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Background: In retrospective analyses, the Pediatric Oncology Group [POG) and the Federation National des Centres de Lutte Contre le Cancer (FNCLCC) histologic grade predict outcome in pediatric non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), but prospective data on grading, clinical features, and outcomes of low-grade NRSTS are limited., Methods: We analyzed patients less than 30 years of age enrolled on Children's Oncology Group (COG) study ARST0332 (NCT00346164) with POG grade 1 or 2 NRSTS. Low-risk patients were treated with surgery alone. Intermediate-/high-risk patients received ifosfamide/doxorubicin and radiotherapy, with definitive resection either before or after 12 weeks of chemoradiotherapy., Results: Estimated 5-year event-free and overall survival were 90% and 100% low risk (n = 80), 55% and 78% intermediate risk (n = 15), and 25% and 25% high risk (n = 4). In low-risk patients, only local recurrence was seen in 10%; none with margins greater than 1 mm recurred locally. Sixteen of 17 intermediate-/high-risk patients who completed neoadjuvant chemoradiotherapy underwent gross total tumor resection, 80% with negative margins. Intermediate-/high-risk group events included one local and seven metastatic recurrences. Had the FNCLCC grading system been used to direct treatment, 29% of low-risk (surgery alone) patients would have received radiotherapy ± chemotherapy., Conclusions: Most low-risk patients with completely resected POG low-grade NRSTS are successfully treated with surgery alone, and surgical margins greater than 1 mm may be sufficient to prevent local recurrence. Patients with intermediate- and high-risk low-grade NRSTS have outcomes similar to patients with high-grade histology, and require more effective therapies. Use of the current FNCLCC grading system may result in overtreatment of low-risk NRSTS curable with surgery alone., (© 2024 Wiley Periodicals LLC.)

Background: Clearing all pulmonary metastases is essential for curing pediatric solid tumors. However, intraoperative localization of such pulmonary nodules can be challenging. Therefore, an intraoperative tool that localizes pulmonary metastases is needed to improve diagnostic and therapeutic resections. Indocyanine green (ICG) real-time fluorescence imaging is used for this purpose in adult solid tumors, but its utility in pediatric solid tumors has not been determined., Methods: A single-center, open-label, nonrandomized, prospective clinical trial (NCT04084067) was conducted to assess the ability of ICG to localize pulmonary metastases of pediatric solid tumors. Patients with pulmonary lesions who required resection, either for therapeutic or diagnostic intent, were included. Patients received a 15-minute intravenous infusion of ICG (1.5 mg/kg), and pulmonary metastasectomy was performed the following day. A near-infrared spectroscopy iridium system was optimized to detect ICG, and all procedures were photo-documented and recorded., Results: ICG-guided pulmonary metastasectomies were performed in 12 patients (median age: 10.5 years). A total of 79 nodules were visualized, 13 of which were not detected by preoperative imaging. Histologic examination confirmed the following histologies: hepatoblastoma (n = 3), osteosarcoma (n = 2), and one each of rhabdomyosarcoma, Ewing sarcoma, inflammatory myofibroblastic tumor, atypical cartilaginous tumor, neuroblastoma, adrenocortical carcinoma, and papillary thyroid carcinoma. ICG guidance failed to localize pulmonary metastases in five (42%) patients who had inflammatory myofibroblastic tumor, atypical cartilaginous tumor, neuroblastoma, adrenocortical carcinoma, or papillary thyroid carcinoma., Conclusions: ICG-guided identification of pulmonary nodules is not feasible for all pediatric solid tumors. However, it may localize most metastatic hepatic tumors and high-grade sarcomas in children., (© 2023 Wiley Periodicals LLC.)

Malignant primary bone tumors are uncommon in the pediatric population, accounting for 3%-5% of all pediatric malignancies. Osteosarcoma and Ewing sarcoma comprise 90% of malignant primary bone tumors in children and adolescents. This paper provides consensus-based recommendations for imaging in children with osteosarcoma and Ewing sarcoma at diagnosis, during therapy, and after therapy., (© 2022 Wiley Periodicals LLC.)

Pediatric soft tissue tumors of the extremity include rhabdomyosarcoma and nonrhabdomyosarcoma neoplasms. This manuscript provides consensus-based imaging recommendations for imaging evaluation at diagnosis, during treatment, and following completion of therapy for patients with a soft tissue tumor of the extremity., (© 2022 Wiley Periodicals LLC.)

Objective: Recent increased awareness and research studies reflect possible associations between opioid exposure and cancer outcomes. Children with neuroblastoma (NB) often require opioid treatment for pain. However, associations between tumor response to chemotherapy and opioid exposure have not been investigated in clinical settings., Methods: This is a single-institution retrospective review of patients with NB treated between 2013 and 2016. We evaluated opioid consumption quantified in morphine equivalent doses (mg/kg) based on nurse- or patient-controlled analgesia during antibody infusions. We also analyzed their associations with change in primary tumor volume and total tumor burden., Results: Of 42 patients given opioids for pain related to anti-disialoganglioside monoclonal antibodies (anti-GD2 mAb), data completion was achieved for 36, and details of statistical analyses were entered. Median total weight-based morphine equivalent (over 8 days) was 4.71 mg/kg (interquartile range 3.49-7.96). We found a statistically insignificant weak negative relationship between total weight-based morphine equivalents and tumor volume ratio (correlation coefficient -.0103, p-value .9525) and a statistically insignificant weak positive relationship between total weight-based morphine equivalent and Curie score ratio (correlation coefficient .1096, p-value .5247)., Conclusion: Our study found no statistically significant correlation between opioid consumption and natural killer (NK) cell-mediated killing of NB cells as measured by effects on tumor volume/tumor load., (© 2022 Wiley Periodicals LLC.)

Purpose: Acute pancreatitis (AP) due to chemotherapy-induced pancreatic injury is a common side effect of treatment for acute lymphoblastic leukemia (ALL), the most common childhood malignancy. The American College of Radiology recommends ultrasound (US) for initial imaging of AP in all populations to assess for ductal obstruction. However, US may be insensitive to diagnose and assess chemotherapy-associated AP., Methods and Materials: The institutional review board approved this retrospective study. Patients with ALL and AP were identified from protocol databases, using Common Terminology Criteria for Adverse Events (CTCAE) version 3. Chemotherapy dosing, amylase/lipase levels, clinical symptoms, and US/computed tomography (CT) reports within 10 days of diagnosis were recorded. All CT images were reviewed for revised Atlanta classification and CT severity index (CTSI)., Results: Sixty-nine patients, aged 2-21 years, experienced 88 episodes of AP, undergoing 98 US and 44 CT. Seventy-two events (82%) occurred within 30 days of asparaginase administration. Sixty-nine episodes (78%) were initially diagnosed by the presence of abdominal pain and pancreatic enzyme elevation. Overall sensitivities for AP detection were 47% using US and 98% for CT. US sensitivity was greatest in CTCAE grade 4 (86%) and necrotizing pancreatitis (67%)., Conclusions: Most cases of AP in children with ALL can be diagnosed with clinical history and labs. US has limited sensitivity in detecting pancreatitis in this population. Imaging to diagnose AP in this patient population could be limited to clinically equivocal cases., (© 2020 Wiley Periodicals LLC.)

Mesoblastic nephroma is the most frequent renal tumor in newborns and young infants, and the cellular type is characterized by an ETV6-NTRK fusion, which constitutively activates the tropomyosin-related kinase (TRK) signaling pathway. Larotrectinib is a highly selective TRK inhibitor with activity in adult and pediatric patients who have TRK fusions. We present a rare case of a patient with mesoblastic nephroma metastatic to bone who had a dramatic response to larotrectinib., (© 2018 The Authors. Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.)

Constitutional mismatch repair deficiency (CMMRD) is a cancer predisposition syndrome associated with a high risk of developing early-onset malignancies of the blood, brain, and intestinal tract. We present the case of a patient with T-lymphoblastic lymphoma at the age of 3 years, followed by Burkitt lymphoma 10 years later. This patient also exhibited numerous nonmalignant findings including café au lait spots, lipomas, bilateral renal nodules, a nonossifying fibroma, multiple colonic adenomas, and a rapidly enlarging pilomatrixoma. The spectrum of malignant and nonmalignant neoplasms in this patient highlights the remarkable diversity, and early onset, of lesions seen in children with CMMRD., (© 2016 Wiley Periodicals, Inc.)

Background: Bone scintigraphy (BS) is used to detect osseous metastases in osteosarcoma. (18) F-fluorodeoxyglucose-positron emission tomography-computed tomography ((18) F-FDG-PET-CT) is being increasingly used for staging. We compared the sensitivity, specificity, and diagnostic accuracy of (18) F-FDG-PET-CT and BS for detecting osseous metastases in osteosarcoma., Methods: We retrospectively reviewed 39 patients with osteosarcoma who had paired PET-CT and BS at diagnosis and/or first recurrence from 2003 to 2012. Imaging studies were reviewed by two pediatric imaging specialists who were blinded to results of the opposing modality and reference standard. Reviewers categorized lesions as benign, malignant, or indeterminate. Reference standard for lesion histology was biopsy or clinical follow-up. Diagnostic performance of PET-CT, BS, and combined modalities were determined., Results: There were 40 examinations from 39 patients and 65 distant lesions were evaluated. Median age was 12 years (range 5-19 years). Four patients had 15 osseous metastases at diagnosis (two biopsied and 13 clinically), and two had five osseous metastases at recurrence (one biopsied and five clinically). For distant sites, sensitivity, specificity, and diagnostic accuracy were 79%, 89% and 86% for PET-CT, 32%, 96%, and 77% for BS, and 95%, 85%, and 88% for PET-CT/BS combined. Sensitivity of PET-CT was superior to BS (P = 0.035); combined imaging modalities were superior to BS (P < 0.001) but not better than PET-CT alone (P = 0.25). Specificity for BS approached significance compared to combined imaging (P = 0.063). Examination-based analysis yielded similar results between individual and combined imaging modalities., Conclusions: (18) F-FDG-PET-CT demonstrated superior sensitivity over BS for detecting osseous metastases, supporting the use of (18) F-FDG-PET-CT for staging of osteosarcoma., Competing Interests: The authors declare that they have no relevant conflicts of interest., (© 2016 Wiley Periodicals, Inc.)

Background: Limb-sparing surgery for osteosarcoma requires taking wide bony resection margins while maximizing preservation of native bone and joint. However, the optimal bony margin and factors associated with recurrence and survival outcomes in these patients are not well established., Procedure: We conducted a retrospective review of outcomes in children and adolescents with newly diagnosed osteosarcoma from 1986 to 2012, where bony resection margins for limb-sparing surgeries were decreased serially from 5 to 1.5 cm. The association between bony margins and other surgicopathological factors with survival and recurrence outcomes was determined., Results: In 181 limb-sparing surgeries in 173 patients, planned and actual bony resection margins were not significantly associated with local recurrence-free survival (LRFS), event-free survival (EFS), and overall survival (OS)-at median 5.8 years follow-up, decreasing planned bony resection margins from 5 to 1.5 cm did not significantly decrease survival outcomes. Multivariable analysis showed that the presence of distant metastases at diagnosis was associated with decreased LRFS, EFS, and OS (P = 0.002, 0.005, and <0.0001, respectively). Post-chemotherapy tumor necrosis ≤90% was associated with decreased EFS and OS (P = 0.001 and 0.022, respectively). Earlier years of treatment and pathologic fractures were associated with decreased OS only (P = 0.018 and 0.008, respectively); previous cancer history and male gender were associated with decreased EFS only (P = 0.043 and 0.023, respectively)., Conclusion: We did not observe significant increase in adverse survival outcomes with reduction of longitudinal bony resection margins to 1.5 cm. Established prognostic factors, particularly histologic response to chemotherapy and metastases at diagnosis, remain relevant in limb-sparing patients. Pediatr Blood Cancer 2015;62:246-251. © 2014 Wiley Periodicals, Inc., Competing Interests: STATEMENT No conflicts of interest to declare., (© 2014 Wiley Periodicals, Inc.)

Background: Chronic transfusions help prevent primary stroke in children with sickle cell anemia (SCA) and abnormal transcranial Doppler (TCD) velocities. However, the effects of transfusions on TCD velocities and brain MRI/MRA findings are incompletely described., Procedure: We reviewed TCD and brain MRI/MRA results in 27 children with SCA and abnormal TCD velocities receiving transfusions to prevent primary stroke. All TCDs were performed by a single examiner, immediately prior to a scheduled transfusion. We also examined the effects of laboratory and clinical parameters on TCD responses to transfusion therapy., Results: For the whole cohort, the average pre-transfusion HbS on transfusions was 31.7 ± 12.3%. The most significant decline in TCD velocities occurred within 10 months of starting transfusions. Follow-up TCD values trended upward with increasing pre-transfusion %HbS levels while on treatment. Half of the children had persistent conditional/abnormal TCD velocities despite transfusions and 28% had new/progressive stenosis on MRA, but none had primary stroke during 73 patient-years of follow-up., Conclusions: For children with SCA and abnormal TCD velocities, transfusions lower TCD velocities and help prevent stroke, but do not always result in normal velocities or protect against progression of cerebral vasculopathy. Improved adherence to transfusion goals may improve on-treatment TCD velocities., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Over the past decade, PET-CT has been used to assess rhabdomyosarcoma (RMS) in children. However, the role of PET-CT in staging RMS is unknown., Procedure: Thirty subjects with RMS, median age 7.3 years, underwent PET-CT before therapy. PET-CTs and conventional imaging (CI) were independently reviewed by two radiologists and two nuclear medicine physicians to determine the presence of metastases. Accuracy, sensitivity, and specificity of PET-CT for detecting metastases were compared to CI using biopsy and clinical follow-up as reference standards. Maximum standardized uptake values (SUV(max)) of primary tumors, lymph nodes, and pulmonary nodules were measured., Results: Primary tumors had an average SUV(max) of 7.2 (range, 2.5-19.2). Accuracy rates for 17 subjects with nodal disease were 95% for PET-CT and 49% for CI. PET-CT had 94% sensitivity and 100% specificity for nodal disease. Of seven pulmonary nodules detected by CI, three were not identified by PET-CT, two were indeterminate, and one was malignant with a SUV(max) (3.4) > twice that of benign nodules. Two subjects had bone disease; both were identified by PET-CT but only one by CI. Four subjects had bone marrow disease, two had positive PET-CTs but none had positive CI. Two subjects had soft tissue metastases detected by PET-CT but not CI., Conclusions: PET-CT performed better than CI in identifying nodal, bone, bone marrow, and soft tissue disease in children with RMS. CI remains essential for detection of pulmonary nodules. We recommend PET-CT for staging of children with RMS. CI with Tc(99m) bone scan can be eliminated., (Copyright © 2012 Wiley Periodicals, Inc.)

Imaging plays a pivotal role in the diagnosis and management of children with hepatoblastoma. However, the continuing evolution of imaging technologies and rarity of hepatoblastoma make validation of imaging approaches challenging. In Europe and other parts of the world staging of hepatoblastoma is based on imaging features while in North America it is based on surgical resectability. In this review we discuss the clinical and imaging features that aid in diagnosing and monitoring children with hepatoblastoma. The potential roles of new imaging techniques are presented, and differences between staging systems are addressed., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Children with sickle cell anemia (SCA) often develop hyposthenuria and renal hyperfiltration at an early age, possibly contributing to the glomerular injury and renal insufficiency commonly seen later in life. The Phase III randomized double-blinded Clinical Trial of Hydroxyurea in Infants with SCA (BABY HUG) tested the hypothesis that hydroxyurea can prevent kidney dysfunction by reducing hyperfiltration., Procedure: 193 infants with SCA (mean age 13.8 months) received hydroxyurea 20 mg/kg/day or placebo for 24 months. (99m) Tc diethylenetriaminepentaacetic acid (DTPA) clearance, serum creatinine, serum cystatin C, urinalysis, serum and urine osmolality after parent-supervised fluid deprivation, and renal ultrasonography were obtained at baseline and at exit to measure treatment effects on renal function., Results: At exit children treated with hydroxyurea had significantly higher urine osmolality (mean 495 mOsm/kg H(2) O compared to 452 in the placebo group, P = 0.007) and a larger percentage of subjects taking hydroxyurea achieved urine osmolality >500 mOsm/kg H(2) O. Moreover, children treated with hydroxyurea had smaller renal volumes (P = 0.007). DTPA-derived glomerular filtration rate (GFR) was not significantly different between the two treatment groups, but was significantly higher than published norms. GFR estimated by the Chronic Kidney Disease in Children (CKiD) Schwartz formula was the best non-invasive method to estimate GFR in these children, as it was the closest to the DTPA-derived GFR., Conclusion: Treatment with hydroxyurea for 24 months did not influence GFR in young children with SCA. However, hydroxyurea was associated with better urine concentrating ability and less renal enlargement, suggesting some benefit to renal function., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Administration of an oral cephalosporin allowed advancement of the dosage of oral irinotecan. This study investigates whether administration of an oral cephalosporin increases the maximum tolerated dose (MTD) of intravenous irinotecan., Procedure: Irinotecan was administered intravenously on Days 1-5 and Days 8-12 of a 21-day cycle with continuous oral cefpodoxime starting 2 days prior to irinotecan. Cohorts of 3-6 pediatric patients with refractory solid tumors were enrolled at 4 dosage levels, starting at the single-agent irinotecan MTD of 20 mg/m(2) /dose., Results: The 17 evaluable patients received 39 courses of therapy. None of the patients treated with 20 mg/m(2) /dose experienced dose-limiting toxicity (DLT). One of six patients treated at 30 mg/m(2) /dose experienced dose-limiting neutropenia. Two of three patients treated with 45 mg/m(2) /dose and two of five treated with 40 mg/m(2) /dose experienced dose-limiting diarrhea, with associated dehydration and anorexia. Two unconfirmed partial responses were observed after one course in a patient with Ewing sarcoma and one with paraganglioma. A child with refractory neuroblastoma had disease stabilization through 12 courses of therapy. Median (range) systemic exposure to SN-38 at the MTD (30 mg/m(2) /dose) was 67 ng-h/mL (36 to 111 ng-h/mL)., Conclusions: The MTD of intravenous irinotecan administered on a protracted schedule was increased by 50% from 20 to 30 mg/m(2) /dose with the addition of oral cefpodoxime. The most prominent DLT remained diarrhea. High interpatient variability in irinotecan pharmacokinetics was observed; however, SN-38 exposure at the MTD was greater than most reported exposures with the 20 mg/m(2) dosage., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: Cardiac failure from myocardial iron deposition is a severe complication in patients with transfusion-related iron overload. Progressive heart damage from iron overload can cause left ventricular systolic and diastolic dysfunction in patients with hematologic disorders. Since nontransfused patients with sickle cell anemia (SCA) have a high incidence of diastolic dysfunction, we investigated the relationships among transfusional iron burden, myocardial iron deposition, and diastolic ventricular dysfunction by T2*-MRI and tissue Doppler echocardiography in iron-overloaded children with SCA., Procedure: Children (> or =7 years) with SCA and iron overload (serum ferritin >1,000 ng/ml or > or =18 lifetime transfusions) were eligible. Serum ferritin and hepatic iron content (HIC) were measured and participants underwent nonsedated T2*-MRI of the heart, echocardiogram, electrocardiogram, and multi-uptake gated acquisition (MUGA) scan. Age-matched normative echocardiographic data were used for comparison., Results: Among 30 children with SCA (median age, 13 years) and iron overload, mean (+/-SD) HIC and serum ferritin were 10.8 mg Fe/g (+/-5.9 mg Fe/g) and 3,089 ng/ml (+/-2,167 ng/ml), respectively. Mean T2*-MRI was 33 msec (+/-7 msec, range, 22-49). Echocardiography showed a high prevalence of diastolic dysfunction (77% and 45% abnormally low mean mitral annular velocity and mean tricuspid annular velocity, respectively); however, echocardiogram and MUGA scan findings were not significantly associated with HIC or T2*-MRI., Conclusions: Diastolic dysfunction is not associated with transfusional iron burden or myocardial iron deposition among children with SCA. Diastolic dysfunction likely results from disease pathophysiology and severity rather than iron overload., (2010 Wiley-Liss, Inc.)

Patients with multi-system Langerhans cell histiocytosis (LCH) who progress on frontline therapy have a dismal outcome. Responses to cladribine have been reported in relapsed LCH, but there are no well defined salvage regimens for LCH is refractory to therapy. The next generation deoxyadenosine analog, clofarabine, has demonstrated activity in patients with leukemia that is refractory to salvage regimens, including other nucleotide congeners; however, no experience exist on the use of clofarabine in LCH. In this report we describe significant single agent activity of clofarabine in disseminated LCH refractory to salvage regimens, including cladribine., ((c) 2008 Wiley-Liss, Inc.)

Background: Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by intra-alveolar accumulation of periodic acid-Schiff (PAS)-positive surfactant components. Leukemia is the cancer most often associated with PAP; prolonged neutropenia and reduction of alveolar macrophages by myeloablative chemotherapy or leukemic infiltration are implicated. Only isolated cases of PAP have been reported, and pediatric experience is limited., Procedure: We reviewed all pathology records (1962-2007) of St. Jude Children's Research Hospital to identify patients with PAP., Results: Five patients had PAP. As expected, all had leukemia and had profound neutropenia at onset of PAP. A diagnosis was made only after PAS staining of bronchoalveolar lavage (BAL), lung biopsy, or autopsy specimens. Two patients had Down syndrome, which is not known to be associated with PAP. The other three patients had undergone hematopoietic stem cell transplantation (HSCT). Two patients showed clinical improvement or histological disappearance of PAP after neutropenia resolved., Conclusions: PAP should be considered in the differential diagnosis of severe respiratory symptoms in neutropenic patients with hematologic malignancy, especially those with Down syndrome, a history of HSCT, or active disease. PAP should be confirmed by PAS staining of a BAL or lung biopsy specimen., ((c) 2008 Wiley-Liss, Inc.)

Background: Recent technical advances in CT imaging and data processing have improved the ability to detect small pulmonary nodules in children with bone and soft-tissue sarcoma undergoing radiologic imaging of the chest., Procedure: We retrospectively studied medical records and CT chest scans at initial diagnosis of 210 children and young adults presenting to a single pediatric tertiary care hospital specialized in oncology for evaluation of bone or soft-tissue sarcoma. We correlated clinical features and CT scan findings with patient outcome and histologic results, when available., Results: Pulmonary nodules (diameter

Background: Although transcranial Doppler ultrasonography (TCD) screening is effective in identifying children with sickle cell anemia (SCA) who are at high risk of stroke, not all children are screened. In 2003, we instituted a comprehensive TCD screening program designed to screen all at-risk children treated at our sickle cell center., Procedure: We evaluated the efficacy of our program by comparing the number of patients screened per year and incidence of first stroke across three periods defined by TCD usage: (1) pre-dating TCD screening, (2) sporadic TCD screening, and (3) comprehensive TCD screening., Results: During Period 2, an average of 52 patients/year were screened. In Period 3, an average of 95 patients/year were screened representing 99% of the at-risk population. Eighteen strokes occurred in Period 1, 22 in Period 2 and three in Period 3. The first stroke incidence was significantly lower in Period 3 compared to Periods 1 and 2 (P = 0.047). Furthermore, of the 25 patients in Periods 2 and 3 who had stroke, only six had received TCD screening (four in Period 2, two in Period 3). These six either declined prophylactic transfusion therapy (n = 2), had co-existing stroke risk factors (n = 2), or did not return for appropriate TCD follow-up (n = 2). Therefore, strokes that occurred were not the result of a failure of TCD screening per se., Conclusions: It is possible to perform TCD screening of most children with SCA. TCD screening is effective in reducing first stroke incidence in these children., ((c) 2008 Wiley-Liss, Inc.)

Introduction: Chronic organ damage is an insidious process in patients with sickle cell anemia (SCA). Although hydroxyurea prevents acute vaso-occlusive events, its effects on the preservation of organ function remain undefined., Patients and Methods: We retrospectively reviewed our single institution experience with children with SCA treated with hydroxyurea for clinical disease severity, who had optional radionuclide liver-spleen (LS) and brain magnetic resonance imaging (MRI)/with angiography (MRA) performed before and during therapy. Studies were reviewed by pediatric radiologists blinded to treatment status. Demographic and laboratory predictors were modeled using logistic regression., Results: A total of 43 children had spleen function measured both at baseline and on therapy. After a median of 2.6 years (range, 0.2-8.6 years) of hydroxyurea at maximum tolerated dose (MTD), six patients (14%) completely recovered splenic function and two (5%) had preserved splenic function. These eight children had a greater hemoglobin (Hb) concentration on hydroxyurea therapy than those without splenic function (9.1 vs. 8.6 gm/dl, P = 0.01). Of 25 children with brain MRI/MRA studies performed before initiating hydroxyurea and on therapy, 24 (96%) had no change in brain ischemic lesions compared with pre-treatment studies, after a median of 2.9 years of treatment., Conclusion: These retrospective data suggest that hydroxyurea at MTD possibly preserves spleen and brain function in children with SCA, and can even result in recovery of splenic function. Higher final Hb concentration during therapy is a significant laboratory predictor of improved splenic function., ((c) 2007 Wiley-Liss, Inc.)

Familial adenomatous polyposis (FAP) is an inherited condition causing numerous adenomatous colorectal polyps and a markedly elevated risk of colon cancer. FAP may be associated with various extracolonic manifestations such as desmoid fibromatosis and osteomas (termed Gardner's syndrome) and brain tumors, usually medulloblastoma or glioma [termed Brain Tumor Polyposis (BTP) syndrome type 2]. We describe a pediatric patient who initially presented with prolactinoma and later was found to have Gardner's syndrome. A germline mutation of the APC (adenomatous polyposis coli) gene was identified. Our case illustrates the association between prolactinoma and FAP, which may represent a rare subtype of Gardner's and BTP syndromes., ((c) 2007 Wiley-Liss, Inc.)

Background: Preclinical models show sequence-dependent synergy with the combination of temozolomide and irinotecan, and a Phase I trial has demonstrated the combination to be tolerable and active in children with relapsed solid tumors. Because responses were seen in patients with Ewing sarcoma (ES) on that trial, additional patients were treated with this combination following study completion., Procedure: We reviewed data from all ES patients treated with temozolomide and irinotecan at four institutions, including seven patients treated on the above Phase I trial., Results: Sixteen patients received a total of 95 courses, with a median of five courses per patient. All patients had either progressive disease (PD) during initial therapy (n = 5) or relapse within 2 years of diagnosis (n = 11). Twelve patients had metastatic disease at diagnosis, including 5 with bone and/or marrow metastases. Patients received oral temozolomide 100 mg/m(2)/day on days 1-5 plus intravenous irinotecan 10-20 mg/m(2)/day on days 1-5 and 8-12, with courses repeated every 21-28 days. We observed 1 complete, 3 partial, and 3 minor responses in 14 evaluable patients, with a median duration of response of 30 weeks. Planned 21-day courses were tolerable and no more toxic than 28-day courses. Myelosuppression was minimal despite heavy pretreatment. Grade 3-4 diarrhea occurred in 11% of courses and was related to higher irinotecan doses. Over 600 irinotecan doses were administered uneventfully at home., Conclusions: Temozolomide and protracted intravenous irinotecan given in 21-day courses was tolerable and active in patients with advanced ES. Home administration of irinotecan with temozolomide was safe and is reasonable palliative therapy. A formal Phase II study using a uniform dose and schedule is warranted to better define activity.

Background: Survivors of Hodgkin lymphoma and other patients who receive neck irradiation are at increased risk of thyroid cancer. Ultrasonography provides an inexpensive and non-invasive method of thyroid screening, but the clinical significance of thyroid nodules detected by ultrasound screening is uncertain., Procedure: We reviewed the demographics, clinical characteristics, method of detection, and outcome of patients who developed thyroid nodules after treatment for pediatric Hodgkin lymphoma at our institution. One radiologist reviewed all imaging studies., Results: Sixty-seven children treated for Hodgkin lymphoma from 1962 to 2001 developed thyroid nodules. The study group represented 9,024 person-years of follow-up after the diagnosis of Hodgkin lymphoma and 581 person-years after diagnosis of a thyroid nodule. A median of 10.5 years (range, 0.2-24.8 years) elapsed between the diagnoses of Hodgkin lymphoma and thyroid nodule(s). All but one patient had received neck irradiation for Hodgkin lymphoma, with a median thyroid radiation dose of 35 Gy (range, 12-45 Gy). Thyroid nodules were found to be malignant in seven patients (10%), at a median of 16.2 years (range, 8.4-23.7 years) after diagnosis of Hodgkin lymphoma. Only one malignancy was found through screening ultrasonography. All patients with thyroid cancer remained disease-free at 0.4-16.2 years of follow-up., Conclusions: Thyroid nodules are common in Hodgkin lymphoma survivors treated with neck irradiation, but the majority of these lesions have an indolent clinical course and do not undergo malignant transformation. Only patients with a palpable mass or clinical symptoms need more extensive evaluation, including Doppler-flow ultrasonography and fine-needle aspiration.