Management and outcomes of adolescent and young adult sarcoma patients: results from the French nationwide database NETSARC.

BACKGROUND: The initial management of patients with sarcoma is a critical issue. We used the nationwide French National Cancer Institute-funded prospective sarcoma database NETSARC to report the management and oncologic outcomes in adolescents and young adults (AYAs) patients with sarcoma at the national level. PATIENTS AND METHODS: NETSARC database gathers regularly monitored and updated data from patients with sarcoma. NETSARC was queried for patients (15-30 years) with sarcoma diagnosed from 2010 to 2017 for whom tumor resection had been performed. We reported management, locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) in AYA treated in French reference sarcoma centers (RSC) and outside RSC (non-RSC) and conducted multivariable survival analyses adjusted for classical prognostic factors. RESULTS: Among 3,227 patients aged 15-30 years with sarcoma diagnosed between 2010 and 2017, the study included 2,227 patients with surgery data available, among whom 1,290 AYAs had been operated in RSC, and 937 AYAs in non-RSC. Significant differences in compliance to guidelines were observed including pre-treatment biopsy (RSC: 85.9%; non-RSC 48.1%), pre-treatment imaging (RSC: 86.8%; non-RSC: 56.5%) and R0 margins (RSC 57.6%; non-RSC: 20.2%) (p < 0.001). 3y-OS rates were 81.1% (95%CI 78.3-83.6) in AYA in RSC and 82.7% (95%CI 79.4-85.5) in AYA in non-RSC, respectively. Whereas no significant differences in OS was observed in AYAs treated in RSC and in non-RSC, LRFS and PFS were improved in AYAs treated in RSC compared to AYAs treated in non-RSC (Hazard Ratios (HR): 0.58 and 0.83, respectively). CONCLUSIONS: This study highlights the importance for AYA patients with sarcoma to be managed in national sarcoma reference centers involving multidisciplinary medical teams with paediatric and adult oncologists.

PAX-FOXO1 fusion status in children and adolescents with alveolar rhabdomyosarcoma: Impact on clinical, pathological, and survival features.

BACKGROUND: Alveolar rhabdomyosarcoma (ARMS) is an aggressive pediatric cancer and cases with fusion PAX3-FOXO1 and PAX7-FOXO1 seem to have a poor prognosis. The aim is to evaluate whether PAX-FOXO1 alterations influence clinical outcome in childhood and adolescence population with ARMS. PROCEDURE: A population-based study was conducted between 2011 and 2016 in patients less than 17 years with a diagnosis of ARMS. Overall survival (OS) depending on fusion status with clinical factors was analyzed. RESULTS: Out of 111 ARMS patients recorded in the French National Childhood Cancer Registry during the 2011-2016 period, 61% expressed PAX3-FOXO1, 15% expressed PAX7-FOXO1, 13% were FOXO1 fusion-positive without PAX specification, and 7% were PAX-FOXO1 negative (n = 4 missing data). Compared to patients with PAX7-FOXO1 positive ARMS, those with PAX3-FOXO1 positive tumor were significantly older (10-17 years: 57.4% vs. 29.4%), and had more often a metastatic disease (54.4% vs. 23.5%). Poorer 5-year OS for patients with PAX3-FOXO1 and PAX not specified FOXO1-positive tumor were observed (44.0% [32.0-55.4] and 35.7% [13.1-59.4], respectively). After adjustment for stage at diagnosis, patients with positive tumor for PAX3-FOXO1 were 3.6-fold more likely to die than those with positive tumor for PAX7-FOXO1. CONCLUSION: At the population level, PAX3-FOXO1 was associated with a significant higher risk of death compared to PAX7-FOXO1-positive and PAX-FOXO1-negative tumors, and could explain poorer 5-year OS observed in adolescence population diagnosed with ARMS. A continuous risk score derived from the combination of clinical parameters with PAX3-FOXO1 fusion status represents a robust approach to improving current risk-adapted therapy for ARMS.

Overall and net survival of patients with sarcoma between 2005 and 2010: Results from the French Network of Cancer Registries (FRANCIM).

BACKGROUND: Sarcomas are rare, heterogeneous, ubiquitously localized malignancies with many histologic subtypes and genomic patterns. The survival of patients with sarcoma has rarely been described based on this heterogeneity; therefore, the authors' objective was to estimate survival outcomes in patients who had sarcomas using the 2020 version of the World Health Organization classification of soft tissue and bone tumors. METHODS: Patients older than 15 years who had incident sarcoma diagnosed between 2005 and 2010 were extracted from 14 French population-based cancer registries covering 18% of the French metropolitan population. Vital status for each patient was actively followed up to June 30, 2013. Net survival (NS) was estimated using the unbiased Pohar-Perme method. RESULTS: Overall, 4202 patients were included. NS declined with increasing age at diagnosis. According to topographic groups, large 5-year NS disparities were observed, ranging from 47% among women with gynecologic sarcomas to 89% among patients with skin sarcomas. Patients with soft tissue, bone, and gastrointestinal sarcomas had 5-year NS rates of 53%, 61%, and 70%, respectively. Similar heterogeneity was observed according to histologic subtypes, with 5-year NS ranging from 19% for patients with angiosarcomas to 96% for patients with dermatofibrosarcomas. Patients with sarcoma who displayed missense mutations had a better 5-year NS (74%); those with MDM2-amplified sarcomas had the worst NS (45%). CONCLUSIONS: NS rates in patients with sarcoma are presented here for the first time based on the 2020 World Health Organization classification applied to population-based registry data. Large prognostic heterogeneity was observed based on age, topographic and histologic groups, and genomic alteration profiles, constituting a benchmark for future studies and clinical trials.

Acute skin toxicity of conventional fractionated versus hypofractionated radiotherapy in breast cancer patients receiving regional node irradiation: the real-life prospective multicenter HYPOBREAST cohort.

BACKGROUND: Large-scale trials have shown that hypofractionated adjuvant breast radiotherapy was as effective in terms of survival and local control as conventional fractionated radiotherapy, and acute toxicity was reduced with hypofractionated radiotherapy. However, there is a lack of data about the toxicity of breast with regional nodal irradiation (RNI). The aim of this study was to assess the effect of fractionation on radiation-related acute skin toxicity in patients receiving RNI in addition to whole-breast or chest wall irradiation, using real-life data. METHODS: We conducted a prospective, multicenter cohort study with systematic computerized data collection integrated into Mosaiq®. Three comprehensive cancer centers used a standardized form to prospectively collect patient characteristics, treatment characteristics and toxicity. RESULTS: Between November 2016 and January 2022, 1727 patients were assessed; 1419 (82.2%) and 308 (17.8%) patients respectively received conventional fractionated and hypofractionated radiation therapy. Overall, the incidence of acute grade 2 or higher dermatitis was 28.4% (490 patients). Incidence was lower with hypofractionated than with conventional fractioned radiation therapy (odds ratio (OR) 0.34 [0.29;0.41]). Two prognostic factors were found to increase the risk of acute dermatitis, namely 3D (vs IMRT) and breast irradiation (vs chest wall). CONCLUSION: Using real-life data from unselected patients with regional nodal irradiation, our findings confirm the decreased risk of dermatitis previously reported with hypofractionated radiation therapy in clinical trials. Expansion of systematic data collection systems to include additional centers as well as dosimetric data is warranted to further evaluate the short- and long-term effects of fractionation in real life.

Incidence and time trends of sarcoma (2000-2013): results from the French network of cancer registries (FRANCIM).

BACKGROUND: The exhaustive collection of new sarcoma cases and their second histologic review offer a unique opportunity to study their incidence and time trends in France according to the major subtypes. METHODS: Data were collected from population-based cancer registries covering 22% of the French population. Crude and world age-standardized incidence rates (ASR) were estimated according to anatomic, histological and genetic groups, age and sex over the 2010-2013 period. RESULTS: Time trends in incidence were calculated by the annual percent change over the 2000-2013 period. During the most recent period (2010-2013), 3942 patients with sarcoma were included. The ASR of soft-tissue and bone sarcomas, and gastro-intestinal stromal tumors (GIST) were 2.1, 1.0 and 0.6, respectively. For the four most frequent histological subtypes (unclassified, leiomyosarcoma, GIST and liposarcoma), the ASR ranged from 0.4 to 0.7. ASRs were 1.9 for complex genomic and 1.3 for recurrent translocation sarcomas. The time-trend analysis showed a significant increase of sarcoma incidence rate between 2000 and 2005, which stabilized thereafter. Incidence rates increased for four histological subtypes (GIST, chondrosarcoma, myxofibrosarcoma, solitary fibrous tumors) and decreased for three (leiomyosarcomas, Kaposi sarcoma and fibrosarcoma). CONCLUSION: To our knowledge, this study is the first to investigate sarcoma incidence based on a systematic pathological review of these cancers and on the updated sarcoma classifications. Due to the paucity of literature on sarcomas, future studies using data from population-based cancer registries should consider a standardized inclusion criterion presented in our study to better describe and compare data between countries.

Adolescent and young adult oncology patients in France: Heterogeneity in pathways of care.

BACKGROUND: In order to evaluate at the population level the impact of the actions developed in France since 2004 to organize the care of adolescents and young adults (AYAs) with cancer, we conducted the present study to provide an unbiased view of the pathway of care of these patients. METHODS: Using a population-based registry, we conducted a review of all cases of cancer diagnosed during 2012 and 2013 in 15- to 24-year-old patients living in nineteen French administrative areas. RESULTS: The median times for diagnosis and treatment of the 993 included AYAs were 9 weeks (3-22) and 1 day (0-20), respectively. Delays in diagnosis were significantly longer in young adults than in adolescents, especially for soft-tissue sarcomas (48.7 weeks vs. 15.4 weeks, P = 0.04) and bone tumors (21.4 weeks vs. 10.1 weeks, P = 0.04). The first physicians seen by patients were mostly general practitioners (67.4%). Most patients (77.5%) were treated in adult units. Management decisions were taken within the context of a multidisciplinary team (MDT) in 85.3% of cases. MDT meetings that involved both pediatric and adult oncologists were uncommon (15.7% of patients). Twenty-six percent of patients were included in randomized or nonrandomized clinical studies. The proportion of inclusion was significantly higher in adolescents (39.5%) than in young adults (16.8%). CONCLUSION: In France, pathways of care for AYAs are heterogeneous. It is necessary to organize a national network of expert centers with adequate medical skills and specific psychosocial support and facilities to provide the best possible care for these patients.

Survival of adolescents with cancer treated at pediatric versus adult oncology treatment centers in France.

BACKGROUND: In France, although children aged less than 15 years with cancer are usually referred to pediatric oncology centers, adolescents may be treated at pediatric or adult oncology centers. The objective was to compare survival according to their site of treatment. PROCEDURE: Using population-based registration, 15- to 19-year-old patients diagnosed with cancer in 2006 or 2007 and living in six French regions (accounting for 41% of the French population) were included. RESULTS: Of the 594 patients included, 33% of the French adolescents were treated at a pediatric oncology center. Compared with those treated at a pediatric center, adolescents treated at an adult center were older, were more likely to have carcinoma and germ-cell tumor, had a longer time to diagnosis, and were less likely to be enrolled in a clinical trial. In addition, the decisions for their management were less likely to be taken in the context of multidisciplinary team meetings. In multivariate analysis, adolescent patients treated at a pediatric center did not have significantly different overall survival (OS) compared with those treated at an adult center (5-year OS: 84.1% [95% confidence interval: 78.6-90.0] versus 87.7% [95% confidence interval: 84.2-91.3]; P = 0.25). CONCLUSIONS: The outcomes of French adolescents with cancer have begun to improve, with 81.2% survival in 2006-2007, with no difference between the types of treatment center. However, for this unique group of diseases, survival is not the unique endpoint. In order to ensure good quality of life after cancer, management of those patients requires specific approaches, designed to reduce the late effects of cancer treatment and improve supportive care.

Survival of European adolescents and young adults diagnosed with cancer in 2000-07: population-based data from EUROCARE-5.

BACKGROUND: Data from EUROCARE have consistently shown lower survival for adolescents and young adults (AYAs; aged 15-24 years) than for children (0-14 years) for most cancers that affect both groups, and modest survival improvements up to 2000-02. AYAs have longer survival than that of adults for most cancers. We used the latest definition of AYAs (aged 15-39 years) and provided estimates of 5-year relative survival for European AYAs with cancer diagnosed in 2000-07, compared with children and adults (40-69 years) with cancer, and assessed survival improvements over time. METHODS: We analysed data from population-based cancer registries of 27 European countries participating in EUROCARE-5. We used the so-called complete method to estimate 5-year, population-weighted relative survival for 19 cancers affecting AYAs and children, and for 27 cancers affecting AYAs and adults. We assessed relative-survival differences between children versus AYAs, and between AYAs versus adults, using the Z test. We used the period approach to estimate 5-year relative survival over time for children and AYAs, and used a generalised linear model to model survival time trends (1999-2007) and to assess the significance of changes over time. FINDINGS: We analysed 56 505 cancer diagnoses in children, 312 483 in AYAs, and 3 567 383 in adults. For all cancers combined, survival improved over time for AYAs (from 79% [95% CI 78·1-80·5] in 1999-2002 to 82% [81·1-83·3] in 2005-07; p<0·0001) and children (from 76% [74·7-77·1] to 79% [77·2-79·4]; p<0·0001). Survival improved significantly in children and AYAs for acute lymphoid leukaemia (p<0·0001) and non-Hodgkin lymphoma (p<0·0001 in AYAs and p=0·023 in children). Survival improved significantly in AYAs only for CNS tumours (p=0·0046), astrocytomas (p=0·040), and malignant melanomas (p<0·0001). Survival remained significantly worse in AYAs than in children for eight important cancers: acute lymphoid leukaemias, acute myeloid leukaemias, Hodgkin's lymphomas, non-Hodgkin lymphomas, astrocytomas, Ewing's sarcomas, and rhabdomyosarcomas (p<0·0001 in all cases), and osteosarcomas (p=0·011). INTERPRETATION: Notwithstanding the encouraging results for some cancers, and overall, we showed poorer survival in AYAs than in children for the eight important cancers. Recent European initiatives to improve outcomes in AYAs might reduce the survival gap between children and AYAs, but this reduction can only be verified by future population-based studies. FUNDING: Italian Ministry of Health, European Commission.

Neonatal Solid Tumors: Incidence and Survival in France.

BACKGROUND: Solid tumors are uncommon in the neonatal period but represent an important cause of mortality and morbidity. PROCEDURE: Using the French National Registry of Childhood Solid Tumors database, all children, from birth to 28 days of age inclusive, with a primary malignant solid tumor diagnosed between 2000 and 2009 in mainland France were identified. Tumors were classified according to the third version of the International Classification of Childhood Cancer. RESULTS: Of total 285 solid tumors over 10 years, the most common cancer was neuroblastoma (47%), followed by germ cell tumors (29%), central nervous system tumors (10%), and soft tissue sarcomas (8%). The annual incidence was 36.6 per million live births. No statistically significant change in time trends of incidence was observed during 2000-2009. Routine ultrasonography during pregnancy established the diagnosis in 52% of cases. Thirteen neonates (4.5%) had congenital abnormalities associated with their tumors. For all solid tumors combined, overall survival was 84.2% (95% CI, 79.4-87.9) at 1 year and 83.8% (95% CI, 79.0-87.6) at 5 years. More favorable prognosis was significantly associated with neonates treated by surgery (65% of cases) compared to those without tumor excision. However, perioperative and postoperative mortality was 8%. CONCLUSIONS: Because of their relative rarity, there is a paucity of objective information on the epidemiology, optimal treatment, and long-term outcome of neonatal solid tumors. But to obtain a clearer picture of the epidemiology of neonatal tumors, it is essential to have some recommendations on the methodological approach used to study them.

[Development of an artificial intelligence system to improve cancer clinical trial eligibility screening]. / Développement d'une solution d'intelligence artificielle pour améliorer le screening en recherche clinique.

INTRODUCTION: The recruitment step of all clinical trials is time consuming, harsh and generate extra costs. Artificial intelligence tools could improve recruitment in order to shorten inclusion phase. The objective was to assess the performance of an artificial intelligence driven tool (text mining, machine learning, classification…) for the screening and detection of patients, potentially eligible for recruitment in one of the clinical trials open at the "Institut de Cancérologie de Lorraine". METHODS: Computerized clinical data during the first medical consultation among patients managed in an anticancer center over the 2019-2023 period were used to study the performances of an artificial intelligence tool (SAS® Viya). Recall, precision and F1-score were used to determine the artificial intelligence algorithm effectiveness. Time saved on screening was determined by the difference between the time taken using the artificial intelligence-assisted method and that taken using the standard method in clinical trial participant screening. RESULTS: Out of 9876 patients included in the study, the artificial intelligence algorithm obtained the following scores: precision of 96 %, recall of 94 % and a 0.95 F1-score to detect patients with breast cancer (n=2039) and potentially eligible for inclusion in a clinical trial. The screening of 258 potentially eligible patient's files took 20s per file vs. 5min and 6s with standard method. DISCUSSION: This study suggests that artificial intelligence could yield sizable improvements over standard practices in several aspects of the patient screening process, as well as in approaches to feasibility, site selection, and trial selection.

Consore: A Powerful Federated Data Mining Tool Driving a French Research Network to Accelerate Cancer Research.

BACKGROUND: Real-world data (RWD) related to the health status and care of cancer patients reflect the ongoing medical practice, and their analysis yields essential real-world evidence. Advanced information technologies are vital for their collection, qualification, and reuse in research projects. METHODS: UNICANCER, the French federation of comprehensive cancer centres, has innovated a unique research network: Consore. This potent federated tool enables the analysis of data from millions of cancer patients across eleven French hospitals. RESULTS: Currently operational within eleven French cancer centres, Consore employs natural language processing to structure the therapeutic management data of approximately 1.3 million cancer patients. These data originate from their electronic medical records, encompassing about 65 million medical records. Thanks to the structured data, which are harmonized within a common data model, and its federated search tool, Consore can create patient cohorts based on patient or tumor characteristics, and treatment modalities. This ability to derive larger cohorts is particularly attractive when studying rare cancers. CONCLUSIONS: Consore serves as a tremendous data mining instrument that propels French cancer centres into the big data era. With its federated technical architecture and unique shared data model, Consore facilitates compliance with regulations and acceleration of cancer research projects.

Cancer incidence and survival in adolescents and young adults in France, 2000-2008.

This study aimed to describe cancer incidence (2000-2008) and survival (2000-2004) in France in adolescents and young adults (AYA). All cases of cancer diagnosed in 15-24 years, recorded by all French population-based registries (14% of the French population), over the 2000-2008 period, were included. Incidence change over time was described with the conventional annual percentage change (cAPC). The survival of cases diagnosed (2000-2004) was estimated using Kaplan-Meier method. A total of 1022 in adolescents and 1396 in young adults were diagnosed. Overall incidence rates were 219.4/10(6) in 15-19 year olds and 293.1/10(6) in 20-24 year olds. The most frequently diagnosed cancers in male AYA were malignant gonadal germ-cell tumors and Hodgkin's disease, and were melanoma, thyroid carcinoma, and Hodgkin's disease in females. The age-standardized rates appeared stable over time in AYA, with a cAPC of +2.0% (P = 0.68). The 5-year overall survival for all cancers was different between genders and age groups, with 78.8% (95%CI: 75.6-82.0) for males and 85.2% (95%CI: 82.2-88.1) for females (P = 0.01), and 78.5% (95%CI: 75.0-82.1) in 15-19 year olds and 84.3% (95% CI: 81.6-87.0) in 20-24 year olds (P = 0.02). Noteworthy, the frequency and the distribution of tumor types in AYA are unique and different from the observed at any other age group. Survival in French AYA has improved over time. Epidemiological data might reflect major trends in the risk factors and preventive interventions. Thus, further research into etiology of cancers affecting AYA should become key priorities for cancer control among AYA.

Treatment of vulvar intraepithelial neoplasia with CO(2) laser vaporization and excision surgery.

OBJECTIVE: To evaluate the recurrence rate after a single treatment of vulvar intraepithelial neoplasia (VIN) with CO(2) laser vaporization. MATERIALS AND METHODS: Fifty women with usual-type or differentiated VIN (grades 2 and 3) treated with CO(2) laser vaporization or surgery excision (cold knife or CO(2) laser) were retrospectively evaluated. RESULTS: Of the 50 patients, 41 (82.0%) had usual-type VIN and 9 (18.0%) had differentiated VIN. Moreover, 24 (48.0%) were treated with surgery excision and 26 (52.0%) underwent CO(2) laser vaporization. Laser-treated patients were significantly younger (p < .01) with more multifocal (p < .05) and multicentric lesions (p < .01) than in the surgery group. Recurrence-free survival (RFS) rates at 1 year were 91.0% for the surgery and 65.2% for the laser vaporization groups (p < .01). At 5 years, RFS rates were unchanged for the surgery group and dropped to 51.3% (p < .01) for the laser group. On the univariate analysis, current smoker (p = .03), multicentric VIN (p = .02), and laser vaporization treatment (p < .01) had a statistically significant impact on RFS. One patient progressed to invasive cancer (2%). CONCLUSIONS: The recurrence rate after CO(2) laser vaporization requires regular, close, and extended monitoring.

Seasonality of main childhood embryonal tumours and rhabdomyosarcoma, France, 2000-2015.

Few studies have investigated the seasonal patterns of embryonal tumours. Based on data from the French National Registry of Childhood Cancers, the present study aimed to investigate seasonal variations in embryonal tumour incidence rates by month of birth and by month of diagnosis. The study included 6635 primary embryonal tumour cases diagnosed before the age of 15 years over the period 2000-2015 in mainland France. Assuming monthly variations in incidence rates were homogeneous over 2000-2015, we used a Poisson regression model to test for overall heterogeneity in standardised incidence ratios (SIRs) by month of birth or diagnosis. The seasonal scan statistic method was used to detect monthly excesses or deficits of embryonal tumour cases over the whole study period. The annual reproducibility of the observed monthly variations was formally tested. An overall heterogeneity in incidence rates by month of birth was observed for rhabdomyosarcoma in boys only. Based on the month of diagnosis, a seasonality was evidenced for unilateral retinoblastoma, with a lower incidence rate in the summer (SIRJul-Aug  = 0.68, 95% CI = 0.52-0.87), whilst the incidence rate of rhabdomyosarcoma tended to be lower in August (SIRAug  = 0.68, 95% CI = 0.52-0.89). No seasonality was detected for the other embryonal tumour groups by month of birth or month of diagnosis. This study is one of the largest to have investigated the seasonality of childhood embryonal tumours. The study showed a seasonal variation in the incidence rates by month of diagnosis for unilateral retinoblastoma and rhabdomyosarcoma. Our findings are likely to reflect a delay in consultation during the summer months. However, the role of seasonally varying environmental exposures cannot be ruled out.

Impact of age on survival according to molecular tumor findings in children and adolescents with soft-tissue and bone sarcoma: The BIOSCA project.

BACKGROUND: Adolescents (15-19 years) with sarcoma are known to have significantly worse survival than children (0-14 years). One possible reason may be that the adolescent sarcomas exhibit specific biological characteristics resulting in differences in clinical presentation and treatment resistance behaviors. The BIOSCA project aims to further explore these age-related differences in survival accounting for molecular tumor characteristic in children and adolescents with sarcoma. METHODS: A retrospective national population-based observational study with documented somatic genetic analyses was conducted between 2011 and 2016 of all patients aged from 0 to 17 years with a diagnosis of sarcoma using the National Registry of Childhood Cancers Database. RESULTS: A total of 1637 children (0-9years: 40%), preadolescents (10-14years: 35%) and adolescents (15-17 years: 25%) with a diagnosis of bone (N = 845) or soft-tissue (N = 792) sarcoma were included. Adolescents had significantly worse outcome for undifferentiated small round cell sarcoma (USRCS), alveolar rhabdomyosarcoma (ARMS), and epithelioid sarcoma. Five-year overall survivals were worse among CIC-rearranged USRCS cases (47% [95%CI:21-69]) as compared to other USRCS, and PAX3::FOXO1 ARMS patients (44% [95%CI:32-55]) as compared to other ARMS. Adjusting for stage and genomic-profiling status, adolescents with USRCS were 1.6-fold more likely to die than children (P = 0.05), while the difference in survival between age of ARMS patients was weaken. Indeed, the prevalence of PAX3::FOXO1 increased significantly with age. CONCLUSION: Age was an independent prognostic factor of outcome only in patients with USRCS, while the association between age and survival of patients with ARMS could be partly explained by differences in prevalence of PAX3::FOXO1.

Pathways of care for adolescent patients with cancer in France from 2006 to 2007.

BACKGROUND: In France, as in other countries, there is a need for a population-based view of access to care and modalities of treatment for adolescents with cancer. PROCEDURE: Using a population-based registration, we report pathways of care for 15-19-year-old patients, diagnosed with cancer in 2006 and 2007, living in six French regions, accounting for 41% of the French population. RESULTS: The median times (inter-quartile range) for diagnosis and treatment of the 594 included adolescents were 8 weeks (3-17) and 3 days (0-16), respectively. First physicians met by the patients were mostly general practitioners (59%). Seventeen percent of patients were firstly seen on emergency wards. Most of the patients (82%) were treated in an adult environment. Management decisions were taken within the context of a multi-disciplinary team (MDT) in 54% of cases. Twenty-seven percent of patients were included in randomized or non-randomized clinical studies: percentage depended on the tumor type and on the number of on-going trials at the study period. Fifteen percent of patients were included in pediatric studies, 7% in adult studies, and 5% in studies including both adults and children. CONCLUSIONS: The pathways of care for French adolescent patients with cancer are heterogeneous. Our results reveal differences in MDT meetings according to tumor types and a lack of effective collaboration between pediatric and adult wards. Efforts must be made to develop cancer networks to ensure that adolescents receive the optimal care in a suitable environment.

Echocardiography as a guide for patent ductus arteriosus ibuprofen treatment and efficacy prediction.

OBJECTIVE: To evaluate echocardiography criteria in predicting the response to ibuprofen treatment. DESIGN: A prospective cohort study of preterm infants untreated or treated with ibuprofen for patent ductus arteriosus. SETTING: Three academic neonatal intensive care units. PATIENTS: Two hundred fifty-two preterm infants of 27-31 wks gestation. INTERVENTIONS: Ibuprofen treatment within the first 5 days of life was indicated when at least two out of four conventional echocardiography criteria were observed: ductal diameter >2 mm, left-right ductal shunt maximum velocity <2 m/sec, mean flow velocity in left pulmonary artery >0.4 m/sec, and end-diastolic flow velocity in left pulmonary artery >0.2 m/sec. MEASUREMENTS AND MAIN RESULTS: Of the infants analyzed, 135 had a closed ductus at an average age of 1.9 ± 0.9 days, and 43 had an open ductus but <2 predefined criteria. Seventy-four infants (29%) received ibuprofen on day 2.2 ± 1.1. Sixteen infants failed ibuprofen and nine had to undergo surgical ligation. The left-right ductal shunt maximum velocity criterion had the best negative predictive value for treatment response, while the ductal diameter criterion had the best positive predictive value. CONCLUSIONS: Echocardiography may be a useful tool to help patent ductus arteriosus management. A combined use of ductal diameter and left-right ductal shunt maximum velocity criteria allows a more accurate prediction of the response of infants with patent ductus arteriosus to ibuprofen treatment.

Thyroid cancers in children and adolescents in France: Incidence, survival and clinical management over the 2000-2018 period.

INTRODUCTION: Thyroid cancer is the first cause of endocrine malignancy among children. Over the past decades, an increase in the incidence rates (IR) has been observed around the world. Our study aimed to describe epidemiology, therapeutic management and survival rates of children and adolescents with thyroid cancer in France. METHODS: A population-based study was conducted between 2000 and 2018 in children and adolescents less than 17 years with a diagnostic of thyroid cancer. RESULTS: A total of 774 thyroid cancers were included: 579 papillary (PTC), 83 follicular (FTC), and 111 medullary carcinomas (MTC). PTC are more frequent in females and in adolescents whereas MTC mainly concerned children, mostly with a familial predisposition. Almost all patients underwent thyroidectomy, completed for most patients with PTC and FTC by radioiodine therapy. Cervical dissection was performed more frequently in patients having PTC and MTC compared to those with FTC. Between 2000 and 2018, thyroid cancers IR in children fluctuated between 1.3 and 3.2 per million, without any significant trend. The median follow-up time was 11.3 years in children, and 5.7 years in adolescents. The 5year-OS was greater than 98.5%. CONCLUSIONS: Population-based studies are crucial for better understanding and delineation of best management of rare diseases as thyroid cancers in pediatric and adolescent population. Considering the very favorable survival, a stratification should be proposed between cases at low risk and cases at high risk of relapse, in order to consider a strategy of therapeutic de-escalation in the most favorable cases.

Factors associated with 5- and 10-year survival among a recent cohort of childhood cancer survivors (France, 2000-2015).

BACKGROUND: Childhood cancer survival currently exceeds 80 % five years after diagnosis in high-income countries. In this study, we aimed to describe long-term trends and to investigate socioeconomic and spatial disparities in childhood cancer survival. METHODS: The study included 28,073 cases recorded in the French National Registry of Childhood Cancers from 2000 to 2015. Contextual census data (deprivation indices, population density, spatial accessibility to general practitioners) were allocated to each case based on the residence at diagnosis. Overall survival (OS) and conditional 10-year OS for 5-year survivors were estimated for all cancers combined and by diagnostic group and subgroup. Comparisons were conducted by sex, age at diagnosis, period of diagnosis, and contextual indicators. Hazard ratios for death were estimated using Cox models. RESULTS: All cancers combined, the OS reached 82.8 % [95 % CI: 82.4-83.3] at 5 years and 80.8 % [95 % CI: 80.3-81.3] at 10 years. Conditional 10-year OS of 5-year survivors reached 97.5 % [95 % CI: 97.3-97.7] and was higher than 95 % for all subgroups except osteosarcomas and most subgroups of the central nervous system. In addition to disparities by sex, age at diagnosis, and period of diagnosis, we observed a slight decrease in survival for cases living in the most deprived areas at diagnosis, not consistent across diagnostic groups. CONCLUSION: Our results confirm the high 5-year survival for childhood cancer and show an excellent 10-year conditional survival of 5-year survivors. Additional individual data are needed to clarify the factors underlying the slight decrease in childhood cancer survival observed in the most deprived areas.

Childhood head and neck cancer in France: Incidence, survival and trends from 2000 to 2015.

INTRODUCTION: Childhood head and neck cancers (HNC) are rare and represent a complex group of anatomical topographies. The aim of this study is to describe the distribution, the incidence and survival rates of children with malignant HNC in France. METHODS: A population-based study was conducted between 2000 and 2015 in children less than 15 years with a diagnosis of HNC using the French National Registry of Childhood Cancers database (RNCE). Age-standardized incidence rates (ASR) and survival analysis were performed. RESULTS: The 1623 included HNC represented 5.6% of all cancers included in the RNCE. The thyroid was the leading tumor site category (26.6%), followed by head and neck soft tissue location (15.4%) and the nasopharynx (10.8%). The most common cancers were thyroid gland carcinomas (26.1%), rhabdomyosarcomas (23.9%) and Burkitt Lymphomas (8.6%). Nasopharynx cancers and soft-tissue sarcomas were statistically more frequent in boys, while thyroid carcinomas were significantly more frequent in girls. The annual ASR was 8.6 new cancer cases per million children. For all HNC combined, the 5-year overall survival (OS) was 87.7% [95%CI: 85.9-89.2]. There was no statistically significant variation in 5-year OS between 2000-2007 and 2008-2015. CONCLUSIONS: Epidemiological data on HNC distribution, incidence and survival contributes to better understand these tumors by quantifying their impact on the French population and assessing their burden. Regarding the exclusion of topographies and some histological origins performed by some authors, this report proposes new recommendations to study HNC in a pediatric population.