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In clinical research and care, information notices are too often reduced to complicated and hard-to-understand mandatory documents. However, every person has the right to transparent and truthful information. These considerations prompted the creation of a multidisciplinary working group in the fall of 2020, headed by the College des relecteurs de l'Inserm. This group associates the different actors involved in the development, evaluation and use of information notices: Health and research professionals, representatives of patient associations or research foundations, ethicists, jurists, scientific educators and communicators. This group has created a set of texts, pictograms and illustrations, adapted to the people concerned and accepted by all actors. These contents will be easily used by professionals through the app Noticeinfobox©. A pilot phase was conducted to generate the notices of the France Genomic Medicine Plan 2025, used for genetic examinations. This app Noticeinfobox© is a response to society's request to be an actor in its own healthcare and to adopt more ethical and responsible research.

Title: Vers un consentement plus éclairé - Rendre l'information accessible. Abstract: Trop souvent, les notices d'information proposées dans le cadre de recherches cliniques se réduisent à des documents réglementaires difficilement compréhensibles. Pourtant, les personnes concernées doivent avoir accès à une information transparente et loyale. Ces considérations ont motivé la création d'un groupe de travail pluridisciplinaire, piloté par le Collège des relecteurs de l'Inserm, associant les acteurs impliqués dans l'élaboration, l'évaluation et l'utilisation de ces notices d'information. Un ensemble de textes, pictogrammes et illustrations, adaptés aux personnes concernées, validés et facilement utilisables via une application a été créé. Une phase pilote, dans le cadre du plan France médecine génomique 2025, a permis de générer des notices simplifiées pour les examens génétiques. Dans cet article, nous présentons le travail réalisé par le groupe de travail « Notices d'information ¼ afin de répondre à la demande sociétale d'être acteur de son parcours de soin et de contribuer à une recherche plus éthique et responsable.

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The aim of this study was to determine the therapy-related risk factors for the occurrence of leukaemia after childhood solid cancer. Among 4204 3-year survivors of a childhood cancer treated in eight French and British centres before 1986, 11 patients developed leukaemia as a second malignant neoplasm (SMN). Compared with the leukaemia incidence in the general French and British populations, the standardised incidence ratio (SIR) of leukaemia was 7.8 (95% CI 4.0-13.4). It decreased from 20.3 (95% CI 8.3-41.2) during the first years of follow-up, to 2.2 (95% CI 0.1-9.7) between 10 and 20 years, but rose again to 14.8 (95% CI 3.7-38.3) 20 or more years after the first cancer. Radiotherapy appeared to increase the risk of leukaemia at moderate weighted doses to active bone marrow; the relative risk (RR) was 4.2 (95% CI 0.8-20.7) for doses ranging from 3 to 6.6 Gy. A greater RR was observed for epipodophyllotoxins and for vinca alkaloids. No specific type of first malignant neoplasm (FMN) was found to lead to a higher risk of secondary leukaemia. Epipodophyllotoxins and vinca alkaloids at high doses and moderate weighted radiation doses to active bone marrow may contribute independently to an increased risk of leukaemia for patients treated for childhood cancer. Our results suggest that the long-term risk of secondary leukaemia could be higher than previously reported.

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BACKGROUND: Although intra-retinal tumor has long been staged presurgically according to the Reese-Ellsworth (R-E) system, retinoblastoma differs from other pediatric neoplasms in never having had a widely accepted classification system that encompasses the entire spectrum of the disease. Comparisons among studies that consider disease extension, risk factors for extra-ocular relapse, and response to therapy require a universally accepted staging system for extra-ocular disease. PROCEDURE: A committee of retinoblastoma experts from large centers worldwide has developed a consensus classification that can encompass all retinoblastoma cases and is presented herein. Patients are classified according to extent of disease and the presence of overt extra-ocular extension. In addition, a proposal for substaging considering histopathological features of enucleated specimens is presented to further discriminate between Stage I and II patients. RESULTS: The following is a summary of the classification system developed-Stage 0: Patients treated conservatively (subject to presurgical ophthalmologic classifications); Stage I: Eye enucleated, completely resected histologically; Stage II: Eye enucleated, microscopic residual tumor; Stage III: Regional extension [(a) overt orbital disease, (b) preauricular or cervical lymph node extension]; Stage IV: Metastatic disease [(a) hematogenous metastasis: (1) single lesion, (2) multiple lesions; (b) CNS extension: (1) prechiasmatic lesion, (2) CNS mass, (3) leptomeningeal disease]. A proposal is also presented for substaging of enucleated Stages I and II eyes. CONCLUSIONS: The proposed staging system is the product of an international effort to adopt a uniform staging system for patients with retinoblastoma to cover the whole spectrum of the disease.

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In developed countries, adolescent death rate is under 1%, predominantly due to accidents. Amongst chronic diseases cancer has a prevalent role. A severe disease plays against the normal subjectivation and autonomization adolescent process. It leads to unbearable restrictions in being on the move with their mates, being proud of their body image, attending school. It increases parents' dependency and induces multiple treatment discomforts. Nursing team has to consider the adolescent as its primary interlocutor, to fulfil his demands of autonomy and to validate his choices, and to contribute to maintaining his links with his parents. Moreover, specific expressions of adolescent's needs in the field of pain control, body intimacy, information, schooling, sublimation's behaviours, sexuality, have to be recognized and satisfied.

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PURPOSE: To assess the specific role of treatment and type of first cancer (FC) in the risk of long-term subsequent breast cancer (BC) among childhood cancer survivors. PATIENTS AND METHODS: In a cohort of 1,814 3-year female survivors treated between 1946 and 1986 in eight French and English centers, data on chemotherapy and radiotherapy were collected. Individual estimation of radiation dose to each breast was performed for the 1,258 patients treated by external radiotherapy; mean dose to breast was 5.06 Gy (range, 0.0 to 88.0 Gy) delivered in 20 fractions (mean). RESULTS: Mean follow-up was 16 years; 16 patients developed a clinical BC, 13 after radiotherapy. The cumulative incidence of BC was 2.8% (95% CI, 1.0% to 4.5%) 30 years after the FC and 5.1% (95% CI, 2.1% to 8.2%) at the age of 40 years. The annual excess incidence increased as age increased, whereas the standardized incidence ratio decreased. On average, each Gray unit received by any breast increased the excess relative risk of BC by 0.13 (< 0.0 to 0.75). After stratification on castration and attained age, and adjusting for radiation dose, FC type, and chemotherapy, a higher risk of a subsequent BC was associated with Hodgkin's disease (relative risk, 7.0; 95% CI, 1.4 to 30.9). CONCLUSION: The reported high risk of BC after childhood Hodgkin's disease treatment seems to be due not only to a higher radiation dose to the breasts, but also to a specific susceptibility.

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Retinoblastoma is usually curable in developed countries. The morbidity and mortality of patients with hereditary retinoblastoma is still threatened by the occurrence of secondary tumours. Between 1971 and 1988, 427 patients with retinoblastoma were treated in the ophthalmologic, paediatric and radiotherapy departments of the Institut Curie. In this study, we report the clinical and therapeutic features and the outcome of 25 patients treated for a second malignant neoplasm, diagnosed between 1997 and 1999 at the Institut Curie. The median time interval between the diagnosis of retinoblastoma and SMN was 11.2 years (range 3.8-20.6 years). Histopathological diagnoses included: 12 osteosarcomas, 12 soft tissue sarcomas and, 1 malignant oligodendroglioma. The second malignant neoplasm was located inside the radiation field in 21 cases and outside in 4. Twenty three patients received pre-operative chemotherapy. Surgery was performed in 16 patients. Post-operative chemotherapy was administered in 12 patients and external beam radiotherapy was used in 2 patients. Response to treatment was evaluable in 24 patients: complete remissions were observed in 14/24, partial remissions in 2/24 and progressive disease in 8/24. Nineteen patients died. Six are still alive, with 4 in complete remission (median follow-up 8.8 years; range 5.8-13.9 years). Despite aggressive therapy, the prognosis of patients with second malignant neoplasm occurring after retinoblastoma is very poor. It is important to provide information to retinoblastoma patients regarding the risk of a second tumour as this may facilitate an early tumour detection.

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Soft tissue sarcoma (STS) is one of the most frequent second primary cancer that occurs during the first 20 years following treatment for a solid cancer in childhood. Our aim was to quantify the risk of STS as a second malignant neoplasm and to investigate its relationship with radiotherapy and chemotherapy. A cohort study of 4,400 3-year survivors of a first solid cancer diagnosed during childhood in France or the United Kingdom, between 1942 and 1985, was followed 15 years on average. In a partially nested case-control study, we matched 25 cases of STS and 121 controls for sex, type of first cancer, age at first cancer and duration of follow-up. Sixteen STS occurred in the cohort, as compared to 0.3 expected from the general population (Standardized Incidence Radio, SIR = 54 (95%CI: 34-89)). The SIR was 113 (95% CI: 62-185) after chemotherapy plus radiotherapy (13 STS), whereas it was 28 (95%CI: 2-125) after chemotherapy alone (1 STS) and 19 (95%CI: 3-60) after radiotherapy alone (2 STS). After adjustment for treatment, there was no evidence of variation in the annual excess of incidence or in the SIR with either age at first cancer or time since 1st cancer. In the case-control study, the risk of a STS was increased with the square of the dose of radiation to the site of STS development and with the administration of Procarbazine. The increased risk of soft tissue sarcoma that occurred after childhood cancer is independently related to exposure to radiotherapy and Procarbazine. A closer surveillance of children treated with this treatment combination is strongly recommended.

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PURPOSE: Metaiodobenzylguanidine (MIBG), specifically taken up in cells of sympathetic origin, provides a highly sensitive and specific indicator for the detection of metastases in neuroblastoma. The aim of this study was to correlate early response to therapy by MIBG scan, using a semiquantitative scoring method, with the end induction response and event-free survival (EFS) rate in stage IV neuroblastoma. PATIENTS AND METHODS: Seventy-five children older than 1 year and with stage IV neuroblastoma had 123I-MIBG scans at diagnosis, after two and four cycles of induction therapy, and before autologous stem-cell transplantation. The scans were read by two independent observers (concordance > 95%) using a semiquantitative method. Absolute and relative (score divided by initial score) MIBG scores were then correlated with overall pretransplantation response, bone marrow response, and EFS. RESULTS: The pretransplantation response rate was 81%, and the 3-year EFS rate was 32%, similar to a concomitant group of 375 stage IV patients. The median relative MIBG scores after two, four, and six cycles were 0.5, 0.24, and 0.12, respectively. The probability of having a complete response or very good partial response before transplantation was significantly higher if the relative score after two cycles was < or = 0.5, or, if after four cycles, the relative score was < or = 0.24. Patients with a relative score of < or = 0.5 after two cycles or a score of < or = 0.24 after four cycles had an improved EFS rate (P =.053 and.045, respectively). CONCLUSION: Semiquantitative MIBG score early in therapy provides valuable prognostic information for overall response and EFS, which may be useful in tailoring treatment.

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Loss of heterozygosity of chromosome 16q occurs in 17-25% of Wilms' tumors. Two cadherin genes mapping to 16q22 were chosen as candidate gens: E-CAD, encoding epithelial cadherin, because it is involved in kidney development and it was recently reported to be a WT1 target; and KSP-CAD because it encodes a kidney-specific cadherin. By RT-PCR analysis in a series of 39 Wilms' tumors, we identified a very low expression of E-CAD and KSP-CAD in 72% and 95% of the tumors, respectively. To ascertain whether down-expression of these genes could be related to WT1 alterations in tumors, we looked for a relationship between WT1 and CAD expression. Our data suggest (i) the existence of alternative mechanisms for regulating E-CAD expression, and (ii) that E-CAD does not belong to the WT1 pathway that is altered in Wilms' tumorigenesis.

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Wilms' tumour (WT) or nephroblastoma is the most frequent kidney cancer in children. In a previous study, we reported alterations to WT1 transcription in 90% of WT tested, with decreased exon 5 +/- isoform ratio being the most frequent alteration (56% of WT). We now report an approach based on cDNA profiling of tumour pools to identify genes likely to be dysregulated in association with a decreased WT1 exon 5 +/- ratio. We compared the expression profiles of pools of tumours classified according to whether this isoform imbalance was present (five tumours) or not (four tumours), using Atlas Cancer cDNA expression arrays. Fourteen of 588 genes tested displayed specific up-regulation (CCND2, PCNA, N-MYC, E2F3, TOP2A, PAK1, DCC and PCDH2) or down-regulation (VEGF, IGFBP5, TIMP3, ARHB, C-FOS and CD9) in the pool of tumours with decreased exon 5 +/- ratio. These results were validated by RT-PCR analysis of four genes (CCND2, PCNA, VEGF and IGFBP5). We extended the analysis of VEGF expression to 51 tumours by real-time RT-PCR and ascertained differential expression of this gene associated with WT1 expression pattern. Moreover, our results suggest that the VEGF expression level may be of prognosis relevance for relapsed patients.

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OBJECTIVE: To evaluate the results of chemothermotherapy for the treatment of retinoblastoma. DESIGN: Non-comparative interventional case series. PATIENTS: Fifty-one children (65 eyes and 103 tumors) were treated with chemothermotherapy in a single institution from January 1995 to May 1998. METHODS: Chemothermotherapy consists of a combination of transpupillary thermotherapy delivered shortly after intravenous (IV) injection of carboplatin (560 mg/m(2)). Each tumor is treated separately with a diode laser using a microscope. Laser intensity, spot size, and duration are adapted to the size of each tumor and to the clinical response. After 8 days, thermotherapy alone is repeated. This cycle is performed from one to six times, every 28 days. The treatment data and outcome are analyzed separately. MAIN OUTCOME MEASURES: Assessment of local tumor control. RESULTS: One hundred three tumors were treated in 65 eyes of 51 children. Age at diagnosis was 0 to 60 months (median, 7 months). Median tumor diameter at the time of treatment was 3.5 mm (range, 1.5-12 mm). Laser modalities were as follows: median intensity, 450 mW (range, 150-1000 mW); median spot size, 1.2 mm (range, 0.3-2.0 mm); and median number of cycles required to obtain tumor control, three. Tumor regression was obtained for 99 tumors (96.1%) after a median follow-up of 30 months (17-61 months). Seven tumors relapsed after initial control (6.8%). Salvage treatment (external beam radiation, iodine plaques, or enucleation) was necessary for a total of 11 tumors (10.7%). The only risk factor for relapse was the initial diameter of the lesion greater than 3.5 mm, whereas the other tumor characteristics or treatment variables were not significantly correlated with relapse. Ninety-seven percent of treated eyes were able to be preserved, and 92% of cases were treated without external beam radiation. CONCLUSIONS: Chemothermotherapy is an effective technique to treat small- to medium-sized retinoblastomas in children, avoiding external beam irradiation.

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PURPOSE: Because of the long-term complications associated with external beam radiation in retinoblastoma, alternative treatment methods have been investigated. We conducted a retrospective study to evaluate the functional results of new treatment modalities. METHODS: Thirty-seven eyes were treated without external beam irradiation in 31 patients. The median diameter of the largest tumor in each eye was 6 mm. Primary chemotherapy was used in 25 cases, chemothermotherapy was used in 32 cases, cryotherapy was used in 28 cases, iodine 125 Plaques were used in 15 cases, diode laser thermotherapy was used alone in 11 cases, and photocoagulation was performed in 5 cases. The median follow-up after diagnosis of retinoblastoma was 41 months. The visual results were evaluated at a median age of 54 months. RESULTS: The median visual acuity of the treated eyes was 20/33. Twenty-four eyes presented a visual acuity better than 20/40, 4 eyes had a visual acuity between 20/200 and 20/40, and 9 eyes had a visual acuity less than 20/200. Maculopathy was observed in 16 cases, associated with papillopathy in 1 case. A cataract was observed in 1 case and a vitreous hemorrhage was observed in another case. Twenty-one eyes did not develop any complications. No corneal dryness and very few lens changes were observed. CONCLUSION: The functional results after local treatments for retinoblastoma are very good. The most frequent complication is maculopathy, particularly when the tumor involves or is situated close to the macula.

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