Relapsed Wilms' tumor in pediatric patients: challenges in low- to middle-income countries-a single-center experience.

BACKGROUND: Wilms' tumor (WT) affects one in 10,000 children and accounts for 5% of all childhood cancers. Although the overall relapse rate for children with WT has decreased to less than 15 %, the overall survival for patients with recurrent disease remains poor at approximately 50 %. The aim of the study to evaluate the outcome of relapsed Wilms' tumor pediatric patients treated at the National Cancer Institute (NCI), Egypt, between January 2008 and December 2015. RESULTS: One hundred thirty (130) patients diagnosed with WT during the study period, thirty (23%) patients had relapsed. The median follow up period was 22.3 months (range 3.6-140 months). The Overall Survival (OS) was 30.9% while the event-free survival (EFS) was 29.8% at a 5-year follow up period. Median time from diagnosis to relapse was 14.4 months. A second complete remission was attained in 18/30 patients (60%). The outcome of the 30 patients; 11 are alive and 19 had died. Three factors in our univariate analysis were prognostically significant for survival after relapse. The first was radiotherapy given after relapse (p = 0.012). The 5-year EFS and OS for the group that received radiotherapy were 41.9% versus 16.7% and 11.1% respectively for those that did not. The second was the state of lymph nodes among patients with local stage III (p = 0.004). Lastly, when risk stratification has been applied retrospectively on our study group, it proved to be statistically significant (p = 0.029). CONCLUSION: Among relapsed pediatric WT, radiotherapy improved survival at the time of relapse and local stage III with positive lymph nodes had the worst survival among other stage III patients.

Global Disparities in Wilms Tumor.

BACKGROUND: Wilms tumor accounts for more than 90% of all malignant kidney neoplasms in children. Survival after diagnosis and treatment is excellent in most high-income countries. Low- and middle-income countries (LMICs) continue to struggle with Wilms tumor detection and treatment. The purpose of this study was to compare the global incidence and outcomes of Wilms tumor. MATERIAL AND METHODS: Wilms tumor incidence data from the World Health Organization (WHO), International Incidence of Childhood Cancer, Volume III, was analyzed according to world region and country socioeconomic status using descriptive statistics and independent-sample Kruskal-Wallis Test. A literature review was also performed to assess outcomes and identify common themes. RESULTS: Wilms tumor was most common in children aged 0-4 y (median incidence 15.1 [IQR 11.8-18.7] ASR/million). High-income countries reported significantly higher median incidence than middle-income countries (8.6 [7.4-9.3] versus 6.1 [4.9-8.7] ASR/million; P < 0.01), although low-income countries reported the highest median incidence overall (9.8 [6.2-16.4] ASR/million). Low-income countries had the fewest countries with registries (n = 6). Overall survival ranged from 70% to 97% in high-income countries, 61%-94% in upper-middle-income countries, 0%-85% in lower-middle-income countries, and 25%-53% in low-income countries. Delay in diagnosis, lack of available treatment, and inadequate follow up contributed to the large variations in outcomes. CONCLUSIONS: Reported Wilms tumor incidence is highest in low-income countries, and these are also the countries that have the lowest survival. Lack of significance may reflect incomplete and absent data reporting from lower income countries. Accurate and comprehensive registries are the first steps to appropriate resource allocation in order to improve outcomes for this highly curable childhood malignancy.

Continuing barriers to care of Wilms tumor in a low-income country.

BACKGROUND/OBJECTIVE: This study evaluates the outcome of Wilms tumor (WT) following introduction of multidisciplinary team management and patient treatment stratification by tumor histology in two referral centers in southeastern Nigeria. METHODS: We analyzed histologically confirmed WT cases managed from January 2008 to June 2017. RESULTS: There were 45 patients, peak age incidence of 2 to 5 years who presented after mean symptom duration of 4.9 months (range, 1-12 months), with mean tumor weight of 1040 g (range, 350-4200 g). Overall, 14 (31.1%) had unfavorable histology of WT. A total of 22 (48.9%) patients received preoperative chemotherapy, 43 (95.6%) received postoperative chemotherapy based on stage of disease and histopathology, but none received adequate radiotherapy. Of these, 19 (44.2%) patients complied with chemotherapy regimen, 15 (33.3%) were lost to follow-up and 12 (26.7%) cases relapsed. With 30 cases available for evaluation and mean follow-up duration of 23 months (range, 6-80 months), the overall 5-year survival is 53.3% (16 cases). Survival in children who complied with postoperative chemotherapy was 73.7%, and abandonment-sensitive survival was 35.6%. Persisting challenges were late presentation, poor compliance to treatment, and lack of radiotherapy treatment. CONCLUSION: Multidisciplinary team management and chemotherapy based on tumor histology might have resulted in slight improvement of outcome since our last report. However, to ensure survival that may approach global benchmarks, there is need for public health measures to improve time to diagnosis, and improvement of facilities and healthcare funding to ensure compliance to all phases of standard therapy.

Cost of Treating Pediatric Cancer at the Butaro Cancer Center of Excellence in Rwanda.

PURPOSE: Improvements in childhood survival rates have been achieved in low- and middle- income countries that have made a commitment to improve access to cancer care. Accurate data on the costs of delivering cancer treatment in these settings will allow ministries of health and donors to accurately assess and plan for expansions of access to care. This study assessed the financial cost of treating two common pediatric cancers, nephroblastoma and Hodgkin lymphoma, at the Butaro Cancer Center of Excellence in rural Rwanda. METHODS: A microcosting approach was used to calculate the per-patient cost for Hodgkin lymphoma and nephroblastoma diagnosis and treatment. Costs were analyzed retrospectively from the provider perspective for the 2014 fiscal year. The cost per patient was determined using an idealized patient receiving a full course of treatment, follow-up, and recommended social support in accordance with the national treatment protocol for each cancer. RESULTS: The cost for a full course of treatment, follow-up, and social support was determined to be between $1,490 and $2,093 for a patient with nephroblastoma and between $1,140 and $1,793 for a pediatric patient with Hodgkin lymphoma. CONCLUSION: Task shifting, reduced labor costs, and locally adapted protocols contributed to significantly lower costs than those seen in middle- or high-income countries.

Is there a socioeconomic variation in survival from renal tumours in children and young people resident in northern England (1968-2012)?

BACKGROUND: Despite strong evidence of a social gradient in cancer survival among UK adults, studies in children and young people remain inconclusive and have not included renal tumours. This study investigated the relationship between socioeconomic status and survival from renal tumours among children and young people. PROCEDURE: Kaplan-Meier estimation and Cox regression were used to analyse survival for all 209 renal tumours in children and young people (0-24 years) diagnosed 1968-2012 and registered by a specialist population-based registry. Sociodemographic and clinicopathologic variables, including paternal occupation at birth, were also analysed. RESULTS: No significant disparity in overall renal tumour and Wilms tumour (WT) survival was observed according to paternal social class [p=0.988 and 0.808, respectively]. The strongest predictor of survival was stage, with late stage (III-IV) disease having a 4-fold higher risk of death compared to early stage (I-II) disease [p<0.001]. Similarly, high mortality-risk was seen for late stage WT in children aged 0-14 years (Hazard Ratio=6.37; 95% CI=2.60-15.59). CONCLUSIONS: This study did not detect a significant social gradient in renal tumour survival. The identification of tumour stage as a strong predictor of survival irrespective of age, necessitates the development of appropriate public health interventions that target early diagnosis and treatment.

Treating childhood cancer in Rwanda: the nephroblastoma example.

INTRODUCTION: Wilms tumor (WT) or nephroblastoma is the commonest childhood cancer in Rwanda. Nephroblastoma is regarded as one of the successes of pediatric oncology with long-term survival approaching 90%. The Objectives to evaluate the feasibility of treating childhood cancer using the nephroblastoma example and to calculate its cost of treatment in Rwanda. METHODS: Prospective study over a 2 year period: 01 Jan 2010- 31 December 2011. A questionnaire was completed by all participants in the study and the following variables were collected at Kigali University Teaching Hospital: age at diagnosis, gender, transport cost, cost of investigations, staging, treatment and outcome, cost of hospitalization, type of medical, surgical, radiological interventions and their costs, number of admissions per patient and factors related to non compliance to treatment. All patients had a confirmed diagnosis on histopathology examination. The cost for treatment was calculated for early and late stage and was expressed in USA dollars. Analysis was done with SPSS 16.0. RESULTS: There were 25 patients diagnosed and treated for WT during the study period. Almost half of the patients 14/25 (56%) had advanced disease, seven children (28%) had stage IV, seven children stage III, six patients (24%) with stage II, while the remaining five (20%) had stage I with high risk tumor. The direct cost of management ranged from1,831.2 USD for early disease to 2,418.7 USD for advanced disease. The cost of transport, investigations and drugs were recorded as main contributing factors to the feasibility and cost of the treatment in 80% of the responses, followed by late presentation (56%) and poor compliance to treatment. CONCLUSION: Most challenges are related to unaffordable treatment and late presentation. The management of WT is feasible in Rwandan setting but efforts should be made in order to improve awareness of childhood cancer, early diagnosis and access to care. The government of Rwanda is committed to improve cancer care in the country and organized the first pediatric international oncology conference in Kigali, in March 2012 to develop National protocols for the top five most common cancers in children.

The Collaborative Wilms Tumour Africa Project; baseline evaluation of Wilms tumour treatment and outcome in eight institutes in sub-Saharan Africa.

AIM: Reported survival of Wilms tumour in sub-Saharan Africa is below 50%. A published International Society of Pediatric Oncology (SIOP) Pediatric Oncology in Developing Countries (PODC) consensus adapted treatment guideline is implemented as a multi-centre prospective clinical trial at eight centres in sub-Saharan Africa. A baseline evaluation has been done to help decide on priorities to improve outcome and to assess improvements over time. METHODS: A retrospective chart review was performed of patients admitted with Wilms tumour in the three years (2011-2013) preceding the collaborative trial. Patient outcome at the end of treatment was documented for all patients diagnosed in 2011 and 2012. Outcome was classified as (1) alive, no evidence of disease; (2) alive with disease; (3) died during treatment and (4) incomplete treatment. Details on treatment facilities, staff and estimated cost of treatment are documented. RESULTS: Every year 114-130 patients are diagnosed. The mean survival at end of treatment is 39% (69/176) ranging from 11% to 61%. Incomplete treatment is the most common cause of treatment failure with 31% (54/176), ranging from 14% to 48% between centres. Twenty-six percent (46/176) of patients died during treatment, ranging from 13% to 37%. Estimated cost of treatment for parents ranged from 100 US$ to 1100 US$ and was considered an important cause of failure to complete treatment. CONCLUSION: Overall two year survival is estimated at 25%. Prevention of incomplete treatment is possible and will positively affect outcome. Sharing similar local challenges in this regional collaborative project helps to identify and implement feasible, sustainable and successful strategies.

Children treated with metronomic chemotherapy in a low-income country: METRO-MALI-01.

BACKGROUND: Metronomic chemotherapy (MC) is defined as the frequent administration of chemotherapy at doses below the maximal tolerated dose and with no prolonged drug-free break. As off-patent chemotherapeutic drugs can be used and given the low toxicity profile of this approach, MC seems to be well adapted to low-income countries. OBJECTIVE: The aim of this study was to assess the efficacy and safety of a vincristine/cyclophosphamide/methotrexate MC regimen given to children with refractory cancer of various tumor types. METHODS: This prospective, pilot, single-center study evaluated the use of MC with a first cycle consisting of weekly vincristine (1.5 mg/m) on days 1, 8, 15, and 22, daily cyclophosphamide (25 mg/m) on days 1 to 21, and twice weekly methotrexate (15 mg/m) on days 21 to 42, followed by a 1-week break. For the following cycles, vincristine was administered only at weeks 1 and 5 of the cycle. This treatment was proposed to children with refractory cancer following treatments with the standard protocols available in our institution and to patients who were not eligible for the protocol. Adverse events were determined through laboratory analyses and investigator observations. RESULTS: From November 2008 to December 2009, 12 children (median age, 3.7 y; range, 2 to 7 y) were included. The most frequent diagnoses were Wilms tumors (6) and retinoblastoma (5). No objective response was observed, but 7 patients experienced disease stabilization (58%) and continued their treatment for 15 to 24 weeks. After a median follow-up of 39 weeks, 6 patients (50%) were alive. Most importantly, in 3 patients (25%), disease remained stable for at least 6 months after completion of treatment. One grade 4 anemia was observed in 1 patient and 1 grade 4 nonfebrile neutropenia in 1 patient. No other grade 3 or 4 toxicities were noted. CONCLUSION: The MC regimen that we report here was well tolerated and was associated with disease stabilization. Most importantly, stabilization could be maintained for over 6 additional months after completion of treatment in 3 patients. The potential of MC in children and young adults in low-income countries warrants further studies.

Effect of duration of treatment on treatment outcome and cost of treatment for Wilms' tumor: a report from the National Wilms' Tumor Study Group.

PURPOSE: National Wilms' Tumor Study (NWTS)-4 was designed to evaluate the efficacy, toxicity, and cost of the administration of different regimens for the treatment of Wilms' tumor (WT). PATIENTS AND METHODS: Between August 6, 1986 and September 1, 1994, 905 previously untreated children aged younger than 16 years with stage II favorable histology (FH) WT (low-risk [LR]), stages III to IV FH WT, or stages I to IV clear-cell sarcoma of the kidney (high-risk[HR]) were randomized after the completion of 6 months of chemotherapy to discontinue (short) or continue for 9 additional months (long) treatment with chemotherapy regimens that included vincristine and either divided-dose (standard [STD]) courses (5 days) or single-dose (pulse-intensive [PI]) treatment with dactinomycin. HR patients also received either divided-dose (STD) courses (3 days) or single-dose (PI) treatment with doxorubicin. RESULTS: The 4-year relapse-free survival (RFS) rates after the second randomization for LR patients were 83.7% for the 190 patients treated with short and 88.2% for the 187 patients treated with long chemotherapy (P = .11). The 4-year RFS rates after the second randomization for HR FH patients were 89.7% for the 256 patients treated with short and 88.8% for the 246 patients treated with long chemotherapy (P = .87). The charge for treatment with the short PI treatment regimens for all children with stages I through IV FH WT was approximately one half of that with the long STD treatment regimens. CONCLUSION: The short administration schedule for the treatment of children with WT is no less effective than the long administration schedule and can be administered at a substantially lower total treatment cost.

Wilms tumor imaging: patient costs and protocol compliance.

PURPOSE: To evaluate the patient costs for imaging and compliance with imaging protocols in pediatric patients in the National Wilms Tumor Study (NWTS) IV. MATERIALS AND METHODS: The medical and imaging records of 60 patients (28 male, 32 female; aged 3 days to 12.6 years) in NWTS IV were reviewed. Initial imaging and follow-up imaging were evaluated separately. Three levels of follow-up compliance were evaluated. RESULTS: The total patient cost for imaging was $442,180: $94,212 for initial and $347,968 for follow-up studies. Many areas of potential cost savings were identified. Protocol compliance was variable. Seventy-five percent of patients underwent studies in full compliance with the initial protocol requirements. For follow-up, compliance was 0%-80% for different studies at different compliance levels. For no study was compliance 100%. CONCLUSION: Imaging costs in pediatric patients with Wilms tumor are substantial. Protocol compliance was not optimal.