Developments in the Surgical Approach to Staging and Resection of Rhabdomyosarcoma

Local treatment; Rhabdomyosarcoma; SurgeryTratamiento local; Rabdomiosarcoma; CirugíaTractament local; Rabdomiosarcoma; CirurgiaAlthough survival after rhabdosarcoma treatment has improved over the years, one third of patients still develop locoregional relapse. This review aims to highlight developments pertaining to staging and local treatment of specific RMS tumor sites, including head and neck, chest/trunk, bladder-prostate, female genito-urinary, perianal, and extremity sites

Outcome of patients with undifferentiated embryonal sarcoma of the liver treated according to European soft tissue sarcoma protocols

Liver; Pediatrics; SarcomaFetge; Pediatria; SarcomaHígado; Pediatría; SarcomaBackground To assess the outcomes of pediatric patients with undifferentiated embryonal sarcoma of the liver (UESL) and treatment including at least surgery and systemic chemotherapy. Methods This study included patients aged up to 21 years with a pathological diagnosis of UESL prospectively enrolled from 1995 to 2016 in three European trials focusing on the effects of surgical margins, preoperative chemotherapy, use of radiotherapy (RT), and chemotherapy. Results Out of 65 patients with a median age at diagnosis of 8.7 years (0.6–20.8), 15 had T2 tumors, and one had lymph node spread, 14 were Intergroup Rhabdomyosarcoma Study (IRS) I, nine IRS II, 38 IRS III, and four IRS IV. Twenty-eight upfront surgeries resulted in five operative spillages and 11 infiltrated surgical margins, whereas 37 delayed surgeries resulted in no spillages (p = .0119) and three infiltrated margins (p = .0238). All patients received chemotherapy, including anthracyclines in 47. RT was administered in 15 patients. With a median follow-up of 78.6 months, 5-year overall and event-free survivals (EFS) were 90.1% (95% confidence interval [CI]: 79.2–95.5) and 89.1% (95% CI: 78.4–94.6), respectively. Two out four local relapses had previous infiltrated margins and two out of three patients with metastatic relapses received reduced doses of alkylating agents. Infiltrated margins (p = .1607), T2 stage (p = .3870), use of RT (p = .8731), and anthracycline-based chemotherapy (p = .1181) were not correlated with EFS. Conclusions Multimodal therapy improved the outcome of UESL. Neoadjuvant chemotherapy for pediatric patients increases the probability of complete surgical resection. The role of anthracyclines and RT for localized disease remains unclear

Surgical treatment of childhood hepatoblastoma in the Netherlands (1990–2013)

Background: Achievement of complete surgical resection plays a key role in the successful treatment of children with hepatoblastoma. The aim of this study is to assess the surgical outcomes after partial liver resections for hepatoblastoma, focusing on postoperative complications, resection margins, 30-day mortality, and long-term survival. Method: Chart reviews were carried out on all patients treated for hepatoblastoma in the Netherlands between 1990 and 2013. Results: A total of 103 patients were included, of whom 94 underwent surgery. Partial hepatectomy was performed in 76 patients and 18 patients received a liver transplant as a primary procedure. In 42 of 73 (58 %) patients, one or more complications were reported. In 3 patients, information regarding complications was not available. Hemorrhage necessitating blood transfusion occurred in 33 (45 %) patients and 9 (12 %) patients developed biliary complications, of whom 8 needed one or more additional surgical interventions. Overall, 5-year disease-specific survival was 82, 92 % in the group of patients who underwent partial hepatectomy, and 77 % in the group of patients who underwent liver transplantation. Conclusions: Partial hepatectomy after chemotherapy in children with hepatoblastoma offers good chances of survival. This type of major surgery is associated with a high rate of surgical complications (58 %), which is not detrimental to survival

Mesenchymal tumor organoid models recapitulate rhabdomyosarcoma subtypes

Rhabdomyosarcomas (RMS) are mesenchyme-derived tumors and the most common childhood soft tissue sarcomas. Treatment is intense, with a nevertheless poor prognosis for high-risk patients. Discovery of new therapies would benefit from additional preclinical models. Here, we describe the generation of a collection of 19 pediatric RMS tumor organoid (tumoroid) models (success rate of 41%) comprising all major subtypes. For aggressive tumors, tumoroid models can often be established within 4-8 weeks, indicating the feasibility of personalized drug screening. Molecular, genetic, and histological characterization show that the models closely resemble the original tumors, with genetic stability over extended culture periods of up to 6 months. Importantly, drug screening reflects established sensitivities and the models can be modified by CRISPR/Cas9 with TP53 knockout in an embryonal RMS model resulting in replicative stress drug sensitivity. Tumors of mesenchymal origin can therefore be used to generate organoid models, relevant for a variety of preclinical and clinical research questions

Alveolar Rhabdomyosarcoma with Regional Nodal Involvement: Results of a Combined Analysis from Two Cooperative Groups

BACKGROUND: Treatment of children and adolescents with alveolar rhabdomyosarcoma (ARMS) and regional nodal involvement (N1) have been approached differently by North American and European cooperative groups. In order to define the better therapeutic strategy, we analyzed two studies conducted between 2005 and 2016 by the European paediatric Soft tissue sarcoma Study Group (EpSSG) and Children’s Oncology Group (COG). METHODS: We retrospectively identified patients with ARMS-N1 enrolled in either EpSSG RMS2005 or in COG ARST0531. Chemotherapy in RMS2005 comprised IVADo (ifosfamide, vincristine, dactinomycin, doxorubicin), IVA and maintenance (vinorelbine, cyclophosphamide); in ARST0531 it consisted on either VAC (vincristine, dactinomycin, cyclophosphamide) or VAC alternating with VI (vincristine, irinotecan). Local treatment was similar in both protocols. RESULTS: The analysis of the clinical characteristics of 239 patients showed some differences between study groups: in RMS2005, advanced IRS Group and large tumors predominated. There were no differences in outcomes between the two groups: 5-year event-free survival (EFS), 49%(95%CI=39–59) and 44%(95%CI=30–58), and overall survival (OS), 51%(95%CI=41–61) and 53.6%(95%CI=40–68), in RMS2005 and ARST0531, respectively. In RMS2005, EFS of patients with FOXO1-positive tumors was significantly inferior to those FOXO1-negative (49.3% vs 73%, p=0.034). In contrast, in ARST0531, EFS of patients with FOXO1-positive tumors was 45% compared with 43.8% for those FOXO1-negative. CONCLUSIONS: The outcome of patients with ARMS N1 was similar in both protocols. However, patients with FOXO1 fusion-negative tumors enrolled in RMS2005 showed a significantly better outcome, suggesting that different strategies of chemotherapy may have an impact in the outcome of this subgroup of patients

Mesenchymal tumor organoid models recapitulate rhabdomyosarcoma subtypes

Rhabdomyosarcomas (RMS) are mesenchyme-derived tumors and the most common childhood soft tissue sarcomas. Treatment is intense, with a nevertheless poor prognosis for high-risk patients. Discovery of new therapies would benefit from additional preclinical models. Here, we describe the generation of a collection of 19 pediatric RMS tumor organoid (tumoroid) models (success rate of 41%) comprising all major subtypes. For aggressive tumors, tumoroid models can often be established within 4–8 weeks, indicating the feasibility of personalized drug screening. Molecular, genetic, and histological characterization show that the models closely resemble the original tumors, with genetic stability over extended culture periods of up to 6 months. Importantly, drug screening reflects established sensitivities and the models can be modified by CRISPR/Cas9 with TP53 knockout in an embryonal RMS model resulting in replicative stress drug sensitivity. Tumors of mesenchymal origin can therefore be used to generate organoid models, relevant for a variety of preclinical and clinical research questions

Surgical treatment of childhood hepatoblastoma in the Netherlands (1990-2013)

Achievement of complete surgical resection plays a key role in the successful treatment of children with hepatoblastoma. The aim of this study is to assess the surgical outcomes after partial liver resections for hepatoblastoma, focusing on postoperative complications, resection margins, 30-day mortality, and long-term survival. Chart reviews were carried out on all patients treated for hepatoblastoma in the Netherlands between 1990 and 2013. A total of 103 patients were included, of whom 94 underwent surgery. Partial hepatectomy was performed in 76 patients and 18 patients received a liver transplant as a primary procedure. In 42 of 73 (58 %) patients, one or more complications were reported. In 3 patients, information regarding complications was not available. Hemorrhage necessitating blood transfusion occurred in 33 (45 %) patients and 9 (12 %) patients developed biliary complications, of whom 8 needed one or more additional surgical interventions. Overall, 5-year disease-specific survival was 82, 92 % in the group of patients who underwent partial hepatectomy, and 77 % in the group of patients who underwent liver transplantation. Partial hepatectomy after chemotherapy in children with hepatoblastoma offers good chances of survival. This type of major surgery is associated with a high rate of surgical complications (58 %), which is not detrimental to surviva

Long-Term Oncological Outcomes of Papillary Thyroid Cancer and Follicular Thyroid Cancer in Children: A Nationwide Population-Based Study

Introduction: Pediatric thyroid carcinoma is a rare malignancy and data on long-term oncological outcomes are sparse. The aim of this study was to describe the long-term oncological outcomes of pediatric papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) in a national cohort, and to identify risk factors for recurrence. Methods: We conducted a nationwide, retrospective cohort study, in which we combined two national databases. Patients aged <18 years, diagnosed with PTC or FTC in the Netherlands between 2000 and 2016, were included. pT-stage, pN-stage, multifocality and angioinvasion were included in a Cox-regression analysis for the identification of risk factors for recurrence. Results: 133 patients were included: 110 with PTC and 23 with FTC. Patients with PTC most often presented with pT2 tumors (24%) and pN1b (45%). During a median follow-up of 11.3 years, 21 patients with PTC developed a recurrence (19%). Nineteen recurrences were regional (91%) and 2 were pulmonary (9%). No risk factors for recurrence could be determined. One patient who developed pulmonary recurrence died two years later. Cause of death was not captured. Patients with FTC most often presented with pT2 tumors (57%). One patient presented with pN1b (4%). In 70%, no lymph nodes were collected. None of the patients with FTC developed a recurrence or died. Conclusion: Pediatric PTC and FTC are two distinct diseases. Recurrence in pediatric PTC is common, but in FTC it is not. Survival for both pediatric PTC and FTC is very good