Search

Introduction: The treatment paradigm in desmoid-type fibromatosis (DF) has changed in recent years from a surgery-based strategy to a multidisciplinary approach that includes systemic therapies. Among various medical therapies, hydroxyurea has been considered of potential interest. This case series summarizes the experience gained at four centers using hydroxyurea in relapsing DF., Methods: Eligibility requirements were age < 21 years, histologically confirmed DF, and progressive or recurrent disease after at least one line of systemic therapy. Hydroxyurea was given orally at an initial dose of 20 mg/kg/day (escalated up to 30 mg/kg/day as necessary, if well tolerated)., Results: The series included 16 patients treated between 2008 and 2016. Hydroxyurea was the second systemic therapy in nine cases, and the third (at least) in seven. There was no reported G3-G4 hematological toxicity, and one case of G3 diarrhea. Dose reductions were reported in three cases (due to G2 neutropenia). The response rate was 18.7% major partial remissions, 37.5% considering any amount of shrinkage, 68.7% considering symptom response or signs of tissue response as well. In patients with no progression, the treatment was continued for 9-24 months., Conclusion: This is the first published series on the efficacy of hydroxyurea in pediatric DF. The response rate was moderate, but similar to that reported for other medical therapies currently considered as treatment options in this disease. Though further, larger series are needed to confirm as much, hydroxyurea has potential as an effective alternative therapy for DF., (© 2018 Wiley Periodicals, Inc.)

Mucormycosis are opportunistic infections mostly observed in immunocompromised patients. We report the case of a 13-year-old girl who suffered a systemic mucormycosis without presenting the usual risk factors. She was undergoing antineoplastic chemotherapy for advanced osteosarcoma of the femur with an uncommunicative pathologic fracture and pulmonary metastasis. Absidia corymbifera was isolated from skin lesions at the primary tumor site. She subsequently developed fungal pulmonary localizations and blood vessel thrombosis. Surgical treatment together with systemic, high doses of liposomal amphotericin B, posaconazole, and caspofungin cured the local infection and controlled systemic lesions. Unfortunately, the break in chemotherapy led to pulmonary metastasis progression.

Targeted neurotrophic tropomyosin receptor kinase (TRK) inhibitors offer a highly specific therapeutic option for patients with infantile fibrosarcoma (IFS) carrying the NTRK gene translocation. International recommendations are needed to define the role of TRK inhibitors (TRKI) for infants with IFS. We analysed retrospective data for all published patients with IFS in the European Paediatric Soft tissue sarcoma Study Group and Cooperative Weichteilsarkomstudiengruppe (CWS) experience and developed a consensus strategy with the Children's Oncology Group. Therapies consisted of tumour resection and/or perioperative chemotherapy for extensive tumours. Among the 172 European patients treated, 162 were alive at the end of the follow-up. Sixty-five patients (40% of all survivors) were treated with surgery alone and 64 patients (39%) with surgery combined with chemotherapy. Radiotherapy was delivered to 3% of survivors (five patients). In addition, 28 survivors (17%) exclusively received chemotherapy. Among the 129 patients treated with surgery, 91% had conservative surgery (118 cases). Overall, nine patients died of disease, one from toxicity (6%) and 20 patients (12%) survived with major functional deficits or had mutilating surgery. Overall, conventional conservative strategies before the era of targeted therapy, even in the case of extensive tumours, demonstrate efficacy in IFS, but are associated with acute and some chronic side effects. TRKI have demonstrated very rapid responses in the vast majority of children with IFS with limited acute toxicity. With the current state of our knowledge, both conventional chemotherapy and TRKI should be regarded as options for patients with localised disease at the physician's and parent's discretion. TRKI should be considered in patients with metastatic disease, and before mutilating surgery when conventional chemotherapy fails. Outside a clinical trial, additional data are needed to resolve the lack of consensus about front-line use of conventional chemotherapy versus TRKI in patients with localised disease. • Neurotrophic tropomyosin receptor kinase inhibitors (NTRKI) are new target drugs. • NTRKI are really efficient against infantile fibrosarcoma (IFS). • Pros and cons of NTRKI for patients with IFS are discussed. • An international consensus is proposed for advanced or refractory IFS. • This paper will help clinicians to better treat children with IFS. [ABSTRACT FROM AUTHOR]

We analysed the cohort of paediatric patients with metastatic non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) treated in the BERNIE protocol, i.e. open-label, multicentre, randomised phase II study evaluating the role of bevacizumab (BO20924/ITCC-006; ClinicalTrials.gov: NCT00643565). Eligible patients were randomised 1:1 to add or not add bevacizumab to nine courses of intensive multi-drug chemotherapy, followed by 12-month maintenance chemotherapy (plus surgery and radiotherapy). The primary end-point was event-free survival (EFS); secondary objectives were objective response rate (ORR) and overall survival (OS). From 2008 and 2013, 49 NRSTS patients (out of 154 cases) were treated, 26 in the standard arm and 23 in the bevacizumab arm. ORR was seen in 10 out of 36 evaluable cases (27.7%), i.e. 4/18 standard arm cases and 6/18 bevacizumab arm cases. Two-year EFS was 27.3% (95% confidence interval [CI] 13.9–42.5) for all NRSTS patients, i.e. 34.9% (95% CI 14.6–56.2) for bevacizumab arm and 22.9% (95% CI 7.1–43.9) for standard arm (p -value = 0.19). Three-year OS (median follow-up 48.6 months) was 35.2%, with no differences in the two arms. Time to event and time to death were 16.3 and 17.2 months for bevacizumab arm and 2.1 and 7.6 months for standard arm, respectively. Patients not receiving any local treatment on primary disease had a worse outcome as compared to others. Treatment results were better for patients receiving surgical resection and worse for those who did not receive any specific treatment. The addition of the anti-angiogenic agent to the standard chemotherapy did not show statistically significant improvement in survival in metastatic NRSTS. • This is the first series of paediatric metastatic NRSTS treated in a randomised phase II trial including a biologic agent. • The addition of the anti-angiogenic agent to the standard chemotherapy did not show significant improvement in survival. • This series may be considered benchmark for this disease category for developing future investigational studies. [ABSTRACT FROM AUTHOR]

We report the clinical findings and results of treatment in the cohort of patients with inflammatory myofibroblastic tumor (IMT) managed according to the European pediatric Soft Tissue Sarcoma Study Group (EpSSG) protocol from 2005 to 2016. Patients (<25 years old) with IMT from 9 countries were prospectively registered via a web-based system. Their histology was reviewed by a national/international pathology panel. Immunohistochemistry for ALK assessment was mandatory. No adjuvant therapy was suggested for initially resected tumors. No specific systemic therapy was recommended for cases of unresectable disease. Among 80 cases of IMT registered, 20 were excluded because pathology review led to a revised diagnosis. Of the remaining 60 patients (median age 9.5 years), 59 had localized, and 1 had multifocal/metastatic disease. The lung was the primary site in 14 cases. IMT developed as a second tumor in 2 cases. Forty cases were ALK-positive, and 20 were ALK-negative. Five-year event-free survival (EFS) and overall survival (OS) were 82.9% and 98.1%, respectively. No clinical variables correlated statistically with the outcome: survival was the same for ALK-positive and ALK-negative cases. The overall response to systemic therapy was 64%: 8/10 cases responded to vinblastine-methotrexate chemotherapy, and 5/5 to ALK-inhibitors. This study demonstrated a good overall prognosis for IMT, even for initially unresectable disease and in ALK-negative cases. Chemotherapy is still a valid option for advanced disease. Larger studies involving both pediatric and adult patients are needed to clarify the role of ALK inhibitors. • Pediatric inflammatory myofibroblastic tumors have good prognosis, even in initially unresectable and ALK-negative cases. • High response to chemotherapy (especially the minimal-morbidity therapy vinblastine and low-dose methotrexate) were observed. • The efficacy of targeted inhibitors seems to point to their use as the standard of care, but larger studies are needed. [ABSTRACT FROM AUTHOR]