Pediatric Sarcoma Patients Research Articles

Conditional survival of pediatric, adolescent, and young adult soft tissue sarcoma and bone tumor patients

BackgroundSurvival estimates for soft tissue sarcomas (STS) and malignant bone tumors (BT) diagnosed in pediatric, adolescent, and young adult patients are not easily available. We present survival estimates based on a patient having survived a defined period of time (conditional survival). Conditional survival estimates for the short-term were calculated for patients from diagnosis to the first five years after diagnosis and for patients surviving in the long-term (up to 20 years after diagnosis). MethodsWe identified 703 patients who were diagnosed with a STS or BT at age ≤25 years from January 1, 1986 to December 31, 2012 at a large pediatric oncology center in Salt Lake City, Utah, United States. We obtained cancer type, age at diagnosis, primary site, and demographic data from medical records, and vital status through the National Death Index. Cancer stage was available for a subset of the cohort through the Utah Cancer Registry. Cox proportional hazards models, adjusted for age and sex, calculated survival estimates for all analyses. ResultsShort-term survival improves over time for both sarcomas. Short-term survival for STS from diagnosis (Year 0) did not differ by sex, but short-term survival starting from 1-year post diagnosis was significantly worse for male patients (Survival probability 1-year post-diagnosis [SP1]:77% [95% CI:71-83]) than female patients (SP1:86% [81–92]). Survival for patients who were diagnosed at age ≤10 years (Survival probability at diagnosis [SP0]:85% [79–91]) compared to diagnosis at ages 16–25 years (SP0:67% [59–75]) was significantly better at all time-points from diagnosis to 5-years post-diagnosis. Survival for axial sites (SP0:69% [63–75]) compared to extremities (SP0:84% [79–90]) was significantly worse from diagnosis to 1-year post-diagnosis. Survival for axial BT (SP0: 64% [54–74] was significantly worse than BT in the extremities (SP0:73% [68–79]) from diagnosis to 3-years post diagnosis. Relapsed patients of both sarcoma types had significantly worse short-term survival than non-relapsed patients. Long-term survival for STS in this cohort is 65% at diagnosis, and improves to 86% 5-years post-diagnosis. BT survival improves from 51% at diagnosis to 78% at 5-years post-diagnosis. ConclusionConditional survival for short- and long-term STS and BT improve as time from diagnosis increases. Short-term survival was significantly affected by patients' sex, age at diagnosis, cancer site, and relapse status.

Racial and ethnic disparities in treatment and survival of pediatric sarcoma

BackgroundChildhood sarcomas are rare and require complex interdisciplinary care including surgery, chemotherapy, and radiation. The goal of this study was to determine if racial or ethnic disparities exist for pediatric sarcoma patients in the United States. MethodsThe United States' National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to identify patients aged 0-21 diagnosed with primary sarcomas from 1973 to 2012. Patients were considered by race and ethnicity. Survival curves were computed using the Kaplan-Meier method and the log-rank test. ResultsA total of 11,502 patients were included in this study. When stratified by race, non-Hispanic black and Hispanic patients were significantly more likely to present with advanced stage disease than white patients. White patients were more likely to receive radiation therapy than black and Hispanic patients (P = 0.01). There was no significant difference between patients who underwent surgery (P = 0.21). Overall survival was better for white patients than black or Hispanic ones. Despite the overall 5-year survival improvement during the study period (56.2%-70.3%), survival disparities between race and ethnicity have grown. ConclusionsRacial and ethnic disparities do exist with respect to stage, treatment, and survival of these rare tumors. Black and Hispanic patients are presenting at more advanced stage and have overall worse survival. This survival disparity has widened over the past 4 decades.

Vascularized Fibula-Based Physis Transfer: A Follow-Up Study of Longitudinal Bone Growth and Complications.

Background:The vascularized free fibula epiphyseal transfer provides an option for the preservation of limb lengthening after resection of the proximal humerus in pediatric sarcoma patients. The purpose of this study was to provide a long-term follow-up of longitudinal growth patterns and outcomes after free fibula epiphyseal transfer in upper extremity reconstruction.Methods:A retrospective review of 4 patients who underwent free fibula epiphyseal transfer after oncologic resection of the proximal humerus for osteosarcoma was performed. Oncologic details that could affect outcomes were included in the review: primary tumor pathology, location of malignancy, and presence of recurrence. Details on the reconstruction included longitudinal growth of the flap from the time of implantation to the most recently available radiograph and postoperative complications. The length of the fibula over time was measured from the humeral head to the olecranon process.Results:All patients were alive at the start of this study. The average longitudinal growth rate of the free fibula epiphyseal transfer was 0.54 ± 0.18 cm/y, and patients demonstrated satisfactory and consistent longitudinal bone growth and hypertrophy over time. All 4 patients suffered from a complication of postoperative fibula graft fracture, and 1 of 4 patients experienced unremitting peroneal nerve damage. All patients demonstrated normal wrist and hand motion with a normal arc of elbow flexion and extension.Conclusion:This study demonstrates that the vascularized fibula epiphyseal transfer offers the ability to preserve longitudinal limb growth and hypertrophy throughout adolescence.

Late toxicity and outcomes following radiation therapy for chest wall sarcomas in pediatric patients

PurposeTo investigate the contribution of radiation therapy to acute and late toxicity in pediatric chest wall sarcoma patients and evaluate dosimetric correlates of higher incidence toxicities such as scoliosis and pneumonitis. Methods and materialsThe data from 23 consecutively treated pediatric patients with chest wall sarcomas of various histologies (desmoid, Ewing, rhabdomyosarcoma, nonrhabdomyosarcoma-soft tissue sarcomas) were reviewed to evaluate the relationship between end-organ radiation dose, clinical factors, and the risk of subsequent late effects (scoliosis, pneumonitis). Cobb angles were used to quantify the extent of scoliosis. Doses to the spine and lung were calculated from the radiation treatment plan. ResultsThe range of scoliosis identified on follow-up imaging ranged from −47.6 to 64° (median, 2.95°). No relationship was identified between either radiation dose to the ipsilateral or contralateral vertebral body or tumor size and the degree or direction of scoliosis. The extent of surgical resection and number and location of resected ribs affected the extent of scoliosis. The dominant predictor of extent of scoliosis at long-term follow-up was the extent of scoliosis following surgical resection. Radiation pneumonitis was uncommon and was not correlated with mean dose or volume of lung receiving 24 Gy; however, 1 of 3 surviving patients who received whole pleural surface radiation therapy developed significant restrictive lung disease. ConclusionsAcute and late radiation therapy–associated toxicities in pediatric chest wall sarcoma patients are modest. The degree of scoliosis following resection is a function of the extent of resection and of the number and location of ribs resected, and the degree of scoliosis at the last follow-up visit is a function of the extent of scoliosis following surgery. Differential radiation therapy dose across the vertebral body does not increase the degree of scoliosis. Severe restrictive pulmonary disease is a late complication of survivors after whole pleural surface radiation therapy.

Investigating the heterogeneity of alkylating agents' efficacy and toxicity between sexes: A systematic review and meta-analysis of randomized trials comparing cyclophosphamide and ifosfamide (MAIAGE study).

A marginal interaction between sex and the type of alkylating agent was observed for event-free survival in the Euro-EWING99-R1 randomized controlled trial (RCT) comparing cyclophosphamide and ifosfamide in Ewing sarcoma. To further evaluate this interaction, we performed an individual patient data meta-analysis of RCTs assessing cyclophosphamide versus ifosfamide in any type of cancer. A literature search produced two more eligible RCTs (EICESS92 and IRS-IV). The endpoints were progression-free survival (PFS, main endpoint) and overall survival (OS). The hazard ratios (HRs) of the treatment-by-sex interaction and their 95% confidence interval (95% CI) were assessed using stratified multivariable Cox models. Heterogeneity of the interaction across age categories and trials was explored. We also assessed this interaction for severe acute toxicity using logistic models. The meta-analysis comprised 1,528 pediatric and young adult sarcoma patients from three RCTs: Euro-EWING99-R1 (n = 856), EICESS92 (n = 155), and IRS-IV (n = 517). There were 224 PFS events in Euro-EWING99-R1 and 200 in the validation set (EICESS92 + IRS-IV), and 171 and 154 deaths in each dataset, respectively. The estimated treatment-by-sex interaction for PFS in Euro-EWING99-R1 (HR = 1.73, 95% CI = 1.00-3.00) was not replicated in the validation set (HR = 0.97, 95% CI = 0.55-1.72), without heterogeneity across trials (P = 0.62). In the pooled analysis, the treatment-by-sex interaction was not significant (HR = 1.31, 95% CI = 0.89-1.95, P = 0.17), without heterogeneity across age categories (P = 0.88) and trials (P = 0.36). Similar results were observed for OS. No significant treatment-by-sex interaction was observed for leucopenia/neutropenia (P = 0.45), infection (P = 0.64), or renal toxicity (P = 0.20). Our meta-analysis did not confirm the hypothesis of a treatment-by-sex interaction on efficacy or toxicity outcomes.

Toward a Better Understanding of the Use of Targeted Therapies in Pediatric Sarcoma Patients

Toward a Better Understanding of the Use of Targeted Therapies in Pediatric Sarcoma Patients

Outcomes of chest wall resections in pediatric sarcoma patients

PurposeChest wall tumors in pediatric patients are rare. This study evaluates outcomes in pediatric patients who have undergone chest wall resections secondary to sarcomas. MethodsA retrospective review was performed for patients <19years old who underwent chest wall resections for sarcoma 1999–2014 at the University of Texas MD Anderson Cancer Center. ResultsOf 44 patients, Ewing's sarcoma (n=18) and osteosarcoma (n=16) were most common. Other sarcomas included synovial sarcoma, chondrosarcoma, and rhabdomyosarcoma. Gore-Tex® or a Marlex™ mesh and methyl methacrylate sandwich was used in 22 patients, and 9 children did not require reconstruction. Twenty-four (54.5%) patients had normal activity, 3 (6.8%) had occasional discomfort, 2 (4.5%) had pain impairing function, 7 (15.9%) required medication or physical therapy for impairment, and 8 (18.2%) needed additional surgery. Five children (11.4%) developed scoliosis, and all of these patients had posterior rib tumors. Median overall survival for the entire cohort was 41.9±11.82months. Histology (p=0.003), location of tumor on the ribs (p=0.007), and surgical margins (p=0.011) were significantly associated with overall survival. Tumors on the middle and posterior (p=0.003) portions of the ribs had a lower chance of death. ConclusionScoliosis is more common in posterior rib resections. Histology, location of the tumor, and surgical margins impact survival, but, type of reconstruction does not. Level of evidenceIII. Type of Study: Treatment Study.

Detection of lymph node metastases in pediatric and adolescent/young adult sarcoma: Sentinel lymph node biopsy versus fludeoxyglucose positron emission tomography imaging-A prospective trial.

Lymph node metastases are an important cause of treatment failure for pediatric and adolescent/young adult (AYA) sarcoma patients. Nodal sampling is recommended for certain sarcoma subtypes that have a predilection for lymphatic spread. Sentinel lymph node biopsy (SLNB) may improve the diagnostic yield of nodal sampling, particularly when single-photon emission computed tomography/computed tomography (SPECT-CT) is used to facilitate anatomic localization. Functional imaging with positron emission tomography/computed tomography (PET-CT) is increasingly used for sarcoma staging and is a less invasive alternative to SLNB. To assess the utility of these 2 staging methods, this study prospectively compared SLNB plus SPECT-CT with PET-CT for the identification of nodal metastases in pediatric and AYA patients. Twenty-eight pediatric and AYA sarcoma patients underwent SLNB with SPECT-CT. The histological findings of the excised lymph nodes were then correlated with preoperative PET-CT imaging. A median of 2.4 sentinel nodes were sampled per patient. No wound infections or chronic lymphedema occurred. SLNB identified tumors in 7 of the 28 patients (25%), including 3 patients who had normal PET-CT imaging of the nodal basin. In contrast, PET-CT demonstrated hypermetabolic regional nodes in 14 patients, and this resulted in a positive predictive value of only 29%. The sensitivity and specificity of PET-CT for detecting histologically confirmed nodal metastases were only 57% and 52%, respectively. SLNB can safely guide the rational selection of nodes for biopsy in pediatric and AYA sarcoma patients and can identify therapy-changing nodal disease not appreciated with PET-CT. Cancer 2017;155-160. © 2016 American Cancer Society.

Off-label use of bevacizumab in relapsed and refractory pediatric sarcoma patients: The Memorial Sloan Kettering Cancer Center Experience.

10569Background: Survival rates for children and young adults with relapsed and/or refractory sarcomas remain poor. Cytotoxic salvage options for these patients are limited and associated with sign...

Abstract A51: Ethnic and gender disparities in limb-salvage rates among pediatric sarcoma patients

Abstract Introduction: Racial and ethnic disparities in limb-salvage surgery have been reported among adult sarcoma patients. The purpose of this work was to explore treatment patterns by ethnicity and gender in a cohort of pediatric sarcoma patients Methods: A retrospective review was conducted of all consecutive patients under the age of 18 treated for sarcoma at the study institution with diagnoses from 1999 to 2011 who underwent surgery for limb salvage or amputation. Statistical analysis of patient demographics (age, sex, ethnicity and BMI) was performed to assess for factors associated with limb salvage surgery. Results: 51 records were identified as pediatric patients who underwent surgery for extremity sarcoma in the defined study period. 5 records were excluded due to inadequate availability of body site or surgery type documentation, leaving a cohort of 46 patients. Hispanic patients were more likely to undergo amputation (10 of 36) compared to non-Hispanics (5 of 10; p = 0.03). Female patients were more likely to have had limb salvage (8 of 17) than males (7 of 29; p = 0.04). Logistic regression analysis showed no difference between likelihood of limb salvage and amputation when stratified by BMI or age. Conclusions: Hispanic ethnicity and male gender were predictors of amputation in a cohort of pediatric sarcoma patients undergoing surgical treatment. Further study should be devoted to identifying underlying factors for ethnic and gender discrepancies between treatment groups. Citation Format: Jeremy Somerson, Isaac Kim, Rajiv Rajani. Ethnic and gender disparities in limb-salvage rates among pediatric sarcoma patients. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A51.

Cyclophosphamide versus ifosfamide for paediatric and young adult bone and soft tissue sarcoma patients.

Alkylating agents, such as cyclophosphamide and ifosfamide, play a major role in the improved survival of children and young adults with bone and soft tissue sarcoma. However, there is still controversy as to their comparative anti-tumour efficacy and possible adverse effects. This is the second update of the first systematic review evaluating the state of evidence on the effectiveness of cyclophosphamide as compared to ifosfamide for paediatric and young adult patients with sarcoma. The primary obective was to compare the effectiveness, that is response rate, event-free survival and overall survival, of cyclophosphamide with that of ifosfamide for paediatric and young adult patients with sarcoma. Secondary objectives were to determine effects of these agents on toxicities (including late effects) and quality of life. We searched CENTRAL (The Cochrane Library 2015, issue 2), MEDLINE/PubMed (from 1966 to March 2015) and EMBASE/Ovid (from 1980 to March 2015) with prespecified terms. In addition, we searched reference lists of relevant articles, conference proceedings and ongoing trial databases (www.controlled-trials.com; searched June 2015). Randomised controlled trials (RCTs) or controlled clinical trials (CCTs) comparing cyclophosphamide and ifosfamide for the treatment of different types of sarcoma in paediatric and young adult patients (aged less than 30 years at diagnosis). Chemotherapy other than either cyclophosphamide or ifosfamide should have been the same in both treatment groups. Two authors independently performed the study selection. No studies meeting the inclusion criteria of the review were identified. No RCTs or CCTs comparing the effectiveness of cyclophosphamide and ifosfamide in the treatment of bone and soft tissue sarcoma in children and young adults were identified. Therefore no definitive conclusions can be made about the effects of cyclophosphamide and ifosfamide in these patients. Based on the currently available evidence, we are not able to give recommendations for clinical practice. More high-quality research is needed.

Fifteen years of irinotecan therapy for pediatric sarcoma: where to next?

Over the past 15 years, irinotecan has emerged as an important agent for treating pediatric sarcoma patients. This review summarizes the activity noted in previous studies, and outlines current issues regarding scheduling, route of administration, and amelioration of side effects. Also discussed are new pegylated and nanoliposomal formulations of irinotecan and its active metabolite, SN-38, as well as future plans for how irinotecan may be used in combination with other conventional cytotoxic as well as targeted agents.

Increased CTLA-4(+) T cells and an increased ratio of monocytes with loss of class II (CD14(+) HLA-DR(lo/neg)) found in aggressive pediatric sarcoma patients.

BackgroundThere is little information regarding the composition of peripheral blood immunity in sarcoma patients and even less in the context of pediatric sarcomas. We describe the immune status using flow cytometry of peripheral blood in patients with osteosarcoma and Ewing sarcoma and demonstrate excessive CD14 in tumor tissues.MethodsPeripheral blood from patients with OS and ES was collected at diagnosis or relapse, and used for immune phenotyping of 74 different leukocyte phenotypes. Blood from young adult healthy volunteers was collected as controls. Tumor tissues were analyzed by immunohistochemistry.ResultsNineteen patients (average age = 14 y) and 16 controls (average age = 25y) were enrolled on study. Of the 74 phenotypes, 14 were different between sarcoma patients and HV. Sarcoma patients’ leukocytes contained a higher percentage of granulocytes (67 % sarcoma vs. 58 % HV; p = 0.003) and fewer lymphocytes (20 % sarcoma vs. 27 % HV; p = 0.001). Increased expression of CTLA-4 was seen in both T cells in sarcoma patients as compared to HV (p = 0.05). Increased CD14+ HLA-DRlo/neg immunosuppressive monocytes were seen in sarcoma patients (p = 0.03); primarily seen in OS. Increased tumor necrosis factor receptor II expression was seen on CD14+ cells derived from sarcoma patients as compared to HV (p = 0.01). Massive infiltration of CD14+ cells was seen in OS (>50 % of cells in the majority of tumors) compared to ES (<10-25 % of cells). In contrast, both OS and ES had limited T cell infiltration (generally <10 % of cells).ConclusionsPediatric sarcoma patients exhibit several immune phenotypic differences that were exacerbated in more severe disease. These phenotypes have the potential to contribute to immune suppression and may indicate potential targets for immune therapies.Electronic supplementary materialThe online version of this article (doi:10.1186/s40425-015-0082-0) contains supplementary material, which is available to authorized users.

Evaluation of Overall Survival (OS) and Event-Free Survival (EFS) of Paediatric Sarcoma Patients at a Single Institution

Evaluation of Overall Survival (OS) and Event-Free Survival (EFS) of Paediatric Sarcoma Patients at a Single Institution

Utility of bone marrow aspiration and biopsy in initial staging of Ewing sarcoma.

The current standard of care for initial staging of pediatric Ewing sarcoma (EWS) patients is to obtain a bilateral bone marrow aspiration and biopsy (BMAB). The incidence of bone marrow (BM) disease in patients deemed non-metastatic by conventional and metabolic imaging and the concordance of BM positivity with other clinical characteristics are not well established. This study is a multi-institutional retrospective review of newly diagnosed EWS patients less than 40 years of age with initial staging that included imaging and BMAB. A total of 116 patients were eligible with 85 patients considered non-metastatic and 31 considered metastatic by imaging. None of the 85 patients with non-metastatic disease were BMAB positive (0%; 95% CI: 0-4.2%); 13 of the 31 patients with metastases were BMAB positive (41.9%; 95% CI: 24.5-60.9%). Primary tumor size was significantly higher in patients with metastases (P = 0.017). Bone metastasis by imaging had high correlation with BMAB positivity (P = 0.0002). In addition, the number of bony metastatic sites was significantly higher in patients with a positive BMAB as compared to those with a negative BMAB (median 3.5 and 0.0, respectively; P < 0.001). BMAB may not be required for initial staging of pediatric and young adult EWS patients deemed non-metastatic by imaging. In patients with metastatic disease, there is a high correlation of BM involvement with multiple bone metastases.

Analysis of Risk Factors for Central Venous Catheter–Related Complications

The incidence of central venous catheter (CVC)-related complications reported in pediatric sarcoma patients is not established as reports in available literature are limited. The analysis of risk factors is part of the strategy to reduce the incidence of CVC complications. The objective of this study was to determine the incidence of CVC complications in children with bone sarcomas and if defined clinical variables represent a risk factor. During an 8-year period, 155 pediatric patients with bone sarcomas were prospectively followed up for CVC complications. Incidence and correlation with clinical features including gender, age, body mass index, histology, disease stage, and use of thromboprophylaxis with low-molecular-weight heparin were analyzed. Thirty-three CVC complications were recorded among 42 687 CVC-days (0.77 per 1000 CVC-days). No correlation between the specific clinical variables and the CVC complications was found. A high incidence of CVC-related sepsis secondary to gram-negative bacteria was observed. The analysis of CVC complications and their potential risk factors in this sizable and relatively homogeneous pediatric population with bone sarcomas has led to the implementation of a multimodal approach by doctors and nurses to reduce the incidence and morbidity of the CVC-related infections, particularly those related to gram-negative bacteria. As a result of this joint medical and nursing study, a multimodal approach that included equipping faucets with water filters, the reeducation of doctors and nurses, and the systematic review of CVC protocol was implemented.

Decitabine facilitates immune recognition of sarcoma cells by upregulating CT antigens, MHC molecules, and ICAM-1

Rhabdomyosarcoma, osteosarcoma, and Ewing's sarcoma are the most common types of sarcoma in children. Despite standard therapy, nearly one third of the patients with Ewing's sarcoma relapse, and there are limited options with curative potential. Immunotherapy is a promising approach as it can target tumor-specific antigens that are specifically expressed on tumors while sparing non-malignant cells. We have demonstrated that a demethylating chemotherapeutic drug, 5-aza-2'-deoxycytidine (decitabine, DAC) can upregulate the expression of cancer-testis (CT) antigens, MHC molecules, and intracellular cell adhesion molecule-1 on pediatric sarcoma cell lines, resulting in enhanced killing of tumor cells by CT antigen-specific cytotoxic T lymphocytes derived from pediatric sarcoma patients. A significant increase in the mRNA expression levels of MAGE-A1 and MAGE-A3 were found in 70 %, and NY-ESO-1 in 80 % of the sarcoma lines following exposure to pharmacological levels of DAC. The high expression levels of MAGE-A1, MAGE-A3, and NY-ESO-1 were sustained in sarcoma lines and primary tumor lines over 30 days after the cessation of DAC. Furthermore, DAC treatment induced upregulation of MAGE-A1, MAGE-A3, or NY-ESO-1 protein expression in seven of nine lines studied. These studies show that demethylating chemotherapy could be combined with CT antigen-directed immunotherapy for treating pediatric sarcoma.

Assessment of Sorafenib and AntiVEGF Combination Therapy Response which Added to Neoadjuvant Therapy in two Pediatric Metastatic Ewing Sarcoma Patients by Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography (18F-PET) Method: It may Determine the Prognosis

Background: The prognosis is still poor in metastatic Ewing sarcoma (ES) patients. We aimed to assess importance of 18F-PET/CT in 2 pediatric local invasive/ metastatic Ewing sarcoma patients which have been performed antiVEGF and Sorafenib besides their neo-adjuvant and adjuvant chemotherapies (ChT) to improve their prognosis. Response to therapy has been followed by 18F-PET/CT in addition to MR imaging. Patients: First patient was a 12 year-old-girl who was suffering from right leg pain and diagnosed with Ewing sarcoma (ES). 18F-PET/CT showed a locally invasive mass with 14x5 cm dimensions located on one third of proximal tibia with a 5,1 SUVmax value was observed . After 4 cycles of conventional ChT beside antiVEGFSorafenib, SUVmax: 2,1 and tumor necrosis was 80%. Patient received local Radiotherapy (RT) and still in remission after 18 months. Second patient was a 13 year-old-girl who admitted with swelling and pain on right scapula. MR imaging revealed a mass causing deterioration on right scapula and surrounding soft tissue. Diagnosed as ES. PET/CT showed that: primary lesion SUV max 12,4 value, beside another metastatic lesion on left fifth rib with 3,4 SUVmax,confirmed by MRI and biopsi. In addition to conventional neo-adjuvant ChT regimen for ES, antiVEGF and sorafenib were added. There was no 18F-PET/CT involvement during pre-surgical evaluation. Tumor necrosis was %98 and surgical border was tumor negative. Postoperative adjuvant chemotherapy with antiVEGF and sorafenib continued untill end of the treatment protocol. Besides, local RT. Primary region of the tumor and metastatic lesion were still 18F-PET/CT imaging negative, by the enf of the therapy. Patient is still well after 15 months. Conclusion: 18F-PET/CT imaging can predict tumor response to neoadjuvant/adjuvant ChT which includes promising antiVEGF and sorafenib therapies in pediatric ES patients in the manner of the primary tumor necrosis ratio and metastatic evaluations.

Sentinel Lymph Node Biopsy in pediatric soft tissue sarcoma patients: Utility and concordance with imaging

BackgroundThe purpose of this study was to report our experience with sentinel lymph node biopsy (SLNB) for pediatric soft tissue sarcomas to add to the limited literature about its feasibility, utility, and concordance with pre-operative imaging, including CT and 18F-FDG PET (PET) scanning. MethodsMedical records of patients with a sarcoma who underwent SLNB as part of their treatment for a soft tissue sarcoma at our institution from 2000 to 2011 were identified and reviewed. ResultsEight patients underwent SLNB for soft tissue sarcoma during the study period. Two patients had positive SLNBs; both of these patients had rhabdomyosarcoma. Three patients with pathologically enlarged lymph nodes on CT scan underwent PET functional imaging prior to SLNB. The PET suggested the presence of nodal disease in all three patients; however, only one of these patients had a positive SLNB. ConclusionsOur series confirms that SLNB is feasible in pediatric sarcoma patients. Small numbers preclude definitive conclusions regarding the utility of SLNB compared with PET, however our data suggest functional imaging alone may not be sufficient to definitively determine lymph node status in these patients. Surgical lymph node sampling may still need to be performed to accurately identify nodal status in pediatric patients with soft tissue sarcoma.

Genomic EWS-FLI1 Fusion Sequences in Ewing Sarcoma Resemble Breakpoint Characteristics of Immature Lymphoid Malignancies

Chromosomal translocations between the EWS gene and members of the ETS gene family are characteristic molecular features of the Ewing sarcoma. The most common translocation t(11;22)(q24;q12) fuses the EWS gene to FLI1, and is present in 85–90% of Ewing sarcomas. In the present study, a specifically designed multiplex long-range PCR assay was applied to amplify genomic EWS-FLI1 fusion sites from as little as 100 ng template DNA. Characterization of the EWS-FLI1 fusion sites of 42 pediatric and young adult Ewing sarcoma patients and seven cell lines revealed a clustering in the 5′ region of the EWS-breakpoint cluster region (BCR), in contrast to random distribution of breakpoints in the FLI1-BCR. No association of breakpoints with various recombination-inducing sequence motifs was identified. The occurrence of small deletions and duplications at the genomic junction is characteristic of involvement of the non-homologous end-joining (NHEJ) repair system, similar to findings at chromosomal breakpoints in pediatric leukemia and lymphoma.