French Society Of Pediatric Oncology Research Articles

Chemo-immunotherapy with dinutuximab beta in patients with relapsed/progressive high-risk neuroblastoma: does chemotherapy backbone matter?

BackgroundAddition of anti-GD2 antibodies to temozolomide-based chemotherapy has demonstrated increased antitumor activity and progression-free survival in patients with relapsed/progressive high-risk neuroblastoma. However, chemo-immunotherapy is not yet approved for this indication. This study presents the chemo-immunotherapy experience in patients with relapsed/progressive high-risk neuroblastoma treated within the off-label use program of the Neuroblastoma Committee of the French Society of Pediatric Oncology (SFCE). MethodsDinutuximab beta (dB) was administered alongside temozolomide-topotecan (TOTEM) or temozolomide-irinotecan (TEMIRI) at first disease relapse/progression or topotecan-cyclophosphamide (TopoCyclo) at further relapse/progression. Real-world data on demographics, treatment, antitumor activity and safety was collected from all patients after inclusion in SACHA-France (NCT04477681), a prospective national registry, which documents safety and efficacy data on innovative anticancer therapies prescribed to patients ≤ 25 years old as compassionate or off-label use. ResultsBetween February 2021 and July 2023, 39 patients with confirmed relapsed/progressive high-risk neuroblastoma (median age 6 years, range 1–24) were treated with dB+TopoCyclo (n = 24) or dB+TOTEM/TEMIRI (n = 15) across 17 centers. In total, 163 chemo-immunotherapy cycles were administered, main toxicities were mild or moderate, with higher incidence of hematological adverse drug reactions with dB+TopoCyclo than dB+TOTEM/TEMIRI. Objective response rate was 42% for dB+TopoCyclo (CI95% 22–63%) and 40% for dB+TOTEM/TEMIRI (CI95% 16–68%). ConclusionSimilar objective response rates for dB+TopoCyclo and dB+TOTEM/TEMIRI in patients with relapsed/progressive high-risk neuroblastoma emphasize the importance of chemo-immunotherapy, irrespective of the chemotherapy backbone.

Measuring Safety and Outcomes for the Use of Compassionate and Off-Label Therapies for Children, Adolescents, and Young Adults With Cancer in the SACHA-France Study

Innovative anticancer therapies for children, adolescents, and young adults are regularly prescribed outside their marketing authorization or through compassionate use programs. However, no clinical data of these prescriptions is systematically collected. To measure the feasibility of the collection of clinical safety and efficacy data of compassionate and off-label innovative anticancer therapies, with adequate pharmacovigilance declaration to inform further use and development of these medicines. This cohort study included patients treated at French pediatric oncology centers from March 2020 to June 2022. Eligible patients were aged 25 years or younger with pediatric malignant neoplasms (solid tumors, brain tumors, or hematological malignant neoplasms) or related conditions who received compassionate use or off-label innovative anticancer therapies. Follow up was conducted through August 10, 2022. All patients treated in a French Society of Pediatric Oncology (SFCE) center. Collection of adverse drug reactions and anticancer activity attributable to the treatment. A total of 366 patients were included, with a median age of 11.1 years (range, 0.2-24.6 years); 203 of 351 patients (58%) in the final analysis were male. Fifty-five different drugs were prescribed, half of patients (179 of 351 [51%]) were prescribed these drugs within a compassionate use program, mainly as single agents (74%) and based on a molecular alteration (65%). Main therapies were MEK/BRAF inhibitors followed by multi-targeted tyrosine kinase inhibitors. In 34% of patients at least a grade 2 clinical and/or grade 3 laboratory adverse drug reaction was reported, leading to delayed therapy and permanent discontinuation of the innovative therapy in 13% and 5% of patients, respectively. Objective responses were reported in 57 of 230 patients (25%) with solid tumors, brain tumors, and lymphomas. Early identification of exceptional responses supported the development of specific clinical trials for this population. This cohort study of the SACHA-France (Secured Access to Innovative Medicines for Children with Cancer) suggested the feasibility of prospective multicenter clinical safety and activity data collection for compassionate and off-label new anticancer medicines. This study allowed adequate pharmacovigilance reporting and early identification of exceptional responses allowing further pediatric drug development within clinical trials; based on this experience, this study will be enlarged to the international level.

Comprehensive nationwide study on the prescription of experimental anticancer therapies for compassionate use in children and adolescents in France.

10019 Background: Compassionate use prescriptions of innovative anticancer therapies are common in pediatric oncology, although rarely reported and activity/safety information mainly based on single/limited institutional retrospective experiences. Methods: In France, early drug access before marketing authorization is granted by the French National Agency for the Safety of Medicines and Health Products (ANSM) in case on unmet need, positive benefit/risk balance of preliminary data and no access within clinical trials. All anticancer prescriptions approved by the ANSM from 01/01/2020 to 31/12/2022 for patients < 18 years-old were analyzed. Patients safety and activity data were collected through the SACHA France study (NCT04477681) in the 2020-2021 period. 2022 data analysis is currently ongoing and will be included in the presentation at ASCO. Results: In the study period, 1022 anticancer compassionate use prescriptions were authorized by ANSM. The most frequently prescribed drug was methotrexate drinkable solution (n = 526) and 383 prescriptions were within the inclusion criteria of the SACHA study (anti-cancer innovative therapies not approved in Europe or new formulation of an already approved drug after 2007). In the 2020-2021 period, 28 different therapies were prescribed to 188 patients in a French Society of Pediatric Oncology (SFCE) center. Of them, 14 patients never received the prescribed drug, mainly due to early death. 107 of 174 (61%) eligible patients from 21 SFCE centers were included in the SACHA study (56% in 2020 and 67% in 2021). Median age at inclusion was 6.0 years (range: 0.3 -17.3). Main cancer types were central nervous system (CNS) tumors (69), followed by non-CNS tumors (24) and leukemia/lymphoma (14). Main prescribed therapies targeted MEK/BRAF (66), EZH2 (11), BLC2 (7) and ALK/ROS1/MET (5). In 40/107 patients (37%) at least a grade ≥2 clinical and/or grade ≥3 biological adverse drug reaction (ADR) was reported, leading to delayed therapy in 15 % of patients. Overall, 10 serious ADRs were reported in 10 patients. At last news, 53/107 patients had stopped their drug, mainly due to disease progression (33), followed by physician decision (11) and toxicity ± physician decision (8). 12-months PFS was 49% (95 IC: 38-60 %), with a median of 334 days of follow-up for patients on therapy. Conclusions: To our knowledge, this is the first comprehensive nation-wide study on compassionate use prescriptions of experimental anticancer therapies to children and adolescents with cancer with prospective safety/activity information in more than 60% of patients. This study underscores the importance, and feasibility, of the close collaboration between academia and regulatory authorities to ensure adequate real-life monitoring of these prescriptions. Supported by Imagine for Margo, Association Hubert Gouin, Fondation du LEEM and the SFCE.

Risk factors in pediatric Malignant Peripheral Nerve Sheath Tumors (MPNST): Results from the French Pediatric Oncology Society (SFCE) cohort

Risk factors in pediatric Malignant Peripheral Nerve Sheath Tumors (MPNST): Results from the French Pediatric Oncology Society (SFCE) cohort

Securing access to innovative anticancer therapies for children, adolescents, and young adults outside clinical trials: The SACHA study of the French Society of Pediatric Oncology (SFCE).

10006 Background: Access to innovative anticancer therapies for children, adolescents and young adults within clinical trials in France is steadily increasing in the last years. However, current clinical trials portfolios are still inadequate and thus pediatric hemato-oncologists regularly prescribe innovative medicines outside their marketing authorization, and/or experimental drugs through compassionate use. Methods: The Secured Access to innovative medicines for CHildren with cAncer (SACHA) is a French prospective observational study developed by the French Society of Pediatric Oncology (SFCE) with Gustave Roussy as the legal sponsor to prospectively collect real-world safety and activity data of innovative therapies administered to patients ≤ 25 years-old with pediatric malignancies (solid tumor or leukemia) or other related conditions, either on compassionate use of experimental drugs or off-label use of anti-cancer medicines that have been first approved in adults after 2007. Prior to SACHA inclusion, multicenter tumor board discussion defining best available therapeutic options for each patient with a relapsed malignancy is mandatory. Results: The SACHA study opened in March 2020 and by February 2022, 283 patients have been included from 29/31 SFCE recruiting centers; median age: 11.0 years (range: 0.3-24.4). Main cancer types were central nervous system (CNS) tumors (47%), followed by non-CNS tumors (40%) and leukemias (13%). Innovative therapies prescribed in > 10 patients with reported objective response rate (ORR) and related CTCAE v.5 grade ≥2 clinical and/or grade ≥3 biological adverse drug reactions (ADRs) are described in Table. Conclusions: SACHA confirms the feasibility of this type of prospective real word registry, with a high participation of French centers. Based on this French experience, the Innovative Therapies for Children with Cancer (ITCC) consortium is currently developing a “SACHA International Project” to be opened in ITCC and collaborating countries. [Table: see text]

CD30+ Anaplastic Large-Cell Lymphoma in Children: Analysis of 82 Patients Enrolled in Two Consecutive Studies of the French Society of Pediatric Oncology

AbstractThe purpose of this study was (1) to investigate the efficacy of chemotherapy regimens designed by the French Society of Pediatric Oncology for childhood anaplastic large-cell lymphoma (ALCL) and (2) to identify prognostic factors in these children. Eighty-two children with newly diagnosed ALCL were enrolled in two consecutive studies, HM89 and HM91. The diagnosis of ALCL was based on immuno-morphological features and all the cases but 2 were investigated using ALK1 antibody directed to the NPM/ALK protein associated with the 2;5 translocation. Treatment consisted of 2 courses of COPADM (methotrexate, cyclophosphamide, doxorubicin, vincristine, and prednisone) and a maintenance treatment of 5 to 7 months. Seventy-eight patients (95%) achieved a complete remission and 21 relapsed. The probability of survival and event-free survival at 3 years was of 83% (72% to 90%) and 66% (54% to 76%), respectively, with a median follow-up of 49 months. In multivariate analysis, visceral involvement, mediastinal involvement, and lacticodeshydrogenase (LDH) level ≥800 UI/L were shown to be predictive of a higher risk of failure. In conclusion, this type of regimen demonstrated efficacy in childhood ALCL. However, therapeutic results have to be improved for children with adverse prognostic parameters such as visceral or mediastinal involvement or a high LDH level.

Impact of the First Wave of COVID-19 on Pediatric Oncology and Hematology: A Report from the French Society of Pediatric Oncology.

Simple SummaryData regarding coronavirus disease 2019 (COVID-19) description are still limited in pediatric oncology. The French society of pediatric oncology (SFCE) initiated a study to better describe COVID-19 presentation and evolution in patients followed in French pediatric oncology and hematology wards. By describing COVID-19 in this specific population, we aimed to identify the patients who may be the most at risk of severe COVID-19 and establish specific recommendations.Data regarding coronavirus disease 2019 (COVID-19) description are still limited in pediatric oncology. The French society of pediatric oncology (SFCE) initiated a study to better describe COVID-19 in patients followed in French pediatric oncology and hematology wards. All patients diagnosed with COVID-19 and followed in a SFCE center were enrolled. Data from medical records were analyzed for all patients enrolled up to the end of May 2020. Data were available for 37 patients. Thirty-one were children under 18 years of age. Nineteen patients were female. Seventeen patients had a solid tumor, 16 had a hematological malignancy and four recently underwent hematopoietic stem cell transplantation (HSCT) for non-oncological conditions. Twenty-eight patients presented symptoms, most often with fever, cough, rhinorrhea and asthenia. Ground-glass opacities were the most frequent radiological finding with abnormalities mostly bilateral and peripherally distributed. Twenty-four patients received chemotherapy a month prior to COVID-19 diagnosis. Most patients did not require hospitalization. Three patients required oxygen at the time of diagnosis. In total, five patients were admitted in an intensive care unit because of COVID-19 and one died from the disease. Children and young adults treated for a cancer and/or with a HSCT may be at risk for severe COVID-19 and should be closely monitored.

Clinical and radiological results of vascularized fibular epiphyseal transfer after bone tumor resection in children

IntroductionVascularized fibular proximal epiphyseal transfer associated to a diaphyseal segment is used to treat childhood epiphyseal defect. The aim of the present study was to analyze surgical technique and long-term clinical and radiological results. Material and methodBetween 1997 and 2008, 7 patients with a mean age of 5.7 years (range, 2-8 years) were operated on for bone malignancy with vascularized fibular epiphyseal transfer: 5 Ewing sarcomas and 2 osteosarcomas, located in the proximal femur (n=3), proximal humerus (n=3) or distal radius (n=1). Mean transplant size was 13.8cm. Vascularization involved a single artery in 5 cases (3 peroneal, 2 anterior tibial) and both in 2 cases. Internal fixation used intramedullary nailing in 6 cases and screwed plate in 1. All patients underwent pre- and post-operative chemotherapy following French Pediatric Oncology Society (SFOP) protocols. ResultsMean follow-up was 11 years (range, 3 years 11 months to >17 years). All patients were alive and in tumor remission. Reconstructed joint function was satisfactory in 85% of cases. Graft thickening indicated integration in all cases. The transferred cartilage had recovered growth in 4 cases. Complications comprised postoperative infection (n =1), consolidation defects (n = 2), fractures (n = 8), malalignment requiring surgical revision (n = 1), and spontaneously resolving common peroneal nerve palsies (n = 2). DiscussionIn young children, vascularized fibular epiphyseal transfer fills bone defect, reconstructs a functional joint and allows continued growth in the resected segment. Growth prostheses, in the authors’ experience, always give poor results in this age-group, and fusion fails to address the growth problem. Patients should be informed about the risk of fracture, persisting over the long term. ConclusionVascularized fibular epiphyseal transfer is a difficult technique, subject to complications, but enables reconstruction of a bone segment involving the epiphysis in young children, conserving function and growth. Level of evidenceIII, retrospective clinical study.

Impact of COVID‐19 on cancer care: A survey from the French Society of Pediatric Oncology (SFCE)

The authors declare that there is no conflict of interest.

Pheochromocytoma and Paraganglioma in Children and Adolescents: Experience of the French Society of Pediatric Oncology (SFCE).

PurposeThe purpose of this work is to assess the clinical outcome of pediatric patients diagnosed with pheochromocytoma and paraganglioma (PPGL) detected in France since 2000.MethodsA retrospective multicenter study was conducted that included all patients younger than 18 years with PPGL diagnosed in France between 2000 and 2016. Patients were identified from 4 different sources: the National Registry of Childhood Solid Tumors, the French Pediatric Rare Tumors Database, the French registry of succinate dehydrogenase (SDH)-related hereditary paraganglioma, and the nationwide TenGen network.ResultsAmong 113 eligible patients, 81 children with available data were enrolled (41 with adrenal and 40 with extra-adrenal PPGL). At diagnosis, 11 had synchronous metastases. After a median follow-up of 53 months, 27 patients experienced a new event (n = 7 second PPGL, n = 1 second paraganglioma [PGL], n = 8 local recurrences, n = 10 metastatic relapses, n = 1 new tumor) and 2 patients died of their disease. The 3- and 10-year event-free survival rates were 80% (71%-90%) and 39% (20%-57%),respectively, whereas the overall survival rate was 97% (93%-100%)at 3 and 10 years. A germline mutation in one PPGL-susceptibility gene was identified in 53 of the 68 (77%) patients who underwent genetic testing (SDHB [n = 25], VHL [n = 21], RET [n = 2], HIF2A [n = 2], SDHC [n = 1], SDHD [n = 1], NF1 [n = 1]). Incomplete resection and synchronous metastases were associated with higher risk of events (P = .011, P = .004), but presence of a germline mutation was not (P = .11).ConclusionsMost pediatric PPGLs are associated with germline mutations and require specific follow-up because of the high risk of tumor recurrence.

Primary meningeal sarcoma in children: a survey from the French Society of Pediatric Oncology (SFCE)

Objectives: To describe the outcome of primary meningeal sarcoma (PMS) in a pediatric population. Methods: We conducted a retrospective study on patients harbouring a PMS based on the French registry of paediatric tumours. Questionnaires were sent to all French paediatric oncologists. Data on patient characteristics and treatments were collected. Pathology and imaging were centrally reviewed. Results: Between August 1989 and May 2010, 12 patients from 6 French centres, aged 3 months to 14.5 years (mean: 3.3 years) were treated for a PMS. Mean follow-up was 12 years (range: 3 months to 24 years). Tumour locations were: frontal (3), parieto-occipital (2), parietal (1), temporal (1), occipital (1), thalamic (1), pontocerebellar angle (1), cerebellar tentorium (1), ambient cistern (1). No metastasis was observed. The first-line treatment was surgery in 10 cases, chemotherapy in 2. Resection was total in 6 cases, partial in 6. Central pathology review concluded to: high-grade undifferentiated sarcoma (8), chondrosarcoma (2), fibrosarcoma (1), myxoid desmoplastic tumour (1). Seven tumours were smaller than 5 cm in size. Eleven patients received 2 to 10 courses of chemotherapy (median: 5) but no response was observed. Four out of 6 patients for whom a total resection was performed were still alive at time of study, compared to 2 when only partial resection was possible. Four out of 6 patients who received radiotherapy are still alive, compared to 1 out of 4 patients without radiotherapy. The 5-year Event-Free Survival (EFS) and Overall Survival (OS) rates were 50%. The median EFS in case of total resection was 39 months versus 16 months in case of partial resection. Neither correlation was found between tumour size and location or between age at diagnosis and EFS/OS. Conclusions: We report the first multicentre case series describing clinical, radiological presentation and outcome of PMS in children. In this short series of very rare tumours, age and tumour size did not seem to be prognostic factors. Total resection and radiotherapy seem to be essential. The role of chemotherapy remains unclear.

Surgical management of thymic epithelial tumors in children: lessons from the French Society of Pediatric Oncology and review of the literature.

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. 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. 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. 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.

Characteristics of Children with Non-Hodgkin Lymphoma Associated with Primary Immune Deficiency Diseases: Descriptions of Five Patients

Background: An increased incidence of non-Hodgkin lymphoma (NHL) has been seen in various primary immune deficiency (PID) cases. The present study aimed to evaluate the clinical characteristics and treatment outcomes of five cases with NHL associated with primary immunodeficiency. Methods: We retrospectively evaluated five patients with primary immunodeficiency who developed NHL. Two patients had ataxia-telangiectasia (A-T), one patient had common variable immunodeficiency (CVID), one patient had Bloom's Syndrome, and one patient had Wiskott-Aldrich syndrome (WAS). Results: All patients were male (median age, 8 years). Stage distribution was stage III in three patients and stage IV in two patients. Three patients had B-cell lymphoma and two had T-cell lymphoma. Reduced doses of Berlin–Frankfurt–Münster (BFM) and French Society of Pediatric Oncology (SFOP) regimens were used in four patients according to histopathological subtype. The two patients with ataxia and one patient with Bloom's Syndrome died of progressive/relapsed disease at months 5, 19, and 6, respectively. The patient with CVID associated with T-cell lymphoma has been in remission for 7 years. A full-dosage regimen of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was successfully used in the patient with WAS and B-cell lymphoma; he was still in remission after 3 years. Conclusion: Primary immunodeficiency diseases are one of the strongest known risk factors for the development of NHL. Management of these patients remains problematic. There is a great need to develop new therapeutic approaches in this group. The use of rituximab in combination with CHOP may provide a promising treatment option for B-cell lymphomas associated with immunodeficiency.

Radio-induced Breast Cancers Display Aggressive Pathological Characteristics: A Retrospective Study by The French Pediatric Oncology Society (SFCE)

Radio-induced Breast Cancers Display Aggressive Pathological Characteristics: A Retrospective Study by The French Pediatric Oncology Society (SFCE)

Unusual Virilization in Girls with Juvenile Granulosa Cell Tumors of the Ovary Is Related to Intratumoral Aromatase Deficiency

Background: Hyperandrogenism is a rare symptom of juvenile ovarian granulosa cell- tumors (JGCTO). This study aimed to determine whether hyperandrogenism was related to overexpression of SOX9, decreased expression of FOXL2 or absent aromatase expression in tumor with particular scheme of expression of P450scc and P450c17α. Methods: Through a nationwide study including the French Society of Pediatric Oncology, 6/30 patients with JGCTO presented with clinical hyperandrogenism and high plasma testosterone. Tumor specimens underwent immunofluorescence (SOX9, FOXL2) and immunochemistry (aromatase, P450scc, P450c17α). Results were compared with patients without hyperandrogenism. Results: SOX9 was expressed in the granulosa cell nucleus in 2/6 cases but also in 9/24 tumors without hyperandrogenism (p = n.s.). FOXL2 was absent or decreased in 3/6 cases of JGCTO with hyperandrogenism with no statistical difference from the group without this symptom. In 6/6 patients, the intratumoral expression of aromatase was absent (n = 5) or dramatically reduced (n = 1). In contrast, 15/24 patients without virilization exhibited conserved aromatase expression in their tumor (p < 0.05). A variable number of tumoral cells expressed P450scc while some interstitial cells were focally immunopositive for P450c17α. Conclusion: Unusual virilization in girls with JGCTO is not explained by a dysregulation in SOX9 or FOXL2 expression, but is related to a localized defect of aromatase expression in granulosa cells and to the ability of interstitial cells to produce testosterone.

Shielding in whole brain irradiation in the multileaf collimator era: Dosimetric evaluation of coverage using SFOP guidelines against in-house guidelines

Compare the planning target volume (PTV) coverage in three different shielding techniques in cranial irradiation. Tertiary care center, prospective study. The whole brain and meninges were contoured in ten planning CT scans, and expanded by 5 mm for the PTV. Shielding was designed using the French Society of Pediatric Oncology (SFOP) guidelines (SFOP plan), in-house recommendation (with 1 cm margin from the orbital roof and sphenoid wing) on a igitally Reconstructed Radiograph (DRR) and a third plan was generated using a 3D conformal radiation technique (3DCRT). The coverage of the PTV was noted using the isodose covering 95% of the PTV(D95), minimum dose within the PTV(D min ), and maximum dose within the PTV(D max ). The location of PTV not covered by the 95% isodose curve was noted. The median dose and maximum dose (D max ) to both eyes and maximum dose D max for the lens were noted. General linear model method repeated the measure of analysis of variance test (ANOVA). PTV coverage was significantly poorer in the SFOP and in-house plans as compared to 3DCRT plan (P=0.04). Median volume of PTV not covered by 95% isodose curve was 4.18 cc, 1.01 cc, and 0 cc in SFOP, in-house, and 3DCRT plan, respectively. In the absence of volumetric planning techniques, SFOP guidelines lead to inadequate coverage and the in-house method is recommended.

Bilateral adrenal neuroblastoma

Bilateral adrenal neuroblastoma is extremely rare. To date, 45 cases have been reported in the literature. We retrospectively identified and reviewed 15 cases of bilateral adrenal neuroblastoma, treated between 1988 and 2004, by the French Society of Pediatric Oncology. We then compared our cohort to the 45 cases reported in literature. Median age at diagnosis was 4 months in our cohort whereas it was 3 months in the literature. The same percentage of infants was found in both series (86.6%). Disease had generally been detected due to metastasis-related symptoms. Ten out of 15 patients in our cohort and 18/39 cases in the literature were classified as stage 4S according to the International Neuroblastoma Staging System (INSS). The incidence of stage 4S was significantly higher than that described in other neuroblastoma cohorts (P = 10(-4)). Five-year overall survival was 90% for stage 4S. In our series, bilateral neuroblastoma was neither associated with familial cases nor with any risk factors. The majority of bilateral neuroblastoma carry a favorable prognosis. Exceptional cases exhibiting risk factors, such as amplified MYCN, are comparable to high-risk unilateral neuroblastoma cases with the same poor prognostic features. The therapeutic strategy could be similar to that used against unilateral neuroblastoma, except for surgery. However, the low incidence of relapse and the risk of adrenal failure if radical surgery is performed, argue against an aggressive surgical approach.

Extraosseous Localized Ewing Tumors: Improved Outcome With Anthracyclines—The French Society of Pediatric Oncology and International Society of Pediatric Oncology

To evaluate the outcome of children with an extraosseous Ewing tumor (EOE) according to treatment. Children with EOE were treated either with the strategy used for malignant mesenchymal tumors (MMTs) by the International Society of Pediatric Oncology (SIOP) or with the French Society of Pediatric Oncology (SFOP) regimen used for osseous Ewing tumors (OET). The MMT strategy included vincristine/actinomycin for small and resected tumors or ifosfamide/vincristine/actinomycin for unfavorable sites or unresectable tumors. Surgical excision was to be attempted after four courses, followed by local irradiation in case of residue. Osseous Ewing (OE) protocol included three courses of cyclophosphamide/doxorubicin followed either by two similar courses in case of good response or two courses of ifosfamide/etoposide in case of no response. After resection of the primary, treatment included conventional chemotherapy in case of good histologic response and high-dose chemotherapy and radiotherapy for poor response. All diagnosis specimens were reviewed by the panel. Between 1989 and 1999, 63 patients were registered. Characteristics of patients treated by both protocols were similar. Five-year overall survival (OS) and event-free survival (EFS) of those treated with the OE protocol are 83% and 75%, respectively, which is significantly better than the OS and EFS of those treated with the MMT strategy (59% and 44%, respectively; P = .04 and .008, respectively). The size of the primary and the type of protocol influenced patients' EFS. In multivariate analysis, only the regimen had an impact on OS and EFS. Our study shows that patients with EOE should be treated with OE regimens, probably because of the use of anthracyclines.

Results of the randomized international FAB/LMB96 trial for intermediate risk B-cell non-Hodgkin lymphoma in children and adolescents: it is possible to reduce treatment for the early responding patients

AbstractA previous study (LMB89) of the French Society of Pediatric Oncology for childhood mature B-cell lymphoma (B-NHL) demonstrated a 92% 3-year event-free survival (EFS) for intermediate-risk group B defined as “non-resected” stage I/II and CNS-negative advanced-stage III/IV (70% of cases). We performed the FAB/LMB96 trial to assess the possibility of reducing treatment in children/adolescents with intermediate-risk B-NHL without jeopardizing survival. “Early responding” patients (tumor response > 20% at day 7) were randomized in a factorial design between 4 arms, 2 receiving half-dose of cyclophosphamide in the second induction course with cyclophosphamide, Oncovin (vincristine), prednisone, Adriamycin (doxorubicin), methotrexate (COPADM) and 2 not receiving the maintenance course M1. A total of 657 patients were randomized (May 1996 to June 2001) and 637 were analyzed. The analysis showed no significant effect of any of the treatment reductions on EFS and survival. The 4-year EFS was 93.4% and 90.9% in the groups with full-dose and half-dose of cyclophosphamide (RR = 1.3, P = .40) and 91.9% and 92.5% in the groups with and without M1 (RR = 1.01, P = .98). There was no interaction between the 2 treatment reductions or between each treatment reduction and LDH level or histologic subtypes (Burkitt/Burkitt-like or large B-cell). Children/adolescents with intermediate-risk B-NHL who have an early response and achieve a complete remission after the first consolidation course can be cured with a 4-course treatment with a total dose of only 3.3 g/m2 cyclophosphamide and 120 mg/m2 doxorubicin.

Phase II Trial of Irinotecan in Children With Relapsed or Refractory Rhabdomyosarcoma: A Joint Study of the French Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group

This phase II study was designed to evaluate the efficacy of irinotecan administered intravenously once every 3 weeks in pediatric patients with recurrent or refractory rhabdomyosarcoma. A total of 35 patients younger than age 20 years, with refractory or relapsed rhabdomyosarcoma for which standard treatments have failed, received irinotecan at 600 mg/m2 administered as a 60-minute infusion every 3 weeks. Concomitant treatments included atropine for cholinergic symptoms, loperamide for diarrhea at the first liquid stool, and preventive antiemetic treatment. Tumor response was assessed every two cycles until progression according to WHO criteria. The best overall response rate to irinotecan was 11.4% (95% CI, 3.2 to 26.7%; 2.9% complete responses, 8.5% partial responses) from all patients recruited. The median times to progression and survival were 1.4 and 5.8 months, respectively. A total of 112 cycles were administered, with a median number of two cycles per patient (range, 1 to 16). The most common grade 3/4 toxicities were neutropenia (46%), abdominal pain or cramping (17%), cholinergic syndrome (14%), nausea/vomiting (11%), anemia (11%), thrombocytopenia (9%), and diarrhea (6%). In heavily pretreated children with a high tumor burden who have been treated with multiagent chemotherapy, irinotecan administered intravenously as a single agent, at 600 mg/m2 every 3 weeks, showed an interesting objective response rate and a good tolerance profile in rhabdomyosarcoma.