The feasibility of implementing Toronto childhood cancer stage guidelines and estimating the impact on outcome for childhood cancers in seven pediatric oncology units in sub-Saharan Africa. A study from the Franco-African Pediatric Oncology Group.

BACKGROUND: The improvement of childhood cancer outcome is determined by early diagnosis, effective treatment, supportive care, and adequate medical follow-up. Stage at diagnosis may reflect timeliness of diagnosis, therefore standardized registration of stage is essential for interpretation of regional differences and time trends in survival. Here, we describe the feasibility of implementing the Toronto Childhood Cancer Stage Guidelines (hereafter Toronto Guidelines [TG]) in the hospital-based cancer registry of the Franco-African Pediatric Oncology Group (GFAOP), and assess the impact of TG stage on outcome in pediatric oncology units (POUs) in seven low- and middle-income countries in sub-Saharan Africa (SSA). METHODS: All cancer patients diagnosed before 15 years of age with one of the 15 cancer types defined in TG, resident in one of the participating countries, and attending one of the selected POUs in 2017-2019 were included. Stage was assigned according to TG. Patients were followed-up for vital status for at least 12 months post diagnosis. Survival at 3, 6, and 12 months was calculated using Kaplan-Meier method and compared between POUs and tumor groups using log-rank test. RESULTS: TG stage was assigned to 1772 of 2446 (89%) cases diagnosed with one of 11 cancer types. It was not possible to assign TG stage to acute lymphoblastic leukemia (ALL) and the three types of the central nervous system tumors included in the TG. One-year overall survival (OS) was 58% [95% confidence interval: 55-60] and varied between POUs. Survival declined with increasing stage for four tumor types and was statistically significant for two. CONCLUSION: Except for ALL and brain tumors, we demonstrated feasibility of TG implementation for childhood solid cancers in participating POUs in SSA, and provided a baseline assessment of childhood cancer outcomes against which future stage distribution and survival can be measured as timelines of diagnosis improve over time within the GFAOP network.

The development of an international childhood cancer hospital register database in 13 African countries. A project of the French African Pediatric Oncology Group (GFAOP).

BACKGROUND AND AIM: The establishment of an international hospital-based register (HBR) for the French African Pediatric Oncology Group (GFAOP) was a necessary step in the group's clinical research program. With help from the Sanofi Espoir Foundation's "My Child Matters" program, the GFAOP resolved to develop an international HBR network to collect quality data on children attending the Pediatric Oncology Units (POUs). METHODS: All children entering POUs from January 2016 to December 2018 were registered using an online questionnaire. Data collection included information on diagnosis, disease stage, demographics, socioeconomic status, and outcome. An intensive training program was developed to improve both data quality and quantity. RESULTS: Among the 3348 children registered, 3230 had a suspected cancer, 681 were not confirmed. A diagnosis was confirmed on radiological, clinical, or histological examination for 2549 children including Burkitt lymphoma (516: 20%)-the most frequent diagnosis, Wilms' tumor (459: 18%), retinoblastoma (357: 14%), and acute lymphoblastic leukemia (345: 13%). Of these, 2187 children were treated. Early deaths, abandonment, economic difficulties, and lack of equipment were some of the reasons offered to explain the numbers of undiagnosed and untreated children. Vital status is known for 1994 children: 1187 died and 807 were alive, 551 of these with a follow-up > 12 months. CONCLUSION: This work has provided reliable data on children attending the POUs, especially clarifying reasons and occasions for care rupture. The data will help to identify material, human resources, and staff training needs, to evaluate progress, and to encourage consideration of pediatric cancer in national cancer plans.

Tumor rupture in hepatoblastoma: A high risk factor?

BACKGROUND: Hepatoblastoma tumor rupture is a high-risk criterion in the SIOPEL 3/4 protocol. Little is known about the outcome of these children. METHODS: Radiological signs of possible tumor rupture, defined as peritoneal effusion, peritoneal nodules, or hepatic subcapsular hematoma, were reported in 24 of 150 patients treated for hepatoblastoma in France from January 2000 to December 2014 after central radiological expert review. RESULTS: Twenty-two patients with available clinical data were included (nine PRETEXT-I/II, six PRETEXT-III, seven PRETEXT-IV, and five had lung metastases). Five patients had a subcapsular hematoma only, and 17 patients had intraperitoneal rupture (subcapsular hematoma and peritoneal effusion). A hepatic biopsy was performed in 19 patients. Intraperitoneal rupture occurred before biopsy in 12 and after biopsy in three (including one with prebiopsy subcapsular hematoma) (missing data: two). All patients were treated with chemotherapy, with high-risk regimens including cisplatin or carboplatin and doxorubicin in 19 and cisplatin or carboplatin alone in three. Liver surgery was performed in 20 patients (including three liver transplants). Fifteen patients (68%) achieved complete remission. With a median follow-up of 5.5 years, 11 events occurred (six progressions and three relapses, including three peritoneal progressions/relapses, one surgical complication, and one second cancer) and eight patients died. One of eight patients with no other high-risk criterion had a relapse. The three-year event-free survival and overall survival rates were 49.6% (95% CI = 30-69) and 68.2% (40-84), respectively. CONCLUSIONS: Tumor rupture is predictive of poor prognosis with risk of peritoneal progression/relapse. However, it should not be a contraindication for liver transplantation.

Treatment of Wilms Tumor in Sub-Saharan Africa: Results of the Second French African Pediatric Oncology Group Study.

PURPOSE: Multidisciplinary management of Wilms tumor has been defined through multicenter prospective studies and an average expected patient cure rate of 90%. In sub-Saharan Africa, such studies are uncommon. After the encouraging results of the first Groupe Franco-Africain d'Oncologie Pédiatrique (GFAOP) study, we report the results of the GFAOP-NEPHRO-02 study using an adaptation of the International Society of Paediatric Oncology 2001 protocol. PATIENTS AND METHODS: From April 1, 2005, to March 31, 2011, seven African units participated in a nonrandomized prospective study. All patients who were referred with a clinical and radiologic diagnosis of renal tumor were screened. Those older than age 6 months and younger than 18 years with a unilateral tumor previously untreated were pre-included and received preoperative chemotherapy. Patients with unfavorable histology or with a tumor other than Wilms, or with a nonresponding stage IV tumor were excluded secondarily. RESULTS: Three hundred thirteen patients were initially screened. Two hundred fifty-seven patients were pre-included and 169 with histologic confirmation of intermediate-risk nephroblastoma were registered in the study and administered postoperative treatment. Thirty-one percent of patients were classified as stage I, 38% stage II, 24% stage III, and 7% stage IV. Radiotherapy was not available for any stage III patients. Three-year overall survival rate was 72% for all study patients and 73% for those with localized disease. CONCLUSION: It was possible to conduct sub-Saharan African multicenter therapeutic studies within the framework of GFAOP. Survival results were satisfactory. Improvements in procedure, data collection, and outcome are expected in a new study. Radiotherapy is needed to reduce the relapse rate in patients with stage III disease.

Treatment of nephroblastoma in Africa: results of the first French African pediatric oncology group (GFAOP) study.

BACKGROUND: The multidisciplinary management of nephroblastoma has been defined through multicentric prospective studies and an average 90% of patients cured expected. In Africa, such studies are uncommon and results are fragmentary or unknown in most of the countries. We report the results of the GFAOPNEPHRO 01 study using SIOP 2001 protocol approach. PROCEDURE: From April 1, 2001 to March 31, 2004, 8 African Pilot Units were selected to participate in a nonrandomized prospective study. All patients referred with a clinical and radiological diagnosis of nephroblastoma were registered, those aged over 6 months and less than 18 years with a unilateral tumor not previously treated were included in this study and received preoperative chemotherapy. Patients with unfavorable histology or with a tumor other than Wilms tumor, and those with stage IV tumor and persistent disease after surgery were secondarily excluded. RESULTS: Of the 229 patients initially registered, 166 were included and finally 133 retained in the study, after surgery. Tumor rupture occurred in 7.5% of the patients. Thirty-five percent were stage I, 22% stage II, 23% stage III, and 18% stage IV. Two-year disease-free survival and 5-year survival are, respectively: 77.9% and 76.7% for localized tumors, 72.7% and 71.6% for all study patients. CONCLUSIONS: It is possible to conduct African multicentric therapeutic studies within the framework of GFAOP. Results in terms of event-free survival and survival are satisfactory. Improvements with respect to procedure, data collection, and outcome are expected in a new study.