Pheochromocytoma and Paraganglioma in Children and Adolescents: Experience of the French Society of Pediatric Oncology (SFCE).

PURPOSE: The purpose of this work is to assess the clinical outcome of pediatric patients diagnosed with pheochromocytoma and paraganglioma (PPGL) detected in France since 2000. METHODS: A retrospective multicenter study was conducted that included all patients younger than 18 years with PPGL diagnosed in France between 2000 and 2016. Patients were identified from 4 different sources: the National Registry of Childhood Solid Tumors, the French Pediatric Rare Tumors Database, the French registry of succinate dehydrogenase (SDH)-related hereditary paraganglioma, and the nationwide TenGen network. RESULTS: Among 113 eligible patients, 81 children with available data were enrolled (41 with adrenal and 40 with extra-adrenal PPGL). At diagnosis, 11 had synchronous metastases. After a median follow-up of 53 months, 27 patients experienced a new event (n = 7 second PPGL, n = 1 second paraganglioma [PGL], n = 8 local recurrences, n = 10 metastatic relapses, n = 1 new tumor) and 2 patients died of their disease. The 3- and 10-year event-free survival rates were 80% (71%-90%) and 39% (20%-57%),respectively, whereas the overall survival rate was 97% (93%-100%)at 3 and 10 years. A germline mutation in one PPGL-susceptibility gene was identified in 53 of the 68 (77%) patients who underwent genetic testing (SDHB [n = 25], VHL [n = 21], RET [n = 2], HIF2A [n = 2], SDHC [n = 1], SDHD [n = 1], NF1 [n = 1]). Incomplete resection and synchronous metastases were associated with higher risk of events (P = .011, P = .004), but presence of a germline mutation was not (P = .11). CONCLUSIONS: Most pediatric PPGLs are associated with germline mutations and require specific follow-up because of the high risk of tumor recurrence.

Germline SUFU mutation carriers and medulloblastoma: clinical characteristics, cancer risk, and prognosis.

Background: Germline mutations of suppressor of fused homolog (SUFU) predispose to sonic hedgehog (SHH) medulloblastoma. Germline SUFU mutations have been reported in nevoid basal cell carcinoma syndrome (NBCCS), but little is known about the cancer risk and clinical spectrum. Methods: We performed a retrospective review of all patients with medulloblastoma and a germline SUFU mutation in France. Results: Twenty-two patients from 17 families were identified with medulloblastoma and a germline SUFU mutation (median age at diagnosis: 16.5 mo). Macrocrania was present in 20 patients, but only 5 met the diagnostic criteria for NBCCS. Despite treatment with surgery and chemotherapy, to avoid radiotherapy in all patients except one, the outcome was worse than expected for SHH medulloblastoma, due to the high incidence of local relapses (8/22 patients) and second malignancies (n = 6 in 4/22 patients). The 5-year progression-free survival and overall survival rates were 42% and 66%. Mutations were inherited in 79% of patients, and 34 additional SUFU mutation carriers were identified within 14 families. Medulloblastoma penetrance was incomplete, but higher than in Patched 1 (PTCH1) mutation carriers. Besides medulloblastoma, 19 other tumors were recorded among the 56 SUFU mutation carriers, including basal cell carcinoma (BCC) in 2 patients and meningioma in 3 patients. Conclusion: Germline SUFU mutations strongly predispose to medulloblastoma in the first years of life, with worse prognosis than usually observed for SHH medulloblastoma. The clinical spectrum differs between SUFU and PTCH1 mutation carriers, and BCC incidence is much lower in SUFU mutation carriers. The optimal treatment of SUFU mutation-associated medulloblastoma has not been defined.

Hereditary breast and ovarian cancer: successful systematic implementation of a group approach to genetic counselling.

The increase in referrals to cancer genetics clinics, partially associated with the "Angelina Jolie effect", presents a challenge to existing services, many are already running at full capacity. More efficient ways to deliver genetic counselling are therefore urgently needed. We now systematically offer group instead of standard individual counselling to patients with suspected Hereditary Breast and Ovarian Cancer. Group sessions last 30 min. The first twenty consist of a presentation by the genetic counsellor, the next ten of a discussion involving a cancer geneticist and a psychologist. A short individual consultation ensues, where personal and family issues are addressed and consent obtained. Blood is drawn afterwards. Satisfaction and knowledge are evaluated. We report data for the Oct-2014-Aug-2015 period. 210 patients attended group counselling, up to eight simultaneously. We always fitted them within a 4-h time frame. Mean satisfaction score was 41/43. Knowledge scores increased from 3.1/6 to 4.9/6 post-counselling (p value < 2.2 × 10-16). Thanks to group counselling, we have withstood increases in referrals without compromising care. The "Angelina Jolie effect" and rapid developments in personalized medicine threaten to overwhelm cancer genetics clinics. In this context, our innovative approach should ensure that all patients have access to approved services.