Mediastinal Germ-cell Tumors Relapse in a Male With Klinefelter Syndrome. Is Longer Surveillance Needed?

Germ cell tumors (GCTs) are a heterogeneous group of pediatric cancers. In up to one-third of male patients, a primary mediastinal location is associated with the presence of Klinefelter syndrome (KS). We describe a case of mediastinal GCT in a patient, with unacknowledged KS, that presented a relapse 7 years from diagnosis, that is, 2 years after the end of the follow-up program usually recommended for patients with GCT. There are no recommendations for screening for KS in patients with mediastinal GCT and there are no specific guidelines for surveillance of GCT in KS patients. Our experience suggests that KS should be suspected in patients with mediastinal GCT, and a longer follow-up plan should be implemented when GCT occurs in patients with KS.

Lung relapse pattern in children with metastatic Wilms tumor.

Wilms tumor is the most common pediatric renal cancer, and lungs represent the major site of metastasis and recurrence. Relapse occurs in 15%, months or years after treatment; so due to the small sample, acquiring more data about the pattern of lung relapse remains a challenge. The aim of our study was to evaluate if pulmonary relapse, detected by computed tomography (CT), occurred at the initial site of lung metastases or in a different location. According to our data, the CT pattern of lung relapse showed high probability of recurrence at the same site of initial metastasis.

Children with progressive and relapsed pleuropulmonary blastoma: A European collaborative analysis.

BACKGROUND: Children with progressive (PD) or relapsed disease (RD) of pleuropulmonary blastoma (PPB) type II/III are known to have a very poor outcome. METHODS: A retrospective review of children registered in national and European databases and trials (2000-2018) with diagnosis of PPB type II/III and PD or RD was performed. RESULTS: A total of 35 patients with PPB were analysed: patients with PD (n = 9) and RD (n = 26). Patients experienced PD at the median age of 3.9 years [range, 0.5-17.8] despite surgery, chemotherapy (CHT, n = 9) and radiotherapy (RT, n = 1) with a median time to progression of 0.58 years [range, 0.02-1.27] from diagnosis. All of them died. Patients suffered from RD at the median age of 4.3 years [1.7-15.1], median delay to relapse 1.03 years [range, 0.03-2.95]. RD occurred locally (n = 12), combined (n = 1) and in metastatic sites (n = 13): central nervous system (n = 11) and unspecified site (n = 2). Patients were treated with salvage CHT (n = 20), surgery (n = 10) ± RT (n = 10). After a median follow-up of 4.2 years [range, 2.1-14.6], a second complete remission (CR) was achieved in nine out of 26 patients. Patients were alive in the second CR (n = 6), in the third CR (n = 1), in partial remission (n = 2) and lost of follow-up (n = 1). Five-year event-free survival (EFS) and overall survival (OS) for patients with RD were both 37% (±19, CI 95%). Local therapy (surgery, RT) had a favourable impact on OS (p = 0.03 and 0.02, respectively). CONCLUSIONS: Cure of patients with RD of PPB type II/III with multimodal treatment is possible but rare. Progressive PPB is fatal and patients need new treatment options.

Integrating irinotecan in standard chemotherapy: A novel dose-density combination for high-risk pediatric sarcomas.

BACKGROUND: Irinotecan is a drug active against pediatric sarcomas with a toxicity profile that theoretically allows for its association with more myelotoxic drugs. We examined the feasibility of a dose-density strategy integrating irinotecan in standard chemotherapy regimens for patients with high-risk sarcomas. METHODS: Between November 2013 and January 2020, 23 patients ≤25 years old were included in the study. Eleven patients newly diagnosed with metastatic disease received nine cycles of IrIVA (irinotecan-ifosfamide-vincristine-actinomycin D; ifosfamide 3 g/m2 on days 1 and 2, vincristine 1.5 mg/m2 on day 1, actinomycin D 1.5 mg/m2 on day 1, irinotecan 20 mg/m2 for 5 consecutive days starting on day 8) as first-line therapy. Two relapsed patients received IrIVA and 10 IrVAC (irinotecan-vincristine-actinomycin D-cyclophosphamide; cyclophosphamide 1.5 g/m2 on day 1 instead of ifosfamide). Feasibility was assessed in terms of toxicity and time to complete the treatment. RESULTS: Seventeen rhabdomyosarcomas, four Ewing sarcomas, two desmoplastic small round cell tumors received a total of 181 cycles (range 2-10). Grade 4 neutropenia occurred in 62.4% of the cycles. Thirteen patients had febrile neutropenia. Diarrhea occurred in 14 cycles. The median time to complete the treatment was 195 days (range 170-231), 83.4% of cycles were administered on time or with a delay <1 week. With a median follow-up of 2.6 years (range 0.2-5.0), 12 patients are alive, nine complete remissions, three with the disease. CONCLUSIONS: A dose-density strategy combining irinotecan with standard chemotherapy is feasible. This approach will be investigated in the next trial coordinated by the European pediatric Soft tissue sarcoma Study Group.

Pleuropulmonary blastoma: a report from the TREP (Tumori Rari in Età Pediatrica) Project.

INTRODUCTION: Pleuropulmonary blastoma (PPB) is a rare, aggressive mesenchymal tumor of childhood. The Italian Tumori Rari in Età Pediatrica (TREP) Registry was the first in Europe dedicated to prospective data collection on rare pediatric tumors. We analyzed data from an Italian series of patients with PPB, focusing on the role of the TREP Project. METHODS: We considered patients aged 0-14 with histologically confirmed diagnosis, registered in population-based cancer registries (before 2000) or the TREP Registry (2000 to 2014), and analyzed data on clinical characteristics, treatment, and outcome. Event-free survival (EFS) and overall survival (OS) were estimated. Relevant prognostic factors were identified performing a univariate analysis. RESULTS: Thirty-seven cases were included (7 type I, 13 type II, 17 type III). The average diagnosis rate rose from 1.10 to 1.73 cases/year after the TREP Project started. All patients underwent surgery, 33 received chemotherapy, and 9 had radiotherapy. The median follow-up was 8.7 years. For type I, II, and III, respectively, the 5-year OS was 85.7% (33.4-97.9), 52.7% (23.4-75.5), and 57.8% (31.1-77.3); the 5-year EFS was 85.7% (33.4-97.9), 52.7% (23.4-75.5), and 52.9% (27.6-73.0). Favorable prognostic factors for EFS were Intergroup Rhabdomyosarcoma Study (IRS) stage I (p = 0.03) and T1 tumor (p = 0.05). A total of 78.3% of patients who had chemotherapy after 2000 received a standardized treatment. CONCLUSIONS: The TREP Registry showed an excellent capacity for registering cases of PPB. Patients received homogeneous treatment after the TREP Project started. Long-term outcomes were excellent for type I and unsatisfactory for type II and III. Tumor invasiveness and IRS stage were of prognostic value.

Myoepithelial carcinoma treatment in children: a report from the TREP project.

BACKGROUND: Myoepithelial carcinoma (MC) of soft tissues is an aggressive tumor that rarely affects children, for whom no established treatment protocols exist. As part of the TREP (Tumori Rari in Età Pediatrica) project - an Italian network dedicated to children and adolescents with very rare tumors - we present a series of patients with MC, who were treated homogeneously and achieved a satisfactory outcome. PROCEDURE: From 2005 to 2012, seven patients (age 0.5-9.2 years) with a diagnosis of MC were registered in the TREP study. After one patient treated with ifosfamide, cisplatin, and etoposide showed tumor shrinkage and experienced long-term disease remission, all subsequent patients were treated with the same chemotherapy regimen. All patients also received radiotherapy. RESULTS: Initial surgical management involved a biopsy in three cases and tumor resection in 4. Response to initial chemotherapy was evaluable in four patients: two had a partial remission, one a minor response and one stable disease. Four patients received external-beam radiotherapy and three had brachytherapy. Overall, six patients are alive in first complete remission with a median follow-up of 2.5 years (0.9-5.1 years). CONCLUSIONS: Though our experience is limited to a small number of patients, our treatment strategy for patients with MC is appears clinically useful and demonstrates how cooperation within the TREP project has enabled enough data to be collected to propose treatment recommendations for pediatric patients with this very rare tumor.

Hydroxyurea treatment can avoid the need for aggressive surgery in pediatric fibromatosis.

Aggressive fibromatosis is a rare tumor of borderline malignancy with a marked local aggressiveness. Surgery is the mainstay of treatment but complete tumor resection is often not easy to achieve without functional and cosmetic sequelae. We report a case of a pretreated child with aggressive fibromatosis who responded to hydroxyurea, avoiding the need for demolitive surgery.

Primary renal soft tissue sarcoma in children.

OBJECTIVE: To describe clinical and treatment characteristics of renal soft tissue sarcomas in children, we analyzed a series of patients enrolled in the protocols coordinated by the Italian Soft Tissue Sarcoma Committee (STSC). METHODS: From 1979 to 2011, 2138 patients with soft tissue sarcomas were registered in different STSC protocols, and 12 had a renal sarcoma: 7 primitive peripheral neuroectodermal tumors, 2 undifferentiated sarcomas, 1 rhabdomyosarcoma, 1 desmoplastic small round cell tumor, and 1 kaposiform hemangioendothelioma. Treatment included conservative surgery, chemotherapy according to the guidelines of the protocols, and radiotherapy for high-risk patients. RESULTS: Nephrectomy was performed in 11 children resulting in a complete tumor resection in 7. In 4 patients, macroscopical (1) or microscopic (3) tumor residuals remained postoperatively. Tumorectomy was performed in patients with congenital renal agenesis. All patients received chemotherapy. Seven patients also received postoperative radiotherapy. Overall, 9 patients are alive in first complete remission with a median follow-up of 6.1 years (range, 1.3-21.1 years). Two of the 7 patients with primitive peripheral neuroectodermal tumors (pPNETs) died after an early relapse: 1 had metastatic disease at diagnosis and the other was initially misdiagnosed with Wilms tumor (WT). One child with desmoplastic small round cell tumor (DSRCT) is alive with disease. Two patients developed signs of ifosfamide-related nephrotoxicity. CONCLUSION: In our analysis, pPNET is the most common type of renal soft tissue sarcoma (STS). Prognosis seems satisfactory with the adoption of an aggressive multidisciplinary approach, especially when complete tumor resection is possible. The replacement of ifosfamide with cyclophosphamide could be considered after nephrectomy.