of SARS-CoV-2, responsible for COVID-19 recognized as a pandemic by the World Health Organisation (WHO) in the early months of 2020 [1] has considerably affected healthcare systems worldwide. Access to healthcare facilities was reserved primarily for patients suffering from severe forms of COVID-19, thus limiting access for other pathologies, notably cancer. In addition, some patients gave up going to their doctor or hospital, for fear of being infected. The

pandemic may also have impacted the diagnosis of cancer in children, particularly when the first symptoms were limited. In addition, once the diagnosis was made, implementation of hospital treatment strategy may have been delayed due to hospital overcrowding. However, very early on, the French Society for the Fight against Cancer and Leukemia in Children and Adolescents (SFCE, Société Française de lutte contre les cancers et les leucémies de l'enfant et de l'adolescent) and the international learned societies on childhood cancer (SIOP, COG and St Jude Global) issued recommendations on the management of pediatric

<footnote><sup>a</sup> Registre National des cancers de l'Enfant, Registre National des Tumeurs Solides de l'Enfant, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France</footnote>

<footnote><sup>b</sup> Registre National des Cancers de l'Enfant, Registre National des Hémopathies Malignes de l'Enfant, Hôpital Paul Brousse, Groupe Hospitalier Universitaire Paris-Sud, Assistance Publique Hopitaux de Paris (AP-HP), Villejuif, France</footnote>

<footnote><sup>c</sup> Equipe OPPaLE Obstetric, Perinatal, and Paediatric Life course Epidemiology, Epidémiologie des Cancers des Enfants et des Adolescents, Centre de Recherche en Epidémiologie et Statistiques (CRESS), INSERM, UMR 1153, Université Paris-Cité, Paris, France</footnote>

<footnote><sup>d</sup> SIREDO Center (Care, Innovation, Research in Pediatric, Adolescent and Young Adults Oncology), Institut Curie and University Paris Cité, Paris, France</footnote>

<footnote><sup>e</sup> Service d'Hématologie, Immunologie et Oncologie pédiatrique, Hôpital Armand Trousseau, APHP, Sorbonne Université, Paris, France</footnote>

<footnote><sup>f</sup> Centre Hospitalier Universitaire de Caen Normandie, Oncohématologie Pédiatrique, Caen 14000, France</footnote>

<footnote><sup>g</sup> Service d'oncohématopédiatrie du CHU de Rennes, Université Rennes, on behalf of the French Society for the Fight against Cancer and Leukemia in Children and Adolescents (SFCE), France</footnote>

<footnote>* Correspondence to: Registre National des Tumeurs Solides de l'Enfant, Université de Lorraine, Faculté de médecine, 9 Avenue de la Foret de Haye, BP 20199, Vandœuvre-lès-Nancy Cedex 54505, France.</footnote>

<footnote>E-mail address: brigitte.lacour@univ-lorraine.fr (B. Lacour).</footnote>
cancers during the pandemic, in order to minimize its impact [2,3]. Despite these early recommendations, several studies have shown delayed diagnosis or interrupted treatment in children with cancer [4–6]. These disruptions were particularly significant in low- and middle-income countries [7], although high-income countries such as the USA and Italy also reported unusual critical cases of pediatric cancers appearing to be due to delayed diagnosis [8,9].

In France, recommendations were issued in March 2020 by the High Council for Public Health focusing on 3 points: prevention of contamination, prioritization of care and organization of health care facilities. Children have never been concerned by the recommendations for prioritization of care [10] and messages for maintaining care have been disseminated by the French Society for the Fight against Cancer and Leukemia in Children and Adolescents, the SFCE, since the beginning of the epidemic [2]. Nevertheless, it was important to assess to what extent the decline in cancer care activities in oncology or hematology departments observed in 2020 may have affected pediatric oncology units and childhood cancer care.

Based on the French National childhood cancer registry, we evaluate the influence of COVID-19 in childhood cancer incidence, stage at diagnosis and time to treatment initiation.

## 2. Methods

### 2.1. Study population

The French National Registry of Childhood Cancer (RNCE, https://rnce.inserm.fr) records every child or adolescent diagnosed with cancer or central nervous system (CNS) benign tumor before the age of 15 until 2011 and before the age of 18 since then. Lacour et al. have previously described the methodology of case registration [11]. All cases recorded between January 1, 2016 and December 31, 2020 were included. Population data were provided by the French Institute of Statistics and Economic Studies (INSEE) for each year from 2016 to 2020.

### 2.2. Data

All the diagnoses were coded using the third revision of the International Classification of Disease for Oncology (ICD-O-3) and grouped according to the third edition of the International Classification of Childhood Cancer (ICCC-3) [12] updated in 2017 (https://iicc.iarc.fr/results).

For most childhood cancers, stage at diagnosis was coded using the Toronto Pediatric Cancer Stage Guidelines [13,14]. Cancer types eligible for this staging include acute lymphoblastic leukemias, lymphomas, ependymomas, medulloblastomas, astrocytomas, neuroblastomas, retinoblastomas, nephroblastomas, hepatoblastomas, bone tumors, rhabdomyosarcomas and non-rhabdomyosarcoma soft tissue sarcomas, and gonadal germ cell tumors. We applied the Toronto Tier 1 staging system to differentiate localized from metastatic or advanced disease in eligible cancer types, except for Hodgkin lymphomas where the Tier 1 stages IIIA, IIIB, IVA and IVB (Ann Arbor) were grouped into the advanced stage and for non-Hodgkin lymphomas for which we considered stage III as advanced rather than limited. In addition, Hodgkin lymphomas, neuroblastomas and nephroblastomas were also staged according to Toronto Tier 2, and retinoblastomas according to the ABC classification [15] which allows a better description of intraocular extension. Furthermore, we also included in eligible cases the extracranial extragonadal malignant germ-cell tumors using the Brodeur classification [16] and the epithelial cancers using the 8th edition of the AJCC TNM staging system [17].

Time to treatment initiation was calculated as the difference in days between the date of diagnosis and the date of treatment initiation.

We took the year 2020 for the COVID-19 period and the period 2016–2019 as the reference period.

### 2.3. Statistical analysis

Incidence rates were calculated for all cancers combined, as well as by gender, age-group, French region and tumor type. Age-standardized incidence rates (ASR) were estimated by the direct method using the world population age distribution. Methods based on Poisson distribution were used to specify the 95 % confidence interval (95 %CI) for the ASR [18]. Continuous and categorical variables were expressed as median (inter quartile range) or percentages, respectively. The proportions of advanced stages at diagnosis during the COVID-19 year and during the reference period were compared using the Pearson's chi-square or Fisher's exact test, as appropriate, and times to treatment initiation were compared using the Wilcoxon signed-rank test. Patients with no treatment (surveillance, palliative from the outset or death before treatment) or missing treatment delay were excluded from this analysis. Numbers of cancer deaths and cancer mortality rates were obtained for the <1 year and 1–24 year age groups on the CepiDC website (https://opendata-cepi dc.inserm.fr/)

All statistical analyses were performed using R 4.3.2 [19].

## 3. Results

The RNCE included 2250 cases in 2020 (960 (42.6 %) with a diagnosis of hematopoietic malignancy and 1290 (57.3 %) with a diagnosis of solid tumor), and 9208 cases in 2016–2019 (3681 (40.0 %) with a diagnosis of hematopoietic malignancy and 5527 (60.0 %) with a diagnosis of solid tumor). The ASR was 161.4 per million person-years [95 %CI: 147.0–177.0] in 2020 and 162.4 per million person-years [95 %CI: 155.1–169.9] during the 2016–2019 reference period (Table 1). No differences in ASR were observed between the COVID-19 year and the reference period, overall or by sex, age-group, cancer type and region. The number of cases by region was too low to assess heterogeneity in incidence rates between regions and to identify region-specific changes between periods. Fig. 1 present the number of childhood cancer cases diagnosed in 2020 by calendar months in comparison to the average number of cases for the respective month during the reference period 2016–2019. A lower number of cases from February to May and September is noteworthy, then offset by a higher number in the other months. The monthly distribution of cases by region is too fluctuating to be analyzed during 2020.

Eligible cases for Toronto staging represented 79.6 % of the cases diagnosed in the COVID-19 year and 81.2 % of the cases diagnosed in the reference period (Table 2). For both periods, the proportion of staged cases was higher in the 0–4 year age group, where embryonal tumors are more common, and in the 15–17 year age group, where lymphomas and gonadal germ-cell tumors are more common.

The proportion of cases diagnosed at a metastatic/advanced stage was 24.8 % in the COVID-19 period and 22.9 % in the reference period (p = 0.10, Table 3). Increased proportions of metastatic/advanced stages were observed for leukemias (25.9 % versus 21.0 % with CNS involvement, p = 0.03) and osteosarcomas (33 % versus 22 %, p = 0.09). However, in the acute lymphoblastic leukemia (ALL), a gradual increase was observed between 2016 and 2020, with the following percentages: 18 % in 2016, 21.5 % in 2017 and 2018, 23 % in 2019 and 26 % in 2020. For neuroblastomas, the proportion of metastatic/advanced stage was the same for both periods, but Tier 2 staging showed that there were more M stage (45.5 % versus 39.0 %) and fewer MS stage (4.1 % versus 10.6 %) during the COVID-19 period (p = 0.09). For retinoblastomas, 2 cases were diagnosed at a metastatic stage in the COVID-19 year while 1 metastatic case was observed over the 4 years of the reference period. The ABC stage did not differ between the 2 periods. For the other tumors (lymphomas, brain tumors, nephroblastomas, hepatoblastomas, Ewing sarcomas, soft tissue sarcomas, germ cell tumors and carcinomas), there were no more advanced stages in the COVID-19 period than in the reference period.

Table 4 compares the median time to treatment after diagnosis (in
<table><caption>**Table 1**
Number of cases and annual incidence rate during the COVID-19 period (2020) and the reference period (2016–2019).</caption><thead><tr><th rowspan="3"></th><th colspan="6">COVID-19 period</th><th colspan="6">Reference period</th></tr><tr><th colspan="2">Number of cases</th><th colspan="4">Incidence rate per million person-years</th><th colspan="2">Number of cases</th><th colspan="3">Incidence rate per million person-years</th></tr><tr><th>N</th><th>%</th><th>Crude rate [95 % CI]<sup>1</sup></th><th>ASR<sup>2</sup> [95 % CI]<sup>1</sup></th><th>N</th><th>%</th><th>Crude rate [95 % CI]<sup>1</sup></th><th>ASR<sup>2</sup> [95 % CI]<sup>1</sup></th><th>N</th><th>%</th><th>Crude rate [95 % CI]<sup>1</sup></th><th>ASR<sup>2</sup> [95 % CI]<sup>1</sup></th></tr></thead><tbody><tr><td>All cancers</td><td>2250</td><td>100.0</td><td>156.7</td><td>[150.3-163.3]</td><td>161.4</td><td>[147.0-177.0]</td><td>9208</td><td>100.0</td><td>158.2</td><td>[155.0-161.5]</td><td>162.4</td><td>[155.1-169.9]</td></tr><tr><td><strong>Sex</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Male</td><td>1227</td><td>54.5</td><td>167.0</td><td>[157.8-176.6]</td><td>172.0</td><td>[151.3-194.8]</td><td>4963</td><td>53.9</td><td>166.6</td><td>[162.1-171.4]</td><td>170.7</td><td>[160.4-181.6]</td></tr><tr><td>Female</td><td>1023</td><td>45.5</td><td>145.8</td><td>[137.0-155.1]</td><td>150.4</td><td>[130.7-172.4]</td><td>4245</td><td>46.1</td><td>149.3</td><td>[144.9-153.9]</td><td>153.6</td><td>[143.6-164.3]</td></tr><tr><td><strong>Age (years)</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>&lt;1</td><td>158</td><td>7.0</td><td>229.1</td><td>[194.8-267.8]</td><td>229.1</td><td>[194.8-267.8]</td><td>697</td><td>7.6</td><td>242.7</td><td>[225.0-261.4]</td><td>242.7</td><td>[225.0-261.4]</td></tr><tr><td>1-4</td><td>593</td><td>26.4</td><td>203.5</td><td>[187.5-220.6]</td><td>203.5</td><td>[187.5-220.6]</td><td>2413</td><td>26.2</td><td>197.7</td><td>[189.9-205.7]</td><td>197.7</td><td>[189.9-205.7]</td></tr><tr><td>5-9</td><td>476</td><td>21.2</td><td>117.5</td><td>[107.2-128.6]</td><td>117.5</td><td>[107.2-128.6]</td><td>2059</td><td>22.4</td><td>124.8</td><td>[119.4-130.3]</td><td>124.8</td><td>[119.4-130.3]</td></tr><tr><td>10-14</td><td>589</td><td>26.2</td><td>139.8</td><td>[128.7-151.5]</td><td>139.8</td><td>[128.7-151.5]</td><td>2206</td><td>24.0</td><td>132.8</td><td>[127.3-138.5]</td><td>132.8</td><td>[127.3-138.5]</td></tr><tr><td>15-17</td><td>434</td><td>19.3</td><td>174.1</td><td>[158.1-191.3]</td><td>174.1</td><td>[158.1-191.3]</td><td>1832</td><td>19.9</td><td>182.9</td><td>[174.6-191.5]</td><td>182.9</td><td>[174.6-191.5]</td></tr><tr><td><strong>Region</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Auvergne-Rhône-Alpes</td><td>282</td><td>12.5</td><td>160.7</td><td>[142.5-180.6]</td><td>166.1</td><td>[125.7-215.9]</td><td>1174</td><td>12.8</td><td>166.6</td><td>[157.2-176.4]</td><td>169.0</td><td>[148.2-192.0]</td></tr><tr><td>Bourgogne-Franche-Comté</td><td>91</td><td>4.0</td><td>161.8</td><td>[130.2-198.7]</td><td>164.6</td><td>[100.0-260.2]</td><td>336</td><td>3.6</td><td>144.8</td><td>[129.8-161.2]</td><td>145.9</td><td>[113.3-185.7]</td></tr><tr><td>Bretagne</td><td>128</td><td>5.7</td><td>184.7</td><td>[154.1-219.6]</td><td>196.2</td><td>[130.1-287.2]</td><td>417</td><td>4.5</td><td>147.5</td><td>[133.7-162.4]</td><td>151.0</td><td>[120.5-187.4]</td></tr><tr><td>Centre-Val de Loire</td><td>75</td><td>3.3</td><td>139.0</td><td>[109.3-174.3]</td><td>151.6</td><td>[86.3-248.7]</td><td>333</td><td>3.6</td><td>150.8</td><td>[135.1-167.9]</td><td>157.2</td><td>[121.9-200.0]</td></tr><tr><td>Corse</td><td>6</td><td>0.3</td><td>94.2</td><td>[34.5-205.0]</td><td>105.0</td><td>[22.0-471.4]</td><td>33</td><td>0.4</td><td>132.5</td><td>[91.2-186.1]</td><td>139.3</td><td>[56.1-293.8]</td></tr><tr><td>Grand Est</td><td>168</td><td>7.5</td><td>148.9</td><td>[127.2-173.2]</td><td>152.1</td><td>[106.2-212.8]</td><td>767</td><td>8.3</td><td>165.8</td><td>[154.3-177.9]</td><td>173.7</td><td>[147.5-203.4]</td></tr><tr><td>Hauts-de-France</td><td>232</td><td>10.3</td><td>169.9</td><td>[148.8-193.3]</td><td>177.4</td><td>[130.7-236.3]</td><td>863</td><td>9.4</td><td>153.6</td><td>[143.6-164.3]</td><td>159.1</td><td>[136.6-184.6]</td></tr><tr><td>Ile-de-France</td><td>421</td><td>18.7</td><td>147.3</td><td>[133.6-162.1]</td><td>151.1</td><td>[121.0-186.6]</td><td>1818</td><td>19.7</td><td>159.3</td><td>[152.0-166.8]</td><td>161.9</td><td>[145.9-179.2]</td></tr><tr><td>Normandie</td><td>121</td><td>5.4</td><td>173.4</td><td>[143.9-207.3]</td><td>175.5</td><td>[113.7-261.7]</td><td>397</td><td>4.3</td><td>137.6</td><td>[124.4-151.9]</td><td>144.2</td><td>[114.5-179.5]</td></tr><tr><td>Nouvelle-Aquitaine</td><td>192</td><td>8.5</td><td>166.4</td><td>[143.7-191.8]</td><td>170.2</td><td>[121.4-233.7]</td><td>822</td><td>8.9</td><td>175.4</td><td>[163.6-187.8]</td><td>176.6</td><td>[150.6-206.1]</td></tr><tr><td>Occitanie</td><td>189</td><td>8.1</td><td>154.0</td><td>[132.5-178.0]</td><td>155.9</td><td>[109.9-216.0]</td><td>752</td><td>8.2</td><td>157.6</td><td>[146.6-169.3]</td><td>163.6</td><td>[138.8-191.8]</td></tr><tr><td>Pays de la Loire</td><td>145</td><td>6.4</td><td>172.7</td><td>[145.8-203.3]</td><td>179.5</td><td>[120.8-258.3]</td><td>559</td><td>6.1</td><td>164.1</td><td>[150.8-178.3]</td><td>167.8</td><td>[138.2-202.3]</td></tr><tr><td>Provence-Alpes-Côte d'Azur</td><td>165</td><td>7.3</td><td>161.1</td><td>[137.5-187.7]</td><td>161.0</td><td>[111.5-226.4]</td><td>707</td><td>7.7</td><td>171.8</td><td>[159.4-184.9]</td><td>176.6</td><td>[149.0-207.9]</td></tr><tr><td>Overseas regions<sup>3</sup></td><td>41</td><td>1.8</td><td>83.1</td><td>[59.7-112.8]</td><td>89.1</td><td>[42.6-170.7]</td><td>230</td><td>2.5</td><td>113.1</td><td>[98.9-128.7]</td><td>118.7</td><td>[87.5-157.9]</td></tr><tr><td><strong>Cancer type</strong></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Leukemia</td><td>611</td><td>27.2</td><td>42.5</td><td>[39.2-46.1]</td><td>46.0</td><td>[38.8-54.3]</td><td>2325</td><td>25.3</td><td>39.9</td><td>[38.3-41.6]</td><td>42.6</td><td>[39.1-46.4]</td></tr><tr><td>Lymphoma</td><td>349</td><td>15.5</td><td>24.3</td><td>[21.8-27.0]</td><td>21.7</td><td>[17.4-27.2]</td><td>1356</td><td>14.7</td><td>23.3</td><td>[22.1-24.6]</td><td>21.1</td><td>[18.9-23.6]</td></tr><tr><td>Central nervous system tumor</td><td>582</td><td>25.9</td><td>40.5</td><td>[37.3-44.0]</td><td>41.4</td><td>[34.4-49.5]</td><td>2266</td><td>24.6</td><td>38.9</td><td>[37.3-40.6]</td><td>39.7</td><td>[36.3-43.5]</td></tr><tr><td>Neuroblastoma</td><td>123</td><td>5.5</td><td>8.6</td><td>[7.1-10.2]</td><td>10.6</td><td>[7.4-14.9]</td><td>542</td><td>5.9</td><td>9.3</td><td>[8.5-10.1]</td><td>11.4</td><td>[9.7-13.4]</td></tr><tr><td>Retinoblastoma</td><td>49</td><td>2.2</td><td>3.4</td><td>[2.5-4.5]</td><td>4.5</td><td>[2.8-7.4]</td><td>202</td><td>2.2</td><td>3.5</td><td>[3.0-4.0]</td><td>4.4</td><td>[3.5-5.6]</td></tr><tr><td>Renal tumor</td><td>86</td><td>3.8</td><td>6.0</td><td>[4.8-7.4]</td><td>7.2</td><td>[4.6-11.0]</td><td>416</td><td>4.5</td><td>7.1</td><td>[6.5-7.9]</td><td>8.4</td><td>[6.9-10.1]</td></tr><tr><td>Hepatic tumor</td><td>22</td><td>1.0</td><td>1.5</td><td>[1.0-2.3]</td><td>1.9</td><td>[0.7-4.3]</td><td>87</td><td>0.9</td><td>1.5</td><td>[1.2-1.8]</td><td>1.7</td><td>[1.0-2.6]</td></tr><tr><td>Bone tumor</td><td>124</td><td>5.5</td><td>8.6</td><td>[7.2-10.3]</td><td>7.6</td><td>[5.3-11.0]</td><td>521</td><td>5.7</td><td>9.0</td><td>[8.2-9.8]</td><td>8.1</td><td>[6.7-9.7]</td></tr><tr><td>Soft tissue sarcoma</td><td>136</td><td>6.0</td><td>9.5</td><td>[7.9-11.2]</td><td>9.6</td><td>[6.4-14.0]</td><td>555</td><td>6.0</td><td>9.5</td><td>[8.8-10.4]</td><td>9.7</td><td>[8.0-11.7]</td></tr><tr><td>Germ cell tumor</td><td>68</td><td>3.0</td><td>4.7</td><td>[3.7-6.0]</td><td>4.7</td><td>[2.6-8.0]</td><td>410</td><td>4.5</td><td>7.0</td><td>[6.4-7.8]</td><td>7.1</td><td>[5.6-8.8]</td></tr><tr><td>Carcinomas</td><td>94</td><td>4.2</td><td>6.5</td><td>[5.3-8.0]</td><td>5.7</td><td>[3.8-8.8]</td><td>503</td><td>5.5</td><td>8.6</td><td>[7.9-9.4]</td><td>7.7</td><td>[6.5-9.3]</td></tr><tr><td>Other</td><td>6</td><td>0.3</td><td>0.4</td><td>[0.2-0.9]</td><td>0.5</td><td>[0.1-2.0]</td><td>25</td><td>0.3</td><td>0.4</td><td>[0.3-0.6]</td><td>0.5</td><td>[0.2-1.1]</td></tr></tbody></table>

<figure><img src="image_2.png" /><figcaption>**Fig. 1.** Absolute number of cases of newly diagnosed childhood cancers cases (0–17 years) in 2020 by calendar months versus the average number of childhood cancer cases during the reference period (2016–2019).</figcaption></figure>

days) for all cases and for metastatic/advanced diseases between the reference period and the COVID-19 year. Overall, 48 children died before treatment (mainly leukemias and CNS tumors), 17 were in palliative care from the start (CNS tumors), 522 were under surveillance before treatment and 98 data were missing (supplementary table 1). Pretreatment surveillance mainly concerned brain tumors, particularly low-grade gliomas for which treatment could be postponed. Neuroblastomas spontaneously regressed or whose first phase of management was surveillance were also involved. Analysis of median time to treatment therefore covered 94 % of all cases, equally distributed between the two periods. Compared to the reference period, results in 2020 were similar for all patients and those with metastatic diseases.

Finally, cancer mortality rates seemed to be stable over 2016–2021 for <1 year and 1–24 years age groups, with no increase in 2020 and 2021 (Supplementary table 2).

## 4. Discussion

This study based on the French national registry of childhood cancers found no change in childhood cancer incidence during the COVID-19 year 2020 compared to the reference period 2016–2019. However two decreases in incidence were observed in 2020 corresponding to periods of strict confinement. Overall, stage at diagnosis during the COVID-19 pandemic also did not differ statistically from that in previous years. No differences were observed in term of median time to treatment.

<footnote n="195">¹⁹⁵ % confidence interval; ²age-standardized rate; ³Guadeloupe, Guyane, Martinique and La Réunion.</footnote>
<caption>**Table 2**</caption>

Proportion of cases with a diagnosis eligible for staging according to the Toronto guidelines by diagnosis group (International classification of childhood cancer. 3rd edition) during the COVID-19 period (2020) and the reference period (2016–2019).

<table><thead><tr><th rowspan="3"></th><th colspan="3">COVID-19 period</th><th colspan="3">Reference period</th></tr><tr><th rowspan="2">Total</th><th colspan="2">Staged</th><th rowspan="2">Total</th><th colspan="2">Staged</th></tr><tr><th>n</th><th>%</th><th>n</th><th>%</th></tr></thead><tbody><tr><td>All cases</td><td>2250</td><td>1790</td><td>79.6</td><td>9208</td><td>7483</td><td>81.3</td></tr><tr><td><strong>Sex</strong></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Male</td><td>1227</td><td>973</td><td>79.3</td><td>4963</td><td>4030</td><td>81.2</td></tr><tr><td>Female</td><td>1023</td><td>817</td><td>79.9</td><td>4245</td><td>3453</td><td>81.3</td></tr><tr><td><strong>Age (years)</strong></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>&lt;1</td><td>158</td><td>125</td><td>79.1</td><td>697</td><td>577</td><td>82.8</td></tr><tr><td>1–4</td><td>593</td><td>513</td><td>86.5</td><td>2413</td><td>2104</td><td>87.2</td></tr><tr><td>5–9</td><td>476</td><td>357</td><td>75.0</td><td>2059</td><td>1616</td><td>78.5</td></tr><tr><td>10–14</td><td>589</td><td>442</td><td>75.0</td><td>2207</td><td>1702</td><td>77.2</td></tr><tr><td>15–17</td><td>434</td><td>353</td><td>81.3</td><td>1832</td><td>1484</td><td>81.0</td></tr><tr><td><strong>Cancer type</strong></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Leukemia</td><td>611</td><td>464</td><td>76.0</td><td>2325</td><td>1812</td><td>77.9</td></tr><tr><td>Lymphoma</td><td>349</td><td>349</td><td>100.0</td><td>1356</td><td>1325</td><td>98.0</td></tr><tr><td>Central nervous system tumor</td><td>582</td><td>320</td><td>55.0</td><td>2266</td><td>1361</td><td>60.1</td></tr><tr><td>Neuroblastoma</td><td>123</td><td>121</td><td>98.0</td><td>542</td><td>528</td><td>97.4</td></tr><tr><td>Retinoblastoma</td><td>49</td><td>49</td><td>100.0</td><td>202</td><td>202</td><td>100.0</td></tr><tr><td>Renal tumor</td><td>86</td><td>70</td><td>81.0</td><td>416</td><td>363</td><td>87.3</td></tr><tr><td>Hepatic tumor</td><td>22</td><td>17</td><td>77.0</td><td>87</td><td>67</td><td>77.0</td></tr><tr><td>Bone tumor</td><td>124</td><td>121</td><td>98.0</td><td>521</td><td>484</td><td>92.9</td></tr><tr><td>Soft tissue sarcoma</td><td>136</td><td>136</td><td>100.0</td><td>555</td><td>555</td><td>100.0</td></tr><tr><td>Germ cell tumor</td><td>68</td><td>49</td><td>72.0</td><td>410</td><td>283</td><td>69.0</td></tr><tr><td>Carcinomas</td><td>94</td><td>94</td><td>100.0</td><td>503</td><td>503</td><td>100.0</td></tr><tr><td>Other</td><td>6</td><td>0</td><td></td><td>25</td><td>0</td><td></td></tr></tbody></table>

In adults, several reports demonstrated a severe impact of COVID-19 pandemic on cancer diagnosis and care in France [20] and abroad [21–23]. Data on pediatric cancers are more limited and less consistent, with analyses hampered by small numbers of cases. In France, as in many high income countries, children are cared for in approved specialist centers, which have been organized from the start of the pandemic to preserve care and apply recommendations issued by public health bodies. Studies in Italy [24] and in the United-States (US) [25] showed a decrease in childhood solid tumors diagnoses during the COVID lockdown with a rebound in the following months, but they did not provide incidence data over the whole 2020 year. Our population-based data showed a slight decrease in the number of cases during the months of lockdown without visible impact on the overall incidence of the year 2020. This absence of decrease in childhood cancer incidence in 2020 was also reported in Canada [26], Greece [27] and Germany [28], and an increase in incidence was observed in Germany for all cancer types.

Based on SIOP-RTSG trial data, Roy et al. described a decrease in Wilms tumors diagnoses during the first three months of the pandemic in Europe (March to May 2020) followed by a slight increase from May to July 2020 [29]. A decrease in pediatric acute lymphoblastic leukemia (ALL) diagnoses has been observed in Norway [30], based on a small number of cases, which were said to possibly result from a decrease in the frequency of common infections during lockdown. Leukemia incidence was unchanged in 2020 in our study. However, we do not expect the impact of the pandemic on ALL incidence to be straightforward [26, 27]. Periods of increased exposure to infections have alternated or coexisted with periods of underexposure to infections due to lockdowns and barrier gestures. Furthermore, the risk of leukemic transformation of B cells following a response to infection depends on their prior carriage of initiating mutations, the age of the child, and his/her experience of immune stimulation in early childhood through social contacts and common infections.

Several publications reported inadequate access to care and consequent delay in diagnosis of childhood cancer during the first peak of the

COVID-19 pandemic [7,8,24,31,32] but they were based on hospital observations and were not confirmed by population-based studies. In our study, we could not analyze diagnostic delay because the date of the first symptoms was not available. We nevertheless studied stage at diagnosis, relevant data for evaluating the impact of the pandemic and its related protective measures. We did not observe an increase in the proportion of patients with metastatic disease as also reported in Canada [26]. A slight increase in the percentage of acute leukemias with CNS involvement has been observed but the increase started before the pandemic may rather reflect progressive improvement in the detection and registration of CNS involvement [33]. Moreover, neuromeningeal involvement in ALL should not be considered as potentially linked to a diagnostic delay but rather as a different disease. Although not statistically significant, our result about retinoblastomas is intriguing. Indeed, only one patient had metastatic disease at diagnosis over the 2016–2019 period while we observed 2 cases with CNS involvement considered as metastatic disease in 2020. An in-depth look at these cases revealed that one patient had a sellar retinoblastoma, an unusual location with a very poor prognosis which was related to inherited RB1 mutation, so this particular disease was not related to a delayed diagnosis. The other patient had a true CNS metastatic disease and could have a true diagnosis delay since he did not come to his appointment at a referral center during the lockdown period. The diagnosis was therefore only made in July, when the patient had a retinal detachment due to tumor progression. Of these two advanced retinoblastomas, the last may be linked to a delay in diagnosis due to the Covid-19 pandemic restrictions. For Wilms tumors, data from the SIOP-RTSG trial [29] showed that European patients included during the peak of the pandemic (March-May) presented with relatively higher tumor volumes and more often with metastatic disease. This observation was limited to the first period of the pandemic, and immediately after, tumor volumes and stage distribution returned to the previous pattern. This is consistent with the lack of change in nephroblastoma stage at diagnosis in 2020 in our study. Regarding bone tumors, although not statistically significant, the proportion of metastatic cases appeared slightly higher in 2020 than in the previous period, particularly for osteosarcomas (33.3 % vs 22.6 %, NS). We did not investigate tumor size at diagnosis but the diagnostic process might be affected by a longer delay in performing biopsy as it was observed in Poland in adult patients [34].

Once the diagnosis of cancer has been made, the pandemic may also have delayed the time to start treatment, through the overburdened or disorganization of hospitals even if recommendations have been made to hospitals to adapt their services to limited resources so that children with cancer could be treated without delay while preserving patient safety [3]. In our data, we did not observe a higher delay between diagnosis and start of treatment during the year 2020 compared with the previous period. There was also no increase in cancer mortality rates in 2020 and 2021 in the <1 year and 1–24 year age groups. It therefore appears that the French services have followed the recommendations with adequate organization to care for the children in good conditions.

Study of the SIOP-RTSG trial [29] also showed that referral and treatment of children diagnosed with a more advanced stage of Wilms tumors was not delayed once they had reached medical services. This is consistent with the findings of a North-American cross-sectional study showing that parents of children with cancer did not report major disruptions to cancer care needs [35].

A significant strength of our study is its reliance on exhaustive data from a nationwide population-based registry without selection biases. It is the first assessment of the impact of the COVID-19 pandemic on incidence rate including disease stage at diagnosis at a national level. The RNCE is one of the oldest and most complete population-based childhood cancer registries worldwide, covering a population of 14.5 million aged from 0 to 17 years, allowing relevant analyses despite the scarcity of cancer in children. Moreover, systematic recording of stage standardized according to Toronto recommendations for all cases diagnosed from 2016 onwards is a real benefit to better characterize
<table><caption>**Table 3**
Proportion of cases diagnosed at a metastatic or advanced stage during the COVID-19 period (2020) and the reference period (2016–2019).</caption><thead><tr><th rowspan="2">Diagnostic group</th><th rowspan="2">Classification</th><th rowspan="2">Stage group</th><th colspan="2">COVID-19 period</th><th colspan="2">Reference period</th><th rowspan="2">p value</th></tr><tr><th>n</th><th>%</th><th>n</th><th>%</th></tr></thead><tbody><tr><td>TOTAL</td><td></td><td>Metastatic/Advanced</td><td>443</td><td>24.8</td><td>1717</td><td>22.9</td><td>0.10</td></tr><tr><td>I.a Acute lymphoblastic leukemias</td><td>Toronto T1</td><td>CNS involvement</td><td>120</td><td>25.9</td><td>380</td><td>21.0</td><td>0.03</td></tr><tr><td>II Lymphomas</td><td>Toronto T1</td><td>Advanced</td><td>116</td><td>33.2</td><td>483</td><td>36.5</td><td>0.29</td></tr><tr><td rowspan="5">Hodgkin lymphomas (II.a)</td><td>Toronto T1</td><td>Advanced (IIIA/ B.IVA/B)</td><td>89</td><td>46.1</td><td>382</td><td>47.9</td><td>0.10</td></tr><tr><td rowspan="4">Toronto T2</td><td>IA/IB</td><td>10</td><td>5.2</td><td>44</td><td>5.6</td><td rowspan="4">0.86</td></tr><tr><td>IIA/IIB</td><td>93</td><td>48.4</td><td>362</td><td>45.9</td></tr><tr><td>IIIA/IIIB</td><td>32</td><td>16.7</td><td>138</td><td>17.5</td></tr><tr><td>IVA/IVB</td><td>57</td><td>29.7</td><td>244</td><td>31.0</td></tr><tr><td>Burkitt lymphomas (II.c)</td><td>Toronto T1</td><td>Advanced (III.IV)</td><td>13</td><td>19.7</td><td>45</td><td>21.8</td><td>0.80</td></tr><tr><td>Other non-Hodgkin lymphomas (II.b)</td><td>Toronto T1</td><td>Advanced (III.IV)</td><td>14</td><td>15.6</td><td>56</td><td>17.4</td><td>0.84</td></tr><tr><td>III Central nervous system tumors</td><td>Toronto T1</td><td>Metastatic/Advanced</td><td>42</td><td>13.1</td><td>150</td><td>11.0</td><td>0.33</td></tr><tr><td>Ependymomas (III.a1). astrocytomas (III.b)</td><td>Toronto T1</td><td>Metastatic/Advanced</td><td>9</td><td>4.2</td><td>21</td><td>2.2</td><td>0.14</td></tr><tr><td>Embryonal tumors (III.c)</td><td>Toronto T1</td><td>Metastatic/Advanced</td><td>33</td><td>31.1</td><td>129</td><td>32.6</td><td>0.87</td></tr><tr><td rowspan="5">IV.a Neuroblastomas. ganglioneuroblastomas</td><td>Toronto T1</td><td>Metastatic/Advanced</td><td>60</td><td>49.6</td><td>262</td><td>49.6</td><td>1.00</td></tr><tr><td rowspan="4">Toronto T2</td><td>L1</td><td>24</td><td>19.8</td><td>123</td><td>23.3</td><td rowspan="4">0.09</td></tr><tr><td>L2</td><td>37</td><td>30.6</td><td>143</td><td>27.1</td></tr><tr><td>M</td><td>55</td><td>45.5</td><td>206</td><td>39.0</td></tr><tr><td>MS</td><td>5</td><td>4.1</td><td>56</td><td>10.6</td></tr><tr><td rowspan="6">V Retinoblastomas</td><td>Toronto T1</td><td>Metastatic/Advanced<sup>a</sup></td><td>2</td><td>4.1</td><td>1</td><td>0.5</td><td rowspan="6">0.18</td></tr><tr><td rowspan="5">ABC</td><td>A</td><td>2</td><td>4.2</td><td>5</td><td>2.5</td></tr><tr><td>B</td><td>6</td><td>12.5</td><td>25</td><td>12.4</td></tr><tr><td>C</td><td>2</td><td>4.2</td><td>18</td><td>9.0</td></tr><tr><td>D</td><td>16</td><td>33.3</td><td>65</td><td>32.3</td></tr><tr><td>E</td><td>22</td><td>45.8</td><td>88</td><td>43.8</td></tr><tr><td rowspan="5">VI.a1 Nephroblastoma</td><td>Toronto T1</td><td>Metastatic</td><td>15</td><td>21.4</td><td>75</td><td>20.7</td><td rowspan="5">1.00</td></tr><tr><td rowspan="4">Toronto T2</td><td>yI/I</td><td>33</td><td>48.5</td><td>151</td><td>41.8</td></tr><tr><td>yII/II</td><td>9</td><td>13.2</td><td>73</td><td>20.2</td></tr><tr><td>yIII/III</td><td>11</td><td>16.2</td><td>62</td><td>17.2</td></tr><tr><td>IV</td><td>15</td><td>22.1</td><td>75</td><td>20.8</td></tr><tr><td>VII.a Hepatoblastoma</td><td>Toronto T1</td><td>Metastatic</td><td>5</td><td>29.4</td><td>15</td><td>22.4</td><td>0.77</td></tr><tr><td>VIII. Malignant bone tumors</td><td>Toronto T1</td><td>Metastatic</td><td>40</td><td>33.1</td><td>137</td><td>28.3</td><td>0.36</td></tr><tr><td>Osteosarcomas. (VIII.a)</td><td>Toronto T1</td><td>Metastatic</td><td>23</td><td>33.3</td><td>58</td><td>22.6</td><td>0.09</td></tr><tr><td>Ewing tumor (VIII.c)</td><td>Toronto T1</td><td>Metastatic</td><td>17</td><td>32.7</td><td>79</td><td>34.8</td><td>0.90</td></tr><tr><td>IX. Soft tissue sarcomas</td><td>Toronto T1</td><td>Metastatic</td><td>25</td><td>18.4</td><td>138</td><td>24.9</td><td>0.14</td></tr><tr><td>Rhabdomyosarcomas (IX.a)</td><td>Toronto T1</td><td>Metastatic</td><td>14</td><td>19.7</td><td>83</td><td>28.1</td><td>0.20</td></tr><tr><td>Non-rhabdomyosarcomas (IX.b. c. d. e)</td><td>Toronto T1</td><td>Metastatic</td><td>11</td><td>16.9</td><td>55</td><td>21.2</td><td>0.56</td></tr><tr><td>X. Germ-cell tumors</td><td>Mixed</td><td>Metastatic/Advanced</td><td>9</td><td>18.4</td><td>56</td><td>19.8</td><td>0.97</td></tr><tr><td>Testicular tumors (X.c. d. e – C62)</td><td>Toronto T1</td><td>Metastatic/Advanced</td><td>7</td><td>50.0</td><td>29</td><td>35.8</td><td>0.48</td></tr><tr><td>Ovarian tumors (X.c. d. e – C56)</td><td>Toronto T1</td><td>Metastatic/Advanced</td><td>1</td><td>4.8</td><td>8</td><td>6.6</td><td>1.00</td></tr><tr><td>Extracranial extragonadal (X.b)</td><td>Brodeur</td><td>Metastatic/Advanced (III. IV)</td><td>1</td><td>7.1</td><td>19</td><td>23.8</td><td>0.30</td></tr><tr><td>XI. Epithelial neoplasms and melanomas</td><td>TNM</td><td>Metastatic/Advanced</td><td>10</td><td>10.6</td><td>39</td><td>7.8</td><td>0.47</td></tr><tr><td>Thyroid carcinomas (XI.b)</td><td>TNM</td><td>Metastatic/Advanced</td><td>3</td><td>8.8</td><td>16</td><td>6.6</td><td>0.91</td></tr><tr><td>Malignant melanomas (XI.d)</td><td>TNM</td><td>Metastatic/Advanced</td><td>2</td><td>22.2</td><td>5</td><td>9.4</td><td>0.58</td></tr><tr><td>Other</td><td>TNM</td><td>Metastatic/Advanced</td><td>5</td><td>9.8</td><td>18</td><td>8.7</td><td>1.00</td></tr></tbody></table>

cancer cases and to be able to assess the impact of the pandemic on the diagnosis of pediatric cancers in France. However, the Toronto staging is not necessary a good indicator of a more advanced stage of the disease linked to a delayed diagnosis. This is particularly the case for the acute leukemias with meningeal involvement, which rather reflects a different disease requiring appropriate treatment but not an advanced stage. For retinoblastoma, Toronto staging considers cases as metastatic as soon as there is CNS involvement, including suprasellar or pineal locations occurring in hereditary retinoblastoma. Another limitation of our study is that it could not provide estimates of the times to diagnosis and possible delays due to COVID, since the date of the first symptoms is not available in the RNCE. Actually these variables were recorded over several years and our quality controls showed us that we were not able to collect these data in a reliable and standardized way across the territory. Finally, having only included the year 2020 is also a limitation of our work, due to the time required to complete data collection in France, which is close to 3 years currently. Nevertheless, the impact in the management of childhood cancers might rather be observed the beginning of the pandemic with its strict lockdown insofar as pediatric oncology remained a priority in terms of management.

## 5. Conclusion

Our nationwide population-based study showed that the 2020 lockdowns, during the main period of COVID-19 pandemic, likely had no impact on diagnosis, stage at diagnosis and management of pediatric cancers in France. However, continued surveillance is needed to assess the potential consequence of COVID and lockdowns over longer periods, particularly the risk of ALL in children who were infants during the pandemic.

### CRediT authorship contribution statement

Virginie Gandemer: Writing – review & editing. Emmanuel Désandes: Writing – review & editing, Supervision, Methodology, Formal analysis, Conceptualization. Jacqueline Clavel: Writing – review & editing, Validation, Supervision, Project administration, Conceptualization. Maud Gédor: Writing – review & editing, Investigation, Formal analysis. Brigitte Lacour: Writing – review & editing. Writing – original draft, Supervision, Project administration, Funding acquisition, Conceptualization. Sandra Guissou: Writing – review & editing, Validation, Investigation. Laure Faure: Writing – review & editing, Validation, Investigation. Claire Poulalhon: Writing – review

<footnote>a 2 cases of advanced retinoblastomas are actually cases with genetic predisposition and sellar localization. These are not really metastases.</footnote>
<caption>**Table 4**</caption>

Median time to treatment after diagnosis (in days) for all cases and for those diagnosed at a metastatic or advanced stage during the COVID-19 period (2020) and the reference period (2016–2019).

<table><thead><tr><th rowspan="3"></th><th colspan="2">All stages</th><th rowspan="3">p value</th><th colspan="2">Metastatic/Advanced stage</th><th rowspan="3">p value</th></tr><tr><th colspan="2">Median [IQR] (days)</th><th colspan="2">Median [IQR] (days)</th></tr><tr><th>COVID-19</th><th>Reference</th><th>COVID-19</th><th>Reference</th></tr></thead><tbody><tr><td>TOTAL</td><td>2 [0;10]</td><td>2 [0;9]</td><td>0.42</td><td>4 [1;13]</td><td>5 [1;13]</td><td>0.43</td></tr><tr><td>Ia Acute lymphoblastic leukemias</td><td>1 [0;3]</td><td>2 [0;3]</td><td>0.37</td><td>1 [0;2]</td><td>1 [0;3]</td><td>0.64</td></tr><tr><td>II Lymphomas</td><td>10 [3;20]</td><td>10 [4;19]</td><td>0.95</td><td>13 [7;21]</td><td>12 [7;19]</td><td>0.31</td></tr><tr><td>Hodgkin lymphomas (II.a)</td><td>15 [10;24]</td><td>14 [9;24]</td><td></td><td>14 [10;22]</td><td>14 [9;20]</td><td></td></tr><tr><td>Burkitt lymphomas (II.c)</td><td>2 [0;5]</td><td>2 [1;5]</td><td></td><td>2 [1;3]</td><td>2 [1;4]</td><td></td></tr><tr><td>Other non-Hodgkin lymphomas (II.b)</td><td>7 [1;14]</td><td>6 [1;13]</td><td></td><td>5 [4;25]</td><td>6 [2;12]</td><td></td></tr><tr><td>III Central nervous system tumors</td><td>0 [0;0]</td><td>0 [0;0]</td><td>0.94</td><td>0 [0;0]</td><td>0 [0;1]</td><td>0.67</td></tr><tr><td>Ependymomas (III.a1). astrocytomas (III.b)</td><td>0 [0;21]</td><td>0 [0;26]</td><td></td><td>9 [0;23]</td><td>0 [0;9]</td><td></td></tr><tr><td>Embryonal tumors (III.c)</td><td>0 [0;0]</td><td>0 [0;0]</td><td></td><td>0 [0;0]</td><td>0 [0;1]</td><td></td></tr><tr><td>IV.a Neuroblastomas. ganglioneuroblastomas</td><td>3 [0;7]</td><td>3 [0;8]</td><td>0.55</td><td>4 [2;7]</td><td>4 [2;8]</td><td>0.89</td></tr><tr><td>V Retinoblastomas</td><td>2 [0;7]</td><td>1 [0;6]</td><td>0.56</td><td>12 [12;12]</td><td>-</td><td>-</td></tr><tr><td>VI.a1 Nephroblastoma</td><td>3 [2;6]</td><td>3 [2;5]</td><td>0.48</td><td>2 [2;5]</td><td>3 [2;5]</td><td>0.36</td></tr><tr><td>VII.a Hepatoblastoma</td><td>5 [3;7]</td><td>5 [2;8]</td><td>0.62</td><td>5 [4;5]</td><td>3 [2;6]</td><td>0.31</td></tr><tr><td>VIII. Malignant bone tumors</td><td>16 [9;22]</td><td>15 [9;23]</td><td>0.62</td><td>13 [7;18]</td><td>13 [8;19]</td><td>0.96</td></tr><tr><td>Osteosarcomas. (VIII.a)</td><td>15 [12;21]</td><td>16 [11;22]</td><td></td><td>15 [12;19]</td><td>14 [9;20]</td><td></td></tr><tr><td>Ewing tumor (VIII.c)</td><td>16 [7;26]</td><td>14 [8;22]</td><td></td><td>8 [6;17]</td><td>13 [7;18]</td><td></td></tr><tr><td>IX. Soft tissue and other extraosseous sarcomas</td><td>10 [1;16]</td><td>8 [0;16]</td><td>0.13</td><td>7 [5; 13]</td><td>10 [4;14]</td><td>0.48</td></tr><tr><td>Rhabdomyosarcomas (IX.a)</td><td>9 [2;14]</td><td>8 [0;13]</td><td></td><td>7 [5;11]</td><td>9 [3;12]</td><td></td></tr><tr><td>Non rhabdomyosarcomas (IX.b. c. d. e)</td><td>12 [0;23]</td><td>9 [0;23]</td><td></td><td>9 [3;16]</td><td>12 [4;21]</td><td></td></tr><tr><td>X Germ-cell tumors</td><td>0 [0;1]</td><td>0 [0;1]</td><td>0.79</td><td>0 [0;5]</td><td>0 [0;4]</td><td>0.96</td></tr><tr><td>Testicular tumors (X.c. d. e – C62)</td><td>0 [0;0]</td><td>0 [0;0]</td><td></td><td>0 [0;3]</td><td>0 [0;0]</td><td></td></tr><tr><td>Ovarian tumors (X.c. d. e – C56)</td><td>0 [0;0]</td><td>0 [0;0]</td><td></td><td>9 [9;9]</td><td>0 [0;12]</td><td></td></tr><tr><td>Extracranial extragonadal (X.b)</td><td>0 [0;8]</td><td>2 [0;7]</td><td></td><td>1 [1;1]</td><td>3 [1;7]</td><td></td></tr><tr><td>XI Epithelial neoplasms. melanomas</td><td>0 [0;0]</td><td>0 [0;0]</td><td>0.15</td><td>10 [0;26]</td><td>0 [0;16]</td><td>0.16</td></tr><tr><td>Thyroid carcinomas (XI.b)</td><td>0 [0;0]</td><td>0 [0;0]</td><td></td><td>0 [0;65]</td><td>0 [0;0]</td><td></td></tr><tr><td>Malignant melanomas (XI.d)</td><td>0 [0;4]</td><td>0 [0;0]</td><td></td><td>24 [19;28]</td><td>0 [0;2]</td><td></td></tr><tr><td>Other</td><td>0 [0;11]</td><td>0 [0;18]</td><td></td><td>5 [2;23]</td><td>16 [3;26]</td><td></td></tr></tbody></table>

& editing. **François Doz:** Writing – review & editing, Validation. **Arnaud Petit:** Writing – review & editing. **Jérémie Rouger:** Writing – review & editing.

## Declaration

The author Professor Doz is an Editor of EJC Paediatric Oncology and was not involved in the editorial review or the decision to publish this article.

## Regulatory statement

This study uses data from the RNCE, which has all the required authorizations (CNIL DR-2013-198.) Patient information is available on the RNCE transparency portal (https://rnce.inserm.fr/recherches/poretail-transparence/).

## Funding

This work was supported by the Institut National du Cancer, France (No. 2022-014).

## Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

## Acknowledgments

The authors are grateful to the numerous investigators who have meticulously contributed to the active search for information in clinical departments. The authors are also grateful to the French services of pediatric hemato-oncology and to the Société Française de lutte contre les Cancers de l'Enfant et de l'Adolescent (SFCE) for their help in access

to medical records and data collection. The authors would also like to express their gratitude to the heads of the Medical Information Departments of all the University Hospitals and Comprehensive Cancer Centers and the Regional Departments of the Medical Control Service of Health Insurance.

## Appendix A. Supporting information

Supplementary data associated with this article can be found in the online version at doi:10.1016/j.ejcped.2025.100240.

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