Integrating a palliative approach into the healthcare provided by the French-African Pediatric Oncology Group's pilot units. Insights from a 3-year training program.

Working alongside local stakeholders, members of the French-African Pediatric Oncology Group developed a 3-year program to train pediatric oncology teams from 15 French-speaking countries in Africa in using analgesics and providing palliative care. This program was rolled out in three phases: initial training, in situ assessment, and advanced training in selected topics. To access this program, multidisciplinary teams had to come up with a project to improve their existing palliative care and pain management practices, and commit themselves to implementing it. All the teams invited agreed to take part in the program, which explicitly broached a subject that is often avoided in oncology teaching. The first phase was rolled out in 2017, with 65 trainees from 19 units attending one of three sessions held in Dakar, Senegal, Abidjan, Côte d'Ivoire, and Rabat, Morocco. The subsequent assessment revealed that only half the teams had started to implement their projects. The advanced training phase was therefore adjusted accordingly. A collective training session held in Marseille was attended by 15 trainees from seven teams whose projects were already underway, while in situ mentoring was provided for six other teams, through French-African twinnings in four cases. The length and openness of the program meant that we were able to identify and share the units' diverse realities, and fine-tune their projects accordingly, as well as plan ways of continuing the training both locally and collectively.

[Hodgkin disease and autoimmunity in children: 11 case reports]. / Maladie de Hodgkin et auto-immunité chez l'enfant : à propos de 11 observations.

The association of lymphoma and autoimmune manifestations has been predominantly studied in adults affected by non-Hodgkin lymphoma. Few publications exist in the literature concerning Hodgkin lymphoma, particularly in children and adolescents. The objectives of this study were to define the characteristics of the link between Hodgkin disease and autoimmunity in childhood. The present 25-year retrospective study was conducted in all centers affiliated with the French Society of Paediatric Oncology (SFCE). Eleven children with Hodgkin disease presented manifestations of disimmunity preceding or following their diagnosis. Four patients had thrombocytopenic purpura, the remaining 7 each had a different autoimmune pathology: lupus syndrome, antiphospholipid syndrome with transient ischemic attack, Evans syndrome, leukocytoclastic vasculitis, autoimmune hemolytic anemia, autoimmune thyroiditis, and juvenile idiopathic arthritis. Lymphoma relapse occurred in 3 patients. Two children died, death being directly attributed to the autoimmune disease in 1 case. Our data suggest that development of autoimmunity is related to significant morbidity. Possible pathophysiological mechanisms include lymphocyte proliferation secondary to chronic inflammation, cell-mediated immune deficiency in Hodgkin disease, molecular mimetics, and antineoplastic phenomena are discussed. A study with a larger patient population is needed to identify the group of children at high risk of autoimmunity for whom additional investigations and modified therapy may be indicated.

Two congenital cases of pigmented epithelioid melanocytoma studied by fluorescent in situ hybridization for melanocytic tumors: case reports and review of these recent topics.

The term 'pigmented epithelioid melanocytoma' (PEM) has recently been proposed as a nosological framework grouping lesions formerly known as animal-type melanomas, sporadic epithelioid blue nevi and Carney complex-associated epithelioid blue nevi. Congenital PEMs have been reported extremely rarely and their prognosis is poorly known. Four-color fluorescent in situ hybridization (FISH) for melanocytic lesions is a recent method developed to assess the malignant potential of ambiguous melanocytic lesions. Here we describe 2 cases of congenital epithelioid and strongly pigmented melanocytic lesions consistent with PEM. No BRAF gene mutation was found in the 2 cases. FISH for melanocytic lesions was also performed. The first case proved entirely negative, whereas the second one showed a positive zone with an extra copy of chromosome 6. The prognosis and management of PEM are discussed, with a review of the available data on the history, demographics, molecular alterations and histopathological aspects of this entity. PEM seems to represent a unique low-grade melanocytic tumor with a limited potential of metastasis to lymph nodes, but a favorable long-term clinical course. The published data about FISH for melanocytic tumors, and especially PEM, are reviewed. Four-color FISH may be a useful tool to assess more accurately the prognosis of these tumors.

Treatment of high risk medulloblastomas in children above the age of 3 years: a SFOP study.

AIM: Improvement of EFS of children older than 3 years with high risk medulloblastoma. METHODS: Between 1993 and 1999, 115 patients (3-18 years, mean 8 years) with high risk medulloblastoma were included. After surgery treatment consisted of chemotherapy ('8in1' and etoposide/carboplatin) before and after craniospinal radiotherapy. RESULTS: Patients were staged using Chang-criteria (PF residue only, M1 and M2/M3) by local investigator as well as by central review panel (82.4% concordance). Chemotherapy was well tolerated without major delays in radiotherapy. With a mean follow up of 81 months (9-119), 5-year EFS was 49.8% and OS 60.1%. In detail according to subgroups EFS was 68.8% for PF residue only, 58.8% for M1 disease and 43.1% for M2/M3. CONCLUSION: M1 patients are legitimate high risk patients. Survival rates are still very low for high risk medulloblastoma patients and future trials should therefore focus on more intensive (chemotherapy/radiotherapy) treatment.

Standard-risk medulloblastoma treated by adjuvant chemotherapy followed by reduced-dose craniospinal radiation therapy: a French Society of Pediatric Oncology Study.

OBJECTIVE: The primary objective of this study was to decrease the late effects of prophylactic radiation without reducing survival in standard-risk childhood medulloblastoma. PATIENTS AND METHODS: Inclusion criteria were as follows: children between the ages of 3 and 18 years with total or subtotal tumor resection, no metastasis, and negative postoperative lumbar puncture CSF cytology. Two courses of eight drugs in 1 day followed by two courses of etoposide plus carboplatin (500 and 800 mg/m(2) per course, respectively) were administered after surgery. Radiation therapy had to begin 90 days after surgery. Delivered doses were 55 Gy to the posterior fossa and 25 Gy to the brain and spinal canal. RESULTS: Between November 1991 and June 1998, 136 patients (median age, 8 years; median follow-up, 6.5 years) were included. The overall survival rate and 5-year recurrence-free survival rate were 73.8% +/- 7.6% and 64.8% +/- 8.1%, respectively. Radiologic review showed that 4% of patients were wrongly included. Review of radiotherapy technical files demonstrated a correlation between the presence of a major protocol deviation and treatment failure. The 5-year recurrence-free survival rate of patients included in this study with all optimal quality controls of histology, radiology, and radiotherapy was 71.8% +/- 10.5%. In terms of sequelae, 31% of patients required growth hormone replacement therapy and 25% required special schooling. CONCLUSION: Reduced-dose craniospinal radiation therapy can be proposed in standard-risk medulloblastoma provided staging and radiation therapy are performed under optimal conditions.

Long-term renal and hearing toxicity of carboplatin in infants treated for localized and unresectable neuroblastoma: results of the SFOP NBL90 study.

BACKGROUND: A secondary end point of the NBL90 protocol (Rubie H et al. Pediatr Oncol 2001;36:247-250) was the concern in this infant population for possible carboplatin-(CBDCA) induced late side effects including impaired renal and hearing functions. PROCEDURE: Glomerular filtration rate (GFR), tubular function (TF), pure tone audiometry (PTA), high-frequency, and transient evoked-otoacoustic emission were prospectively assessed in 30 children alive and disease-free 6 years after the end of the treatment. RESULTS: Median age at diagnosis and at assessment was 4.7 months and 7 years, respectively. Blood pressure was < or =97.5 centile in all children. The mean estimated GFR was 114 +/- 13 ml/min/1.73 m(2) by Schwartz formula [range 87-145]. TF assessment failed to demonstrate any impairment. 29/30 children had grade 0 ototoxicity and all transient evoked otoacoustic emission were normal. CONCLUSIONS: With a 6-year follow-up the combination of VP16 and carboplatin given at conventional doses is safe on renal and hearing functions in infants with unresectable neuroblastomas treated according to SFOP NB90.

[Bronchial erosion of mediastinal lymphadenopathy associates with Hodgkin's disease]. / Fistulisation d'adénopathies médiastinales dans les bronches en rapport avec une maladie de Hodgkin.

INTRODUCTION: Erosion of mediastinal adenopathy into the bronchial tree is classically associated with tuberculosis. We describe two cases of of such bronchial erosion with Hodgkin's disease. CASE REPORT: The first case was of a seventy-year old man with a history of pulmonary silicosis. A sub-carenal mass was identified during investigation of chronic cough. The bronchoscopy revealed an inflammatory stenosis due to Hodgkin's disease. The second case was of a thirteen-year old child whose Hodgkin's disease was thought to be in remission following treatment. The erosion of mediastinal adenopathy into the main left bronchus produced complete left pulmonary atalectasis, which required endobronchial stenting. CONCLUSIONS: In both cases, rigid bronchoscopy provided a histological diagnosis with diagnosis of Hodgkin's disease in the first case, and identification of recurrence in the other one. These cases are unusual. Such complications are usually complications of radiotherapy. Classically, erosion of mediastinal adenopathy into the bronchial tree is tuberculous in origin but they can be neoplasic.

Lymphocyte-predominant Hodgkin's lymphoma in children: therapeutic abstention after initial lymph node resection--a Study of the French Society of Pediatric Oncology.

PURPOSE: To clarify treatment strategy for lymphocyte-predominant Hodgkin's lymphoma (LPHL), the French Society of Pediatric Oncology initiated a prospective, nonrandomized study in 1988. Patients received either standard treatment for Hodgkin's lymphoma or were not treated beyond initial adenectomy. PATIENTS AND METHODS: From 1988 to 1998, 27 patients were available for study. Twenty-four patients were male, and median age was 10 years (range, 4 to 16 years). Twenty-two, two, and three patients had stage I, II, and III disease, respectively. Thirteen patients (stage I, n = 11; stage III, n = 2) received no further treatment after initial surgical adenectomy (SA). Fourteen patients received combined treatment (CT; n = 10), involved-field radiotherapy alone (n = 1), or chemotherapy alone (n = 3). The two groups were comparable for clinical status, treatment, and follow-up. RESULTS: Twenty-three of 27 patients achieved complete remission (CR). With a median follow-up time of 70 months (range, 32 to 214 months), overall survival to date is 100%, and overall event-free survival (EFS) is 69% +/- 10% (SA, 42% +/- 16%; CT, 90% +/- 8.6%; P <.04). If we considered only the patients in CR after initial surgery (n = 12), EFS was no longer significantly different between the two groups. Patients with residual mass after initial surgery (n = 15) had worse EFS if they did not receive complementary treatment (P <.05). CONCLUSION: Although based on a small number of patients, our study showed that (1). no further therapy is a valid therapeutic approach in LPHL patient in CR after initial lymph node resection, and (2). complementary treatment diminishes relapse frequency but has no impact on survival.

Postoperative chemotherapy without irradiation for ependymoma in children under 5 years of age: a multicenter trial of the French Society of Pediatric Oncology.

PURPOSE: To evaluate a strategy that avoids radiotherapy in first-line treatment in children under 5 years of age with brain or posterior fossa ependymoma, by exclusively administering 16 months of adjuvant multiagent chemotherapy after surgery. PATIENTS AND METHODS: Between June 1990 and October 1998, 73 children with ependymoma (82% with high-grade tumors) were enrolled onto this multicenter trial. Children received adjuvant conventional chemotherapy after surgery consisting of seven cycles of three courses alternating two drugs at each course (procarbazine and carboplatin, etoposide and cisplatin, vincristine and cyclophosphamide) over a year and a half. Systematic irradiation was not envisaged at the end of chemotherapy. In the event of relapse or progression, salvage treatment consisted of a second surgical procedure followed by local irradiation with or without second-line chemotherapy. RESULTS: Conventional chemotherapy was well tolerated and could be administered in outpatient clinics. No radiologically documented response to chemotherapy more than 50% was observed. With a median follow-up of 4.7 years (range, 5 months to 8 years), the 4-year progression-free survival rate in this series was 22% (95% confidence interval [CI], 13% to 43%) and the overall survival rate was 59% (95% CI, 47% to 71%). Overall, 40% (95% CI, 29% to 51%) of the patients were alive having never received radiotherapy 2 years after the initiation of chemotherapy and 23% (95% CI, 14% to 35%) were still alive at 4 years without recourse to this modality. In the multivariate analysis, the two factors associated with a favorable outcome were a supratentorial tumor location (P =.0004) and complete surgery (P =.0009). Overall survival at 4 years was 74% (95% CI, 59% to 86%) for the patients in whom resection was radiologically complete and 35% (95% CI, 18% to 56%) for the patients with incomplete resection. CONCLUSION: A significant proportion of children with ependymoma can avoid radiotherapy with prolonged adjuvant chemotherapy. Deferring irradiation at the time of relapse did not compromise overall survival of the entire patient population.

[Expanding mature pineal teratoma syndrome. Case report]. / Tératome mature évolutif pinéal. A propos d'un cas.

We present a case of growing teratoma syndrome of the pineal region. To our knowledge, this is the fourth case reported in the literature. A 13-year-old boy was referred for intracranial hypertension and bilateral papillary edema. CT scan showed a pineal region tumor with obstructive hydrocephalus. After CSF (cerebrospinal fluid) shunting, MRI showed that the tumor had a heterogenous signal enhancement. The tumor marker HCG (human chorionic gonadotrophin) was elevated in CSF and serum. After three cycles of chemotherapy, MRI showed an important increase in tumor size with morphologic modifications. However, HCG in CSF and serum returned to normal. Surgical resection was performed and histological examination of the whole specimen showed mature teratoma. On postoperative MRI, there was a small area of signal enhancement of the left thalamus. Radiotherapy was given. The child was in complete remission 15 months after the diagnosis. Growing teratoma syndrome is a mixed germ cell tumor with a secreting portion that responds to chemotherapy and a non secreting portion of mature teratoma that continues to grow under chemotherapy. The treatment should include chemotherapy for the malignant secreting portion and surgery for the mature teratoma.

Prognostic factors in children with localized malignant nonseminomatous germ cell tumors.

PURPOSE: Prognostic factors were studied in children older than 1 year who were treated with chemotherapy for extracranial localized malignant non seminomatous germ cell tumors. PATIENTS AND METHODS: Data from two consecutive protocols were pooled. The TGM 85 (1985-1989) protocol consisted of alternating courses of cyclophosphamide, dactinomycin and vinblastine, bleomycin, and cisplatin at a dose of 100 mg/m(2) per course. The TGM 90 (1990-1994) protocol was initiated with carboplatin 400 mg/m(2) substituted for cisplatin as the only modification to the previous protocol. RESULTS: We examined alpha-fetoprotein (AFP) levels, disease stage, and primary site and identified three prognostic groups. Patients with a poor prognosis had either an AFP level >/= 10,000 ng/mL or stage III disease and a sacrococcygeal or mediastinal primary site; such patients represented 46% of the patient population and experienced a 43% 3-year failure-free survival rate and a 77% overall survival rate. Patients with a good prognosis had an AFP level less than 10,000 ng/mL, stage I or II disease, and a testicular, ovarian, perineal, or retroperitoneal primary site; such patients represented 22% of the patient population and experienced no treatment failures. The other patients were classified in the intermediate prognosis group and represented 37% of the patient population, with an 81% 3-year failure-free survival rate and a 92% overall survival rate. CONCLUSION: Initial AFP level, disease stage, and primary site are the most important prognostic factors in this analysis. Prognostic models for pediatric germ cell tumors should allow the stratification of patients for a risk-adapted approach to treatment.

Combined treatment modality for intracranial germinomas: results of a multicentre SFOP experience. Société Française d'Oncologie Pédiatrique.

Conventional therapy for intracranial germinomas is craniospinal irradiation. In 1990, the Société Française d'Oncologie Pédiatrique initiated a study combining chemotherapy (alternating courses of etoposide-carboplatin and etoposide-ifosfamide for a recommended total of four courses) with 40 Gy local irradiation for patients with localized germinomas. Metastatic patients were allocated to receive low-dose craniospinal radiotherapy. Fifty-seven patients were enrolled between 1990 and 1996. Forty-seven had biopsy-proven germinoma. Biopsy was not performed in ten patients (four had diagnostic tumour markers and in six the neurosurgeon felt biopsy was contraindicated). Fifty-one patients had localized disease, and six leptomeningeal dissemination. Seven patients had bifocal tumour. All but one patient received at least four courses of chemotherapy. Toxicity was mainly haematological. Patients with diabetus insipidus (n = 25) commonly developed electrolyte disturbances during chemotherapy. No patient developed tumour progression during chemotherapy. Fifty patients received local radiotherapy with a median dose of 40 Gy to the initial tumour volume. Six metastatic patients, and one patient with localized disease who stopped chemotherapy due to severe toxicity, received craniospinal radiotherapy. The median follow-up for the group was 42 months. Four patients relapsed 9, 10, 38 and 57 months after diagnosis. Three achieved second complete remission following salvage treatment with chemotherapy alone or chemo-radiotherapy. The estimated 3-year survival probability is 98% (CI: 86.6-99.7%) and the estimated 3-year event-free survival is 96.4% (CI: 86.2-99.1%). This study shows that excellent survival rates can be achieved by combining chemotherapy and local radiotherapy in patients with non-metastatic intracranial germinomas.

Cross-cultural adaptation of a health status classification system in children with cancer. First results of the French adaptation of the Health Utilities Index Marks 2 and 3.

Our objective was to adapt and validate the Health Utilities Index Mark 2 (HUI 2) and HUI 3 health status classification systems self-report questionnaire in a population of children with cancer, a group of 42 children already included in a multi-centre database designed by the Group on Brain Tumors in Children of the French Society for Pediatric Oncology. Children were recruited during a routine consultation. Most of them had completed treatment. The version of the questionnaire for French adults was adapted linguistically for children. Open-ended queries by children about the comprehensiveness of the questions and very low non-response rates showed a good acceptability of the questionnaire. The main psychometric properties of the HUI 2 and HUI 3 classification systems were assessed in 3 groups of raters (child, parent, physician): construct validity was tested against the rating of the child's health state on a Likert scale and through comparison with clinical data, and internal consistency was determined through multi-trait analysis. Weighted and unweighted kappa values were used to measure the inter-rater agreement between the child's, parent's and physician's assessment of the child's health state. The convergent validity was satisfactory, with better results when the physician's assessment was used. The most affected attributes were the expected ones (i.e., cognition, pain and emotion). Disagreement was observed between the 3 raters, more often in the same direction: taking the child's assessment as the reference, the parents tended to under-estimate the health status while physicians tended to over-estimate it.

[Malignant melanoma in a 7-year-old child. A report of a dramatic case]. / Mélanome malin chez une enfant de 7 ans. A propos d'un cas dramatique.

Malignant melanoma developed on the scalp at the site of a congenital nevus in a 7-year-old girl. At birth, simple observation was proposed, despite the recognized desirable but non-urgent indication for excision, in order to avoid subjecting the infant to general anesthesia. At the first sign of a change in the macroscopic appearance of the nevus, surgical resection was performed, but the short-term outcome was fatal.... This case focuses our attention on malignant progression of even small congenital nevi and emphasizes the need for early preventive and systematic resection even when the patient's age of the patient requires general anesthesia.

[Langerhans cell granulomatosis of the orbit. Apropos of an anatomo-clinical case]. / Granulomatose à cellules de Langerhans monotissulaire de l'orbite. A propos d'une observation anatomo-clinique.

Langerhans' cell granulomatosis of the orbit was observed in a 7-year-old boy successfully treated by a simple biopsy. Recovery can be established one year after the biopsy on the basis of bone defect healing on the standard X-ray of the skull.

[Orbital rhabdomyosarcoma in children. Apropos of 2 cases]. / Rhabdomyosarcome orbitaire de l'enfant. A propos de 2 observations.

Rhabdomyosarcoma accounts for 5% of childhood malignant tumours; in 10% it occurs in the orbit where it is the most frequent malignant tumour. Rhabdomyosarcoma is a mesenchymatous tumour with striated muscular differentiation. However, this myogenous differentiation is sometimes undiscernable on standard histological examination and requires immunohistochemical and ultrastructural studies to be shown. Treatment depends on the assessment of local extension, principally based on tomodensitometry. When the tumour is limited to the orbit, survival rate may reach 100% with todays therapeutic protocols. When the orbital walls are invaded the tumour is parameningeal and recovery can only be achieved by increasing chemotherapy at the cost of long-term side effects. Hence, this tumour must be diagnosed and treated very early. The authors report two cases of rhabdomyosarcoma dealing with the two main histological forms of the tumour and with their evolutive risks.

[Rapid diagnosis of tuberculous meningitis by polymerase chain reaction. A case in an infant]. / Diagnostic rapide de la méningite tuberculeuse par polymerase chain reaction. Une observation chez un nourrisson.

A fifteen-month-old child was admitted with a week history of isolated fever. On CSF (Cerebral Spinal Fluid) examination, hyperproteinorachy, hyperglycorachy and hypochlorurachy were found. The diagnosis of tuberculosis meningitis was suspected but usual tests were unable to find Mycobacterium tuberculosis in CSF, urine and sputum. Only the Polymerase Chain Reaction detected the Mycobacterium tuberculosis genome in the CSF. A specific treatment was started immediately. Apyrexia was obtained within 2 days; the outcome was favorable, without sequelae.

Cerebral non-Hodgkin's lymphoma discovered when treating Hodgkin's disease.

Case report of the appearance of a highly malignant cerebral non-Hodgkin's lymphoma of a diffuse large cell type, type B, occurring at the immediate onset of chemotherapy for a stage IV (mediastino-pulmonary) Hodgkin's disease (nodular sclerosis) diagnosed in a 16-year-old boy. The treatment of this cerebral lymphoma associated primary chemotherapy with high dose methotrexate, high dose aracytine, etoposide, and ifosfamide. The chemotherapy proved to be highly efficient, producing complete remission. Thoracic and abdominal irradiation for Hodgkin's disease was performed concomitantly with chemotherapy for the non-Hodgkin's lymphoma. This treatment was followed by 36 Gy of cerebral irradiation. Thirty-six months after the discovery of the cerebral non-Hodgkin's lymphoma the patient was still disease-free and doing well.

[Orbital and muscular relapse of Burkitt's lymphoma]. / Rechute orbitaire et musculaire d'un lymphome de Burkitt.

We report the case of a child presenting with abdominal Burkitt's lymphoma in whom a relapse presented as orbital and muscle involvement. This clinical feature is extremely rare. Two muscle and one orbital biopsies were necessary to obtain proper diagnosis. A new extension check-up showed bone marrow invasion and normal cerebrospinal fluid. This relapse was successfully treated by conventional chemotherapy and consolidated with high-dose chemotherapy, total body irradiation and autologous bone marrow transplantation. Eighteen months after transplantation, the child may be considered as definitively cured.