Purpose Treatment recommendations for localized paratesticular rhabdomyosarcoma (PT RMS) differ in North America and Europe. We conducted a pooled analysis to identify demographic features and treatment choices that affect outcome. Patients and Methods We retrospectively analyzed the effect of nine demographic variables and four treatment choices on event-free survival (EFS) and overall survival (OS) from 12 studies conducted by five cooperative groups. Results Eight hundred forty-two patients with localized PT RMS who enrolled from 1988 to 2013 were included. Patients age ≥ 10 years were more likely than younger patients to have tumors that were > 5 cm, enlarged nodes (N1), or pathologically involved nodes ( P ≤ .05 each). With a median follow-up of 7.5 years, Kaplan-Meier estimates for 5-year EFS and OS were 87.7% and 94.8%, respectively. Of demographic variables, cooperative group, era of enrollment, age category, tumor size, Intergroup Rhabdomyosarcoma Study group, and T stage affected EFS ( P ≤ .05 each). Surgical assessment of regional nodes, which was performed in 23.5% of patients—usually in those age ≥ 10 years or with suspicious or N1 nodes—was the only treatment variable associated with EFS by univariable and multivariable analyses ( P ≤ .05 each) in patients age ≥ 1 year. A variable selection procedure on a proportional hazards regression model selected era of enrollment, age, tumor size, and surgical assessment of regional nodes as significant ( P ≤ .05 each) in the EFS model, and era of enrollment, age, tumor size, and histology ( P ≤ .05 each) in the OS model. Conclusion Localized PT RMS has a favorable prognosis. Age ≥ 10 years at diagnosis and tumor size larger than 5 cm are unfavorable prognostic features. Surgical assessment of regional nodes is important in patients age ≥ 10 years and in those with N1 nodes as it affects EFS.

LSC is superior concerning minor complications and cosmesis, whereas quality-of-life is similar in the long term.

No abstract

Infantile myofibromatosis (IM), which is typically diagnosed in young children, comprises a wide clinical spectrum ranging from inconspicuous solitary soft tissue nodules to multiple disseminated tumors resulting in life-threatening complications. Familial IM follows an autosomal dominant mode of inheritance and is linked to PDGFRB germline variants. Somatic PDGFRB variants were also detected in solitary and multifocal IM lesions. PDGFRB variants associated with IM constitutively activate PDGFRB kinase activity in the absence of its ligand. Germline variants have lower activating capabilities than somatic variants and, thus, require a second cis-acting hit for full receptor activation. Typically, these mutant receptors remain sensitive to tyrosine kinase inhibitors such as imatinib. The SIOPE Host Genome Working Group, consisting of pediatric oncologists, clinical geneticists and scientists, met in January 2020 to discuss recommendations for genetic testing and surveillance for patients who are diagnosed with IM or have a family history of IM/PDGFRB germline variants. This report provides a brief review of the clinical manifestations and genetics of IM and summarizes our interdisciplinary recommendations.

Abstract. Multidrug resistance (MDR) is a common problem in the treatment of childhood rhabdomyosarcoma (RMS).A complete reversal of MDR is currently not possible. The aim of this study was to investigate the role of glutathione-Stransferase (GST) as mechanism of MDR in childhood RMS and to analyze possible reversal strategies. Female athymic mice underwent xenotransplantation with embryonal or alveolar RMS cells and were treated with vincristine. Gene expression analysis using Affymetrix HU-Gene 1.0 arrays revealed 2314 differentially expressed genes between the groups in alveolar RMS and 1387 in embryonal RMS. Ingenuity pathway analysis revealed a cluster of 5 overexpressed genes of the GST family in animals treated with vincristine, putative mediating the development of MDR. In order to analyze possible GST activity after chemotherapy with other commonly used drugs (doxorubicin, topotecan), cell culture experiments with alveolar and embryonal RMS cells were carried out. Specific GST activity was quantified using the clorodinitrobenzol conjugation with glutathione. Increased GST activity was found after incubation with cytotoxic agents in all cell lines. Highest induction of GST activity was found in embryonal RMS (up to 12-fold). After incubation with the GST inhibitors, tumor cell viability was decreased depending on the type of tumor cell and inhibitor used. We detected a novel mechanism for MDR in childhood RMS mediated via genes and proteins of the GST family. Reversal of these effects may be achieved by GST inhibitors in part. The GST family represents a promising target for further treatment strategies in childhood RMS.

No abstract

Background Biliary rhabdomyosarcoma (RMS) is the most common biliary tumor in children. The management of affected patients contains unique challenges because of the rarity of this tumor entity and its critical location at the porta hepatis, which can make achievement of a radical resection very difficult. Methods In a retrospective chart analysis we analysed children suffering from biliary RMS who were registered in three different CWS trials (CWS-96, CWS-2002P, and SoTiSaR registry). Results Seventeen patients (12 female, 5 male) with a median age of 4.3 years were assessed. The median follow-up was 42.2 months (10.7–202.5). The 5-year overall (OS) and event free survival (EFS) rates were 58% (45–71) and 47% (34–50), respectively. Patients > 10 years of age and those with alveolar histology had the worst prognosis (OS 0%). Patients with botryoid histology had an excellent survival (OS 100%) compared to those with non-botryoid histology (OS 38%, 22–54, p = 0.047). Microscopic complete tumor resection was achieved in almost all patients who received initial tumor biopsy followed by chemotherapy and delayed surgery. Conclusion Positive predictive factors for survival of children with biliary RMS are age ≤ 10 years and botryoid tumor histology. Primary surgery with intention of tumor resection should be avoided.

These data support the assumption that the absorptive capacity of the intestinal mucosa for water may be improved by topically acting steroids and suggest that this occurs independently of their anti-inflammatory effect.