Neuroblastoma is the most frequent extra-cranial pediatric solid tumor, occurring in young children, 90% being less than 5 years at diagnosis. It remains a therapeutic challenge since survival of ...high-risk neuroblastoma patients that represent around 50% of the patients is around 50% in spite of extensive combined treatments. Immunotherapy based on the use of antibodies directed to GD2, a ganglioside strongly expressed by almost all neuroblastoma cells, has been developed during the last decade. In SIOPEN studies have shown that dinatuximab beta (Qarziba
) is effective on refractory/relapsed patients and improves survival when administered in the first line maintenance treatment. Other strategies are currently explored using combination with chemotherapy at relapse and evaluating the benefits of an earlier administration during the induction treatment. In addition, more selective antibodies are also developed to decrease toxicity, especially neuropathic pain that is one of the major toxic effect.
Background
Heterogeneous data have been reported on high‐dose chemotherapy (HDCT) with autologous stem cell rescue (ASCR) in Wilms tumors (WTs). We aimed to define its safety and efficacy in the ...French cohort, and to compare this management to current international recommendations.
Methods
Data prospectively collected from children, adolescents, and young adults with WT treated with HDCT/ASCR between 2000 and 2016 in French centers were retrospectively analyzed. Toxicity was reported according to CTCAE v4.03.
Results
Fifty‐four patients received HDCT/ASCR (first line, n = 13; recurrence, n = 41). Their median age at the time of ASCR was 5.3 years (range 2.2–21.6). Main nonhematological acute grades 3–4 toxicities were digestive and renal. No significant difference of toxicity rate was observed among HDCT regimens and schedules. Two patients died shortly after ASCR (renal and multiorgan failure), and one heavily pretreated patient died of late respiratory failure. The selection criteria applied to define those patients eligible for HDCT/ASCR retrospectively matched to those currently used in the International Society of Pediatric Oncology (SIOP) UMBRELLA protocol for 38 patients, with encouraging survival rates compared to published data. The objective response rate to HDCT was 21%, with a disease control rate after HDCT of 85%. After a median follow‐up of 7 years, the 5‐year event‐free survival (EFS) and overall survival (OS) were 54% (95% CI: 32%–76%) and 62% (95% CI: 31%–82%) for frontline patients, and 57% (95% CI: 39%–71%) and 69% (95% CI: 52%–81%) at recurrence.
Conclusion
HDCT was feasible and showed encouraging results in well‐defined settings. Data from the current prospective protocol will help to better evaluate HDCT impact on survival.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
•Perinatal exposures due to maternal habits like smoking, alcohol consumption and domestic use of pesticides are suspected risk factors of Wilms’ tumor.•Our population-based case control-study shows ...that household insecticide use during pregnancy may be associated to an increased risk of Wilms’ tumor.•The study does not suggest any role of parental smoking or maternal drinking in the etiology of Wilms’ tumor.
Wilms’ tumor is the most frequently diagnosed renal tumor in children. Little is known about its etiology. The aim of this study was to investigate the potential role of specific exposures related to parental habits such as parental smoking, maternal alcohol consumption and the use of household pesticides during pregnancy.
The ESTELLE study was a nationwide case-control study that included 117 Wilms’ tumor cases and 1100 control children from the general French population, frequency-matched by age and gender. Unconditional logistic regression was used to estimate odds ratios and 95 % confidence intervals.
After controlling for matching variables and potential confounders, the maternal use of any type of pesticide during pregnancy was associated with the risk of Wilms’ tumor in children (OR 1.6 95 % CI 1.1–2.3). Insecticides were the most commonly reported type of pesticide and there was a positive association with their use (OR 1.7 95 % CI 1.1–2.6. The association was stronger when they were used more often than once a month (OR 1.9 95 % CI 1.2–3.0. Neither maternal smoking during pregnancy nor paternal smoking during preconception/pregnancy was associated with a risk of Wilms’ tumor (ORs 1.195 % CI 0.7–1.8 and 1.1 95 % CI 0.7–1.7, respectively). No association was observed with maternal alcohol intake during pregnancy (OR 1.2 95 % CI 0.8–2.0).
Our findings suggest an association between the maternal use of household pesticides during pregnancy and the risk of Wilms’ tumor.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Patients with Beckwith–Wiedemann syndrome (BWS) or isolated hemihypertrophy (HH) treated for a Wilms tumor (WT) carry an increased risk of developing metachronous lesion. There are no ...guidelines on precise indications for nephron sparing surgery (NSS) in unilateral WT (UWT). The objective of this retrospective study was to delineate the indications of NSS in patients with BWS/HH treated for WT and to evaluate their outcome.
Procedure
All cases of BWS/HH treated for a WT according to SIOP protocols from 1980 to 2013 were reviewed. Patients were divided into two groups (G): isolated UWT (G1) and bilateral lesions (G2) with two subgroups: bilateral tumors suspected of malignancy (G2a), and unilateral tumor suspected of malignancy with contralateral nephroblastomatosis (G2b).
Results
Forty‐six patients were included (34 G1, three G2a, and nine G2b). Nine NSS and 25 total nephrectomies (TN) were performed in G1, two bilateral NSS and one NSS with contralateral TN in G2a, and eight NSS and one TN in G2b. The 3‐year event‐free survival was 92.3% (95% CI 77.9–97.5%). One death occurred after a local relapse following a TN for a stage III stromal WT (G1) and another after a combined local and distant relapse following a NSS for a stage I diffuse anaplastic WT (G2b). There were two metachronous WT (4%), 3 years after a TN (G1) and 12 years after a NSS (G2b).
Conclusions
NSS is recommended in bilateral WT and may be an option in selected UWT patients with BWS/HH because it was not associated with an increased risk of local relapse.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
The purpose of this study was to evaluate whether levels of neuroblastoma mRNAs in bone marrow and peripheral blood from stage M infants (≤12 months of age at diagnosis, MYCN amplified) ...and toddlers (between 12 and 18 months, any MYCN status) predict event‐free survival (EFS).
Methods
Bone marrow aspirates and peripheral blood samples from 97 infants/toddlers enrolled in the European High‐Risk Neuroblastoma trial were collected at diagnosis in PAXgene™ blood RNA tubes. Samples were analyzed by reverse transcription quantitative polymerase chain reaction according to standardized procedures.
Results
Bone marrow tyrosine hydroxylase (TH) or paired‐like homeobox 2b (PHOX2B) levels in the highest tertile were associated with worse EFS; hazard ratios, adjusted for age and MYCN status, were 1.5 and 1.8 respectively. Expression of both TH and PHOX2B in the highest tertile predicted worse outcome (p = 0.015), and identified 20 (23%) infants/toddlers with 5‐year EFS of 20% (95%CI: 4%–44%). Prognostic significance was maintained after adjusting for over‐fitting bias (p = 0.038), age and MYCN status. In peripheral blood, PHOX2B levels in the highest tertile predicted a two‐fold increased risk of an event (p = 0.032), and identified 23 (34%) infants/toddlers with 5‐year EFS of 29% (95%CI: 12%–48%). Time‐dependent receiver operating characteristic analysis confirmed the prognostic value of combined TH and PHOX2B in bone marrow and of PHOX2B in peripheral blood during the first year of follow‐up.
Conclusions
High levels of bone marrow TH and PHOX2B and of peripheral blood PHOX2B at diagnosis allow early identification of a group of high‐risk infant and toddlers with neuroblastoma who may be candidates for alternative treatments. Integration with additional biomarkers, as well as validation in additional international trials is warranted.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Opsoclonus myoclonus syndrome (OMS), often called "dancing eyed syndrome," is a rare neurological condition associated with neuroblastoma in the majority of all childhood cases. Genomic copy number ...profiles have shown to be of prognostic significance for neuroblastoma patients. The aim of this retrospective multicenter study was to analyze the genomic copy number profiles of tumors from children with neuroblastoma presenting with OMS at diagnosis. In 44 cases of neuroblastoma associated with OMS, overall genomic profiling by either array-comparative genomic hybridization or single nucleotide polymorphism array proved successful in 91% of the cases, distinguishing tumors harboring segmental chromosome alterations from those with numerical chromosome alterations only. A total of 23/44 (52%) tumors showed an segmental chromosome alterations genomic profile, 16/44 (36%) an numerical chromosome alterations genomic profile, and 1 case displayed an atypical profile (12q amplicon). No recurrently small interstitial copy number alterations were identified. With no tumor relapse nor disease-related deaths, the overall genomic profile was not of prognostic impact with regard to the oncological outcome in this series of patients. Thus, the observation of an excellent oncological outcome, even for those with an unfavorable genomic profile of neuroblastoma, supports the hypothesis that an immune response might be involved in tumor control in these patients with OMS.
Abstract Background Peritoneal carcinomatosis from abdominal tumors is an uncommon condition in children usually associated with dismal prognosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) ...following complete macroscopic surgery has been demonstrated to be safe and of benefit in selected cases. Experience in pediatrics is scarce. Methods We retrospectively reviewed the medical files of patients under the age of 18 years with an abdominal malignancy and peritoneal carcinomatosis who had been treated with HIPEC in our institution between March 2001 and April 2012. HIPEC had been administered using the open technique with oxaliplatin (300 mg/m2 ) and irinotecan (200 mg/m2 ) or oxaliplatin alone (460 mg/m2 ) in the peritoneal cavity for 30 minutes at 43 °C and an intravenous perfusion of leucovorin (20 mg/m2 ) and 5-fluorouracil (400 mg/m2 ). Results Nine patients had undergone HIPEC. Grade 3–4 complications had occurred in seven patients and were intraabdominal (n = 3) or extraabdominal (n = 8). No procedure-related deaths had occurred. Four patients are alive and in complete remission after a median follow-up of 4.9 years (1.7–9.6). However one relapsed after HIPEC and required additional salvage therapy. Conclusions HIPEC could be considered in patients with peritoneal carcinomatosis from primary abdominal tumors. Its complications are manageable by an experienced multidisciplinary team. There are four long-term survivors, one after a relapse.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background
Liver metastases are rare in children with Wilms tumor (WT), and their impact on the outcome is unclear.
Patients and methods
The French cohort of patients with WT presenting liver ...metastases at diagnosis and enrolled in the International Society of Pediatric Oncology (SIOP) 2001 study was reviewed.
Results
From 2002 to 2012, 906 French patients were enrolled in the SIOP2001 trial. Among them, 131 (14%) presented with stage IV WT and 18 (1.9%) had liver metastases at diagnosis. Isolated liver metastases were displayed in four of them. After preoperative chemotherapy, persistent liver disease was reported in 14/18 patients, and 13 of them underwent metastasectomy after nephrectomy. In resected liver lesions, the same histology of the primary tumor was reported for three patients, blastemal cells without anaplasia were identified in one patient with DA‐WT, and post‐chemotherapy necrosis/fibrosis was identified for the other 10 patients. For the four patients who had liver and lung surgery, both sites had nonviable cells with post‐chemotherapy necrosis/fibrosis. Six patients had hepatic radiotherapy. Sixteen patients achieved primary complete remission and were alive at the last follow‐up (median follow‐up: 6.4 years). The only two deceased patients presented diffuse anaplasia histology. The five‐year EFS and OS were 83% (60%‐94%) and 88% (66%‐97%), respectively.
Conclusion
Liver involvement does not appear to be an adverse prognostic factor in metastatic WT. The role of hepatic surgery and radiotherapy remains unclear, and should be carefully considered in case of persistent liver metastases, according to histology and radiological response to other metastatic sites.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A previously unrecognized syndrome with congenital neutropenia and various organ abnormalities has been described recently, caused by mutations in the gene encoding glucose-6-phosphatase, catalytic ...subunit 3 (G6PC3).
A 10-year-old boy from Ecuador suffering from severe neutropenia and multiple nonhematopoietic abnormalities was admitted to our department. We identified a novel mutation in the G6PC3 gene (c. 765_delAG; p.S255fs).
This is the first case of G6PC3 deficiency in a patient from South America, caused by a novel mutation in the G6PC3 gene. Our results give insights into the molecular and clinical variability of this disease.
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