High-dose chemotherapy in soft tissue sarcoma in children

Soft tissue sarcomas (STS) are highly malignant tumours that constitute 5-6% of all malignant childhood neoplasms. Of these, rhabdomyosarcoma (RMS) is the most common in children, and has a characteristic two-peak age incidence, 2-5 and 15-19 years. Most children with RMS are cured with conventional chemotherapy and local therapy (surgery with or without radiotherapy). Children with metastatic disease at presentation, particularly those older than 10 years or with bone marrow or bone involvement have a much poorer outcome. In this subgroup, high-dose therapy with stem cell rescue has been studied over the last two decades. Various single or multiagent chemotherapy regimens with or without radiotherapy and autologous stem cell rescue have been used as consolidation treatment with little success. Recent trials using sequential high-dose chemotherapy in the early phase of treatment have proved to be feasible, but the beneficial effect has to be confirmed. The role of purging remains unclear. Collaboration between different international groups is urgently required, in an attempt to improve the poor outcome of children with high risk STS

Symptomatic severe hypertriglyceridaemia with asparaginase therapy in acute lymphoblastic leukaemia (ALL) and lymphoblastic lymphoma:is rechallenging safe?

Severe hyperlipidaemia with asparaginase therapy is rare. We report six cases, four of which developed significant problems with severe hyperlipidaemia during induction therapy for ALL and lymphoblastic lymphoma. The median triglyceride level was 22.3 mmol/L and the median cholesterol level was 12.3 mmol/L. None of the patients showed signs or symptoms of pancreatitis. Three children were re-exposed with Peg asparaginase, and one with Erwinia asparaginase, without recurrence of hyperlipidaemia or other symptoms. These cases highlight the dilemma in managing such rare cases of symptomatic hypertriglyceridaemia secondary to asparaginase and steroid therapy

Anterior mediastinal masses - A multidisciplinary pathway for safe diagnostic procedures.

OBJECTIVE The objective of this study was to report our multidisciplinary diagnostic approach for patients with anterior mediastinal masses (AMM). METHODS A retrospective review of patients with AMM at a tertiary pediatric surgical oncology centre (January 2011-December 2016) was performed. We analyzed data on clinical presentation, mode of tissue diagnosis, anesthetic techniques, and complications. RESULTS Of the 44 patients admitted with AMM (median age 11 years, 27 males and 17 females), 22 had respiratory symptoms. Imaging revealed tracheobronchial compression in 26 children. Twenty patients had a lymph node biopsy. Ten patients had image-guided core biopsy of the mediastinal mass, and 2 had mediastinoscopic biopsy of a paratracheal lymph node. One patient with likely recurrence of a relapsed metastatic ethmoid carcinoma did not have a biopsy. The diagnosis was made from alternative tissues, such as pleural fluid in 4 and peripheral blood in 7 patients. Twenty-five anesthetics were assessed, as 14 patients required no or only local anesthesia, and 5 had unavailable anesthetic notes. Eighteen of 25 patients were anesthetized maintaining spontaneous breathing, mostly by means of ketamine sedation. There were no major anesthetic complications. CONCLUSION Safe tissue diagnosis of anterior mediastinal masses can be obtained by a personalized multidisciplinary approach. Use of alternative tissues, local anesthesia, and ketamine sedation help minimize the need for general anesthesia, muscle paralysis, and controlled ventilation. LEVEL OF EVIDENCE IV (Case Series with no Comparison Group)

Isolated parenchymal lung involvement in children with stage IV Hodgkin's disease: results of the UKCCSG HD8201 and HD9201 studies

We retrospectively reviewed the case notes of 27 patients who were diagnosed with stage IV Hodgkin's disease (HD) because of isolated parenchymal pulmonary involvement on chest radiograph and computerized tomography scan (excluding subcategory E). Ten were boys and 15 had B symptoms. Median age at diagnosis was 13.6 years (range 6.1-16.2). All received 6-8 cycles of ChlVPP (chlorambucil, vinblastine, procarbazine and prednisolone) and two had additional whole lung irradiation (12 Gy). Ten patients (37%) relapsed or progressed. Seven survive following second-line therapy while three died, two of HD and one of secondary acute myeloid leukaemia 4 years from diagnosis. At the time of analysis, the median follow-up of patients was 56 months (range 9-127). The event-free survival (EFS) was 58.4% (95% CI 38.5-75.8%) at both 5 and 10 years from diagnosis, and the overall survival (OS) was 84.2% (95% CI 61.8-94.6%) at both 5 and 10 years from diagnosis. We conclude that the outcome for HD patients defined as stage IV, because of isolated parenchymal lung involvement, is encouraging and compares favourably with other extra lymphatic organ involvement. Combination chemotherapy is effective in achieving long-term remission and whole lung irradiation is unnecessary

The reliability of bone marrow cytology as response criterion in metastatic neuroblastoma

Background The quantitative assessment of neuroblastoma cell content in bone marrow aspirates for response evaluation has been introduced recently. Data on the concordance of interobserver reports are lacking so far. Methods Investigators of seven European countries representing national reference or large oncological centers convened in 2016. They agreed to quantitatively assess routine bone marrow smears of the participating institutions and to discuss the discrepant results in joint meetings. Results From 2017 through 2019, three cytology rounds with 24, 28, and 28 bone marrow samples were run evaluating the representativity of the smears (yes/[restricted]/no) and the presence of tumor cells (yes/no and %). The comparison of the reports using kappa (Fleiss) and alpha (Krippendorff) statistics demonstrated no robust reliabilities. The agreement on the representativity was moderate to poor, on the presence of tumor cells moderate to good, and on the percentage of tumor cells slight to moderate. Though the value of cytology is unquestioned to detect even tiny metastatic cells in bone marrow, the investigators unanimously agreed that a reliable quantification of the tumor cell content in bone marrow smears is unrealistic. For the key issue of representativity, a new practical definition was developed. Conclusion For any work with bone marrow aspirates, the representativity of the material is of paramount importance. A practical definition is proposed. A reliable quantitative cytological assessment of tumor cell content in bone marrow aspirates is not feasible in metastatic neuroblastoma. Therefore, its use as response criterion should be reconsidered