No abstract

Rhabdomyosarcoma (RMS) is a high-grade malignant neoplasm, with a morphologic appearance mimicking that of developing skeletal muscle. Over the last 30 years, patient outcomes have improved with the incorporation of multimodal therapies, including chemotherapy, radiation therapy, and surgery. The overall cure rates exceed 70%, with patients who have low-, intermediate-, and high-risk disease experiencing long-term survival rates of >90%, 70%, and <30%, respectively. Historically, RMS was classified according to histology; however, recent advances have revealed new molecular subgroups that allow us to more accurately identify high-, intermediate-, and low-risk disease. In this review, we discuss recent advances made in understanding RMS tumor biology and propose how this understanding can drive a new classification system that can guide clinical approaches for treatment de-escalation in patients with expected favorable outcomes and escalation for those with expected poor outcomes.

BACKGROUND:Children diagnosed with cancer are at a significantly higher risk of developing a thrombotic event (TE) compared to the general population. The rarity of these events makes it difficult to discern the specific risk factors; however, age, sex, presence of central venous lines, inherited thrombophilia and mediastinal mass may play a role. The primary aim of this study is to identify prognostic characteristics of children diagnosed with non-lymphoblastic lymphomas associated with a greater risk of developing a thrombotic event early on in their disease, with an increased focus on mediastinal mass characteristics. METHODS:Retrospective chart review of pediatric patients diagnosed with non-lymphoblastic lymphoma between 2004 and 2014 at St. Jude Children's Research Hospital.RESULTS: TE occurred in 8.5% (n=28/330) of individuals at a median of 21 days from diagnosis of a non-lymphoblastic lymphoma, with 60% of TEs occurring within 30 days of diagnosis. Of the variables evaluated, only presence of a PICC [OR: 3.14 (95% CI: 1.24-7.98; p=0.02)] and degree of superior vena cava (SVC) compression of >25% increased the odds of developing a TE [OR: 2.2 (95%CI: 1.01-4.93; p=0.048)]. CONCLUSION:Pediatric patients with non-lymphoblastic lymphoma are at increased risk of developing TEs. In contrast to previous studies, presence of a mediastinal mass alone was not associated with a higher risk of TE, but individuals with a mediastinal mass with 25% or greater degree of SVC compression were more likely to develop a TE. This finding highlights a high-risk group of children that may benefit from prophylactic anticoagulation.

Although outcomes for patients with high-risk neuroblastoma improved after the addition of a chimeric anti-GD2 monoclonal antibody (dinutuximab) as treatment for minimal residual disease, nearly half of these patients die of disease. Recent studies demonstrated efficacy of the combination of chemotherapy with anti-GD2 mAb in patients with relapsed or newly diagnosed disease. This retrospective case series describes 6 patients treated at St Jude Children’s Research Hospital with an induction regimen containing dinutuximab and chemotherapy, followed by consolidation and postconsolidation therapy. The treatment was well tolerated with expected toxicities. All patients completed induction therapy and demonstrated a clinical response. Further studies are warranted.