Hélène Sudour‐Bonnange

Extracranial germ cell tumours in children and adolescents: Results from the French TGM13 protocol

AbstractBackgroundChemotherapy for non‐seminomatous germ cell tumours (NSGCT) exposes to dose‐dependent toxicities. The TGM13‐NS protocol (EudraCT 2013‐004039‐60) aimed to decrease the chemotherapy burden compared to the previous TGM95 protocol while maintaining the 5‐year event‐free survival (EFS) at 80% or more.ProcedurePatients less than 19 years of age with disseminated NSGCT were enrolled (May 2014 to May 2019) and stratified into four groups: two intermediate‐risk (IR: localised tumour with low tumour markers [TM]) groups treated with VBP (vinblastine–bleomycin–cisplatin): three courses for IR1 (ovarian tumour any age/testis tumour less than or equal to 10 years) and four courses for IR2 (extragonadal tumour 10 years or less) groups, and two high‐risk (HR: metastatic and/or high TM) groups treated with etoposide–cisplatin and either ifosfamide (VIP) or bleomycin (BEP): three courses for HR1 (ovarian tumour any age/testis tumour less than or equal to 10 years and low TM/testis tumour more than 10 years and very low TM) groups and four courses for HR2 (remainder) groups.ResultsOne hundred fifteen patients were included: median age of 12.8 years (0.4–18.9); tumour sites: 44 ovaries, 37 testes and 34 extragonadal. The 5‐year EFS and overall survival (OS) were 87% (95% CI: 80–92) and 95% (89–98), respectively (median follow‐up: 3.5 years, range: 0.2–5.9), similar to those of the TGM95 protocol (5‐year EFS 89% (84–93), 5‐year OS 93% (89–95), p = .561). The 5‐year EFS were 93% (95% CI: 80–98), 88% (71–95) and 79% (62–90) for ovarian, testicular and extragonadal tumours, respectively. The 5‐year EFS varied (p = .02) according to the risk groups: 90% (66–97), 64% (30–85), 95% (72–99) and 87% (74–94) for IR1, IR2, HR1 and HR2, respectively. TM decline adjusted to tumour site, and alpha‐fetoprotein (AFP) level revealed a prognostic impact of time to normalisation on EFS: HR = 1.03 (1.003–1.007).ConclusionRisk‐adapted and globally decreased chemotherapy burden maintains excellent outcomes, exclusive of the IR2 group, which warrants more intensive chemotherapy.

Outcome and late effects of patients treated for childhood vaginal malignant germ cell tumors

AbstractPurposeVaginal malignant germ cell tumors (MGCT) are rare, occurring in children less than 2 years old and raise the question of the optimal local treatment.MethodsWe included children treated for vaginal MGCT according to the French TGM‐95/2013 regimen. Patients were classified as standard risk (SR: localized disease and alpha‐fetoprotein (AFP) < 10,000 ng/mL) or high risk (HiR: metastatic and/or AFP > 10,000 ng/mL) and were treated, respectively, with three to five VBP (vinblastine–bleomycin–cisplatin) or four to six VIP (etoposide–ifosfamide–cisplatin), followed by conservative surgery and/or brachytherapy in case of post‐chemotherapy residuum.ResultsFourteen patients were included (median age = 12 months), of which six (43%) were classified as HiR. AFP levels were normalized after first‐line chemotherapy in all cases but one. A vaginal post‐chemotherapy residuum (median size = 8 mm, range: 1–24 mm) was observed in 13/14 patients, treated by complete resection in seven of 13 (viable cells in three of seven), incomplete resection in four of 13 (viable cells in two of four), with adjuvant brachytherapy in two of 13, and exclusive brachytherapy in two of 13 (viable cells in one of six). Among the six patients with viable disease, four patients received adjuvant chemotherapy. One patient (SR) experienced immediate postoperative relapse despite presenting no viable residual cells and was treated with four VIP cycles and brachytherapy. At last follow‐up (median = 4.6 years, range: 0.5–16), all patients were alive in complete remission. Five patients suffered from vaginal sequelae with synechiae and/or stenosis (of whom four had undergone brachytherapy).ConclusionChildhood vaginal MGCTs show a highly favorable prognosis with risk‐adapted chemotherapy and local treatment of post‐chemotherapy residuum (preferably by conservative surgery with partial vaginectomy). Brachytherapy could be an alternative when conservative surgery is not deemed possible or in cases of incomplete resection with residual viable cells.

Oncological and endocrinological outcomes for children and adolescents with testicular and ovarian sex cord‐stromal tumors. Results of the TGM13 National Registry

Abstract Rationale Sex cord‐stromal tumors (SCST) are hormonally active and rare. The aim was to describe their endocrinological presentation and outcomes. Method Patients (< 19 years) registered in the TGM13 registry between 2014 and 2021 for SCST were selected. Results Sixty‐three ovarian SCST (juvenile granulosa tumor (JGT) n  = 34, Sertoli‐Leydig cell tumor (SLCT) n  = 17, other SCST n  = 12) were included. Median age was 13.1 years (0.4‐17.4). Germline DICER1 pathogenic variant was present in 9/17 SLCT. Sixty‐one were FIGO stage I (IC n  = 14). Adjuvant chemotherapy was administered for 15. Seven had recurrence (FIGO IA n  = 3, IX n  = 2, III n  = 2), leading to one death. With a median follow‐up of 42 months (2.5‐92), the 3‐year progression‐free survival (PFS) was 89% (95% CI 76%‐95%). Median age was 6.4 years (0.1‐12.9) among the 15 testicular SCST (Leydig cell tumor n  = 6, JGT n  = 5, Sertoli cell tumor n  = 3, mixed SCST n  = 1). Tumor‐nodes‐metastases (TNM) stage was pSI in 14. Eight underwent a tumorectomy, 7 an orchiectomy. None experienced recurrence. Endocrinological data were reviewed for 41 patients (18 prepubescent). Endocrine symptoms were present at diagnosis in 29/34 females and 2/7 males (gynecomastia). After a median follow‐up of 11 months, 15 patients had persistent endocrine abnormalities: gynecomastia/breast growth (2 males, 1 prepubescent female), precocious/advanced puberty (4 prepubescent females), and hirsutism/menstruation disorders/voice hoarseness/hot flashes (8 pubescent females). The mean height at the last follow‐up was within normal ranges (+0.3 standard deviation). Conclusions SCSTs have a favorable prognosis. Tumorectomy appears safe with testicular primary. Endocrinological disorders, common at diagnosis, may persist warranting endocrinological follow‐up.