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Purpose: Describe clinical characteristics and outcome of Li-Fraumeni syndrome (LFS)-associated osteosarcomas., Methods: TP53 germline pathogenic/likely pathogenic variant carriers diagnosed with osteosarcoma in France between 1980 and 2019 were identified via the French Li-Fraumeni database at Rouen University Hospital. Sixty-five osteosarcomas in 52 patients with available clinical and histological data were included. The main clinical characteristics were compared with data from National Cancer Institute's SEER (Surveillance, Epidemiology, and End Results) for patients of the same age group., Results: Median age at first osteosarcoma diagnosis was 13.7 years (range: 5.9-36.7). Compared to unselected osteosarcomas, LFS-associated osteosarcomas occurred more frequently in patients less than 10 years of age (23% vs. 9%), and when compared with osteosarcomas in patients less than 25 years were characterized by an excess of axial (16% vs. 10%) and jaw sites (15% vs. 3%) and histology with predominant chondroblastic component and periosteal subtypes (17% vs. 1%). Metastases incidence (25%) was as expected in osteosarcomas. After the first osteosarcoma treatment, the rate of good histologic response (62%) and the 5-year progression-free survival (55%, 95% confidence interval [CI]: 42.6-71.1) were as expected in unselected series of osteosarcomas, whereas the 5-year event-free survival was 36.5% [95% CI: 25.3-52.7] due to the high incidence of second malignancies reaching a 10-year cumulative risk of 43.4% [95% CI: 28.5-57.5]., Conclusion: In osteosarcoma, young age at diagnosis, axial and jaw sites, histology with periosteal or chondroblastic subtype, and synchronous multifocal tumors should prompt suspicion of a germline TP53 mutation. Standard treatments are effective, but multiple malignancies impair prognosis. Early recognition of these patients is crucial for tailored therapy and follow-up., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background: Conservative treatments of intraocular retinoblastoma often consist of chemotherapy and focal treatments. The protocols vary and currently may combine two or three drugs, with different number of cycles, associated to the ocular treatments. In case of macular/paramacular involvement, tumor location and retinal scars induced by focal treatments often have a major negative impact on final visual outcome., Methods: This study aimed to include children affected by bilateral intraocular macular/paramacular retinoblastoma in a prospective phase II study. The protocol consisted of six cycles of a three-drug combination (vincristine, etoposide, carboplatin), and the addition of macula-sparing transpupillary thermotherapy (TTT) to the third cycle. The primary endpoint was the local control rate without external beam radiotherapy (EBR) and/or enucleation., Results: Nineteen patients (26 eyes) were included from July 2004 to November 2009. Thirteen eyes belonged to group V of the Reese-Ellsworth classification and 10 to group D of the International Intraocular Retinoblastoma Classification. Macular/paramacular tumors were treated with chemotherapy alone in nine eyes, and with chemotherapy associated with macula-sparing TTT in 17 eyes. Four eyes experienced macular relapse. At a median follow up of 77 months, 23 eyes (88.5%) were saved without EBR, two were enucleated and one received EBR. The median visual acuity of the 24 saved eyes was 20/50. No severe adverse effect was observed., Conclusion: Six cycles of a three-drug combination associated with macula-sparing TTT achieved good tumor control, improved eye preservation rates without EBR, and decreased macular damage, often providing satisfactory visual results with long-term follow up., (© 2020 Wiley Periodicals LLC.)

Objective: To describe the clinical characteristics and outcome of patients with Li-Fraumeni-associated rhabdomyosarcoma (RMS)., Method: Retrospective analysis of data from 31 French patients with RMS diagnosed before the age of 20 years associated with a TP53 pathogenic germline variant. Cases were identified through the French Li-Fraumeni database. Central histologic review was performed in 16 cases., Results: The median age at diagnosis was 2.3 years, and the median follow-up was 9.1 years (0.3-34.8). The main tumor sites were head and neck (n = 13), extremities (n = 8), and trunk (n = 8). The local pathology report classified the 31 tumors in embryonal (n = 26), alveolar (n = 1), pleomorphic (n = 1), and spindle-cell (n = 1) RMS (missing = 2). After histological review, anaplasia (diffuse or focal) was reported in 12/16 patients. Twenty-five patients had localized disease, three had lymph node involvement, and three distant metastases. First-line therapy combined surgery (n = 27), chemotherapy (n = 30), and radiotherapy (n = 14) and led to RMS control in all, but one patient. Eleven patients relapsed, and 18 patients had second malignancies. The 10-year event-free, progression-free, and overall survival rates were 36% (95% CI: 20-56), 62% (95% CI: 43-77) and 76% (95% CI: 56-88), respectively. The 10-year cumulative risk of second malignancies was 40% (95% CI: 22-60)., Conclusion: The high incidence of multiple primary tumors strongly influences the long-term prognosis of RMS associated with TP53 pathogenic germline variants. Anaplastic RMS in childhood, independently of the familial history, should lead to TP53 analysis at treatment initiation to reduce, whenever possible, the burden of genotoxic drugs and radiotherapy in carriers and to ensure the early detection of second malignancies., (© 2020 Wiley Periodicals LLC.)

Background: Retinoblastoma (Rb) is the most common intraocular primary malignancy in children. In industrialised countries, the cure rate is about 95%. We present the results of a prospective study on the management of Rb in the paediatric oncology unit of Gabriel Touré Teaching Hospital and African Institute of Tropical Ophthalmology, from November 1, 2011 to December 31, 2015., Procedure: The aims of this prospective study were to evaluate the treatment of localised Rb, ocular prosthesis after enucleation, conservative management for bilateral Rb as well as survival rates in all patients. Patients with early stage Rb at diagnosis were included. The treatment was performed according to the retinoblastoma treatment guidelines of the French-African Paediatric Oncology Group., Results: Eighty-eight patients were included in the study. Sex ratio was 1:1 (M = 44, F = 44). Median age at diagnosis was 3 years (range: 2 months-5 years). Unilateral intraocular Rb was predominant (n = 50; 56.8%). Conservative treatments were performed on nine eyes in nine patients. Overall survival and event-free survival of the entire cohort at the end of 4 years were 73% (95% CI 60.8-81.2%) and 59% (95% CI 47.9-69.5%), respectively, with a median follow-up of 3.7 years (0.1-5.6 years). In conclusion, early enucleation in early stage of Rb can improve outcomes in resource-limited countries. Delayed enucleation and refusal of adherence to treatment are still major concerns and remain a barrier to improving overall patient survival., (© 2018 Wiley Periodicals, Inc.)

Background: Solid pseudopapillary neoplasms of the pancreas (SPPN) can relapse very late, but little is known about risk factors for recurrence and optimal treatment. We aimed to identify risk factors for recurrence and to analyze treatment modalities in all French pediatric cases of SPPN over the past 20 years., Material and Methods: Data were collected from pediatric oncologists and surgeons, and also from adult pancreatic surgeons in order to identify late recurrences., Results: Fifty-one patients (41 girls) were identified. Median age at diagnosis was 13.1 years [8.7-17.9]. Abdominal pain was the commonest presenting symptom (32/49, 65%). The tumor was located in the pancreatic head in 24 patients (47%). Preoperative biopsy or cytology was performed in 14 cases (28%). All patients were operated with a median of 23 days [0-163] after diagnosis. The rate of postoperative morbidity was 29%. With a median follow-up of 65 months [0.3-221], the overall and event-free survival was 100% and 71%, respectively. Seven patients (13.7%) relapsed with a median of 43 months [33-94] after initial surgery. Six were treated surgically, either alone (n = 3) or with perioperative chemotherapy (n = 2) or hyperthermic intraperitoneal chemotherapy (n = 1). One patient in whom further treatment was not feasible was still alive at last news. Risk factors for recurrence were positive surgical margins (P = 0.03) and age less than 13.5 years at diagnosis (P = 0.03)., Conclusions: SPPN recurrence in this pediatric series was a rare and late event that did not undermine overall survival. Complete surgical removal of recurrent tumors appears to be the best option., (© 2016 Wiley Periodicals, Inc.)

Background: Germline non-polyalanine repeat expansion mutations in PHOX2B (PHOX2B NPARM) predispose to peripheral neuroblastic tumors (PNT), frequently in association with other neurocristopathies: Hirschsprung disease (HSCR) or congenital central hypoventilation syndrome (CCHS). Although PHOX2B polyalanine repeat expansions predispose to a low incidence of benign PNTs, the oncologic phenotype associated with PHOX2B NPARM is still not known in detail., Methods: We analyzed prognostic factors, treatment toxicity, and outcome of patients with PNT and PHOX2B NPARM., Results: Thirteen patients were identified, six of whom also had CCHS and/or HSCR, one also had late-onset hypoventilation with hypothalamic dysfunction (LO-CHS/HD), and six had no other neurocristopathy. Four tumours were "poorly differentiated," and nine were differentiated, including five ganglioneuromas, three ganglioneuroblastomas, and one differentiating neuroblastoma, hence illustrating that PHOX2B NPARM are predominantly associated with differentiating tumors. Nevertheless, three patients had stage 4 and one patient had stage 3 disease. Segmental chromosomal alterations, correlating with poor prognosis, were found in all the six tumors analyzed by array-comparative genomic hybridization. One patient died of tumor progression, one is on palliative care, one died of hypoventilation, and 10 patients are still alive, with median follow-up of 5 years., Conclusions: Based on histological phenotype, our series suggests that heterozygous PHOX2B NPARM do not fully preclude ganglion cell differentiation in tumors. However, this tumor predisposition syndrome may also be associated with poorly differentiated tumors with unfavorable genomic profiles and clinically aggressive behaviors. The intrafamilial variability and the unpredictable tumor prognosis should be considered in genetic counseling., (© 2015 Wiley Periodicals, Inc.)

Purpose: Outcome of T-cell lymphoblastic lymphoma (T-LBL) in children is around 75-85% of event-free survival. The role of early intensification to improve outcome while using short infusions of high dose methotrexate (HDMTX) and shorter maintenance treatment was addressed by the French Society of Pediatric Oncology (SFOP) group., Methods: From 1997 through 2003, 79 children (52 males; median age 10.5 years) were prospectively registered into the SFOP LMT 96 trial. The LMT96 protocol, with elements from the protocol of the Berlin-Frankfurt-Münster (BFM) Group included four main modifications: (a) 10 courses of HD-MTX (3 g/m(2) ) delivered over the first 44 weeks; (b) early intensification with cyclophosphamide together with the first course of HD-MTX; (c) a maintenance phase that included 6 monthly intensified chemotherapy pulses; and (d) treatment duration of 18 months for stages I-III., Results: Eighty-nine percent of patients had an initial mediastinal involvement. With a median follow-up of 87 months, the 5-year event-free survival was 85% and overall survival 89%. Nine patients relapsed, eight during treatment. The early intensification did not change the pattern of relapses. Only 58% of patients experienced grade 3-4 neutropenia during the induction phase, 13% patients experienced grade 3 and 4 mucositis, and 5% patients experienced diabetes. The early intensification did not delay phases of chemotherapy., Conclusions: Early intensification in treatment for T-LBL in children is manageable. Three-hour infusion of HD-MTX did not jeopardize patient outcome. Our results are comparable with those of other international protocols in spite of shorter maintenance treatment for stages I-III., (© 2015 Wiley Periodicals, Inc.)

Purpose: We report the results of a French multicenter retrospective study based on a period of more than 30 years and a review of the literature in order to more clearly define the surgical approach and specific pediatric risk factors., Methods: Clinical data of children comprising all histologic subtypes of thymic epithelial tumors (TET) treated between 1979 and 2009 in French pediatric oncology centers were retrospectively analyzed and discussed in the light of a review of all pediatric cases reported in the literature., Results: Nine cases were identified, corresponding to five females and four males with a median age of 13 years (range: 7.5-17). Histologic subtypes were type AB (n = 1), type B (n = 5) and type C (n = 3). Treatment consisted of tumor resection (4 R0, 4 R1, 1 R2) via right anterior thoracotomy, posterolateral thoracotomy, left thoracoscopy, sternotomy and cervicosternotomy, and/or chemotherapy, mainly cyclophosphamide-doxorubicin-cisplatin (CAP; n = 5), and/or radiotherapy (n = 4). Two patients with TET type C died. All other patients are alive with a median follow-up of 4 years (range: 1.5-20). Review of a total of 93 pediatric cases reported in the literature showed statistically significant associations between less favorable histologic subtypes and male gender (P = 0.012), advanced Masaoka stage (P < 0.001) and quality of resection (P < 0.001) respectively., Conclusions: A review of the literature and our series identified several risk factors to take into account in the therapeutically decision. Complete resection through a sternotomy is highly recommended., (© 2014 Wiley Periodicals, Inc.)

Background: To evaluate long-term survival of the first cohort of stage-4 neuroblastoma patients treated with the N7 induction chemotherapy, surgery of the primary tumor and high-dose chemotherapy (HDC) containing Busulfan-Melphalan (Bu-Mel) followed by autologous stem cell transplantation (ASCT)., Procedure: From 1998 to 1999, 47 children were included in the NB97 trial and treated with induction chemotherapy according to the N7 protocol, followed by surgery of the primary tumor. HDC (Busulfan, 600 mg/m(2) Melphalan, 140 mg/m(2) ) was administered in patients with partial response of metastases with no more than 3 mIBG spots. Radiotherapy was delivered to the primary tumor site when tumors displayed MYCN amplification., Results: Thirty-nine patients received Bu-Mel (83%): 23 who had achieved complete response (CR) of metastases, 20 after induction treatment and 3 after second-line chemotherapy, and 16 in partial response (PR). The toxicity of the whole treatment was manageable. The main HDC related-toxicity was hepatic veno-occlusive disease grade > 2 occurring in 15% of the patients. The 8-year EFS of the whole cohort was 34% (95% CI, 22-48%). The 8-year EFS of the 39 patients who received Bu-Mel and ASCT was 41% (95% CI, 27-57%). Patients who achieved a CR of metastases at the end of induction chemotherapy had a significantly better outcome than the others (8-year EFS, 52% vs. 20%; P = 0.02)., Conclusions: The long-term results of this first prospective cohort of patients with metastatic disease treated with the N7 induction chemotherapy and HDC (Bu-Mel) confirm published data with stable survival curves but with a longer follow-up., (© 2013 Wiley Periodicals, Inc.)

Purpose: Describe the epidemiology, clinical profiles and outcomes associated with head and neck (H&N) involvement in children/adolescents with B-cell non-Hodgkin lymphoma (B-NHL)., Methods: Analysis of children/adolescents with H&N B-NHL prospectively enrolled in the SFOP LMB-89 trial (July 1989-June 1996)., Results: One hundred and twelve of 561 patients (20%) had H&N involvement. The mean age of the patients was 8.4 years. Murphy staging differed between the H&N patients and the others (P < 0.0001): 9% versus 5% of the patients presented with stage I disease, 36% versus 11% presented with stage II disease, 12% versus 59% presented with stage III disease, 17% versus 10% with stage IV disease and 27% versus 16% with B-AL. Twenty-nine H&N patients (26%) had CNS involvement at diagnosis versus 8.5% in the group without H&N involvement (P < 0.0001). Patients were treated according to the LMB89 protocol: 3 H&N patients were allocated to group A, 70 to group B and 39 to group C. Ninety-seven percent of H&N patients achieved CR and event-free and overall survival at 4 years was 95.5% (5 deaths in patients with CNS disease). On multivariate analysis, EFS was significantly better in H&N patients than in non-H&N patients (P = 0.021), but not OS (P = 0.11)., Conclusion: The H&N site is the second most common location for B-NHL at diagnosis and is more frequently associated with disseminated disease and CNS involvement than other sites. However, outcomes are no worse for these patients than for the rest of the population., (© 2013 Wiley Periodicals, Inc.)

Background: To improve outcome and overall survival (OS) in high-risk neuroblastoma, NB96 induction therapy was intensified using sequential high-dose chemotherapy and autologous stem cell rescue., Procedure: Twenty children were included in this pilot study undertaken at seven reference centers in France, between May 1995 and October 1996. Induction began with one cycle of conventional chemotherapy followed by six sequential cycles of high-dose chemotherapy comprising two cycles of etoposide 800 mg/m(2)/day over 3 days, two cycles of cyclophosphamide 2,000 mg/m(2)/day over 3 days, and two cycles of carboplatin 400 mg/m(2)/day over 5 days, followed by stem cell rescue., Results: Thirteen patients (13/20) received this induction with acceptable toxicity and adequate stem cell harvest. Of these, nine (9/13) underwent surgery according to the protocol, while one patient was given a consolidation regimen prior to surgery. No toxic death was recorded. At the end of induction, complete remission was achieved in 10 cases (50%), with six still alive in July 2009. The 5-year event-free survival and OS were 35 ± 11% and 40 ± 11%, respectively., Conclusion: NB96 therapy is feasible and tolerated without lethal toxicity. Nevertheless, given the small sample size and absence of randomization in our study, the effectiveness of this strategy based on metastasis complete response rates and long-term outcome was not superior to other intensive chemotherapy regimens., (Copyright © 2011 Wiley-Liss, Inc.)

Background: The French African Group of Pediatric Oncology was set-up to improve quality of care for children with cancer. Preliminary observations on the efficacy in Burkitt lymphoma (BL) of a cyclophosphamide monotherapy (CPM) have been published. We report the results of a multicentric prospective study combining first-line CPM and a multidrug second-line chemotherapy (SC) for refractory/relapsed patients., Procedure: Patients ≤ 18 years with Burkitt or Burkitt-like lymphoma, were included in six countries (Burkina-Faso, Cameroon, Ivory Coast, Madagascar, Mali, and Senegal). All patients received three weekly CPM courses (1.2 g/m(2) IV with intrathecal methotrexate and hydrocortisone), stage 3/4 patients received three further courses. SC added methotrexate, vincristine, cytarabine, and prednisone., Results: There were 178 patients included (42 stage 1/2, 134 stage 3/4, and 2 unknown). Isolated facial localization was found in 41 patients, diffuse abdominal involvement in 120 patients including 65 with both. Nine early deaths were reported, toxicity occurred in 136/743 courses (83 patients) and was predominantly hematological. After CPM, complete remission (CR) rate was 47% with a 33% EFS. Because of rapid progression 76/108 eligible patients (85 primary refractory and 23 relapses) received SC resulting in 35.7% CR but a 21% toxic death rate. The OS of the whole strategy was 50.5% and correlated to stage., Conclusion: A prospective multicentric study on BL was feasible in very low-income countries. CPM can be recommended in stage 1-2 because of optimal cost/benefit ratio. However, more intensive strategies, still adapted to socio-economic conditions, are required for advanced stages 3 and 4.

We report the case of a 6-year-old female who presented a cervical intradural extra-spinal tumor, initially considered as a Langerhans cell histiocytosis. Additional histological slides revealed a Dirofilaria repens dirofilariasis. The particularity of this case is the intradural location of this filariasis, which usually has a subcutaneous or conjunctival location in human., ((c) 2009 Wiley-Liss, Inc.)

Background: Neuroblastic tumors (NTs) are occasionally associated with watery diarrhea, due to Vasoactive Intestinal Peptide (VIP) secretion. Most reports are single cases and suggest a great homogeny within this sub-group of NTs., Procedures: We conducted a retrospective analysis of the French experience of NTs associated with watery diarrhea due to VIP-secretion. VIP secretion was confirmed by seric dosage and/or immunohistochemistry., Results: Twenty-two patients met the diagnostic criteria between 1988 and 2007. Most of patients suffered from weight loss and metabolic disorders. In 16 cases, digestive symptoms preceded the diagnosis of the tumor ("Primary VIP secreting NTs"); 15 were localized and all showed a differentiated histology. Interestingly, in another 6 patients with high-risk NT, diarrhea occurred at the time of chemotherapy or retinoic acid therapy ("Secondary VIP secreting NTs"). Differentiation in response to treatment was documented in 4 cases. In all cases, only surgical excision of the tumor was able to control the digestive symptoms. Twenty children are alive and 13 are disease-free., Conclusion: VIP secreting NTs are usually associated with differentiation; they can also secondarily arise from a high-risk tumor upon treatment. Primary surgery constitutes first-line treatment., ((c) 2009 Wiley-Liss, Inc.)

We report on the case of a 10-month-old female infant with a metastatic neuroblastoma which became MIBG-negative at time of relapse. We discuss the different hypothesis associated with this particular outcome, and the potential utility of FDG-PET as an alternative to follow up the residual disease at this stage.