Vaginal malignant germ cell tumors (MGCT) are rare, occurring in children less than 2 years old and raise the question of the optimal local treatment.
We 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.
Fourteen 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).
Childhood 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.
Background
Chemotherapy 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.
Procedure
Patients 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.
Results
One 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).
Conclusion
Risk‐adapted and globally decreased chemotherapy burden maintains excellent outcomes, exclusive of the IR2 group, which warrants more intensive chemotherapy.
Choriocarcinoma in neonates and infants (N‐CC) is an extremely rare, but aggressive cancer, frequently observed with concomitant maternal disease. A retrospective, bi‐national study of patients ...treated in France and Poland for infantile choriocarcinoma analysed eight cases of N‐CC, median age of 6 weeks. All tumours were diffuse. Six patients received a platinum‐based regimen, and five had delayed surgery on residual distant tumour sites. At the end of follow‐up, four patients were in complete remission and four had died of the disease. In all but two cases, mothers had simultaneous metastatic choriocarcinoma. Even if the outcome remains poor, patients could be cured with multimodal therapy.
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.
We report survival and late effects analysis of TGM95 study for childhood (≤18 years) ovarian nonseminomatous germ cell tumors (NS‐GCT). Patients with localized tumors (FIGO‐stage IA) had no adjuvant ...treatment (low‐risk, LR). Patients with advanced‐stage received 3‐5 VBP (vinblastin‐bleomycin‐cisplatin) in intermediate‐risk group (IR: FIGO‐stage IC‐II‐III and AFP < 15 000 ng/mL) or 4‐6 VIP (etoposide‐ifosfamide‐cisplatin) in high‐risk group (HiR: metastatic or AFP ≥ 15 000 ng/mL). Seventy‐seven patients were included (median age = 12 years): 14 LR (13 FIGO‐stage IA, 1 retrospectively IC), 26 IR (12 IC, 12 II‐III, 2 not‐available) and 37 HiR (2 IA with AFP ≥ 15 000 ng/mL, 27 II‐III, 8 IV). After a median follow‐up of 13.4 years, 12 events (eight relapses) and six deaths (two GCT‐related, two due to acute myeloid leukemia and two noncancer related) occurred. All relapses (6 LR, 1 IR) occurred within 2 years. Four contralateral mature teratomas were observed within 8 years. Five‐year EFS and OS were 88.2% (95%CI = 79‐94%) and 94.6% (95%CI = 87‐98%). Seven patients (9%) had bilateral gonadectomy. Among 51 survivors at 2 years aged >15 years (median = 26 years) with remaining ovarian tissue, all had developed spontaneous puberty and 21 (41%) had at least one pregnancy (including two with infertility treatment). Among 69 patients treated with platinum‐based chemotherapy, chronic‐kidney‐disease was diagnosed in four patients (three after VIP) and significant ototoxicity occurred in three (all grade‐2). Childhood ovarian NS‐GCTs have an excellent prognosis with few late effects. The low‐intensive etoposide‐free VBP regimen could be an alternative in children with IR disease especially in cases of tumor rupture. The risk of contralateral mature teratoma needs regular monitoring of the remaining ovary.
Background
Disorders of sex development (DSD) are rare conditions. Although they are known to predispose to germ cell tumors (GCT), there is a paucity of information regarding the circumstances of ...DSD discovery.
Design/methods
All patients with DSD registered in two French pediatric GCT protocols (TGM95 and 13) were analyzed.
Results
Sixteen patients were identified among 276 ovarian, 160 testicular, and 24 mediastinal GCT. Eleven phenotypic females (median age 15 years) exhibited gonadal GCT, including 10 with a 46,XY karyotype and gonadal dysgenesis and one with 46XX,45X0 mosaicism. None had genital anomalies, seven had spontaneous pubertal changes, and one had spontaneous menarche. The tumors were bilateral in four cases. DSD was diagnosed after the GCT diagnosis in seven cases. The reasons for karyotyping were bilateral tumors (3), gonadoblastoma/streak gonad/absence of egg follicles (3), or systematic for GCT (1). The karyotyping was performed before the GCT diagnosis in four cases: for polymalformative syndrome (2) or primary amenorrhea (2). Four males (median age 14 years) exhibited mediastinal GCT (metastatic in two cases) indicative of Klinefelter syndrome, despite typical phenotypes in all cases. The remaining patient had severe hypospadias, leading to the discovery of 46,XY/45,X0 mosaicism before the diagnosis of testicular nonseminomatous GCT at 16 years of age.
Conclusion
DSD are often uncovered at the time of GCT diagnosis (11/16 cases). This should prompt oncologists to rule out a DSD in patients with GCT, even in case of pubertal development. Earlier recognition of Klinefelter syndrome could potentially lead to GCT detection at an earlier stage.
Tumor rupture in hepatoblastoma: A high risk factor? Pondrom, Morgane; Pariente, Daniele; Mallon, Brenda ...
Pediatric blood & cancer,
September 2020, 2020-09-00, 20200901, Letnik:
67, Številka:
9
Journal Article
Recenzirano
Background
Hepatoblastoma tumor rupture is a high‐risk criterion in the SIOPEL 3/4 protocol. Little is known about the outcome of these children.
Methods
Radiological signs of possible tumor rupture, ...defined as peritoneal effusion, peritoneal nodules, or hepatic subcapsular hematoma, were reported in 24 of 150 patients treated for hepatoblastoma in France from January 2000 to December 2014 after central radiological expert review.
Results
Twenty‐two patients with available clinical data were included (nine PRETEXT‐I/II, six PRETEXT‐III, seven PRETEXT‐IV, and five had lung metastases). Five patients had a subcapsular hematoma only, and 17 patients had intraperitoneal rupture (subcapsular hematoma and peritoneal effusion). A hepatic biopsy was performed in 19 patients. Intraperitoneal rupture occurred before biopsy in 12 and after biopsy in three (including one with prebiopsy subcapsular hematoma) (missing data: two). All patients were treated with chemotherapy, with high‐risk regimens including cisplatin or carboplatin and doxorubicin in 19 and cisplatin or carboplatin alone in three. Liver surgery was performed in 20 patients (including three liver transplants). Fifteen patients (68%) achieved complete remission. With a median follow‐up of 5.5 years, 11 events occurred (six progressions and three relapses, including three peritoneal progressions/relapses, one surgical complication, and one second cancer) and eight patients died. One of eight patients with no other high‐risk criterion had a relapse. The three‐year event‐free survival and overall survival rates were 49.6% (95% CI = 30‐69) and 68.2% (40‐84), respectively.
Conclusions
Tumor rupture is predictive of poor prognosis with risk of peritoneal progression/relapse. However, it should not be a contraindication for liver transplantation.
Objective
To describe characteristics and outcome of pediatric ovarian immature teratomas (IT) to better define the place of chemotherapy.
Methods
Children with ovarian IT enrolled in TGM95 and ...TGM2013 studies were analyzed. Norris grading and International Federation of Gynecology and Obstetrics staging system were used.
Results
Thirty‐six cases were identified with a median age of 11 years (range = 1‐18): 35 of 36 stage I (17 stage IA, 13 stage IC, and 5 stage IX), including seven patients with gliomatosis peritonei (GP), and 1 stage IIIB (IT peritoneal implants). Centrally reviewed Norris grading was performed in 31 cases: 14 grade I and 17 grade II/III tumors. All patients underwent upfront surgery: 19 unilateral oophorectomy, 14 unilateral adnexectomy, 2 unilateral cystectomy, and 1 bilateral cystectomy. No extensive GP surgery was performed. Six patients received adjuvant vinblastin, bleomycin, and cisplatinum because of tumor rupture (n = 5, including two patients with GP) or stage III (n = 1). After a median follow‐up of 39.5 months (range = 6‐238), two events occurred 10 and 11 months after diagnosis: one bilateralization (initial stage IX, grade I) and one IT peritoneal relapse (initial stage IA, grade II), respectively. Both were successfully rescued by platinum‐based chemotherapy and delayed surgery. No stage IC patients treated without adjuvant chemotherapy relapsed (four grade I and three grade III). None of the seven patients with GP progressed. Five‐year event‐free survival and overall survival were 94% (95% CI = 81‐98%) and 100%.
Conclusions
The current series confirms the excellent prognosis of pediatric ovarian IT, arguing for conservative surgical approach in GP and against systematic adjuvant chemotherapy, even in ruptured tumors.
Background
Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder due to a mutation in NF1 gene, resulting in phenotypically heterogeneous systemic manifestations. Patients with NF1 ...are prone to develop neoplasms of the central nervous system (CNS) and are particularly at risk for optic pathway gliomas (OPG). Epilepsy is another recognized neurologic complication in patients with NF1, with a prevalence estimated between 4% and 14%. Several case reports and early phase clinical trials have demonstrated that the mitogen‐activated protein kinase inhibitors (MEKi) are effective in NF1‐low‐grade gliomas (LGGs), but their influence on seizure activity in humans has not been established.
Case study
Here, we report a patient with NF1 and developmental and epileptic encephalopathy (DEE) harboring pharmacoresistant tonic seizures, and progressive optic pathway glioma (OPG). By using a MEKi therapy for her OPG, we observed an end to epileptic seizures as well as a significant improvement of interictal EEG abnormalities, despite a lack of tumor reduction.
Conclusion
MEK inhibitor therapy should be considered for patients with NF1 and refractory epilepsy.
Continuous intravenous (IV) infusion has been shown to be the best option to administer vancomycin because of its time‐dependent bactericidal activity. Available IV vancomycin dosing guidelines in ...pediatrics with normal renal function leads to less than 50% of patients achieving a vancomycin serum concentration (Css) in the target range (15–20 mg/L). The primary objective of this study was to prospectively validate an age‐based dosing regimen in pediatric oncology–hematology. The secondary objective was to investigate the influence on Css attainment of different variables. A continuous IV dosing nomogram was built by retrospective study (2000–2010) on Bayesian dosing adjustments performed in 161 patients. This study assessed the prospective validation of this age‐based nomogram and the influence on Css attainment of variables as the gender, underlying disease (oncology or hematology), and hematopoietic stem cell transplantation (HSCT) before receiving vancomycin therapy. A total of 94 patients aged from 4.3 months to 17.9 years old with normal renal function were eligible for the prospective validation. Fifty‐five of those patients (58.5%) achieved the target range of vancomycin Css. There was no significant difference between age groups (P = 0.816) and no influence of gender (P = 0.500). There was a nonsignificant trend to a better target attainment in oncology patients (69.2% vs. hematology 54.4%, P = 0.142) and patients who did not undergo HSCT (63.3% vs. 33.3%, P = 0.031). This study proposed an age‐based nomogram prospectively validated which near 60% of patients of each age class achieving the target range of Css.
