Primary Leptomeningeal Medulloblastoma in Adults: A Diagnostic Challenge-Case Report and Systematic Review.

Primary leptomeningeal medulloblastoma (PL-MB) in adults is a rare disease with a severe prognosis. A 35-year-old woman presented with headaches, diplopia, and gait ataxia, with triventricular hydrocephalus and descent of the cerebellar tonsils beyond the foramen magnum. Endoscopic third ventriculostomy was performed. Six months later, headaches recurred. Dilatation of the supratentorial ventricular system and massive cerebellar swelling without contrast-enhancing nodularities were reported. Occipitocervical decompression with duraplasty was performed. A bioptic diagnosis of PL-MB was made. Craniospinal irradiation and chemotherapy were administered. After 18 months, no recurrence was observed. Few cases of PL-MB have been reported: patients die before treatment or within a few days after surgery. Our long-term survival could be ascribable to a slow clinical presentation and an early diagnosis that allowed surgical treatment and the administration of a combined chemoradiotherapy protocol. Cerebellar swelling, even without associated enhancing lesions, with or without hydrocephalus, should be a neuroradiological alarm sign, and PL-MB should be considered.

Cardiologic Long-Term Follow-Up of Patients Treated With Chest Radiotherapy: When and How?

Introduction: Radiotherapy may cause valvular (VHD), pericardial, coronary artery disease (CAD), left ventricular dysfunction (LVD), arrhythmias. The risk of radiation induced heart disease (RIHD) increases over time. The current guidelines suggest a screening for RIHD every 5 years in the long-term survivors who had been treated by chest RT. Methods: We reviewed the clinical and instrumental data of 106 patients diagnosed with RIHD. In one group (Group A: 69 patients) RIHD was diagnosed in an asymptomatic phase through a screening with ECG, echocardiogram and stress test. A second group (37 patients) was seen when RIHD was symptomatic. We compared the characteristics of the two groups at the time of RT, of RIHD detection and at last follow-up. Results: Overall, 64 patients (60%) had CAD (associated to other RIHD in 18); 39 (36.7%) had LVD (isolated in 20); 24 (22.6%) had VHD (isolated in 10 cases). The interval between the last negative test and the diagnosis of moderate or severe RIHD was <5 years in 26 patients, and <4 years in 18. In group A, 63% of the patients with CAD had silent ischemia. The two groups did not differ with regard to type of tumor, cardiovascular risk factors, use of anthracycline-based chemotherapy, age at RT treatment, radiation dose and interval between RT and toxicity detection. The mean time from RT and RIHD was 16 years in group A and 15 in group B. Interventional therapy at RIHD diagnosis was more frequent in group B (54 vs. 30%, p < 0.05). At last follow-up, 27 patients had died (12 of cancer, 9 of cardiac causes, 6 of other causes); mean ejection fraction was 60% in group A and 50% in group B (p < 0.01). Patients with ejection fraction ≤ 50% were 14.5% in group A and 40% in group B (p < 0.01). Conclusions: Clinically relevant RIHD become evident at a mean interval of 16 years after RT. The most frequent clinical manifestations are CAD and LVD. RIHD diagnosis in asymptomatic patients may preserve their cardiac function with timely interventions. We suggest -after 10 years from radiotherapy- a screening every 2-3 years.

Whole Lung Irradiation after High-Dose Busulfan/Melphalan in Ewing Sarcoma with Lung Metastases: An Italian Sarcoma Group and Associazione Italiana Ematologia Oncologia Pediatrica Joint Study.

PURPOSE: To analyze toxicity and outcome predictors in Ewing sarcoma patients with lung metastases treated with busulfan and melphalan (BU-MEL) followed by whole-lung irradiation (WLI). METHODS: This retrospective study included 68 lung metastatic Ewing Sarcoma patients who underwent WLI after BU-MEL with autologous stem cell transplantation, as part of two prospective and consecutive treatment protocols. WLI 12 Gy for <14 years old and 15 Gy for ≥14 years old patients were applied at least eight weeks after BU-MEL. Toxicity, overall survival (OS), event-free survival (EFS) and pulmonary relapse-free survival (PRFS) were estimated and analyzed. RESULTS: After WLI, grade 1-2 and grade 3 clinical toxicity was reported in 16.2% and 5.9% patients, respectively. The five-year OS, EFS and PRFS with 95% confidence interval (CI) were 69.8% (57.1-79.3), 61.2% (48.4-71.7) and 70.5% (56.3-80.8), respectively. Patients with good histological necrosis of the primary tumor after neoadjuvant chemotherapy showed a significant decreased risk of pulmonary relapse or death compared to patients with poor histological necrosis. CONCLUSIONS: WLI at recommended doses and time interval after BU-MEL is feasible and might contribute to the disease control in Ewing sarcoma with lung metastases and responsive disease. Further studies are needed to explore the treatment stratification based on the histological response of the primary tumor.

Musculoskeletal manifestations of childhood cancer and differential diagnosis with juvenile idiopathic arthritis (ONCOREUM): a multicentre, cross-sectional study.

BACKGROUND: Presenting symptoms of childhood cancers might mimic those of rheumatic diseases. However, the evidence available to guide differential diagnosis remains scarce. Preventing wrong or delayed diagnosis is therefore important to avoid incorrect administration of glucocorticoid or immunosuppressive therapy and worsening of prognosis. As such, we aimed to assess the prevalence and characteristics of presenting musculoskeletal manifestations in patients at cancer onset and to identify the factors that differentiate childhood malignancies with arthropathy from juvenile idiopathic arthritis. METHODS: We did a multicentre, cross-sectional study at 25 paediatric haemato-oncology centres and 22 paediatric rheumatology centres in Italy. We prospectively recruited patients who were younger than 16 years that were newly diagnosed with cancer or juvenile idiopathic arthritis. We excluded patients with glucocorticoid pre-treatment (>1 mg/kg per day of oral prednisone or equivalent for ≥2 consecutive weeks). We collected data for patients with a new diagnosis of cancer or juvenile idiopathic arthritis using an electronic case report form on a web-based platform powered by the Cineca Interuniversity Consortium. The primary outcome was to describe the frequency and characteristics of musculoskeletal manifestations at cancer onset; and the secondary outcome was to identify factors that could discriminate malignancies presenting with arthropathy, with or without other musculoskeletal symptoms, from juvenile idiopathic arthritis using multivariable logistic regression analysis. FINDINGS: Between May 1, 2015, and May 31, 2018, 1957 patients were eligible, of which 1277 (65%) had cancer and 680 (35%) had juvenile idiopathic arthritis. Musculoskeletal symptoms occurred in 324 (25% [95% CI 23·0-27·8]) of 1277 patients with cancer, of whom 207 had arthropathy. Patients with malignant bone tumours had the highest frequency of musculoskeletal symptoms (53 [80%] of 66), followed by patients with Langerhans histiocytosis (16 [47%] of 34), leukaemia (189 [32%] of 582), soft-tissue sarcomas (16 [24%] of 68), and neuroblastoma (21 [19%] of 109). In the 324 patients with cancer and musculoskeletal symptoms, the most common complaints were joint pain (199 [61%]), followed by limb bone pain (112 [35%]). Joint involvement had a prevalent monoarticular pattern (100 [48%] of 207) and oligoarticular pattern (86 [42%] had 2-4 joints involved and 20 [10%] had >4 joints involved), with the most frequently involved joints being the hip (88 [43%] of 207) and knee (81 [39%]). On multivariable analysis, limb bone pain was the independent variable most strongly associated with cancer (odds ratio [OR] 87·80 [95% CI 18·89-408·12]), followed by weight loss (59·88 [6·34-565·53]), thrombocytopenia (12·67 [2·40-66·92]), monoarticular involvement (11·30 [4·09-31·19]), hip involvement (3·30 [1·13-9·61]), and male sex (2·40 [1·03-5·58]). Factors independently associated with juvenile idiopathic arthritis were morning stiffness (OR 0·04 [95% CI 0·01-0·20]), joint swelling (0·03 [0·01-0·09]), and involvement of the small hand joints (0·02 [0-1·05]). INTERPRETATION: Our study provides detailed information about presenting musculoskeletal manifestations of childhood cancers and highlights the clinical and laboratory features that are most helpful in the differential diagnosis with juvenile idiopathic arthritis. FUNDING: Associazione Lorenzo Risolo.

Medulloblastoma and central nervous system germ cell tumors in adults: is pediatric experience applicable?

Medulloblastoma and central nervous system (CNS) germ cell tumors are very rare in adults, while they account for 25% and 5% of brain tumors in children, respectively (Pastore et al. Eur J Cancer 42:2064-208, 2006). Pediatric experiences, mostly from randomized and controlled clinical trials, have led to different tailored treatments, based on various risk factors, including histology, and extent of disease. For medulloblastoma, biological features have recently emerged that enable therapies to be scaled down in some cases, or pursued more aggressively in the event of chromosomal and/or genetic alterations (Massimino et al. Crit Rev Oncol Hematol 105:35-51, 2016). Such refinements are still impossible for adult patients due to the lack of similar clinical trials that might provide the same or a different understanding regarding patients' prognosis, long-term survival, quality of life, and acute and late toxicities. This review aims to contribute to the debate on the treatment of adults with these two diseases and promote the creation of broad-based, national and international trials to advance our knowledge in this area and to share the skills between pediatric and adult oncologists as adolescent and young adults (AYA) brain tumor national boards are currently requiring.

Sleep disorders in children with brain tumors: a pilot study based on a sleep disorder questionnaire.

PURPOSE: The aim of this study is to compare the prevalence of sleep disorders (SD) between children treated for brain tumors and healthy children, and to define the type of SD. METHODS: A case-control study was performed from October 2014 to April 2015. Inclusion criteria were patients between 2 and 16 years with "cases" defined as children affected by central nervous system tumors at least 3 months after the end of treatment (surgery and/or radiotherapy and/or chemotherapy) at the time of evaluation and "controls" as healthy children. Children's sleep quality was assessed with a questionnaire administered to parents (Child's Sleep Habits Questionnaire, CSHQ). A total score greater than 41 is suggestive for the presence of disturbed sleep. The risk of SD was estimated by the odds ratio (OR) and their 95% confidence intervals (95% CI) through logistic regression models. RESULTS: Twenty-nine cases and 87 controls (in a 1:3 model) were enrolled, for a total of 116 subjects. The prevalence of SD resulted of 82.8% among cases and 64.4% in controls. A statistically significant difference between the two groups (OR 2.65; 95% CI 0.92-7.65) was not reached. Analyzing singular disturbances, parasomnias and night awakenings showed a statistically significant difference between the two groups (OR 4.32; 95% CI 1.08-17.34). CONCLUSIONS: Our study revealed a trend toward SD in children with brain tumor when compared to healthy population. Hovewer, analyzing specific subtypes of SD some significant differences were obtained. A significant difference was obtained only for specific subtypes of SD. Further investigations could better define the real burden of SD.

Winners' Cup: a national football tournament brings together adolescent patients with cancer from all over Italy.

Società Scientifiche Italiane Insieme per gli Adolescenti con Malattie Onco-ematologiche (SIAMO) is an Italian nationwide scheme that focuses on adolescent patients with cancer. Some of its activities include promoting dedicated local projects at the various oncology centers all over the country and organizing events to improve awareness regarding cancer in adolescence. It is with these aims in mind that it organized the Winners' Cup, a football tournament between Italian adolescents who had (or had had) pediatric cancers. There were 144 young people 15 to 24 years old who arrived from 16 different treatment centers around the country to take part in the tournament and share their stories. Such an event had never been attempted before, in Italy at least. The Winners' Cup was a great success and an opportunity to focus attention on the particular clinical, psychological, and social needs of cancer patients in this age group.

Helical tomotherapy in children and adolescents: dosimetric comparisons, opportunities and issues.

Helical Tomotherapy (HT) is a highly conformal image-guided radiation technique, introduced into clinical routine in 2006 at the Centro di Riferimento Oncologico Aviano (Italy). With this new technology, intensity-modulated radiotherapy (IMRT) is delivered using a helicoidal method. Here we present our dosimetric experiences using HT in 100 children, adolescents and young adults treated from May 2006 to February 2011. The median age of the patients was 13 years (range 1-24). The most common treated site was the central nervous system (50; of these, 24 were craniospinal irradiations), followed by thorax (22), head and neck (10), abdomen and pelvis (11), and limbs (7). The use of HT was calculated in accordance to the target dose conformation, the target size and shape, the dose to critical organs adjacent to the target, simultaneous treatment of multiple targets, and re-irradiation. HT has demonstrated to improve target volume dose homogeneity and the sparing of critical structures, when compared to 3D Linac-based radiotherapy (RT). In standard cases this technique represented a comparable alternative to IMRT delivered with conventional linear accelerator. In certain cases (e.g., craniospinal and pleural treatments) only HT generated adequate treatment plans with good target volume coverage. However, the gain in target conformality should be balanced with the spread of low-doses to distant areas. This remains an open issue for the potential risk of secondary malignancies (SMNs) and longer follow-up is mandatory.