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BACKGROUND Accurate and swift tissue diagnosis is extremely important for the timely initiation of treatment in pediatric oncology. In our department, ultrasound-guided core needle biopsy (US-guided CNB) is used for tissue diagnosis. In 2016, we added on-site cytology, allowing for an immediate primary diagnosis. We retrospectively reviewed our performance in terms of safety and accuracy for CNBs and on-site cytology. METHODS All pediatric biopsies performed in our hospital between February 2016 and December 2020, were included. Patient clinical, procedural and follow-up data were collected. CNB pathology and cytology results were compared to the final pathologic diagnosis. RESULTS We included 71 patients for which 72 biopsies with on-site touch imprint (TI) cytology were performed; the average latency time to biopsy was 1 day. Altogether, we had 61 tumors, (58 malignant, 3 benign) and 11 other lesions. On-site cytology diagnosed 58 malignant tumors, 3 benign tumors and 11 non-tumor tissues. The cytologist correctly differentiated tumor from inflammation in all cases, and diagnosed the precise tumor type in 57 cases, with an accuracy of 94% for final diagnosis. We had no complications related to the procedure or sedation. CONCLUSION US-guided CNB with on-site TI cytology for suspected malignancy in the pediatric population is highly available, safe, and accurate, with real-time diagnosis in most cases. This accelerated diagnostic route has a huge impact on patient care.

OBJECTIVE. Percutaneous imaging-guided core needle biopsies (CNBs) for cancer diagnosis in pediatric patients are gaining interest because of their availability, lower rate of complications, and high diagnostic power compared with traditional surgical biopsies. Nevertheless, their precise role in the diagnostic algorithm of pediatric oncology is still unknown. The purpose of this study was to report our accumulated 16-year experience with CNB; discuss the availability, safety, and diagnostic accuracy of the procedure and the adequacy of ancillary testing; and compare our findings with the available literature. MATERIALS AND METHODS. Pediatric ultrasound-guided CNBs performed in our hospital between November 2003 and December 2019 were retrospectively studied. Data collection included demographics, clinical and procedural parameters, complications, and final diagnosis. RESULTS. A total of 597 biopsies were performed in 531 patients (132 performed in known oncologic patients and 465 performed to establish diagnosis). The median time between the biopsy request and the procedure was 1 day. Of 432 biopsies performed in patients with malignancies, 12 (2.8%) had false-negative results. In 165 cases of benign pathologic findings, all had true-negative results. Ancillary testing was adequate in all malignant cases. Overall sensitivity, specificity, and accuracy rates were 97.2%, 100%, and 98.0%, respectively. Five biopsies (0.8%) resulted in complications, including one major bleed and one track seeding. CONCLUSION. Our experience shows that ultrasound-guided CNB for suspected malignancy in pediatric patients has a high safety profile, availability, and accuracy rate compared with surgical biopsy. Our fast-track strategy enables early initiation of designated therapy and has the potential to become the procedure of choice.

Rhabdomyosarcoma (RMS) is the most common form of soft tissue sarcoma in children. We report the results of the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 study, which prospectively evaluated the reduction of chemotherapy in patients with embryonal RMS (ERMS) after initial surgery.Between October 2005 and December 2016, all patients with localised ERMS with an initial microscopically complete resection (IRS group I) with lymph node-negative (N0) were prospectively enrolled in the low-risk (n = 70, subgroup A; age 10 years and tumour size ≤ 5 cm) or standard-risk group (n = 108, subgroup B; age ≥ 10 years or tumour size 5 cm. Subgroup A received 8 courses of vincristine and dactinomycin (VA) for 22 weeks; subgroup B received 4 courses of VA with ifosfamide (IVA) and 5 courses of VA for 25 weeks.The 5-year event-free survival (EFS) and overall survival (OS) were 90.8% (95% confidence interval [CI]: 85.0-94.4) and 95.7% (95% CI: 90.5-98.1), respectively (n = 178). The EFS and OS were 95.5% (95% CI: 86.8-98.5) and 100% (subgroupA), and 87.8% (95% CI: 79.3-93.0) and 93.0% (95% CI: 84.8-96.8)(subgroup B), respectively. Bearman stage 2 veno-occlusive disease (VOD) occurred in 4 very young patients.VA treatment for 8 courses was effective and well tolerated by the subgroup of patients with low-risk ERMS (group A). Four courses of IVA and 5 courses of VA instead of 9 courses of IVA also has very good results. Careful monitoring for liver toxicity is important in very young patients. European union drug regulating authorities clinical trials EUDRACT No. 2005-000217-35.

Procedure Congenital rhabdomyosarcoma (RMS) represents a challenging disease due to its characteristics and the difficulties in delivering treatment in this immature population. Methods We analyzed treatment and outcome of patients with congenital RMS, defined as tumor diagnosed in the first 2 months of life, enrolled in the European paediatric Soft tissue sarcoma Study Group protocols. Results Twenty-four patients with congenital RMS were registered. All, except one patient (PAX3-FOXO1-positive metastatic RMS), had favorable histology and localized disease. Three patients had VGLL2-CITED2/NCOA2 fusion. Complete tumor resection was achieved in 10 patients. No radiotherapy was given. Chemotherapy doses were adjusted to age and weight. Only two patients required further dose reduction for toxicity. The 5-year event-free survival (EFS) and overall survival (OS) were 75.0% (95% confidence interval [CI] 52.6-87.9) and 87.3% (95% CI 65.6-95.7), respectively. Progressive disease was the main cause of treatment failure. Conclusion Patients with congenital RMS presented with a favorable disease, allowing weight- and age-adjusted doses of chemotherapy and avoidance of irradiation, without compromising the outcome.

Decisions on medication treatment in children dying from cancer are often complex and may result in polypharmacy and increased medication burden. There is no information on medication burden in pediatric cancer patients at the end of life (EOL).To characterize medication burden during the last hospitalization in children dying from cancer.We performed a retrospective cohort study based on medical records of 90 children who died from cancer in hospital between 01 January 2010 and 30 December 2018. Demographic and clinical information were collected for the last hospitalization. We compared medication burden (number of medication orders) at hospitalization and at time of death and examined whether changes in medication burden were associated with clinical and demographic parameters.Median medication burden was higher in leukemia/lymphoma patients (6 orders) compared to solid (4 orders) or CNS tumor patients (4 orders, P = 0.006). Overall, the median number of prescriptions per patient did not change until death (P = 0.42), while there was a significant reduction for some medication subgroups (chemotherapy [P = 0.035], steroids [P = 0.010]).Patients dying in the ICU (n=15) had a higher medication burden at death (6 orders) than patients dying on wards (3 orders, P = 0.001). There was a trend for a reduction in medication burden in patients with "Do not resuscitate" (DNR) orders (P = 0.055).Polypharmacy is ubiquitous among pediatric oncology patients at EOL. Disease type and DNR status may affect medication burden and deprescribing during the last hospitalization.

Medical marijuana (MM) is widespread in many medical fields, including oncology, with limited use in pediatric oncology where research is scarce and often shows conflicting results. This research focuses on alleviating side effects of anticancer treatment as an integral part of supportive and palliative care of children with cancer. We report our experience with MM treatment in 50 children, adolescents, and young adults with different types of cancer during 2010-2017. The main indications for prescriptions were nausea and vomiting, decreased mood, disturbed sleep, and pain. The medication was supplied to 30 patients via oil drops (60%) and 11 via smoking (22%), followed by vaporization, capsules, or combinations of various routes. Positive effects were reported by verbal children and parents in 80% of cases. MM was generally well tolerated with few patients reporting toxicity, with the most common adverse reactions being burning in the throat and anxiety attacks in subjects who chose to smoke the product. We conclude that MM may serve as a potentially useful complementary therapy to conventional supportive treatment of children suffering from cancer at the end of life. Further research is needed on the safety and efficacy and the consequences of prolonged use in pediatric populations.

Every year approximately 450–500 new pediatric patients are diagnosed with various types of cancer in Israel, and approximately 90–100 of these children succumb to their disease every year. Although the number of childhood deaths each year may seem small, the emotional, social, and financial impacts are extraordinary. Pediatric palliative care (PPC) in Israel exists and functions on three levels: hospital, community, and hospice. All these three levels of PPC are connected to and dependent on each other and deliver their services to pediatric oncology patients who spend most of their time at home after being regarded as incurable. In Israel, an absolute majority of children with chronic and life-limiting conditions, including cancer, die in hospital. The reasons for this are several and reflect medical, psychosocial, and organizational aspects characteristic of the last phase of life of pediatric oncology patients in the country. The relative scarcity of both human and material resources for providing highly professional and comprehensive pediatric palliative care at the community level, as well as an underdeveloped pediatric hospice network, further complicates the current situation. For the improved development of PPC at the homes of children with advanced and progressive cancer, many improvements in such fields as continuous professional education and creation of financial mechanisms directed at stimulation and reimbursement policy in the field should be considered and implemented.

Introduction Very little is known about the characteristics of mesothelial tumours in the paediatric population. In adults with malignant mesothelioma, the pemetrexed-based regimen with cytoreductive surgery (CRS) is a standard of care in limited tumours, but long-term survival is uncommon. Material and methods The European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT) retrospectively reviewed children, adolescents and young adults (≤21 year) diagnosed with mesothelial tumours treated between 1987 and 2018. Results Thirty-three patients were identified, 15 male and 18 female patients. One patient's exposure to asbestos was documented. Primary tumour was mainly in the peritoneum (23 patients). Histology was multicystic mesothelioma of the peritoneum (MCM) (six patients) or malignant mesothelioma (MM) (27 patients). Among MM, the first-line treatment comprised preoperative chemotherapy (14 cases), surgery only (three cases), chemotherapy only (five cases), adjuvant chemotherapy (three cases) or palliative treatment (two cases). The response rate to cisplatin–pemetrexed was 50% (6/12 cases). CRS with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) was performed in 19 patients (upfront in three, after neoadjuvant therapy in 12, or after tumour progression in six patients, including three twice). After a median follow-up of 6.7 years (range, 0–20), five-year overall and event-free survivals were 82.3% (95% CI, confidential interval ((CI), 67.8–99.9) and 45.1% (95% CI, 28.4–71.7), respectively. All patients with MCM are alive after surgery (five patients) and CRS-HIPEC (one patient). Conclusions Paediatric mesothelioma is exceptional and seems to be different from its adult counterpart with few asbestos exposures, more peritoneal primary, and a better outcome. The cisplatin–pemetrexed regimen showed promising efficacy. Relapses could be salvaged with active therapy including CRS-HIPEC.

Background: For more than three decades, standard treatment for rhabdomyosarcoma in Europe has included 6 months of chemotherapy. The European paediatric Soft tissue sarcoma Study Group (EpSSG) aimed to investigate whether prolonging treatment with maintenance chemotherapy would improve survival in patients with high-risk rhabdomyosarcoma. Methods: RMS 2005 was a multicentre, open-label, randomised, controlled, phase 3 trial done at 102 hospitals in 14 countries. We included patients aged 6 months to 21 years with rhabdomyosarcoma who were considered to be at high risk of relapse: those with non-metastatic incompletely resected embryonal rhabdomyosarcoma occurring at unfavourable sites with unfavourable age (≥10 years) or tumour size (>5 cm), or both; those with any non-metastatic rhabdomyosarcoma with nodal involvement; and those with non-metastatic alveolar rhabdomyosarcoma but without nodal involvement. Patients in remission after standard treatment (nine cycles of ifosfamide, vincristine, dactinomycin with or without doxorubicin, and surgery or radiotherapy, or both) were randomly assigned (1:1) to stop treatment or continue maintenance chemotherapy (six cycles of intravenous vinorelbine 25 mg/m2 on days 1, 8, and 15, and daily oral cyclophosphamide 25 mg/m2, on days 1–28). Randomisation was done by use of a web-based system and was stratified (block size of four) by enrolling country and risk subgroup. Neither investigators nor patients were masked to treatment allocation. The primary outcome was disease-free survival in the intention-to-treat population. Secondary outcomes were overall survival and toxicity. This trial is registered with EudraCT, number 2005-000217-35, and ClinicalTrials.gov, number NCT00339118, and follow-up is ongoing. Findings: Between April 20, 2006, and Dec 21, 2016, 371 patients were enrolled and randomly assigned to the two groups: 186 to stop treatment and 185 to receive maintenance chemotherapy. Median follow-up was 60·3 months (IQR 32·4–89·4). In the intention-to-treat population, 5-year disease-free survival was 77·6% (95% CI 70·6–83·2) with maintenance chemotherapy versus 69·8% (62·2–76·2) without maintenance chemotherapy (hazard ratio [HR] 0·68 [95% CI 0·45–1·02]; p=0·061), and 5-year overall survival was 86·5% (95% CI 80·2–90·9) with maintenance chemotherapy versus 73·7% (65·8–80·1) without (HR 0·52 [95% CI 0·32–0·86]; p=0·0097). Toxicity was manageable in patients who received maintenance chemotherapy: 136 (75%) of 181 patients had grade 3–4 leucopenia, 148 (82%) had grade 3–4 neutropenia, 19 (10%) had anaemia, two (1%) had thrombocytopenia, and 56 (31%) had an infection. One (1%) patient had a grade 4 non-haematological toxicity (neurotoxicity). Two treatment-related serious adverse events occurred: one case of inappropriate antidiuretic hormone secretion and one of a severe steppage gait with limb pain, both of which resolved. Interpretation: Adding maintenance chemotherapy seems to improve survival for patients with high-risk rhabdomyosarcoma. This approach will be the new standard of care for patients with high-risk rhabdomyosarcoma in future EpSSG trials. Funding: Fondazione Città della Speranza, Association Léon Berard Enfant Cancéreux, Clinical Research Hospital Program (French Ministry of Health), and Cancer Research UK., SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND Therapy outcomes for childhood acute lymphoblastic leukemia (ALL) had substantially improved in the last decades, but variability across racial and ethnic groups was identified in some clinical studies. In this study, we aimed to investigate whether such a difference in outcome is found in the diverse ethnicities in Israel as well. METHODS A retrospective study was conducted among 1154 patients (855 Jews, 195 Muslims, 52 Bedouins, 26 Druze, and 26 others) aged 1 to 21 years, who were diagnosed with ALL between 1989 and 2011 and were treated according to the same Berlin-Frankfurt-Muenster-based Israel National Study protocols. RESULTS Bedouins had a higher incidence of t(1;19) (16% vs 3% for non-Bedouins) and a lower incidence of high-hyperdiploidy (10% vs 25% for non-Bedouins) (P = 0.01). Five-year event-free survival (EFS) and overall survival (OS) were poorer for the Bedouins (60.3% ± 7.2% and 63.1% ± 7.2%, respectively) compared with the Jews, Muslims, and Druze (80.4% ± 1.4%, 77.3% ± 3.2%, and 84% ± 7.3%, respectively, for EFS [P = 0.02], and 86.3% ± 1.2%, 82.3% ± 2.9%, and 88.3% ± 6.4%, respectively, for OS [P = 0.002]). Adherence to intensive chemotherapy was similar between the Muslims and the Bedouins. CONCLUSIONS Our findings suggest that the Bedouins, a highly inbred ethnic Arab people, may be considered a higher risk group that may need more intensive chemotherapy and/or supportive care in order to improve their outcome.

Nasopharyngeal carcinoma (NPC) is a rare and locally aggressive form of childhood cancer. Treatment of NPC includes chemotherapy and radiotherapy. With current treatment protocols, survival rates for patients with nonmetastatic disease is over 80%. Data regarding very late events including long-term treatment-related morbidities and second malignancies are scarce. We present our data on 42 patients with NPC treated in Israel between 1989 and 2014, and followed until 2019. During follow up, five patients had disease recurrence, and four children developed secondary malignancy. Median time to diagnosis of secondary malignancy was 105 months. Eighty-eight percent of patients have long-term treatment-related morbidities.

Background It is currently expected that about 20% of children with cancer will ultimately die. Writing advanced life directives sufficiently long before the actual death of a child ensues allows both parents and medical staff to develop optimal treatment plans in the best interests of the child. Aim of the study The aim of the study was to evaluate factors that may influence the process of decision-making regarding Do-Not-Resuscitate (DNR) status. Methods Retrospective single institution study. Results Totally, 79 patients died between September 01, 2011 and August 31, 2017. Median age of the children was 10.5 years (range, 1 to 24 y). Forty-five were males. There were 37 Muslims, 27 Jews, 9 Druze, and 6 Christians. Twenty-one patients had sarcomas, 20 had CNS tumors, 10 had neuroblastoma, 17 had leukemias/lymphomas, 11 had carcinomas, and other rare tumors as well as nonmalignant diseases. No statistically significant association between all evaluated factors and DNR order status was found. Conclusions It is possible that, other than demographic, clinical-associated, or therapy-associated factors play an important role in the process of decision-making regarding DNR. We feel that sincere communication between parents, their child (when appropriate) and medical and psychosocial staff may have a more crucial role when such decisions have to be made.

Background: Rhabdomyosarcoma is an aggressive tumour that can develop in almost any part of the body. Doxorubicin is an effective drug against rhabdomyosarcoma, but its role in combination with an established multidrug regimen remains controversial. Therefore, we aimed to evaluate the possible benefit of early dose intensification with doxorubicin in patients with non-metastatic rhabdomyosarcoma. Methods: We did a multicentre, open-label, randomised controlled, phase 3 trial involving 108 hospitals from 14 countries. We included patients older than 6 months but younger than 21 years with a pathologically proven diagnosis of rhabdomyosarcoma. We assigned each patient to a specific subgroup according to the EpSSG stratification system. Those with embryonal rhabdomyosarcoma incompletely resected and localised at unfavourable sites with or without nodal involvement, or those with alveolar rhabdomyosarcoma without nodal involvement were considered at high risk of relapse. These high-risk patients were randomly assigned (1:1) to receive either nine cycles of IVA (ifosfamide 3 g/m2 given as a 3-h intravenous infusion on days 1 and 2, vincristine 1·5 mg/m2 weekly during the first 7 weeks then only on day 1 of each cycle [given as a single intravenous injection], and dactinomycin 1·5 mg/m2 on day 1 given as a single intravenous injection) or four cycles of IVA with doxorubicin 30 mg/m2 given as a 4-h intravenous infusion on days 1 and 2 followed by five cycles of IVA. The interval between cycles was 3 weeks. Randomisation was done using a web-based system and was stratified (block sizes of four) by enrolling country and risk subgroup. Neither investigators nor patients were masked to treatment allocation. The primary endpoint was 3-year event-free survival assessed by the investigator at each centre in the intention-to-treat population. Patients who received at least one dose of study treatment were considered in the safety analysis. In agreement with the independent data monitoring committee, the study was closed to patient entry on Dec 16, 2013, after futility analysis. This trial is registered with EudraCT, number 2005-000217-35, and is currently in follow-up. Findings: Between Oct 1, 2005, and Dec 16, 2013, 484 patients were randomly assigned to receive each chemotherapy regimen (242 in the IVA group and 242 in the IVA plus doxorubicin group). Median follow-up was 63·9 months (IQR 44·6–78·9). The 3-year event-free survival was 67·5% (95% CI 61·2–73·1) in the IVA plus doxorubicin group and 63·3% (56·8–69·0) in the IVA group (hazard ratio 0·87, 95% CI 0·65–1·16; p=0·33). Grade 3–4 leucopenia (232 [93%] of 249 patients in the IVA plus doxorubicin group vs 194 [85%] of 227 in the IVA group; p=0·0061), anaemia (195 [78%] vs 111 [49%]; p

Nodular sclerosing Hodgkin lymphoma (HL) has an excellent prognosis in children. The syncytial variant (SV) of HL in adults represents a clinic pathologic entity with a worse outcome. We report the clinical features and the course of the disease of three children with refractory HL. The three patients with SV were analyzed in a retrospective multi-institutional study conducted in Israel in 51 children diagnosed with refractory or recurrent HL between 1997 and 2014. All the three children developed multiple recurrences soon after diagnosis. All three received at least three different chemotherapy combinations with autologous bone marrow transplantation for two patients, allogenic bone marrow transplantation in one, and immunotherapy in one. One patient died of disease, one is in complete response of the disease but developed a second metastatic malignancy, and one is alive without disease. This retrospective study shows that SV histology may be a prognostic factor for poor outcome in children diagnosed with HL.

In 2005, the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) proposed a conservative treatment algorithm-consisting of an initial wait-and-see strategy, non-mutilating surgery, and minimal-morbidity chemotherapy (in the case of tumour progression)-for paediatric patients with desmoid-type fibromatosis. We aimed to investigate the outcomes of this algorithm.In this case series, patients (25 years) with desmoid-type fibromatosis from 57 centres in eight countries were prospectively registered through a web-based system. Diagnosis was based on histological analysis of the tumour specimen after biopsy or surgery, and we classified patients by tumour site, clinical stage (TNM system), and post-surgical stage (Intergroup Rhabdomyosarcoma Study system). Progression-free survival was defined as the time from diagnosis until disease progression (clinical or radiological progressive disease, relapse, or death from any cause).From Oct 1, 2005, to July 31, 2016, 173 patients (median age 11·4 years [IQR 4·0-14·1], 88 [51%] male patients) were registered. After excluding patients with missing data, 54 (35%) patients had no immediate therapy (wait-and-see strategy), 47 (31%) had immediate surgery, and 53 (34%) had immediate chemotherapy after diagnosis. 5-year progression-free survival was 36·5% (95% CI 27·8-45·2) overall, 26·7% (14·2-41·0) in the wait-and-see group, 41·2% (25·8-55·9) in the surgery group, and 42·8% (27·2-57·6) in the chemotherapy group (overall log-rank p=0·17; wait-and-see vs surgery p=0·12; wait-and-see vs chemotherapy p=0·13). In multivariable analysis, large tumour size (5 cm) was associated with worse progression-free survival (hazard ratio 2·25, 95% CI 1·34-3·76; p=0·0021). Apart from one patient in the chemotherapy group who died from a secondary tumour (head and neck anaplastic embryonal rhabdomyosarcoma), all patients were alive at the time of analysis. 13 (8%) patients had biopsy only (no further treatment), 65 (42%) had chemotherapy only, 31 (20%) had surgery only, 36 (23%) had both chemotherapy and surgery, and nine (6%) had radiotherapy in addition to other therapies.In paediatric patients with desmoid-type fibromatosis, the EpSSG conservative strategy did not compromise outcomes and could be adopted to reduce treatment burden.S Wisnia and la Città della Speranza Foundation.

Background. Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment for many nonmalignant disorders, such as autoimmune disorders, inborn metabolic disorders, hemoglobinopathies, and immunodeficiency disorders. Autoimmune complications (AICs) after HSCT, such as autoimmune cytopenias, autoimmune hepatitis, primary biliary cirrhosis, and autoimmune cutaneous manifestations, are still neither well defined nor characterized.Patients. Between 2000 and 2012, 92 patients (47 males, 45 females) were treated with HSCT in our hospital, 51 with congenital hemoglobinopathies, 19 with primary immunodeficiency disease, 10 with metabolic disorders, five with Fanconi anemia, three with aplastic anemia, and four with familial hemophagocytic lymphohistiocytosis.Results. Mean age at HSCT was 6.4 years (range, 0.2–32 years) and mean duration of followup after HSCT was 6.81 years (range, 1–11 years). Sixteen (17.4%) patients developed chronic GVHD and five (5.4%) showed sclerodermatous features. Five (5.4%) patients were diagnosed with scleroderma manifestations, six (6.5%) with vitiligo, six (6.5%) with autoimmune hemolytic anemia (AIHA), six (6.5%) with idiopathic thrombocytopenia, three (3.3%) with mild leucopenia, two (2.2%) with aplastic anemia, two (2.2%) (one boy, one girl) with autoimmune thyroid disease, and one (1.1%) with autoimmune hepatitis.Conclusions. It was concluded that AICs are clinically significant complications after HSCT that contribute to morbidity but not to mortality. AICs are more frequent after HSCT for metabolic disorders, and sclerodermatous GVHD is more significant in children who underwent allogeneic HSCT for hemoglobinopathies. The potential to identify risk factors for AICs could lead to less morbidity and mortality and to maintain the patient’s quality of life.

Recent improvements in therapy of children with cancer have resulted in an increase in cure rates which lead to long-term survivorship. Assessment of short- and long-term complications and late effects of cancer therapies is accomplished by pediatric oncologists and multi-disciplinary team, including continuation of care from pediatric to adult primary care. The late complications of cancer treatment include growth and development, reproduction, vital organ function (cardiac, pulmonary, renal, gastrointestinal), dental, ocular, esthetic sequellae, and second neoplasms (benign or malignant), which are cited as the second most frequent cause of death in the Children Cancer Survivors Study cohort. Long-term follow-up guidelines for survivors of childhood cancers has been established by international specialists, the main aim is to decrease severe late complications by individualizing prevention care and treatment. Preventive measures include reduction of radiotherapy doses, or omission, introduction of new radiotherapy techniques, decrease doses of alkylating drugs, and anthracyclines, cardio protectors, fertility preservations guidelines, new surgical techniques, introduction of biological treatments. The multidisciplinary team monitors certain treatments including risk-based care not only of the tumor, but also premorbid conditions, and health behaviors. More comprehensive and high-quality evaluations of survivorship programs are needed, for long term outcome, quality of life and psychosocial support.

Background The influence of socio-economic and religious background on decisions made by parents of children with incurable cancer regarding DNR orders is not fully understood. Procedure A retrospective analysis of medical charts of patients who died between January 2000 and January 2011 was performed. The following data were sought: written evidence of DNR discussion with parents, religious background, educational level, monthly income. Results There was evidence of a discussion on DNR in 73/90 charts. DNR consent was obtained in 14/17 (82.4%) cases where at least one parent had >15 years of education versus in only 24/45 (53.3%) cases where both parents had ≤15 years education as determined by univariate analysis (P = 0.03). DNR consent was also more likely to be obtained among parents of children with income >10,000 NIS (24/30, 80.0% vs. 20/38, 52.6%, P = 0.013). Parents of Jewish (22/30, 73.3%), Islamic (16/26, 61.5%), and Christian (8/9, 88.9%) background were equally likely to provide DNR consent. However, Druze families were less likely to do so (2/8, 25.0%, P = 0.036). Conclusions The process of decision-making to a DNR request was associated with parents' educational level and monthly family income, and not by religious background, with the exception of Druze families. Pediatr Blood Cancer 2014;61:265–268. © 2013 Wiley Periodicals, Inc.

Purpose Our goal was to describe adolescent cancer incidence and survival in Israel, and to identify demographic and epidemiologic variations among adolescents with cancer. Patients and Methods We used data from the Israel National Cancer Registry in order to examine the incidence and survival of adolescent cancer in Israeli adolescents aged 15–19 years, diagnosed during the years 1998–2009. Cases were analyzed according to sex, ethnicity and geographical region, as well as comparison to other countries in the region and other western countries. Results Among the 1,532 new cases of adolescent cancer, there was a total incidence rate of 226 cases per million. The incidence rate for males was higher than for females (230 and 222, respectively) and higher for Jewish adolescents than for Arab adolescents (235 and 194, respectively). The largest groups were Lymphomas (69 per million), Malignant Epithelial Neoplasms (49 per million), and Leukemias (21 per million). We estimated the survival probability updated to December 2009, and calculated the 5-year survival for new cases until the end of 2004. The overall survival at 5 years was 78%, with 62% for the Arabic population and 81% for the Jewish population, dependent on the diagnosis. Conclusions The results of this study show little difference in the predominance of some adolescent cancers in comparison with other developed countries. This study may add more information for further investigation of the genetic and environmental factors that cause adolescent cancer in Israel. As well as delineate the genetic basis for ethnic origin disparities in survival. Pediatr Blood Cancer 2013;60:1848–1854. © 2013 Wiley Periodicals, Inc.

Background Current evidence indicates sub-optimal incidence of fertility preservation (FP) in eligible patients. We present herein our designated multidisciplinary program for FP in pediatric and adolescent population and present our data on FP in female patients. Methods Pediatric patients (age 0–18) who were candidate for highly gonadotoxic treatments were referred to FP program for a multidisciplinary discussion and gonadal risk-assessment followed by either oocyte cryopreservation or ovarian cryopreservation (OCP) for female patients, and sperm banking for male patients. The OCP protocol consists of aspiration of oocytes from small antral follicles and in-vitro maturation followed by cryopreservation, as well as ovarian tissue cryopreservation. Results The establishment of a designated FP program resulted in a significant increase in referral and subsequent FP procedures of all eligible patients. Sixty-two female patients were referred for FP discussion during a period of 36 months; 41 underwent OCP; 11 underwent oocyte cryopreservation and six were declined due to parental decision. The median age was 13.2y (range 18 months-18y). Thirty-two (51.6 %) were chemotherapy-naïve. Seventeen patients (27 %) had sarcoma, 16 patients (26 %) had acute leukemia. The mean number of mature oocytes that were eventually vitrified was significantly higher in chemotherapy-naïve patients compared with chemotherapy-exposed patients (mean 12 oocytes (1–42) versus 2 (0–7)). Conclusion Multidisciplinary programs that encompass experts of all relevant fields, skilled laboratory resources and a facilitated path appear to maximize the yield. We observed a considerable higher referral rates following launching a designated program and earlier OCP in chemo-naïve patients that culminated in a better fertility preservation procedure.

Hematopoietic stem cell transplantation (HSCT) remains the only potentially curative treatment for severe hemoglobinopathy (HGP). Late complications (LCs) are all events occurring beyond two years post-HSCT. We retrospectively analyzed prevalence, factors influencing occurrence, and prognosis of LCs post-HSCT for HGP.Between 2000 and 2011, 47 patients (21 males, 26 females; 43 with beta thalassemia major, four with sickle cell disease) who had survived more than two years post-HSCT for HGP were retrospectively reviewed. Mean age at HSCT was 7.7 years (1.1-32 years); mean follow-up was 7.1 years (2-11.6 years); 11 patients were splenectomized; mean ferritin level was 3022 ng/mL (350-10900); and seven patients underwent a second HSCT.Endocrinological complications were observed with primary gonadal failure in 16/20 mature females and 4/11 mature males, in five patients with primary hypothyroidism and in four with insulin-dependent diabetes mellitus (DM). Skeletal complications were observed in 10 with secondary osteoporosis; 22 patients had elevated transaminase levels; two had hepatitis B reactivation. Neurological, cardiac and ocular manifestations were relatively rare. A higher incidence of LCs was observed in splenectomized than in nonsplenectomized patients: cGVHD -64% versus 13% (P = .003); endocrine abnormalities -91% versus 30.5%, (P = .001); elevated transaminase levels -73% versus 33% (P = .043); mortality -18% versus 2.7% (NS).LCs post-HSCT for HGP are common and heterogeneous. Etiology is multifactorial with iron overload (IO), class, splenectomy, age, chronic GVHD, and corticosteroid (CS) treatment. Our data may help build follow-up guidelines to limit, detect, and treat any LCs and improve quality of life.

Pediatric cancer palliative care is characterized by diversity of care delivery models; effect of cancer on the family as the central focus of care and consideration of culture, spirituality, communication, and ethical standards. In Israel, children who are in palliative care are treated by the staff of the centers and about 70 to 80 % of the children are dying in the pediatric Hematology Oncology departments and units. Special efforts are also made in the pediatric departments in order to better treat adolescents in terminal phases. Palliative care education program in Israel was started several years ago together with adult palliative care specialists, the Israeli pediatric oncologists still witness many barriers for treatment amongst parents as well as in medical pediatric teams especially in pain management. During the last years, the Israeli pediatric palliative care teams improved the management of all symptoms in a dying child with special attention to existential, emotional and social demands of the child and the whole family. Education of the medical and nursing team is imperative, training in pharmacology and metabolism of antalgic drugs is also mandatory in order to better manage symptom control of the children at the end of life.

During modern treatment of children with bone sarcomas, the children undergo multiple diagnostic imaging procedures, including bone scan (BS) with Tc99m. The aim of the BS is to establish the metastatic status of the skeletal system at the time of initial diagnosis and thereafter. We retrospectively reviewed 85 medical charts of patients with osteosarcoma (n = 40) and Ewing sarcoma (n = 45) who had been treated in our department between 01.01.1995 and 01.11.2009. Every patient underwent routine imaging studies including BS at the time of initial diagnosis and before local treatment. Median age of all patients was 15.5 years (range, 8 to 29). Fifteen patients had metastases at diagnosis. All patients were treated with neoadjuvant chemotherapy. No patient with localized disease developed metastatic disease to the skeletal system before local treatment; those with localized disease who developed metastases did so some time after completion of the treatment plan. As the probability of developing bone metastatic disease while receiving therapy is very low, routine BS in asymptomatic patients before local treatment may safely be omitted.

Aim : We evaluated the roles of the doctor and the medical system in Israel in the diagnostic delay of childhood malignancies. Methods : We investigated the factors affecting the delay in the diagnosis of childhood malignancies in 315 children with solid malignancies, diagnosed and treated in Rambam Medical Center (RMC), between 1993 and 2001. Those factors were divided into two groups: ‘Healthcare-system-related parameters', (factors directly related to the medical system), and ‘Patient-related parameters' (factors that are not part of the medical system, but directly affect medical judgment and decisions, including factors related to the tumor). We also took into consideration epidemiological, social, and medical issues. Results : The main ‘Healthcare-system-related parameters', which were found to influence the delay in diagnosis, were the type of medical authority that was initially consulted; the specialty of the first doctor; the number of additional doctors whom the child had visited, and the number of times the child had visited the first doctor. The main ‘Patient-related parameters' found to have an impact on the delay in diagnosis were the age of the child, the tumor type, and the presenting symptom. Conclusions : The education and awareness of doctors at the primary healthcare clinics must be improved. We suggest ways of improving the approach of doctors and managing a child with a suspected malignancy.

The study explored the adjustment of Arab mothers of children diagnosed with cancer, as shown by the mothers' distress and quality of life. The aim was twofold: to examine the associations between educational level, psychosocial resources and adjustment indices and to assess the moderating effects of psychosocial resources on the education and adjustment association. The sample consisted of 100 Arab mothers who completed questionnaires assessing demographic and illness variables, mastery, social support, psychological distress and quality of life. High levels of education and psychosocial resources contributed to low distress and high levels of quality of life. Mastery and social support moderated the effects of education on adjustment: Under low levels of education, higher mastery was related to lower distress and higher quality of life, and higher social support was related to lower distress. Education, mastery and social support are important resources in the context of adjustment to cancer. In addition, psychosocial resources are important factors for adjustment under low levels of education and should be taken into consideration when developing intervention programmes for Arab parents coping with their child's cancer.

The acquired form of pure red cell aplasia (PRCA) presents either as an acute self-limited disease, predominantly seen in children, or as a chronic illness more frequently seen in adults with rare spontaneous remissions. A 14-year-old boy presented with pallor, without hepatosplenomegaly, jaundice, lymphadenopathy, petechiae, or any other apparent abnormalities. Isolated anemia in the presence of normal white cell and platelet counts with a marrow of normal cellularity and absence of erythroblasts but normal myeloid cells and megakaryocytes revealed the diagnosis of PRCA. All possible investigations excluded secondary causes of PRCA. The patient required packed red cell transfusions every 2 to 3 weeks. He failed therapy with intravenous immunoglobulin, corticosteroids, cyclosporine A plus corticosteroids, antithymocyte globulin, anti-CD 20 (rituximab), and erythropoietin (EPO). He showed a severe, resistant, and transfusion-dependent PRCA. Spontaneous remission with normal hemoglobin and reticulocyte levels was dramatic 6.5 years after the diagnosis of PRCA and 3.6 years after his last treatment.

Objectives This study examined how dispositional optimism, health vulnerability, and time perspective were related to adolescent and young adult (AYA) cancer survivors' career decision-making (CDM) and quality of life (QOL). Secondarily, how cultural factors relate to CDM and QOL among Israeli-Jewish and Israeli-Arab cancer survivors was explored. Methods Fifty-one cancer survivors (68.6% females, 80.4% Israeli-Jewish, 19.6% Israeli-Arab, Mage = 21.45 years), at least 6 months post-active treatment (Mtime = 5.75 years) completed self-report questionnaires. Results Multiple regression analyses indicated that optimism, vulnerability, and past negative, present fatalistic, and future time perspective were significantly associated with QOL (F(6, 47) = 6.80, P

We present the first reported case of a child with familial expansile osteolysis syndrome (FEO) who developed osteogenic sarcoma (OS) of the iliac bone. A 17-year-old adolescent presented with pain and a mass on the left pelvis. He was from a family with several members who had been diagnosed with FEO, from which he also suffered. The median life expectancy of affected members of the family was reported as 25 to 30 years, with death ensuing as a result of various respiratory and cardiac complications of severe skeletal deformations, characteristic of increased bone turnover as seen in FEO. Biopsy of the patient's mass revealed chondroblastic OS. He was treated according to the P9754 protocol for patients with newly diagnosed nonmetastatic OS. Chemotherapy consisted of HD-MTX, ifosfomide, doxorubicin, and cisplatin. Complete resection of the tumor was carried out, but the patient subsequently developed metastatic disease and died (histologic response to neoadjuvant chemotherapy-85%). The patient's alkaline phosphatase level that was highly elevated before the start of chemotherapy, dropped significantly during treatment, with repeated elevation soon after definitive surgery, while he was recuperating and not on treatment. We speculate that chemotherapy affected not only the malignant cells of OS but normal osteoblasts as well, with a decreasing level of alkaline phosphatase even in the absence of any clinical and radiographic signs of OS. We also think that increased bone turnover, characteristic of a condition such as FEO, may facilitate de novo development of OS.

We analyzed the results of the French-American-British-LMB 96 protocol performed in 9 centers in Israel on 88 patients with B-cell non-Hodgkin lymphoma treated from 2000 to 2005.The majority of the patients was male (63/88, 72%), with a median age of 8.9 years (range, 2.5 to 20 y). Ethnic origin was Jewish in 73% (64/88), and Arabic in 27%. Fifty (57%) patients were classified as Burkitt lymphoma, 5 (5.7%) as Burkitt-like lymphoma, 22 (25%) as diffuse large B cell (DLBC), and 9 (10.2%) as Burkitt leukemia with over 25% of their bone marrow (BM) involved. Initial disease sites included the abdomen in 43%, head and neck in 45%, and mediastinum in 7%. Stage I: 9.1%; stage II: 28.4%; stage III: 45.5%, stage IV: 17%. Two patients had BM involvement alone, 5 patients had central nervous system (CNS) involvement alone, and 4 had both CNS and BM. The children were divided into 3 groups according to risk factors, with 5 in group A, 69 in group B, and 14 in group C.With a median follow-up of 3 years (12 mo to 7.6 y), the Kaplan-Meier for event-free survival (EFS) and overall survival (OS) according to whole group treatment was 88.6% and 90.9%, group A was 100% and 100%; group B was 89.9% and 92.8%; and group C was 78.6% and 78.6%. There were no untoward events or deaths in group A, whereas 6 patients relapsed in group B, 4 of whom died (all relapsed during the first year), with tumor lysis syndrome in 3 patients and death of toxicity in 1 patient who had multiorgan failure 2 days after initiation of COP. Three patients in group C relapsed and died (all patients relapsed during the first 6 months), with tumor lysis syndrome in 4 patients but no deaths from toxicity. EFS for LDH less than twice was 96.4%, EFS for LDH more than twice was 73.3% (P=0.002). OS according to primary site: bone and ovary: 100%; head and neck: 95%; abdomen: 92%; mediastinum: 50%. The difference between the mediastinal primary site to all other primary sites was statistically significant with P=0.003. All the mediastinal tumors were of DLBC origin but no significant differences in outcome were found when DLBC was compared with other histologies (DLBC: 81.8%, other B line: 90.9%). OS for patients of Arabic ethnic origin was 79.2%, for Jewish patients was 95.3%, P=0.02. We could not determine any prognostic factors that were different between the groups, which raises the question of a genetic influence.In nonresected mature B-cell lymphoma of childhood and adolescence with no BM or CNS involvement, a 93% cure rate can be achieved, similar to the French-American-British/LMB 96 trial. Patients with primary DLBC mediastinal mass had a significantly reduced OS, indicating the need for a different therapeutic approach.

Objectives: To assess insulin-related metabolism following hematopoietic stem cell transplantation (HSCT) in childhood. Study design: Thirty-four patients who underwent HSCT were compared with 21 patients with similar diseases who were not transplanted. Median follow-up was 3.6 yr after HSCT. Anthropometric parameters, fasting plasma glucose and insulin levels, hemoglobin A1c (HbA1c) and lipid profile were measured and compared. Results: HbA1c was significantly higher (p = 0.001) in the study group. Two (5.8%) patients in the study group developed type 2 diabetes mellitus. Among thalassemic patients, significantly lower insulin resistance indices (p = 0.05) and fasting plasma insulin levels (p = 0.033) were found in the study group compared with the control group. Conclusions: Attentive follow-up of insulin-related metabolism following HSCT in children is needed. The significance of the higher HbA1c values in the study group remains to be evaluated in a larger cohort of patients.

The aim of this pilot study was to determine heparanase plasma levels (HP) at diagnosis and at restaging in children diagnosed with Hodgkin lymphoma and to investigate whether this parameter provides prognostic information for response to treatment after induction therapy.HP levels of 19 pediatric patients (mean age: 10.3 years (y) (range, 4-18 y), 9 girls, 10 boys) with Hodgkin lymphoma were assayed at diagnosis and at restaging. HP levels were determined using an ELISA anti-human heparanase immunoassay kit. According to diagnosis, CAT scan and/or FDG/ PET-CT fusion were performed to assess response to treatment after 2-3 courses of chemotherapy. Two patients received VAMP protocol (1 stage IA, 1 stage IIA), 1 received AV-PC (nonbulky stage IIA), 4 received COPP/ABV (3 stage IIA bulky, 1 stage IIIA nonbulky), 4 received ABVE-PC (2 stage IIB, 1 stage IIA bulky, 1 stage IIIA bulky), 2 received ABVD (1 stage IIA bulky, 1 stage IIIA), and 6 received escalated BEACOPP (1 stage IIIB, 3 stage IVA, 2 stage IVB).Changes in HP levels were found to correlate with response to treatment for most of the children. At diagnosis, average HP level was 1019 pg/mL (range, 141-5733 pg/mL), decreasing at restaging to 588 pg/mL (range, 62-3267 pg/mL) (p = .034). At diagnosis, the average HP of the 16 patients in CR or VGPR was 1104 pg/mL; it had decreased at restaging to 586 pg/mL (p = .032). At diagnosis, the average HP level for the 3 patients with TP or PR was 1704 pg/mL; it had increased to 1938 pg/mL at restaging (p = .166). Due to the small number of patients, no correlation was observed between HP levels at diagnosis, staging, or any other clinical prognostic factor.Changes in plasma HP levels correlated with response to treatment for children diagnosed with Hodgkin lymphoma. This provides a rationale for exploring clinical interest in plasma heparanase measurements of a larger group, using the test for clinical trials of antiangiogenic therapies.

Despite comprehensive management of pediatric sarcomas, only 60% to 70% of children become long-term survivors. This study was undertaken to evaluate whether regular follow-up improves overall survival of children with recurrent sarcomas. The medical charts of 107 children diagnosed with soft tissue and bone sarcomas were reviewed, of whom 29 relapsed. They were divided into 2 groups according to the way of relapse diagnosis: due to complaints/physical examination (14) or on routine imaging studies (15). All were followed by regular physical examination and imaging studies (chest computed tomography, magnetic resonance imaging, and bone scan/positron emission tomography-computed tomography scan with fluorodeoxyglucose) at regular intervals. Analysis of the results showed that (1) regular imaging studies do not facilitate earlier recognition of relapse in children with sarcomas; (2) regular follow-up with imaging studies does not influence overall survival of children with sarcomas; (3) other diagnostic and treatment approaches are needed to improve the survival of children with recurrent sarcomas.

In an attempt to abrogate the deleterious effects of graft-versus-host disease (GVHD), allogeneic transplantation for nonmalignant diseases was performed using high-dose CD34-cell infusion, partial T cell depletion, and no posttransplantation GVHD prophylaxis. Between 1998 and 2004, 16 patients with matched related donors were treated. Median age was 1.5 years (range, 5 months-18 years). The conditioning regimen consisted of busulphan 16 mg/kg, cyclophosphamide 200 mg/kg, antithymocyte globulin (ATG) 25 mg/kg, and fludarabine 200 mg/m 2 . No GVHD prophylaxis was given. High doses of CD34 cells, positively selected by immunomagnetic beads, were infused at a median dose of 10.7 × 10 6 CD34/kg (range, 7.4-50 × 10 6 ). A total of 1 × 10 5 /kg T cells were given. All patients engrafted, with no graft rejections. All were alive and well at a median of 37 months posttransplantation (range, 18-89 months). Only 1 patient developed chronic GVHD. No episodes of severe infection occurred during or after transplantation. Immunologic reconstitution with CD3/CD4 T cells > 200/μL was observed at a median of 117 days and that with naive T cells (CD4/CD45RA) at a median of 188 days posttransplantation. Our findings suggest that allogeneic transplantation from a matched family donor for nonmalignant disorders can be successfully performed using high doses of CD34 cells, moderate T cell depletion, and no posttransplantation immunosuppression.

Anaplastic large cell lymphoma (ALCL) is a well-known entity, but there are no data on prognosis according to the age of the patient, especially in infants. A 2-month-old girl was admitted with a 2-week history of coughing, fever, and lymphadenopathy. Physical examination revealed mild respiratory distress, an erythematous macular rash on her trunk, massive cervical lymphadenopathy, splenomegaly, and very mild ascites. Chest radiograph showed bilateral pulmonary infiltrates, pleural effusion, and a mediastinal mass. CBC count showed WBC: 172,000/microL (PMN 40%, lymphocytes 47%, monocytes 3%); hemoglobin concentration: 8.7 g/dL; platelets: 390,000/microL. Cervical lymph node biopsy revealed anaplastic lymphoma with positive staining to ALK 1 and TIA 1. Immunophenotypic analysis of peripheral and bone marrow lymphoid cells showed an aberrant T-cell immunophenotype, including expression of CD3, CD45R0+, CD43+, and CD30+. Cytogenetic analysis performed on blood and bone marrow samples demonstrated the translocation t(2;5) (p23;q35), and trisomy 47. After leucophoresis, the child received chemotherapy according to the ALCL-99-EICNHL protocol, and was started on corticosteroids and cyclophosphamide, which resulted in marked improvement. After the second course, WBC decreased to 6000/microL without tumor lysis syndrome, but the child developed bacterial and fungal disseminated infections and died of septic shock with multiorgan failure. This report is of a rare case of infant anaplastic lymphoma and excellent response to treatment. Unfortunately, she did succumb to overwhelming infection. More reports of similar cases may determine the cause and prognosis of such children, helping to tailor therapy according to the age of the child and other prognostic factors, especially bone marrow involvement.

GPC 0.37 0.59 0.36 0.27 GNR 0.35 0.12 0.3 0.23 Viral 0.72 1.28 1.34 0.0002 Adeno 0.15 0.38 0.25 0.03 BK 0.03 0.1 0.33

The goal of this study was to identify second opinion consultations by physicians and to determine patient and family factors that appeared to contribute to a second opinion being sought.One hundred and fifty consecutive parents of children with cancer recently treated in our Department of Pediatric Hematology Oncology were interviewed by telephone. The questionnaire included epidemiological data, details about the disease, timing of the second opinion consultation, reasons for seeking a second opinion, and the outcome of the consultation.Thirty-seven (24.7%) parents sought a second opinion. Advice was sought from other physicians in the hospital or at other clinics. There was a correlation to a higher socioeconomic status (P = .003) and to the number of educational years (P = .001). Most of the parents sought a second opinion because they wanted confirmation about the treatment protocol and the professional level of the hematologist oncologist/surgeon and the institution.Second opinion consultations were not uncommon and were mainly secondary to the desire for reassurance. Pediatric oncologists should ensure that patients and their families feel comfortable requesting a second opinion consultation.

(18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) imaging has been used in the assessment of paediatric malignancies. PET/CT increases the diagnostic accuracy in adult cancer patients. The present study assesses the incremental value of FDG PET/CT in paediatric malignancies.A total of 118 (18)FDG PET/CT studies of 46 paediatric patients were reviewed retrospectively. PET and PET/CT results were classified as malignant, equivocal or benign, compared on a site- and study-based analysis, and also compared with the clinical outcome.Three hundred and twenty-four sites of increased FDG uptake were detected. Discordant PET and PET/CT interpretations were found in 97 sites (30%) in 27 studies (22%). PET yielded a statistically significant higher proportion of equivocal and a lower proportion of benign lesion and study results (p0.001) than PET/CT. With PET there were 153 benign (47%), 84 (26%) equivocal and 87 (27%) malignant sites, while PET/CT detected 226 benign (70%), 10 (3%) equivocal and 88 (27%) malignant lesions. PET/CT mainly improved the characterisation of uptake in brown fat (39%), bowel (17%), muscle (8%) and thymus (7%). The study-based analysis showed that 17 equivocal and seven positive PET studies (20%) were interpreted as benign on PET/CT, while three equivocal studies were interpreted as malignant. The study-based sensitivity and specificity of PET/CT were 92% and 78% respectively.PET/CT significantly improved the characterisation of abnormal (18)FDG foci in children with cancer, mainly by excluding the presence of active malignancy in sites of increased tracer activity.

Alveolar rhabdomyosarcoma (ARS) accounts for 20% to 30% of childhood rhabdomyosarcoma and is known to have a worse prognosis than embryonal rhabdomyosarcoma. Metastatic disease is more frequent in patients with alveolar tumors and these children with metastatic disease fare poorly, with a 5-year survival between 20% and 30%. Therefore, ARS represents a significant diagnostic and therapeutic challenge that requires techniques to provide better assessment of the disease than provided by traditional means. F18 fluorodeoxyglucose-positron emission tomography (FDG-PET) depicts the increased metabolism in abnormal tissues, enabling accurate evaluation of suspicious regional and metastatic disease. The new combined PET/CT systems can further improve PET interpretation and affect patient management. The value of FDG in patients with soft tissue sarcomas has been demonstrated in several series, but none specifically in ARS. This report assesses the use of FDG-PET/CT in the detection of regional and metastatic nodes in 3 children diagnosed with ARS of the extremities. All the 3 patients we present had focally increased tracer uptake in nodal stations on a pretherapy PET performed at diagnosis. Tissue confirmation available in 2 patients was negative in 1 patient and positive for metastatic nodal spread in the other. Metastatic axillary disease was possibly also present in the third patient according to his later course of disease.

Introduction Nasopharyngeal carcinoma (NPC) in children is distinguishable from the adult form by its close association with Epstein-Barr virus (EBV) infection, a higher rate of undifferentiated histology, and a greater incidence of advanced locoregional disease. Patients and Methods Sixteen NPC patients, ≤20 years of age were identified from our 1976–2001 tumor registry records. Clinical stage, treatment, recurrence, and survival were evaluated. Sections were stained by immunohistochemistry for p53, Bcl-2, Ki67, and c-Kit and by in situ hybridization for EBER. Obtained data were compared to 32 adult patients. All patients had undifferentiated or non-keratinizing NPC. Results EBER was positive in 100% of children, compared to 90% of adults. Comparing children to adults, median Ki67 index was 49% and 30%, p53 positive tumors were 69% and 94%, positive Bcl-2 was 63% and 72%, and positive c-Kit was 88% and 28%, respectively. Conclusion No parameter had significant predictive values for survival, although c-Kit expression had a trend for better prognosis in the pediatric group. By univariate analysis of all 48 cases, positive c-Kit was associated with better survival (P = 0.029), largely due to the better survival of the pediatric group. By multivariate analysis, increased stage (P = 0.006) and older age (P = 0.044) correlated with worse prognosis. © 2004 Wiley-Liss, Inc.

High doses of methotrexate (MTX) have been incorporated in the treatment of osteogenic sarcoma since the 1970s. Unfortunately, high-dose MTX (HD-MTX) can cause untoward side effects that may complicate the proper management of these patients. Two cases of MTX-induced acral erythema are described and the possible implications of this complication are reviewed, with a discussion of the pathophysiology of this adverse effect. Two young female patients suffering from osteogenic sarcoma received HD-MTX (12 g/m2) according to the chemotherapeutic protocol. A 17-year-old patient with osteogenic sarcoma of the head developed painful acral erythema of her palms and soles after the fifth dose of MTX, and a 22-year-old patient with osteosarcoma of the femur developed severe acral erythema after the sixth dose. The severity of the reaction was significant enough to cancel further treatment with HD-MTX in both patients. All symptoms resolved without sequellae several weeks later in both cases. Acral erythema may pose a significant albeit transient phenomenon adversely influencing chemotherapy in patients suffering from osteosarcoma and treated with HD-MTX. The pathophysiology of this side effect is not completely understood and further investigation of the pharmacokinetics of HD-MTX in this patient population is needed.

This is the 11th official document of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology, instituted in 1991. There is a tendency for some physicians to make blanket statements against the use of non-proven, nonconventional therapies, even when these therapies are not harmful. There is an equal and opposite tendency on the part of many parents to do all that they possibly can for their children, including using any non-conventional therapy they feel might do some good. The health care team must open a healthy dialogue with parents that will lead to a clear distinction between those complementary therapies that are harmful and those that are not, indeed, might even be helpful psychologically if not therapeutically.

The goal of this study was to evaluate the frequency and timing of "do not resuscitate" (DNR) orders among pediatric oncology patients with progressive solid tumors. A retrospective evaluation of the medical charts of 36 patients who died in our department over the last 4 years was made. There were 21 males and 15 females with a mean age of 10 years (range, 1-22 years). Fourteen patients had brain tumors, 12 had sarcomas, 5 had lymphomas, 4 had neuroblastomas, and 1 suffered from hepatocellular carcinoma. A DNR order was registered in the medical charts of 22 (61%) patients. The DNR was ordered within less than 24 h of death in 5 patients. Median time from DNR order until death was 5 days (range, 0.25-82 days). Place of death was home for 5 (14%) patients, 3 of whom had DNR orders; pediatric oncology ward for 28 (78%), 19 of whom had DNR orders); ICU for 3 (8%), none with a DNR order. Mean time from last day of anticancer treatment until death was 63 days in the group with DNR orders and 56.5 days in the group without DNR orders (p = NS). The study showed that (1) DNR orders were written in only about half the charts of patients with progressive cancer; (2) in several cases, DNR orders were given close to death; and (3) advanced discussion of DNR with parents is needed to reduce parental and medical staff stress accompanying the death of a child and optimizing management of the terminal phase of the disease.

A 14-year old girl was diagnosed as suffering from an immature teratoma. As removal of the teratoma was technically unfeasible, the patient was started on interferon alpha2beta, 3 MU/day, 5 days per week. On this therapy, the growth of the teratoma was stopped and the patient has been well for the past 50 months. She continues to be treated with interferon alpha2beta, with almost no side effects and no restrictions of her everyday activities, with a good quality of life. She is able to attend school regularly, travels abroad frequently, and participates fully in everyday activities normal for her age and social conditions. Her Karnofsky performance status is 100. This case demonstrates the efficacy of interferon alpha2beta therapy in certain instances of growing teratoma syndrome, even when the tumorous mass is initially quite large.