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.
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.
To assess the associations between congenital abnormalities and pediatric malignancies and evaluate the potential underlying molecular basis by collecting information on pediatric patients with ...cancer and congenital abnormalities.
Tumeur Et Développement is a national, prospective, and retrospective multicenter study recording data of children with cancer and congenital abnormalities. When feasible, blood and tumoral samples are collected for virtual biobanking.
From June 2013 to December 2019, 679 associations between pediatric cancers and congenital abnormalities were recorded. The most represented cancers were central nervous system tumors (n = 139; 20%), leukemia and myelodysplastic syndromes (n = 123; 18.1%), and renal tumors (n = 101; 15%). Congenital abnormalities were not related to any known genetic disorder in 66.5% of cases. In this group, the most common anomaly was intellectual disability (22.3%), followed by musculoskeletal (14.2%) and genitourinary anomalies (12.4%). Intellectual disability was mostly associated with hematologic malignancies. Embryonic tumors (neuroblastoma, Wilms tumor, and rhabdomyosarcoma) were associated with consistent abnormalities, sometimes with a close anatomical neighborhood between the abnormality and the neoplasm.
In the first Tumeur Et Développement analysis, 3 major themes have been identified: (1) germline mutations with or without known cancer predisposition, (2) postzygotic events responsible for genomic mosaicism, (3) coincidental associations. New pathways involved in cancer development need to be investigated to improve our understanding of childhood cancers.
Background
Treatment of extremity rhabdomyosarcomas (RMS) includes chemotherapy, surgery, and radiotherapy. Lymph node irradiation is recommended in the presence of regional node involvement at ...diagnosis. The aim of this study was to analyze the correlation between the pattern of relapse of non-metastatic extremity RMS and the initial therapies delivered.
Methods
All patients with localized extremity RMS prospectively treated in France in the MMT-95 and RMS-05 protocols were selected. Extent of disease and pattern of relapse were evaluated by clinical examination and imaging.
Results
We identified 59 patients with clinical characteristics corresponding to unfavorable prognostic factors. Twenty patients (34%) were considered to have lymph node involvement at diagnosis. Regional node biopsy was performed in 32 patients (54%) and modified the lymph node stage in 8 of the 59 patients (14%). Seventy-three percent of patients received radiotherapy. Fifty-two patients achieved first remission. Overall, 26 patients underwent complete tumor resection, 17 had R1 margins, and 5 were not operated due to early tumor progression. With a median follow-up of 82 months (range: 5–287), 18 relapses had occurred, at least locoregional in 12 cases. The 5‑year local and nodal control rates were 73% (63–86%) and 86% (77–95%), respectively. Five-year progression-free and overall survival were 57% (95%CI 45–72%) and 70% (95%CI 58–84%), respectively.
Conclusion
The main sites of extremity RMS relapse are locoregional. Nodal failures in non-irradiated fields are not uncommon. We recommend systematic biopsy of in-transit nodes, especially in alveolar RMS and/or RMS with regional positive nodes at diagnosis to ensure their negativity.
Background
Rhabdomyosarcoma (RMS) in infants is a particular entity with various clinical presentations and outcomes. To better understand the clinical heterogeneity of RMS in infants, an integrative ...clinical, histological, and molecular analysis was performed.
Methods
From 1989 to 2015, 37 infants aged less than 6 months with a diagnosis of RMS and archival tumor materials were identified in France. Clinical data, central pathologic review, and molecular profile including RNA sequencing were analyzed.
Results
Nineteen patients (51%) had embryonal RMS (ERMS) (including three highly differentiated ERMS with PTCH deletion), eight (22%) had spindle cell RMS (SRMS) (three VGLL2‐, one NTRK‐, and two (B)RAF‐fusions), six (16%) had alveolar RMS (ARMS) (all FOXO1‐ or PAX3‐fusion), two had unclassified RMS, and two poorly differentiated RMS were retrospectively diagnosed as rhabdoid tumors (RT) with loss of INI1 expression. The two RT patients died of rapid disease progression. Five‐year event‐free (EFS) and overall survival (OS) for RMS were 62% (95%CI, 47‐82) and 52% (95%CI, 37‐72). Eleven patients (31%) relapsed and four (11%) had primary refractory disease (all ERMS). In univariate analysis, EFS and OS were only associated with histology subtype, with 100% survival of known fusion‐positive SRMS. RNA cluster expression showed three main clusters: ARMS, ERMS, and “VGLL2‐fusion” cluster, consisting of SRMS and ERMS.
Conclusions
Biopathology findings from this study support the different prognosis of infantile RMS. New fusion‐positive SRMS has a very good outcome which may allow more conservative treatment in the future.
This study reported integrative clinical, histological, and molecular analysis of infants with RMS. Biopathology findings support the different prognosis of infantile RMS with new fusion‐positive spindle cell RMS having a very good outcome which may allow more conservative treatment in the future.
French patients (≤18years) treated for dysgerminoma between 1985 and 2005 in TGM-85, 90, 95 protocols were included. Treatment was based on primary unilateral oophorectomy followed by prophylactic ...lymph node irradiation (1985–1998) or a wait-and-see strategy (1998–2005) for localised completely resected tumours (pS1) or by platinum-based chemotherapy for advanced diseases.
Forty-eight patients (median age 12.8 years) were included. Six patients had gonadal dysgenesis. Two had bilateral dysgerminoma. Twenty-eight patients had loco-regional dissemination, seven with para-aortic lymph nodes. None had distant metastases. Primary surgery was performed in 47/48 patients. Among the 15 patients with pS1 tumour: seven did not receive adjuvant treatment, six had lymph node irradiation and two received chemotherapy. Among the 32 patients with advanced tumour, 31 received cisplatinum-based (n = 25) or carboplatin-based (n = 8) regimen with lymph node irradiation for one of them and one did not receive adjuvant treatment. With a median follow-up of 14 years, all patients are alive in complete remission. Five events occurred: 2 contralateral dysgerminomas, 1 peritoneal relapse and 2 second neoplasms (teratoma and melanoma). Bilateral oophorectomy was necessary for 12 patients. Desire of pregnancy was expressed for 17/36 patients with unilateral oophorectomy, which succeeded in 13 cases (5 medically assisted). 2/17 had ovarian failure. The renal function was normal in 24/25 evaluated patients treated with platinum, ifosfamide or irradiation. The hearing function was evaluated on 17/36 patients treated with platinum: 12 Brock grade-0, 3 brock grade-1 and 2 grade-4.
Dysgerminoma has an excellent prognosis even in advanced cases with conservative surgery and platinum-based chemotherapy. However the disease and/or treatment resulted in a high rate of bilateral oophorectomies and a significant impact on future fertility.
•Description of the largest series of children with dysgerminoma.•Very good prognosis of this disease whatever the stage.•Advanced stages are well treated with conservative surgery and chemotherapy.•Long-term follow-up, some issues in gonadal function after conservative surgery.
This study investigates invasive fungal infections (IFIs) in patients with acute myelogenous leukemia who were included in the Enfant Leucemie Aigue 02 protocol between 2005 and 2011. Among 387 ...patients, 15 had aspergillosis, 9 had candidiasis, and 2 had mucormycosis. The most frequent localization of IFIs was in the lungs. It was found that after a median of 34 months, 2 deaths were attributable to IFI without any difference in survival between the groups with and without IFI.
Background
The role of tumor molecular profiling in directing targeted therapy utilization remains to be defined for pediatric tumors. We aimed to evaluate the feasibility of a sequencing and ...molecular biology tumor board (MBB) program, and its clinical impact on children with solid tumors.
Procedure
We report on a single‐center MBB experience of 60 pediatric patients with a poor prognosis or relapsed/refractory solid tumors screened between October 2014 and November 2015. Tumor molecular profiling was performed with panel‐based next‐generation sequencing and array comparative genomic hybridization.
Results
Mean age was 12 ± 5.7 years (range 0.1–21.5); main tumor types were high‐grade gliomas (n = 14), rare sarcomas (n = 9), and neuroblastomas (n = 8). The indication was a poor prognosis tumor at diagnosis for 16 patients and relapsed (n = 26) or refractory disease (n = 18) for the remaining 44 patients. Molecular profiling was feasible in 58 patients. Twenty‐three patients (40%) had a potentially actionable finding. Patients with high‐grade gliomas had the highest number of targetable alterations (57%). Six of the 23 patients subsequently received a matched targeted therapy for a period ranging from 16 days to 11 months. The main reasons for not receiving targeted therapy were poor general condition (n = 5), pursuit of conventional therapy (n = 6), or lack of pediatric trial (n = 4).
Conclusions
Pediatric molecular profiling is feasible, with more than a third of patients being eligible to receive targeted therapy, yet only a small proportion were treated with these therapies. Analysis at diagnosis may be useful for children with very poor prognosis tumsors.
We investigated the role of household exposure to pesticides in the etiology of childhood hematopoietic malignancies. /// The national registry-based case-control study ESCALE (Etude sur les cancers ...de l'enfant) was carried out in France over the period 2003-2004. Population controls were frequency matched with the cases on age and sex. Maternal household use of pesticides during pregnancy and paternal use during pregnancy or childhood were reported by the mothers in a structured telephone questionnaire. Insecticides (used at home, on pets, or for garden crops), herbicides, and fungicides were distinguished. We estimated odds ratios (ORs) using unconditional regression models closely adjusting for age, sex, degree of urbanization, and type of housing (flat or house). /// We included a total of 764 cases of acute leukemia (AL), 130 of Hodgkin lymphoma (HL), 166 of non-Hodgkin lymphoma (NHL), and 1,681 controls. Insecticide use during pregnancy was significantly associated with childhood AL OR = 2.1; 95% confidence interval (CI), 1.7-2.5, both lymphoblastic and myeloblastic, NHL (OR = 1.8; 95% CI, 1.3-2.6), mainly for Burkitt lymphoma (OR = 2.7; 95% CI, 1.6-4.5), and mixed-cell HL (OR = 4.1; 95% CI, 1.4-11.8), but not nodular sclerosis HL (OR = 1.1; 95% CI, 0.6-1.9). Paternal household use of pesticides was also related to AL (OR = 1.5; 95% CI, 1.2-1.8) and NHL (OR = 1.7; 95% CI, 1.2-2.6); but for AL the relationships did not remain after adjustment for maternal pesticide use during pregnancy. /// The study findings strengthen the hypothesis that domestic use of pesticides may play a role in the etiology of childhood hematopoietic malignancies. The consistency of the findings with those of previous studies on AL raises the question of the advisability of preventing pesticide use by pregnant women.
Complete surgical resection constitutes the mainstay of treatment for locally aggressive, rarely metastazing tumor and low-grade soft tissue sarcomas (LAS). Local relapse is the most common tumor ...event, especially in the presence of positive margins (R1 margins). The aims of this study are to assess the impact of the national network on patient care and to evaluate the role of immediate re-excision in children, adolescents and young adults with incompletely resected LAS.
National retrospective multicenter study of all young patients (≤25 years) included in the Sarcoma “ConticaBase” treated for LAS between 2005 and 2017 for whom pathology/biology review was available via the national NETSARC + network.
A total of 96 patients were identified (median age: 16 years). Tumors were localized in 99% of cases (1 N+ tumor). With a median follow-up of 4.7 years (range: 0.1–11.9), eight local relapses and two distant metastases were observed. No patient died. Overall 5-year event-free survival (EFS) was 90.4% 95%CI, 84.3–97. Five year EFS for R1 patients (n = 51) with (n = 24) and without (n = 27) immediate re-excision was 90.5% 95%CI, 78.8–100.0 and 80.3% 95%CI, 64.7–99.9, respectively (p = 0.34). The 37 patients directly treated in a reference center more commonly had a diagnostic biopsy (78% vs. 21%; p < 0.001), more complete surgery (R0: 65% vs. 14%; p < 0.001) and less commonly underwent re-excision (16% vs. 54%; p < 0.001).
This large series indicates that LAS are rare in young patients and have a favorable prognosis. Immediate management in reference centers is associated with better standard of care. The main tumor events are local relapses.
•Large study on young patients with low grade sarcomas•Initial care in expert centers allows a better management•Molecular biology has a central role in the diagnosis characterization•Complete tumor resection is the therapeutic cornerstone•The question of immediate re-excision after incomplete surgery is discussed
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