Adriana Fonseca

Germ cell tumors (GCTs) are rare in childhood, representing only 3.5% of childhood cancers, but a common malignancy in adolescents and young adults (AYAs), accounting for 13.9% of neoplasms in adolescents between age 15 and 19 years. The overall outcomes of patients treated for GCTs are excellent. However, as seen in other cancers, outcomes for AYA patients are significantly worse. Understanding the reasons for this observation has led to different approaches to diagnosis, staging, and treatment. The Malignant Germ Cell International Consortium was created to bring together pediatric, gynecologic, and testicular cancer specialists to promote research initiatives and provide evidence-based approaches in the management of GCTs across different age groups. Collaboration between multiple subspecialties is essential to further understand the disease continuum, the underlying biologic characteristics, and the development of appropriate therapeutic approaches. This review focuses on the unique characteristics of patients with extracranial GCTs in the AYA group.

Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.763-0.925) with 15 relapsed individuals identified. Maintenance chemotherapy is identified as a strong predictor of relapse, with individuals receiving high doses of cyclophosphamide or ifosphamide having only one very late molecularly confirmed relapse (p = 0.032). The anatomical location of recurrence is metastatic in 12 of 15 relapses, with 8 of 12 metastatic relapses in the lateral ventricles. Maintenance chemotherapy, specifically cumulative cyclophosphamide doses, is a significant predictor of relapse across WNT MB. Future efforts to de-escalate therapy need to carefully consider not only the radiation dose but also the chemotherapy regimen and the propensity for metastatic relapses.

BACKGROUND: Orthotopic liver transplantation (OLT) is considered the standard for children with hepatoblastoma (HB) in whom complete surgical resection is not possible. However, OLT is not always available or feasible. OBJECTIVE: To describe the outcome of children with HB who were initially deemed unresectable and underwent complex hepatectomy with planned close margins, and ultimately avoided OLT. METHODS: Demographic data, surgical and pathologic details, and survival information were collected from children treated for HB between January 2010 to December 2015. RESULTS: Among six children (median age 12 months (3-41 months)), PRETEXT classification was III (n = 2), III/IV (n = 1), and IV (n = 3). Patients received a median of six cycles (range 4-7) of platinum-based induction chemotherapy; five received doxorubicin. Experienced pediatric surgeons performed extended right and left hepatectomy in five and one patients, respectively, with assistance of an experienced liver transplant surgeon (n = 4). Microscopic margins were positive (n = 2) and negative but close (n = 4; 2-5 mm). Two patients required vascular reconstruction of the vena cava. At median follow-up of 3.3 years (1.7-4.6 years), there was no evidence of local recurrence. One patient had recurrence of pulmonary disease 3 months after surgery. CONCLUSIONS: Patients with advanced HB treated with complex surgical resections with positive or close negative margins had good outcomes without OLT. We suggest that planned positive or close microscopic margins in highly selected HB patients may spare the morbidity of OLT and offer an alternative for those ineligible for OLT. Our experience illustrates the importance of a multidisciplinary team specialized in the management of liver tumors.